Background: Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC) and inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1ß and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. Design, Setting, and Participants: The study included two independent cohorts of n=92 and n=102 patients who underwent radical cystectomy for BC. Specimen from BC and benign urothelium (n=22 and n=39) were processed to a tissue microarray and immunohistochemically stained for IL-1ß, IL-1RA, AKT and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. Outcome measurements and statistical analysis: Association with outcome was assessed using Wilcoxon Kruskal-Wallis tests, Chi-square tests or linear regression, dependent on the variable’s category. Kaplan–Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Results: Both, IL-1ß and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p<0.005). IL-1ß was associated with vascular invasion (210 vs. 183, p<0.02), lymphatic invasion (210 vs. 180, <0.05) and G3 cancer (192 vs. 188, <0.04). Survival analysis revealed favorable RFS, CSS, and OS in case of high IL-1ß expression (p<0.02, <0.03 and <0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1ß expression on RFS, CSS and OS. IL-1ß and IL-1ß/IL-1RA ratio were positively correlated to AKT expression (p<0.05 and <0.01, respectively). Additionally, high expression of Ki-67 (>15%) correlated with higher levels of IL-1β (p=0.01). Conclusions: Overexpression of IL-1ß and IL-1RA is frequently found in BC, with a prognostic significance observed for IL-1ß protein expression. The observed link between the IL-1ß / IL-1RA axis and AKT signaling may indicate possible autophagy activation processes beside the known tumor-promoting effects of AKT.

Pre-eclampsia is a hypertension disorder during pregnancy, significantly affects maternal morbidity and mortality worldwide. A Case-control research was done on 100 pregnant mothers as respondents: 50 case (pre-eclampsia) and 50 control groups (healthy pregnant mothers). Selected case the following characteristics: were patients that visited the Syamrabu Bangkalan Public Hospital; were third-generation Madura natives; aged between 20-40 years old; had a gestational age of over 20mgg; had blood pressure above 140/90mmHg; and single pregnancies. Control had the following characteristics: were healthy pregnant women without pre-eclampsia or chronic hypertension; were third-generation Madura natives; had a gestational age of over 20mgg; aged between 20-40 years; and without pregnancy complications. The results showed of those with PE, 45 had the AA genotype (homozygote) (90%), five had AC (heterozygote) (8%) and one had CC (homozygote) (2%). As for those without PE, 33 had the AA genotype (homozygote) (73.3%), 11 had AC (heterozygote) (26.7%), none had CC (homozygote) (0%). PE and non-PE cases mostly had the AA genotype (homozygote) and A alleles. AT1R 1166 A/C polymorphism was found to be a significant risk factor for pre-eclampsia, while potassium level had no significant effect on it. Meaning further research is needed on different ethnicities and races.

Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The aim of the present study was to assess the impact of pretreatment serum levels of 27 selected cytokines on progression-free survival (PFS) and overall survival (OS) in MM patients before first-line therapy with bortezomib-based regimens. Serum cytokine levels were assayed with a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad) including IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. A total of 61 MM patients were examined. Most patients received a bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy regimen. In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240-0.8291, p = 0.0302), and ASCT (HR 0.3722, 95% CI: 0.1826-0.7585, p=0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046-0.438, p=0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471-9.949, p=0.0059) and two cytokine levels- IL-1Ra (HR 1.017, 95% CI: 1.004-1.030, p= 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037-0.698, p = 0.0147) were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.

A novel coronavirus (2019-nCoV) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. 2019-nCoV was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Previous studies have found ACE2 is abundantly present in humans in the epithelia of the lung and small intestines, and they found ACE2 expression in the basal layer of the non-keratinizing squamous epithelium in nasal and oral mucosa and the nasopharynx. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 expression in the nasal, mouth, lung, and colon tissues. We find that the number of ACE2-expressing cells in the nasal tissue and mouth is comparable to the number of ACE2-expressing cells in the lung tissue and colon. We also find that ACE2 tends to be co-expressed with HLA-DRB1, which plays a central role in the immune system by presenting peptides derived from extracellular proteins, in the nasal, mouth, lung, and colon tissues at single-cell resolution. We hope this provides valuable information for virus-prevention strategy and therapeutic strategy development.

Zika virus (ZIKV) is a notable arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV infection has been linked to variations in endogenous retroviruses (ERVs) and interleukins within the placenta. ERVs, remnants of ancient viral infections integrated into the genome, include syncytin receptors crucial for placental development. Interleukins, immune response regulators, aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. Since ZIKV can infect trophoblast cells, we investigated the relationship between ZIKV infections and ERV and interleukin modulations. Investigating the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asia-Brazilian) using Taqman and RT2 Profiler PCR Array assays. While early ZIKV infection (24-48 hours) did not induce differential ERV and interleukin expression, future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and cytokines essential for placental formation and function.

This paper presents a system for identification of wind features, such as gusts and wind shear. These are of particular interest in the context of energy-efficient navigation of Small Unmanned Aerial Systems (UAS). The proposed system generates real-time wind vector estimates and a novel algorithm to generate wind field predictions. Estimations are based on the integration of an off-the-shelf navigation system and airspeed readings in a so-called direct approach. Wind predictions use atmospheric models to characterize the wind field with different statistical analyses. During the prediction stage, the system is able to incorporate, in a big-data approach, wind measurements from previous flights in order to enhance the approximations. Wind estimates are classified and fitted into a Weibull probability density function. A Genetic Algorithm (GA) is utilized to determine the shaping and scale parameters of the distribution, which are employed to determine the most probable wind speed at a certain position. The system uses this information to characterize a wind shear or a discrete gust and also utilizes a Gaussian Process regression to characterize continuous gusts. The knowledge of the wind features is crucial for computing energy-efficient trajectories with low cost and payload. Therefore, the system provides a solution that does not require any additional sensors. The system architecture presents a modular decentralized approach, in which the main parts of the system are separated in modules and the exchange of information is managed by a communication handler to enhance upgradeability and maintainability. Validation is done providing preliminary results of both simulations and Software-In-The-Loop testing. Telemetry data collected from real flights, performed in the Seville Metropolitan Area in Andalusia (Spain), was used for testing. Results show that wind estimation and predictions can be calculated at 1 Hz and a wind map can be updated at 0.4 Hz. Predictions show a convergence time with a 95% confidence interval of approximately 30 s.

The soil organic matter (SOM) content and stability in natural gypsum soils and soils from mining/industrial areas were compared, in terms of their physical, chemical and micromorphological properties, to determine whether the old brownfield soils were acting as carbon (C) sinks, counteracting increasing carbon dioxide concentrations in the atmosphere. The mining/industrial soils were 50–400 years old, so had been left sufficiently long for full self-restoration. Despite having very different origins, both natural and brownfield soils stored similar amounts of SOM, and had similar pH values, calcium carbonate contents and textures. They were also fully covered with similar grass plant communities. The mining/industrial soils exhibited similar microstructures to the gypsum soils and were often quite porous. The most striking difference between them and the natural gypsum soils was that the mining/industrial soils were strongly polluted with zinc, lead and cadmium. The 50-year-old brownfield soils differed from the others in terms of having a lower state of SOM transformation, with a much higher C/N ratio, lower aggregate water resistance index, lower dehydrogenase activity and greater areas of undecomposed or slightly decomposed plant residues. These parameters in the older (150–400 years) brownfield soils were similar to those of the natural soils.

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

We report the relative humidity (R.H.) sensing response of a resistive sensor, employing sensing layers based on a ternary nanohybrid comprising holey carbon nanohorns (CNHox), potassium chloride (KCl), and polyvinylpyrrolidone (PVP) at mass ratios 7/1/2, 6.5/1.5/2, and 6/2/2 (w/w/w/w). The sensing structure comprises a silicon substrate, a SiO2 layer, and interdigitated transducer (IDT) electrodes. The sensing film is deposited on the sensing structure via the drop-casting method. The sensing layers' morphology and composition are investigated through Scanning Electron Microscopy (S.E.M.) and RAMAN spectroscopy. The ternary hybrid-based thin film resistance increases when the sensors are exposed to R.H., ranging from 0% to 100%. The manufactured devices show a room temperature response comparable to a commercial capacitive R.H. sensor and are characterized by excellent linearity, rapid response time, and good sensitivity. The presented sensors exhibit superior performance in terms of sensitivity compared to other similarly manufactured and tested sensors that employ a CNHox-based sensing layer. We explain the sensing role of each constituent of the ternary hybrid nanocomposites based on their chemical and physical properties, electronic properties, and affinity for water molecules. Different alternative sensing mechanisms are considered and discussed, such as the decreasing number of holes in the holey CNHox at the interaction with water molecules, proton conduction, and PVP swelling.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

In this paper the one-to-one correspondences and equivalences between ideals, primals, filters and grills are introduced. It is shown the local functions and the topological spaces induced by them are the same. From this point of view, the topological properties with respect to one topology can be derived from topological properties valid in the corresponding topology.

Background: Monocyte-derived dendritic cells (mo-DCs) play a vital role in the innate immune response by activating Th17 cells, which in turn release the pro-inflammatory cytokine IL-17. We hypothesised that following repetitive mechanical strain, tenocytes activate monocyte-derived dendritic cells, which in turn, drive the pathogenesis of tendinopathy. Aim: The aim of the study was to determine if monocyte-derived dendritic cells are upregulated in a human tendinopathy model. Method: Torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from 7 patients undergoing arthroscopic shoulder surgery. Healthy control samples of subscapularis tendon were collected from 5 patients undergoing arthroscopic stabilization surgery. Tendon biopsy samples were evaluated immunohistochemically by quantifying the presence of monocyte-derived dendritic cells (CD11C and CD206). Results: Tendinopathic tendon samples exhibited significantly greater (2-3-fold) monocyte-derived dendritic cell expression when compared with healthy control tissue (P < .05). Conclusion: This study provides evidence for a monocyte-derived dendritic cell upregulation in early-stage human tendinopathy.

A method based on ultra performance liquid chromatography with diode array detector (UPLC-DAD) was developed for quantitative analysis of five active compounds and chemical fingerprint analysis of Rosa rugosa. Ten batches of Rosa rugosa collected from different plantations in the Xinjiang region of China were used to establish the fingerprint. The feasibility and advantages of the used UPLC fingerprint were verified for its similarity evaluation by systematically comparing chromatograms with professional analytical software recommended by State Food and Drug Administration (SFDA) of China. In quantitative analysis, the five compounds showed good regression (R²=0.999 5) within the test ranges and the recovery of the method was in the range of 94.2–103.8%. The similarities of the fingerprints of 10 batches of the samples were more than 0.981. The developed UPLC fingerprint method is simple, reliable and validated for the quality control and identification of Rosa rugosa. Additionally, simultaneous quantification of five major bioactive ingredients in the Rosa rugosa samples was conducted to interpret the consistency of the quality test. The results indicated that the UPLC fingerprint as a characteristic distinguishing method combining similarity evaluation and quantification analysis, can be successfully used to assess the quality and to identify the authenticity of Rosa rugosa.

The article presents a model for optimizing biomass supply chains using the linear programming framework integrated with a Geographic Information System. Based on the distance from a given type of biomass resource, its calorific value, price, and transportation costs, the model identifies the optimal source of biomass, allowing it to cover the demand for the required total energy value with the lowest possible costs. The case study includes the Połaniec power plant in southeastern Poland and potential sources of forest biomass and agricultural straw within 100 km of the plant. Unit costs of biomass varied depending on biomass availability and energy demands. For energy demand on the level of 1 PJ yearly, the lowest unit costs of biomass (4.08 €/MJ) were when all kinds of biomass were available, and the highest (5.47 €/MJ) was when only stacked wood was available. As energy demand increased, unit costs increased, and the ability to meet this demand with just one type of biomass decreased. The energy biomass sector can utilize the model to benefit both biomass producers and their final buyers.

Miniature sensors are key components for the applications in the Internet of Things (IoT), wireless sensor networks, autonomous vehicles, smart cities and smart manufacturing. As a miniature and self-powered magnetic sensor, Wiegand sensor possesses the advantageous traits including changing-rate-independent output, low cost, and remarkable repeatability and reliability. Typical Wiegand sensor requires hard magnetic pole pieces that provide external fields for triggering voltage outputs that are called Wiegand pulses. However, the wire-shaped sensing element of Wiegand sensor is the critical issue that limits the design, selection, and adoption of the external triggering magnets. Currently, the widely used pole piece materials are rare-earth magnets. However, adopting rare-earth magnets brings strong stray fields, causing electromagnetic interference (EMI) problem. In this study, patterned CoNiP hard magnets were electrodeposited on flexible substrates through microfabrication. Origami magnetization was utilized to control the resultant stray fields, and hence the pole piece of CoNiP magnets can successfully trigger the output of Wiegand pulse. In comparison, the output voltage of the triggered pulse acquired through the patterned CoNiP magnets is comparable to that by using the rare-earth magnets. Furthermore, both the volume (meanwhile the weight) of the Wiegand sensor and the EMI issue can be significantly reduced and mitigated by the CoNiP magnets.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p<0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

Abstract: Objectives: To establish the expression profile of N6-methyladenosine(m6A) modifications in the hippocampus of mice with diabetic cognitive impairment (DCI) and elucidate the potential regulatory mechanism. Methods: A DCI model was established by feeding a high-fat diet to C57BL/6J mice. m6A and RNA sequencing was conducted to profile the m6A-tagged transcripts in the hippocampus. Results: Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing analyses yielded differentially m6A-modified and expressed genes in the hippocampus of DCI mice, which were enriched in pathways involving synaptic transmission and axonal guidance. Mechanistic analyses revealed a remarkable change in m6A modification levels through alteration of the mRNA expression of m6A methyltransferases (METTL3 and METTL14) and demethylase (FTO) in the hippocampus of DCI mice. Conclusions: We identified a co-mediated specific RNA regulatory strategy that broadens the epigenetic regulatory mechanism of RNA-induced neurodegenerative disorders associated with metabolic and endocrine diseases.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

Background: The aim of this experimental work was to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants, all the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female and the presence of sex-linked features. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, and can be a valid tool in gender determination but the absence of a database greatly limits its use. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

The involvement of NK and other cytotoxic cells is considered the first defense' line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells, the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers, some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. Despite having demonstrated multiple correlations, it should be noted that immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality, mainly attributed to accelerated atherosclerosis. Methods: Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. Biomarkers of inflammation, red blood cells (RBCs) redox balance, estrogen receptor alpha (ER-α) expression as well as ERK 1/2 phosphorylation content were evaluated in RA patients at baseline and six months after treatment with disease modifying anti‐rheumatic drugs (DMARDs). Results: For the first times we demonstrated that in RA patients: i) disease activity score (DAS-28) positively correlated with RBC ER-α expression, and negatively with total antioxidant capacity of plasma; ii) RBC ER-α expression positively correlated with systemic inflammatory biomarkers and oxidative stress parameters as well as ERK 1/2 phosphorylation; and iii) DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. Conclusion: Our data strongly suggest that RBCs could also participate in vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.

Acute myeloid leukemia (AML) is a hematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterized as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukemias. Furthermore gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications and chromatin remodelling. However, recently, RNA modification (m6A-methylation) also termed ‘epitranscriptomics’ has emerged as a new layer of epigenetic regulation due to its diverse role in various biological processes. In this review, we have summarized the therapeutic potential of m6A-modifiers in controlling haematological disorders especially acute myeloid leukemia (AML). It is a type of blood cancer affecting specific subsets of blood-forming hematopoietic stem/progenitor cells (HSPCs) which proliferate rapidly and acquire self-renewable capacities with impaired terminal cell-differentiation and apoptosis leading to abnormal accumulation of white blood cells, and thus an alternative therapeutic approach is required urgently. Here, we have described how RNA m6A-modification machineries EEE (Editor/writer: Mettl3, Mettl14; Eraser/remover: FTO, ALKBH5 and Effector/reader: YTHDF-1/2) could be reformed into potential druggable candidate or as RNA modifying drug (RMD) to treat leukemia. Moreover, we have shed-light on the role of microRNA and suppressor of cytokine signalling (SOCS/CISH) in increasing anti-tumor immunity towards leukemia. We anticipate, our investigation will provide a fundamental knowledge in nurturing the potential of RNA modifiers in discovering novel therapeutics or immunotherapeutic procedures.

Staphylococcus aureus is a Gram-positive bacterium causing a range of mild to life-threatening infections including bone infections such as osteomyelitis. S. aureus is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study four different S. aureus strains, 2SA-ST239-III, 5SA-ST5-II, 10SA-ST228-I, and 14SA-ST22-IVh were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following a successful invasion and persistence. Methicillin-sensitive S. aureus (MSSA) ATCC-12598-ST30 was used as control. Despite the demonstrated similar abilities of internalization and persistence of ATCC-12598-ST30, 2SA-ST239-III, and 14SA-ST22-IVh strains in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the decrease in cell viability was due to the different behavior of the considered strains, with the number of intracellular bacteria playing a limited role. We focused our attention on different cellular biochemical functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show that: 1) ATCC-12598-ST30 and 2SA-ST239-III were the only two clones able to persist and maintain their number into the cellular hostile environment during the entire period of infection; 2) 2SA-ST239-III was the only clone able to significantly increase the gene expression (3 and 24 h) and protein secretion (24 h) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; 3) the same clone determined a significant up-regulation of transforming growth factor-β1 (TGF-β1) and the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h post infection; 3) neither the MSSA nor the four MRSA strains induced oxidative stress phenomena in MG-63 cells, although a very different expression pattern towards nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation was observed among the different clones. Our results can open a new way of considering therapies, going in the direction of an individualized therapeutic strategy that should take into account the difference existing between MSSA and MRSA as well as the distinctive features of the different clones. Not only, therefore, a different antibiotic approach but also a starting point for considering different host factors, i.e. the modulation of specific cytokines such as IL-6, TNF-α, and TGF-β1.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

The relationship between perception of anxiety and quality of life in caregivers of children with autism was verified. To verify quality of life, the Short Form Healthy Survey Item was used; perception of anxiety was assessed using the Beck Anxiety Inventory. 80 caregivers of children with autism participated, with 68.7% of caregivers being mothers. Of the total number of caregivers, 68.8% had a severe level of anxiety. Regarding quality of life, they demonstrated greater impairment in Limitation due to physical aspects, Limitation due to emotional aspects, Vitality and Pain. Caregivers with severe anxiety levels had worse quality of life in the domains of pain (p = 0.012), social aspects (p =< 0.001), limitation due to emotional aspects (p = 0.001) and mental health (p =< 0.001). However, in the functional capacity domain, caregivers with a moderate level of anxiety had a better physical capacity score (p = 0.001). There was a negative correlation between the general anxiety score and the general physical (p = 0.029) and general emotional component of quality of life (p =< 0.001). It was found that caregivers of children with ASD present losses related to psychological factors, quality of life and the lack of social support.

Large-scale hydrological modeling in China is challenging given the sparse meteorological stations and large uncertainties associated with atmospheric forcing data.Here we introduce the development and use of the China Meteorological Assimilation Driving Datasets for the SWAT model (CMADS) in the Heihe River Basin(HRB) for improving hydrologic modeling, by leveraging the datasets from the China Meteorological Administration Land Data Assimilation System (CLDAS)(including climate data from nearly 40000 area encryption stations, 2700 national automatic weather stations, FengYun (FY) 2 satellite and radar stations). CMADS uses the Space Time Multiscale Analysis System (STMAS) to fuse data based on ECWMF ambient field and ensure data accuracy. In addition, compared with CLDAS, CMADS includes relative humidity and climate data of varied resolutions to drive hydrological models such as the Soil and Water Assessment Tool (SWAT) model. Here, we compared climate data from CMADS, Climate Forecast System Reanalysis (CFSR) and traditional weather station (TWS) climate forcing data and evaluatedtheir applicability for driving large scale hydrologic modeling with SWAT. In general, CMADS has higher accuracy than CFRS when evaluated against observations at TWS; CMADS also provides spatially continuous climate field to drive distributed hydrologic models, which is an important advantage over TWS climate data, particular in regions with sparse weather stations. Therefore, SWAT model simulations driven with CMADS and TWS achieved similar performances in terms of monthly and daily stream flow simulations, and both of them outperformed CFRS. For example, for the three hydrological stations (Ying Luoxia, Qilian Mountain, and ZhaMasheke) in the HRB at the monthly and daily Nash-Sutcliffe efficiency ranges of 0.75-0.95 and 0.58-0.78, respectively, which are much higher than corresponding efficiency statistics achieved with CFSR (monthly: 0.32-0.49 and daily: 0.26 – 0.45). The CMADS dataset is available free of charge and is expected to a valuable addition to the existing climate reanalysis datasets for deriving distributed hydrologic modeling in China and other countries in East Asia.

In this study, we define screening maps for Italy that classify sites based on their potential for triggering landslides. To this end, we analyze seismic hazard maps and hazard disaggregation results on a national scale considering four spectral periods (0.01s, 0.2s, 0.5s, and 1.0s) and three return periods (475, 975, and 2475 years). First, joint distributions of magnitude (M) and distance (R) from hazard disaggregation are analyzed by means of an innovative approach based on image processing techniques to find all modal scenarios contributing to the hazard. In order to obtain the M-R scenarios controlling the triggering of earthquake-induced landslides at any computation node, mean and modal M-R pairs are compared to empirical curves defining the M-R bounds associated with landslide triggering. Three types of landslides are considered (i.e., disrupted slides and falls, coherent slides, and lateral spreads and flows). As a result, screening maps for all of Italy showing the potential for triggering landslides based on the level of seismic hazard are obtained. The maps and the related data are freely accessible at the following web address: https://distav.unige.it/rsni/slideq.php.

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution—a hydrogen peroxide–sodium bicarbonate mixture—on the surface properties and contact angles of and osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and then ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. MG-63 osteoblasts were cultured on the specimens, and their adhesion to the specimen surface and their proliferation were examined using staining and the MTT assay, respectively. Additional etching with the etching solution caused the formation of nano/micro hierarchical structures, increased the surface roughness, and enhanced the hydrophilicity. Osteoblast adhesion and proliferation were found to improve on the modified surfaces. The eco-friendly etching method has the potential to enhance the biological properties of Ti implant surfaces and to thereby improve the dental implant performance.

Apoptosis and cell cycle arrest induction are targeted in the strategy of cancer therapy. Furthermore, bacterial toxin such as shiga-like toxin producing Escherichia coli has been suggested to be used as novel therapeutic agent against tumor malignancies either as independent anti-neoplastic agents or in combination treatment with chemo or radiotherapy. The aim of study was to investigate the potency of shiga-like toxin originated from local strains of E. coli O157:H7 as a new cancer therapy. As many as 10 culture cells T47D cell line were subjected by crude extract Shiga like toxin originated from five local isolates of E. coli O157:H7 i.e. KL-48(2), SM-25(1), SM-7(1), DS-21(4), and one isolate ATCC 43894 as a control with IC50 doses, respectively. The treatment was observed for 24 h, with two replications. An FITC-Annexin V and PI assay was used to observe apoptosis and necrosis effect, and simultaneously with cell cycle analysis using propidium iodide (PI) staining. Results of study showed T47D cell treated with Shiga-like toxin from local strain KL-48 (2) show the lowest viable cell, followed by SM 7(1), ATCC 43894, SM-25(1), DS-21(4) and contrary with control with each percentages as 15.20, 16.36, 22.17, 22.64, 33.86, and 94.36%, respectively. The results were also confirmed by the induction of the cell cycle arrest in phase G0-G1 as inactive phase, i.e. 66.41, 63.37, 61.52, 55.36 and 47.28% for T47D cell treated with toxin of KL-48(2), ATCC 43894, SM 25(1), SM 7(1), and DS 21(4), respectively. These results show tendency deleterious effect of Shiga-like toxin from local isolates on T47D cell, so that concluded they have potency as a good anticancer drug in Gb3-expressing breast cancer.

Companies are increasingly focusing on sustainable business practices. Internal and external stakeholders’ expectations manifest in legal requirements, national and international standards, and market and customer expectations, among other things, must be considered. In addition to profit maximization as the usual target for corporate management, management must consider environmental sustainability aspects such as resource efficiency, greenhouse gas intensity, and a company's emissions behavior. In addition, social aspects relating to the company's employees, the immediate urban environment, the situation in the supply chain, and effects on the market environment must increasingly be considered. Specifically, companies are faced with the chal-lenge of dealing with conflicting objectives regarding the various aspects of sustainability and, if necessary, weighing them up against each other. These trade-offs must be made against the company's socio-economic and ecological environment, corporate strategy, and sustainability goals. This paper provides an overview of current approaches and research gaps on this topic through a literature review. It shows a lack of methods and frameworks to specifically deal with trade-offs and conflicts of goals.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p<0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring V. cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 cholera patients enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titers. At this saliva titer, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between Vibrio Cholerae saliva and serum antibodies (rho=0.66, p<0.001). In conclusion, saliva-based diagnostic cholera tests has high diagnostic accuracy, and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.

Type III interferon (IFN-λs) exhibit potent antiviral activity and immunomodulatory effects in specific cells. Nucleotide fragements of bovine ifn-λ (boifn-λ) gene was synthetized after codon optimization. The boifn-λ gene was then amplified by splicing by overlap extension PCR (SOE PCR), resulting in serendipitous acquisition of the mutated boIFN-λ3V18M. Recombinant plasmids pPICZαA-boIFN-λ3/λ3V18M were constructed and the corresponding proteins were expressed in Pichia pastoris with high-level extracellular soluble form. Dominant expression strains of boIFN-λ3/λ3V18M were selected by Western blot and ELISA, cultured on a large scale, and the recombinant proteins purified by ammonium sulphate precipitation and ion exchange chromatography, yielding 1.5g/L and 0.3 g/L, with 85% and 92% purity, respectively. The antiviral activities of boIFN-λ3/λ3V18M exceeded 106 U/mg, were neutralized with IFN-λ3 polyclonal antibodies, were susceptible to trypsin, and retained stability within defined pH and temperature ranges. Furthermore, boIFN-λ3/λ3V18M exerted antiproliferative effects on MDBK cells without cytotoxicity at 104 U/mL. Overall, boIFN-λ3 and boIFN-λ3V18M did not differ substantially in biological activity, except for reduced glycosylation of the latter. Development of boIFN-λ3 and comparative evaluation with the mutant provide theoretical insights into antiviral mechanisms of boIFN-λs and provide material for therapeutic development.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

Aurora Kinase A being overexpressed in majority of cancers, appear to be an attractive therapeutic target. However, a Phase III clinical trial of Alisertib, a selective AURKA inhibitor, resulted in no better response compared to the comparator arm of chemotherapeutic regimen raising question regarding ability of the same to target the undetectable stem cell functions. In silico analysis indicated regulation of AURKA by the stemness factors Oct4 and Sox2. TCGA data indicated positive correlation of each of the factors with AURKA which were eventually validated in cell lines, patient tissues and blood by flow cytometry along with Oct4 binding on AURKA promoter being detected by ChIP assay. However, indirect immunofluorescence and cell cycle analyses indicated proliferation-independent AURKA functions during asymmetric cell division, a characteristic feature of stem cells. Thorough screening of the AURKA positive cells in patient samples denoted epithelial to mesenchymal transition and significant upregulation of Vimentin, a mesenchymal marker and ABCG2, a drug resistance marker under Oct4 or Sox2 influence. Overall, our study demonstrated combinatorial selection Oct4, Sox2, AURKA, Vimentin and ABCG2 for diagnostics and intervention of circulating breast cancer stem cells as a blood-based, cost-effective and simple approach which will be beneficial in reducing relapse.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells that has a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template in molecular imprinting. The magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs) were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer-Emmett-Teller (BET) analysis and superconducting quantum interference device (SQUID) analysis. Natural killer-92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and the quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found significantly enhance the activity of natural killer cells toward HepG2 cells by increasing expression of NK-kB, caspase 8 and especially caspase 3.

Introduction: Previous studies have suggested that the tyrosine kinase receptor RET plays a sig-nificant role in the hematopoietic potential in mice and could also be used to expand cord-blood derived hematopoietic stem cells (HSCs). The role of RET in the human iPSC-derived hematopoi-esis has not been tested so far. Methods: To test the implication of RET on the hematopoietic potential of iPSCs, we activated its pathway with the lentiviral overexpression of RETWT or RETC634Y mutation in normal iPSCs. An iPSC derived from a patient harboring the RETC634Y mutation (iRETC634Y) and its CRISPR-corrected isogenic control iPSC (iRETCTRL) were also used. Hematopoietic potential was tested using 2D cul-tures and evaluated regarding the phenotype and the clonogenic potential of generated cells. Results: Hematopoietic differentiation from iPSCs with RET overexpression (WT or C634Y) led to a significant reduction in the number and in the clonogenic potential of HSCs (CD34+/CD38-/CD49f+) as compared to control iPSCs. Similarly, the hematopoietic potential of iRETC634Y was reduced as compared to iRETCTRL. Transcriptomic analyses revealed a specific ac-tivated expression profile for iRETC634Y compared to its control with evidence of overexpression of genes which are part of the MAPK network with negative hematopoietic regulator activities. Conclusion: RET activation in iPSCs is associated with an inhibitory activity in iPSC-derived hematopoiesis, potentially related with MAPK activation.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Deep Learning (DL) oriented document processing is widely used in different fields for extraction, recognition, and classification processes from raw corpora of data. The article examines the application of deep learning approaches, based on different neural network methods, including Gated Recurrent Unit (GRU), Long Short-Term Memory (LSTM), and Convolutional Neural Networks (CNN). The compared models were combined with two different word embedding techniques, namely: Bidirectional Encoder Representations from Transformers BERT and Gensim Word2Vec. The models are designed to evaluate the performance of architectures based on neural network techniques for the classification of CVs of Moroccan engineering students at ENSAK(National School of Applied Sciences of Kenitra, Ibn Tofail University). The used dataset included resumes collected from engineering students at ENSAK in 2023 for a project on the employability of Moroccan engineers in which new approaches were applied, especially machine learning, deep learning, and big data. Accordingly, 867 resumes were collected from five specialties of study (Electrical Engineering, Networks and Systems Telecommunications, Computer Engineering, Automotive Mechatronics Engineering, Industrial Engineering). The results revealed good performance of the proposed models based on the BERT embedding approach compared to models based on the Gensim Word2Vec embedding approach. Accordingly, the CNN-GRU/Bert model achieved slightly better accuracy with 0.9251 compared to other hybrid models.

To date, viruses closely related to SARS-CoV-2 have been reported in four bat species: Rhinolophus acuminatus, Rhinolophus affinis, Rhinolophus malayanus, and Rhinolophus shameli. Here, we analysed 343 sequences of the mitochondrial cytochrome c oxidase subunit 1 gene (CO1) from georeferenced bats of the four Rhinolophus species identified as reservoirs of SARS-CoV-2-like viruses. Haplotype networks were constructed in order to investigate patterns of genetic diversity among bat populations of Southeast Asia. No strong geographic structure was found for the four Rhinolophus species, suggesting high dispersal capacity. The ecological niche of SARS-CoV-2 like viruses was predicted using the four localities of bat SARS-CoV-2-like viruses and the localities where bats showed identical or very similar CO1 haplotypes than virus-positive bats. The ecological niche of SARS-CoV-like viruses was deduced from the localities where bat SARS-CoV-like viruses were previously detected. The results show that the ecological niche of SARS-CoV2-like viruses includes several regions of mainland Southeast Asia whereas that of SARS-CoV-like viruses is mainly restricted to China. In agreement with these results, human populations in Laos, Vietnam, Cambodia, and Thailand appear to be much less affected by the Covid-19 pandemic than other countries of Southeast Asia. In the climatic transitional zone between the two ecological niches (southern Yunnan, northern Laos, northern Vietnam, and possibly Hainan and Taiwan), genomic recombination between highly divergent viruses is more likely to occur. Since recombinant viruses can threaten the benefit of vaccination campaigns, these regions should be under surveillance.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

We developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. Near-infrared laser irradiation stimulated the generation of reactive oxygen species, causing short-term reactive molecular species and spatial-temporal restricted photodamage to the biological targets. The reactive molecular species and spatial-temporal restricted photodamage enhanced the release and uptake of chemotherapy drugs and increased the sensitivity to chemotherapy drugs in ovarian cancer cells. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and −27.8 ± 0.42 mV, respectively. SN38/IR820-Lipo@FSH exhibited good drug-loading properties and the in vitro release was slow. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited good tumor-targeting ability and anti-ovarian cancer activity in vivo. The SN38/IR820-Lipo@FSH exhibited specific targeting to A2780 ovarian cancer cells. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the regulation of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats were used (according to Langendorff) to study the effects of capsaicin (CS), capsazepine (CZ) and CZ+CS treatments. The hearts were divided into three subgroups; 1) perfusion, 2) ischemia and 3) ischemia-reperfusion. In all groups we studied cardiac work and levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue. Western blots were used to determine the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac work and the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

There is remarkable morphologic and genetic heterogeneity in acute myeloid leukemia (AML). In a small percentage of cases of AML, increased eosinophils and/or basophils are present in the bone marrow and sometimes in the peripheral blood. This is often a puzzling diagnostic situation but also an important finding that requires special investigation. Unique chromosomal rearrangements have been correlated with an increased number of eosinophils and basophils in AML. Identification of the underlying genetic lesion that promotes eosinophilia and basophilia can dramatically change both the prognosis and the treatment of the patient. Thus clinicians must be vigilant in searching for the cause of eosinophilia and/or basophilia in patients with AML, since the different causes may lead to different treatments and survival outcomes. In this article we examine the significance of increased eosinophils and/or basophils in the context of AML, provide guidance that simplifies the differential diagnosis, and prognostic and therapeutic information about specific subtypes of AML associated with eosinophilia and/or basophilia. Evidence supporting personalized (molecularly targeted) therapy for these patients is also presented.

We propose a method for creating parallel Bessel-like vortical optical needles with an arbitrary axial intensity distribution via superposition of different cone-angle Bessel vortices. We analyze the interplay between the separation of individual optical vortical needles and their respective lengths and introduce a super-Gaussian function as their axial profile. We also analyze the physical limitations to observe well-separated optic needles, as they are influenced by mutual interference of the individual beams. To verify our theoretical and numerical results, we generate controllable spatial arrays of individual Bessel beams with various numbers and spatial separations by altering the spectrum of the incoming laser beam via the spatial light modulator. We demonstrate experimentally how to implement such beams using a diffractive mask. The presented method facilitates the creation of diverse spatial intensity distributions in three dimensions, potentially finding applications in specific microfabrication tasks or other contexts. These beams may have benefits in laser material processing applications such as nanochannel machining, glass via production, modification of glass refractive indices, and glass dicing.

Abstract: Efforts for carbon emission reduction have been identified as a major climate change mitigation target in the Paris Agreement. The 26th Conference of Parties to the United Nations Framework Convention on Climate Change highlighted the worldwide effort for cleaner and greener mining, urging the mineral industry to embrace greener operational emissions reduction technologies and strategies. Ghana pledged at the Paris Conference to reduce CO2 emissions by 15% and increase renewable energy share to 10% of the national energy mix. Here the fundamental question is how Ghana’s mining industry can contribute to CO2 emission reduction efforts. This paper investigates barriers to low-carbon emission policy implementation among mining companies in Ghana. The questionnaire survey was conducted among Ghana’s four large-scale gold mining companies. As the sample number of available companies is limited, we used a descriptive analysis to assess the responses. The results show that the companies expressed widely different ways to respond to the issues of cost, a government policy/regulations for carbon emission reduction, and the adoption/acquisition of low-carbon technologies. Those companies that are relatively less prepared for this endeavor emphasized the uncertainties of securing sufficient energy in case of using low-carbon technologies. They also expressed a need for more trained workers to handle low-carbon technologies. All companies agreed with a expected high cost of adopting low-carbon options. There was a communication gap with the relevant government ministry about low-carbon mining options where the government should be able to facilitate the involvement of othe low technology providers, such as solar PV installation.

The lymphocyte function–associated antigen-1 (LFA-1) (also CD11a/CD18 and αLβ2), is just one of many integrins in the human body, but its significance derives from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1. A more detailed examination of LFA’s role within B-cell chronic lymphocytic leukemia is made. Finally, we discuss the role of LFA-1-harboring exosomes in tumor growth and metastasis.

Bulk composition, mineralogy and microchemistry of various fractions of the filling of the Crater No. 4 at Emmerting were investigated. Here we present mainly the fine fractions, which, in contrast to pebbles larger than ca. 4 cm, are relatively poor in material affected by melting. A 0.1 mm long meteorite fragment without ablation features was found, and remelted fragments of the same body have been identified. The projectile was dominated by enstatite, also containing forsterite, basic plagioclase, Ni-rich pyrrhotite and troilite, kamacite, silica, and probably merrillite. The molten fragments contain porous Mg-rich glass (indicating temperature &gt; 1500 °C), minor Fe oxides, and occasionally uncommon Ni-rich minerals. The bulk composition and electron microprobe show that the amount of meteoritic material is low (&lt;&lt; 1 %), and it is not unequivocally manifested even in platinum-group elements abundances and osmium isotope ratios (the latter, however, were only measured in two samples). This can be explained by dilution of the filling by particles brought after the crater formation, and by probably achondritic composition of the projectile. Relatively large hollow spheroid Fe oxide particles were observed in thin sections from the magnetic fraction. A Mn oxide hollow spherule has also been found. In magnetically separated filling from the nearby Crater No. 5, bulk chemical composition points to contamination with several metals and metalloids probably due to influence of recent alluvial sediments. Therefore, the extent of meteoritic contamination in this crater may be even smaller.

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We have previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its’ potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicate its’ potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, especially in pediatric malignant gliomas. We also summarize BMP4 delivery strategies, with a focus on biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

This article evaluates Europe's building sector's circular economy (CE). This industry is respon-sible for 42% of energy consumption, more than 50% of extracted materials, 30% of Europe's wa-ter and waste generation, and 35% of greenhouse gas (GHG) emissions. This study focuses on peer-reviewed articles from Scopus and Web of Science databases. Of the first 1750 publications, 2.9% were eligible for a full-text reading and analysis. Most of the trending studies, 92%, pro-mote the circular economy concept through construction materials rather than analyzing the im-pact of the construction sector on the environment and finding solutions for better implementa-tion, and 41% promote recycling and reuse as the only options. New Design solutions are in 12% of the studies, six-fold more than Law and Legislation, only 2%. Finding an optimal combination of assessing the life cycle of buildings and components and searching for different ways of man-aging the Construction and Demolition Waste at end-of-life is between 33% and 39%. Ultimately, one evaluated CE proposed frameworks for the building industry based on 10R principles varia-tions. One presents an alternative framework for a circular strategy for the building industry that focuses on Upcycling, replacing the Recover principle.

The NP method was used to elucidate the contributions of vehicles and coal combustion to seasonal and long-term atmospheric PM-bound Pyr and 1-NP concentrations in Kanazawa, Kitakyushu, Shenyang, and Shanghai in the Western Pacific region from 1997 to 2021. Among the four cities, Kanazawa demonstrated the lowest Pyr concentration. The contribution of vehicles to Pyr before and after 2010 were 35% and 5%, respectively. The 1-NP concentration reduced by a factor of more than 1/10. These changes can be attributed to the emission control from vehicles. Kitakyushu revealed the second lowest Pyr and the lowest 1-NP concentrations. Coal combustion was found to be the main contributor to Pyr, while its contribution to 1-NP increased from 9% to 19%. The large contribution of coal combustion is attributed to iron manufactures. Shenyang demonstrated the highest atmospheric Pyr concentration with its largest seasonal change. Vehicles are the largest contributors to 1-NP. However, coal combustion, including winter coal heating, contributed 97% or more to Pyr and more than 14% to 1-NP. Shanghai revealed the second highest Pyr and 1-NP concentrations, but the former was substantially lower than in Shenyang. Coal combustion was the major contributor, but the contribution of vehicles to Pyr was larger before 2010 similar to Kanazawa.

It has been previously shown that aldehyde dehydrogenase (ALDH) family member ALDH1A1 has a significant association with acute myeloid leukemia (AML) patient risk group classification, and that AML cells lacking ALDH1A1 expression can be readily killed by chemotherapy. In the past, however, a redundancy between the activities of subgroup members of the ALDH family has hampered conclusive evidence for addressing the role of specific ALDH genes. We here describe the bioinformatics evaluation of all nineteen member genes of the ALDH family as prospective actionable targets for the development of methods aimed to improve AML treatment. We implicate ALDH1A1 in the development of recurrent AML, and we show that from the nineteen members of the ALDH family, ALDH1A1 and ALDH2 have the strongest association with AML patient risk group classification. Furthermore, we discover that the sum of the expression values for RNA from the genes ALDH1A1 and ALDH2 has a stronger association with AML patient risk group classification and survival than either one gene alone. In conclusion, we identify ALDH1A1 and ALDH2 as prospective actionable targets for the treatment of AML in high risk patients. Substances that inhibit both enzymatic activities can constitute potentially effective pharmaceutics.

Abstract: Dispersal strategies of a species can affect its invasion success. Investigation into the dispersal strategies of invasive species in relation to different factors helps our understanding of the invasion mechanisms and provides knowledge for population management and invasion evaluation. Tetranychus ludeni Zacher (Acari: Tetranychidae) is an invasive species, which is native to Europe but now cosmopolitan. Here, we examined the effects of age and density on dispersal in mated females. Our results show that older females with more eggs were more likely to disperse and moved longer distances than younger ones with fewer eggs. Older females spread most of their eggs out of the natal habitats and over longer distances, which reduced competition and increased offspring fitness. Females significantly increased dispersal probability and distance with the increase of population density to avoid crowding. The synchronization of dispersal and reproduction, along with the positive density-dependent dispersal strategy, may facilitate habitat colonization and invasion speed of T. ludeni.

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

-- This paper examines the critical role of business analysis in shaping small and medium-sized enterprises’ strategies for better odds of success in the ever-evolving Nigerian economy and within the competitive markets. Business analysis ability, as a knowledge-supporting factor, focuses on understanding consumer needs, planning, data collection, analysis, and presentation to decision-makers. The process begins with strategic planning and meticulous data collection, facilitating a deep understanding of the business and consumer behavior and process potential. Analytical skills unearth the true potential of organizational processes, particularly in product creation, resulting in distinctive and highly valued products. Such products align with theories like the resource-based view or VRIO theory, driving increased sales volume—a key performance metric. By leveraging analytical capabilities, Nigerian SMEs can navigate complex market dynamics, create value-driven businesses, and differentiate themselves from competitors thus increasing the odds of success. This paper sets the stage for further research into the impact of business analysis on organizational success within dynamic market landscapes.

A flavonoid Astragalin (kaempferol-3-O-β-D-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O- β-D-isomaltotrioside, Ast-Gal) on dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through up-regulation of surface markers, such as CD80, CD86, and MHC II in a dose-dependent manner, while Ast had little effects. Also, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as IL-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 mAb to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly increased IFN- γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs, and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

Rubber compounds based on styrene-butadiene rubber, ethylene-propylene-diene-monomer rubber and the combinations of both rubbers were cured with different sulfur and peroxide curing systems. In sulfur curing systems, two type of accelerators, namely N-cyclohexyl-2-benzothiazole sulfenamide, tetramethylthiuram disulfide and combinations of both accelerators were used. In peroxide curing systems, dicumyl peroxide, and combination of dicumyl peroxide with zinc diacrylate or zinc dimethacrylate, respectively were applied. The work was focused on investigation of the curing system composition as well as type of the rubber or rubbers combinations on curing process, cross-link density and physical-mechanical properties of vulcanizates. The dynamic-mechanical properties on the selected vulcanizates were examined, too. The result revealed correlation between the cross-link density and physical-mechanical properties. Similarly, there was recorded certain correlation between cross-linking degree and glass transition temperature. The tensile strength of vulcanizates based on rubbers combinations was higher when compared to that based on pure rubbers, which points out the fact that by rubbers combination, not only the features of both elastomers can be combined, but also improved tensile characteristics can be achieved. When compared to vulcanizates cured with dicumyl peroxide, materials cured with sulfur system exhibited higher tensile strength. By application of co-agents in peroxide vulcanization, the tensile strength overcame the tensile behavior of sulfur cured vulcanizates.

Objectives: To assess the short-term impact of a single global stretching session on plantar pressures and lumbar range of motion (RoM) over one week in sedentary university students. Design: A randomised controlled trial with two parallel groups. Participants: Sixty-four university students were randomly assigned to a stretching group or control group. The stretching group received a single session of global stretching and the control group remained seated for the same length of time as the stretching session. Main outcome measures: Lumbar RoM and plantar pressures were assessed before, immediately after, 48 hours after, and 7 days after intervention. Results: Group-by-time interaction was significant for lumbar lateral flexion (p = 0.044), right maximal pressure (p = 0.003), left maximal pressure (p = 0.008), right mean pressure (p = 0.025), left mean pressure (p = 0.002), and maximal pressure minus mean pressure in right foot (p = 0.007). The model with plantar pressures showed a significant difference for group-by-time interaction (p = 0.010).Conclusion: Global stretching seems to counteract the ill-effects of prolonged sitting up to seven days with respect to plantar pressure in standing without improving lumbar ROM

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

This paper analyses the application of deep learning techniques for predicting wave overtopping events in port environments using sea state and weather forecasts as inputs. The study was conducted in the outer port of Punta Langosteira, A Coruña, Spain. A video recording infrastructure was installed to monitor overtopping events from 2015 to 2022, identifying 3709 overtopping events. The data collected was merged with actual and predicted data for the sea state and weather conditions during the overtopping events, creating three datasets. We used these datasets to create several machine learning models to predict whether an overtopping event would occur based on sea state and weather conditions. The final models achieved a high accuracy level during the training and testing stages: 0.81, 0.73, and 0.84 average accuracy during training and 0.67, 0.48, and 0.86 average accuracy during testing, respectively. The results of this study have significant implications for port safety and efficiency, as wave overtopping events can cause disruptions and potential damage. Using deep learning techniques for overtopping prediction can help port managers take preventative measures and optimize operations, ultimately improving safety and helping to minimize the economic impact that overtopping events have on the port's activities.

Abstract Introduction: Poor structural quality of health facilities for tuberculosis (TB) diagnosis and treatment contributes to unfavorable health outcomes among TB patients. Improving the quality of healthcare services helps to avert TB-related morbidity. Despite these facts, the level of structural quality of health facilitieSs to deliver TB services is not in line with what the national TB and leprosy program (NTLP) recommends. Hence, the present study was conducted to assess the structural quality of health facilities to deliver quality TB services to TB patients among public health facilities in the Sidama region.Objectives: To determine the quality of the structural domain of TB services at public health facilities in the Sidama region of southern Ethiopia.Methods: An institution-based cross-sectional study was conducted from June to July 2023 among randomly selected public health facilities in the Sidama region. We included 40 randomly selected public health facilities that delivered TB services in the study area. Data was collected by experienced data collectors using facility audits, clinical observation checklists, structured questionnaires, and in-depth interviews. An Open Kit Mobile (ODK) application was used to collect data and exported to SPSS version 26. All statistical analysis was done using SPSS version 26.Results: The overall mean quality score for the structural dimension was 50.25 among the 40 health facilities audited in the study area.Conclusion: The quality of TB services regarding structural dimensions was poor in the study area. Therefore, any strategies must give careful attention to increasing the comprehensive structural dimension of quality TB services.

Abstract: Field studies with large-stemmed plants Artemisia dubia (wormwood) have been carried out at Vėžaičiai Branch LAMMC since 2018. According to three years of experimental results, annual dry matter (DM) yield varied from 7.94 to 10.14 t ha-1. Growing conditions, nitrogen ap-plication level and harvesting time had significant impacts on Artemisia dubia productivity. This article presents the results of research on preparation and use of Artemisia dubia biomass for en-ergy conversion and evaluation of technological-technical and environmental parameters of these plants utilization for solid biofuel. For experiments were used 6 variants of Artemisia dubia samples, which were grown in 2021: plants were cut three times and two fertilization options were used: (1) no fertilization and (2) fertilization with 180 kg ha-1 of nitrogen fertilizer. These harvested plants were chopped, milled and were pressed into the pellets. The physi-cal-mechanical characteristics (mоisture content, density and strength) of Artemisia dubia pellets were investigated. During this study, it was found that the density in dry mass (DM) of pellets ranged from 1119.86 to 1192.44 kg m-3. The pellet moisture content ranged from 8.80 to 10.49%. After testing of pellet strength, it was found that the pellets which were made from plant bio-mass PK-1-1, were the most resistant to compression, they withstood 560.36 N of pressure. Dry fuel lower heating value (LHV) of pellets was sufficiently high and was very close to pine saw-dust pellets, it varied from 17.46±0.25 MJ kg-1 to 18.14±0.28 MJ kg-1. The ash content of burned pellets ranged from 3.62±0.02% to 6.47±0.09%. Emissions of harmful pollutants – CO2, CO, NOx and unburnt hydrocarbons (CxHy) did not exceed the maximum permissible levels. Summariz-ing the results of investigated properties, cоmbustion and emissiоns of Artemisia dubia pellets, it can be concluded that this biofuel can be used for production of pressed biofuel and it is charac-terized by sufficient high quality, efficient combustion and permissible emissions to the envi-ronment.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

Abstract: Canine ehrlichiosis is a zoonotic disease transmitted by ticks, posing a formidable challenge to both veterinary and public health sectors worldwide. Across continents and regions, the prevalence rates of Ehrlichia canis exhibit significant variation, underlining the necessity for a nuanced and globally informed approach to understanding and combating this disease. The review navigates through this complexity, shedding light on the intricate pathogenesis of the illness. Central to this understanding is the bacterium's adept manipulation of the host's immune response, contributing to the diverse clinical manifestations observed in infected animals. Diagnostic methodologies, crucial for timely intervention and management, are subjected to critical assessment. From traditional microscopy to modern molecular techniques and serology, each approach is scrutinized for its strengths and limitations. By acknowledging these nuances, the review aims to equip practitioners with the knowledge necessary to make informed diagnostic decisions. A central tenet of this review is the advocacy for an integrated "One Health" approach. By leveraging advancements in genomics, proteomics, and artificial intelligence, there is a potential to enhance diagnostic accuracy and develop innovative therapeutic and preventive strategies globally. This collaborative approach recognizes the interconnectedness of human, animal, and environmental health, offering a holistic framework for tackling complex zoonotic diseases like canine ehrlichiosis. In conclusion, this review serves as a beacon of knowledge, illuminating the multifaceted landscape of canine ehrlichiosis. Through its synthesis of scientific literature and emphasis on methodological rigor, it provides a foundation upon which future research and interventions can be built. With a unified commitment to "One Health" principles and the integration of cutting-edge technologies, there exists the potential to mitigate the impact of this disease and safeguard both animal and human well-being worldwide

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.

Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

Autophagy, an alternative cell death mechanism, is also termed programmed cell death type II. Autophagy in cancer treatment needs to be regulated. In our study, autophagy inhibition by desipramine or the autophagy inhibitor chloroquine (CQ) enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 [death receptor (DR5)] expression and subsequently TRAIL-induced apoptosis in TRAIL-resistant A549 lung cancer cells. Genetic inhibition of DR5 substantially reduced desipramine-enhanced TRAIL-mediated apoptosis, proving that DR5 was required to increase TRAIL sensitivity in TRAIL-resistant cancer cells. Desipramine treatment upregulated p62 expression and promoted conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, indicating that autophagy inhibition occurred at the final stages of autophagic flux. Transmission electron microscopy analysis showed the presence of condensed autophagosomes, which resulted from the late stages of autophagy inhibition by desipramine. TRAIL, in combination with desipramine or CQ, augmented the expression of apoptosis-related proteins cleaved caspase-8 and cleaved caspase-3. Our results contributed to the understanding of the mechanism underlying the synergistic anti-cancer effect of desipramine and TRAIL and presented a novel mechanism of DR5 upregulation. These findings demonstrated that autophagic flux inhibition by desipramine potentiated TRAIL-induced apoptosis, suggesting that appropriate regulation of autophagy is required for sensitizing TRAIL-resistant cancer cells to TRAIL-mediated apoptosis.

Fibroin-chitosan composites, especially those containing nanohydroxyapatite, show potential for bone tissue regeneration. The physicochemical properties of these biocomposites depend on the compatibility between their components. In this study, the intermolecular interactions of fibroin and chitosan were analyzed using a molecular dynamics approach. Two types of systems were investigated: one containing acetic acid and the other containing calcium (Ca²⁺) and hydrogen phosphate (HPO₄²⁻) ions mimicking hydroxyapatite conditions. After obtaining the optimal equilibrium structures, the distributions of several types of interactions including hydrogen bonds, ionic contacts, and hydrophobic contacts along with the structural and energetical features were examined. The calculated binding energy values for the fibroin-chitosan complexes confirm their remarkable stability. The high affinity of fibroin for chitosan can be explained by the formation of a dense network of interactions between considered biopolymers. These interactions were found to be primarily hydrogen bonds and ionic contacts involving ALA, ARG, ASN, ASP, GLN, GLU, GLY, LEU, PRO, SER, THR, TYR, and VAL residues. As it was established, the complexation of fibroin with chitosan maintains the β-sheet conformation of the peptide. β-Sheet fragments in fibroin are involved in the formation of significant amount of hydrogen bonds and ionic contacts with chitosan.

In this study, a new type of temperature sensor device was developed. The circular electrode of the thermal sensitive sensor was modified with TMT and O₂ plasma to enhance the conductivity by forming a thin SnOxCy layer on the electrode surface. The Nano-Au particles were subjected to O₂ plasma pretreatment to form peroxide groups on the surface. The thermally sensitive sensor was made by mixing the above-treated Nano-Au particles with N-isopropylacrylamide (NIPAAm) to form solution and then UV-induced grafting polymerization of the NIPAAm-containing solution onto the electrode substrate. The composite hydrogels on the electrode introduce thermo-sensitive polymeric surface films for temperature sensing. Using ambient environment resistance test to measure the resistance, the LCST (lower critical solution temperature) of Nano-Au (MUA) mixed with NIPAAm hydrogel was found to be 32 °C. At ambient temperatures higher than LCST, the electrode resistance decreases linearly.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. AML with mutated Nucleophosmin1 (NPM1-mut) is the largest of the genetically defined groups, involving about 30% of adult AMLs and is currently recognized as a distinct entity in the actual AML classifications. NPM1-mut AML usually occurs in de novo AML and is associated predominantly with a normal karyotype and relatively favorable prognosis. However, NPM1-mut AMLs are genetically, transcriptionally, and phenotypically heterogeneous. Furthermore, NPM1-mut is a clinically heterogenous group. Recent studies have in part clarified the consistent heterogeneities of these AMLs and have strongly supported the need for an additional stratification aiming to improve the therapeutic response of the different subgroups of NPM1-mut AML patients.

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the molecular characteristics of the HDAC6 protein, as well as its overexpression in CML leukemic stem cells, which make it a promising therapeutic target for the treatment of CML.

Hemangioblasts give rise to endothelial progenitor cells (EPCs), which also express the cell surface markers CD133 and C-kit. They may differentiate into the outgrowth endothelial cells (OECs) that control neovascularization in the developing embryo. Reduced levels of EPC in circulation have been linked to human cardiovascular disorders, according to numerous studies. Furthermore, preeclampsia and senescence have been linked to levels of EPCs produced from cord blood. Uncertainties surround how preeclampsia affects the way EPCs function. It is reasonable to speculate that preeclampsia may have an impact on the function of fetal EPCs during the in utero period; however, given the present literature's suggestion that maternal vasculopathies, including preeclampsia, damage fetal circulation. Additionally, the differentiation potential and general activity of EPCs may serve as an indicator of the health of the fetal vascular system since they promote neovascularization and repair during pregnancy. Thus, the purpose of this review is to compare, through assessment of their quantity, differentiation potency, angiogenic activity, and senescence, the angiogenic function of fetal EPCs obtained from cord blood for normal and pregnancy problems. This will shed light on the relationship between the angiogenic function of fetal EPCs and pregnancy complications, which could have an effect on the management of long-term health issues like metabolic and cardiovascular disorders in offspring with abnormal vasculature development.

Buildings consume 30% of the total energy consumption around the globe and 29% of the energy consumption in Egypt which in 2022 had a total population of 102 million, out of which 43 % live in urban areas . The operation of buildings contributes to around 30% of global CO2 emissions due to their high energy consumption (IEA, 2022a). Among the efforts made towards improving the energy efficiency of buildings are Advanced Energy Design Guides (AEDGs), building rating systems, codes, and standards. Furthermore, numerous research studies that are either literature review studies, experimental studies, or computational studies addressed the topic of energy efficiency in buildings. These are all examined in this literature review with the purpose of identifying the research gap in available research with a focus on Egypt. The identified gap is the development of a prescriptive path for the GPRS energy efficiency category based on whole building energy simulations.

In this article, we investigate two types of double dispersion equations in two dierent dimensions. Double dispersion equation were derived to describe long nonlinear wave evolution in a thin hyperelastic rod. Conservation laws are obtained for these equations by the application of the multiplier method. Finally, travelling waves and line travelling waves are respectively considered for these two equations.

The objective of this paper was to give an overview of the expressed preference (EP) techniques of environmental valuation. These methods offer estimation of the value of a resource not necessarily willingness to pay (WTP) or willingness to Accept (WTA) compensation rather upper and lower values. The method of measuring individuals’ willingness to pay is usually based on contingent valuation method (CVM). This research focuses on defining, categorizing, and applicability of various environmental valuation techniques that have been and can be applied in attaching value to a given resource using expressed/Revealed preference methods. The study serves as a supplementary synthesis and discussion to the board of knowledge of resource valuation methods. More specifically, selected methods to discussed herein include; contingent valuation method, hedonic pricing model, travel cost method, trade-off game method, the costless-choice method, Delphi method, Replacement Cost Method, Relocation Cost Method, Opportunity cost method, and Cost-benefit Method. In the last part, applicability of the methods is fully illustrated to support future studies on resource valuation.

A population dynamics epidemic model is developed that incorporates age of infection and age of vaccination. The model analyzes pre-symptomatic and symptomatic periods of an infected individual in terms of infection age. The model analyzes the efficacy of vaccination in terms of vaccination age. The model is applied to the 2003 SARS epidemic in Taiwan and the current COVID-19 epidemic in New York State.

Circular RNAs (circRNAs), which are a class of non-coding RNA with covalently closed loops, play important roles in epigenetics regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, why circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “backsplicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis- and trans-elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated why circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

I review the solution of QCD in two spacetime dimensions. Following the analysis of Baluni, for a single flavor the model can be analyzed using Abelian bosonization. The theory can be analyzed in strong coupling, when the quarks are much lighter than the gauge coupling. In this limit, the theory is given by a Luttinger liquid.

Abstract: Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phe-notypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with the phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reac-tions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilu-tion and E-test by minimal inhibitory concentration (MIC) measurements. Over 30.0% (69/225) of isolates showed colistin resistance by agar dilution assessment (MIC> 2.0 μg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, mcr-3; and co-occurrence occurred in 2 isolates). Clinical breakout MIC val-ues (≥ 4 μg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens include twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudo-monas parafulva. mcr-genes appeared to be significantly associated with phenotypic colistin resistance phe-nomena (p=0.000), with 100% colistin-resistant isolates showing MDR phenomena. Age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacte-ria have emerged in Bangladesh, which warrants further research to determine their spread and instigate ac-tivities to reduce resistance.

Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

histology, the processing and staining of cells, tissues and organs to highlight contrast, visualize and analyze their microstructure under microscopy, encompasses a vast array of techniques used to confirm, refine, or refute the macroscopic findings in forensic investigations, for example in the case of autopsies. This review presents several applications of histological protocols, staining methods and techniques to case studies, with the aim of illustrating the established, current and potential applications of histological investigations to forensic sciences. The list of disciplines include anthropology, cytology, dendrochronology, diatomology, entomology, fiber analysis, palynology,human and veterinary pathology, taphonomy and thanatology.

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in patients with pneumonia (called COVID-19) in Wuhan, Hubei Province, China. SARS-CoV-2 shares high sequence similarity and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as does severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes for SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not been determined. Here, we investigate the expression pattern of ACE2 in adult human testis at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells. Gene ontology analyses indicate that GO categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia while male gamete generation related terms are down-regulated. Cell-cell junction and immunity related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction related GO terms are decreased. These findings provide evidence that human testes are a potential target of SARS-CoV-2 infection which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood. This study aims at understanding the molecular features within CTCs in relation to their metastatic potential. Using in vitro CTC models, in which breast cancer cell lines are cultured in non-adherent conditions simulating the microenvironment in the blood stream, we found that suspension culture resulted in resistance to TNF-related apoptosis inducing ligand (TRAIL)-mediated cell death. Such a resistance was directly correlated with a reduction in surface and total levels of DR5 protein. In the non-adherent state, cells underwent rapid autophagic flux characterized by an accumulation of autophagosome organelles. Notably, DR5 was translocated to autophagosomes and underwent lysosomal degradation. Our data suggest that CTCs may evade TNF cytokine mediated immune surveillance through downregulation of DR expression. The data warrants further studies in cancer patients to find the status of DRs and other molecular features within primary CTCs in relation to disease progression or chemoresistance.

Premalignant lesions in the bronchial epithelium represent early stages of squamous cell lung carcinoma, challenging to detect with conventional methods. While previous studies have focused on gene expression, here we examine transcriptomic alterations associated with lesion development with the emphasis on protein-coding transcripts. We reanalyzed publicly available RNAseq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript abundances were quantified using kallisto, and differential expression and transcript usage analysis was conducted using the sleuth and RATs packages. Functional characterization included overrepresentation analysis (clusterProfiler), weighted co-expression network analysis (WGCNA), and network analysis (Enrichr-KG). We detected 5,906 differentially expressed transcripts, with significant enrichment in pathways related to oxidative phosphorylation and mitochondrial function. Transcript-level WGCNA identified single module correlated with dysplasia status, enriched in cilium-related biological processes. Analysis of hubs within this module highlighted key genes including RABL2B, DNAH1, EFHC1 and VWA3A, and revealed transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant lesion biology. By examining transcripts rather than genes, we identified potential biomarkers associated with early lung carcinogenesis.

Distinguishing circular RNA (circRNA) reads from reads derived from the linear host transcript is a challenging task because of sequence overlap. We developed a computational approach, CiLiQuant, that determines the relative circular and linear abundance of transcripts and gene loci using backsplice and forward splice junction reads generated by existing mapping and circRNA discovery tools.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

Background: While outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients. Methods: We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients. Results: The median age at diagnosis was 80 years (range: 75-96). In the first-line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third-line and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e. 3-month BCR::ABL1 IS <10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, with 16.6%, 35.7%, and 51.7% achieving DMR at the same timepoints. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade ≥ 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (p=0.033). Overall, median follow-up was 46.62 months (range: 1.8-206.2), and 43 patients died due to non CML related causes. Three patients died due to disease progression to advanced (n=1) and blastic (n=2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63-0.81), with no significant difference between patients treated with standard doses of TKI compared to those treated with reduced doses (p=0.35). Conclusions: TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.