Evaluation of the Quality of Management Guidelines for Children and Adolescents With Autism Spectrum Disorder.

OBJECTIVE: To systematically assess the quality of management guidelines for children and adolescents with autism spectrum disorder, analyze key management recommendation differences and causes among guidelines, and provide better guideline assessments for clinical workers. METHODS: Clinical guidelines for managing children and adolescents with autism were systematically retrieved from a database. Four reviewers independently evaluated the guidelines using the assessment guideline tool, Appraisal of Guidelines for Research and Evaluation II (AGREE II), and the intra-group correlation coefficient (ICC) was used to measure the consistency of the assessment guidelines among the four reviewers and the differences and reasons for the recommendations and supporting evidence were compared and analyzed. RESULTS: A total of ten management guidelines for children and adolescents with autism spectrum disorder published from 2014 to 2022 were included in this study, with high overall agreement between raters (range of intra-group correlation coefficients: 53.3% ∼ 85.0%), and areas with better median scores and ranges in Protocol II were as follows: domain 1 (scope and purpose, median = 86.1%, 59.7%-98.6%), Domain 4 (clarity of statements, median = 88.2%, 38.9%-100.0%) and domain 6 (independence of editors, median = 71.9%, 0.0%-100.0%). Among the ten guidelines the guidelines published by the Scott Intercollegiate Guidelines Network in 2016 and by the National Institute for health and care excellence in 2021 scored high and were recommended for adoption, 88.7%, 84.9%, respectively. CONCLUSION: There is considerable variation between the quality of guidelines for the management of children and adolescents with autism spectrum disorders.

An overview of environmental risk factors for type 2 diabetes research using network science tools.

Objective: Current studies lack a comprehensive understanding of the environmental factors influencing type 2 diabetes, hindering an in-depth grasp of the overall etiology. To address this gap, we utilized network science tools to highlight research trends, knowledge structures, and intricate relationships among factors, offering a new perspective for a profound understanding of the etiology. Methods: The Web of Science database was employed to retrieve documents relevant to environmental risk factors in type 2 diabetes from 2012 to 2024. Bibliometric analysis using Microsoft Excel and OriginPro provided a detailed scientific production profile, including articles, journals, countries, and authors. Co-occurrence analysis was employed to determine the collaboration state and knowledge structures, utilizing social network tools such as Gephi, Tableau, and R Studio. Additionally, theme evolutionary analysis was conducted using SciMAT to offer insights into research trends. Results: The publications and themes related to environmental factors in type 2 diabetes have consistently risen, shaping a well-established research domain. Lifestyle environmental factors, particularly diet and nutrition, stand out as the most represented and rapidly growing topics. Key focal hotspots include sedentary and digital behavior, PM2.5, ethnicity and socioeconomic status, traffic and greenspace, and depression. The theme evolutionary analysis revealed three distinct paths: (1) oxidative stress-air pollutants-PM2.5-air pollutants; (2) calcium-metabolic syndrome-cardiovascular disease; and (3) polychlorinated biphenyls (PCBs)-persistent organic pollutants (POPs)-obesity. Conclusions: Digital behavior signifies a novel approach for preventing and managing type 2 diabetes. The influence of PM2.5 and calcium on oxidative stress and abnormal vascular contraction is intricately linked to microvascular diabetes complications. The transition from PCBs and POPs to obesity underscores the disruption of endocrine function by chemicals, elevating the risk of diabetes. Future studies should explore the connections between environmental factors, microvascular complications, and long-term outcomes in diabetes.

Prevalence of intrinsic capacity decline among community-dwelling older adults: a systematic review and meta-analysis.

BACKGROUND: The concept of intrinsic capacity (IC) was introduced to define healthy aging and active aging based on functional capacity, yet there is limited understanding of the risk of IC decline at a population level. AIMS: To consolidate existing evidence for rates of IC decline and risk factors among community-dwelling adults 60 years or older. METHODS: According to the PRISMA guidelines, the literature search was independently conducted by two researchers in 8 databases from inception to January 2024 without language restrictions using combinations of free words and subject words. Qualities of included studies were assessed using Joanna Briggs Institute's (JBI's) critical appraisal checklist for prevalence studies. To pool the data, a random-effect meta-analysis was performed, followed by subgroup analysis and sensitivity analysis. All analyses were performed by Stata14.0. RESULTS: From 1594 records, 15 studies were extracted with 33,070 participants for meta-analysis. The pooled prevalence of IC decline in community settings was 67.8% (95% CI: 57.0-78.5%; P < 0.001). The prevalence of IC decline in China (66.0%; 95% CI: 53.2-78.9%) was found to be slightly lower than in other countries/regions (73.0%; 95% CI: 59.8-86.3%); however, this difference was not statistically significant. Other subgroup analyses revealed no statistically significant differences in prevalence. Age, hypertension, diabetes, gender, education level, living status, smoking, regular exercise, marital status, and osteoarthritis are associated with IC decline. CONCLUSION: More than two-thirds of older adults in the community are affected by IC decline, and age, hypertension, diabetes, female sex, low education level, living alone, smoking, irregular exercise, unmarried, and osteoarthritis are all risk factors for IC decline.

Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

The Global Research Trends on Intrinsic Capacity of Older Adults: A Bibliometric and Visual Analysis of Papers Published During 2015-2023.

Objective: The concept of intrinsic capacity (IC) revolves around healthy aging and active aging. Since the Introduction of the concept by the World Health Organization in 2015, a series of studies have been conducted by scholars from multiple fields. However, no bibliometric analysis has systematically investigated this issue. We aim to identify the current landscape and frontier trends of scientific achievements on IC in older adults through bibliometric approaches. Methods: Quantitative analysis of publications relating to IC in older adults from 2015 to 2023 was interpreted and graphed through the Web of Science Core Collection database on December 5, 2023. A variety of quantitative variables was analyzed, including publication and citation counts, H-index, and journal citation reports. Co-authorship, citation, co-citation, and co-occurrence analyses were performed for countries/regions, institutions, authors, and keywords using the VOSviewer and CiteSpace. Results: A total of 952 original and review articles in English were identified. The European countries possessed an absolute advantage in this field. The most contributive institution was the University of São Paulo. The most productive author is Cesari Matteo from France, followed by Qaisar Rizwan from the United Arab Emirates. However, a relatively low level of research cooperation existed between institutions and authors. Important topics mainly include the connotations, theoretical framework models, evaluation, screening tools, and application scenarios of IC. Among the promising hotspots, "biological aging", "ICOPE", "Covid-19", "prevention", "inflammation", "caf22", "prevalence", and "randomized controlled trial" displayed relatively latest average appearing year. Conclusion: Global trends indicate a growing scientific output on IC in older adults, and developed countries are leading the way. There is still room for improvement in research team collaboration. The focus gradually shifts from theoretical research to empirical research. It is recommended to pay attention to the latest hot spots, such as "biological aging", "ICOPE implementation", "post-COVID-19 syndrome", and "biomarkers".

Plant-derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold.

Plant-derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti-inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural regeneration promotion, inflammation inhibition, and innovation and application of regenerative scaffolds. Unfortunately, the utilization of PE in SCI therapy remains unexplored. Herein, we isolated PE from the traditional Chinese medicinal herb, Lycium barbarum L. and discovered their inflammatory inhibition and neuronal differentiation promotion capabilities. Compared with exosomes derived from ectomesenchymal stem cells (EMSCs), PE demonstrated a substantial enhancement in neural differentiation. We encapsulated isoliquiritigenin (ISL)-loaded plant-derived exosomes (ISL@PE) from L. barbarum L. within a 3D-printed bionic scaffold. The intricate construct modulated the inflammatory response following SCI, facilitating the restoration of damaged axons and culminating in ameliorated neurological function. This pioneering investigation proposes a novel potential route for insoluble drug delivery via plant exosomes, as well as SCI repair. The institutional animal care and use committee number is UJS-IACUC-2020121602.

Neuropsychological and psychiatric outcomes among community-dwelling young Chinese older adults affected by falls in the past year with and without vision impairment.

OBJECTIVE: This study was to investigate the differences between young older adults with and without vision impairment on neuropsychological and psychiatric outcomes following falls during the past year and to identify predictors of cognitive decline or mental distress. METHODS: A secondary analysis of 668 young older Chinese adults aged 65 ∼ 79 years old with a history of falls was conducted from the cross-sectional survey data in the 2018 wave of the Chinese Longitudinal Health Longevity Survey (CLHLS). RESULTS: Participants with vision impairment scored significantly higher on anxiety and depression and lower on cognitive function and SWB than those without vision impairment. And vision impairment was a significant predictor of adverse outcomes for all four neuropsychological and psychiatric measures. CONCLUSION: Neurocognitive deficits, psychological problems, and decreased self-sufficiency are quite common among community-dwelling older adults with visual impairment who have a history of falls within a year.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

Effects of nanoplastic exposure routes on leaf decomposition in streams.

Polystyrene nanoparticles (PS NPs) released from plastic products have been demonstrated to pose a threat to leaf litter decomposition in streams. Given the multitrophic systems of species interactions, the effects of PS NPs through different exposure routes on ecosystem functioning remain unclear. Especially dietary exposure, a frequently overlooked pathway leading to toxicity, deserves more attention. A microcosm experiment was conducted in this study to assess the effects of waterborne and dietary exposure to PS NPs on the litter-based food chain involving leaves, microbial decomposers, and detritivores (river snails). Compared to waterborne contamination, dietary contamination resulted in lower microbial enzyme activities and a significantly higher decrease in the lipid content of leaves. For river snails, their antioxidant activity was significantly increased by 20.21%-69.93%, and their leaf consumption rate was significantly reduced by 16.60% through the dietary route due to the lower lipid content of leaves. Besides, the significantly decreased nutritional quality of river snails would negatively influence their palatability to predators. The findings of this study indicate that dietary exposure to PS NPs significantly impacts microbial and detritivore activities, thus affecting their functions in the detritus food chain as well as nutrient cycling.

Effect of ph on migration patterns and degradation pathways of sulfamethazine in soil systems.

Sulfonamide antibiotics (SAs) are widely used antimicrobial agents in livestock and aquaculture, and most of them entering the animal's body will be released into the environment as prodrugs or metabolites, which ultimately affect human health through the food chain. Both acid deposition and salinization of soil may have an impact on the migration and degradation of antibiotics. Sulfamethazine (SM2), a frequently detected compound in agricultural soils, has a migration and transformation process in the environment that is closely dependent on environmental pH. Nevertheless, scarcely any studies have been conducted on the effect of soil pH changes on the environmental behavior of sulfamethazine. We analyzed the migration and degradation mechanisms of SM2 using simulation experiments and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) techniques. The results showed that acidic conditions limited the vertical migration of sulfadimidine, and SM2 underwent different reaction processes under different pH conditions, including S-C bond breaking, S-N bond hydrolysis, demethylation, six-membered heterocyclic addition, methyl hydroxylation and ring opening. The study of the migration pattern and degradation mechanism of SM2 under different pH conditions can provide a solid theoretical basis for assessing the pollution risk of sulfamethazine degradation products under acid rain and saline conditions, and provide a guideline for remediation of antibiotic contamination, so as to better prevent, control and protect groundwater resources.

Chitosan alleviates symptoms of Parkinson's disease by reducing acetate levels, which decreases inflammation and promotes repair of the intestinal barrier and blood-brain barrier.

ABSTRACT: Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically short-chain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood-brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood-brain barriers, thereby alleviating symptoms of Parkinson's disease.

Response of a simulated aquatic fungal community to nanoplastics exposure and functional consequence on leaf decomposition.

Nanoplastics pose a potential threat to a wide variety of aquatic organisms. Despite the awareness of this existing hazard, the impact of nanoplastics on natural fungal communities remains a research gap. In this study, five dominant fungi species, isolated from a stream ecosystem, were used to explore the effects of different nano-polystyrene (nano-PS) particles concentrations on a simulated fungal community. Specifically, the evaluation was conducted regarding the fungal growth, reproductivity, structural composition, and ecological function in leaf litter decomposition. A 15-day exposure experiment showed that 100 µg/L nano-PS significantly reduced the microcosm pH. The extracellular enzyme activities of ß-glucosidase, leucine-aminopeptidase, and peroxidase were significantly promoted by nano-PS exposure for 5 days or 15 days. Total sporulation rate significantly decreased after the 15-day exposure to 1 and 100 µg/L nano-PS and significantly increased under 10 µg/L nano-PS. In contrast, nano-PS concentrations had no effects on fungal biomass. In addition, the reduced relative abundance of Geotrichum candidum lowered its contribution to leaf decomposition, resulting in a decreased litter decomposition rate of a 24.5-27.9 % after exposure. This suggests that 1-100 µg/L nano-PS inhibited leaf decomposition by inhibiting fungal reproduction and reducing the contribution of specific fungal species. In addition, the findings highlight the importance of exploring the potential mechanisms of the interaction between nanoplastics and fungal species.

Screening Antioxidant Components in Different Parts of Dandelion Using Online Gradient Pressure Liquid Extraction Coupled with High-Performance Liquid Chromatography Antioxidant Analysis System and Molecular Simulations.

Utilizing online gradient pressure liquid extraction (OGPLE) coupled with a high-performance liquid chromatography antioxidant analysis system, we examined the antioxidative active components present in both the aerial parts and roots of dandelion. By optimizing the chromatographic conditions, we identified the ferric reducing-antioxidant power system as the most suitable for online antioxidant reactions in dandelion. Compared to offline ultrasonic extraction, the OGPLE method demonstrated superior efficiency in extracting chemical components with varying polarities from the samples. Liquid chromatography-mass spectrometry revealed twelve compounds within the dandelion samples, with nine demonstrating considerable antioxidant efficacy. Of these, the aerial parts and roots of dandelion contained nine and four antioxidant constituents, respectively. Additionally, molecular docking studies were carried out to investigate the interaction between these nine antioxidants and four proteins associated with oxidative stress (glutathione peroxidase, inducible nitric oxide synthase, superoxide dismutase, and xanthine oxidase). The nine antioxidant compounds displayed notable binding affinities below -5.0 kcal/mol with the selected proteins, suggesting potential receptor-ligand interactions. These findings contribute to enhancing our understanding of dandelion and provide a comprehensive methodology for screening the natural antioxidant components from herbs.

Biopolymer Materials in Triboelectric Nanogenerators: A Review.

In advancing the transition of the energy sector toward heightened sustainability and environmental friendliness, biopolymers have emerged as key elements in the construction of triboelectric nanogenerators (TENGs) due to their renewable sources and excellent biodegradability. The development of these TENG devices is of significant importance to the next generation of renewable and sustainable energy technologies based on carbon-neutral materials. This paper introduces the working principles, material sources, and wide-ranging applications of biopolymer-based triboelectric nanogenerators (BP-TENGs). It focuses on the various categories of biopolymers, ranging from natural sources to microbial and chemical synthesis, showcasing their significant potential in enhancing TENG performance and expanding their application scope, while emphasizing their notable advantages in biocompatibility and environmental sustainability. To gain deeper insights into future trends, we discuss the practical applications of BP-TENG in different fields, categorizing them into energy harvesting, healthcare, and environmental monitoring. Finally, the paper reveals the shortcomings, challenges, and possible solutions of BP-TENG, aiming to promote the advancement and application of biopolymer-based TENG technology. We hope this review will inspire the further development of BP-TENG towards more efficient energy conversion and broader applications.

Magnetic Material in Triboelectric Nanogenerators: A Review.

Nowadays, magnetic materials are also drawing considerable attention in the development of innovative energy converters such as triboelectric nanogenerators (TENGs), where the introduction of magnetic materials at the triboelectric interface not only significantly enhances the energy harvesting efficiency but also promotes TENG entry into the era of intelligence and multifunction. In this review, we begin from the basic operating principle of TENGs and then summarize the recent progress in applications of magnetic materials in the design of TENG magnetic materials by categorizing them into soft ferrites and amorphous and nanocrystalline alloys. While highlighting key role of magnetic materials in and future opportunities for improving their performance in energy conversion, we also discuss the most promising choices available today and describe emerging approaches to create even better magnetic TENGs and TENG-based sensors as far as intelligence and multifunctionality are concerned. In addition, the paper also discusses the integration of magnetic TENGs as a power source for third-party sensors and briefly explains the self-powered applications in a wide range of related fields. Finally, the paper discusses the challenges and prospects of magnetic TENGs.

Association of barium deficiency with Type 2 diabetes mellitus incident risk was mediated by mitochondrial DNA copy number (mtDNA-CN): a follow-up study.

Accumulating evidence indicates that plasma metal levels may be associated with Type 2 diabetes mellitus (T2DM) incident risk. Mitochondrial function such as mitochondrial DNA copy number (mtDNA-CN) might be linked to metal exposure and physiological metabolism. Mediation analysis was conducted to determine the mediating roles of mtDNA-CN in the association between plasma metals and diabetes risk. In the present study, we investigated associations between plasma metals levels, mtDNA-CN, and T2DM incident in the elderly population with a 6-year follow-up (two times) study. Ten plasma metals [i.e. manganese, aluminum, calcium, iron, barium (Ba), arsenic, copper, selenium, titanium, and strontium] were measured using inductively coupled plasma mass spectrometry. mtDNA-CN was measured by real-time polymerase chain reaction. Multivariable linear regression and logistic regression analyses were carried out to estimate the relationship between plasma metal concentrations, mtDNA-CN, and T2DM incident risk in the current work. Plasma Ba deficiency and mtDNA-CN decline were associated with T2DM incident risk during the aging process. Meanwhile, plasma Ba was found to be positively associated with mtDNA-CN. Mitochondrial function mtDNA-CN demonstrated mediating effects in the association between plasma Ba deficiency and T2DM incident risk, and 49.8% of the association was mediated by mtDNA-CN. These findings extend the knowledge of T2DM incident risk factors and highlight the point that mtDNA-CN may be linked to plasma metal elements and T2DM incident risk.

A Human Friendly Self-Assembled Triboelectric Sensor for Multifunctional Tactile Sensing.

Obtaining bioenergy from human movement is not only a prospective complementation to electrochemical power supply such as batteries in portable electronics but also a decipherable process for developing self-powered sensors that can simultaneously monitor the physiological movement. In this study, a low-cost, robust, and environmentally friendly triboelectric nanogenerator (TENG) was prepared with enhanced mechanical stability and tunneling conductivity on the base of cotton fabric. The as-designed TENG may produce energy sustainably by physical movements, and it can yield an amazing 417 V open-circuit voltage, 11.7 µA short-circuit current, and 237.60 mW/m2 excellent power density, showcasing its potential for efficient energy conversion in the single-electrode mode. Besides, such a design also shows real-time tactile perception ability toward human physiological signal and body motion where intelligent application of these environmental benign TENGs in sports and writing training were demonstrated, thus providing vital instruction for the creation of versatile and sustainable TENGs in the Internet of Things era.

Multi-metabolomics and intestine microbiome analysis: YZC extract ameliorates septic-ALI by modulating intestine microbiota to reduce TMAO/NLRP3 signaling.

BACKGROUND: Sepsis causes inflammation in response to infection, often leading to acute lung injury (ALI). Yazhicao (Commelina communis L., YZC) is widely distributed in the global tropics and has good anti-respiratory inflammatory activity; however, the protection of YZC against septic-ALI has not been established. PURPOSE: The role of YZC in septic-ALI will be investigated in this study. METHODS AND RESULTS: In this study, YZC was shown to inhibit excessive inflammation and alleviate septic-ALI. Network pharmacology predicts that Quercetin, Acacetin and Diosmetin have the potential to serve as the pharmacological substance basis of YZC in alleviating septic-ALI. The metabolomics results indicated that YZC could improve the metabolic disorders caused by septic-ALI, which were mostly concerned with energy metabolism and amino acid metabolism, with Trimethylamine (TMA)/Trimethylamine N-oxide (TMAO) being potential small molecule metabolic markers for the clinical diagnosis and treatment of septic-ALI. YZC inhibits the initiation and progression of septic-ALI by controlling the TMA/TMAO metabolites. Our results also suggest that YZC protects the intestinal barrier from damage. Furthermore, our research indicated that YZC reduces TMAO synthesis by inhibiting TMA production through remodeling the intestine microbiota. We investigated the mechanism of YZC-mediated protection against septic-ALI and showed that YZC reduced the expression of proteins associated with NLRP3 inflammatory vesicles in the lung by inhibiting the expression of NF-κB. CONCLUSION: These results show that YZC inhibits the NF-κB/NLRP3 signaling pathway by regulating metabolic and intestinal flora disorders in septic-ALI mice to reduce TMAO synthesis. This study presents a theoretical groundwork for the advancement of novel medications and clinical use of YZC to enhance septic-ALI and furnishes a theoretical rationale for regulating intestinal microbiota as a therapeutic instrument to treat sepsis and septic-ALI.

Pharmacokinetic/Pharmacodynamic Assessment of the Structural Refinement of Clopidogrel Focusing on the Balance between Bioactivation and Deactivation.

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel. Our approaches were grounded in the molecular framework of clopidogrel and incorporated the C2-pharmacophore design from prasugrel. The selection of ester or carbamate substituents at the C2-position facilitated the generation of the 2-oxointermediate through hydrolysis, akin to prasugrel, thereby bypassing the issue of CYP2C19 dependency. The bulky C2-pharmacophore in our approach distinguishes itself from prasugrel's acetyloxy substituent by exhibiting a moderated hydrolysis rate, resulting in a more gradual formation of the active metabolite. Excessive and rapid release of the active metabolite, believed to be linked with an elevated risk of bleeding, is thus mitigated. Our proposed structural modification retains the hydrolysis-sensitive methyl ester of clopidogrel but substitutes it with a deuterated methyl group, shown to effectively reduce metabolic deactivation. Three promising compounds demonstrated a pharmacokinetic profile similar to that of clopidogrel at four times the dose, while also augmenting its antiplatelet activity. SIGNIFICANCE STATEMENT: Inspired by the structure-pharmacokinetic relationship of clopidogrel and prasugrel, a range of clopidogrel derivatives were designed, synthesized, and assessed. Among them, three promising compounds have been identified, striking a delicate balance between efficacy and safety for antiplatelet therapy. Additionally, the ozagrel prodrug conjugate was discovered to exert a synergistic therapeutic effect alongside clopidogrel.

Effects of root-applied biochar on soil nitrogen transformation and root nitrogen metabolism of cucumber seedlings in facility continuous cropping soils.

The problem of soil barrier caused by excessive accumulation of nitrogen is common in continuous cropping soil of facility agriculture. To investigate the modulating effects of biochar amendment on soil nitrogen transformation in greenhouse continuous cropping systems, we conducted a pot experiment with two treatments, no biochar addition (CK) and 5% biochar addition (mass ratio). We analyzed the effects of biochar addition on soil microbial community structure, abundances of genes functioning in nitrogen cycling, root growth and nitrogen metabolism-related genes expressions of cucumber seedlings. The results showed that biochar addition significantly increased plant height, root dry mass, total root length, root surface area, and root volume of cucumber seedlings. Rhizosphere environment was improved, which enhanced root nitrogen absorption by inducing the up-regulation of genes expressions related to plant nitrogen metabolism. Biochar addition significantly increased soil microbial biomass nitrogen, nitrate nitrogen, and nitrite nitrogen contents. The abundances of bacteria that involved in nitrogen metabolism, including Proteobacteria, Cyanobacteria, and Rhizobiales (soil nitrogen-fixing bacteria), were also significantly improved in the soil. The abundances of genes functioning in soil nitrification and nitrogen assimilation reduction, and the activities of enzymes involved in nitrogen metabolisms such as hydroxylamine dehydrogenase, nitronate monooxygenase, carbonic anhydrase were increased. In summary, biochar addition improved soil physicochemical properties and microbial community, and affected soil nitrogen cycling through promoting nitrification and nitrogen assimilation. Finally, nitrogen adsorption capacity and growth of cucumber plant was increased.