Search

Phosphate (PO 4 (III)) contamination in water bodies poses significant environmental challenges, necessitating efficient and accurate methods to predict and optimize its removal. The current study addresses this issue by predicting the adsorption capacity of PO 4 (III) ions onto biochar-based materials using five probabilistic machine learning models: eXtreme Gradient Boosting LSS (XGBoostLSS), Natural Gradient Boosting, Bayesian Neural Networks (NN), Probabilistic NN, and Monte-Carlo Dropout NN. Utilizing a dataset of 2952 data points with 16 inputs, XGBoostLSS demonstrated the highest R 2 (0.95) on new adsorbents. SHapely Additive exPlanations analysis showed that adsorption experimental conditions had the most significant impact (43%), followed by synthesis conditions (29%) and adsorbent characteristics (28%). Optimized conditions included an initial PO 4 (III) concentration of 125 mg/L, carbon content of 11.5%, oxygen content of 23%, a contact time of 1440 min, a heating rate of 5 °C/min, 200 rpm, and a surface area of 410 m 2 /g, using Ra-LDO adsorbent synthesized from rape cabbage feedstock. This study developed and presented a practical online framework for predicting PO 4 (III) removal onto biochar using a web-based graphical user interface., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Stiffness-customized passive-dynamic ankle-foot orthoses (PD-AFOs) have been shown to reduce the mechanical cost of transport (COT) of individuals post-stroke. However, the mechanisms underlying this reduced COT are unknown. Therefore, this study aimed to identify the factors driving COT reduction with PD-AFO use for individuals post-stroke. Results showed that changes in limb work were strongly correlated to changes in COT with the PD-AFO compared to No AFO in the paretic (tau = 0.637, p < 0.001) and non-paretic (tau = 0.621, p < 0.001) limbs. There was also a strong correlation between changes in limb work and changes in COT compared to SOC AFO in the paretic (tau = 0.569, p < 0.001) and non-paretic (tau = 0.503, p = 0.003) limbs. Conversely, changes in stride length and changes in COT were not correlated. Changes in COT between No AFO and PD-AFO were moderately correlated to the number of constituents that performed less mechanical work for both the paretic (tau = -0.462, p = 0.009) and non-paretic (tau = -0.402, p = 0.025) limbs. Compared to walking with SOC AFOs, there was a moderate correlation between COT and the number of constituents in the paretic limb (tau = -0.458, p = 0.011) but not the non-paretic limb (tau = -0.247, p = 0.173). These findings indicate that PD-AFOs reduce COT primarily through small changes in work across many lower limb constituents. Understanding how COT reduction occurs can help optimize PD-AFO design and possibly other rehabilitation interventions for individuals post-stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Theileria annulata (T. annulata) is intra-erythrocytic protozoan parasite which is more prevalent in tropical and sub-tropical countries. It has a significant economic impact on the productivity of the dairy industry, and buparvaquone is used to treat infected animals in the prevalent regions of the world. Systematically, buparvaquone targets the cyto-b gene to break the electron transport chain (ETC) and Theileria annulata peptidyl-prolyl isomerase 1 (TaPIN1) gene to destabilize transcription factor JUN (c-JUN) to inhibit proliferation of infected cells, which ultimately leads to the death of T. annulata. The reported studies on drug resistance is due to inappropriate drug application, evolutionary characteristics of the cytochrome b (cyto-b) gene and oncogenic signaling pathways gene (TaPIN1) make the parasite resistant against buparvaquone. Hence, this systematic review was designed to find out non-synonymous mutation in genes (cyto-b and TaPIN1) responsible for drug resistance reported from Tunisia, Turkey, Egypt, Sudan, Iran, Pakistan, China and Germany with reference to the T. annulata Ankara strain of cyto-b (accession no. XM&#95;949625.1) and TaPIN1 (accession no. TA18945) wild type genes. Non-synonymous point mutations were found in cyto-b (Q 01 at 130-148 and Q 02 at 253-262 regions) and TaPIN1 (A53P and A53T) genes. These point mutations are responsible for developing buparvaquone resistance against T. annulata infection. These genes can be used as biomarkers for the identification of drug resistance in any endemic area. To avoid the complication of drug resistance, development of genetically resistant cattle breeds, potent vaccines and anti-theilerial drugs (Trifloxystrobin and anti-cancerous) are currently required to control proliferating economically important T. annulata parasites., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm 2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The current study was designed to investigate the effect of A. indica (Neem) leaf extracts (ethanolic and aqueous) in yeast-induced pyrexia and acetic acid-induced writhing in rat models to evaluate the antipyretic and analgesic biomarkers and its phytochemical screening with computational analysis. For the antipyretic activity model 60 albino rats (160-200g) of either sex were divided into 4 groups and all groups were injected with yeast to induce pyrexia. Out of 4 groups, first group (control) consisted of 6 rats, treated with normal saline, the second group (standard) comprised 6 rats, treated with paracetamol. Third and fourth experimental groups consisted of 48 rats, treated with A. indica leaf ethanolic and aqueous extracts at doses of (50, 100, 200 and 400mg/kg b.w). For analgesic activity group division was the same and all groups were injected with acetic acid to induce pain TNF-α and IL-6 levels were measured using ELISA kits after blood samples were taken and serums were separated. An acute toxicity study was performed. In molecular docking, nimbandiol and nimbolide were used as ligand molecules to target protein Tnf-α and IL-6. In both activities at the dose of 400mg/kg, group III showed significant inhibition (p<0.05). Biomarkers showed significant results at the dose of 400mg/kg. Phytochemical screening was performed to reveal the existence of various active constituents. In molecular docking, nimbandiol and nimbolide showed -5 and -5.3 binding energies respectively, as compared to the standard drug paracetamol with -4.2 binding energy to TNF-Alpha protein. Therefore, A. indica extracts can be used as a valuable drug for the treatment of pain and fever.

Vaccination is a cornerstone of public health, providing immunity against various diseases. However, vaccine hesitancy, as defined by the World Health Organization (WHO), poses a significant challenge to global health efforts. This cross-sectional study explores the prevalence and determinants of vaccine hesitancy among 401 students at King Faisal University. The sample primarily comprises young individuals (97.4% aged 18-24) and predominantly female participants (79%), with 90.5% residing in Al-Ahsaa. Our findings indicate that 75.4% of students adhere to the vaccination schedule, and 55.8% recognize the health benefits of vaccines. Notably, while 1.5% express skepticism, 45.8% strongly agree on the safety of vaccines, and 47.3% acknowledge their effectiveness. Interestingly, only 30.4% feel well-informed about vaccination recommendations, and 47.1% recognize the media's influence on vaccine hesitancy. A significant majority (68.5%) demonstrate high awareness, mainly relying on healthcare professionals (63.4%) for information. Concerns regarding side effects (58.8%) and doubts about vaccine efficacy (21.2%) are prevalent among participants. In conclusion, while the majority of students exhibit high knowledge levels and low hesitancy, concerns about side effects and trust in vaccine efficacy remain critical barriers. Targeted interventions are essential to enhance vaccine uptake and effectively address the factors contributing to vaccine hesitancy., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. King Faisal University Ethics Committee issued approval KFU-REC-2023-DEC-ETHICS1723. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Albash et al.)

Objectives: Post-hoc analyses of the MERINO trial highlight the uncertainty associated with establishing piperacillin-tazobactam (PTZ) susceptibility in extended-spectrum beta-lactamase-producing Enterobacterales. Herein, we compare the concordance of susceptibility for PTZ among the VITEK 2, disc diffusion, and Etest with broth microdilution (BMD) as the reference standard., Methods: Ninety-four consecutive ceftriaxone non-susceptible Escherichia coli and Klebsiella pneumoniae bloodstream isolates were identified from patients at three hospitals in Montréal, Québec. BMD was used as the reference standard against which disc diffusion, VITEK 2 (AST-N391), and Etest susceptibility testing were compared. Errors were categorized as very major (false susceptible), major (false resistant), and minor (other)., Results: Overall, 68/94 (72.3%) of isolates were susceptible to PTZ by BMD. Disc diffusion made no major or very major errors (0%; 97.5% CI: 0-3.8%). The VITEK 2 system had a major error rate of 2.5% (95% CI: 0.003-0.089%) and a very major error rate of 26.7% (95% CI: 0.08-0.55%); however, all isolates with VITEK 2 minimal inhibitory concentrations (MICs) of ≤4 μg/mL were susceptible. Finally, the Etest had a major error rate of 6.3% (95% CI: 0.02-0.14%), but no very major errors. Combining VITEK 2-determined susceptibility with a second test led to an increase in the number of correctly classified susceptible organisms., Discussion: The VITEK 2 system, and to a lesser extent the Etest, risk major errors. Used alone, the VITEK 2 system also risks very major errors if the estimated MIC is > 4 μg/mL. Combining VITEK 2 with disc diffusion in isolates with an estimated MIC of 8-16 μg/mL could prevent both major and very major errors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context.—: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine., Objectives.—: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4., Design.—: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist who recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT., Results.—: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5., Conclusions.—: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training., Competing Interests: Chen is an employee of Need Inc and owns Need Inc equity. The other authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

This review article delves into the vital aspects of cotton, emphasizing its global significance as a crucial agricultural commodity. The paper comprehensively explores the composition of cotton and surveys the diverse methods employed for the removal of cotton lint from seeds. Conventional delinting methods, including mechanical and chemical approaches, are scrutinized in terms of their advantages and drawbacks. However, the primary focus of this review is on highlighting the emerging significance of biological delinting methods. By harnessing the power of microbial enzymes and organisms, biological approaches offer a promising alternative for efficient lint removal. The authors discuss the environmental advantages associated with biological delinting, positioning it as a sustainable solution that mitigates the ecological impact of traditional methods. Furthermore, the article contextualizes these delinting methods within the framework of Sustainable Development Goals (SDGs) and underscores the importance of adopting eco-friendly practices in the cotton industry to align with SDG goals. By accentuating the potential of biological delinting in contributing to sustainable agriculture and responsible production, the review advocates for a paradigm shift towards more environmentally conscious approaches in the cotton sector. Overall, the article aims to provide a comprehensive perspective on cotton delinting methods, emphasizing the pivotal role of biological alternatives in fostering a sustainable and goal-oriented future for the cotton industry., Competing Interests: Author AA was employed by FB Genetics Four Brothers Group Pvt. Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zahra, Qadir, Khan, Kamal, Zahra, Ali, Zafar, Razzaq and Jiang.)

This study presents a comprehensive investigation into Ni X Co 1-x Fe 2 O 4 (x = 0.5) spinel nanoparticles synthesized through a one-pot hydrothermal method using Co(NO 3 ) 2 .6H 2 O and Ni(NO 3 ) 2 .6H 2 O salts. XRD, FTIR, FESEM, and VSM analyses confirmed a cubic structure of Ni X Co 1-x Fe 2 O 4 (x = 0.5) nanoparticles without impurities. These nanoparticles exhibit efficient Zn (II) adsorption characteristics, following Langmuir isotherm and pseudo-second-order kinetics. The maximum adsorption capacity was measured to be 666.67 mg g -1 at pH = 7, with mechanisms involving both electrostatic attraction and cation exchange. Desorption studies indicate more than 75% Zn (II) recovery in an acidic environment (pH = 2) after three cycles. Computational analysis was used to validate the experimental results through Molecular Dynamics simulations, initially focusing on Ni X Co 1-x Fe 2 O 4 (x = 0.5). Further exploration involved variations in x at 0.25 and 0.75 to identify the optimal Ni and Co ratio in this bivalent cation spinel ferrite. Computational analyses reveal the superior performance of Ni X Co 1-x Fe 2 O 4 (x = 0.75) in Zn (II) removal, supported by radial distribution analysis, VdW energy, Coulombic energy, mean square displacement (MSD), root mean square displacement (RMSD), and interaction energy. This comprehensive study provides valuable insights into the adsorption behavior and structural stability of Ni X Co 1-x Fe 2 O 4 nanoparticles, showcasing potential applications in Zn (II) removal., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear., (© 2024. The Author(s).)

Phosphodiesterase 4 (PDE4), crucial in regulating the cyclic adenosine monophosphate (cAMP) signaling pathway, significantly impacts liver pathophysiology. This article highlights the comprehensive effects of PDE4 on liver health and disease, and its potential as a therapeutic agent. PDE4's role in degrading cAMP disrupts intracellular signaling, increasing pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This contributes to liver inflammation in conditions such as hepatitis and non-alcoholic steatohepatitis (NASH). Additionally, PDE4 is a key factor in liver fibrosis, characterized by excessive extracellular matrix deposition. Inhibiting PDE4 shows promise in reducing liver fibrosis by decreasing the activation of hepatic stellate cells, which is pivotal in fibrogenesis. PDE4 also influences hepatocyte apoptosis a common feature of liver diseases. PDE4 inhibitors protect against hepatocyte apoptosis by raising intracellular cAMP levels, thus activating anti-apoptotic pathways. This suggests potential in targeting PDE4 to prevent hepatocyte loss. Moreover, PDE4 regulates hepatic glucose production and lipid metabolism, essential for liver function. Altering cAMP levels through PDE4 affects enzymes in these metabolic pathways, making PDE4 a target for metabolic disorders like type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Since PDE4 plays a multifaceted role in liver pathophysiology, influencing PDE4's mechanisms in liver diseases could lead to novel therapeutic strategies. Still, extensive research is required to explore the molecular mechanisms and clinical potential of targeting PDE4 in liver pathologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Wheat ( Triticum aestivum L.) is an essential food crop in terms of consumption as well as production. Aflatoxin exposure has a widespread public health impact in economically developing nations, so there is a need to establish preventive techniques for these high-risk populations. Pre-harvest and post-harvest practices are the two strategies used to control aflatoxin contamination, which include the use of genetically modified crops that show resistance against Aspergillus infection, the use of pesticides, changing the planting and harvesting time of crops, and physical, chemical, and biological methods. In this research, aflatoxin detection and quantification were performed in different wheat varieties to determine quantitative differences in comparison to the European Commission's limit of 4 ppb aflatoxins in wheat. TLC for qualitative and the ELISA kit method for quantitative analysis of aflatoxins were used. Out of 56 samples, 35 were found contaminated with aflatoxins, while the remaining 21 samples did not show any presence of aflatoxins. Out of the 35 contaminated samples, 20 samples showed aflatoxin contamination within the permissible limit, while the remaining 15 samples showed aflatoxin concentration beyond the permissible level, ranging from 0.49 to 20.56 ppb. After quantification, the nine highly contaminated wheat samples were detoxified using physical, chemical, and biological methods. The efficiency of these methods was assessed, and they showed a significant reduction in aflatoxins of 53-72%, 79-88%, and 80-88%, respectively. In conclusion, the difference in aflatoxin concentration in different wheat varieties could be due to genetic variations. Furthermore, biological treatment could be the method of choice for detoxification of aflatoxins in wheat as it greatly reduced the aflatoxin concentration with no harmful effect on the quality of the grains.

Significant progress has been made in designing advanced membranes; however, persistent challenges remain due to their reduced permeation rates and a propensity for substantial fouling. These factors continue to pose significant barriers to the effective utilization of membranes in the separation of oil-in-water emulsions. Metal-organic frameworks (MOFs) are considered promising materials for such applications; however, they encounter three key challenges when applied to the separation of oil from water: (a) lack of water stability; (b) difficulty in producing defect-free membranes; and (c) unresolved issue of stabilizing the MOF separating layer on the ceramic membrane (CM) support. In this study, a defect-free hydrolytically stable zirconium-based MOF separating layer was formed through a two-step method: first, by in situ growth of UiO-66-NH 2 MOF into the voids of polydopamine (PDA)-functionalized CM during the solvothermal process, and then by facilitating the self-assembly of UiO-66-NH 2 with PDA using a pressurized dead-end assembly. A stable MOF separating layer was attained by enriching the ceramic support with amines and hydroxyl groups using PDA, which assisted in the assembly and stabilization of UiO-66-NH 2 . The PDA-s-UiO-66-NH 2 -CM membrane displayed air superhydrophilicity and underwater superoleophobicity, demonstrating its oil resistance and high antifouling behavior. The PDA-s-UiO-66-NH 2 -CM membrane has shown exceptionally high permeability and separation capacity for challenging oil-in-water emulsions. This is attributed to numerous nanochannels from the membrane and its high resistance to oil adhesion. The membranes showed excellent stability over 15 continuous test cycles, which indicates that the developed MOFs separating layers have a low tendency to be clogged by oil droplets during separation. Machine learning-based Gaussian process regression (GPR) models as nonparametric kernel-based probabilistic models were employed to predict the performance efficiency of the PDA-s-UiO-66-NH 2 -CM membrane in oil-in-water separation. The outcomes were compared with the support vector machine (SVM) and decision tree (DT) algorithm. This efficiency includes various metrics related to its separation accuracy, and the models were developed through feature engineering to identify and utilize the most significant factors affecting the membrane's performance. The results proved the reliability of GPR optimization with the highest prediction accuracy in the validation phase. The average percentage increase of the GPR model compared to the SVM and DT model was 6.11 and 42.94%, respectively.

Introduction: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI)., Methods: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function., Results: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%)., Discussion: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI., Highlights: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials., Competing Interests: G.B.-L., T.C.L., T.B., Z.N.S., M.S., and E.G.M. are co-investigators on a proposal for a PCP treatment platform trial for people with and without HIV. T.B. has been the principal investigator of clinical trials sponsored by Shionogi Pharmaceuticals, Atea Pharmaceuticals, and Astra Zeneca Pharmaceuticals; he is currently recruiting to a clinical trial, sponsored by Mundpharma, of rezafungin for PCP. T.B. did not contribute to the rezafungin or echinocandin sections.

Roots are the main sensing organ, initiating multiple signaling pathways in response to abiotic factors, including nutrients, drought, and salt stress. A focus on improving the root system architecture is a key strategy to mitigate these stresses in wheat crop. In the present study, a diversity panel comprising indigenous landraces and historical cultivars from Pakistan was characterized for the root system architecture (RSA) and important loci were identified using a genome-wide association study (GWAS). RSA of the diversity panel was characterized 30 days after sowing in brunch tubes, and root images were taken. A high-throughput root imaging analysis using Rhizovision software was performed by setting the scale to extract the eight RSA traits and four plant biomass-related traits. GWAS identified 323 association signals for 12 root and biomass traits present on all wheat chromosomes, while the most important and reliable genetic loci (based on pleotropic loci and candidate genes) were identified on chromosomes 2A, 2B, 5A, 5D, 6A, 7B, and 7D for RSA. SNP annotation and transcriptome profiling identified nine candidate genes regulating the RSA and plant biomass traits, including ROOTLESS WITH UNDETECTABLE MERISTEM1, MYB TRANSCRIPTION FACTOR4, BRASSINOSTEROID INSENSITIVE1, SLENDER RICE1, AUXIN-RESPONSIVE FACTOR25, SCARECROW, NARROW LEAF2, PIN-FORMED1 AND PHOSPHATE TRANSCRIPTION FACTOR1. This study provided pre-breeding information for deep-rooting genotypes and associated markers that will accelerate the incorporation of such traits in breeding., (© 2024 Scandinavian Plant Physiology Society.)

Introduction: Hyperpyrexia, algesia and inflammation are pathological disorders which are treated with synthetic as well as herbal medications., Aims: The basic aim of the present study is to evaluate the ethnopharmacological activities of phytoconstituents that are present in C. colocynthis (fruit extract) by using in vivo and in silico studies., Methods: Thirty-six albino rats were used in our studies with an average weight between 150-170 g. Anti-inflammatory activity was investigated using carrageenan (an extract from a red seaweed) that induced edema in albino rat paws. However, in antipyretic and analgesic activity studies, yeast and acetic acid were used to cause pyrexia or algesia, respectively. Different doses of acetone fruit extract were used to treat inflammation, pyrexia and algesia., Results: Our results showed that the maximum percentage inhibition of acetonic fruit extract in anti-inflammatory and analgesic activities was observed at 70% and 100%, respectively, with 400 mg/kg doses, and in pyretic activity the maximum inhibitory percentage was 86% with a 100 mg/kg dose. In in silico analysis, we have shown that bioactive compounds (α-spinasterol, ascorbic acid and chlorogenic acid) found in fruit extract have outstanding inhibition properties that involves proteins PTGS2, TLR2 and TRPV4. C. colocynthis fruit extract shows results that are statistically significant (p < 0.005) and comparable to a reference drug. Acetonic fruit extract of C. colocynthis can be used as a natural and safe remedy with no side effects., Conclusion: Both in vivo and in silico studies on chlorogenic acid, ascorbic acid and α-spinasterol have shown that these are inhibitory compounds that can be used for boosting the immune response., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Wheat (Triticum aestivum ) is a major crop around the globe and different techniques are being used for its productivity enhancement. Germplasm evaluation to improve crop productivity mainly depends on accurate phenotyping and selection of genotypes with a high frequency of superior alleles related to the trait of interest. Therefore, applying functional kompetitive allele-specific PCR (KASP) markers for drought-related genes is essential to characterise the genotypes for developing future climate-resilient wheat crop. In this study, eight functional KASP markers and nine morphological traits were employed to evaluate the 40 wheat genotypes for drought tolerance. Morphological traits showed significant variation (P ≤0.05) among the genotypes, except tiller count (TC), fresh root weight (FRW) and dry root weight (DRW). PCA biplot showed that 63.3% phenotypic variation was explained by the first two PCs under control treatment, while 70.8% variation was explained under drought treatment. It also indicated that root length (RL) and primary root (PR) have considerable variations among the genotypes under both treatments and are positively associated with each other. Hence, the findings of this study suggested that both these traits could be used as a selection criterion to classify the drought-tolerant wheat genotypes. KASP genotyping accompanied by morphological data revealed that genotypes Markaz, Bhakar Star, China 2, Aas and Chakwal-50 performed better under drought stress. These outperforming genotypes could be used as parents in developing drought-tolerant wheat genotypes. Hence, KASP genotyping assay for functional genes or significant haplotypes and phenotypic evaluation are prerequisites for a modern breeding program.

Drought stress poorly impacts many morphological and physio-biochemical processes in plants. Pea ( Pisum sativum L.) plants are highly nutritious crops destined for human consumption; however, their productivity is threatened under drought stress. Thiamine (vitamin B1) is well-known essential micronutrient, acting as a cofactor in key metabolic processes. Therefore, this study was designed to examine the protective effect of foliar application of thiamine (0, 250, and 500 ppm) on two varieties of pea plants under drought stress. Here, we conducted the pot experiment at the Government College Women University, Faisalabad, to investigate the physio-biochemical and morphological traits of two pea varieties (sarsabz and metior) grown under drought stress and thiamine treatment. Drought stress was applied to plants after germination period of 1 month. Results showed that root fresh and dry weight, shoot fresh and dry weight, number of pods, leaf area, total soluble sugars, total phenolics, total protein contents, catalase, peroxidase, and mineral ions were reduced against drought stress. However, the application of thiamine (both 250 and 500 ppm) overcome the stress and also enhances these parameters, and significantly increases the antioxidant activities (catalase and peroxidase). Moreover, the performance of sarsabz was better under control and drought stress conditions than metior variety. In conclusion, the exogenous application of thiamine enabled the plants to withstand drought stress conditions by regulating several physiological and biochemical mechanisms. In agriculture, it is a great latent to alleviate the antagonistic impact of drought stress on crops through the foliar application of thiamine.

Background: Salinity is one of the main abiotic factors that restrict plant growth, physiology, and crop productivity is salt stress. About 33% of the total irrigated land suffers from severe salinity because of intensive underground water extraction and irrigation with brackish water. Thus, it is important to understand the genetic mechanism and identify the novel genes involved in salt tolerance for the development of climate-resilient rice cultivars., Methods and Results: In this study, two rice genotypes with varying tolerance to salt stress were used to investigate the differential expressed genes and molecular pathways to adapt under saline soil by comparative RNA sequencing at 42 days of the seedling stage. Salt-susceptible (S3) and -tolerant (S13) genotypes revealed 3982 and 3463 differentially expressed genes in S3 and S13 genotypes. The up-regulated genes in both genotypes were substantially enriched in different metabolic processes and binding activities. Biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and plant signal transduction mechanisms were highly enriched. Salt-susceptible and -tolerant genotypes shared the same salt adaptability mechanism with no significant quantitative differences at the transcriptome level. Moreover, bHLH, ERF, NAC, WRKY, and MYB transcription factors were substantially up-regulated under salt stress. 391 out of 1806 identified novel genes involved in signal transduction mechanisms. Expression profiling of six novel genes further validated the findings from RNA-seq data., Conclusion: These findings suggest that the differentially expressed genes and molecular mechanisms involved in salt stress adaptation are conserved in both salt-susceptible and salt-tolerant rice genotypes. Further molecular characterization of novel genes will help to understand the genetic mechanism underlying salt tolerance in rice., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure-tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable-adjusted linear regressions. 75% of participants had hearing loss and 15% of participants had retinopathy. The association between retinopathy, microaneurysms, and blot hemorrhages with better speech-frequency pure tone average was -2.81 (95% confidence interval [CI]: -5.72 to 0.10), -4.75 (95% CI: -8.73 to -0.78), and -5.34 (95% CI: -8.68 to -2.00), respectively. The presence of retinopathy, microaneurysms, and blot hemorrhages was inversely associated with hearing loss. Further studies are needed to better understand the potential relationship between microvascular pathologies of the eye and ear., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Here, we performed RNA-seq based expression analysis of root and leaf tissues of a set of 24 historical spring wheat cultivars representing 110 years of temporal genetic variations. This huge 130 tissues RNAseq dataset was initially used to study expression pattern of 97 genes regulating root growth and development in wheat. Root system architecture (RSA) is an important target for breeding stress-resilient and high-yielding wheat cultivars under climatic fluctuations. However, root transcriptome analysis is usually obscured due to challenges in root research due to their below ground presence. We also validated the dataset by performing correlation analysis between expression of RSA related genes in roots and leaves with 25 root traits analyzed under varying moisture conditions and 10 yield-related traits. The Pearson's correlation coefficients between root phenotypes and expression of root-specific genes varied from -0.72 to 0.78, and strong correlations with genes such as DRO1, TaMOR, ARF4, PIN1 was observed. The presented datasets have multiple uses such as a) studying the change in expression pattern of genes during time, b) differential expression of genes in two very important tissues of wheat i.e., leaf and roots, and c) studying customized expression of genes associated with important phenotypes in diverse wheat cultivars. The initial findings presented here provided key insights into understanding the transcriptomic basis of phenotypic variability of RSA in wheat cultivars., (© 2023. The Author(s).)

Spices are contaminated with aflatoxins (AFs) and Sudan dyes which are classified as class Group 1 and Group 3 human carcinogens by the International Agency for Research on Cancer (IARC) respectively and their prolonged exposure may raise a human health concern. A total of 474 samples of red chili and turmeric were collected from Lahore city and were subjected to quantitative and qualitative AFs and Sudan dyes analysis by thin layer chromatography (TLC) respectively. The number of red chili and turmeric samples with ≥10 μg/kg of total AFs (European Union standard limit) were 70% and 33% respectively and considered unfit for human consumption. The presence of Sudan dyes in red chili and turmeric samples was 67% and 27% respectively. The mean estimated daily intake (EDI) among females and males was 0.0019 μg/kg bw/day, 0.0012 μg/kg bw/day for red chili, and 0.0008 μg/kg bw/day, 0.0006 μg/kg bw/day for turmeric respectively. The mean value of margin of exposure (MOE) among females and males for ingestion of AFs-contaminated red chili and turmeric was 210.25, 332.13, 501.02, and 699.31 respectively. Therefore, the current study demands a continuous monitoring plan and the implementation of novel techniques to enhance the product's quality and protect public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study offers a comparison between three different types of thermoresponsive (TR) and thermo-pH-salt (TPR) multiresponsive polymers including homopoly( N -isopropylacrylamide) (PNIPAAm), copolymers with three different monomers, 2-hydroxyethyl methacrylate (HEMA), N,N -dimethylacrylamide (DMAAm), and styrene (S) at three different concentrations (5, 10, and 20 mol %), and a PNIPAAm terpolymer with 5, 10, and 20 mol % 2-((dimethylamino)methyl)-4-methylphenyl acrylate (DMAMCA) and 10 mol % HEMA, DMAAm, and S monomers. All polymers were chemically analyzed with 1 H NMR and Fourier transform infrared spectroscopy (FT-IR) as well as gel permeation chromatography (GPC) for the molecular weights and dispersity and differential scanning calorimeter (DSC) for the glass transition temperatures. The cloud point, also known as the phase separation temperature ( C p ), was determined for all polymers by a turbidity test using a UV-vis spectrophotometer; a micro-differential scanning calorimeter was used for measuring the cloud point in deionized water. The influence of a tertiary amine cationic group of DMAMCA changed the behavior of TR copolymers into TPR by shifting the cloud point of the TPR to higher values in acidic solutions (lower pH) and to lower values in alkaline solutions. The C p was measured at different concentrations of Hofmeister kosmotropic and chaotropic anion salt solutions in a range of pH solutions for the terpolymers. It demonstrated the same behavior as mentioned in pH solutions besides the effect of salt ions. By measuring the T c and C p of these polymers, we can exploit various applications of stimuli-responsive materials for sensors and biomedical technology., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Aloe barbadensis is a stemless plant with a length of 60-100 cm with juicy leaves which is used for its remedial and healing properties in different suburbs of various countries. The present study was conducted to investigate the effect of A. barbadensis leaf extract (aqueous and ethanolic) in yeast induced pyrexia and acetic acid induced writhing in rat model to evaluate the antipyretic biomarkers and its phytochemical screening with computational analysis. For analgesic activity model 60 Albino rats (160-200 kg) were divided into four groups. Of the 4 groups, control consisted of 6 rats (Group I) treated with normal saline, standard comprised of 6 rats treated with drug diclofenac (Group I). Experimental groups consisted of 48 rats, treated with A. barbadensis ethanolic and aqueous leaf extracts at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg (Group III. IV). For antipyretic activity group division was same as in analgesic activity. All groups were treated the same as in the analgesic activity except for the second group which was treated with paracetamol. In both antipyretic and analgesic activity at the dose of 400 mg/kg, group III showed significant inhibition. TNF-α and IL-6 showed significant antipyretic activity at a dose of 400 mg/kg. For molecular docking aloe emodin and cholestanol were used as ligand molecules to target proteins Tnf-α and IL-6. Acute oral toxicity study was performed. There was no mortality even at the dose of 2000 mg/kg. Quantitative and qualitative phytochemical screening was performed for the detection of various phytochemicals. Hence, A. barbadensis leaf extracts can be used in the form of medicine for the treatment of pain and fever.

MXene is an incredibly promising two-dimensional material with immense potential to serve as a high-performing separating or barrier layer to develop advanced membranes. Despite the significant progress made in MXene membranes, two major challenges still exist: (i) effectively stacking MXene nanosheets into defect-free membranes and (ii) the high fouling tendency of MXene-based membranes. To address these issues, we employed sulfonated polydopamine (SPD), which simultaneously serves as a binding agent to promote the compact assembling of Ti 3 C 2 T x MXenes (MX) nanosheets and improves the antifouling properties of the resulting sulfonated polydopamine-functionalized MX (SPDMX) membranes. The SPDMX membrane was tested for challenging surfactant-stabilized oil-in-water separation with an impressive efficiency of 98%. Moreover, an ultrahigh permeability of 1620 LMH/bar was also achieved. The sulfonation of PD helps in improving the antifouling characteristics of SPDMX by developing a strong hydration layer and enhancing the oleophobicity of the membrane. The underwater SPDMX membrane appeared superoleophobic with an oil contact angle of 153°, whereas the ceramic membrane exhibited an oil contact angle of 137°. The SPDMX membranes showed an improved flux recovery (31%) compared to the nonsulfonated counterpart. This work highlights the appropriate functionalization of MXene as a promising approach to developing MXene membranes with high permeation flux and better antifouling characteristics for oily wastewater treatment.

7-Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5- and 3-T scanners. We sought to characterize the intensity of acoustic noise from 7- versus 3-T scanners. A-weighted sound pressure levels from 5 types of pulse sequences used for brain and inner ear imaging in 3- and 7-T scanners were measured. Time-averaged sound level and maximum sound levels generated for each sequence were compared. Time-averaged sound levels exceeded 95 dB and reached maximums above 105 dB on the majority of 3- and 7-T scans. The mean time-averaged sound level and maximum sound level across pulse sequences were greater in 7- than 3-T (105.6 vs 91.4, P  = .01; 114.0 vs. 96.5 dB, P  < .01). 7- and 3-T magnetic resonance imaging scanners produce high levels of acoustic noise that exceed acceptable safety limits, emphasizing the need for active and passive noise protection., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Competing Interests: The authors declare no conflict of interest.

Background PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril-valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril-valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril-valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril-valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril-valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril-valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68-0.80). The protective effect of sacubitril-valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66-0.86]; P <0.01; men: HR, 0.71 [95% CI, 0.64-0.79]; P <0.01; P interaction 0.03). A protective effect for both sexes was seen only among those with systolic dysfunction. Conclusions Treatment with sacubitril-valsartan is more effective at reducing death and admission to the hospital for heart failure compared with ACEIs/ARBs similarly among men and women with systolic dysfunction; sex differences in the effectiveness of sacubitril-valsartan in diastolic dysfunction requires further investigation.

Sugarcane is one of the critical commercial crops and principal sources of ethanol and sugar worldwide. Unfavorable conditions and poor seed setting rates hinder variety development in sugarcane. Countries like Pakistan directly import fuzz (true seed) and other propagation material from the USA, China, Brazil, etc . In this study, we imported fuzz from China, developed 29 genotypes germinating in the glasshouse, and evaluated at field conditions along with two local checks (CPF-251 and HSF-240). Morphophysiological data were recorded, including plant height (PH), cane length (CL), internodal length (IL), tiller number (TN), brix percentage (B), cane diameter (CD), chlorophyll a (Chl. a ), chlorophyll b (Chl. b ), and total chlorophyll (T. Chl). Results showed highly significant ( p < 0.001) differences among the sugarcane accessions for all the studied traits. High broad-sense heritability (81.89% to 99.91%) was recorded for all the studied parameters. Genetic Advance (GA) ranges from 4.6% to 65.32%. The highest GA was observed for PH (65.32%), followed by CL (63.28%). Chlorophyll leaching assay was also performed at different time points (0, 50, 100, 150, and 200 min). All the genotypes showed the same leaching trend at all times, and better performing genotypes showed less leaching compared to poor performing, indicating the high amount of cutin and wax on the leaf surface. Correlation analysis showed that PH, CL, IL, and TN had significant associations. Principal components analysis (PCA) further confirms these results. Based on PCA and correlation results, PH, CL, IL, and TN can be utilized as a selection criterion for sugarcane improvement. Genotypes such as NS-4a, NS-5, NS-6, NS-8, NS-9, and NS-15 are recommended for future breeding programs related to sugarcane variety development., Competing Interests: Sajid Fiaz is an Academic Editor for PeerJ., (©2023 Saleem et al.)

Objective: To determine the natural history of cystic vestibular schwannomas (VS)., Study Design: Retrospective cohort., Setting: Single tertiary academic hospital., Patients: Adults diagnosed with cystic VS who had at least 2 MRIs performed at least 6 months apart between 2008 and 2016 with no intervening treatment., Main Outcome Measures: Volumetric growth rates of both the entire tumor and individual cystic and solid components were measured. Linear growth rate of the entire tumor was assessed using the largest diameter parallel to the petrous face at the cerebellopontine angle (CPA)., Results: Twenty-one patients met inclusion criteria. The average volumetric growth rate of the tumor was 1.1 ± 2 (range: -1.2 to 7.8), while the average growth rate of the cystic component was 0.8 ± 1.6 (range: -0.5 to 5.3) cm 3 /year. The CPA diameter of the tumor demonstrated an average linear growth rate of was 1.2 ± 4.4 (range: -8to 13.5) mm/year. With regards to tumor diameter, 9/21 (42.9%) remained stable, 3/21 (14.2%) decreased in size, while 9/21 (42.9%) increased in size., Conclusions: Cystic tumors demonstrate a wide variability in growth rate. Larger, multi-center studies will be required to further compare this relationship to solid tumors.

The current study investigated the in-vivo and in-silico anti-inflammatory effect of Aloe barbadensis in edema induced rat and its blood biomarkers. 60 albino rats (160-200 g) were divided into 4 groups. The 1st group (control) comprised of 6 rats that were treated with saline. The 2nd group (standard) comprised of 6 rats that were treated with diclofenac. The 3rd and 4th experimental groups consisted of 48 rats, treated with A. barbadensis gel ethanolic and aqueous extracts respectively at doses of 50, 100, 200 and 400 mg/kg. According to paw sizes, groups III and IV showed 51% and 46% inhibition respectively at the 5th hour, as compared to group II with 61% inhibition. Correlation was negative between biomarkers in group III, while, positive in group IV. Blood samples were collected; C-reactive protein and interleukin-6 were measured using commercially available ELISA kits. Similarly, biomarkers showed significant effect in dose-dependent manner. In molecular docking, for CRP both ligands aloe emodin and emodin showed -7.5 kcal/mol binding energy as compared to diclofenac with -7.0 kcal/mol. For IL-1beta, both ligands showed -4.7 kcal/mol binding energy as compared to diclofenac -4.4 kcal/mol. Hence, we concluded that A. barbadensis extracts can be used as an effective drug for managing inflammation.

Extensive pesticides (herbicides) use is negatively disturbing the environment and humans. Pesticide bioremediation with eco-friendly techniques bears prime importance. This study aimed to isolate and characterize three different herbicides (metribuzin, clodinafop- propargyl, MCPA (2-methyl, 4 chlorophenoxyacetic acids) and Bromoxynil) degrading bacterial strains from agricultural fields of Punjab University, Pakistan. Among the 12 bacterial isolates, 5 were metribuzin degrading, 3 were clodinafop propargyl degrading and, 4 were MCPA and Bromoxynil degrading bacteria. Morphological, microscopic, and molecular characterization revealed that the majority of these bacterial strains were gram-negative and belonged to Bacillus and Pseudomonas genera. The isolates A6, B3, and C1 were subjected to respective herbicide degradation and the data was confirmed through GC-MS analysis. The effect of herbicide concentrations, pH, and temperature on bacterial growth was determined at OD600. The strain A6 degraded 14.8% metribuzin out of the provided concentration of 50 ppm by following the deamination pathway. While the isolates B3 and C1 degraded 23.2% and 33.9% clodinafop, MCPA and bromo-xynil, respectively, at a spiking concentration of 50ppm. The clodinafop, MCPA and Bromoxynil were metabolized into less toxic products i.e., dicarboxylic acids and 2-methyl phenol respectively, and metabolized via decarboxylation and dehalogenation mechanism. The present study evaluates the herbicides degrading bacterial strains that could potentially be used for bioremediation of agricultural contaminated sites.

Antibiotic resistance is looming problem in broiler production globally and there has been an increasing interest to look for sustainable alternatives to antibiotics. Yeast and its derived products are recognized as potential feed additives because of their beneficial impacts on poultry. Particularly, yeast exhibited positive effects on the humoral immunity by increasing serum immunoglobulin (Ig) A levels. Moreover, yeast and its products showed immune adjuvant-like properties that helped the broilers chicken to develop faster and stronger innate immune response under pathogenic challenges. Use of yeast and its products as prebiotic/probiotic improves the gut architecture mainly by improving the gut development and gut microbiome, reduction in colonization of pathogens through competitive exclusion, binding of toxins and enhancing digestion and absorption of nutrients. These unique properties of yeast and yeast products enhance animal welfare and productivity; warrant them to be used as a promising feed additive. This article, therefore, provides insights into the functional role of yeast and its products in the broiler diets and highlights its importance as a commercially viable alternative of synthetic antibiotic growth promoters in the broiler feed industry.

Wheat grain quality, an important determinant for human nutrition, is often overlooked when improving crop production for stressed environments. Climate change makes this task more difficult by imposing combined stresses. The scenarios relevant to climate change include elevated CO 2 concentrations (eCO 2 ) and extreme climatic events such as drought, heat waves, and salinity stresses. However, data on wheat quality in terms of climate change are limited, with no concerted efforts at the global level to provide an equitable and consistent climate risk assessment for wheat grain quality. Climate change induces changes in the quality and composition of wheat grain, a premier staple food crop globally. Climate-change events, such as eCO 2 , heat, drought, salinity stress stresses, heat + drought, eCO 2  + drought, and eCO 2  + heat stresses, alter wheat grain quality in terms of grain weight, nutrient, anti-nutrient, fiber, and protein content and composition, starch granules, and free amino acid composition. Interestingly, in comparison with other stresses, heat stress and drought stress increase phytate content, which restricts the bioavailability of essential mineral elements. All climatic events, except for eCO 2  + heat stress, increase grain gliadin content in different wheat varieties. However, grain quality components depend more on inter-varietal difference, stress type, and exposure time and intensity. The climatic events show differential regulation of protein and starch accumulation, and mineral metabolism in wheat grains. Rapid climate shifting impairs wheat productivity and causes grain quality to deteriorate by interrupting the allocation of essential nutrients and photoassimilates. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Paeonia emodi Wall. ex Royle is commonly known as Himalayan paeony has great importance as a food and medicine. The practice of Paeonia emodi Wall. ex Royle is very ancient and it is conventionally used for a wide range of illnesses in the folk system of medicine because of its wide beneficial phytochemical profile. The main purpose of the current review was the synthesis of recent data on botany, ethnopharmacology, phytochemistry and potential pharmacological mechanisms of action of Paeonia emodi Wall. ex Royle, thus offering new prospects for the development of new adjuvant natural therapies. Using scientific databases such as PubMed/MedLine, Scopus, Web of Science, ScienceDirect, Google Scholar, Springer, and Wiley, a comprehensive literature search was performed for Paeonia emodi Wall. ex Royle. For searching, we used the next MeSH terms: "Biological Product/isolation and purification", "Biological Products/pharmacology", "Drug Discovery/methods", "Ethnopharmacology, Medicine", "Traditional/methods", "Paeonia/chemistry", "Plant Extracts/pharmacology", "Phytochemicals/chemistry", "Phytochemicals/pharmacology", "Plants, Medicinal". The results of the most recent studies were analyzed and the most important data were summarized in tables and figures. Phytochemical research of Paeonia emodi Wall. ex Royle has led to the isolation of triterpenes, monoterpenes, phenolic acids, fatty acids, organic compounds, steroids, free radicals and some other classes of primary metabolites. In addition, diverse pharmacological activities like antibacterial, antifungal, anticoagulant, airway relaxant lipoxygenase and beta-glucuronidase inhibiting activity, radical scavenging activity, phytotoxic and insecticidal activities have been reported for Paeonia emodi Wall. ex Royle. Different bioactive compounds of Paeonia emodi Wall. ex Royle has proven their therapeutic potential in modern pharmacological and biomedical research to cure numerous gastrointestinal and nervous disorders. In future, further in vitro and in vivo therapeutic studies are required to identify new mechanisms of action, pharmacokinetics studies, and new pharmaceutical formulations for target transport and possible interaction with allopathic drugs. Also, new research regarding quality evaluation, toxicity and safety data in humans is needed., (© 2023. The Author(s).)

Nanotechnology has enormous potential for sustainable agriculture, such as improving nutrient use efficiency, plant health, and food production. Nanoscale modulation of the plant-associated microbiota offers an additional valuable opportunity to increase global crop production and ensure future food and nutrient security. Nanomaterials (NMs) applied to agricultural crops can impact plant and soil microbiota, which offers valuable services to host plants, including the acquisition of nutrients, abiotic stress tolerance, and disease suppression. Dissecting the complex interactions between NMs and plants by integrating multi-omic approaches is providing new insights into how NMs can activate host responses and functionality as well as influence native microbial communities. Such nexus and moving beyond descriptive microbiome studies to hypothesis-driven research will foster microbiome engineering and open up opportunities for the development of synthetic microbial communities to provide agronomic solutions. Herein, we first summarize the significant role of NMs and the plant microbiome in crop productivity and then focus on NMs effects on plant-associated microbiota. We outline three urgent priority research areas and call for a transdisciplinary collaborative approach, involving plant scientists, soil scientists, environmental scientists, ecologists, microbiologists, taxonomists, chemists, physicists, and stakeholders, to advance nano-microbiome research. Detailed understanding of the nanomaterial-plant-microbiome interactions and the mechanisms underlying NMs-mediated shifts in the microbiome assembly and functions may help to exploit the services of both nano-objects and microbiota for next-generation crop health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

African Americans are at significantly greater risk of hypertension and worse cardiovascular outcomes than other racialized groups, yet hypertension intervention effects remain limited. Thus, it is necessary to understand the potential mechanisms whereby interventions may be more effectively targeted to improve health. Supported by prior research evidence and guided by the Biobehavioral Family Model, this study examined associations between family relationship quality, psychological wellbeing, and self-management behaviors for African Americans with hypertension. Data were pooled from three Midlife Development in the U.S. projects, resulting in a sample of 317 African Americans (63.4% female, M age  = 53.32) with self-reported high blood pressure in the past 12 months. We tested four cross-sectional multiple mediator models, with depressed mood and environmental mastery mediating associations between family strain and exercise, smoking, problematic alcohol use, and stress-eating. Environmental mastery mediated the association between greater family strain and decreased odds of achieving recommended exercise levels; greater odds of reporting problematic alcohol use; and greater stress-eating. Though family strain was associated with depressed mood in each model, this variable did not serve as an indirect pathway to self-management behaviors. Family strain, and the potential pathway identified via environmental mastery, may be a meaningful predictor of disease self-management for African Americans with hypertension. Longitudinal studies are needed to examine directionality and to support intervention trials for improving self-management and hypertension outcomes., (© 2022 Family Process Institute.)

Drought is one of the major abiotic stresses which negatively affects plant growth and development. The current study evaluated the effects of drought on the growth, physiology, and biochemical attributes of wheat seedlings; and examined the role of foliar application of ZnO nanoparticles in alleviating drought-induced effects. Two wheat cultivars i.e., Anaj-2017 and FSD-2018 were grown in soil-filled pots and were subjected to 100% field capacity (FC) (well watered) and 50% of FC (drought stress). Whilst different treatments of ZnO nanoparticles spray included no spray, water spray, and 50, 100, and 150 ppm ZnO. Results demonstrated that drought caused a significant reduction in seedling fresh and dry weights, photosynthetic pigmentation, and antioxidant activities compared with a well-watered treatment. Nevertheless, the application of 100 and 150 ppm of ZnO nanoparticles effectively ameliorated the negative effects of drought and enhanced the performance of both cultivars under drought. Data revealed a significant increase in fresh and dry weight of shoot and root with the application of ZnO nanoparticles. A substantial increase of 73.68% and 28.51% in chlorophyll "a" and 26.15% and 50.02% in chlorophyll "b" was recorded with the application of 100 ppm of ZnO nanoparticles in Anaj-2017 and FSD-2018, respectively over control (0 ppm). The application of these nanoparticles also triggered the antioxidant defense system and protected the crop from oxidative damage. Averaged across different stress treatments, application of 150 and 100 ppm of ZnO nanoparticles increased the peroxidase activity by 60% and 72% in FSD-2018, and 15% and 23% in Anaj-2017, respectively compared with no spray. FSD-2018 outperformed Anaj-2017 regarding its overall performance under ZnO treatments and drought conditions. In a nutshell, it can be concluded that ZnO nanoparticles ameliorated the negative impacts of drought by improving the growth, physiology, and antioxidant defense of both wheat cultivars., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Patients with vestibular loss have reduced wayfinding ability, but the association between vestibular loss and impaired steering spatial navigation is unclear., Objective: To evaluate whether vestibular loss is associated with reduced steering navigation performance in a virtual reality (VR) environment containing obstacles., Methods: 17 ambulatory adults with vestibular loss were age/sex-matched to healthy controls. Participants traversed a VR hallway with obstacles, and their navigation performance was compared using metrics such as collisions, time, total distance travelled, and speed in single and multivariate analysis., Results: In univariate analysis there was no significant difference in collisions between vestibular patients and controls (1.84 vs. 2.24, p = 0.974). However, vestibular patients took more time, longer routes, and had lower speeds to complete the task (56.9 vs. 43.9 seconds, p < 0.001; 23.1 vs. 22.0 meters, p = 0.0312; 0.417 vs. 0.544 m/s, p < 0.001). These results were confirmed in multivariate analysis., Conclusions: This study found that patients with vestibular loss displayed slower gait speeds and traveled longer distances, though did not make more collisions, during a VR steering navigation task. Beyond the known influence of vestibular function on gait speed, vestibular loss may also contribute to less efficient steering navigation through an obstacle-laden environment, through neural mechanisms that remain to be elucidated.

The Earth's geomagnetic field (GMF) is an inescapable environmental factor for plants that affects all growth and yield parameters. Both strong and weak magnetic fields (MF), as compared to the GMF, have specific roles in plant growth and development. MF technology is an eco-friendly technique that does not emit waste or generate harmful radiation, nor require any external power supply, so it can be used in sustainable modern agriculture. Thus, exposure of plants to MF is a potential affordable, reusable and safe practice for enhancing crop productivity by changing physiological and biochemical processes. However, the effect of MF on plant physiological and biochemical processes is not yet well understood. This review describes the effects of altering MF conditions (higher or lower values than the GMF) on physiological and biochemical processes of plants. The current contradictory and inconsistent outcomes from studies on varying effects of MF on plants could be related to species and/or MF exposure time and intensity. The reviewed literature suggests MF have a role in changing physiological processes, such as respiration, photosynthesis, nutrient uptake, water relations and biochemical attributes, including genes involved in ROS, antioxidants, enzymes, proteins and secondary metabolites. MF application might efficiently increase growth and yield of many crops, and as such, should be the focus for future research., (© 2022 German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

Acinetobacter baumannii (A. baumannii) is one of the members of ESKAPE bacteria which is considered multidrug resistant globally. The objective of this study is to determine the protein docking of different antibiotic resistance gene (ARGs) in A. baumannii. In silico analysis of antibiotic resistance genes against carbapenem are the blaOXA-51, blaOXA-23, blaOXA-58, blaOXA-24, blaOXA-143, NMD-1 and IMP-1 in A. baumannii. The doripenem, imipenem and meropenem were docked to blaOXA-51 and blaOXA-23 using PyRx. The top docking energy was -5.5 kcal/mol by imipenem and doripenem and meropenem showed a binding score of -5. 2 kcal/mol each and blaOXA-23 energy was -4.3 kcal/mol by imipenem and meropenem showed a binding score of -2.3 kcal/mol, while doripenem showed the binding score of -3.4 kcal/mol. Similarly, doripenem imipenem and meropenem were docked to blaOXA-58, IMP-1, Rec A and blaOXA-143, with docking energy was -8.8 kcal/mol by doripenem and meropenem each while imipenem showed a binding score of -4.2 kcal/mol and with IMP-1 demonstrated their binding energies. was -5.7 kcal/mol by meropenem and doripenem showed a binding score of -5.3 kcal/mol, while imipenem showed a binding score of -4.5 kcal/mol. And docking energy was -4.9 kcal/mol by imipenem and meropenem showed binding energy of -3.6 kcal/mol each while doripenem showed a binding score of -3.9 kcal/mol in RecA and with blaOXA-143 docking energy was -3.0 kcal/mol by imipenem and meropenem showed a binding score of -1.9 kcal/mol, while doripenem showed the binding score of -2.5 kcal/mol respectively. Doripenem, imipenem, and meropenem docking findings with blaOXA-24 confirmed their binding energies. Doripenem had the highest docking energy of -5.5 kcal/mol, meropenem had a binding score of -4.0 kcal/mol, and imipenem had a binding score of -3.9 kcal/mol. PyRx was used to dock the doripenem, imipenem, and meropenem to NMD-1. Docking energies for doripenem were all - 4.0 kcal/mol, whereas meropenem had docking energy of -3.3 kcal/mol and imipenem was -1.50 kcal/mol. To the best of our knowledge the underlying mechanism of phenotypic with genotypic resistance molecular docking regarding carbapenem resistance A. baumannii is unclear. Our molecular docking finds the possible protein targeting mechanism for carbapenem-resistant A.baumannii., (© 2022. The Author(s).)

Flavonoids are characterized as the low molecular weight polyphenolic compounds universally distributed in planta . They are a chemically varied group of secondary metabolites with a broad range of biological activity. The increasing amount of evidence has demonstrated the various physiological functions of flavonoids in stress response. In this paper, we provide a brief introduction to flavonoids' biochemistry and biosynthesis. Then, we review the recent findings on the alternation of flavonoid content under different stress conditions to come up with an overall picture of the mechanism of involvement of flavonoids in plants' response to various abiotic stresses. The participation of flavonoids in antioxidant systems, flavonoid-mediated response to different abiotic stresses, the involvement of flavonoids in stress signaling networks, and the physiological response of plants under stress conditions are discussed in this review. Moreover, molecular and genetic approaches to tailoring flavonoid biosynthesis and regulation under abiotic stress are addressed in this review.

Intestinal parasitic infection is one of the major challenges in obtaining optimal production and maintaining the health and welfare of all animals including cattle and buffaloes. Anti-parasitic treatments appear to be a reliable countermeasure. However, the effectiveness and selection of suitable anthelmintics require situational assessments in a given locality. In the current study, the efficacy and impact of benzimidazole (albendazole) were assessed in a total of 400 (100 each) on the performance of buffaloes, buffalo-heifer, cattle, and cattle-heifers at two commercial dairy farms in the Province of Punjab, Pakistan. Additionally, the cost-benefit ratio was calculated by assessing the inputs (medication, feed, and labor cost) and outputs (milk and weight gain). The qualitative and quantitative examination of helminth eggs in each type of animal indicated a prevalence of 73.3, 78.3, 76.6, and 85.0% in cattle, cattle-heifers, buffaloes, and buffaloes-heifers, respectively. Specifically, a highest rate (10.0-13.3%) of Haemonchus sp. infection was only observed in cattle and heifers, while Fasciola sp. infections (10.0-11.6%) were the most often found species in buffaloes and heifers. The highest anthelmintic impacts (egg per gram of feces, p < 0.001) were observed on day 14 post-medication. Until 60 days of post-anthelmintic treatment, an average increase of 0.8 and 0.7 L in milk production per day in cattle and buffaloes, respectively while a total of 11.45 and 9.45 kg body weight were noticed in cattle-heifer and buffaloes-heifer, respectively. Cumulative cost-benefit analysis indicated a positive correlation between treated and non-treated animals. These findings reiterate the importance of anthelmintic drugs in reducing the impacts of parasites on the productivity, health, and well-being of an animal under high infection challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KL declared a shared affiliation with the author MTA to the handling editor at the time of review., (Copyright © 2022 Rashid, Zahra, Chudhary, Rehman, Aleem, Alouffi, Mohammed, Rashid, Ehsan, Malik, Hussain Dilber, Bakhsh and Almutairi.)

Milk thistle ( Silybum marianum (L.)) is a wild medicinal herbal plant that is widely used in folk medicine due to its high content of secondary metabolites (SMs) and silymarin; however, the data regarding the response of milk thistle to salinity are still scarce and scanty. The present study evaluated the effect of salinity on a geographically diverse population of milk thistle and on the role of medium supplementation (MS) with ascorbic acid, thiourea, and moringa leaf extract in improving the SMs and growth-related attributes under salinity stress (SS). For germination, a 120 mM level of salinity was applied in the soil during the seedling stage. After salinity development, predetermined levels of the following compounds were used for MS: thiourea (250 µM), moringa leaf extract (3%), and ascorbic acid (500 µM). The data regarding growth attributes showed that SS impaired plant growth and development and increased SM production, including alkaloids, anthocyanin, and saponins. Moreover, ascorbic acid, followed by moringa leaf extract, was the most effective in improving growth by virtue of increased SMs, especially under salt stress conditions. The present study demonstrated that milk thistle could withstand moderate doses of SS, while MS improved all the growth parameters by increasing the accumulation of SMs., Competing Interests: The authors declare no conflict of interest.

Due to the emergence of antibiotic resistance, bacteriophage therapy appears to be an ideal weapon to utilize against pathogenic bacteria. This study aimed to isolate, identify and characterize the lytic bacteriophage effective against the multidrug-resistant Acinetobacter baumannii clinical isolates. The isolated bacteriophage caused lysis by applying the double-layer agar technique on A. baumannii up to 99% in 18 hours of incubation at 37 º C. The bacterial growth reduction assay exhibited that JHA phage had high adsorption rates and could rapidly inhibit bacterial growth. The pH and thermal stability testing showed that JHA phage was stable in vast ranges of pH from 5 to 9 but its activity was highest at pH7 (1860000±1000 pfu/mL). It was stable in broad ranges of temperatures from 25 º C to 60 º C but the highest activity was found at 37 º C (1300000±30000 pfu/mL). One-step growth test results showed that it has a short latent period, strong lytic ability, high burst size and adsorption rates and was host specific. Scanning electron microscopy (SEM) of JHA phage demonstrated icosahedral heads and tailless particles. Transmission electron microscopy (TEM) revealed JHA phage belongs to Tectiviridae family. All the characteristics of JHA phage possess lytic activity against A. baumannii strains and exhibit novel candidates to use as an alternative competitor to antibiotics in controlling such infections.

Background: The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use., Objectives: To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements., Data Sources: Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022., Study Eligibility Criteria: Randomised controlled trials; all languages., Participants: All hospitalized adults with COVID-19., Interventions: Remdesivir, in comparison to either placebo, or standard of care., Assessment of Risk of Bias: We used the ROB-2 criteria., Methods of Data Synthesis: The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important., Results: We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5-1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79-0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88-1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen., Conclusions: Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Contamination of edible oils with aflatoxins (AFs) is a universal issue due to the detrimental effects of aflatoxins on human health and the fact that edible oils are a major source of fungal growth, particularly storage fungi ( Aspergillus sp.). The objective of this study was to assess aflatoxin B 1 (AFB 1 ) in edible oil used in fried food in order to determine the risk of cancer from AFB 1 exposure through cooked food using the FAO/WHO's and EFSA's margin of exposure (MOE) quantitative liver cancer risk approaches. Using Mycosep 226 columns and HPLC-FLD, 100 samples of cooking oils (soybean, canola, and sunflower oil) from different food points were analyzed for contamination with aflatoxins. Of all the samples tested, 89% were positive for total aflatoxins and AFB 1 , with 65% indicating AF concentrations beyond permitted levels. Canola oil was found to contain higher levels of AFB 1 and AFs than soybean and sunflower oil. Almost 71 percent of canola oil samples (range of 54.4-281.1 µg/kg) were contaminated with AF levels higher than the proposed limits of the European Union (20 µg/kg). The consumption of canola oil samples used in fried foods had MOE values that were significantly lower as compared to sunflower and soybean oils, indicating that risk reduction is feasible. Additionally, compared to soybean and sunflower oil, canola oil exhibited a greater threat of liver cancer cases linked to AFB 1 exposure (17.13 per 100,000 males over 35 and 10.93 per 100,000 females over 35). Using a quantitative liver cancer approach, health risk valuation demonstrated that males and females over the age of 35 are at significant risk of developing liver cancer. The health risk assessment exposed that the males and female over the age of 35 are at considerable risk of liver cancer by using a quantitative liver cancer approach. The innovation of this study lies in the fact that no such study is reported related to liver cancer risk evaluation accompanied with AFB 1 exposure from consumed edible oil. As a result, a national strategy must be developed to solve this problem so that edible oil products are subjected to severe regulatory examination.