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Aging involves metabolic changes that lead to reduced cellular fitness, yet the role of many metabolites in aging is unclear. Understanding the mechanisms of known geroprotective molecules reveals insights into metabolic networks regulating aging and aids in identifying additional geroprotectors. Here we present AgeXtend, an artificial intelligence (AI)-based multimodal geroprotector prediction platform that leverages bioactivity data of known geroprotectors. AgeXtend encompasses modules that predict geroprotective potential, assess toxicity and identify target proteins and potential mechanisms. We found that AgeXtend accurately identified the pro-longevity effects of known geroprotectors excluded from training data, such as metformin and taurine. Using AgeXtend, we screened ~1.1 billion compounds and identified numerous potential geroprotectors, which we validated using yeast and Caenorhabditis elegans lifespan assays, as well as exploring microbiome-derived metabolites. Finally, we evaluated endogenous metabolites predicted as senomodulators using senescence assays in human fibroblasts, highlighting AgeXtend's potential to reveal unidentified geroprotectors and provide insights into aging mechanisms., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

A simple, accurate, and robust reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantification of Baclofen in rat plasma. The method demonstrated high degree of linearity (r 2  = 0.9936) across a concentration range of 10-50 μg/mL. Precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), and robustness were evaluated according to ICH guidelines. The LOD and LOQ were found to be 0.076197 and 0.23090 μg/mL, respectively. This method provides an efficient approach for Baclofen quantification in plasma, making it suitable for pharmacokinetic and bioavailability studies. The novelty of this study lies in its optimization for routine use in laboratories, ensuring reproducibility with minimal variations across different conditions and analysts., (© 2024 John Wiley & Sons Ltd.)

Purpose: The early post-transplant period after liver transplantation is critical, as recipients are highly susceptible to sepsis due to their immune-compromised state. This study aimed to identify the association between preoperative procalcitonin and early post-transplant sepsis and mortality at one month after living donor liver transplantation (LDLT)., Methodology: All patients who underwent LDLT from July 2021 to December 2021 were recruited prospectively. Participants were divided into two groups based on preoperative PCT levels: elevated (>0.5 ng/ml) and low levels (<0.5 ng/ml). Serum procalcitonin (PCT) levels were measured on the day of transplant and on postoperative days 3 and 7. The relationship between preoperative PCT and post-transplant sepsis was evaluated using a Chi-square test, and receiver operating characteristic (ROC) curves were generated., Results: Sepsis occurred in 48.3% of patients, with a significant association between elevated preoperative PCT levels and early post-transplant sepsis (p=0.023). The ROC curve for preoperative PCT showed moderate predictive ability (area under curve (AUC)=0.664), while PCT levels on postoperative day 3 demonstrated better discriminatory power (AUC=0.790). PCT levels measured on day 7 also had good diagnostic accuracy, with an AUC of 0.843 and a significant difference between the sepsis and non-sepsis groups (p=0.002). The length of ICU stay was significantly longer in the sepsis group (p=0.009).  Conclusion: Elevated preoperative PCT levels can predict early post-transplant sepsis in LDLT patients. PCT monitoring may enhance risk stratification and guide perioperative management, improving post-transplant outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee at Institute of Liver and Biliary sciences, New Delhi issued approval IEC/2020/73/NA05. 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, Satija et al.)

Background Live donor liver transplantation, a widely practiced procedure, involves resecting a portion of a healthy donor's liver for transplantation. Despite advancements, it poses challenges like cardiovascular instability and electrolyte imbalances, with maintaining acid-base balance being critical. This study compares the effects of 0.9% normal saline and PlasmaLyte A® on acid-base status and postoperative liver function. Methodology This prospective observational study was conducted over one year among 40 healthy adults aged 18-60 years undergoing donor hepatectomy. Patients were alternately allocated to receive either 0.9% saline (Group 1; n = 20) or PlasmaLyte A® (Group 2; n = 20). Key parameters, including acid-base status, hemodynamic parameters, and postoperative liver function, were monitored at various intervals. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA), with appropriate statistical tests. A p-value <0.05 was considered statistically significant. Results The study included 40 patients, with 20 in each group. No significant differences were observed between the groups concerning age, gender, weight, hemodynamic parameters, and urine output. However, significant differences were found in acid-base parameters. Group 2 showed better preservation of acid-base balance with higher pH and HCO₃ levels. Patients in Group 1 exhibited a significant decrease in HCO₃ levels during surgery, while those in Group 2 maintained a more stable metabolic profile. Furthermore, nine patients in Group 1 required sodium bicarbonate supplementation for metabolic acidosis, compared to only three in Group 2. Postoperative liver function tests revealed no significant differences between the two groups, although a trend toward better outcomes was observed in Group 2. Conclusions PlasmaLyte A® demonstrated superior preservation of acid-base balance compared to 0.9% normal saline, with less need for bicarbonate supplementation. While liver function outcomes were similar, the balanced solution showed a trend toward better metabolic stability, suggesting it may offer safer and more effective fluid management in liver transplantation surgery., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee, Sir Ganga Ram Hospital issued approval EC/01/16/947. 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, Satija et al.)

Beryllium-7 ( 7 Be) was created by proton irradiation of natural ( nat B) and enriched ( 10 B) boron targets. The targets were dissolved in nitric acid, and the 7 Be was separated from the bulk boron target material by cation-exchange chromatography. An average recovery of (99.4 ± 3.7)% was obtained for 6 separations. The purified 7 Be sample was placed into a batch-mode ion source to create a 7 Be beam that was delivered at an average rate of 5 × 10 5 pps to end users at the National Superconducting Cyclotron Laboratory., 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.)

Intensive care unit (ICU) patients are prone to develop infections by hospital prevalent organisms. The aim of the study was to determine the bacteriological profiles and their drug resistance pattern among different infections in ICU patients of a tertiary care hospital. The record-based retrospective data of culture reports of the patients admitted to all the ICUs of a tertiary care hospital during the period from January 2020 to May 2022 were analyzed. A total of 3,056 samples were obtained from 2308 patients. The infection rate among ICU patients was found to be 53.40%. Isolates belonged equally to males (50.86%) and females (49.14%). The most common culture-positive clinical specimen received was blood (39.08%) followed by respiratory samples (29.45%). Acinetobacter sp. (33.02%) was the most common organism isolated from various clinical specimens, followed by Klebsiella pneumoniae (20.89%), and Escherichia coli (13.8%). More than 80% of Acinetobacter species were found to be resistant to third-generation cephalosporins, aminoglycosides, and carbapenems, whereas minocycline (56.31% S) and colistin (100% S) were the most effective drugs. Klebsiella sp. was found to be more resistant than E.coli , and the least resistance was observed to be tetracycline (43.97%) and doxycycline (55.84%). Among Staphylococcus aureus , 82.78% of strains were methicillin-resistant (MRSA). Vancomycin-resistant Enterococci (VRE) sp. accounted for 16.67% of the isolates. Evidence-based knowledge regarding the local bacterial organisms and their antimicrobial resistance pattern is pivotal in deciding empirical drug therapy, ultimately leading to the management of antimicrobial resistance (AMR)., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Garima Gautam et al.)

Cellular genome is considered a dynamic blueprint of a cell since it encodes genetic information that gets temporally altered due to various endogenous and exogenous insults. Largely, the extent of genomic dynamicity is controlled by the trade-off between DNA repair processes and the genotoxic potential of the causative agent (genotoxins or potential carcinogens). A subset of genotoxins form DNA adducts by covalently binding to the cellular DNA, triggering structural or functional changes that lead to significant alterations in cellular processes via genetic (e. g., mutations) or non-genetic (e. g., epigenome) routes. Identification, quantification, and characterization of DNA adducts are indispensable for their comprehensive understanding and could expedite the ongoing efforts in predicting carcinogenicity and their mode of action. In this review, we elaborate on using Artificial Intelligence (AI)-based modeling in adducts biology and present multiple computational strategies to gain advancements in decoding DNA adducts. The proposed AI-based strategies encompass predictive modeling for adduct formation via metabolic activation, novel adducts' identification, prediction of biochemical routes for adduct formation, adducts' half-life predictions within biological ecosystems, and, establishing methods to predict the link between adducts chemistry and its location within the genomic DNA. In summary, we discuss some futuristic AI-based approaches in DNA adduct biology., (© 2023 Wiley-VCH GmbH.)

Melanoma, a highly aggressive skin cancer, is often driven by BRAF mutations, such as the V600E mutation, which promotes cancer growth through the MAPK pathway and contributes to treatment resistance. Understanding the role of non-coding RNAs (ncRNAs) in these processes is crucial for developing new therapeutic strategies. This review aims to elucidate the relationship between ncRNAs and BRAF mutations in melanoma, focusing on their regulatory roles and impact on treatment resistance. We comprehensively reviewed current literature to synthesize evidence on ncRNA-mediated regulation of BRAF-mutant melanoma and their influence on therapeutic responses. Key ncRNAs, including microRNAs and long ncRNAs, were identified as significant regulators of melanoma development and therapy resistance. MicroRNAs such as miR-15/16 and miR-200 families modulate critical pathways like Wnt signaling and melanogenesis. Long ncRNAs like ANRIL and SAMMSON play roles in cell growth, invasion, and drug susceptibility. Specific ncRNAs, such as BANCR and RMEL3, intersect with the MAPK pathway, highlighting their potential as therapeutic targets or biomarkers in BRAF-mutant melanoma. Additionally, ncRNAs involved in drug resistance, such as miR-579-3p and miR-1246, target processes like autophagy and immune checkpoint regulation. This review highlights the pivotal roles of ncRNAs in regulating BRAF-mutant melanoma and their contribution to drug resistance. These findings underscore the potential of ncRNAs as biomarkers and therapeutic targets, paving the way for innovative treatments to improve outcomes for melanoma patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the current scenario, pulmonary disease has become a prime burden for morbidity and mortality alongside tremendous social and economic crises throughout the world. Numerous conventional drug delivery system and treatment approach targeting the respiratory region has been driven out. However, effective and accurate recovery has not been achieved yet. In this regard, nanotechnological- based inhalable drug delivery strategy including polymeric, lipidic, or metallic-based respirable microparticles plays an indispensable role in circumventing numerous challenges faced during traditional treatment. Excellent aerodynamic performance leads to enhanced lung targetability, reduced dosing frequency and hence systemic toxicities, as well as improved pharmaceutical attributes, and therefore pharmacokinetic profiles are interminable factors associated with nanotechnologicalbased inhalable delivery. In this review, we comprehensively explored recent advancements in nanotechnologically engineered inhalable formulations targeting each of the mentioned pulmonary diseases. Moreover, we systematically discussed possible respiratory or systemic toxicities about the indeterminate and undefined physicochemical characteristics of inhaled particles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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Within the pediatric population, bronchial asthma is one of the most prevalent chronic respiratory system diseases. The number of exacerbations, severity, and duration of symptoms all have a significant impact on children's life quality. In the last decades, the prevention and management strategies of this pathology have focused on maintaining or even increasing the pulmonary function to maximum levels in early childhood, as it has been demonstrated that functional deficits at this level occurring before school age cause pathological manifestations later, in adulthood. The epithelium of the airways and implicitly that of the lung is the first barrier against the lesions caused by pro-oxidative factors. Both oxidative and antioxidative factors can be of endogenous origin (produced by the body) or exogenous (from the environment or diet). Good functioning of antioxidant defense mechanisms from the molecular level to the tissue level, and a balance between pro-oxidative factors and anti- oxidative factors, influence the occurrence of compensatory mechanisms at the level of the respiratory epithelium, causing the delay of local responses to the stress induced by chronic inflammation (bronchial remodeling, thickening of airway smooth muscles, bronchoconstriction, bronchial hyper-reactivity). These mechanisms underlie the pathophysiological changes in asthma. Numerous studies carried out among the pediatric population inclusively have demonstrated the effectiveness of antioxidants in the prophylaxis, slowing down and preventing the progression of this pathology. This review complements the scientific articles, aiming at emphasizing the complexity of oxidative physio-pathological pathways and their importance in the occurrence, development, and therapeutic response in asthma, providing a good understanding of the relationship between oxidative and antioxidative factors, and being a source of future therapeutic strategies. [ABSTRACT FROM AUTHOR]

We present the study of millisecond-resolved polymer brush swelling dynamics using infrared spectroscopy with a home-built quantum cascade laser-based infrared spectrometer at a 1 kHz sampling rate after averaging. By cycling the humidity of the environment of the polymer brush, we are able to measure the swelling dynamics sequentially at different wavenumbers. The high sampling rate provides us with information on the reconformation of the brush at a higher temporal resolution than previously reported. Using spectroscopic ellipsometry, we study the brush swelling dynamics as a reference experiment and to correct artefacts of the infrared measurement approach. This technique informs on the changes in the brush thickness and refractive index. Our results indicate that the swelling dynamics of the polymer brush are poorly described by Fickian diffusion, pointing toward more complicated underlying transport. [ABSTRACT FROM AUTHOR]

Tocopherols, potent bioactive compounds with anticancer properties, remain understudied in herbal medicinal plants, presenting a significant knowledge gap in the field of natural anticancer agents. This review evaluates tocopherol-containing plants for their anticancer potential, analyzing Scopus publications from 2016 to 2024. Fifteen herbal medicinal plants were identified as promising candidates, including Bulbine anguistifolia Poelln, Punica granatum L., Moringa oleifera, Kigelia pinnata, and Typhonium flagelliforme Lodd. The review explores tocopherols' anticancer mechanisms, including apoptosis induction and cell cycle arrest. Factors influencing tocopherols' anticancer effects are examined, such as their forms (α, β, γ, δ), concentrations, plant parts utilized, and their stability in various plants. Additionally, emerging research on semi-synthetic tocopherol derivatives is analyzed, highlighting their potential as adjuvants in chemotherapy and their role in enhancing drug delivery and reducing side effects. This comprehensive analysis aims to advance the development of plant-based anticancer pharmaceuticals and improve cancer treatment strategies. By elucidating the mechanisms and potential of tocopherol-containing plants, this review provides a foundation for future research in plant-based anticancer therapies. It emphasizes the need for further investigation into these plants' anticancer properties, potentially leading to novel, more effective, and less toxic cancer therapies. The findings presented here contribute to a nuanced understanding of how tocopherol-containing plants can be leveraged in the development of future anticancer drugs. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between dietary flavonoids and bronchitis, emphysema and asthma. Method: A total of 11743 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007–2008, 2009–2010 and 2017–2018. Of these, 47.7% were male and 52.3% female. Dietary flavonoid intake assessed using FDNNS and 24-hour dietary recall data. Inclusion of demographics (gender, age, education, family income), behavioral factors (BMI, smoking, drinking status, diet), chronic disease information (diabetes, hypertension) as covariates to eliminate confounding. Stepwise logistic regression was used to analyze the association between total dietary flavonoid intake and the risk of chronic respiratory disease. Weighted quantile sum regression (WQS) was used to analyze the association between 29 dietary flavonoids and the risk of chronic respiratory disease. Restricted cubic spline was used to analyze the dose-response relationship between dietary flavonoid intake and risk of chronic respiratory disease. Results: Stepwise logistic regression results showed that higher flavonoid intake in men was associated with a lower risk of CB and asthma (OR of CB: 0.55(0.31–0.97); OR of asthma: 0.72(0.52–0.99)), and WQS results showed a mixed health effect for total flavonoids and chronic respiratory tract in response to the 29 flavonoid fractions (OR of asthma: 0.97(0.94–0.99); OR of emphysema: 0.95(0.90–0.99)). Glycitein had the highest health contribution of 26.2% for emphysema; Eriodictyol had the highest health contribution of 32.13% for asthma, respectively. The RCS showed a dose-response relationship between flavonoids and respiratory tract health. The maximum dose for ingesting flavonoids to gain respiratory health benefits is 1500 mg/d. Conclusion: Higher dietary flavonoid intake was associated with lower chronic respiratory risk in adult U.S. men. Also 29 dietary flavonoid components have an overall health effect on respiratory health. Glycitein and Eriodictyol may have potential health effects on the respiratory system. 1500 mg/day may be the Tolerable Upper Intake Level of dietary flavonoids for respiratory health in U.S. adults. [ABSTRACT FROM AUTHOR]

In this study, Echium amoenum (known as borage) petals, popular as a medicinal herb, was used for producing copper nanoparticles (CuO NPs) for the first time. Since borage metabolites are bioactive, they were used as bioreductive agents for synthesizing CuO NPs. For this, phytochemical compositions of EA extract were analyzed qualitatively before fabricating CuO NPs. Various measurements were conducted to characterize the CuO NPs, including UV–vis, FTIR, SEM–EDS, TEM, XRD, DLS, and the zeta potential. Additionally, EA-CuO NPs were examined for antimicrobial, free radical scavenging and cytotoxic activities. The surface plasmon resonance peak of the EA-CuO NPs was identified as 346.6 nm based on UV–visible spectroscopy. FTIR spectra proposed possible functional groups associated with EA-CuO NP formation. According to the SEM and TEM images, the EA-CuO NPs were spherical and ranged from 30 to 40 nm. The crystallites were estimated to be particulate at 28.5 nm in size, with the copper-to-oxygen ratio of 60.16:24.96 determined by XRD and EDX. There was an approximate IC50 value of 35.46 µg/ml for the DPPH and 70.11 µg/ml for the H2O2 scavenging activity of EA-CuO NPs. A MIC value of 80 µg/ml was obtained for EA-CuO NPs against Staphylococcus aureus, Staphylococcus saprophytic, and Klebsiella pneumonia. However, MIC values for EA-CuO NPs against Pseudomonas aeruginosa and Candida species were 160 and 600 µg/ml, respectively. Based on the findings, EA-CuO nanoparticles have the potential to be used as an alternative to antibiotics to treat antibiotic-resistant pathogens. Given this, it would be prudent to conduct detailed studies into the mechanism of action and side effects of EA-CuO NPs before they are applied as antimicrobial agents for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Compounds of natural origin found in varying quantities in plant-based products constitute a highly significant category, possessing structural significance as well as the capacity to regulate oxidative processes. The activity of these compounds may be modulated by the composition of the biological environment in which they operate, the pH of the environment, or the presence of metal cations in plants or plant extracts. A successful complexation reaction was mainly confirmed by FT-IR, observing the shift from the original transmittance of catechin bonds, especially O-H ones. This work shows the synthetic methodology and the optimization process that took place to synthesize a catechin–copper complex, which demonstrated antioxidant activity. It was tested for iron chelation ability, hydroxyl radicals, and the inhibition of lipoxygenase (15-LOX). An antidiabetic assay was performed by determining the inhibition of alpha-amylase and alpha-glucosidase, finding that the synthesized complex had similar inhibitory potential as pure catechin. The antibacterial tests showed results against Staphylococcus aureus and the antifungal properties of the complex against Candida albicans. [ABSTRACT FROM AUTHOR]

Conventional antibiotic and multidrug treatments are becoming less and less effective and the discovery of new effective and safe antibacterial agents is becoming a global priority. Returning to a natural antibacterial product is a relatively new current trend. Terrestrial biota is a rich source of biologically active substances whose antibacterial potential has not been fully utilized. The aim of this review is to present the current state-of-the-art terrestrial biota-derived antibacterial agents inspired by natural treatments. It summarizes the most important sources and newly identified or modified antibacterial agents and treatments from the last five years. It focuses on the significance of plant- animal- and bacteria-derived biologically active agents as powerful alternatives to antibiotics, as well as the advantages of utilizing natural antibacterial molecules alone or in combination with antibiotics. The main conclusion is that terrestrial biota-derived antibacterial products and substances open a variety of new ways for modern improved therapeutic strategies. New terrestrial sources of known antibacterial agents and new antibacterial agents from terrestrial biota were discovered during the last 5 years, which are under investigation together with some long-ago known but now experiencing their renaissance for the development of new medical treatments. The use of natural antibacterial peptides as well as combinational therapy by commercial antibiotics and natural products is outlined as the most promising method for treating bacterial infections. In vivo testing and clinical trials are necessary to reach clinical application. [ABSTRACT FROM AUTHOR]

The widespread adoption of encrypted communication protocols has significantly enhanced network security and user privacy, simultaneously elevating the importance of encrypted traffic analysis across various domains, including network anomaly detection. The Transport Layer Security (TLS) 1.3 protocol, introduced in 2018, has gained rapid popularity due to its enhanced security features and improved performance. However, TLS 1.3's security enhancements, such as encrypting more of the handshake process, present unprecedented challenges for encrypted traffic analysis, rendering traditional methods designed for TLS 1.2 and earlier versions ineffective and necessitating the development of novel analytical techniques. This comprehensive survey provides a thorough review of the latest advancements in TLS 1.3 traffic analysis. First, we examine the impact of TLS 1.3's new features, including Encrypted ClientHello (ECH), 0-RTT session resumption, and Perfect Forward Secrecy (PFS), on existing traffic analysis techniques. We then present a systematic overview of state-of-the-art methods for analyzing TLS 1.3 traffic, encompassing middlebox-based interception, searchable encryption, and machine learning-based approaches. For each method, we provide a critical analysis of its advantages, limitations, and applicable scenarios. Furthermore, we compile and review key datasets utilized in machine learning-based TLS 1.3 traffic analysis research. Finally, we discuss the main challenges and potential future research directions for TLS 1.3 traffic analysis. Given that TLS 1.3 is still in the early stages of widespread deployment, research in this field remains nascent. This survey aims to provide researchers and practitioners with a comprehensive reference, facilitating the development of more effective TLS 1.3 traffic analysis techniques that balance network security requirements with user privacy protection. [ABSTRACT FROM AUTHOR]

The need for delivery systems based on biopolymers led this study to the synthesis of a new type of polysaccharide film. Thus, two distinct types of films were obtained in which amide-type anesthetics were incorporated. In the composition of type A films, κ-carrageenan and glycerol are found, while in the composition of type B films, hydroxyethyl cellulose (HEC) is also included. The addition of the second polysaccharide (HEC) to the base composition makes the B-type films exhibit parafilm-like elasticity. FTIR study indicates successful incorporation of anesthetics without affecting the integrity of the polysaccharide matrix. Through TG/DTG and DSC studies, it is highlighted that the active substances are stable in the range of 37–100 °C, as well as the polysaccharides that have been chosen as a film base. Thus, all the data obtained from this study indicate that these films can be used as a local anesthetic carrier for possible transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Background: A variety of medicinal plants are used in traditional medicine in Lubumbashi for the management of hemorrhoidal diseases. However, no investigation has been conducted to gather the knowledge required for this type of management in the region. The present study was conducted to inventory the plants used in Lubumbashi to treat hemorrhoidal diseases and to relate their ethnomedical characteristics. Methods: This study was conducted between March 2022 and February 2023 by interviews using semi-structured questionnaire with households (n = 1520), herbalists (n = 25), and traditional healers: THs (n = 59). Results: The 1,604 respondents (sex ratio M/F = 0.9; mean age: 56 ± 3 years; experience: 12 ± 3 years) provided information on 100 taxa, 84 of which are used against internal hemorrhoids, Phyllanthus amarus being the most cited (Citation Index, CI: 0.76). Most of them are trees (38%) or shrubs (32%), belonging to 90 genera and 45 families dominated by the Fabaceae (10%) and Asteraceae (9%). They are indicated in 76 other pathologies, dominated by gastrointestinal disorders (GID), wounds and sexually transmitted infections (CI > 0.57). From these 100 taxa, 117 anti-hemorrhoidal formulations were derived, 11 of which combined more than one plant. In all these recipes, the leaf is the most commonly used part (> 60%) and the liniment (> 45%) is the most popular form of application. For the first time, this study reports 14 taxa as plants used in the treatment of hemorrhoids. Among these taxa, Ficus stuhlmannii, Ficus laurifolia, and Ocimum centraliafricanum are listed as medicinal plants for the first time. Khaya nyasica, and Syzygium cordatum, each with 11 uses, have the highest traditional medicinal value. Conclusion: The findings of this study indicate that a significant number of medicinal plants are used in traditional medicine in Lubumbashi for the treatment of hemorrhoidal diseases. Some of these plants are endemic to the biodiversity area, while others are shared with other cultures and regions. A series of pharmacological studies is currently underway with the objective of validating the anti-hemorrhoidal properties of these plants and in order to identify phytochemical compounds responsible of this activity. [ABSTRACT FROM AUTHOR]

Copper nanoparticles (CuNPs) are tiny materials with special features such as high electric conductivity, catalytic activity, antimicrobial activity, and optical activity. Published reports demonstrate their utilization in various fields, including biomedical, agricultural, environmental, wastewater treatment, and sensor fields. CuNPs can be produced utilizing traditional procedures; nevertheless, such procedures have restrictions like excessive consumption of energy, low production yields, and the utilization of detrimental substances. Thus, the adoption of environmentally approachable "green" approaches for copper nanoparticle synthesis is gaining popularity. These approaches involve employing plants, bacteria, and fungi. Nonetheless, there is a scarcity of data regarding the application of microbial bioflocculants in the synthesis of copper NPs. Therefore, this review emphasizes copper NP production using microbial flocculants, which offer economic benefits and are sustainable and harmless. The review also provides a characterization of the synthesized copper nanoparticles, employing numerous analytical tools to determine their compositional, morphological, and topographical features. It focuses on scientific advances from January 2015 to December 2023 and emphasizes the use of synthesized copper NPs in wastewater treatment. [ABSTRACT FROM AUTHOR]

Background: Numerous cellular, humoral, and molecular processes are involved in the intricate process of wound healing. Pharmacological relevance: Numerous bioactive substances, such as ß-sitosterol, tannic acid, gallic acid, protocatechuic acid, quercetin, ellagic acid, and pyrogallol, along with their pharmacokinetics and bioavailability, have been reviewed. These phytochemicals work together to promote angiogenesis, granulation, collagen synthesis, oxidative balance, extracellular matrix (ECM) formation, cell migration, proliferation, differentiation, and re-epithelialization during wound healing. Findings and novelty: To improve wound contraction, this review delves into how the application of each bioactive molecule mediates with the inflammatory, proliferative, and remodeling phases of wound healing to speed up the process. This review also reveals the underlying mechanisms of the phytochemicals against different stages of wound healing along with the differentiation of the in vitro evidence from the in vivo evidence There is growing interest in phytochemicals, or plant-derived compounds, due their potential health benefits. This calls for more scientific analysis and mechanistic research. The various pathways that these phytochemicals control/modulate to improve skin regeneration and wound healing are also briefly reviewed. The current review also elaborates the immunomodulatory modes of action of different phytochemicals during wound repair. [ABSTRACT FROM AUTHOR]

Background: Berberine, a phytochemical, possesses remarkable potential for multitargeted drug therapy in microbial infections, wound healing and anti-inflammatory applications. However, its clinical utility in skin and other diseases is constrained due to its high aqueous solubility and inadequate dermal and intestinal absorption, resulting in low absolute bioavailability. Objectives: The current investigation endeavors to develop a microemulsion loaded with berberine to enhance its solubility and therapeutic effects specifically for skin diseases, while comparing its efficacy with a simple emulsion. Materials and Methods: In this study, an optimized oil-in- water (o/w) type of emulsion and microemulsion were formulated utilizing berberine isolated from Berberis aristata roots, along with soy lecithin, oleic acid, Tween 80, and ethanol. The microemulsion and emulsion were subjected to characterization employing parameters such as FTIR, particle size, zeta potential, transmittance, viscosity, and stability. The formulations were assessed for their therapeutic effects through in vitro antioxidant, anti-inflammatory, and anti, microbial assays, encompassing six strains of micro, organisms comprising bacteria and fungi. Results: The investigation successfully generated a thermodynamically stable o/w type of microemulsion, which exhibited improved transparency and formed a clear solution. Characterization results, including particle size, zeta potential, viscosity, and conductivity measurements, fell within the acceptable range. The therapeutic evaluation demonstrated a substantial enhancement in the in vitro antioxidant, anti-inflammatory, and anti, microbial activity of berberine microemulsion compared to the plain berberine solution. Conclusion: This study concludes that berberine can be effectively incorporated into a microemulsion system. When topically applied, the microemulsion form exhibits significantly higher therapeutic efficacy against skin diseases compared to the conventional emulsion of berberine. [ABSTRACT FROM AUTHOR]

The fields of statistical physics and single-cell genomics have traditionally evolved independently, each contributing unique insights to their respective domains. However, recent advances have unveiled intriguing parallels between these seemingly disparate disciplines. This paper delves into the remarkable similarities underlying the fundamental principles governing both systems, shedding light on their shared mathematical frameworks, information processing dynamics and emergent behaviours. We explore how energy landscapes in statistical physics correspond to gene expression landscapes, and how the study of disordered phenomena may shed light on the cellular heterogeneity observed in gene expression profiles. Some parallels between phase transitions and critical transitions in cellular differentiation processes are discussed. Emergent behaviours and collective phenomena, central to both fields, offer opportunities for cross-disciplinary insights. By examining these similarities, we can potentially transfer analytical tools and methodologies between these domains. In summary, this paper underscores some unexpected yet profound parallels between statistical physics and single-cell genomics. By embracing the shared mathematical and conceptual frameworks, researchers can unlock new avenues for discovery, enriching our understanding of complex systems ranging from the microscopic world of molecules to the intricate processes governing cellular behaviour. [ABSTRACT FROM AUTHOR]

The coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM‐TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of Mycobacterium tuberculosis (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro‐inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM‐related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate. [ABSTRACT FROM AUTHOR]

Ocular drug delivery has been major challenge to pharmacologist and drug delivery scientist due to its unique anatomy and physiology. Nanosuspension by their inherent ability to improve the saturation solubility of the drug, represent an ideal for ocular delivery of hydrophobic drugs and nanoparticulate nature of drug allows prolong residence time in cul-de-sac, giving sustained release of drug. In this study Polymeric nanoparticles of azelastine hydrochloride were developed by stabilizer HPMC E5 (1%), Brij 35 (0.5%) and Poloxamer 188 (2%) polymer to prolong retention time of formulation. In order to optimize particle size, zeta potential and drug release of nanoparticles, different concentration of stabilizer and polymer was used in the formulation development. From all prepared nanosuspension formulations, significant drug release was observed compared to pure drug. Physicochemical characterization of the selected samples using differential scanning calorimetry, Brookfield viscometer, FT-IR spectroscopy, powder X-ray diffraction shows polymorphic transition of azelastine hydrochloride nanoparticles. This polymorphic transition can be one of the factors responsible for improving of residence in cul-de-sac, giving sustained release of drug. The optimized formulation was found to be stable and clear with mean particle size 164.4 nm, PDI 0.471, zeta potential -15.1 and pH 4.5 that is non-irritant to ocular cavity. The in-vitro drug release study showed that the optimized nanosuspension released 99.24% of the drug within 9 hours. The formulated nanosuspension was exhibited stable over period of 3 month and non-irritant with a sustain release action. [ABSTRACT FROM AUTHOR]

Background: Genetic improvement for Striga hermonthica (Sh) and S. asiatica (Sa) resistance is the most economical and effective control method to enhance the productivity of maize and other major cereal crops. Hence, identification of quantitative trait loci (QTL) associated with Striga resistance and economic traits will guide the pace and precision of resistance breeding in maize. The objective of this study was to undertake a genome-wide association analysis of grain yield and Sh and Sa resistance among tropical and sub-tropical maize populations to identify putative genetic markers and genes for resistance breeding. 126 maize genotypes were evaluated under controlled environment conditions using artificial infestation of Sh and Sa. The test genotypes were profiled for grain yield (GY), Striga emergence counts at 8 (SEC8) and 10 (SEC10) weeks after planting, and Striga damage rate scores at 8 (SDR8) and 10 (SDR10) weeks after planting. Population structure analysis and genome-wide association mapping were undertaken based on 16,000 single nucleotide polymorphism (SNP) markers. Results: A linkage disequilibrium (LD) analysis in 798,675 marker pairs revealed that 21.52% of pairs were in significant linkage (P < 0.001). Across the chromosomes, the LD between SNPs decayed below a critical level (r2 = 0.1) at a map distance of 0.19 Mbp. The genome-wide association study identified 50 significant loci associated with Sh resistance and 22 significant loci linked to Sa resistance, corresponding to 39 and 19 candidate genes, respectively. Conclusion: The study found non-significant QTL associated with dual resistance to the two examined Striga species Some of the detected genes reportedly conditioned insect and pathogen resistance, plant cell development, variable senescence, and pollen fertility. The markers detected in the present study for Sa resistance were reported for the first time. The gene Zm00001eb219710 was pleiotropic, and conditioned GY and SEC10, while Zm00001eb165170 affected SDR8 and SDR10, and Zm00001eb112030 conditioned SDR8 and SDR10 associated with Sh resistance. The candidate genes may facilitate simultaneous selection for Sh and Sa resistance and grain yield in maize after further validation and introgression in breeding pipelines. Overall, we recommend breeding maize specifically for resistance to each Striga species using germplasm adapted to the endemic region of each parasite. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (P. aeruginosa) pneumonia can have serious physiological consequences, particularly when P. aeruginosa biofilms are formed. Although inhaled therapy is preferred, inhaled drugs tend to get trapped by pulmonary mucus, which hinders efficient antibiotic permeability through mucus and biofilms. In this study, we prepare poly[2-(pentamethyleneimino)ethyl methacrylate]-block-poly[2- (N-oxide-pentamethyleneimino)ethyl methacrylate] (PPEMA-b-PPOEMA) micelles loaded with azithromycin (AZM) using reversible addition–fragmentation chain transfer (RAFT) polymerization to achieve effective treatment of P. aeruginosa pneumonia. The zwitterionic structure on the surface of the micelle facilitates the successful traversal of the mucus and optimal concentration within the biofilm. Furthermore, the protonation of piperidine in the polymer enables the micelles to exhibit a positive charge in the acidic environment of a bacterial infection, enhancing AZM’s interaction with the bacterium. Both in vivo and in vitro experiments demonstrate that this transmucosal zwitterionic polymer, in combination with a charge reversal strategy, effectively promotes the enrichment of micelles at the site of bacterial infection, thereby increasing the number of antibiotics reaching the bacterial interior and demonstrating remarkable antibacterial synergy. Overall, this work offers a promising approach for trans-airway drug delivery in the treatment of pneumonia. [ABSTRACT FROM AUTHOR]

Cell membranes are crucial elements in living organisms, serving as protective barriers and providing structural support for cells. They regulate numerous exchange and communication processes between cells and their environment, including interactions with other cells, tissues, ions, xenobiotics, and drugs. However, the complexity and heterogeneity of cell membranes—comprising two asymmetric layers with varying compositions across different cell types and states (e.g., healthy vs. diseased)—along with the challenges of manipulating real cell membranes represent significant obstacles for in vivo studies. To address these challenges, researchers have developed various methodologies to create model cell membranes or membrane fragments, including mono- or bilayers organized in planar systems. These models facilitate fundamental studies on membrane component interactions as well as the interactions of membrane components with external agents, such as drugs, nanoparticles (NPs), or biomarkers. The applications of model cell membranes have extended beyond basic research, encompassing areas such as biosensing and nanoparticle camouflage to evade immune detection. In this review, we highlight advancements in the engineering of planar model cell membranes, focusing on the nanoarchitectonic tools used for their fabrication. We also discuss approaches for incorporating challenging materials, such as proteins and enzymes, into these models. Finally, we present our view on future perspectives in the field of planar model cell membranes. [ABSTRACT FROM AUTHOR]

Cervical and ovarian cancers account for the majority of deaths among women. Due to the failure of conventional therapies to completely cure these diseases, research has shifted focus to traditional and plant-based medicines. This study aimed to assess the potential anticancer activity of tamarind leaf extract on ovarian cancer PA-1 and cervical cancer HeLa cell lines. The extract was prepared using Soxhlet equipment with ethanol as the solvent and fractionated using Thin Layer Chromatography (TLC) under bioassay guidance. Anticancer activity was determined through in vitro tests, including MTT assay, fluorescence microscopy, trypan blue assay, LDH activity assay, caspase-9 activity assay, analysis of DNA fragmentation, Annexin V/PI staining and flow cytometry. Bioactive compound characterization was performed using gas chromatography-mass spectrometry (GC-MS) followed by NIST library search, to understand the underlying principles behind the anticancer attributes of tamarind leaf. The results revealed that treatment with tamarind leaf ethanol extract drastically reduced HeLa and PA-1 cell viabilities to 26.8% and 11.9%, respectively, after 72 hours. The yellow fraction (TLYF) of the extract was identified as the bioactive component through bioassay-guided fractionation. Trypan blue assay results showed cell concentrations reduced to 1.3x105 and 1.2x105 cells/mL compared to about 3.6x105 cells/mL in control HeLa and PA-1 cells. Cell cycle analysis demonstrated that TLYF reduced overall cell count, with a significant decrease in S and G2/M phases, and increased percentage of cells (50.9 and 18.8%) in early and late apoptotic stages as per annexin V/PI staining. Caspase assay confirmed apoptosis initiation through caspase-9 activation in cancer cells induced by TLYF. According to GC-MS data, apigenin, an anticancer compound reported in several fruits, was found in tamarind leaf. It can be assumed that apigenin in tamarind leaf might be the reason for its profound antiproliferative effects against cancer cells. [ABSTRACT FROM AUTHOR]

Rhodamine 6G (R6G) and 4-nitro-2,1,3-benzoxadiazole (NBD) linked through a spacer molecule spermidine (spd), R6G-spd-NBD, produces a fluorescent probe with pH-sensitive FRET (Förster (fluorescence) resonance energy transfer) effect that can be useful in a variety of diagnostic applications. Specifically, cancer cells can be spotted due to a local decrease in pH (Warburg effect). In this research, we applied this approach to intracellular infectious diseases—namely, leishmaniasis, brucellosis, and tuberculosis, difficult to treat because of their localization inside macrophages. R6G-spd-NBD offers an opportunity to detect such bacteria and potentially deliver therapeutic targets to treat them. The nanogel formulation of the R6G-spd-NBD probe (nanoparticles based on chitosan or heparin grafted with lipoic acid residues, Chit-LA and Hep-LA) was obtained to improve the pH sensitivity in the desired pH range (5.5–7.5), providing selective visualization and targeting of bacterial cells, thereby enhancing the capabilities of CLSM (confocal laser scanning microscopy) imaging. According to AFM (atomic force microscopy) data, nanogel particles containing R6G-spd-NBD of compact structure and spherical shape are formed, with a diameter of 70–100 nm. The nanogel formulation of the R6G-spd-NBD further improves absorption and penetration into bacteria, including those located inside macrophages. Due to the negative charge of the bacteria surface, the absorption of positively charged R6G-spd-NBD, and even more so in the chitosan derivatives' nanogel particles, is pronounced. Additionally, with a pH-sensitive R6G-spd-NBD fluorescent probe, the macrophages' lysosomes can be easily distinguished due to their acidic pH environment. CLSM was used to visualize samples of macrophage cells containing absorbed bacteria. The created nanoparticles showed a significant selectivity to model E. coli vs. Lactobacillus bacterial cells, and the R6G-spd-NBD agent, being a mild bactericide, cleared over 50% E.coli in conditions where Lactobacillus remained almost unaffected. Taken together, our data indicate that R6G-spd-NBD, as well as similar compounds, can have value not only for diagnostic, but also for theranostic applications. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8+ T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8+ T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB. Editor's summary: T cell dysfunction is a defining feature of many tumor types, but how tumor-specific T cells progress to a terminally exhausted state and which populations are targeted by immune checkpoint blockade (ICB) remains incompletely understood. Using single-cell transcriptomics, Morgan et al. profiled T cell differentiation states across different anatomical sites including tumors, draining lymph nodes, and the white pulp of the spleen from tumor-bearing mice treated with ICB. A population of splenic intermediate-exhausted T cells supplied most of the ICB-elicited tumor-specific T cell response, which required low levels of cross-presented tumor antigen in the spleen. Together, these findings identify the spleen as an important site for generating a tumor-specific T cell response after ICB. —Claire Olingy [ABSTRACT FROM AUTHOR]

Canine oral malignant melanoma (COMM) is the most common neoplasm in the oral cavity characterized by local invasiveness and high metastatic potential. Hypoxia represents a crucial feature of the solid tumor microenvironment promoting cancer progression and drug resistance. Hypoxia-inducible factor-1α (HIF-1α) and its downstream effectors, vascular endothelial growth factor A (VEGF-A), glucose transporter isoform 1 (GLUT1), C-X-C chemokine receptor type 4 (CXCR4), and carbonic anhydrase IX (CAIX), are the main regulators of the adaptive response to low oxygen availability. The prognostic value of these markers was evaluated in 36 COMMs using immunohistochemistry. In addition, the effects of cobalt chloride–mediated hypoxia were evaluated in 1 primary COMM cell line. HIF-1α expression was observed in the nucleus, and this localization correlated with the presence or enhanced expression of HIF-1α-regulated genes at the protein level. Multivariate analysis revealed that in dogs given chondroitin sulfate proteoglycan-4 (CSPG4) DNA vaccine, COMMs expressing HIF-1α, VEGF-A, and CXCR4 were associated with shorter disease-free intervals (DFI) compared with tumors that were negative for these markers (P =.03), suggesting hypoxia can influence immunotherapy response. Western blotting showed that, under chemically induced hypoxia, COMM cells accumulate HIF-1α and smaller amounts of CAIX. HIF-1α induction and stabilization triggered by hypoxia was corroborated by immunofluorescence, showing its nuclear translocation. These findings reinforce the role of an hypoxic microenvironment in tumor progression and patient outcome in COMM, as previously established in several human and canine cancers. In addition, hypoxic markers may represent promising prognostic markers, highlighting opportunities for their use in therapeutic strategies for COMMs. [ABSTRACT FROM AUTHOR]

Drug delivery is essential to provide correct treatments in many ways. The critical points in any drug delivery method are patient compliance, maximum efficacy in therapy, minimum toxicity, and enabling new medical treatments. Pulmonary drug delivery is one way of delivering therapeutics locally and systemically. The lung microenvironment and mechanical and biological barriers must be surpassed for successful drug delivery. This makes the delivery challenging. Formulations that can be delivered through the lung and have a responsive character are of great interest since they can hold the key to the successful delivery of therapeutics. This review has gathered fundamental studies related to materials (polymeric, lipidic, inorganic, and biomolecules) that are responsive to pH, enzymes, ROS, magnetism, and other variables, and it shows the advances and applications in pulmonary drug delivery for different diseases in vitro as well as in vivo. [ABSTRACT FROM AUTHOR]

DNA adductomics is the global study of all DNA adducts and was first proposed in 2006 by the Matsuda group. Its development has been greatly credited to the advances in mass spectrometric techniques, particularly tandem and multiple-stage mass spectrometry. In fact, liquid chromatography-mass spectrometry (LC-MS)-based methods are virtually the sole technique with practicality for DNA adductomic studies to date. At present, DNA adductomics is primarily used as a tool to search for DNA adducts, known and unknown, providing evidence for exposure to exogenous genotoxins and/or for the molecular mechanisms of their genotoxicity. Some DNA adducts discovered in this way have the potential to predict cancer risks and/or to be associated with adverse health outcomes. DNA adductomics has been successfully used to identify and determine exogenous carcinogens that may contribute to the etiology of certain cancers, including bacterial genotoxins and an N-nitrosamine. Also using the DNA adductomic approach, multiple DNA adducts have been observed to show age dependence and may serve as aging biomarkers. These achievements highlight the capability and power of DNA adductomics in the studies of medicine, biological science, and environmental science. Nonetheless, DNA adductomics is still in its infancy, and great advances are expected in the future. [ABSTRACT FROM AUTHOR]

In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient‐derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function‐associated single‐cell RNA sequencing (FascRNA‐seq) platform allowing both phenotypic evaluation and scRNA‐seq at single‐organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA‐seq data of individual pLCOs with their responses to anti‐PD‐1 (αPD‐1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti‐tumor immunity, to identify potential tumor‐reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA‐seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Today, food scientists are interested in more rational use of crops that possess desirable nutritional properties, and buckwheat is one of the functional pseudocereals that represents a rich source of bioactive compounds (BACs) and nutrients, phytochemicals, antimicrobial (AM) agents and antioxidants (AOs), which can be effectively applied in the prevention of malnutrition and celiac disease and treatment of various important health problems. There is ample evidence of the high potential of buckwheat consumption in various forms (food, dietary supplements, home remedies or alone, or in synergy with pharmaceutical drugs) with concrete benefits for human health. Contamination as well as other side-effects of all the aforementioned forms for application in different ways in humans must be seriously considered. This review paper presents an overview of the most important recent research related to buckwheat bioactive compounds (BACs), highlighting their various functions and proven positive effects on human health. [ABSTRACT FROM AUTHOR]

The acid pollution produced from coal gangue piles is a global environmental problem. Terminal technologies, such as neutralization, precipitation, adsorption, ion exchange, membrane technology, biological treatment, and electrochemistry, have been developed for acid mine drainage (AMD) treatment. These technologies for treating pollutants with low concentrations over a long period of time in coal gangue piles appear to be costly and unsustainable. Conversely, in situ remediation appears to be more cost-effective and material-efficient, but it is a challenge that coal producing countries need to solve urgently. The primary prerequisite for preventing acidic pollutants is to clarify the oxidation mechanisms of coal gangue, which can be summarized as four aspects: pyrite oxidation, microbial action, low-temperature oxidation of coal, and free radical action. The two key factors of oxidation are pyrite and coal, and the four necessary conditions are water, oxygen, microorganisms, and free radicals. The current in situ remediation technologies mainly focus on one or more of the four necessary conditions, forming mixed co-disposal, coverage barriers, passivation coatings, bactericides, coal oxidation inhibitors, microorganisms, plants, and so on. It is necessary to scientifically and systematically carry out in situ remediation coupled with various technologies based on oxidation mechanisms when carrying out large-scale restoration and treatment of acidic coal gangue piles. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive analysis of the critical issue of water insecurity and its multifaceted impact on and relationship to the human rights and environmental justice conditions within Rohingya refugee camps located in New Delhi, India. A comprehensive mixed-methods approach was employed to investigate water-related challenges within a refugee camp in Madanpur Khadar, region in Delhi. Qualitative methods including focused group discussions and one-on-one household interviews were conducted to allow residents' perceptions from diverse groups and examine their experiences. Structured surveys were administered to gather quantitative data on water access, sanitation, health, and socio-economic factors. Additionally,, literature surveys and document archival research provided contextual insights. This study underscores the pressing water, sanitation, and hygiene (WaSH) challenges faced by Rohingya refugees in the area, revealing irregular water supply, impacting residents' daily lives and hygiene practices. The majority of families in the camp, with an average of 6 members in each family, can only collect 30–40 L of water to meet all their needs, from consumption to personal hygiene, which is significantly insufficient. This situation has resulted in severe health consequences for the camp residents. Alarmingly, over 90% of the female respondents reported experiencing issues such as urinary infections. This paper gives a comprehensive analysis of the multidimensionality of rights that intersect with and are affected by WaSH issues. The poor WaSH conditions in the camp directly hinder the fulfillment of fundamental human rights. It not only disrupts the basic sanitation need but has negative economic repercussions and causes mental distress. This study concludes by targeted recommendations aimed at improving the conditions prevailing within the camp. [ABSTRACT FROM AUTHOR]