The accumulation of high levels of lead or lead ions in a human body is harmful, particularly to children. Its neurotoxic effect is profound, damaging the central and peripheral nervous systems, resulting in stunted growth, behavioral problems and learning disabilities. The major source of lead or lead ions comes from the drinking water and tap water. The assessment of the water quality, including lead or lead ion content, is usually completed by a regional water department professional. This assessment is time-consuming and requires expensive instruments and skilled operators. Therefore, there is a need to produce a simple-use and relatively inexpensive method to detect lead or lead ions in water samples. This research has developed a simple-use, cost effective sensor system for the detection of lead ions in tap water. An under-potential deposited bismuth sub-layer on a thin gold film based electrochemical sensor was designed, manufactured and evaluated. Differential pulse voltammetry (DPV) measurement technique was employed in this detection. Tap water from the Cleveland, Ohio, USA regional water district was the test medium. Concentrations of lead ion in the range of 8 X 10^-8 M to 8 x 10^-4 M were evaluated. This DPV detection system required 3 -6 minutes to complete the detection measurement. A longer measurement time of 6 minutes was used for the lower lead ion concentration. The selectivity of this lead ion sensor was very good, and Fe III, Cu II, Ni II and Mg II at a concentration level of 5×10^-4 M did not interfere with the lead ion measurement.

Oral cancer ranks sixth among Taiwan's top 10 cancers, and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. Migration and invasion assays confirmed OSCC cells' EMT capabilities, whereas flow cytometry and Western blotting identified the molecular pathways. ALA dramatically reduced cell growth in a concentration dependent manner, according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, expression of Twist and EMT-related proteins, expression of MMP2/-9 proteins and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation, then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins, or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

Background: Ovarian cancer is the leading cause of death from gynecological malignancies with serous carcinoma being the most common histopathologic subtype. Epithelial-Mesenchymal Transition (EMT) correlates with an increased metastatic potential, whereas the transcription factor SOX11 is overexpressed in diverse malignancies. Methods: In the present study, we aim to evaluate the potential role of the immunohistochemical expression of SOX11 in 30 serous ovarian carcinomas in association with E-cadherin and Vimentin expression as well as with patients’ clinicopathological data. Results: Most of the examined cases showed concurrent expression of E-cadherin and Vimentin, whereas SOX11 was expressed in a minority of the cases (26,7%). Interestingly, the positive cases had more frequently a metastatic disease at the time of diagnosis compared to the negative cases (p=0.09), an association, however, of marginal significance. Moreover, there was a negative correlation between E-Cadherin and SOX11 expression (p=0,0077) and a positive correlation between Vimentin and SOX11 expression (p=0,0130). Conclusions: The present work, for the first time, provides preliminary evidence SOX11 overexpression alongside E-cadherin loss in the promotion of EMT in serous ovarian cancer, thereby endorsing tumor metastasis.

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), E-cadherin, and claudin-4 (epithelial–mesenchymal transition markers) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p < 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with decreased E-cadherin expression (p = 0.0055) and claudin-4 expression (p = 0.029); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had a disease control rate of 66.7% and 11.8%, respectively (p = 0.049). Lipopolysaccharide positivity was associated with TGF-β signaling and epithelial–mesenchymal transition and was considered to promote therapeutic resistance to nivolumab.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

A novel low-power MOS-only voltage reference is presented. The Enz-Krummenacher-Vittoz (EKV) model is adopted to provide a new perspective on the operating principle. The normalized charge density, introduced as a new variable, serves as an indicator when trimming the output temperature coefficient. The proposed voltage reference consists of a specific current generator and a 5-bit trimmable load. Thanks to the well-match between the current source stage and the output stage, the non-linear temperature dependence of carrier mobility is automatically canceled out. The circuit is designed in 55 nm COMS technology. The operating temperature ranges from -40 ∘C to 120 ∘C. The average temperature coefficient of the output voltage can be reduced to 21.7 ppm/∘C by trimming. The power consumption is only 23.2 nW with a supply voltage of 0.8 V. The line sensitivity and the power supply rejection ratio at 100 Hz are 0.011 %/V and -89 dB respectively.

Introduction: Nephrotic syndrome (NS) remains the most frequent mode of presentation of glo-merular diseases in children; in addition, the NS is primitive, i.e., idiopathic in 90% of cases with an average age of onset between 2 and 10 years. The objective of our study was to describe the char-acteristics and outcome of NS in children from 3 major hospitals from one of the poorest countries worldwide (Chad). Patients and Methods: Observational, cross-sectional, descriptive and multicenter study which took place over a period of 36 months (January 1,2019-December 31,2021) carried out in 3 hospitals in N’Djamena (Chad). All children aged 1-15 years presenting with NS were included. Results: Out of 16,776 children hospitalized or followed-up in outpatient clinics, 24 cases of NS were identified, giving a prevalence of 0.14%. The median age at presentation was 6.16(1-10) years. Nineteen children were male (sex ratio 3.8). There were 8 impure NS (33.3%). Edema was present in all patients, oliguria in 29.16%(n=7), and arterial hypertension in 20.83%(n=5) of cases. Mean proteinuria, albuminemia and total proteins were 2.86g/L, 19.13g/L and 30.41g/L respectively. Median serum creatinine was 87.3 µmol/L(75-1375µmol/L); three patients had acute renal failure on admission. Four patients had secondary NS. All patients (n=20) with idiopathic NS had received corticosteroid therapy; steroid-sensitivity was found in 90% of patients. Those who were not ster-oid-sensitive or relapsed underwent kidney biopsy (n=7); the most represented histological lesion was focal segmental glomerulosclerosis (FSGS; n=4), followed by minimal change disease (n=2), and membranoproliferative glomerulonephritis (n=1). The median length of hospitalization stay was 10.67 (5-27) days. None of the patients with idiopathic NS died. At last follow-up sixteen patients (80%) achieved long-term complete remission with normal renal function; however, 4 had subse-quent relapses. 16 patients. One patient with secondary NS died. Conclusion: In Chad childhood idiopathic nephrotic syndrome involves mostly young male; steroid sensitivity is as high as 95% and in the long-term 80% of the patients are in remission with normal renal function.

In this paper, a new multi parameter iterative algorithm is proposed to address the PageRank problem based on the multi-splitting iteration method described by Gu et al . The proposed method in each iteration needs to solve two linear subsystems by splitting the coefficient matrix, therefore, we consider inner and outer iteration to find the approximate solutions of these linear subsystems. It can be shown that the iterative sequence generated by the multi parameter iterative algorithm finally converges to the PageRank vector when the parameters satisfy the certain conditions. Numerical experiments show that the proposed algorithm has better convergence and numerical stability than the existing algorithms.

Land resources have been under tremendous anthropogenic pressure with the consequence of their degradation. It is therefore necessary that the land resources must be managed effectively for sustainable development. Different from the developed countries, carbon inventories and data bank to monitor carbon sequestration potential of different ecosystems are unavailable in India. Micro-level studies are essential for sustainable land use management for a land scarce nation like India. To achieve the desirable goal of the present study, a total of 33 tree-based land uses were identified from forested and agricultural landscapes. Of these total land uses, five were in forest landscapes and rest in agricultural landscapes categorized into forest tree plantations (8 land uses), agroforestry (nine land uses), commercial crop plantations (six land uses) and fruit orchards (five land uses). A stratified random nested quadrate sampling method was adopted for vegetation analysis of the different land uses. The SOC, biomass and carbon accumulation in the tree-based land uses were significantly different from each other. Mixed forest soil had the highest amount of SOC, primary nutrients, standing biomass carbon, and ecosystem carbon. Positive correlations were observed between SOC, total standing biomass, litter production, and ecosystem carbon. The sequence of best tree based land uses in terms of total SOC (up to 60 cm depth), total plant biomass, total plant biomass carbon and ecosystem carbon was mixed species forest (126.67, 781.21, 390.61 and 517.27) > sole tree species stands in forest landscape (109.71, 192.56, 96.28 and 205.98) > tea plantations (103.19, 77.07, 38.54 and 141.74) > homegardens (90.34, 97.38, 48.69 and 139.02) > mixed plantation of Anthocephalus cadamba + Swietenia macrophylla (60.07, 111.86, 55.93 and 116.02) > Swietenia macrophylla based agroforestry (62.49, 83.82, 41.91 and 104.40) > mixed plantation of Tectona grandis + Milvus migrans (60.0, 85.97, 42.99 and 102.90). Similarly, the order of the major land uses was forest > commercial crop plantation > forest tree plantations > agroforestry > fruit orchards. The overall average ecosystem carbon accumulation in forests was 3.24 times more than the land uses in agricultural landscapes. The ecosystem carbon accumulation in the tree-based land uses in both forest and agricultural landscape was highly variable and was significantly different from each other. Land use conversion from forest to agriculture can reduce more than half of the carbon stock, but converting into homegardens, tree plantations or agroforestry enhanced carbon storage of the land use systems. The present findings can be used as baseline information for developing prediction models for probable effects of different land use, future intervention and sustainable management of land use systems.

The quantification of sea surface temperature (SST) through space platforms has revolutionized how we obtain information at a global level. However, the main disadvantage of obtaining SST with satellite images consists of its inherent coarse spatial resolution. One solution could be the use of downscaling algorithms to create sequences of matrices at a higher resolution. We used the same SST data source from the MODIS-Aqua sensor at three spatial resolutions of 9 km, 4.5 km, and 1 km in the Gulf of California. Based on an open-source algorithm, the original SST images were downscaled to 4.5 km, 1 km, 500 m, 250 m, and 125 m per pixel scales. Results indicate a strong linear relationship between the original SST-MODIS data and the modeled data for all spatial resolutions. This study demonstrates the feasibility of an open-source downscaling algorithm to enhance the spatial resolution of SST images in a marginal sea.

Validation of satellite sea surface salinity (SSS) products is typically based on comparisons with in-situ measurements at a few meters depth, that are mostly done at a single location and time. The difference in term of spatio-temporal resolution between the in-situ near-surface salinity and the two-dimensional satellite SSS results in a sampling mismatch uncertainty. The Climate Change Initiative (CCI) project has merged SSS from three satellite missions. Using an optimal interpolation, weekly and monthly SSS and their uncertainties are estimated at a 50 km spatial resolution over the global ocean. Over the 2016-2018 period the mean uncertainty on weekly CCI SSS is 0.13, whereas the standard deviation of weekly CCI minus in-situ Argo salinities is 0.24. Using high resolution SSS simulations, we estimate the expected uncertainty due to the CCI versus Argo sampling mismatch. Most of the largest spatial variability of the satellite minus Argo salinity are observed in regions with large mismatch. A quantitative validation is performed by considering the statistical distribution of the CCI minus Argo salinity normalized by the sampling and retrieval uncertainties. This quantity should follow a Gaussian distribution with a standard deviation of 1, if all uncertainty contributions are properly considered. We find that 1) the sampling mismatch can explain most of the observed differences between Argo and CCI data, especially for monthly products and in dynamical regions (river plumes, fronts), 2) overall, the uncertainties are well estimated in CCI version 3, much better compared to CCI version 2. There are a few dynamical regions where discrepancies remain, and where the satellite SSS, their associated uncertainties and the sampling mismatch estimates should be further validated.

Global malaria epidemiology has changed in the last decade with a substantial increase in cases and death being recorded. Over 90% of global cases and deaths occur in Sub-Saharan Africa (SSA). Tanzania accounts for about 4% of all cases and deaths reported in recent years. It is believed that several factors contribute to the resurgence of malaria, parasite resistance to antimalarials and mosquito resistance to insecticides being at the top of the list. The presence of sub-microscopic infections poses a significant challenge to malaria rapid diagnostic tests (mRDT), particularly in low-endemic areas. Our cross-sectional surveys in Handeni and Moshi, Tanzania assessed the effect of low parasite density on mRDT. A significant difference (P˂0.001) in malaria prevalence by mRDT, light microscopy (LM) and nested polymerase chain reaction (PCR) was found among age groups. In comparison to all other groups, school-age children (5-15 years) had the highest prevalence of malaria. Based on the results of this study, mRDT may miss up to 6% of cases of malaria mainly due to low-density parasitaemia. Routinely used mRDT will likely miss the sub-microscopic parasitemia which will ultimately contribute to the continued spread of malaria and hinder efforts to control and eliminate it.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.

This paper examines the asymmetrical relationship between exchange rate and consumer prices in 40 Sub-Saharan African (SSA) countries from 1990q1 to 2017q4. The exchange rate pass-through (ERPT) to consumer prices is estimated for each country by using the nonlinear autoregressive distributed lags (NARDL) framework and dynamic panel estimators robust to cross-sectionally correlated errors. Firstly, our findings suggest an asymmetrical ERPT in the SSA region during the short-term, whereas there are mixed results across sub-regions in the long-term. Next, we find incomplete and significant ERPT to consumer prices in the entire SSA region which is higher during the depreciation of the local currency than after appreciations. Third, we find nonlinear ERPT with respect to the size of the exchange rate. The pass-through is higher during large exchange rate changes than after small changes. Finally, we find that the pass-through is greater in the countries with fixed exchange rate regime (CFA franc zone) having low inflationary environment than in the other SSA countries with flexible exchange rate regime and high inflation levels. As a result, policymakers should take into account these asymmetries and non-linearities to improve the credibility of monetary policy, strengthen trade liberalization and establish competitive market structures in the Sub-Saharan region.

The unsustainability of the services related to water, sanitation and hygiene in informal settlements in Sub-Saharan Africa services is deeply embedded in current societal and governance structures, cultures and practices; it is context-dependent and involves numerous actors with different interests. The field of sustainability transitions research addresses such persistent and large scale societal challenges, with transition management being one of its widely applied governance approach. By drawing on an analysis of the root causes of unsustainability and unreliability of WASH services in three case studies in Sub-Saharan Africa (Arusha-Tanzania, Dodowa-Ghana, Kampala-Uganda), we explore how a transition management approach can be designed to support a transition towards sustainable Water, Sanitation and Hygiene (WASH) in Sub-Saharan Africa. We distinguish the following contextual dimensions related to the unsustainability of WASH services: a) Multiplicity of WASH practices, structures and arrangements, b) Governance capacities for WASH services and maintenance, c) Landownership for sustainable access to WASH, d) Public participation in decision-making related to WASH, e) socio-economic structures governing access to WASH. These dimensions prompt the identification of conceptual and application challenges for transition management. Based on these challenges, recommendations were formulated for the design of a prescriptive transition management process that is not only functional but also emancipatory of character.

Abstract: Rice is one of the most important food crops in sub-Saharan Africa. Climate change, variability, and economic globalization threaten to disrupt rice value chains across the subcontinent, undermining their important role in economic development, food security, and poverty reduction. This paper maps existing research on the vulnerability of rice value chains, synthesizes the evidence and the risks posed by climate change and economic globalization, and discusses agriculture and rural development policies and their relevance for the vulnerability of rice value chains in sub-Saharan Africa. Important avenues for future research are identified. These include the impacts of multiple, simultaneous pressures on rice value chains, the effects of climate change and variability on parts of the value chain other than production, and the forms and extent to which different development policies hinder or enhance the resilience of rice value chains in the face of climatic and other pressures.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Objective: Aims to investigate the effects of empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, on renal fibrosis in male diabetic Sprague-Dawley (SD) rat model. Methods: Streptozotocin(STZ) were injected to establish diabetes model, EMPA (10 mg/kg·d) or normal saline (NS) were administered for four weeks. The changes in renal fibrosis-related biomarkers, include vimentin (VIM), collagen types I(Col-I), collagen types III(Col-III), fibroblast-specific protein 1(FSP-1), connective tissue growth factor (CTGF), fibronectin (FN) were evaluated. Renal pathology, serum glucose levels and urinary protein excretion were also assessed. Results: Biomarkers of renal fibrosis were significantly reduced in the EMPA group compared to those in the NS group after 4-week treatment, including VIM (519.84±83.37 vs. 663.27±91.84 ng/ml, P<0.05), Col-I (21.27±1.46 vs. 25.71±2.82 ng/ml , P<0.05) and Col-III (7.06±1.12 vs. 9.43±1.36 ng/ml, P<0.05), FSP-1 (4.38±0.81 vs. 5.70±0.78 ng/ml, P<0.05), and CTGF (1147±217 vs. 1556±235 pg/ml, P<0.05),respectively. Nevertheless, compared to normal control (NC) group, the levels of renal fibrosis-related biomarkers in the EMPA group showed no significant differences except for VIM, which was VIM (336.66±28.87 vs. 519.84±83.37 ng/mL, P<0.001). NS group rats showed notable renal tubular dilation and casts, EMPA group exhibited only mild tubular dilation. Conclusion: These findings suggest that empagliflozin reverse renal fibrosis potentially through inhibiting CTGF-mediated epithelial-mesenchymal transition.

Background: Epithelial-mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between epithelial and mesenchymal stage is essential for tissue homeo-stasis. Many of the genes promoting mesenchymal transformation has been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify genes responsible for maintaining the epithelial phenotype and in-hibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expres-sion was determined by qPCR and Western blot analysis. Knockout of CTGF was done using the CTGF sgRNA CRISPR/CAS9. Tumorigenic potential was determined using NCG mice. Results: Knocked-out of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as Anoikis resistance, cytoskel-eton remodeling, increased cell stiffness, and acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for conserva-tion of epithelial structure and function. These findings provide a new window to understand the early stages on mesenchymal transformation

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by pathological processes involving autoimmunity, vasculopathy, and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluation binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera is evaluated for the potential to activate keratinocytes in tissue culture and to induce signaling in TLR2 &amp; 3 reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes, and activation of these cells leading to release of IL-1α, representing a potential initiating pathway in this disease.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we have studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1 and HPAFII, we show that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73 - but not the isoform - interfered with cell migration as shown by xCELLigence technology. Our findings highlight the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identify direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism.

Chronic pulmonary diseases such as asthma, COPD, and Idiopathic pulmonary fibrosis are significant causes of mortality and morbidity worldwide. Currently, there is no radical treatment for many chronic pulmonary diseases, and the treatment options focus on relieving the symptoms and improving lung function. Therefore, efficient therapeutic agents are highly needed. Bronchial epithelial cells and airway smooth muscle cells and their crosstalk play a significant role in the pathogenesis of these diseases. Thus, targeting the interactions of these two cell types could open the door to a new generation of effective therapeutic options. However, the studies on how these two cell types interact and how their crosstalk adds up to respiratory diseases are not well established. With the rise of modern research tools and technology, such as lab-on-chip, organoids, co-culture techniques, and advanced immunofluorescence imaging, a substantial degree of evidence about these cell interactions emerged. Hence, this contribution aims to summarize the growing evidence of bronchial epithelial cells and airway smooth muscle cells crosstalk under normal and pathophysiological conditions. The review first deliberates the effects of both healthy and stressed epithelial cells on airway smooth muscle cells, taking into account three themes; contraction, migration, and proliferation. Then, it discusses the impact of airway smooth muscle cells on the epithelium in inflammatory settings. Later, it examines the role of airway smooth muscle cells in the early development of bronchial epithelial cells and their recovery after injury.

Ocular drug delivery is one of the most challenging administration routes due to the very low drug bioavailability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD), an anti-inflammatory cannabinoid. CBD-loaded mixed PMs are physically stabilized by ionotropic crosslinking of the CS domains with sodium tripolyphoshate and spray-drying. These mixed PMs display CBD loading capacity of 20% w/w and sizes of 100-200 nm, and spherical morphology (cryogenic-transmission electron microscopy). The good compatibility of the unloaded and CBD-loaded PMs is assessed in a human corneal epithelial cell line. Then, we confirm the permeability of CBD-free PMs and nanoencapsulated CBD in cornea cell monolayers under liquid-liquid and air-liquid conditions. Overall, our results highlight the potential of these polymeric nanocarriers for ocular drug delivery.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

In this paper, a relatively new hyper convolution spectra for characterization liquid, viscoelastic and solid samples is presented. Special attention is paid to the biophysical characterization of epithelial tissues and early detection of cancer of the skin, cervix, colon, and oral cavity. The method is based on the use of two types of white light, diffuse and polarized, from the same LED light sources. Based on the subtraction of the intensity values of these two lights and using the hyper convolution algorithm, the ratio of paired and unpaired electrons of tissue is obtained. This ratio correlates well with the state of the tissue: normal, irritating, precancerous, and cancerous. First, a proof-of-concept studies were performed, and later clinical studies on samples from one thousand two hundred fifteen people were performed. It showed that hyper Opto-Magnetic Imaging Spectroscopy (OMIS) can detect epithelial tissue cancers with an accuracy of 85-96%. Bearing in mind that the OMIS method also acquires the biophysical characteristics of the deeper skin layers (epidermis, basement membrane, dermis) by analysing convolution spectra of RGB channels of both diffuse and polarized white light, it is possible to apply this method in cosmetics (skin hydration, collagen, and elastin states, etc.). During OMIS applications, we noticed places where improvements could be made to increase method’s accuracy using advanced machine learning methodologies.

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer associated to asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and the Epithelial Mesenchymal Transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos related primary oxidative damage is counteracted in the lung by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet fully understood. Moreover, asbestos exposure has been associated to induced EMT event, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in a possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells: as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Take as a whole, these results show, for the first time, a crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, so improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

Metabolic surgery can promote integrated physiologic improvement to ameliorate metabolic illness, particularly type 2 diabetes. Nevertheless, the therapeutic scope has been limited by unexpectedly inconsistent surgical outcomes. Therefore, the purpose of this study is to overcome the obstacles by determining the core mechanism of conflicting results. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified types of duodenal-jejunal bypass procedures, were compared to comprehend specific surgical patterns from distinctive perspectives. Patients in exclusively nonobese groups are subjected to avoid compounding by weight fluctuations. During intestinal anastomosis, the epithelial identity of the succeeding intestine is replaced by that of the proximal epithelium through altered crosstalk between the epithelium and opposing mesenchymal cells. The rapid turnover rate and compensatory proliferation of the succeeding intestine accelerate the propagation of the replaced epithelium. Propagation of replaced epithelium could provoke inconsistent outcomes of metabolic surgery. The major determinants of the conflicting results of metabolic surgery are inadequate duodenal exclusion and inappropriate length of the biliopancreatic limbs. The replaced enteroendocrine cells during regeneration provoke inconsistent outcomes of metabolic surgery. The critical factors are the type and density of enteroendocrine cells distributed at the terminal end of the preceding proximal intestine.

Characterization of cancer cells and neural stem cells indicates that tumorigenicity and pluripotency are coupled cell properties determined by neural stemness, and tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. Neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells lose their epidermal fate and assume the neural default fate and consequently, turn into neuroectodermal cells. They further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or a conjoined twin. During tumorigenesis, cells progressively lose their original cell identity and gain of neural stemness, and consequently, gain of tumorigenicity and pluripotency, due to various intra-/extracellular insults in cells of a postnatal animal. Tumorigenic cells can be induced to differentiation into normal cells and integrate into normal embryonic development within an embryo. However, they form tumors and cannot integrate into animal tissues/organs in a postnatal animal because of lack of embryonic inducing signals. Combination of studies of developmental and cancer biology indicates that neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal. Tumorigenicity is the manifestation of aberrant occurrence of pluripotent state in a postnatal animal. Pluripotency and tumorigenicity are both but different manifestations of neural stemness in pre- and postnatal stage, respectively, of animal life. The unique property of neural stemness is derived from the evolutionary advantage of neural genes and the neural-biased state of the last common unicellular ancestors of metazoan. Based on these findings, I discuss about some confusion in cancer research, propose to distinguish the causality and associations and discriminate causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research.

Mathematical modeling is crucial in investigating the pandemic of the ongoing coronavirus disease (COVID-19). The primary target area of the SARS-CoV-2 virus is epithelial cells in the human lower repertory track. During this viral infection, infected cells can initiate innate and adaptive immune responses to viral infection. Immune response in COVID -19 infection can lead to longer recovery time and more severe secondary complications. We formulate a target cell limited mathematical model by incorporating a saturation term for SARS-CoV-2 infected epithelial cell loss reliant on infected cell levels. Forward and backward bifurcation between disease-free and endemic equilibrium points has been analyzed. Global stability of both disease-free and endemic equilibrium is provided. We have seen that the disease-free equilibrium is globally stable for $R_0<1$, and endemic equilibrium exists and is globally stable for $R_0>1$. Impulsive application of drug dosing has been applied for the treatment of covid-19 patients. Also, the dynamics of the impulsive system are discussed when a patient takes drug holidays. The numerical simulations are performed in support of our analytical findings and for the qualitative analysis of the system's dynamics with and without impulse drug dosing.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance, culminating in relapse and metastatic disease continue to be associated with fatal disease. Cancer stem cells (CSCs) are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterised in many cancers with data illustrating that CSCs display great abilities to self-renew, withstand therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ABC membrane transporters, activation of several survival signaling pathways and increased immune evasion DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we re-visit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

Ultra-short 230 fs laser pulses of 515 nm wavelength were tightly focused into 700 nm focal spots and utilised in opening ~ 400 nm nano-holes in a Cr etch mask that was tens-of-nm thick. Nano-holes ablated at slightly above the threshold of ablation irradiance became nano-disks and nano-rings at slightly lower pulse energies. Subtle sub-1 nJ pulse energy control was harnessed to pattern large surface areas with controlled nano-alloying of Si and Cr. This technique is extendable to vacuum-free large area patterning of nanolayers by alloying them at distinct locations with sub-diffraction resolution. Such metal masks with nano-hole opening can be used for formation of random patterns of nano-needles with sub-100 nm separation when applied to dry etching of Si.

This paper investigates how agroecology in Africa is researched for two purposes. First, we present evidence of links between agroecology and food and nutrition security in sub-Saharan Africa. Second, we investigate which pathways of influence are dominant in the existing research and which pathways are under-represented. To achieve these objectives we anchor our analysis within feminist economics, thereby making use of the concepts of social reproduction and agency in our analysis of the literature. By employing a systematic literature review of empirical studies from African countries, starting from 1996 to 2020, we consolidate evidence that agroecology has contributed to food and nutrition security by acting toward sustainability at the farm level. However, our review shows in a second step that social and household dimensions of agroecology at the level of households and territories are not well documented in research linking agroecology to food security and nutrition in sub-Saharan Africa. Given that sustainable production practices such as agroecological practices are not mutually exclusive from the social activities of farmers and cultural contexts in which farmers are embedded, it is important to consider social and ecological processes concomitantly when assessing the value of Agroecology programs.

Abstract: Diabetes mellitus (DM) is associated with severe COVID-19 infection and complications. This study assessed COVID-19 vaccine acceptance and hesitancy in diabetes and explored reasons for nonvaccinating. This was a web-based cross-sectional survey using a mixed-method approach conducted between March-May 2021 corresponding to most SSA countries' early vaccine rollout period. Participants were those aged ≥18 years with self-reported DM in 11 Sub-Saharan African (SSA) countries. Responses to comments on reasons for vaccine hesitancy and facilitators for vaccine uptake were analyzed. Of the 73 participants with DM, 65.8% were males older than 35 years (86.3%), had post-secondary education (90%), and a significant proportion was from South Africa (39.7%), Nigeria (28.8%) and Ghana (13.7%). 64.4% had COVID-19 symptoms, 46.6% were tested for COVID-19, of which 19.2% tested positive. Few participants (6.8%) had taken the COVID-19 vaccination, 65.8% were willing to take the vaccine, while 26.0% either refused or hesitated to take the vaccine. The main reasons identified for not taking the vaccine were: advice from religious leaders, concerns about the vaccine safety, its effects, and efficacy, mistrust of the pharmaceutical companies, the conspiracy theories around the vaccines, the process of production, and the personal belief of the participants. However, participants stated they would take the vaccine if given more education about it, receive positive feedback from those vaccinated, are rewarded for taking the vaccine or if vaccination becomes a condition for travel and employment. The findings of this study showed that uptake of the COVID-19 vaccine was very low in this high-risk group. It is imperative that efforts to increase the uptake of vaccines, such as the provision of education and relevant information, are made.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.

Lead exposure is associated with poor cognitive development in children. Very few studies in sub-Saharan Africa (SSA) have studied blood lead levels (BLLs) and non-gasoline sources of exposure in children. Data from a birth cohort in Benin (2011-2013) suggested that 58% of one-year-old children had BLLs > 50 ug/L. We aimed to investigate the prevalence of elevated BLLs (>50 µg/L and >100 µg /L) among 425 of these children at six-years-of-age in 2016-18 and to compare BLLs between age one-year and six-years and study sources of lead at six years. BLLs were analyzed by inductively coupled plasma mass spectrometry. Multiple linear regression and quantile regressions were used to study potential sources of lead. The prevalence of BLLs >50 µg/L in children was 59.5% [Geometric Mean (GM) 56.4 µg/L, 95% CI: 54.1 - 58.7] at six years of age compared to 54.8% [GM 56.5 µg/L, 95% CI: 53.4-59.6] at one year of age. The prevalence of children with BLLs >100 µg/L decreased from 14.4% at one year of age to 8.2% at six years of age. After adjustment for all other covariates, consumption of peanut more than once per month was significantly associated with a 22.0% (95% CI: 4.6, 42.5) increment in BLLs at six years compared with no consumption. Consumption of bushmeat killed by lead bullets at six years was associated with an increase in the higher percentiles of BLLs (P75) compared with the absence of this source. Other potential sources of lead associated with BLLs with marginal significance were consumption of rice, paternal occupational exposure, and the presence of activity with the potential use of lead. This prospective cohort confirms the persistently high prevalence of elevated BLLs in children residing in a rural region in the south of Benin as well as the presence of multiple and continuous sources of lead. These results highlight the need for prevention programs to reduce and eliminate lead exposure in children.

Sustainable development goals (SDGs) are a global agenda consisting of 17 goals which are to be achieved in 2030 by all member states. SDGs are more holistic goals i.e. these goals are closely interrelated and they affect the progress of one another. Sub-Saharan Africa countries are, once more lagging behind in the implementations of SDGs despite the efforts by governments, non-government organisations and international agencies. Rwanda, South Africa and Zambia where the three Sub-Saharan Africa countries on which the study focused. The three countries in this study were chosen on the basis that they cater to the general overview of African countries performance on SDGs. To conduct this study, a desk research method was adopted and secondary data was utilised. An in-depth analysis was done on the on three subs Saharan African countries i.e. Rwanda, South Africa, Zambia. Those goals where serious attention is needed are goals 1-9, 16 and 17. Most Sub-Saharan African countries performed better on goals 11, 12 and 15. It was concluded that the achievement of Sustainable development goals remains a mere dream for Sub Saharan Africa unless serious interventions are made.

The importance of ICTs for dissemination of information to farmers has been verified by extension practitioners, information and communication scholars, policy makers and development agencies. Information related to new seed varieties, production technologies, livestock breeds, vaccines, including weed and pest control, as well as relevant market information is constantly required by smallholder farmers. The identification of specific attributes among smallholder farmers which contributes to their adoption of a proposed ICT-based information source provides an important tool for developing interventions which address the information needs of farmers. Using a literature survey methodology, pertinent studies related to adoption of ICTs, farmers’ information source usage and relevant frameworks were identified, including applicable theories and models in technology adoption and information behaviour. In the proposed framework, the socio-economic characteristics of smallholder farmers were posited as key variables influencing smallholder farmers, within a farming system, to adopt ICT-based information sources. The framework contributes to discern the prospects of adopting ICT-based information sources by individual farmers within a farming system, and may also envisage other related welfare outcomes and market participation pathways among smallholder farmers. The review also addresses the paucity of conceptual discourse, while contributing to a growing pool of research on ICT in African agriculture.

The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR ago-nist, GW4064, and FXR knockout (KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight junction markers (claudin1, Zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR KO mice had decreased levels. FXR KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, Cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR KO mice versus wild-type mice post-LPS exposure emphasize the pivotal role of FXR in pre-serving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

ABSTRACT: Objectives: Oncostatin M (OSM), a member of the interleukin (IL)-6 family of cytokines, is known to elicit pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is not yet known how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in sinonasal specimens of CRS patients, and we compared the results with a panel of inflammatory cytokine levels and clinical features. Materials and Methods: We classified CRS patients as eosinophilic (ECRS, n=36) or non-eosinophilic (non-ECRS, n=35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, and we compared their cases with those of 68 non-CRS subjects. We also examined stimulatory effects of OSM on the expression levels of cytokine receptors by using the human bronchial epithelium cell line BEAS-2B. Results: An RT-PCR showed that the OSM mRNA levels were significantly increased in the ethmoid sinus mucosa of the CRS patients. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1β, IL-13, and OSMR-β. In BEAS-2B cells, OSM treatment induced significant increases in the OSMR-β, IL-1R1, and IL-13Ra mRNA levels. Conclusions: Our findings indicate that OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions.

A key step in providing management/treatment options to men with suspected prostate cancer (PCa) is categorizing the risk for the presence of benign, low risk, intermediate risk, or high-risk disease. Our novel modality brings new evidence, based on the long-known hallmark characteristic of PCa – decreased Zinc (Zn), which is the most direct metabolic sign of malignancy and its aggressiveness. To date, this approach has not been adopted for clinical use for a number of reasons that are described in this article and which have been addressed by our approach: Zn has to be measured on fresh samples, prior to fixating in formalin, therefore samples have to be scanned during the biopsy session; as Zn depletion occurs in the glands, where the tumors develop, estimation of the glands’ levels in the scanned tissue along with their compactness, are essential for accurate diagnosis. Combined with the Zn depletion, this facilitates a reliable assessment of the disease aggressiveness. Data gathered in the clinical study described here indicate that in addition to improving the biopsy quality by real-time interactive guidance, a malignancy score can now be established for the entire prostate, allowing higher granularity personalized risk stratification and more decisive treatment decisions for all PCa patients.

Trueperella pyogenes is a common opportunistic pathogen which is one of the main causes of postpartum endometritis in dairy cows. As a substitute for antibiotics, the probiotic Lactobacillus rhamnosus GR-1 has been used in a wide range of clinical treatments. Our experiments were designed to establish a model of anti-damage which LGR-1 was used to protect bovine endometrial epithelial cells (BEECs) from inflammatory damage and cell destruction caused by T. pyogenes. Increased expression of NLRP3 inflammasomes and cytokines was observed following T. pyogenes challenge, but this increase was relieved by LGR-1 pretreatment. Immunofluorescence and Western blot analyses revealed that T. pyogenes infection also results in the damage of tight junction proteins in BEECs. The expression levels of Claudin-1, Occludin, and ZO-1 were decreased in cells only infected with T. pyogenes but not in cells pretreated with LGR-1. Moreover, the detection of the anti-apoptotic protein Bcl-2 and apoptotic proteins BAX, cytochrome c, as well as the activating effector caspase-3 revealed that T. pyogenes induced apoptosis of BEECs, which was also confirmed by DAPI staining to observe the morphological changes of the nuclei of cell apoptosis and by TUNEL staining to locate the cells undergoing apoptosis. Our data indicate that LGR-1 ameliorates the T. pyogenes–induced barrier dysfunction of BEECs and pre-application of LGR-1 could be an effective strategy for controlling T. pyogenes infection.

Background: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. Methods: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion-leaders, national decision-makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. Results: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. Conclusions: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

Background: Waterborne diseases pose a significant global public health threat, compelling enhanced comprehensive surveillance. This study investigates the current infectious disease and antimicrobial resistance (AMR) surveillance systems, including wastewater and environmental surveillance (WES), in three sub-Saharan African countries: Tanzania, Burkina Faso, and the Democratic Republic of the Congo (DRC). The three countries have their specificities regarding wastewater networks and logistic systems. So, emphasizing the need to strengthen existing disease surveillance, the paper advocates for incorporating WES systems specifically designed for countries' context to monitor waterborne and re-emerging pathogens, as well as AMR.Methods: National workshops were conducted to assess the current clinical and environmental surveillance systems and identify priority pathogens for new environmental monitoring. Data were collected through surveys from experts in academia, research, policy, and healthcare. Results: Prioritized pathogens for WES include waterborne (poliovirus, Salmonella Typhi, Vibrio cholerae), respiratory (influenza A&B, SARS-CoV-2), other (Measles and Rubella, Mycobacterium tuberculosis). Recommended AMR pathogens include drug-resistant Mycobacterium tuberculosis, Salmonella spp., methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase and carbapenemase-producing E. coli. Tanzania, Burkina Faso, and the DRC employ DHSI2-based centralized electronic systems for clinical data collection, complemented by Excel and paper-based registries. The WES approach is commonly employed for monitoring poliovirus and rarely for AMR and other pathogens. Discussion and conclusions: WES is a valuable tool for early detection of locally circulating human-derived pathogens, aiding in outbreak detection, data-driven epidemic response, and prevention. The availability of WES results underscores the importance of effective sanitation for safeguarding human, animal, and environmental health. WES is a pivotal tool for integrated risk management, preventing waterborne outbreaks, protecting drinking water sources, and ultimately gaining various UN Sustainable Development Goals. The study highlights the importance of customized WES systems in line with each country's context, emphasizing localized approaches for effective monitoring of waterborne pathogens and AMR.

Food and nutrition insecurity, affecting 30% of the global population in 2020, poses a significant challenge to achieving Sustainable Development Goal (SDG) 2 - Zero Hunger. Urbanization, particularly in sub-Saharan African cities e.g. Lagos, Nigeria, exacerbates these issues, impacting resources and contributing to informal settlements. There is emphasis on innovative solutions in urban farming, with Recirculating Aquaculture Systems (RAS) emerging as one of the promising approach due to its efficiency in space and capital utilization. However, maintaining optimal conditions in RAS, crucial for SDG 2 and 11, requires robust water quality monitoring. This study explores the availability of digital tools for water quality monitoring in small-scale urban RAS, evaluating handheld devices and IoT sensors' reliability through t-test statistical method. The results aim to guide practitioners in selecting effective monitoring tools, contributing valuable insights for sustainable aquaculture in urban areas, particularly in sub-Saharan Africa, where access to affordable digital solutions is pivotal for success and can attract youth to agri-food technologies.

Agroecology is a holistic approach to farming that emphasizes the use of local resources and ecological processes to increase productivity, reduce environmental impact, and enhance resilience. Despite its potential benefits, the adoption of agroecological practices in Sub-Saharan Africa has been slow. This paper examines the opportunities for promoting agroecology in the region, including the growing demand for organic and sustainable food, the availability of local knowledge and resources, and the potential for agroecology to improve rural livelihoods and support climate change adaptation. The premise is that the promotion of agroecology faces several challenges. which include, inadequate policy and institutional support, lack of access to credit and markets, limited extension services, and weak land tenure systems. The paper draws on case studies from across Sub-Saharan Africa to illustrate the opportunities and challenges of promoting agroecology in the region. These case studies highlight the diversity of agroecological practices and the importance of context-specific approaches. Overall, the paper maintains that agroecology has the potential to transform agriculture in Sub-Saharan Africa, but that realizing this potential will require concerted efforts from governments, civil society, and the private sector.

The larvicidal potential of olive mill waste water (OMWW) extract against mosquito larvae was evaluated. We exposed second instar Culex laticinctus (Edwards) and Aedes albopictus (Skuse) larvae to increasing OMWW concentrations. In addition, we tested the effects of long term exposure to a low OMWW concentration on larval development. The two mosquito species responded differently to OMWW extracts. Larval Cx. laticinctus showed higher vulnerability to increasing OMWW concentrations in comparison to Ae. albopictus. By contrast, Cx. laticinctus exposed to a low OMWW concentration until pupation did not exhibit survival differences, but rather sex-specific development responses. These trends were not observed in Ae. albopictus whose survival was significantly reduced following long exposer to OMWW extraction. These results showed that OMWW, which is known as agricultural byproduct waste, may be reused as a biopesticide.

The urban population in developing countries, especially sub-Saharan Africa, is rapidly increas-ing. As towns and cities grow, so does the demand for fish protein. While flow-through aqua-culture can provide fresh, healthy and nutritious fish protein, it is plagued by extensive land re-quirement as well as effluent discharge, thus, unsuitable for city regions. Alternatively, small-scale Recirculating Aquaculture System (RAS) could improve food and nutritional security (FNS), livelihoods as well as reduce environmental degradation in urban areas despite land and water constraints. The question however remains - what are the key technical, business and managerial issues, surrounding small-scale RAS in urban farming? This study reviews the RAS prototype of the Sustainable Aquaponics for Nutritional and Food Security in Urban Sub-Saharan Africa (SANFU) II project based on mass balance and stock density, relevant for fish survival and/or availability as well as net cash-flow analyses. The results suggest that small-scale RAS are technically and financially viable only with family labor having proper aquaculture monitoring and management skills. Furthermore, access to adequate equipment and inputs as well as electricity for the recirculating system are crucial. Urban innovation actors will adopt RAS if operations are profitable given that family labor is employed.

The energy transition requires integration of different energy carriers, including electricity, heat, and transport sectors. Energy modeling methods and tools are essential to provide a clear insight into the energy transition. However, the methodologies often overlook the details of small-scale energy systems. The study states an innovative approach to facilitate sub-national energy systems with 100% renewable penetration and sectoral integration. An optimization model, OSeEM-SN, is developed under the Oemof framework. The model is validated using the case study of Schleswig-Holstein. The study assumes three scenarios representing 25%, 50%, and 100% of the total available biomass potentials. OSeEM-SN reaches feasible solutions without additional offshore wind investment, indicating that they can be reserved for supplying other states’ energy demand. The annual investment cost varies between 1.02 bn – 1.44 bn €/yr for the three scenarios. The electricity generation decreases by 17%, indicating that with high biomass-based combined heat and power plants, the curtailment from other renewable plants can be decreased. Ground source heat pumps dominate the heat mix; however, their installation decreases by 28% as the biomass penetrates fully into the energy mix. The validation confirms OSeEM-SN as a beneficial tool to examine different scenarios for sub-national energy systems.

SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitution in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution pattern (type and location), and major substitution changes. The majority of the substitutions are distinct, occurred mostly in a particular location, and leads to a change in amino acid's biochemical properties. In terms of mutational changes, Envelope (E) and Membrane (M) proteins are relatively stable than Nucleocapsid (N) and Spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that Heptapeptide Repeat, Fusion peptides, Transmembrane in S protein, and N-terminal and C-terminal domains in N protein are remarkably mutated, and also found few deleterious mutations in these domains.

Most of the existing influence maximization algorithms are not suitable for large-scale social networks due to their high time complexity or limited influence propagation range. Therefore, a D-RIS influence maximization algorithm is proposed based on the independent cascade model and combined with the reverse reachable set sampling. Under the premise that the influence propagation function satisfies monotonicity and submodularity, the D-RIS algorithm uses automatic debugging method to determine the critical value of the number of reverse reachable sets, which not only obtains a better influence propagation range, and greatly reduce the time complexity. The experimental results on the two real data sets of Slashdot and Epinions show that D-RIS algorithm is close to the CELF algorithm and higher than RIS algorithm, HighDegree algorithm, LIR algorithm and pBmH algorithm in influence propagation range. At the same time, it is significantly better than the CELF algorithm and RIS algorithm in running time, which indicates that D-RIS algorithm is more suitable for large scale social network.

Land use and land cover change (LULCC) is a critical factor for enhancing the soil erosion risk and land degradation process in the Wabi Shebelle Basin. Up-to-date spatial and statistical data on basin-wide erosion rates can provide an important basis for planning and conservation of soil and water ecosystems. The objectives of this study were to examine the magnitude of LULCC and consequent changes in the spatial extent of soil erosion risk, and identify priority areas for Soil and Water Conservation (SWC) in the Erer Sub-Basin, Wabi Shebelle Basin, Ethiopia. The soil loss rates were estimated using an empirical prediction model of the Revised Universal Soil Loss Equation (RUSLE) outlined in the ArcGIS environment. The estimated total annual actual soil loss at the sub-basin level was 1.01 million tons in 2000 and 1.52 million tons in 2018 with a mean erosion rate of 75.85 t ha^–1 y^–1 and 107.07 t ha^–1 y^–1, respectively. The most extensive soil loss rates were estimated in croplands and bare land cover, with a mean soil loss rate of 37.60 t ha^–1 y^–1 and 15.78 t ha⁻¹ y⁻¹, respectively. The soil erosion risk has increased by 18.28% of the total area, and decreased by 15.93%, showing that the overall soil erosion situation is worsening in the study area. We determined SWC priority areas using the Multi-Criteria Decision Rule (MCDR) approach, indicates that the top three levels identified for intense SWC account for about 2.50%, 2.38%, and 2.14%, respectively. These priority levels are typically situated along the steep slopes in Babile, Fedis, Fik, Gursum, Gola Oda, Haramaya, Jarso, and Kombolcha districts that need emergency SWC measures.

Imperceptible vibratory noise stimulation has shown to be an effective means of improving stability for both whole body postural control and simple motor control tasks. While the physiological mechanism affording this improvement is uncertain, it is suspected that sensory noise stimulation may elicit a stochastic resonance-like effect within the somatosensory system. A stochastic resonance effect describes the phenomenon in which noise added to a non-linear system improves signal detection rather than degrading it. One hallmark of stochastic resonance is the existence of an optimal noise level which elicits the best system performance. There is disagreement in the literature regarding the presence of an optimal stimulation level for motor stability in humans. The goals of this study were to: 1) determine optimal stimulation level as a function of an individual’s sub-sensory threshold level, and 2) to determine whether performance of a force stability task was significantly better when subjects received stimulation at this identified optimal level compared to other sub-sensory threshold stimulation levels. Eighteen (18) participants completed an isometric finger flexion task with visual feedback while receiving noise stimulation scaled to varying percentages of their individual sub-sensory threshold level. Performance for this force stabilization task was quantified as the root-mean-square (RMS) error between the target force and the actual generated force values. Despite controlling all other signal properties and varying only amplitude, optimal noise stimulation values still varied widely across participants (10-100% sub-sensory threshold level). Statistical modeling revealed a significant improvement in task performance with optimal noise stimulation compared to other sub-sensory stimulation levels (p ≤ 0.019) with estimated marginal mean differences in force errors ranging from 0.13 to 0.23 N. Moderate significant Spearman correlations (r_s = 0.49 and r_s = 0.56, respectively) were found between finger flexion maximal voluntary contraction (MVC) and sub-sensory threshold level and MVC and optimal stimulation level. A strong, significant Spearman correlation (r_s = 0.65) was observed between sub-sensory threshold level and optimal stimulation level. Although these correlations do not provide a means to predict optimal stimulation level as a function of these other measures, optimal stimulation level appears to increase with sub-sensory threshold and MVC.

In this paper, the overall performance of Cu-(In,Ga)-Se₂ (CIGSe) solar cells was improved in the ultraviolet (UV)–visible wavelength region by two-segment process. In which, adjusting DC sputtering powers (20–40 W) for absorbers (segment I), and metal-alloy compositions (CdS, ZnO/CdS, ZnMgO/CdS and ZnMgO) for buffers (segment II) were explored and characterized. Upon choosing the optimal-30-W CIGSe-absorber (with 0.95-CGI ratio) sputtered by the segment-I process, the Cu-rich film can distinctly boost grain growth, thus reducing the trap state density. After segment-II process as the toxic-CdS alternative, the optimal Zn_0.9Mg_0.1O-alloy buffer can reach the best conversion efficiency (η = 8.70%) was attained for the environmental protection. Meanwhile, and the overall internal/external quantum efficiencies (IQE/EQE) were improved by 13.15%, respectively for the 2.48–3.62-eV bandgap (short wavelength) range. The developed photovoltaic (PV) module (with 9 optimum-CIGSe cells) exhibits acceptable stability with a variance within ±5% over the 60-day experiment. This discovery in PV-device research contributes to a new scientific understanding of renewable energy. Furthermore, this study undeniably enhances the progress of practical applications for PV-modules in alignment with sustainable development goals. It also actively supports the development of eco-friendly communities.

Boswellia trees are the source of frankincense, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and anti-microbial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, there were no significant effects on Fusobacterium nucleatum growth and biofilm formation. Using colony-forming units quantification and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the therapeutic potential for preventing and/or treating periodontal diseases. Future studies will identify molecular components of B. serrata extracts responsible for the beneficial effects.

(1) Background: The chemotherapeutic drug cisplatin exerts toxic side effects causing acute kidney injury. Mesenchymal stromal cells can ameliorate cisplatin-induced kidney injury. We hypothe-size that the MSC secretome orchestrates the vicious cycle of injury and inflammation by acting on proximal tubule epithelial cells (PTECs) and macrophages individually, but further by coun-teracting their cellular crosstalk. (2) Methods: Conditioned medium (CM) from adipose stromal cells was used, first assessing its effect on cisplatin injury in PTECs. Second, effects of cisplatin and CM on macrophages were measured. Lastly, in an indirect co-culture system the interplay between the two cell types was assessed. (3) Results: First, CM rescued PTECs from cisplatin-induced apoptosis by reducing oxidative stress and expression of nephrotoxicity genes. Second, while cisplatin exerted only minor effects on macrophages, CM skewed macrophage phenotypes to the anti-inflammatory M2-like phenotype and increased phagocytosis. Finally, in the co-culture system, CM suppressed PTEC death by inhibiting apoptosis and nuclei fragmentation. CM lowered TNF-α release. While cisplatin inhibited macrophage phagocytosis, PTECs, and CM to a greater extent, enhanced it. CM strongly dampened the inflammatory macrophage cytokine secretion triggered by PTECs. (4) Conclusion: ASC-CM surpasses the PTEC-macrophage cross-talk in cisplatin injury. The positive effects on reducing cisplatin cytotoxicity, on polarizing mac-rophages and on fine-tuning cytokine secretion underscores MSCs CM benefit to prevent kidney injury progression.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is the desmoplastic reaction of the tumor stroma, the formation of which is orchestrated by transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that the TGF-β pathway is controlled by transcriptionally active p73 (TAp73) through secretion of biglycan (Bgn) via intermittent expression of the TGF-β signaling intermediates, Smad3 and Smad4. Genetic knockout of TP73, and, as a consequence, deficient induction of Smad3/Dpc4 and secretion of Bgn led to activation of TGF-β signaling through a (Smad-independent) ERK pathway, favoring epithelial-mesenchymal transition (EMT) and cell motility. Except for BGN, these functions of TAp73 have recently been shown to also operate in human PDAC cells and are reminiscent of what we previously observed for the small GTPase, RAC1b. This prompted us to hypothesize that TAp73 and RAC1b are part of the same tumor-suppressive pathway in human PDAC cells. The two objectives of this study, therefore, were to reveal i) if the regulatory interactions between TAp73 and Bgn previously discovered in murine PDAC-derived cells also operate in their human counterparts, and ii) if RAC1b collaborates with TAp73 in these tumor-suppressive activities in human PDAC cells. Using a variety of experimental approaches, including mutual rescue experiments, we were able to show that the previously proposed tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human cells and that RAC1b is as an upstream activator of this pathway. Our findings highlight the complex role of TGF-β in pancreatic tumorigenesis and might have implications for therapeutic approaches targeting this growth factor for inhibition.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Besides, from pharmacogenomic research it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1 and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarkers microRNA could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

Sarocladium and Fusarium species are commonly identified as causal agents of rice sheath rot disease worldwide. However, limited knowledge exists about their genetic, pathogenic, and toxigenic diversity in sub-Saharan African (SSA) countries, where an increasing incidence of this disease has been observed. This study aimed at identifying, characterizing, as well as assessing the genetic, pathogenic, and toxigenic diversity of the pathogens associated with rice sheath rot disease in Mali, Nigeria, and Rwanda. In this study seventy fungal isolates were obtained from rice plants displaying disease symptoms on research and farmer’s fields in Mali, Nigeria, and Rwanda. Thus, an extensive comparative analysis was conducted to assess their genetic, pathogenic, and toxigenic diversity. The Fusarium spp. were characterized using the translation elongation factor (EF-1α) region, while a concatenation of Internal Transcribed Spacer (ITS) and Actin-encoding regions were used to resolve Sarocladium species. Phylogenetic analysis revealed four Fusarium species complexes. The dominant complex in Nigeria was the Fusarium incarnatum-equiseti species complex (FIESC), comprising F. hainanense, F. sulawesiense, F. pernambucatum, and F. tanahbumbuense, while F. incarnatum was found in Rwanda. The Fusarium fujikuroi species complex (FFSC) was predominant in Rwanda and Mali, with species such as F. andiyazi, F. madaense, and F. casha in Rwanda, and F. annulatum and F. nygamai in Mali. F. marum was found in Nigeria. Furthermore, Fusarium oxysporum species complex (FOSC) members, F. callistephi and F. triseptatum, were found in Rwanda and Mali, respectively. Two isolates of F. acasiae-mearnsii, belonging to the Fusarium sambucinum species complex (FSAMSC) were obtained in Rwanda. Isolates of Sarocladium which were previously classified in three phylogenetic groups were resolved into three species which are: attenuatum, oryzae and sparsum. S. attenuatum was dominant in Rwanda, while S. oryzae and S. sparsum were found in Nigeria. Also, the susceptibility of FARO44, a rice cultivar released by Africa Rice Centre (AfricaRice) was tested against isolates from the four Fusarium species complexes and the three Sarocladium species. All isolates evaluated could induce typical sheath rot symptoms albeit with varying disease development levels. In addition, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine variation in the in vitro mycotoxins of the Fusarium species. Regional differences were observed in the in vitro mycotoxins profiling. Out of the forty-six isolates tested, nineteen were able to produce one to four mycotoxins. Notably, very high zearalenone (ZEN) production was specific to the two F. hainanense isolates from Ibadan-Nigeria, while Fusarium nygamai isolates from Mali produced high amounts of fumonisins. To the best of our knowledge, it seems this study is the first to elucidate genetic, pathogenic, and toxigenic diversity of Fusarium species associated with the rice sheath rot disease complex in selected countries in SSA.

The main target of this study was to evaluate the impact of future climate change on the available surface water resources in the Dhidhessa Sub-basin, Abbay Basin, Ethiopia. For the prediction, high-resolution Regional Climate Models (RCMs) from multiple climate models with data from Representative Concentration Pathways (RCPs) prepared by the CCAFS were used. The predictions of future discharge (stream flow) were based on climate scenarios data of baseline period of 1991 to 2020 and for the future with two time windows, 2044 (2030–2059) and 2084 (2070–2099), on a monthly time step after bias correction was conducted to both precipitation and temperature in the future climate under each RCP scenario. After sensitivity analysis, calibration (1994–2011), and validation (2012–2020) of the model for the Dhidhessa Sub-basin with the SUFI-2 program in the SWAT-CUP model, the SWAT model was used to determine water balance and stream flow from the SWAT model system. The SWAT model performed well in predicting stream flow in the Dhidhessa Sub-basins, with a coefficient of determination (R2) ranging from 0.8 to 0.94 and a Nash Sutcliffe value (NSE) ranging from 0.76 to 0.89. The percent decrease in mean annual stream flow from 2044 and 2084 were 10 %, in 2044, and 6.3% in 2084 respectively. The seasonal result under short-term 2044 of stream flow present change significantly decreased in spring, winter, and autumn with 20.2%, 67.4%, and 67.4% respectively. While summer season increased by 43.1%, under short-term 204. In long-term 2084 percent change declined except summer seasons, with 14.7%, 58.1%, and 3.3%, change in spring, winter, and autumn, respectively, and summer, with 51.1% increased and With RCP4.5 (1.64%) and RCP8.5 (2.1%) changed. In the future Dhidhessa stream flow increases and decreases from the baseline era. The decreasing stream flow in 2044 and 2084 will negatively affect agricultural production. This study revealed that any effect on this river resulting in a drop in flow will have a direct impact on ongoing water resource development and socio-economic development of the area.

In this contribution, we present a high-speed multiplex grating spectrometer based on a spectral coding approach that is founded on principles of compressive sensing. The spectrometer employs a single-pixel InGaAs detector to measure the signals encoded by an amplitude spatial light modulator (digital micromirror device, DMD). This approach leads to a speed advantage and multiplex sensitivity advantage atypical for standard dispersive systems. Exploiting the 18.2 kHz pattern rate of the DMD, we demonstrate 4.2 ms acquisition times for full spectra with a bandwidth of 450 nm (5250 cm-1 – 4300 cm-1; 1.9 µm – 2.33 µm). Due to the programmability of the DMD, spectral regions of interest can be chosen freely, thus reducing acquisition times further, down to the sub-millisecond regime. The adjustable resolving power of the system accessed by means of computer simulations is discussed, quantified for different measurement modes, and verified by comparison with a state-of-the-art Fourier-transform infrared spectrometer. We show measurements of characteristic polymer absorption bands in different operation regimes of the spectrometer. The theoretical multiplex advantage of 8 was experimentally verified by comparison of the noise behavior of the spectral coding approach and a standard line-scan approach.

Urban cities in sub-Saharan Africa (SSA) are faced with ambient air pollution. This is an important public health problem with models and limited monitoring data indicating high concentrations of pollutants such as fine particulate matter (PM_2.5). Going through most global air quality index maps, however, information about ambient pollution from SSA is scarce. We evaluated the feasibility and practicality of longitudinal measurements of ambient PM_2.5 using low-cost air quality sensors (Purple Air-II-SD) across thirteen locations in seven countries in SSA. Devices were used to gather data over a 30-day period with the aim of assessing the efficiency of its data recovery rate and identifying challenges experienced by users in each location. The median data recovery rate was 94% (range: 72% to 100%). The mean 24-hour concentration measured across all sites was 38 µg/m³ with the highest PM_2.5 period average concentration of 91 µg/m³ measured in Kampala, Uganda and lowest concentrations of 15 µg/m³ measured in Faraja, The Gambia. Kampala-Uganda and Nnewi-Nigeria recorded the longest periods with concentrations>250µg/m³. Power outages, SD memory card issues, internet connectivity problems and device safety concerns were important challenges experienced when using Purple Air-II-SD sensors. Despite some operational challenges, this study demonstrated that it is reasonably practicable and feasible to establish a network of low-cost devices to provide data on local PM_2.5 concentrations in SSA countries. Such data are crucially needed to raise public-, societal and policymaker awareness about air pollution across SSA.

The coronavirus disease 2019 (COVID-19) pandemic is the defining global health and socioeconomic crisis of our time and represents the greatest challenge faced by the world since the end of the Second World War. The academic literature indicates that climatic features, specifically the temperature and absolute humidity, are very important factors affecting infectious pulmonary disease epidemics (e.g., SARS, MERS); however, the influence of climatic parameters on COVID-19 remains extremely controversial. The goal of this study is to quantify the existing relationship between several daily climate parameters (temperature, relative humidity, accumulated precipitation, solar radiation, wind direction and intensity, and evaporation), local morphological parameters, and new daily positive swabs for COVID-19, which represents the only parameter that can be statistically used to quantify the pandemic. The daily deaths parameter was not considered because it is not reliable due to frequent administrative errors. Daily data on meteorological conditions and new cases of COVID-19 were collected for the Lombardy area from March 1, 2020, to April 20, 2020. This region in Italy exhibited the largest number of official deaths in the world per million inhabitants, with a value of approximately 1700 per million on june 30, 2020. Moreover, the apparent lethality was approximately 17% in this area, mainly due to the considerable housing density and the extensive presence of industrial and craft areas. The Mann-Kendall test and multivariate statistical analysis showed that none of the considered climatic variables exhibited statistically significant relationships with the epidemiological evolution of COVID-19, at least in the spring months in temperate subcontinental climate areas, with the exception of solar radiation, which was directly related and showed an otherwise low explained variability of approximately 20%. Furthermore, the average temperatures of two highly representative meteorological stations of Molise and Lucania, the most weakly affected by the pandemic. The temperatures at these stations were approximately 1.5°C lower than that in the cities in Lombardy of Bergamo and Brescia, again confirming that a significant relationship between the increase in temperature and decrease in virology from COVID-19 was not evident, at least in the Italian peninsula.

Aflatoxins continue to raise health concerns as unavoidable and widespread natural contaminants of foods and feeds with serious impact on health, agricultural and livestock productivity, and food safety. They are secondary metabolites produced by Aspergillus species distributed on three main sections of the genus (section Flavi, section Ochraceorosei, and section Nidulantes). Aflatoxin-producing species, mainly A. flavus and A. parasiticus thrive under hot and humid conditions in the field or during storage, which are met in tropical and sub-tropical regions. Poor economic status of a country exacerbates the risk and the extent of crop contamination due to faulty storage conditions that are usually suitable for mold growth and mycotoxin production; temperature of 22 to 29°C and water activity of 0.90 to 0.99. This situation paralleled the prevalence of high liver cancer and the occasional acute aflatoxicosis episodes that have been associated with these regions. Few of the presently known aflatoxins (>18) have been sufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has by far been the most studied; and yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity, which are the best known still suffer from many limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the algal hepatotoxic microcystins, the mechanisms of this synergy remain unclear. A review of publications on the incidence and concentrations of aflatoxins in selected foods and feeds from countries whose crops are classically known for their highest contamination with aflatoxins, reveals that despite the intensive efforts made to reduce such an incidence, there has been no clear tendency, with the possible exception of South Africa, towards sustained improvements. The levels and incidence are essentially influenced by the rainfall and temperature during the cultivation year or two successive years with alternating dry and wet seasons. This review aimed to update the main aspects of aflatoxin production, occurrence and incidence in selected countries, and associated adverse health effects. In addition to AFB1 which was the main focus of the review, other aflatoxins were addressed whenever relevant data were available.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

Metabolic surgery can promote comprehensive physiological improvements to alleviate metabolic disorders, particularly for patients with type 2 diabetes. Nevertheless, the therapeutic scope has been limited owing to unexpectedly inconsistent surgical outcomes. Therefore, this study to overcome these obstacles by determining the fundamental mechanism underlying the conflicting outcomes. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified duodenal-jejunal bypass (DJB) procedures, were compared to understand the specific surgical patterns from different perspectives comprehensively. Patients in the nonobese group were exclusively included to prevent confounding effects from overweight patients with type 2 diabetes. Following intestinal anastomosis, the epithelial identity of the succeeding intestine was replaced by that of the proximal epithelium owing to altered crosstalk between the epithelium and opposing mesenchymal cells. Subsequent intestinal compensatory proliferation and rapid turnover rate accelerate the spread of the replaced epithelium. The main factors contributing to inconsistent outcomes of metabolic surgery are inadequate duodenal exclusion and inappropriate biliopancreatic limb length. Replacement of enteroendocrine cells during regeneration can lead to inconsistent outcomes in metabolic surgery. The type and density of enteroendocrine cells distributed at the terminal end of the proximal intestine play a significant role in diverse outcomes of metabolic surgery.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

This study leverages the relationships between the Great Plains low-level jet (GP-LLJ) and the circumglobal teleconnection (CGT) to enhance the 30-day rainfall forecast skill in the Northern Great Plains (NGP). The assessment of 30-day simulated precipitation using the Climate Forecast System (CFS) is contrasted with the North American Regional Reanalysis, searching for sources of precipitation predictability associated with extended wet and drought events. We analyze the 30-day sources of precipitation predictability using (1) the characterization of dominant statistical modes of variability of 900-mb winds associated with the GP-LLJ, (2) the large-scale atmospheric patterns based on 200-mb geopotential height (HGT), and (3) the use of GP-LLJ and CGT conditional probability distributions using a continuous correlation threshold approach to identify when and where the forecast of NGP precipitation occurs. Two factors contributing to the predictability of precipitation in the NGP are documented. We found that multi-scale geospatial interactions occur at the daily and sub-seasonal time windows. The CFS reforecast suggests that the ability to forecast sub-seasonal precipitation increases in response to the enhanced simulation of the GP-LLJ and CGT. Finally, the multi-dimensional analysis of covariance reveals that high-precipitation forecasting skill is associated with a better prognostic of GP-LLJ and CGT.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

With the ongoing COVID pandemic, the emergence of a novel omicron variant in November 2021 has chaos the world. Despite mass vaccination, this omicron has spread rapidly raising concerns around the globe. The Omicron variant has a vast array of mutations as compared to another variant of concern with overall 50 mutations where 30 mutations are present in its spike protein. This mutation has led to immune escape and more transmissibility compared to other variants, including Delta. A cluster of mutations (H655Y, N679K, and P681H) present at the omicron spike protein could aid in transmission. Currently, no virus-specific data are available to predict the efficacy of anti-viral and mAbs drugs. However, two monoclonal antibody drugs: Sotrovimab and Evusheld are authorized for emergency use in COVID patients. This virus is not fading away soon. The easiest solution and less expensive measure to fight against this pandemic are following COVID appropriate protocols.There is need to strengthen the level of research for development of potential vaccines and anti-viral drugs. It is also important to monitor and expand genomic surveillance to keep track of the emergence of new variants thus avoiding the spread of new diseases worldwide. This article highlights the emergence of omicron and vast number of mutation in its protein. In addition, recent advancement in drugs approved by FDA to treat COVID patients has been listed and focused in this paper.

Despite the ongoing land administration reforms being implemented across sub-Saharan Africa (SSA), including Ghana as viable pathway to achieve tenure security and greater efficiency in land administration, the subject of land dispute resolution has received relatively less attention. Whereas customary tenure institutions play a central role in land administration (controlling ~80% of all land in Ghana), they remain at the fringes of the formal land dispute adjudicatory process. Recognizing the pivotal role traditional institutions as development agents and potential vehicles for promoting good land governance, recent discourse on land tenure have geared towards mainstreaming traditional land disputes institutions into the architecture of formal judicial process via alternative dispute resolution pathways. Yet little is known at least empirically as to the operations of traditional dispute resolution institutions in the contemporary context. This study therefore explores the importance of traditional dispute resolution institutions in the management of land-related disputes in southcentral and western Ghana. Drawing on data collated from 380 farming households operating 746 plots. The results show that contrary to the conventional thinking that traditional institutions are anachronistic and not fit for purpose, they remain strong and preferred forum for land dispute resolution (proving resilient and adaptable) given the changing socio-economic and tenurial conditions. Yet these forums have differing implications for different actors within the customary spheres accessing them. The results highlight practical ways for incorporating traditional dispute resolution in the overall land governance setup in Ghana and elsewhere in sub-Saharan Africa. This has implications for redesigning context-specific and appropriate land-use policy interventions that address local land dispute resolution.

This study investigated the speciation, transformation and availability of P during indigenous vegetable production by employing a combination of chemical and spectroscopic techniques. The study focused upon sites in two ecozones of SSA, the Dry Savanna (lna, Benin Republic) and Rainforest (Ilesha, Nigeria). Both sites were cultivated with two indigenous vegetable species; local amaranth (Amaranthus cruentus (AV)) and African eggplant (Solanum macrocarpon (SM)). The soils were treated with 5 t/ha poultry manure and urea fertilizer at the rate of 0, 20, 40, 60 and 80 kg N/ha. Soil samples were collected before planting and after harvest. Phosphorus K-edge X-ray absorption near-edge structure (XANES) spectroscopy was used to determine P speciation in these soils. Quantitative analysis showed that adsorbed and organic P were the two dominant P species in the manure amended Dry Savanna (DS) soils before planting and after harvest in soils cultivated with both AV and SM, with the addition of urea (40 kg N/ha) causing an increase in the organic P form in Dry Savanna soils cultivated with AV. Soils of the Rainforest (RF) cultivated with AV initially had large amounts of apatite P in the manure amended soils prior to planting which was transformed to adsorbed and organic P after harvest. Urea addition to the Rainforest soils shifted the dominant P species from organic P to adsorbed and apatite P, which is likely to limit P availability. Soils cultivated with SM had similar proportions of both organic and adsorbed P forms, with 40 kg N/ha addition slightly increased the proportion of adsorbed P.

In the present work we study the properties of geodesic sub-$ (\alpha,b,s) $-preinvex functions on Hadamard manifolds and establish some basic properties in both general and differential cases. Further, we study sufficient conditions of optimality and proved some new inequalities under geodesic sub-($ \alpha,b,s $)-preinvexity.

Background: This study analyzes sex-based differences in renal structure and response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Methods: ApoE-/- mice (8 weeks old) received enalapril (5 mg/kg/day, subcutaneous) or PBS as a control for an additional 14 weeks. Each group consisted of six males and six females. Results: Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in females), and the hypertrophy of PECs in males. Conclusion: This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

Epithelial-to-mesenchymal transition (EMT) plays a role in chronic obstructive pulmonary diseases (COPD). Cyclic adenosine monophosphate (cAMP) can inhibit transforming growth factor-β1 (TGF-β1) mediated EMT. Although compartmentalization via A-kinase anchoring proteins (AKAPs) is central to cAMP signaling, functional studies on their therapeutic value in the lung EMT process are lacking. Bronchial epithelial (BEAS-2B, primary HAE cells) were exposed to TGF-β1. Epithelial (E-cadherin, ZO-1) and mesenchymal markers collagen Ӏ (mRNA, protein) were analyzed. St-Ht31 disrupted AKAP-PKA interactions. TGF-β1 release was measured by ELISA. TGF-β1-sensitive AKAPs Ezrin, AKAP95 and Yotiao were silenced using siRNA. Cell migration was analyzed by wound healing assay, xCELLigence, Incucyte. Prior to TGF-β1, dibutyryl-cAMP (dbcAMP), fenoterol, rolipram, cilostamide, forskolin were used to elevate intracellular cAMP. TGF-β1 induced morphological changes, decreased E-cadherin but increased collagen Ӏ and cell migration, a process reversed by PF-670462. TGF-β1 altered (mRNA, protein) expression of Ezrin, AKAP95 and Yotiao. St-Ht31 decreased E-cadherin (mRNA, protein), but counteracted TGF-β1-induced collagen Ӏ upregulation. Cigarette smoke (CS) increased TGF-β1 release, activated TGF signaling, augmented cell migration and reduced E-cadherin expression, a process blocked by TGF-β1 neutralizing antibody. Silencing of Ezrin, AKAP95 and Yotiao diminished TGF-β1-induced collagen Ӏ expression, as well as TGF-β1-induced cell migration. Fenoterol, rolipram, and cilostamide, in AKAP silenced cells pointed to distinct cAMP compartments. We conclude that Ezrin, AKAP95 and Yotiao promote TGF-β1-mediated EMT, linked to a TGF-β1 release by CS. AKAP members define the ability of fenoterol, rolipram and cilostamide to modulate the EMT process, and are potential relevant targets in the treatment of COPD.

In this paper, we succeed to discover the new exact wave solutions to the truncated M-fractional complex three coupled Maccari’s system by utilizing the Sardar sub-equation scheme. The obtained solutions are in the form of trigonometric and hyperbolic forms. These solutions have many applications in nonlinear optics, fiber optics, deep water-waves, plasma physics, mathematical physics, fluid mechanics, hydrodynamics and engineering where the propagation of nonlinear waves is important. Achieved solutions are verified with the use of Mathematica software. Some of the achieved solutions are also described graphically by 2-dimensional, 3-dimensional and contour plots with the help of Maple software. The gained solutions are helpful for the further development of concerned model. Finally, this technique is simple, fruitful and reliable to handle the nonlinear FPDEs.

In this paper, we prove that the sub convexlikeness introduced by V. Jeyakumar [1], and the subconvexlikeness defined in V. Jeyakumar [2] are equivalent in loccallly convex topological spaces. And then, we work with set-valued vector optimization problems and obtain some vector saddle-point theorems and vector Lagrangian theorems.

The essential oils (EOs) obtained from aromatic plants are rich in natural compounds with interesting biological effects. The aim of this study was to evaluate the chemical composition of EOs of Mentha pulegium (MP-EO) and Mentha suaveolens (MS-EO) collected from Morocco, and their antioxidant properties and antibacterial activity against Salmonella enterica and Listeria monocytogenes. The EOs were extracted by hydro-distillation, while the chemical compositions were determined by GC-MS. The antioxidant activity was evaluated by DPPH and FRAP assay. Antibacterial activity was tested with disc diffusion assay; determination of minimum inhibitory concentration, minimum bactericidal concentration and the evaluation of sub-lethally injured cell were also performed. The results of chemical composition showed the presence of compounds not still reported in EOs obtained from these plants. MS-EO was characterized by the best antioxidant and antibacterial activity vs S. enterica and L. monocytogenes respect to MP-EO. The EOs tested in this study were rich in compounds with interesting activities and they could be applied in the medical fields, as well as in food industries as natural preservatives against tested food borne pathogens.

Effective discharge, which represents the flow, or range of flows, that transport the most sediment over long term, was determined based on the mean daily flow discharge and mean daily suspended sediment discharge recorded between 1994 and 2014 at four gauging stations along the Trotuș River. This study proposes an efficient method for the estimation of effective discharge based on observed values of the suspended sediment load. By employing this method the suspended sediment load is no longer either under- or overestimated as in the cases when the assessment is based on sediment rating curves. The assessment on effective discharge was performed at two distinct levels: for the entire data series during the investigated time spans and, subsequently, for flows less than the bankfull discharge. The effectiveness curves of the suspended sediment transport characteristics revealed highly multimodal characteristics with many peaks, indicating ample ranges for the effective discharges. The main effective discharge corresponded to large flood events, which are typical for the upper end of the discharge range, whereas the secondary effective discharges corresponded to sub-bankfull flows, which are more frequent. The changes that occurred in the channel bed are reflected by the temporal variations in the effective discharge.

The main objective of this study was to compare the removal efficiency of nutrients using Lactuca sativa, Medicago sativa and Phragmites australis in subsurface flow constructed wetlands with horizontal flow. In order to test water quality, fabricated reactors designed and the plants cultivated in the soil while their root were inside the wastewater. A long time study carried out from spring till end of autumn (9 months) in order to evaluate the difference in removal rate based on the seasonal changes. The highest removal rate was during summer which followed by spring and autumn. Thus, the effect of plants on the removal efficiency of organic matter (COD, BOD), TSS and nutrient (P and TN) appeared to be dependent on the seasonal growth. Phragmites australis the most sensitive species in order the removal of nutrient from wastewater.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.

Maize is an important staple food crop in sub-Saharan Africa (SSA). However, the average grain yield on farmers’ fields falls considerably short of the demand of the region’s population. In addition, the normal endosperm maize widely consumed in SSA is deficient in vitamin A. Drought, a consequence of climate change, is a major constraint to maize production, resulting in seasonal low grain yield in farmers’ fields. The objectives of this study were to assess the performance of newly developed extra-early maturing provitamin A hybrids under managed drought and well-watered conditions, compare the outcomes of multiple trait base-index and multi-trait genotype-ideotype distance index selection procedures, and identify drought-tolerant hybrids with stable performance across contrasting environments for commercialization in SSA. One hundred and ninety provitamin A hybrids and six checks were evaluated under managed drought and well-watered conditions at Ikenne for two seasons between 2021 and 2023. A 14*14-lattice design was used for the field evaluations under both research conditions. Drought stress was achieved by the complete withdrawal of irrigation water 25 days after planting. Results revealed significant differences among the hybrids under drought and well-watered conditions. Grain yield, ears per plant, and plant aspect under managed drought were correlated to the same traits under well-watered conditions suggesting that the expression of these traits is governed by common genetic factors. Twenty-nine hybrids were identified as top-performing drought-tolerant hybrids by the multiple trait base index and multiple-trait genotype–ideotype distance index. Of the selected outstanding 29 hybrids, 34% were derived from crosses involving the tester TZEEIOR 197, demonstrating the outstanding genetic potential of this inbred line. Further analysis of the 29 selected hybrids revealed TZEEIOR 509 × TZEEIOR 197 as the hybrid that combined the most drought-tolerant adaptive traits. However, the hybrids TZEEIOR 526 × TZEEIOR 97, TZEEIOR 384 × TZEEIOR 30, TZEEIOR 515 × TZEEIOR 249, TZEEIOR 510 × TZEEIOR 197, TZEEIOR 479 × TZEEIOR 197, and TZEEIOR 458 × TZEEIOR 197 were identified as the most stable hybrids across drought and well-watered conditions. These hybrids should be extensively tested in multi-location trials for deployment and commercialization in SSA.

This paper presents a design and performance analysis of a 10-element 5G massive MIMO antenna array for sub-6GHz mobile handsets, specifically for LTE bands 42 (3400-3600 MHz), 43 (3600-3800 MHz), 48/49 (3550-3700 MHz) applications. The proposed antenna array consists of 10 closely spaced linearly polarized inverted-F antennas with a compact size of 20 × 9 mm2 of a single element. The proposed antenna array provides high gain, high efficiency, and low correlation between the antenna elements, which results in improved channel capacity, increased data rate, and enhanced signal quality. The performance of the antenna array is evaluated in terms of the radiation pattern, gain, efficiency, and correlation coefficient. The simulation and measured results show that the proposed antenna array achieves an approximate peak gain of 3.1 dBi at the resonance frequency, a total efficiency of 65 %, and a low correlation coefficient of 0.06 between the antenna elements. Therefore, the proposed 5G massive MIMO antenna array is a promising candidate for sub-6 GHz mobile handsets, particularly for LTE bands 42/43/48/49 applications.

The holy grail of Artificial Intelligence (AI) has been to mimic human intelligence using computing machines. Autopoiesis which refers to a system with well-defined identity and is capable of re-producing and maintaining itself and cognition which is the ability to process information, apply knowledge, and change the circumstance are associated with resilience and intelligence. While classical computer science (CCS) with symbolic and sub-symbolic computing has given us tools to decipher the mysteries of physical, chemical and biological systems in nature and allowed us to model, analyze various observations and use information to optimize our interactions with each other and with our environment, it falls short in reproducing even the basic behaviors of living organisms. We present the foundational shortcomings of CCS and discuss the science of infor-mation processing structures (SIPS) that allows us to fill the gaps. SIPS allows us to model su-per-symbolic computations and infuse autopoietic and cognitive behaviors into digital machines. They use common knowledge representation from the information gained using both symbolic and sub-symbolic computations in the form of system-wide knowledge networks consisting of knowledge nodes and information sharing channels with other knowledge nodes. The knowledge nodes wired together fire together to exhibit autopoietic and cognitive behaviors.

On 9 March 2020, two cases of COVID-19 were reported in Burkina Faso. As of 10 April 2020, a total number of 484 cases (404 cases in the Kadiogo province) were reported nationwide. Real-time forecasts of COVID-19 are important to inform decision-making in the country. Here, we propose an approach that tests the performance of four models (Exponential Growth model, the Generalized Growth model (GGM), the Generalized Logistic Growth, and Richards Growth model) to select the model that best fit data and to generate short-term forecasting (5-, 10-, and 15-day forecasts from 11 to 25 April 2020) in Kadiogo, the epicenter of the outbreak. Using daily number of confirmed COVID-19 cases, the results suggests that GGM performed the best out of the 4 models. Overall, our GGM predictions suggested an average total number of cumulative cases of 514 (95% CI, 464–559), 629 (95% CI, 559–691), and 750 (95% CI, 661–840) between 11 to 15 April, 16 to 20 April, and 20 to 25 April 2020, respectively. COVID-19 in this province was best approximated by sub exponential growth rather than exponential or logistic growth. Current data suggest that COVID-19 cases would continue to increase over the next 15-days.

Titanium micro-scale topography results in excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1–5 µm) and sub-micro-scale (0.1–0.5 µm) topographies and machined titanium. Average roughness was 12.5 ± 0.65 nm, 123 ± 6.15 nm, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. The micro-rough surface showed the fewest cells attaching during the initial stage and the lowest proliferation. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface and lowest on the machined surface. Bone-to-implant integration was strongest for the micro-rough surface, consistent with it having the greatest ability to retain cells in vitro. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation and enhances the rate of osteoblastic differentiation over that of micro-rough titanium; however, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking compared to that of micro-rough titanium.

By imposing the condition of non-vanishing expectation values for the amplitude and phase of field operators, pure quantum states are identified composed of two consecutive number states. These pure states also deliver noise-free radiation modes restricting the “half-photon noise” to the expectation value of the lowest level of dynamic and coherent number states. As a result, instantaneous phase-sensitive amplification of photons is easily controlled and direct evaluation of time or distance - varying wavefront distributions of photons and phases can be carried out for sub-Poissonian distributions of photons without the need for quasi-probabilities.

Technology is in the way to reaching in its climax but the basic understanding of science in many phenomena is still awaited. Scientific research reveals strong analogy between electron and photon. Atoms that execute suitable electronic transitions, on absorbing heat energy at shunt level, excite their electrons. De-excitation of an electron under the gravitational force of its nucleus, where inertia is involved, results depicting energy in the shape like Gaussian distribution. The wavelength of photon remains in inter-state electron’s gap where the source of generating energy in wave-like fashion is due to electronic transitions under confined electron-dynamics; energy configures under electron’s trajectory in the excitation period is due to inertia-levitation-inertia behaviours while energy configures under electron’s trajectory in the de-excitation period is due to inertia-gravitation-inertia behaviours. Silicon atom is a model system of it. Uninterrupted confined inter-state electron-dynamics results into configure energy in a wave-like fashion that can travel immeasurable length and on interruption from the point of generation, it becomes a photon. Such photons increase wavelength on decreasing energy while travelling through inherently built gap of splitted inert gas atoms where they give light (glow) on reaching wavelength in the visible range. Here, I discuss that heat energy is due to merged photons, photons characteristic current are due to photons having wavelength in inter-state electron’s gap and light is due to photons, following the wavelength in the visible range. Force of repulsion or attraction in certain materials engages the phenomenon of levitism or gravitism where inertia is exempted. All structural motifs and dynamics are subjected to characteristic photons as long as atoms are under neutral behavior of field force. A structural design delivers straight-forward application on dealing photons at different wavelengths. Here, materials science explores matter at electronic level while absorbing heat energy and generating photon energy. Thus, devise science to describe.