Genome wide identification of phenylalanine ammonia-lyase (PAL) gene family in Cucumis sativus (cucumber) against abiotic stress.

Phenylalanine ammonia lyase (PAL) is a widely studied enzyme in plant biology due to its role in connecting primary metabolism to secondary phenylpropanoid metabolism, significantly influencing plant growth, development, and stress response. Although PAL genes have been extensively studied in various plant species but their exploration in cucumber has been limited. This study successfully identified 11 CsPAL genes in Cucumis sativus (cucumber). These CsPAL genes were categorized based on their conserved sequences revealing patterns through MEME analysis and multiple sequence alignment. Interestingly, cis-elements related to stress were found in the promoter regions of CsPAL genes, indicating their involvement in responding to abiotic stress. Furthermore, these gene's promoters contained components associated with light, development and hormone responsiveness. This suggests that they may have roles in hormone developmental processes. MicroRNAs were identified as a key regulators for the CsPAL genes, playing a crucial role in modulating their expression. This discovery underscores the complex regulatory network involved in the plant's response to various stress conditions. The influence of these microRNAs further highlights the complicated mechanisms that plants use to manage stress. Gene expression patterns were analyzed using RNA-seq data. The significant upregulation of CsPAL9 during HT3h (heat stress for 3 h) and the heightened upregulation of both CsPAL9 and CsPAL7 under HT6h (heat stress for 6 h) in the transcriptome study suggest a potential role for these genes in cucumber's tolerance to heat stress. This comprehensive investigation aims to enhance our understanding of the PAL gene family's versatility, offering valuable insights for advancements in cucumber genetics.

Prudent Use of Blood Cultures for Hospitalized Patients With Cirrhosis.

Background No reliable risk stratification method is available to guide the extent of infectious work-up among hospitalized patients with cirrhosis. Therefore, we aimed to create a risk stratification method for obtaining blood cultures from hospitalized patients with cirrhosis. Methods This was a retrospective cohort study using the Healthcare Cost and Utilization Project - National Readmission Database 2019. Adult patients who were not immunocompromised comprised the final cohort. The primary outcome was the incidence of bacteremia among hospitalized patients with cirrhosis. Secondary outcomes included length of hospital stay, inpatient mortality, and 30-day readmission rate among cirrhosis patients with and without bacteremia. After propensity score matching, the χ2 test was used to assess the primary outcome and inpatient mortality. The Wilcoxon signed-rank test was used to compare the length of hospital stay. Readmission rates were compared via survival analysis. Concomitant bacterial infection, cirrhosis causes, and complications were assessed as potential risk factors for bacteremia using binomial regression. Results The risk ratio (RR) of bacteremia was 1.66 (95% confidence interval (CI): 1.55-1.78) among patients with cirrhosis compared to those without cirrhosis. A concomitant bacterial infection was found to have a strong association with bacteremia in patients with cirrhosis (RR: 3.3, 95% CI: 3.03-3.59). Among cirrhosis patients without concomitant bacterial infection, the incidence of bacteremia was 0.76% (<1%). Among the causes of cirrhosis, primary sclerosing cholangitis was found to have a strong association with bacteremia (RR: 3.88, 95% CI: 2.3-6.04, P < 0.001). Patients with cirrhosis who had bacteremia were hospitalized three days longer than those without bacteremia. There was no difference in inpatient mortality or 30-day readmission rates between cirrhotic patients with and without bacteremia. Conclusion This study suggests that, in the absence of another concomitant bacterial infection and primary sclerosing cholangitis, we can avoid unnecessary blood cultures among immunocompetent patients with cirrhosis. However, given some inherent limitations associated with the database (such as the unavailability of vitals or laboratory values), additional studies are needed to validate its findings.

Genome wide identification of the NPR1 gene family in plant defense mechanisms against biotic stress in chili (Capsicum annuum L.).

Chili pepper cultivation in the Indian subcontinent is severely affected by viral diseases, prompting the need for environmentally friendly disease control methods. To achieve this, it is essential to understand the molecular mechanisms of viral resistance in chili pepper. The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) genes are known to provide broad-spectrum resistance to various phytopathogens by activating systemic acquired resistance (SAR). An in-depth understanding of NPR1 gene expression during begomovirus infection and its correlation with different biochemical and physiological parameters is crucial for enhancing resistance against begomoviruses in chili pepper. Nevertheless, limited information on chili CaNPR genes and their role in biotic stress constrains their potential in breeding for biotic stress resistance. By employing bioinformatics for genome mining, we identify 5 CaNPR genes in chili. The promoter regions of 1,500 bp of CaNPR genes contained cis-elements associated with biotic stress responses, signifying their involvement in biotic stress responses. Furthermore, these gene promoters harbored components linked to light, development, and hormone responsiveness, suggesting their roles in plant hormone responses and development. MicroRNAs played a vital role in regulating these five CaNPR genes, highlighting their significance in the regulation of chili genes. Inoculation with the begomovirus "cotton leaf curl Khokhran virus (CLCuKV)" had a detrimental effect on chili plant growth, resulting in stunted development, fibrous roots, and evident virus symptoms. The qRT-PCR analysis of two local chili varieties inoculated with CLCuKV, one resistant (V1) and the other susceptible (V2) to begomoviruses, indicated that CaNPR1 likely provides extended resistance and plays a role in chili plant defense mechanisms, while the remaining genes are activated during the early stages of infection. These findings shed light on the function of chili's CaNPR in biotic stress responses and identify potential genes for biotic stress-resistant breeding. However, further research, including gene cloning and functional analysis, is needed to confirm the role of these genes in various physiological and biological processes. This in-silico analysis enhances our genome-wide understanding of how chili CaNPR genes respond during begomovirus infection.

The contribution of quality management practices to student performance: Mediated by school culture.

School management is responsible and accountable for implementing educational policies into practice effectively and efficiently to provide quality education. Simultaneously, school management can grasp the core features of the whole school process and identify the relationship among three variables: quality management practices, school culture, and student performance. The current study aims to explore the school principals' perception about quality management practices and its relationship with school culture and student performance in the public secondary schools of Punjab province, Pakistan. In order to achieve the objectives of the study, the study adopted an exploratory sequential mix-methods research design. The researcher conducted a systematic literature review of sixty-three previous studies and interviews with eleven school principals for the qualitative data. Based on results obtained from the qualitative phase, a questionnaire was prepared and dispatched to 150 school principals to get quantitative data. Successively 120 valid responses were received. SEM analysis was performed to get quantitative results. The study's preliminary conclusion demonstrated a positive connection between quality management and student performance in public secondary schools, and quality management was also a significant predictor of school culture. Further, school culture served as a complete mediator between quality management and student performance.

Diagnostic potential of various laboratory tests for Irritable Bowel Syndrome (IBS): A systematic review.

Objective: To identify possible tests along with their accuracies that may be used to diagnose irritable bowel syndrome. METHODS: The systematic review comprised literature search on Cochrane Library, PubMed, Science Direct and Elsevier databases for randomised controlled trials and cohort studies conducted from January 1, 2015, to December 31, 2022, using appropriate key words and Boolean operators. Focus was kept on studies that reported irritable bowel syndrome diagnosis as the primary outcome. The risk of bias was assessed using quality assessment, data abstraction, and synthesis version 2. RESULTS: Of the 2,798 studies initially identified, 10(0.35%) were analysed in detail. Of them, 4(40%) used enzyme-linked immunosorbent assay kits to test for anti-cytolethal distending toxin B and anti-vinculin levels, 2(20%) used the kits for serum cytokine profiling and serum calprotectin levels, and 4(40%) used either magnetic resonance imaging scans, faecal metabolic profiling, intestinal biopsy analysis with immunostaining or polymerase chain reaction for differential transferribonucleic acid-derived small ribonucleic acid. Out of the 4(40%) studies on anti-cytolethal distending toxin B and anti-vinculin levels, optical densities >1.56 and >1.60 recorded 100% specificity for irritable bowel syndrome with diarrhoea, but sensitivity was 22%. In contrast, rectal biopsies for cell densities of somatostatin and peptide YY showed high sensitivity and specificity for irritable bowel syndrome ranging 80-90%. Conclusion: Enzyme-linked immunosorbent assay testing for anti-cytolethal distending toxin B and anti-vinculin as well as rectal biopsies for cell densities could be potential diagnostic tests for irritable bowel syndrome.

Genome-wide analysis and identification of Carotenoid Cleavage Oxygenase (CCO) gene family in coffee (coffee arabica) under abiotic stress.

The coffee industry holds importance, providing livelihoods for millions of farmers globally and playing a vital role in the economies of coffee-producing countries. Environmental conditions such as drought and temperature fluctuations can adversely affect the quality and yield of coffee crops.Carotenoid cleavage oxygenases (CCO) enzymes are essential for coffee plants as they help break down carotenoids contributing to growth and stress resistance. However, knowledge about the CCO gene family in Coffee arabica was limited. In this study identified 21 CCO genes in Coffee arabica (C. arabica) revealing two subfamilies carotenoid cleavage dioxygenases (CCDs) and 9-cis-epoxy carotenoid dioxygenases (NCED) through phylogenic analysis. These subfamilies exhibited distribution patterns in terms of gene structure, domains, and motifs. The 21 CaCCO genes, comprising 5 NCED and 16 CCD genes were found across chromosomes. Promoter sequencing analysis revealed cis-elements that likely interact with plant stress-responsive, growth-related, and phytohormones, like auxin and abscisic acid. A comprehensive genome-wide comparison, between C. arabica and A. thaliana was conducted to understand the characteristics of CCO genes. RTqPCR data indicated that CaNCED5, CaNCED6, CaNCED12, and CaNCED20 are target genes involved in the growth of drought coffee plants leading to increased crop yield, in a conditions, with limited water availability. This reveals the role of coffee CCOs in responding to abiotic stress and identifies potential genes useful for breeding stress-resistant coffee varieties.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Integrative metagenomic dissection of last-resort antibiotic resistance genes and mobile genetic elements in hospital wastewaters.

Hospital wastewater is a critical source of antimicrobial resistance (AMR), which facilitates the proliferation and spread of clinically significant antimicrobial resistance genes (ARGs) and pathogenic bacteria. This study utilized metagenomic approaches, including advanced binning techniques, such as MetaBAT2, MaxBin2, and CONCOCT, which offer significant improvements in accuracy and completeness over traditional binning methods. These methods were used to comprehensively assess the dynamics and composition of resistomes and mobilomes in untreated wastewater samples taken from two general hospitals and one cancer hospital. This study revealed a diverse bacterial landscape, largely consisting of Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, with notable variations in microbial composition among hospitals. Analysis of the top 15 genera showed unique microbial pattern distribution in each hospital: Aeromonas was predominant in 1stHWTS (49.39 %), Acidovorax in the CAHWTS at 16.85 %, and Escherichia and Bacteroides in the 2ndHWTS at 11.44 % and 11.33 %, respectively. A total of 114 pathogenic bacteria were identified, with drug-resistant Aeromonas caviae and Escherichia coli being the most prevalent. The study identified 34 types and 1660 subtypes of ARGs, including important last-resort antibiotic resistance genes (LARGs), such as blaNDM, mcr, and tet(X). Using metagenomic binning, this study uncovered distinct patterns of host-resistance associations, particularly with Proteobacteria and Firmicutes. Network analysis highlighted the complex interactions among ARGs, mobile genetic elements (MGEs), and bacterial species, all contributing to the dissemination of AMR. These findings emphasize the intricate nature of AMR in hospital wastewater and the influence of hospital-specific factors on microbial resistance patterns. This study provides support for implementing integrated management strategies, including robust surveillance, advanced wastewater treatment, and strict antibiotic stewardship, to control the dissemination of AMR. Understanding the interplay among bacterial communities, ARGs, and MGEs is important for developing effective public health measures against AMR.

Advances in biodegradable materials: Degradation mechanisms, mechanical properties, and biocompatibility for orthopedic applications.

Mg-based and Zn-based biodegradable materials have the potential to become the next-generation implant materials to treat bone diseases, because of their desired degradation and mechanical properties. This article reviews the status of these implant materials. The required properties of biodegradable materials such as biodegradability, mechanical properties, and biocompatibility for performance evaluation were briefly discussed. The influence of fabrication techniques, microstructure, alloying elements, and post-processing techniques on the properties of Mg and Zn-based materials was addressed. The degradation mechanism by dissolution, oxidation, and interaction with human body cells was discussed. The biocompatibility of Mg and Zn-based biodegradable materials was analyzed. The significance of in vitro and in vivo biocompatibility testing was highlighted, emphasizing the superiority of in vivo results over cell line studies. This article identifies the many Mg and Zn-based biodegradable materials and summarizes the key findings.

Composite superplastic aerogel scaffolds containing dopamine and bioactive glass-based fibers for skin and bone tissue regeneration.

Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines.

Temporal changes in the levels of virus and betasatellite DNA in B. tabaci feeding on CLCuD affected cotton during the growing season.

Cotton, a key source of income for Pakistan, has suffered significantly by cotton leaf curl disease (CLCuD) since 1990. This disease is caused by a complex of phylogenetically-related begomovirus (genus Begomovirus, family Geminiviridae) species and a specific betasatellite (genus Betasatellite, family Tolecusatellitidae), cotton leaf curl Multan betasatellite. Additionally, another DNA satellite called alphasatellite (family Alphasatellitidae), is also frequently associated. All these virus components are vectored by a single species of whitefly (Bemisia tabaci). While many factors affect cotton productivity, including cotton variety, sowing time, and environmental cues such as temperature, humidity, and rainfall, CLCuD is a major biotic constraint. Although the understanding of begomoviruses transmission by whiteflies has advanced significantly over the past three decades, however, the in-field seasonal dynamics of the viruses in the insect vector remained an enigma. This study aimed to assess the levels of virus and betasatellite in whiteflies collected from cotton plants throughout the cotton growing season from 2014 to 2016. Notably, begomovirus levels showed no consistent pattern, with minimal variations, ranging from 0.0017 to 0.0074 ng.µg-1 of the genomic DNA in 2014, 0.0356 to 0.113 ng.µg-1 of the genomic DNA in 2015, and 0.0517 to 0.0791 ng.µg-1 of the genomic DNA in 2016. However, betasatellite levels exhibited a distinct pattern. During 2014 and 2015, it steadily increased throughout the sampling period (May to September). While 2016 showed a similar trend from the start of sampling (July) to September but a decline in October (end of sampling). Such a study has not been conducted previously, and could potentially provide valuable insights about the epidemiology of the virus complex causing CLCuD and possible means of controlling losses due to it.

Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell-Mediated Biomedical Applications.

Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research. Microfluidics offers an intriguing platform to produce stem cell-laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet-based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale-up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell-related biomedical applications.

Quantification and polymeric characterization of microplastics in composts and their accumulation in lettuce.

Organic fertilizers have become a vector for the transport of microplastics (MPs), which pose human health concerns through the food chain. This study aimed to quantify and characterize MPs in eight different compost samples of various raw materials and their subsequent translocation to lettuce (Lacuta sativa) grown on contaminated composts. The results revealed that the MP abundance ranged from 3810 to 16530 MP/kg. Municipal solid waste compost (MSWC) had highest abundance (16082 ± 632 MP/kg), followed by leaf compost (LC) and organic compost (OC) (6299 ± 1011 and 3680 ± 419 MP/kg, respectively). MPs of <100 µm in size were most dominant in MSWC and LC. Fragments and fibers were the prevalent shape types, with white/transparent colored MPs being more abundant. Polyethylene (PE), polypropylene (PP) and polyethylene terephthalate (PET) were the dominant polymers. MPs accumulation in the lettuce leaves was greatest in the lettuce plants grown on MSWC, followed by those grown on LC and OC, indicating that MSWC grown lettuce is not suitable for human consumption. The decrease in the growth (leaf length, number of leaves, leaf fresh and weights) and physiological (membrane stability index, relative water contents) parameters of lettuce was in line with the trend of MP accumulations. Hence, it is highly important to regulate the plastic contents in compost because it is a threat to ecosystems and human health.

Distribution of Aspergillus species and risk factors for aspergillosis in mainland China: a systematic review.

Background: Aspergillus, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body via the airways and causing a disease called aspergillosis. This study comprehensively analyzed data on aspergillosis in published articles from mainland China to investigate the prevalence of Aspergillus, and risk factors, mortality rate, and underlying condition associated with aspergillosis. Methods: Published articles were retrieved from Google Scholar, PubMed, and Science Direct online search engines. In the 101 analyzed studies, 3558 Aspergillus isolates were meticulously collected and classified. GraphPad Prism 8 was used to statistically examine the epidemiology and clinical characteristics of aspergillosis. Results: Aspergillus fumigatus was prominently reported (n = 2679, 75.14%), followed by A. flavus (n = 437, 12.25%), A. niger (n = 219, 6.14%), and A. terreus (n = 119, 3.33%). Of a total of 9810 patients, 7513 probable cases accounted for the highest number, followed by confirmed cases (n = 1956) and possible cases (n = 341). In patients, cough emerged as the most common complaint (n = 1819, 18.54%), followed by asthma (n = 1029, 10.48%) and fever (1024, 10.44%). Of total studies, invasive pulmonary aspergillosis (IPA) was reported in 47 (45.53%) studies, exhibiting an increased prevalence in Beijing (n = 12, 25.53%), Guangdong (n = 7, 14.89%), and Shanghai (n = 6, 12.76%). Chronic pulmonary aspergillosis (CPA) was reported in 14 (13.86%) studies. Among the total of 14 studies, the occurrence of CPA was 5 (35.71%) in Beijing and 3 (21.42%) in Shanghai. Allergic bronchopulmonary aspergillosis (ABPA), was reported at a lower frequency (n = 8, 7.92%), Guangdong recorded a relatively high number (n = 3, 37.5%), followed by Beijing (n = 2, 25.0%), and Shanghai (n = 1, 12.5%). Percentage of death reported: IPA had the highest rate (n = 447, 68.87%), followed by CPA (n = 181, 27.88%) and ABPA (n = 14, 2.15%). Among the aspergillosis patients, 6220 had underlying conditions, including chronic lung disease (n = 3765, 60.53%), previous tuberculosis (n = 416, 6.68%), and organ transplant or organ failure (n = 648, 10.41%). Aspergillosis was also found in patients using corticosteroid therapy (n = 622, 10.0%). Conclusion: This review sheds light on the prevalence patterns of Aspergillus species, risk factors of aspergillosis, and gaps in surveillance that could be helpful for the control and treatment of aspergillosis and guide the researchers in future studies. Registration: This systematic review was prospectively registered on PROSPERO: Registration ID CRD42023476870.

The Pathogenesis of Foot-and-Mouth Disease Virus Infection: How the Virus Escapes from Immune Recognition and Elimination.

Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes vesicular lesions in the mouth, feet, and mammary glands, as well as severe systemic symptoms such as fever, salivation, and lameness. The pathogenesis of FMDV infection involves complex interactions between the virus and the host immune system, which determine the outcome of the disease. FMDV has evolved several strategies to evade immune recognition and elimination, such as antigenic variation, receptor switching, immune suppression, and subversion of innate and adaptive responses. This review paper summarizes the current knowledge on the pathogenesis of FMDV infection and the mechanisms of immune evasion employed by the virus. It also discusses the challenges and opportunities for developing effective vaccines and therapeutics against this important animal disease.

Coupling of phycoremediation and phytoremediation technologies to treat tannery effluents with rainwater dilutions.

From tannery effluent (TE) severely polluted with heavy metals (HMs viz., Cr, Cu, Cd, and Pb), hydrophytic phytoextraction remains a challenge as transplanted plants succumb to death on facing acclimatization shock. Current study was aimed at diluting TE with harvested rainwater (HR) for improving HM phytoextraction potential of Phragmites australis (a hydrophyte) assisted with phycoremediation of coupled algae (viz., Oedogonium sp. and Pithophora sp.). The TE:HR dilutions (TEDs) 0, 25, 50, 75, and 100% (v/v) included three sets: set-1 included algae only, set-2 included P. australis only and set-3 included P. australis coupled with combined algal inoculum. Results showed that P. australis assisted with HR dilution and combined algal inoculum showed significantly greater uptake of HMs from each of the TEDs than respective control treatments. Combined algal application in the TEDs proved phycoremediation assistants based on their bioaccumulation factor (BF). The dry biomass of P. australis in TEDs applied with phycoremediation assistants remained greater than uninoculated ones. Overall, HM translocation factor (TF) of P. australis for Cr, Cu, Cd, and Pb remained ≥ 1. The study concludes that HM phytoextraction is substantially increased when concentrated TE is diluted with HR and assisted with phycoremediation of HM tolerant algae.

Exploring the mechanism of action of spirooxindoles as a class of CDK2 inhibitors: a structure-based computational approach.

Cyclin-dependent kinase 2 (CDK2) regulates cell cycle checkpoints in the synthesis and mitosis phases and plays a pivotal role in cancerous cell proliferation. The activation of CDK2, influenced by various protein signaling pathways, initiates the phosphorylation process. Due to its crucial role in carcinogenesis, CDK2 is a druggable hotspot target to suppress cancer cell proliferation. In this context, several studies have identified spirooxindoles as an effective class of CDK2 inhibitors. In the present study, three spirooxindoles (SOI1, SOI2, and SOI3) were studied to understand their inhibitory mechanism against CDK2 through a structure-based approach. Molecular docking and molecular dynamics (MD) simulations were performed to explore their interactions with CDK2 at the molecular level. The calculated binding free energy for the spirooxindole-based CDK2 inhibitors aligned well with experimental results regarding CDK2 inhibition. Energy decomposition (ED) analysis identified key binding residues, including I10, G11, T14, R36, F82, K89, L134, P155, T158, Y159, and T160, in the CDK2 active site and T-loop phosphorylation. Molecular mechanics (MM) energy was identified as the primary contributor to stabilizing inhibitor binding in the CDK2 protein structure. Furthermore, the analysis of binding affinity revealed that the inhibitor SOI1 binds more strongly to CDK2 compared to the other inhibitors under investigation. It demonstrated a robust interaction with the crucial residue T160 in the T-loop phosphorylation site, responsible for kinase activation. These insights into the inhibitory mechanism are anticipated to contribute to the development of potential CDK2 inhibitors using the spirooxindole scaffold.

Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.