The Novel Coronavirus (COVID-19) is a positive-sense single-stranded RNA ((+)ssRNA) virus. The COVID-19 Main Proteases play very important role in the propagation of the Novel Coronavirus (COVID-19). It has already killed more than 8000 people around the world and thousands of people are getting infected every day. Therefore, it is very important to identify a potential inhibitor against COVID-19 Main Proteases to inhibit the propagation of the Novel Coronavirus (COVID-19). We have applied a drug repurposing approach of computational methodology, depending on the synergy of molecular docking and virtual screening techniques, aimed to identify possible potent inhibitors against Novel Coronavirus (COVID-19) from FDA approved antiviral compounds and from the library of active phytochemicals. On the basis of recently resolved COVID-19 Main Protease crystal structure (PDB:6LU7), the library of 100 FDA approved antiviral compounds and 1000 active components of Indian Medicinal Plants extracted for screening against COVID-19 Main Protease. The compounds were further screened using Pyrex virtual screening tool and then best inhibitors, top 19 compounds optimally docked to the COVID-19 Main Protease structure to understand the participation of specific amino acids with inhibitors at active sites. Total 19 best compounds were identified after screening based on their highest binding affinity with respect to the other screened compounds. Out of 19, 6 best compounds were further screened based on their binding affinity and best ADME properties. Nelfinavir exhibited highest binding energy -8.4 kcal/mol and strong stability with the TRP207, ILE281, LEU282, PHE3, PHE291, GLN127, ARG4, GLY283, GLU288, LYS5, LYS137, TYR126, GLY138, TYR126, SER139 and VAL135 amino acid residues of COVID-19 Main Protease participating in the interaction at the binding pocket. In addition to Nelfinavir (-8.4), Rhein (-8.1), Withanolide D (-7.8), Withaferin A (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4) also showed good binding affinity and best ADME properties. Our findings suggest that these compounds can be used as potential inhibitors against COVID-19 Main Protease, which could be helpful in inhibiting the propagation of the Novel Coronavirus (COVID-19). Moreover, further in vitro and in vivo validation of these findings would be very helpful to bring these inhibitors to next level study.

The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here we provide the current state-of-the-art of using exosome or exosome-inspired systems for drug delivery. We review the various approaches investigated and the shortcomings of each approach. Finally the challenges identified up-to-date in this field are summarized.

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

In 2023, the technological landscape witnessed an unprecedented surge of transformative innovations, including Web 3.0 and machine learning, poised to revolutionize various aspects of our daily lives. At the forefront of this revolution stands artificial intelligence (AI), which has evolved from a concept once confined to science fiction into an indispensable force reshaping industries on a global scale. Notably, recent years have seen remarkable strides in AI functionalities, particularly in machine learning, computer vision, and natural language processing. These advancements have empowered AI to generate diverse interactions and media autonomously. This study ultimately provides invaluable insights into the dynamic intersection of AI and Advertising, con-tributing to a deeper comprehension of this evolving field. This study conducts a comprehensive review of Artificial Intelligence within the advertising domain, employing network analysis. By meticulously examining the evolution of AI through co-occurrences of terms, keywords, and co-authorship analysis, we aim to unveil the relationship of AI & Advertising through the lens of Generative models to identify pivotal trends, core concepts, and seminal studies that have profoundly influenced the industry. The analysis charts the trajectory leading to the emergence of Generative Artificial Intelligence (GenAI), a transformative development poised to revolutionize advertising practices and consumer engagement. In tandem with these objectives, the results highlight vital trends, emphasizing the growing prominence machine learning tools and techniques such as deep learning techniques and advanced natural language processing methods like word2vec, GANs, and more in shaping the future of advertising practices.

The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.

Hypertension (HTN) is the foremost contributor to cardiovascular diseases (CVD), which remain a leading cause of death. However, adherence to the properly prescribed dosage form is critical and challenging for patients with chronic diseases such as HTN to prevent illness progression and death. The study’s objective was to develop AMB-loaded subcutaneous implants to reduce the frequency of administration, thus improving patient compliance during HTN management. AMB subcutaneous implants were prepared using continuous hot melt extrusion technology using PCL and PLGA with dimensions of 7.5 cm (length) by 2 mm (diameter). The implants were characterized for thermal characteristics, drug-excipient incompatibilities, surface morphology, fracturability, in vitro release, and stability studies. DSC showed that the drug was in the crystalline state in the fabricated implants. Scanning Electron Microscopy (SEM) revealed a smooth surface. The lead formulation presented good drug content, showed an extended drug release profile over 30 days, and followed zero-order release kinetics with a mean dissolution time of 15 days. The formulation was stable over 30 days in accelerated stability conditions (the last time point was tested, 40℃/75% RH), and the release profile was similar to the initial drug release profile. The lead formulation showed good fracturability during textural analysis. Therefore, the hot melt extruded implants could be an alternative management strategy for conventional amlodipine besylate (AMB) formulation.

The primary purpose of this study was to determine the prevalence of drug-drug interaction (DDI) and duplicate therapy in chronic patients in a completely random study population engaged in digital health apps. In this cross-sectional study, polypharmacy checks for 100 completely anonymous patients were analyzed for the occurrence of DDIs and duplicate therapy. Logistic regression models were used to identify factors associated with DDIs and duplicate therapy. DDIs and duplicate therapy prevalence were 34% and 33%, respectively. Chi-Square test discovered a significant association between the DDIs and duplicate therapy variables. Logistic regression models showed a strong association between the number of medications taken and higher odds of DDIs occurring in our population only. In conclusion, our study shows that polypharmacy is a determining factor for the occurrence of unwanted DDIs, and the prevalence of duplicate therapy and DDIs is around 33%, increasing an issue regarding patient safety and its burden to the healthcare system.

Overt hyperthyroidism during pregnancy is associated with risk of maternal-fetal complications. The antithyroid drugs (ATD) have a potential risk for teratogenic effects and fetal–neonatal hy-pothyroidism. This study evaluated ATD treatment and thyroid function control during preg-nancy, and pregnancy outcome in women with hyperthyroidism. Patients and methods: retro-spective analysis of 36 single fetus pregnancies in 29 consecutive women (median age 30.3 ± 4.7 years) with hyperthyroidism diagnosed before or during pregnancy; a control group of 39 healthy euthyroid pregnant women was used. Results: 26 women had Graves’ disease (GD, 33 pregnan-cies), 1 had a hyperfunctioning autonomous nodule, 2 had gestational transient thyrotoxicosis (GTT). Methimazole (MMI) was administered in 22 pregnancies (78.5%), Propylthiouracil (PTU) in 2 (7.1%), switch from MMI to PTU in 4 (14.2%), no treatment in 8 pregnancies (3 with subclinical hyperthyroidism, 5 euthyroid with previous GD remission before conception). One spontaneous abortion at 5 weeks (3.4% of pregnancies) and 1 premature delivery at 32 weeks with perinatal death in 24h (3.4%) were recorded in 2 of the 8 pregnancies of GD patients diagnosed shortly before (< 6 weeks) or during gestation. In women treated more than 6 months until conception (20 pregnancies): a) median ATD doses were lower than those in women diagnosed shortly before or during pregnancy; b) ATD was withdrawn in 40% of pregnancies in trimester (T) I, all on MMI < 10 mg/day (relapse in 14.2%), and in up to 55% in TIII; c) TSH level was below normal in 37%, 35% and 22% of pregnancies in T I, II and III respectively; FT4 was increased in 5.8% (T I) and sub-normal in 11.75% in TII and III; d) one fetal death due to a true umbilical cord knot was recorded. Hyperthyroidism relapsed postpartum in 83% of GD patients (at median 3 ± 2.6 months). One child had neonatal hyperthyroidism (3.3% of live children in GD women) and a small atrial sept defect (4% of live children in ATD treated women). Mean birth weight did not differ from that of the control group. Conclusion. In hyperthyroid women with long-term ATD control before con-ception, drugs could be withdrawn in TI in a third of them, and fetal complications were rare. Frequent serum TSH and FT4 monitoring is needed in order to maintain optimal thyroid function during pregnancy.

In this paper we propose the generation of synthetic small and more sophisticated molecule structures that optimize the binding affinity to a target (ASYNT-GAN). To achieve this we leverage on three important achievements in A.I.: Attention, Deep Learning on Graphs and Generative Adversarial Networks. Similar to text generation based on parts of text we are able to generate a molecule architecture based on an existing target. By adopting this approach, we propose a novel way of searching for existing compounds that are suitable candidates. Similar to question and answer Natural Language solutions we are able to find drugs with highest relevance to a target. We are able to identify substructures of the molecular structure that are the most suitable for binding. In addition, we are proposing a novel way of generating the molecule in 3D space in such a way that the binding is optimized. We show that we are able to generate compound structures and protein structures that are optimised for binding to a target.

HIV treatment strategies against viral enzymes are continuously hampered by viral drug resistance. Recent findings show that viral substrate Gag contributes to HIV-1 Protease Inhibitor (PI) resistance, leading to demands for new strategies in HIV treatment where Gag is recognized as a drug target. To successfully target Gag, there is a need of in-depth understanding of the Gag polyprotein and the effects of Gag mutations. Here, we propose new strategies in designing novel Gag inhibitors against existing and novel emerging Gag mutations via a structural understanding of the Gag-Protease relationship in PI resistance. In this review, we discuss the role of both novel and previously reported mutations, revealing insights to how they aid in PI resistance, and how new Gag inhibitors can be designed.

The COVID-19 pandemic remains a serious public health problem globally. During winter flu seasons, more aggressive SARS-CoV-2 infections with fatalities have been documented, indicating that influenza co-infections may significantly impact the disease outcome of COVID-19. Both influenza and SARS-CoV-2 viruses share many similarities in their transmission and cellular tropism for their replication in the human respiratory tract. However, it is still unclear how the two pathogens interplay to ensure their survival in the same lung microenvironment. In addition, clinical studies on influenza co-infections in COVID-19 patients do not provide conclusive evidence on how influenza co-infection mechanistically modifies the disease outcome in COVID-19. This mini-review discusses various viral as well as host factors that potentially influence the survival or synergism of these two respiratory pathogens in the infected lung microenvironment.

Objective: The study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. Methods: In 2022, a total of 4,684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes were determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. Results: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5,47)=18.233, p&lt;0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5,47)=2.037, p=0.091). Conclusion: The study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

This study explores how young people’s mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. This is important to understand so that policy and practice professionals can support those affected, prepare, and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16–18-year-olds (N = 21) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From artwork, four themes were identified; trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, relationships, hobbies, habits, and education or work were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This implies that young people’s mental health services should collaborate with other sectors to address wider life determinants in a holistic way, and that clearer guidance and support in these areas could mitigate the negative mental health impacts of major environmental changes on young people.

Combustion power plants emit carbon dioxide (CO₂), a major contributor to climate change. Direct emissions measurement is cost-prohibitive globally, while reporting varies in detail, recency, and granularity. To fill this gap and greatly increase the number of power plants worldwide with independent emissions monitoring, we developed and applied machine learning (ML) models using power plant plumes as proxy signals to estimate electric power generation and CO₂ emissions using Landsat 8, Sentinel-2, and PlanetScope imagery. Our ML models estimated power plant activity on each image snapshot, and then an aggregation model predicted plant utilization over a 30-day period. Lastly, emissions factors specific to region, fuel, and plant technology were used to convert estimated electricity generation to CO₂ emissions. Models were trained with reported hourly generation data in the US, Europe, and Australia and were validated with additional generation and emissions data from the US, Europe, Australia, Türkiye, and India. All results with sufficiently large sample sizes indicate that our models outperformed baseline approaches. In conducting external validation to compare modeled versus reported annual generation and emissions in the countries where available, we calculated the root mean square error overall for modeled countries with validation data as respectively 1.75 TWh (236 plants across 17 countries over 4 years) and 2.04 Mt CO₂ (207 plants across 17 countries over 4 years). Ultimately, we applied our ML method to plants that comprise 32% of global power plant CO₂ emissions averaged over 2015-2022. This dataset is the most comprehensive independent and free-of-cost global power plant point-source emissions monitoring system currently known to the authors and is publicly available at climatetrace.org to support global emissions reduction.

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IRs T cells and to assess the levels of serum soluble PD-1, PDL-2, and Tim3 in Taiwanese RA patients. Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and Tim3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/Tim3. In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT on CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 on CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests proved to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR (p=0.0084, N=46), DAS28-CRP (p=0.007, N=47), and hsCRP (p=0.002, N=56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% (p=0.0089, N=46) and CD8+ TIM3+% (p=0.0305, N=46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% (p<0.0001, N=31) and CD3+CD279+% (p=0.0084, N=30). Co-IRs expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and Tim3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA, in accordance to our findings.

"Chemical absorption is currently the most advanced technique for capturing carbon dioxide after combustion. A fascinating approach within amine-based technology for post-combustion carbon removal is the utilization of aqueous ammonia as a solvent, leading to a method called chilled ammonia capture. This study aims to enhance the performance of chilled ammonia capture through a thermodynamic assessment, focusing on crystalline configuration.""This study explores the development of an improved second generation chilled ammonia capture process, which involves the formation of solids to enhance capturing efficiency. The simulation software ASPEN is employed to model the expanded UNIQUAC Thermodynamics hypothesis. The modeling encompasses both the conventional carbon ammonia capture process and the more advanced carbon ammonia capture system powered by a crystallizerIn this study, the energy costs associated with implementing different technologies for carbon ammonia capture in typical ultra supercritical power plants are evaluated. The introduction of solid formation in the carbon ammonia capture system has yielded promising results. The findings indicate that the energy required for the carbon ammonia capture system, which utilizes a crystallizer, is approximately 10% lower compared to the overall cost associated with the conventional carbon ammonia capture system. These results highlight the potential for significant energy savings and improved efficiency in carbon capture processes

As the worldwide demand for meat per person is continuously increasing, there is a corresponding rise in the number of livestock animals, leading to an increase in livestock manure. Selecting appropriate treatment technologies for livestock manures is still a complex task and considerable debates over this issue persist. To develop a more comprehensive understanding of the manure treatment framework, this review was undertaken to assess the most utilized manure management technologies and underscore their respective challenges. Anaerobic digestion has become a commercial reality for treating livestock manures. However, the mono-digestion of single substrates comes with certain drawbacks associated with manure characteristics. Anaerobic co-digestion, involving the utilization of multiple feedstocks, holds the potential to overcome these limitations. Extensive research and development have underscored numerous intrinsic benefits co-digestion. These include improved digestibility resulting from synergistic effects of co-substrates and enhanced process stability. This review underscores the limitations associated with the mono-digestion of livestock manures and critically evaluates the advantages of their co-digestion with carbon-rich substrates. Additionally, this review delves into key livestock manure management practices globally, emphasizing the significance of co-digesting livestock manures while addressing the progress and challenges in this field.

Alkali-activated materials, sometimes called geopolymers, can be used as alternative cementitious materials to conventional Portland cement. There is a significant current interest in these materials due to their low CO2 footprint. Typical applications of alkali-activated materials are within civil engineering, however, potential applications as well cementing material within oil & gas are also being studied with emerging interest. This paper presents a systematic study of compressive strength development from 1 to 28 days for metakaolin-based alkali-activated cement. The results show that compressive strength is highly dependent upon the initial Si/Al ratio in the mix design, as well as the concentration of the activator solution. Furthermore, due to the relatively low initial reactivity of the used metakaolin material, different types of co-binders were included in the slurry composition to improve early strength development. The two different co-binders tested were another, more reactive metakaolin material and Blast Furnace Slag (GGBFS). It was found that both these co-binders performed as intended, by ensuring early strength development via precipitation of K-A-S-H and C-A-S-H gels, respectively, and also by enabling subsequent strength development due to improved dissolution of the low-reactive metakaolin.

In the present study, we implemented species distribution models (SDMs) to determine the potential invasive distribution range of a cichlid fish, Nile tilapia, Oreochromis niloticus, in a very sensitive inland water system in the southeastern Arabian Peninsula where it is now established and spreading. By using the “Biomod2” package, and the latest CMIP6 climate data, four single species distribution models and EM were built, and the results were evaluated by operating characteristic (ROC) and the true skill statistic (TSS). Based on the relative importance of climate factor analysis the mean diurnal range and precipitation seasonality were useful predictors of habitat suitability for O. niloticus. The response curve analysis indicated that the presence probability of O. niloticus decreased with increasing mean diurnal range and decreasing precipitation seasonality. The suitable distribution ranges for O. niloticus in the studied area were mainly distributed in the northeast of this region. The ensemble model results specified a significant impact of climate change on O. niloticus distribution, so highly suitable areas for this species will be reduced, while areas with low to moderate suitability increase slightly or remain unchanged. Based on the available data, Nile tilapia fulfills all four criteria to be considered as an invasive species: colonization in a new area, direct or indirect impacts of anthropological activity on its distribution range, geographical discontinuity between its native area (Africa) and the Arabian Peninsula (remote dispersal), and finally, its successful breeding in situ without human assistance resulting establishment of this biopollutant. Species distribution modeling provides insights into the factors that can reduce the risks and negative impacts of this biological pollutant on aquatic ecosystems of the southeastern Arabian Peninsula which harbors about 22 recognized fish species in 16 genera, 10 families, seven orders, and a class including 20 natives (seven endemic) species.

Technology Readiness Levels (TRLs) is a well-established and widely used approach for defining the readiness of new technology. To this extent, it assesses technology maturity against specific benchmarks, ranging from 1 (concept) to 9 (market solution). Although this is a useful classification service, allowing us to establish a common language, there are cases where we find that this conceptual approach fails to adequately highlight the maturity of certain innovative endeavors and effectively steer their development to higher TR levels. We will present an empirical case where the TRL approach presented a critical shortcoming in highlighting the true and effective readiness of a specific technological development and could not suggest the next natural step in ascending the maturity ladder. We will seek to generalize for the case of co-creation at large, analyze why co-creation may be poorly serviced by the current TRL model and suggest an amendment that would allow the observed shortcoming of the traditional TRL approach to be overcome and its use extended also in such co-creative settings.

Anthracnose is one of primary diseases in tea plants that affects tea yield and quality. The geographical distribution, occurrence regularity, and agronomic measures of tea plants with anthracnose have been researched for decades. However, the pathogenic cause of anthracnose in tea plants is diverse in different regions of the world. Identifying the specific pathogenic fungi causing tea anthracnose is an essential control measure to mitigate this disease. In this study, 88 Diaporthales and 45 Colletotrichum isolates were obtained from 3 different types of diseased tea leaves. Based on multilocus phylogenetic and morphological analysis, 3 known species, including Discula theae-sinensis, Diaporthe ueckerae, Diaporthe lithocarpus, and 3 indistinguishable species of Diaporthales were identified. In adddition, 8 known species of Colletotrichum, C. fructicola, C. camelliae, C. aenigma, C. siamense, C. henanense, C. karstii, C. tropicicola, C. gigasporum, were identified. This study is the first to report C. tropicicola and C. gigasporum in tea plant in China. Discula theae-sinensis was the most common species in this study and caused disease lesions around wounded areas of tea leaves. The dual trials in vitro indicated Discula theae-sinensis and Colletotrichum were slight inhibition. Co-inoculating Discula theae-sinensis and C. fructicola was superior to single inoculation at low concentration.

The two-component compound formed by codeine and cyclopentobarbital was produced by grinding techniques and by evaporation from alcoholic solutions. The cocrystal nature of this phase was established unequivocally by single crystal X-ray structure determination. The asym-metric unit contains one formula unit. In the cyclopentobarbital molecule, the cyclopentenyl ring is disordered over two positions related by a rotation of approximately 180° about its C‒C bond to the pyrimidine ring. The two NH groups of the cyclopentobarbital molecule form N—H···N and N—H···O bonds to piperidine and hydroxyl groups, respectively, belonging to different codeine molecules. In addition, the hydroxyl and methoxy groups of neighboring codeine molecules are linked by O—H···O interactions, resulting H-bonded framework structure of codeine and cyclo-pentobarbital molecules. The cocrystal was also characterized by thermal analysis, X-ray powder diffraction and IR spectroscopy.

Two novel dsRNA mycoviruses were found in different isolates of Diplodia fraxini, NW FVA 1581 and NW FVA 1706, which were isolated from a root, associated with stem collar necrosis of Fraxinus excelsior L. Both mycelia are infected by a novel fusagravirus, which was named Diplodia fraxini fusagravirus 1 (DfFV1), and isolate NW FVA 1706 is additionally infected by a novel partitivirus, which was denominated as Diplodia fraxini partitivirus 1 (DfPV1). The one-segmented, bicistronic genome of DfFV1 is composed of about 8,500 bp. Their ORFs are connected by a 1 slippery heptamer sequence and the 3’ terminal ORF is coding for the viral RdRp. The genome of DfPV1 is composed of three, monocistronic dsRNA segments ranging from 1,755 bp (dsRNA 1) over 1,588 bp (dsRNA 2) to 1,233 bp (dsRNA 3). Based on genome organization and phylogenetic positions, DfFV1 was assigned to the proposed family of “Fusagraviridae” and DfPV1 to the genus Gammapartitivirus within the family of Partitiviridae. Ultra-structural analysis showed that polysomal structures were stabilized in the single infection and none of these structures could be isolated in the double infection. It is assumed that DfFV1 has an opportunistic lifestyle, being either protected by ribosomes or by transcapsidation from particles of DfPV1.

With the rapid development of electronic and communication technology in military radar, the demand for microwave absorbing materials in low-frequency with thin layer is growing increasingly. In this study, flexible Co3O4/CC (carbon cloth) composites derives from Co-MOFs (metal-organic frameworks)/CC are prepared by hydrothermal and thermal treatment processes. The flexible precursors of Co-MOFs/CC are calcined with different calcination temperatures, which the material structure, dielectric properties and microwave absorption performance are changed. With the increase of calcination temperature, the minimum reflection loss of the corresponding Co3O4/CC composites gradually moves to the lower frequency with thinner thickness. In addition, the Co3O4/CC composites with 25 wt% filler loading ratio exhibit the minimum reflection loss (RL) of -46.59 dB at 6.24 GHz with 4.2 mm thickness. When the thickness is 3.70 mm, the effective absorption bandwidth is 3.04 GHz from 5.84 to 8.88 GHz. This study not only proves that the composite Co3O4/CC is a kind of outstanding microwave absorbing material with better flexibility, but also provides a useful inspiration for the low frequency and broadband microwave absorbing material.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.

Biotin-based proximity labeling approaches, such as BioID, have demonstrated their use for the study of mitochondria proteomes in living cells. The use of genetically engineered BioID cell lines enables the detailed characterization of poorly characterized processes such as mitochondrial co-translational import. In this process, translation is coupled to the translocation of the mitochon-drial proteins, alleviating the energy cost typically associated with the post-translational import relying on chaperone systems. However, the mechanisms are still unclear with only few actors identified but none that have been described in mammals yet. We thus profiled the TOM20 prox-isome using BioID, assuming that some of identified proteins could be molecular actors of the co-translational import in human cells. The obtained results showed a high enrichment of RNA bind-ing proteins close to the TOM complex. However, for the few selected candidates, we could not demonstrate a role in the mitochondrial co-translational import process. Nonetheless, we were able to demonstrate additional uses of our BioID cell line. Indeed, the experimental approach used in this study is thus proposed for the identification of mitochondrial co-translational import effec-tors and for the monitoring of protein entry inside mitochondria with a potential application in the prediction of mitochondrial protein half-life.

By enhancing the bitumen properties with the additives produced from wastes not only can be improved the performance of flexible pavements but also can be contributed to the environment. This research aims to produce a novel pyrolytic char from different wastes and to investigate the usability of this char as an additive in bitumen. In this study, firstly, the pyrolytic char was produced from co-pyrolysis of three different wastes including waste paper cups, polypropylene (PP) and polyethylene terephthalate (PET) wastes. Properties of the char were determined by using CHN (carbon, hydrogen, nitrogen) and Fourier transform infrared spectroscopy (FTIR) analyses. The high temperature rheological properties of binders were evaluated by using DSR (dynamic shear rheometer), RV (rotational viscometer), softening point and penetration tests. Additionally, specific gravity, storage stability, high temperature performance grades (PG) and temperature susceptibilities of binders were determined. Test results showed that this pyrolytic char enhanced the high temperature properties of neat bitumen by increasing softening point, viscosity, rutting resistance and high temperature PG. And, it can be said that the bituminous binder modified with this pyrolytic char had a good storage stability when it was used at 8% ratio in neat bitumen.

Diethyldithiocarbamate (DDTC) has been employed in the sulfide ore flotation process, due to its excellent collection performance. Herein, we investigated the interfacial adsorption behavior of DDTC on four mineral phases of high-sulfur residue — sulfur, pyrite, sphalerite and lead sulfate. The adsorption behavior — adsorption structure and energy and electron localization function cross section — of DDTC and H2O were explored using density function theory calculation. The result was helpful to construct a co-adsorption model of DDTC and H2O, which was validated by the pure minerals flotation operation and the characterization of fourier transform infrared spectra. The co-adsorption model indicated that the DDTC adsorption on the sulfur, sphalerite and lead sulfate was weak with physical bonding, while its adsorption on the pyrite was strong with chemical bonding. Practical bench-scale operation of high-sulfur residue flotation was performed, whose result was different from that obtained from the pure mineral flotation. To explain the difference, our developed model predictions and the mineral fugacity pattern analysis on the high-sulfur residue flotation were synergistically used. Overall, this work first proposed the co-adsorption model of DDTC and H2O and provided important insights into the interfacial adsorption in the high-sulfur residue flotation.

Metchnikovellids (Microsporidia: Metchnikovellida) are poorly studied hyperparasitic micro-sporidia that live in gregarines inhabiting the intestines of marine invertebrates, mostly poly-chaetes. Our recent studies showed that the diversity of the metchnikovellids might be signifi-cantly higher than previously thought, even within a single host. Four species of metchnikovellids were found in the gregarines inhabiting the gut of the polychaete Pygospio elegans from littoral populations of the White and Barents Seas: the eugregarine Polyrhabdina pygospionis is the host for Metchnikovella incurvata and M. spiralis, while the archigregarine Selenidium pygospionis is the host for M. dogieli and M. dobrovolskiji. The most common species in the White Sea is M. in-curvata, while M. dobrovolskiji prevails in the Barents Sea. The gregarines within a single worm could be infected with different metchnikovellid species. However, co-infection of one and the same gregarine with several species of metchnikovellids has never been observed. The difference in prevalence and intensity of metchnikovellid invasion apparently depends on the features of the life cycle and on the development strategies of individual species.

New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.

The emergence of the circular economy, and the evolving paradigms in the treatment and management of wastewater, have opened up an opportunity for co-digestion of organic waste (i.e., food waste) with sewage sludges to enhance resource recovery at wastewater treatment plants (WWTPs). This paper reviewed the potential for anaerobic co-digestion of food waste and sewage sludges, as well as alternative sustainable food waste handling systems in South Africa. The promotion of the circular economy by the latest national solid waste management strategy and the ongoing efforts for resource recovery by the wastewater sector suggests that anaerobic co-digestion of food waste and sewage sludge is possible in South Africa. Furthermore, an integrated food waste disposer (FWD) system was identified as a sustainable alternative for food waste handling. To formulate a roadmap for future food waste and sewage sludge co-digestion implementation, a multi-disciplinary investigation is required to bridge the literature gap.

Despite knowledge concerning stakeholders and the economic advantages of consultation, collaboration and innovation, analysis of the sustainability implications of the geothermal industry has tended to take a high-level or systemic overview of national performance. This study seeks to begin to fill this gap in the academic and grey literature, investigating the following research question: how do projects in the Icelandic geothermal energy sector create co-benefits with stakeholders and reflect the integration of sustainable energy development (SED)? The focus of its analysis is on identifying who are the stakeholders, what are the sustainability benefits co-created with stakeholders, and when in the project lifecycle do these occur. Based on eleven semi-structured interviews with project managers in Iceland’s geothermal industry, the study identifies a broad array of stakeholders in the sector, including national and municipal governments and public sector institutions, businesses, the public, employees and landowners. The sustainability co-benefits of Iceland’s geothermal power projects are broad and cut cross all six themes of SED and multiple phases of the project lifecycle. Although the sustainability benefits are very apparent, trade-offs are reported between the pursuit of an economically efficient energy system and nature conservation. This relates to unsustainable utilization of the resources and the environmental externalities of power production and consumption. Efforts to mitigate these effects are ongoing and the further pursuit of SED is likely in Iceland given its recognition within the nation’s new energy policy and to meet ambitious greenhouse gas emissions reduction targets in the government’s climate action plan. These are issues that are prominent in other nations seeking to decarbonize energy systems through increased utilization of geothermal resources.

Water is essential for all living things however its pain has become serious. Many industrial activities cause its pollution by the release of polluting byproduct. Waste water treatment is hence necessary. In this context, the waste water of the textile industry containing Red Acid 52 was treated by the solid waste of the washed natural phosphate byproduct. Natural phosphate was also studied. The solid materials were first characterized by chemical analysis, Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The phosphate materials were after that, tested in the adsorption of the Red Acid 52. The experimental data indicated that the phosphate waste rock allowed the removal of Red Acid 52. Its maximum retention capacity attained 18.4 mg.g-1. Calcinations of materials inhibits the removal capacity found reduced by 60 to 70%. The adsorption kinetics of the Red Acid 52 on the material is well described by the pseudo second order model while the adsorption isotherms are identified by the Langmuir model. Hereafter, the thermodynamic study revealed that the adsorption process is spontaneous and exothermic. Keywords: Waste water, Phosphate co-product, Adsorption, Red Acid 52.

In recent years, hetero atom incorporated specially structured metal-free carbon nanomaterials have drawn huge attention among researchers. In comparison to the un-doped carbon nanomaterials, hetero atoms like nitrogen, sulphur, boron, phosphorous etc. incorporated nanomaterials become well-accepted as potential electrocatalysts in water splitting, supercapacitors and dye-sensitized solar cells. This review emphasizes on the mostly popular synthetic strategies utilized in last two decades and their excellent performance in electrocatalytic studies.

G-protein coupled receptors (GPCRs) are large protein families known to be important in many cellular processes. They are well known for their allosteric activation mechanisms. They are drug targets for several FDA-approved drugs. We have investigated the diversity of the ligand binding site for these class of proteins against their cognate ligands using computational docking, even if their structures are known in the ligand-complexed form. The cognate ligand of some of these receptors dock at allosteric binding site, with better score than the binding at the conservative site. Further, ligands obtained from GLASS database, which consists of experimentally verified GPCR ligands, also show allosteric binding to GPCRs. The allosteric binders show strong affinity to the binding site, though the residues at the binding site are not conserved across GPCR subfamilies.

There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

Introduction The COVID-19 virus was initially reported in Dec 2019 as the causative agent of a pneumonia breakout in Wuhan China. This virus rapidly spread from China to Europe and the East Coast of the United States eventually reaching the South West United States and indigenous tribes in mid -March. Since, then the indigenous tribes have been devasted by the virus which the Governor of New Mexico has likened as an existential threat. Methodology A PubMed search was performed utilizing the words: Navajo Indian, Indigenous Indian, Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal Results: Navajo’s and other indigenous peoples may have elevated levels of ACE2 receptors in their lungs and other tissues allowing greater susceptibility to the COVID-19 virus. Increased levels of diabetes and protein nutrition are directly related to increased morbidity and mortality in this group while obesity, COPD, and heart diseas are not. The increased morbidity and mortality is exasperated by an inability to test for COVID-19 Conclusion: The infectivity rate of Navaho’s on the reservation is 22 times higher than the national average with a death rate near 4%. Comorbidites account for some of the increased morbidity and mortality while lack of access to adequate health care unnecessarily magnifies the poor outcome. The threat to indigenous tribes in the Southwest of COVID-19 is dire.

Carbon dioxide has become a global challenge, where the emissions have become more than what could be handled. In this regard, conversion of CO2 to value added chemicals and thus recycling CO2 became a viable option. One of these options is the use of a process in strong development: oxycombustion. However, the gases resulting from this process contain some traces of impurities that can hinder the recovery of CO2 such as NO and CO. This work has therefore focused on the study of the reaction of NO reduction by CO in an oxidizing medium, using catalytic materials based on various supported noble metals. These materials were extensively characterized by a variety of methods including BET surface area measurements, hydrogen chemisorption, Transmission Electron Microscopy (TEM) and H2 temperature programmed reduction (H2-TPR). The obtained results show that the catalytic behaviour of M/Al2O3 catalysts in CO oxidation and NO reduction with CO in oxidative conditions depends mainly on the nature of the metal. The best result for these both reactions is obtained with Pt/Al2O3 catalyst. The Pt nanoparticles existing in the metallic form (Pt°) showed by TPR could explain the activity.

On the eve of the Brexit process, in the context of a rising Euroscepticism that fuels the modest confidence of European citizens in their national and European institutions, the article assesses the efficiency and effectiveness of the European Parliament within the framework of the ordinary legislative procedure (co-decision). After defining and formulating the main indicators, the paper analyses the micro- and macro-performance of the European Parliament within the decision-making process from a quantitative-qualitative and a qualitative-quantitative perspective, highlighting the relativizing factors and the responsiveness of the European decision-making process to the Europeans’ needs.

ZnO films with Ti atoms incorporated (TZO) in a wide range (0-18 at. %) have been grown by reactive co-sputtering on silicon and glass substrates. The influence of the titanium incorporation in the ZnO matrix on the structural and optical characteristics of the samples has been determined by Rutherford backscattering spectroscopy (RBS), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The results indicate that the samples with low Ti content (< 4 at. %) exhibit the wurtzite-like structure, with the Ti+4 ions substitutionally incorporated into the ZnO structure, forming Ti-doped ZnO films. In particular, very low concentration of Ti (<0.9 at. %) leads to a significant increase of the crystallinity of the TZO samples. Higher Ti contents give rise to a progressive amorphization of the wurtzite-like structure so samples with high Ti content (≥18at. %), displays an amorphous structure indicating the XPS analysis a predominance of Ti-O-Zn mixed oxides. The energy gap, obtained from absorption spectrophotometry, increases from 3.2 eV for pure ZnO films to 3.6 eV for those with the highest Ti content. Ti incorporation in the ZnO samples below 0.9 at. % rises both, the blue (380 nm) and green (550 nm) bands of the photoluminescence (PL) emission, thereby indicating a significant improvement of PL efficiency of the samples.

Cu,N-TiO₂ nanotube (Cu,N-TNT) is prepared through a novel magnetron sputtering and anodic oxidation method. Then the morphology, structure and physicochemical property of Cu,N-TNT was analyzed by XRD, SEM, TEM, EDX and UV-vis-DR. The results indicate that the evenly doped copper is beneficial to the transformation of the TNT from anatase to rutile and play a key role in the morphology of the Cu,N-TNT. The doped Cu and N in the TNT influence the growth orientation of the TiO₂ crystals, which result in the lattice distortion and wider the interplanar spacing 60s-Cu,N-TNT has less band gap and stronger absorption intensity in visible region than other Cu,N-TNT samples, which make the combination rate of photogenerated electron and photogenerated hole decrease greatly, thus beneficial to its physicochemical property.

Polymer-based piezoelectric biomaterials have already proven their relevance for tissue engineering applications. Further, the morphology of the scaffolds plays also an important role in cell proliferation and differentiation. The present work reports on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), a biocompatible, biodegradable and piezoelectric biopolymer that has been processed in different morphologies, including films, fibres, microspheres and 3D scaffolds. Further, the corresponding magnetically active PHBV-based composites were also produced. The effect of the morphology on physico-chemical, thermal, magnetic and mechanical properties of pristine and composites samples was evaluated, as well as their cytotoxicity. It was observed that the morphology does not strongly affect the properties of the pristine samples but the introduction of cobalt ferrites induces changes in the degree of crystallinity that could affect the applicability of prepared biomaterials. Young modulus is dependent of the morphology and also increases with the addition of cobalt ferrites. Both, pristine and PHBV/cobalt ferrite composite samples are no cytotoxic, indicating their suitability for tissue engineering applications.

This paper presents a new methodology that provides the analysis of surface texture changes in areas adjacent to the volcano and its impact product of volcanic activity. To do this, algorithms from digital image processing such as the co-occurrence matrix and the wavelet transform are used. These methods are working on images taken by the Landsat satellite platform sensor 5 TM and Landsat 7 ETM + sensor, and implemented with the purpose of evaluating superficial changes that can warn of surface movements of the volcano. The results were evaluated by similarity metrics for grayscale images, and validated in two different scenarios that have the same type of eruption, but differ, essentially, in climate and vegetation. Finally, the proposed algorithm is presented, setting the parameters and constraints for implementation and use.

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which causes considerable economic losses to the poultry industry worldwide. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing S1 and N proteins, mono-expressing S1 or N proteins alone of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, boosting with the same dose 14 days later, and following challenge with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels as well as the percentages of CD4+ and CD8+ T lymphocytes were detected within 28 days post-vaccination (dpv). The morbidity, mortality, and re-isolation of virus from the tracheas and kidneys of challenged birds were evaluated at 5 days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocyte in rHBM-S1-N group were higher than those of rHBM-S1 and rHBM-N groups, especially the cellular immunity response. At 5 dpc, the mortality, morbidity and virus re-isolation rate of rHBM-S1-N were slightly higher than those of H120 group, but were lower than those of rHBM-S1 group and rHBM-N group. The present study demonstrated that the protection of recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing S1 or N protein alone. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various drugs in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model information is based on three published manuscripts; therefore, this is a follow-up study. The model will also serve as a practical guide to monitor and evaluate epidemiological TB management plans.

BRAF is one of the most frequently mutated oncogenes, with an overall frequency of about 50%. Targeting BRAF and its effector mitogen-activated protein kinase kinase 1/2 (MEK1/2) is now a key therapeutic strategy for BRAF-mutant tumors, and therapies based on dual BRAF/MEK inhibition showed significant efficacy in a broad spectrum of BRAF tumors. Nonetheless, BRAF/MEK inhibition therapy is not always effective for BRAF tumor suppression, and significant challenges remain to improve its clinical outcomes. First, certain BRAF tumors have an intrinsic ability to rapidly adapt to the presence of BRAF and MEK1/2 inhibitors by bypassing drug effects via rewired signaling, metabolic, and regulatory networks. Second, almost all tumors initially responsive to BRAF and MEK1/2 inhibitors eventually acquire therapy resistance via an additional genetic or epigenetic alteration(s). Overcoming these challenges requires identifying the molecular mechanism underlying tumor cell resistance to BRAF and MEK inhibitors and analyzing their specificity in different BRAF tumors. This review aims to update this information.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various medications and antibiotics in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and con-trolling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model will also serve as a guide to monitor and evaluate epidemiological TB management plans.

The paradigm of molecular communications is applied to the concrete case for delivering electrically charged nanoparticles to tumor. Once them have been injecetd in blood it is expecetd an optimal outcome as to reduce toxicity and minimal dispersion of drugs in the blood stream. With a fraction of nanoparticles arrives to surface of tumor, the scattered part of injected ones can minimize the success of scheme of drug delivery. In this paper is presented a theory based at the sequence electrodynamics-diffusion-Bayes theorem. The resulting probability of Bayes at the end of sequence, might be telling us that dynamical processes based in the injection of electrically charged nanoparticles might be dictated by stochastic formalism more that biochemical approaches by which makes impossible to know the success or fail of drug delivery dynamics. Illustrations demonstrating the transition of a linear to nonlinear scenario are presented

Nanosystems-based antifungal agents have emerged as an effective strategy to address issues related to drug resistance, drug release, and toxicity. Among the different materials used for drug delivery, multifunctional polymers have proven to be ideal due to their versatility. This review provides an overview of the various types of nanoparticles used in antifungal drug delivery systems, with a particular emphasis on the types of polymers used. The review focuses on the application of drug delivery systems and the release behavior of these systems. Furthermore, the review summa-rizes the critical physical properties and relevant information utilized in antifungal polymer nanomedicine delivery systems, and briefly discusses the application prospects of these systems.

Background: Although Tuberculosis (TB) is one of the oldest diseases known to mankind, many practitioners are still unaware of various aspects of management of TB including drug resistant TB. To be able to make an impact on the disease burden we need to understand the knowledge, attitude and practices (KAP) of practitioners, both in government and private sector, towards TB case management. Methodology: A random cross-sectional survey of 99 respondents to assess the KAP towards TB case management using a digital semi-structured questionnaire which was pre-tested and administered to allopathic practitioners from across States in North and Central India. Results: 77% responders were government doctors and 23% were private practitioners. Chest physicians accounted for 61% of the responders. 26% of government and 78% of private doctors relied on sources which are difficult to validate for their knowledge on drug resistant TB management. There were large variations seen in knowledge on modes of transmission, standard precautions, extent of drug resistant TB, diagnostics as well as treatment regimen for drug resistant TB. Conclusion: The knowledge of both sector doctors especially amongst private practitioners with respect to the awareness of extent, diagnosis, and treatment and infection control measures for drug resistant TB is suboptimal which translates to poor diagnostic, therapeutic and infection control choices amongst private practitioners. If India has to achieve the targets for TB Elimination by 2025, serious work needs to be done to upgrade the knowledge of the private sector doctors on drug resistant tuberculosis. The Ministry of Health and Family Welfare, GoI needs to have regular educational programs for the private practitioners coupled with awareness campaigns and frequent surveys to assess the knowledge, attitude and practices being followed in the private sector for TB management including drug resistant TB.

Both Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are main injurious cutaneous medication reactions that mostly affect the epidermis and mucus membranes. TEN and SJS affecting nearly 1 or 2/1,000,000 people per year, and can recognized as medical crises since they may be deadly. Mucocutaneous discomfort, hemorrhagic erosions, erythema, and more or less severe epidermal separation that appear as ulcer and patches of dermic loss are their defining characteristics. The sole difference between TEN and SJS at this time is the degree of skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug reactions (cADRs). In the majority of cases, drugs are considered as the principal reason of SJS/TEN, but herpes simplex virus and Mycoplasma pneumoniae infections are also recognized causes, along with lesser number of cases in which the cause is still unknown. Among the drugs with a "high" likelihood of producing TEN/SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, other sulfonamide antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is strong genetic evidence for SJS and TEN in Han Chinese due to the substantial association between the human leukocyte antigen (HLA-B*1502) and SJS brought on by CBZ. The diagnosis is made mostly based on clinical symptoms and the histological study of a dermal biopsy. Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS) are among the differential diagnoses. The management of patients with SJS/TEN is complicated by the high risk of mortality, necessitating early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative drug, specialized supportive care, and high-dose injectable Ig therapeutic interventions. The reported fatality rates for SJS are 1-5% on average and 25-35% for TEN; it can be even higher in patients who are elderly or who have a significant amount of epidermal detachment on their skin. More than 50% of TEN patients who survive the disease experience long-term consequences.

Nanotechnology is making significant transformation to our world, especially in healthcare and the treatment of diseases. It is widely used in different medical applications, such as in treatment and detection. Targeting diseased cell with nanomedicines is one of the numerous applications of nanotechnology. Targeted drug delivery systems for delivering various types of drugs to specific sites are such a dynamic area in pharmaceutical biotechnology and nanotechnology. Compared to conventional drugs, nanomedicines have a higher absorption and bioavailability rate, improving efficacy and minimizing side effects. There are several drug delivery systems including metallic nanoparticles, polymers, liposomes, and microspheres, but one of the most important is the niosomes, which are produced by nonionic surfactants. Because of the amphiphilic nature and structure, hydrophilic or hydrophobic drugs can be loaded into niosome structures. Other compounds, including cholesterol, can also be applied to the niosomes' backbone to rigidize the structure. Several variables such as the type of surfactant in niosome production, the preparation method, and the hydration temperature can affect the structure of the niosomes. Nevertheless, in-silico design of drug delivery formulations requires molecular dynamic simulation tools, molecular docking, and ADME (absorption; distribution; excretion; metabolism) properties, which evaluate physicochemical features of formulation and ADME attitudes before synthesis, investigating the interaction between nano-carriers and specific targets. Hence, experimenting in-vitro and in-vivo is essential. In this review, the basic aspects of niosomes are described including their structure, characterization, preparation methods, optimization with in-silico tools, factors affecting their formation, and limitations.

Drug discovery has been initially attributed to coincidence or trial and error where the traditional approach was complex, lengthy, and expensive. Conventional drug discovery methods require the costly random screening of synthesized compounds or natural products. Another downside for this approach is the wide dependency on the experimental use of animals for in vi-vo testing. Currently, in silico modeling has become a vital tool for drug discovery and repurposing, and molecular docking is being used to find the best matching between a ligand and a molecule. Practical application of in silico docking will predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana. Originally investigated for its pesticide capability, BEA is now considered as a molecule of interest for its potentially diverse biotechnological applications in the pharmacological industry and the field of medicine. In this manuscript, we will provide an overview of the repurposing of BEA into a potentially superior therapeutic molecule in a broad range of diseases. Furthermore, considerable attention has been given to the fundamental role of in silico techniques to i) further investigate the spectrum of this secondary metabolite and ii) elucidate the pathways of BEA for its promising therapeutic action

With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.

Introduction Tuberculosis is common in Pakistan. Due to various factors including socioeconomic factors, compliance is poor to anti-tuberculosis drugs, leading to resistance. We aim to determine the prevalence of Multidrug resistance (MDR) tuberculosis in Pakistani population.Methods A prospective observational study was conducted from April 1, 2019, to December 31, 2019, in the Pulmonology department of a tertiary care hospital in Pakistan. Culture and sensitivity were assessed using a sputum sample or, in cases of an absent sputum sample, from Broncho alveolar lavage.ResultsApproximately 71.3% percent patients who had tuberculosis were found to be resistant to Isoniazid and around 48.6% did not respond to Rifampin. Multi-drug resistant was found in 29.4% participants.ConclusionMulti-drug resistance tuberculosis is very prevalent in Pakistan, which may increase burden on health care system and may lead to various complications of tuberculosis.

The influence of lignin modification on drug release and pH-dependent releasing behaviour of oral solid dosage form was investigated using three different formulations. The first formulation contains microcrystalline cellulose (MCC101) as excipient and paracetamol as active pharmaceutical ingredient (API). The second formulation includes Alcell lignin and MCC 101 as excipient and paracetamol, and the third formulation consists of carboxylated Alcell lignin, MCC 101 and paracetamol. Direct compaction was carried out in order to prepare the tablets. Lignin can be readily chemically modified due to the existence of different functional groups in its structure. The focus of this investigation is on lignin carboxylation and its influence on paracetamol control release behaviour at varying pH. Results suggest that carboxylated lignin tablets had the highest drug release, which is linked to their faster disintegration and lower tablet hardness.

Objective: To evaluate the status of receiving education on rational drug use, the criteria in medical drug selection, and level of knowledge of dentists working in a dentistry faculty in Turkey. Material and Methods: This was a descriptive study based on a questionnaire. One hundred seventeen (74%) dentists volunteered to participate in the study. The questionnaire consisted of 20 questions investigating sociodemographic features and rational drug use. Results: The mean age of the dentists was 30.8 ± 7.2 years, and 62.4% were men. The mean period of professional experience was 8.9±7.1 years. The most frequently used resources of references while prescribing medicine were Vademecum (medical drug guide) (61.5%), the internet (59.0%), and colleagues (49.6%). The most frequently reported condition described as ‘good’ was drug indications (43.6%). The dentists had a moderate level of information about posology, and administration route (48.7%), pharmacologic features (48.7%), and contraindications (46.2%). The number of dentists who stated that they considered cost while prescribing was low [always (6%), and frequently (15.4%)]. Rational drug use education had been received by 23.9% of the dentists. Conclusions: The dentists were found to have a lack of adequate and effective education on rational use of drugs. Regular and continuous education before and after graduation is a necessity for dentists and for their patients.

Same-day desensitization (SDD) is a procedure in which desensitization to the drug suspected of causing the hypersensitivity reaction (HR) is performed on the same day as the patient's reaction. In rapid drug desensitization (RDD), desensitization to the suspected drug is performed after an allergological study. The aim of the study was to analyze the diagnostic capacity of the allergist in Oncology Day Hospital (ODH) to establish the phenotype of the HR, in the context of SDD, based exclusively on clinical biomarkers. This is a study of patients treated with desensitization on the same day they had a HR. Later an allergological study (clinical history, skin test, risk assessment, serological biomarkers, drug provocation test if applicable) was performed prior to the following administrations. A total of 35 successful SDDs were performed. A high concordance (91.5% of patients) was found between the phenotype suspected by the allergist after the initial assessment of the patient prior to SDD and the final phenotype after subsequent allergological study performed in the Allergy Department. The presence of the allergist at the ODH allows, in addition to initial treatment according to phenotype, desensitization on the day of the reaction. This will lead to personalized and precision allergology.

In this study, a simple machine learning-based quantitative structure-activity relationship (QSAR) model was developed to predict the inhibitory potency (pIC50 values) of FLT3 tyrosine kinase inhibitors, pivotal in treating Acute Myeloid Leukemia (AML). Distinctively, our model leverages an extensive and diverse dataset, 14 times larger than those employed in prior studies within this field, enabling an unparalleled scope of compound analysis. This vast dataset, combined with further exploration of molecular descriptors, enabled predictions of extraordinary precision, covering a broader spectrum of FLT3 inhibitors than was previously possible. The Random Forest Regressor (RFR) algorithm, selected for its superior predictive performance, was trained with 1080 inputs and validated through comprehensive external and internal methods. It achieved an remarkable coefficient of determination (R^2) of 0.941 and a standard deviation of 0.235 on a test set of 270 compounds, highlighting the efficacy of model in predicting FLT3 inhibitory activity. Key molecular descriptors were identified, enhancing our understanding of structural requirements for inhibitor potency. Additionally, we developed a user-friendly computational tool that enables the rapid prediction of pIC50 values. Utilizing this tool, potential FLT3 inhibitors were identified through ligand-based virtual screening. This study represents a major advancement in FLT3 inhibitor discovery by utilizing a simple QSAR-machine learning model. It enables more efficient and precise identification of potential drug candidates at an early stage, promising a faster development of targeted therapies and streamlining the ligand-based drug design process.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those &gt;55 years of age, ~four times more commonly observed in men than women. The most important risk factor for developing bladder cancer is tobacco smoking, which accounts for ∼50% of cases followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC is highly aggressive and remains generally incurable since these cancers are associated with intrinsic and acquired drug resistance. UCC is highly lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss the novel therapies to improve the management of mUCC.

Gastro-retentive floating microspheres were developed as a result of the recent advancements in floating delivery systems for drugs (FDDS), which included the uniform dispersion of multiparticulate dosage forms along the GIT. This could lead to more consistent drug absorption and a lower risk of local irritation. Microballoons (MB), a multi-unit extended release with a sphere-shaped cavity encased in a tough polymer shell, have been developed as a dosage form with exceptional buoyancy in the stomach. This preparation for constrained intestinal absorption is made to float on top of gastric acid, that has a relative density lower than 1.By using enteric acrylic polymers and the emulsion solvent diffusion method, microballoons are prepared and filled to drug in one‘s outer polymer casings. Enteric acrylic plastics are used to generate microballoons that are drug-loaded in one‘s external polymer casings and dissipate in a solution of dichloromethane and ethanol. Cavity development in microparticles seems to be particularly correlated with dichloromethane evaporation. Microballoons with a drug distributed or dispersed all through the particle-matrix have the potential for a controlled drug release and float continuously for more than 12 hours in vitro out over the surface of an acidified dissolution medium with surfactant. The drug is released slowly and at the desired rate as the microballoons glide over the components of the stomach, increasing gastro-retention time and lowering fluctuations in plasma concentration.

Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and these efforts continue to be con-troversial. Drug repurposing strategies are a promising alternative to de-novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can be revealed only after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which could be associated with potential side effects of these therapeutics. The approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.

COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, TMPRSS2, and AP2-associated protein kinase 1. In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of drug candidates to target receptors, providing insight into their potential efficacy. However, it is crucial to consider both the advantages and limitations of these studies and to complement them with experimental validation to ensure the efficacy and safety of identified drug candidates.

Drugs-drugs interactions(DDI) are entities composed of different chemical substructures (functional groups). In existing methods that predict drug–drug interactions based on the usage of substructures, each node is considered the center of a substructure, and adjacent nodes eventually become centers of similar substructures, resulting in redundancy. Furthermore, the significant differ- ences in structure and properties among compounds can lead to unrelated pairings, making it difficult to integrate information. This heterogeneity negatively affects the prediction results. To address these issues, we propose a drug–drug interaction prediction method based on substructure signature learning (DDI-SSL). This method extracts useful information from local subgraphs surrounding drugs and effectively utilizes substructures to assist in predicting drug side effects. Additionally, a deep clustering algorithm is used to aggregate similar substructures, allowing any individual subgraph to be reconstructed using this set of global signatures. Furthermore, we developed a layer-independent collaborative attention mechanism to model the mutual influence between drugs, generating signal strength scores for each class of drugs to mitigate noise caused by heterogeneity. Finally, we evaluated DDI-SSL on a comprehensive dataset and demonstrated improved performance in DDI prediction compared to state-of-the-art methods.

The study aimed to identify clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019–2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, total number of DDIs was significantly higher among prescribed medications compared with the list of taken drugs (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among prescribed and taken medications, correspondingly (p < 0.05). Median DDI numbers between prescribed versus taken medications were Me = 2, IQR 0-7 and Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among prescribed medications compared with taken medications (p < 0.05). Women were taking significantly more drugs and had higher rates of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, patient engagement in reporting adverse drug reactions, and genetic profiling of patients to avoid potentially serious DDIs.

Background: This article evaluates the perception of drug use control and strategies in Valencia City (Spain) in a general and clinical population, in two independent studies. Material and Methods: 1071 people participated. In the Study 1 (n= 924) the entire sample came from general population (GP), and in the Study 2 (n=147), 68 were drug users being treated in an Addictive Behaviors Unit (ABU), and 79 people of the GP. The drug use control perception and strategies in both subgroups were compared. The participants filled in the Drug Use Strategies Scale and a Drug Use Survey. Results: A high level of perception of drug control in GP was obtained (72,7% in the Study 1 and 67,5% in the Study 2), and 32.5% in ABU subgroup. People in the PG and drug users in treatment differ in some control strategies. A predictive profile of the perception of control was obtained for the Study 2. Conclusion: The high degree of perception of controlling drug use in the GP, and partially in drug users being treated, and the specific control strategies reported suggests that moderate use and drug control strategies are a great value alternative to bear in mind compared to abstinence.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine and so on. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. However, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidences of antioxidant effects support the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. A study suggests that daily intake of 100 mg of flavonoids through diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/ therapeutic molecules.

In 2019, Chinese government implemented the first round of National Centralized Drug Procurement (NCDP) pilot (so-called "4+7" policy) in mainland China, achieved a prominent price reduction of 52% on average for 25 bidding winning products. Under cross-price elasticity theory, the price behavior of pharmaceutical enterprises for policy-related drugs might change. This study used drug purchasing data from the Centralized Drug Procurement Survey in Shenzhen 2019, and applied single-group Interruption Time Series (ITS) design to examine the impact of "4+7" policy on the drug price index (DPI) of policy-related drugs. The ITS analysis showed that the DPI of winning (-0.183 per month, p&lt;0.0001) and non-winning (-0.034 per month, p=0.046) products significantly decreased after the implementation of "4+7" policy. No significant difference was found for the immediate change of DPI for alternative drugs (p=0.537), while a significant decrease in change trend was detected in the post-"4+7" policy period (-0.003 per month, p=0.014). The DPI of the overall policy-related drugs significantly decreased (-0.261 per month, p&lt;0.0001) after "4+7" policy. These findings indicate that the price behavior of pharmaceutical enterprises changed under NCDP policy, while the price linkage effect is still limited. It is necessary to further expand the scope of centralized purchased drugs and strengthen the monitoring of related drugs regarding price change and consumption structure.

Nanoprecipitation by liquid anti-solvent precipitation is one of the most versatile methods to produce pure drug nanoparticles (PDNPs) owing to the ability to optimize the properties of the product. Nevertheless, nanoprecipitation shows broad particle size distribution and low physical stability, leading to high batch-to-batch variability and challenging the bench-to-bedside translation. Microfluidics has emerged as a powerful tool to produce PDNPs in a simple, reproducible, and cost-effective manner with excellent control over NP size. In this work, we designed and fabricated T- and Y-shaped Si-made microfluidics device and used it to produce pure NPs of three kinase inhibitors of different lipophilicity and water-solubility, namely imatinib, dasatinib and tofacitinib, without the use of colloidal stabilizers. PDNPs display sizes in the 90-350 nm range (dynamic light scattering) and a rounded shape (high-resolution scanning electron microscopy). Analysis by X-rays diffraction and differential scanning calorimetry confirmed that this method results in highly amorphous NPs. In addition, we show that the flow rate of solvent, the anti-solvent, and the channel geometry of the device play a key role in the size of the generated NPs.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.

SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease (Mpro) are available. The reported structure of the target Mpro was utilized in this study to identify potential drugs for COVID-19 using molecular docking based virtual screening of all approved drugs. The results of this study confirm preliminary reports that some of the drugs approved for treatment of other viral infections have the potential for treatment of COVID-19. Selected antiviral drugs, approved for human therapeutic applications, were ranked for potential effectiveness against COVID-19, based on predicted binding energy to the target Mpro of SARS-CoV-2, and novel candidates for drug repurposing were identified in this study. In addition, potential mechanisms for beneficial off target effects of some drugs in clinical trials were identified by using molecular docking.

This study represents a significant stride in advancing furan chemistry, presenting the synthesis of high-molecular-weight polyfurfuryl alcohol (PFA) resin (Mw = 118,959 g/mol) from furfuryl alcohol (FA) using a co-catalytic system as against the conventional single-catalytic methods. The resulting PFA resin is fully characterised, and we conclude that it exhibits good shelf life and potential in diverse applications, serving as a standalone moulded material or contributing to composites, coatings, adhesives, and nanostructured carbons.

Decarbonization of air mobility requires the decarbonization of its energy. While biofuels will play an important role, other low carbon energy carriers based on electricity are considered: battery electrification, liquid hydrogen (LH₂) or eFuel, a hydrogen-based energy carrier. Each energy carrier has its own conversion steps and losses and its own integration effects with the aircraft. These combinations lead to different energy requirements and must be understood to compare their cost and CO₂ emissions. Since they are all electricity-based, this study compares these energy carriers using the well to rotor methodology when applied to a standard Vertical Take-Off and Landing (VTOL) air mobility mission. This novel approach allows one to understand that the choice of the energy carrier dictates the propulsive system architecture, leading to integration effects with the aircraft which can significantly change the energy required, from 400 to 2665 kWh for the same mission. These deviations lead significant differences in CO₂ emissions and costs. Battery electrification is impacted by the battery manufacturing but has the lowest electricity consumption. It is an optimum solution but only until the battery weight can be lifted. In all scenarios eFuel is more efficient than LH₂. We conclude that carrying the most efficient molecule in an aircraft pays the extra energy cost spent on the ground. Finally, we found that for each of these energy carriers, it is the electricity carbon intensity and price which will dictate the cost and CO₂ emissions of an air mobility mission.

Three different populations of sulfated polysaccharides can be found in the cell wall of the red alga Botryocladia occidentalis. In a previous work, the structures of the two more sulfated polysaccharides were revised. In this work, NMR-based structural analysis was performed on the least sulfated polysaccharide and its chemically modified derivatives. Results have revealed the presence of both 4-linked α- and 3-linked β-galactose units having the following chemical features: more than half of the total galactose units are not sulfated, the α-units occur primarily as 3,6-anhydro-galactose units either 2-O-methylated or 2-O-sulfated, and the β-galactose units can be 4-O-sulfated or 2,4-O-disulfated. SPR-based results indicated weaker binding of the least sulfated galactan to thrombin, factor Xa, and antithrombin, but stronger binding to heparin cofactor II than unfractionated heparin. This report together with our previous publication completes the structural characterization of the three polysaccharides found in the cell wall of the red alga B. occidentalis and correlates the impact of their composing chemical groups with the levels of interaction with the blood co-factors.

Reflux esophagitis, a treatment for gastric ulcers known as Ilaprazole (Ila), is not stable during storage and handling at room temperature, requiring storage at 5 degrees celsius. In this study, to address these issues with Ila, coformers rich in oxygen (O) and hydroxyl (OH) groups capable of forming hydrogen bonds with were selected. These coformers included Xylitol (Xyl), Meglumine (Meg), Nicotinic acid (Nic), L-Aspartic acid (Asp), and L-Glutamic acid (Glu). A 1:1 physical mixture of Ila and each coformer was prepared, and the potential for cocrystal for-mation was predicted using differential scanning calorimetry (DSC) screening. The results indi-cated the potential for cocrystal formation in the Ila/Xyl physical mixture. Subsequently, Ila and Xyl were mixed in ethyl acetate (EA) in a 1:1 ratio, and after 28 hours of slurry, the formation of Ila/Xyl cocrystal was confirmed through solid-state CP/MAS 13C NMR spectrum analysis, showing intermolecular hydrogen bonding and conformational changes. Furthermore, the 1:1 ratio of Ila/Xyl cocrystal was confirmed through solution-state NMR (1H, 13C, and 2D) molecular structure analysis. To assess the stability of Ila/Xyl cocrystal at room temperature, it was stored and com-pared with Ila at 25±2°C and relative humidity (RH) of 65±5% over three months. The results showed that the purity of Ila/Xyl cocrystal remained at 99.8% from the initial purity of 99.75% over the three months, while Ila was predicted to decrease from an initial 99.8% purity to 90% after three months. Additionally, at 25±2°C and RH 65±5%, a specific impurity B in Ila/Xyl cocrystal was observed to be 0.03% over three months, whereas Ila was predicted to increase from an initial 0.032% to 2.28% after three months. To evaluate the dissolution rate of Ila/Xyl cocrystal, a formulation was prepared and compared with Ila at pH 10, with a dosage equivalent to 10mg of Ila. The results showed that Ila/Xyl cocrystal reached 55% within 15 minutes and 100% within 45 minutes, while Ila was predicted to reach 32% at 15 minutes and 100% only after 60 minutes. However, overall, the Ila/Xyl cocrystal showed results equivalent to or exceeding the dissolution rate of Ila. Therefore, it is predicted that the Ila/Xyl cocrystal will maximize its effectiveness as a more convenient crystal structure for formulation development, allowing storage and preservation at room temperature without the need for the problematic 5°C refrigeration during ambient con-ditions and storage, addressing the issues associated with Ila.

The effects of co-addition CeO2 and SiC particles on the morphology, surface cracks, microstructure, precipitated phases and wear property of plasma beam spraying Fe55-based coatings on 1025 steel were investigated by optical microscopy (OM), scanning electron microscopy (SEM), energy-dispersive X-ray spectrometer (EDS), ultra-deep field microscope and wet sand rubber wheel friction tester, respectively. The results showed that the dendrite exhibited a directional growth pattern perpendicular to the substrate and the transitional states of microstructure with the co-addition CeO2 and SiC particles. With addition of CeO2 or SiC affected the flowability of molten steel at macro level, leading to a reduction in the liquid phase diffusion coefficient DL of Cr and C and resulted in a decrease in the G/R ratio. The dendrites changed into equiaxed grains. The main phase composition of Fe55 welding layer is Cr7C3, γ-Fe. The grain boundaries consisted mainly of a reticular eutectic structure. The worn-out uniformly surface of the Fe55+1.5 wt% SiC+0.01wt% CeO2 with Ra was 0.28 μm was smoother than that of other samples. The sub-wear mechanisms during the friction process were microploughing and microcutting. The hardness and toughness of Fe55+1.5 wt% SiC+0.01wt% CeO2 were well-matched, avoiding excessive microcutting and microplastic deformation.

A new copper(I) complex, [Cu2(L)2dppm](PF6)2 (1) [L = 3-(2-Pyridyl)-5,6-diphenyl-1,2,4-triazine and dppm: Bis(diphenylphosphino)methane] was prepared and characterized by IR, 1H-NMR, 31P-NMR spectroscopy, elemental and thermogravimetric analysis, and single-crystal X-ray diffraction technique. Complex 1 is a dinuclear compound, showing that L and dppm act as tridentate and bidentate chelating ligands, respectively. The two Cu(I) atoms exhibit a distorted tetrahedral coordination sphere embedded in N3P environments. The supramolecular interactions in the solid-state structure are characterized by C−H···N, C−H···F, C-H···π and π···π intermolecular interactions that were analyzed by inspection of the Hirshfeld surface and fingerprint plots. Additionally, the complex was studied experimentally in solution by UV–Vis spectroscopy and cyclic voltammetry; also, theoretical studies with Time-Dependent Density Functional Theory (TD-DFT) were performed. Moreover, the optical and electrochemical properties have been studied, focusing on the band gap. Compound 1 has been used as a co-sensitizer in a dye-sensitized solar cell, showing good activity.

The major challenge for membrane distillation (MD) is membrane wetting resistance induced by pollutants in the feed solution. The proposed solution for this issue was to fabricate membranes with hydrophobic properties. Hydrophobic electrospun Poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) nanofibers membranes were produced for brine treatment using the direct contact membrane distillation (DCMD) technique. These nanofibers membranes were prepared from three different polymeric solution compositions to study the effect of solvent composition in the electrospinning process. Further, the effect of the polymer concentration was investigated by preparing polymeric solutions with three different polymer percentages: 6, 8, and 10%. All nanofibers membranes obtained from electrospinning were post-treated at varying temperatures. The effects of thickness, porosity, pore size, and LEP were studied. The hydrophobicity was determined by contact angle measurements, which were investigated by optical contact angle goniometry. The crystallinity and thermal properties were studied by DCS and XRD, while the functional groups were studied by FTIR. The morphological study was performed by AMF and described the roughness of nanofibers membranes. Finally, all nanofibers membranes have enough of a hydrophobic nature to be used in DCMD. PVDF membrane filter disc and all nanofibers membranes were applied in DCMD to treat brine water. The resulting water flux and permeate water quality were compared, and it was discovered that all produced nanofibers membranes showed good behavior with varying water flux, but the salt rejection was greater than 90%. A membrane prepared from DMF/acetone 5-5 with 10% PVDF-HFP provided perfect performance, with an average water flux of 44 kg.m-2.h-1 and salt rejection of 99.8%.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

The reliability of Underwater Wireless Sensor Networks (UWSNs) is measured in terms of energy consumption (EC), end-to-end delay(E2E) and packet delivery ratio (PDR). The adverse effects of channel may cause data loss. Reducing delay up to possible extend improves the reliability of the network, also increasing the number of nodes in a particular network increase reliability. Besides, increasing the number of nodes improve reliability but also increase power consumption. In order to overcome these shortcomings, the two routing protocols are proposed in this paper, namely Delay and Reliability Aware Routing (DRAR) protocol and Cooperative Delay and Reliability Aware Routing (Co-DRAR) protocol for UWSNs. In DRAR protocol, network is divided into two equal regions where two sink nodes(SNs) are positioned at upper region of the network and two SNs are placed at the mid region of the network. The protocol choose the relay node based on residual energy (RE), distance and Bit Error Rate (BER). These parameters protect the data packets from corruption and also provide stable path (where nodes remain active for longer period and do not die quickly). The protocol uses single link and may get worse sometimes while changing channel circumstances. To address this problem, cooperative routing scheme is added to DRAR protocol in order to developed its enhanced version known as Co-DRAR protocol. The protocol works by allowing the destination to receive multiple copies of data packets in order to decide the quality of packets. The proposed protocols DRAR and Co-DRAR perform routing irrespective to geographical position of sensors nodes conversely to the some of conventional routing protocols that's way our propose protocol better perform than the well-known protocol i.e. Depth base routing (DBR) in terms of EC, E2E, PDR, dead nodes, packet drop ratio and number of alive nodes (ANs).

The management of urban water has evolved from single-function systems to more sustainable designs promoting society and nature as inputs to engineer novel infrastructure. In transdisciplinary research, co-design refers to a design thinking strategy in which people jointly frame a problem-solution. This article presents a conceptual framework to assess a case study focusing on the process of co-design and implementation of green infrastructure as a prototype for stormwater management. The evaluation is carried out from a self-reflective post-implementation perspective. Research activities are translated into the framework to evaluate conditions shaping the trajectory of the prototype. As a result, key aspects driving the research regarding levels of stakeholder participation and dimensions of power are identified. Planning resilient co-design strategies to retrofit urban spaces is necessary to avoid unintended consequences, especially at the initial experimental stages. This study aims to contribute to the continuous improvement of pilot strategies in urban spaces by providing a framework for a structured evaluation of research experiences.

Background. To improve maternal and child health, it is essential to adhere to health-promoting and preventive measures. However, reliable information as well as effective tools are not easy to identify in this field. Our cross-sectional study investigated the needs and expectations of expectant and new mothers and fathers -primary users of an app supporting the first 1000 days of life. Methods. Between May and August 2022, we recruited expectant and new parents by administering a 71-item 5-point Likert scale questionnaire related to content, functionalities, and technical features of a hypothetical app. We stratified responses by sociodemographic characteristics and then performed ward hierarchical clustering. Results. The 94 women and 69 men involved in our study generally agreed with the proposed content, but expressed low interest in certain app functionalities, especially those related to interaction mechanism and interactivity. Women were generally more demanding than men, and family income declined as the needs and expectations increased. Conclusions. Our findings, resulting from the engagement of end-users, may be useful for designers and technology providers to implement mHealth solutions that, in addition to conveying reliable information, are tailored to the needs and preferences of end-users in the first 1000 days of life.

Pharmaceutically active compounds and organic pollutants are becoming a major environmental dispute possessing serious threat to the water bodies and terrestrial ecosystem. Microorganisms are capable of the self-purification process, and hence the microbial degradation is considered a lucrative method to counteract the therapeutic and recalcitrant pollutants. Pharmaceutical toxicants in aquatic system can be treated by conventional wastewater treatment, but slow sludge settling, presence of mixture of pharmaceuticals and recalcitrant compounds often pose a potential ecological risk. Some microbial strains are very effective in reducing the chemical oxygen demand (COD), biological oxygen demand (BOD), total dissolved solids (TDS), and turbidity in pharmaceutical industrial wastewater treatment. The natural microbial community has a significant role in the ecological processes of pharmaceutical and organic compounds, including non-steroidal anti-inflammatory drugs, analgesics, blood lipid regulators and other micropollutants. Specific bacterial isolates can act as biodegraders, and fungal treatment could offer protection to the ecosystem. These microorganisms use the pollutants as their sole carbon source and transform the contaminants by co-metabolic pathways. Natural attenuation by native microorganisms, biostimulation and bioaugmentation are the processes employed to degrade the target contaminant. Microorganisms may also be genetically engineered to improve the neutralization efficiency, which would assist in the mineralization of the pollutants. Thus, employing microorganisms to detoxify the pollutants probably enhances the sustainable potential biodegradability, improves water quality standards and ensures eco-friendly alternative bioremediation strategy.

In the next decade, further digitalisation of the entire wind energy project lifecycle is expected to be a major driver for reducing project costs and risks. In this paper, a literature review on the challenges related to implementation of digitalisation in the wind energy industry is first carried out, showing that there is a strong need for new solutions that enable co-innovation within and between organisations. Therefore, a new collaboration method called the WeDoWind Ecosystem is developed and demonstrated. The method is centred around specific "challenges", which are defined by "challenge providers" within a topical "space" and made available to participants via a digital platform. The data required in order to solve a particular "challenge" is provided by the "challenge providers" under the confidentiality conditions they specify. The method is demonstrated via a case study, the EDP Wind Turbine Fault Detection Challenge. Six submitted solutions using diverse approaches are evaluated. Two of the methods perform significantly better than EDP’s existing method in terms of Total Prediction Costs (saving up to €120,000). The WeDoWind Ecosystem is found to be a promising solution for enabling co-innovation in wind energy, providing a number of tangible benefits for both challenge and solution providers.

There are two contrary opinions regarding the risk if mainland China (MC) moves away from its zero-COVID policy. Some experts think the risk shall be much lower than influenza as per MC’s own COVID-19 case fatality rate (CFR), while some other experts think the risk shall be much higher than influenza as per the COVID-19 CFRs of other regions. We elucidate here that this and multiple other striking differences in the CFR between various scenarios all support and substantially resulted from the view that good IDM is highly powerful to mitigate COVID-19, where IDM (isolation-disinfection-maintenance) means isolation of COVID-19 cases from other people, disinfection of their living environments, and health maintenance (e.g., rest, nutrition, breathing). The high effect of good IDM is also supported by the theoretic functions of IDM in minimizing co-infections and maintaining body functions, and the fact that all the 505 COVID-19 deaths reported in MC in 2022 before May 5 died directly of severe underlying diseases with COVID-19. Although it is tough for people in poverty to obtain good IDM, good IDM can be feasible at home for the most mild cases and in hospitals for the most severe cases. Therefore, good IDM can be crucial to mitigating COVID-19 worldwide. It also suggests that the risk for China to end its zero-COVID policy depends on China’s control policies or measures. Based on the effect of IDM, the cautious co-existence policy was proposed for COVID-19 control. This policy could reduce the whole death toll in MC because good IDM is non-specific and can reduce deaths of various other diseases. The cautious co-existence policy (non-specific) and the vaccination policy (specific) aid each other to mitigate COVID-19, and they cannot replace each other. Those who are qualified in health for vaccination should be vaccinated against COVID-19 timely.

The purpose of this study was to identify the factors that affect the mortality among adult HIV/TB co-infected patients and to see the nutritional difference among mortality in residence level. Retrospective cohort studies of 417 patients which fulfill our criteria were included. Multilevel logistic regression models were used. MLwiN and SPSS software are used to estimate the parameter. The variance of the random factor in the empty model was significant which indicates that there were residential differences in TB-HIV co-infected mortality and it shows multilevel analysis was an appropriate approach for further analysis. The prevalence of HIV/TB co-infected patients' death was 12.9% in study time. Functional status, age of patients, WHO clinical stages, nutritional status, CD4 counts, regimen, and BMI were found to be significant determinants of HIV/TB co-infected mortality. In our study, patients with the bedridden category of functional status, the fourth stages of WHO clinical stages (stage IV), patients with higher age, patients whose treatments were second-line regimen and low CD4 cell counts were more at risk of death. The study also revealed that; poor nutritional status increased the risk of mortality among HIV/TB co-infected patients and it varies among the residence of the patients (rural area were more at risk).

Threats emerging from microplastics pollution in the marine environment have received much global attention. This review assessed sources, fate, and impacts of microplastics in marine ecosystems and identified gaps. Most studies document ubiquity of microplastics and associated environmental effects. Effects include impacts to marine ecosystems, risks to biodiversity, and threats to human health. Microplastic leakage into marine ecosystems arises from plastic waste mismanagement and a lack of effective mitigative strategies. This review identified a scarcity of microplastics mitigation strategies across different stakeholders. Lack of community involvement in microplastic monitoring or ecosystem conservation exists due to limited existence of stakeholder co-management initiatives. Although some management strategies exist for controlling the effects of microplastics (often implemented by local and global environmental groups); a standardized management strategy to mitigate microplastics in coastal areas is urgently required. There is a need to identify focal causes of microplastic pollution in the marine environment through further environmental research. This would extend to creating more effective policies as well as harmonized and extended efforts of educational campaigns and incentives for counteraction and plastic waste reduction, while mandating stringent penalties for polluting the marine environment. This will help reduce microplastic leakage into the environment.

It was recently demonstrated that a co-planar capacitive sensor could be applied to the evaluation of materials without the disadvantages associated with the other techniques. This technique effectively detects changes in the dielectric properties of the materials due to, for instance, imperfections or variations in the internal structure, by moving a set of simple electrodes on the surface of the specimen. An AC voltage is applied to one or more electrodes and signals are detected by others. This is a promising inspection method for imaging the interior structure of the numerous materials, without the necessity to be in contact with the surface of the sample. In this paper, Finite Element (FE) modelling was employed to simulate the electric field distribution from a co-planar capacitive sensor and the way it interacts with a non-conducting sample. Physical experiments with a prototype capacitive sensor were also performed on a Plexiglas sample with sub-surface defects, to assess the imaging performance of the sensor. A good qualitative agreement was observed between the numerical simulation and experimental result.

Currently, one of the biggest issues when developing an ODS alloy is the competition established between the different oxide precursors during the precipitation of oxides which nature depends on their chemical composition. In the presence of various precursors, usually the one with the highest affinity to oxygen leads to the absence of the other oxides. In this work, a new process to equilibrate the local concentration of species and to decrease the competition among them is explained. A unique compound, containing the diverse oxide precursors as one complex oxide, is introduced in a prealloyed 14Cr Steel powder via mechanical alloying. Thus, generating environments enriched in Y, Ti and Zr which, after consolidation, refine the oxides precipitation improving the thermal stability of the alloy. SPS were used as consolidation technique to guarantee shorter sintering times and to maintain the nanostructure obtained. Mechanical properties were tested by tensile tests and Vickers microhardness.

Background: Co-infections of SARS-CoV-2 with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We asses s the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.