Assessment of progression of pulmonary fibrosis based on metabonomics and analysis of intestinal microbiota.

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1ß, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

In this study, metabolomics technology and intestinal microbiota 16S rRNA gene sequencing were used to search for biomarkers with significant differences in each stage of pulmonary fibrosis. Finally, the variation characteristics of each stage of the disease were discussed. The hope is to provide new insights into the development of diagnostic biomarkers and potential therapeutic targets at all stages.

Organophosphate Esters in Building Materials from China: Levels, Sources, Emissions, and Preliminary Assessment of Human Exposure.

Source characteristics and health risks of indoor organophosphate esters (OPEs) are limited by the lack of knowledge on emission processes. This study attempted to integrate the contents and emissions of OPEs from indoor building materials to assess human health effects. Thirteen OPEs were investigated in 80 pieces of six categories of building materials. OPEs are ubiquitous in the building materials and ∑13OPE contents varied significantly (p < 0.05) from 72.8 ng/g (seam agent) to 109,900 ng/g (wallpaper). Emission characteristics of OPEs from the building materials were examined based on a microchamber method. Depending on the sample category, the observed initial area-specific emission rates of ∑13OPEs varied from 154 ng/m2/h (carpet) to 2760 ng/m2/h (wooden floorboard). Moreover, the emission rate model was developed to predict the release levels of individual OPEs, quantify source contributions, and assess associated exposure risks. Source apportionments of indoor OPEs exhibited heterogeneities in multiple environmental media. The joint OPE contribution of wallpaper and wooden floorboard to indoor dust was up to 94.8%, while latex paint and wooden floorboard were the main OPE contributors to indoor air (54.2%) and surface (76.1%), respectively. Risk assessment showed that the carcinogenic risks of tris(2-chloroethyl) phosphate (3.35 × 10-7) were close to the acceptable level (1 × 10-6) and deserved special attention.

Epidemiological analysis reveals a surge in inflammatory bowel disease among children and adolescents: A global, regional, and national perspective from 1990 to 2019 - insights from the China study.

Background: The burden of inflammatory bowel disease (IBD) among children and adolescents is rising globally, with substantial variation in levels and trends of disease in different countries and regions, while data on the burden and trends were sparse in children and adolescents. We aimed to assess the trends and geographical differences in children and adolescents aged zero to 19 in 204 countries and territories over the past 30 years. Methods: Data on IBD among children and adolescents was collected from the Global Burden of Disease (GBD) 2019 database from 1990 to 2019. We used the GBD data and methodologies to describe the change in the burden of IBD among children and adolescents involving prevalence, incidence, disability-adjusted life years (DALYs), and mortality. Results: Globally, the IBD prevalence cases increased between 1990 and 2019. Annual percentage changes (AAPC) = 0.15; 95% confidence interval (CI) = 0.11-0.19, and incidence cases of IBD increased from 20 897.4 (95% CI = 17 008.6-25 520.2 in 1990 to 25 658.6 (95% CI = 21 268.5-31 075.6) in 2019, representing a 22.78% increase, DALYs cases decreased between 1990 and 2019 (AAPC = -3.02; 95% CI = -3.15 to -2.89), and mortality cases of IBD decreased from 2756.5 (95% CI = 1162.6-4484.9) in 1990 to 1208.0 (95% CI = 802.4-1651.4) in 2019, representing a 56.17% decrease. Decomposition analysis showed that IBD prevalence and incidence increased significantly, and a trend exhibited a decrease in underlying age and population-adjusted IBD DALYs and mortality rates. Correlation analysis showed that countries with high health care quality and access (HAQ) had relatively higher IBD age-standardised prevalence rate (ASPR) and age-standardised incidence rate (ASIR), but lower age-standardised DALYs rate (ASDR) and age-standardised mortality rate (ASMR). Conclusions: Global prevalence and incidence rate of IBD among children and adolescents have been increasing from 1990 to 2019, while the DALYs and mortality have been decreasing. Rising prevalence and rising incidence in areas with historically low rates will have crucial health and economic implications.

Comparative Transcriptomic Assessment of Chemosensory Genes in Adult and Larval Olfactory Organs of Cnaphalocrocis medinalis.

The rice leaf folder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), is a notorious pest of rice in Asia. The larvae and adults of C. medinalis utilize specialized chemosensory systems to adapt to different environmental odors and physiological behaviors. However, the differences in chemosensory genes between the olfactory organs of these two different developmental stages remain unclear. Here, we conducted a transcriptome analysis of larvae heads, male antennae, and female antennae in C. medinalis and identified 131 putative chemosensory genes, including 32 OBPs (8 novel OBPs), 23 CSPs (2 novel CSPs), 55 ORs (17 novel ORs), 19 IRs (5 novel IRs) and 2 SNMPs. Comparisons between larvae and adults of C. medinalis by transcriptome and RT-qPCR analysis revealed that the number and expression of chemosensory genes in larval heads were less than that of adult antennae. Only 17 chemosensory genes (7 OBPs and 10 CSPs) were specifically or preferentially expressed in the larval heads, while a total of 101 chemosensory genes (21 OBPs, 9 CSPs, 51 ORs, 18 IRs, and 2 SNMPs) were specifically or preferentially expressed in adult antennae. Our study found differences in chemosensory gene expression between larvae and adults, suggesting their specialized functions at different developmental stages of C. medinalis. These results provide a theoretical basis for screening chemosensory genes as potential molecular targets and developing novel management strategies to control C. medinalis.

Discovery of Transfer Factors in Plant-Derived Proteins and an In Vitro Assessment of Their Immunological Activities.

Repeated exposure to pathogens leads to evolutionary selection of adaptive traits. Many species transfer immunological memory to their offspring to counteract future immune challenges. Transfer factors such as those found in the colostrum are among the many mechanisms where transfer of immunologic memory from one generation to the next can be achieved for an enhanced immune response. Here, a library of 100 plants with high protein contents was screened to find plant-based proteins that behave like a transfer factor moiety to boost human immunity. Aqueous extracts from candidate plants were tested in a human peripheral blood mononuclear cell (PBMC) cytotoxicity assay using human cancerous lymphoblast cells-with K562 cells as a target and natural killer cells as an effector. Plant extracts that caused PBMCs to exhibit enhanced killing beyond the capability of the colostrum-based transfer factor were considered hits. Primary screening yielded an 11% hit rate. The protein contents of these hits were tested via a Bradford assay and Coomassie-stained SDS-PAGE, where three extracts were confirmed to have high protein contents. Plants with high protein contents underwent C18 column fractionation using methanol gradients followed by membrane ultrafiltration to isolate protein fractions with molecular weights of <3 kDa, 3-30 kDa, and >30 kDa. It was found that the 3-30 kDa and >30 kDa fractions had high activity in the PBMC cytotoxicity assay. The 3-30 kDa ultrafiltrates from the top two hits, seeds from Raphanus sativus and Brassica juncea, were then selected for protein identification by mass spectrometry. The majority of the proteins in the fractions were found to be seed storage proteins, with a low abundance of proteins involved in plant defense and stress response. These findings suggest that Raphanus sativus or Brassica juncea extracts could be considered for further characterization and immune functional exploration with a possibility of supplemental use to bolster recipients' immune response.

Ecological vulnerability of China's Yellow River Basin: evaluation and socioeconomic driving factors.

The Yellow River Basin (YRB) is a typical ecologically fragile area in both the Chinese and global contexts. This paper built a sensitivity-resilience-pressure model to evaluate the ecological vulnerability (EV) of the YRB at the grid and prefecture-level regional scales; explored the spatiotemporal characteristics of EV; and scrutinized the impacts of socioeconomic driving factors on EV. The results showed that (1) at the grid and prefecture-level regional scales, EV decreased from the upper to lower reaches, and high vulnerability was observed in the provincial capital city. Mild and severe vulnerability constituted the main EV types in the YRB. (2) The EV index of the YRB decreased from 2.71 to 2.56 in the study period, indicating that the ecological environment improved in the YRB. The slightly and lightly vulnerable areas experienced shrinking-expansion changes, and the overall areas of these two EV types showed expanding trends, while the areal changes and overall trends of the moderately, severely, and extremely vulnerable areas were contrary to those of the slightly and lightly vulnerable areas. (3) The impacts of socioeconomic driving factors on EV dynamically strengthened with the improvement of the socioeconomic level. After considering the interactions of all socioeconomic factors, the explanatory power of the spatial differentiation of EV was enhanced, and the influence of these factors became more prominent.

[Spatio-temporal Variations in PM2.5and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration].

To coordinate the contradiction between economic development and environmental pollution and achieve the sustainable development of the economy and society, the spatio-temporal variations in PM2.5 were analyzed based on PM2.5 concentration and meteorological data of the Yangtze River Delta (YRD) urban agglomeration. Wavelet transform coherence (WTC), partial wavelet coherence (PWC), and multiple wavelet coherence (MWC) were used to analyze the multi-scale coupling oscillation between PM2.5 and meteorological factors in the time-frequency domain. The results showed that:① the concentration of PM2.5 in the YRD decreased from northwest to southeast, and the spatial range with high PM2.5 concentration decreased annually. The spatial distribution characteristics of the seasonal average PM2.5 concentration were similar to those of the annual average PM2.5 concentration. PM2.5 concentration exhibited the seasonal variation characteristics of high in winter, low in summer, and transitioning between spring and autumn. ② PM2.5 concentration decreased from 2015 to 2021, and the compliance rate increased. The difference in annual average PM2.5 concentration was decreased with dynamic convergence characteristics. The convergence of PM2.5 concentration in summer was greater than that in winter. During the whole study period, the daily average PM2.5 concentration showed a "U" distribution, and the proportion of days with excellent and good PM2.5 levels were 49.72% and 41.45%, respectively. ③ The wavelet coherence between PM2.5 and meteorological factors was different in different time-frequency domains. The main factors affecting PM2.5 were different in different time-frequency scales. At all time-frequency scales, WTC and PWC showed that wind speed and temperature were the best explanatory variables of PM2.5 variation, respectively. ④ The larger the time-frequency scale, the stronger the interaction of multi-factor combinations to explain PM2.5 variations. The synergistic effect of temperature and wind speed could better explain the variation in PM2.5. These results can provide reference for air pollution control in the YRD.

High-performance cost efficient simultaneous wireless information and power transfers deploying jointly modulated amplifying programmable metasurface.

Programmable metasurfaces present significant capabilities in manipulating electromagnetic waves, making them a promising candidate for simultaneous wireless information and power transfer (SWIPT), which has the potential to enable sustainable wireless communication in complex electromagnetic environments. However, challenges remain in terms of maximum power transmission distance and stable phase manipulation with high-power scattered waves. Additionally, waveform limitations restrict average scattered power and rectifier conversion efficiency, affecting data transmission rates and energy transmission distance. Here we show an amplifying programmable metasurface (APM) and a joint modulation method to address these challenges. The APM mitigates the peak-to-average power ratio and improves maximum power, phase response stability, average output power, and rectifier conversion efficiency. Through experimental validation, we demonstrate the feasibility of the SWIPT system, showcasing simultaneous LED array powering and movie video transmission. This innovative SWIPT system holds promise for diverse applications, including 6 G wireless communications, IoT, implanted devices, and cognitive radio networks.

Assessment of Resident and AI Chatbot Performance on the University of Toronto Family Medicine Residency Progress Test: Comparative Study.

BACKGROUND: Large language model (LLM)-based chatbots are evolving at an unprecedented pace with the release of ChatGPT, specifically GPT-3.5, and its successor, GPT-4. Their capabilities in general-purpose tasks and language generation have advanced to the point of performing excellently on various educational examination benchmarks, including medical knowledge tests. Comparing the performance of these 2 LLM models to that of Family Medicine residents on a multiple-choice medical knowledge test can provide insights into their potential as medical education tools. OBJECTIVE: This study aimed to quantitatively and qualitatively compare the performance of GPT-3.5, GPT-4, and Family Medicine residents in a multiple-choice medical knowledge test appropriate for the level of a Family Medicine resident. METHODS: An official University of Toronto Department of Family and Community Medicine Progress Test consisting of multiple-choice questions was inputted into GPT-3.5 and GPT-4. The artificial intelligence chatbot's responses were manually reviewed to determine the selected answer, response length, response time, provision of a rationale for the outputted response, and the root cause of all incorrect responses (classified into arithmetic, logical, and information errors). The performance of the artificial intelligence chatbots were compared against a cohort of Family Medicine residents who concurrently attempted the test. RESULTS: GPT-4 performed significantly better compared to GPT-3.5 (difference 25.0%, 95% CI 16.3%-32.8%; McNemar test: P<.001); it correctly answered 89/108 (82.4%) questions, while GPT-3.5 answered 62/108 (57.4%) questions correctly. Further, GPT-4 scored higher across all 11 categories of Family Medicine knowledge. In 86.1% (n=93) of the responses, GPT-4 provided a rationale for why other multiple-choice options were not chosen compared to the 16.7% (n=18) achieved by GPT-3.5. Qualitatively, for both GPT-3.5 and GPT-4 responses, logical errors were the most common, while arithmetic errors were the least common. The average performance of Family Medicine residents was 56.9% (95% CI 56.2%-57.6%). The performance of GPT-3.5 was similar to that of the average Family Medicine resident (P=.16), while the performance of GPT-4 exceeded that of the top-performing Family Medicine resident (P<.001). CONCLUSIONS: GPT-4 significantly outperforms both GPT-3.5 and Family Medicine residents on a multiple-choice medical knowledge test designed for Family Medicine residents. GPT-4 provides a logical rationale for its response choice, ruling out other answer choices efficiently and with concise justification. Its high degree of accuracy and advanced reasoning capabilities facilitate its potential applications in medical education, including the creation of exam questions and scenarios as well as serving as a resource for medical knowledge or information on community services.

Low-cost Prussian blue analogues for sodium-ion batteries and other metal-ion batteries.

As a class of promising cathodes in the field of large-scale power storage systems especially for alkali-metal-ion batteries (MIBs), Prussian blue (PB) and its analogues (PBAs) have received wide research attention due to their open framework, high theoretical specific capacity, and simple synthesis method. For large-scale applications, cathode materials with low-cost and long cycle life are preferred. However, only a few of the review papers have concentrated on the detailed analysis of low-cost PBAs, including Fe-based and Mn-based PBAs, which also show excellent electrochemical performance. This review aims to first provide an all-sided understanding of low-cost PBAs in terms of their application and recent progress in MIBs. Then, the major challenges such as inferior electrochemical properties of low-cost PBAs are discussed. Meanwhile, we provide feasible strategies to prepare PBA electrodes with advanced electrochemical performance. Finally, we present some personal perspectives and guidance for future research, aiming to narrow the gap between laboratory investigation and practical application.

Impact of Diagnosis-Related Groups on Inpatient Quality of Health Care: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to comprehensively evaluate the effectiveness of Diagnosis-related group (DRG) based payment on inpatient quality of care. A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science from their inception to December 30, 2022. Included studies reported associations between DRGs-based payment and length of stay (LOS), re-admission within 30 days and mortality. Two reviewers screened the studies independently, extracted data of interest and assessed the risk of bias of eligible studies. Stata 13.0 was used in the meta-analysis. A total of 29 studies with 36 214 219 enrolled patients were analyzed. Meta-analysis showed that DRG-based payment was effective in LOS decrease (pooled effect: SMD = -0.25, 95% CI = -0.37 to -0.12, Z = 3.81, P < .001), but showed no significant overall effect in re-admission within 30 days (RR = 0.79, 95% CI = 0.62-1.01, Z = 1.89, P = .058) and mortality (RR = 0.91, 95% CI = 0.72-1.15, Z = 0.82, P = .411). DRG-based payment demonstrated statistically significant superiority over cost-based payment in terms of LOS reduction. However, owing to limitations in the quantity and quality of the included studies, an adequately powered study is necessary to consolidate these findings.

[Contamination and Probabilistic Health Risk Assessment of Heavy Metals in Agricultural Soils Around a Lead-Zinc Smelter].

In order to identify the contamination and health risks of heavy metals in agricultural soils, a total of 56 surface soil samples (0-20 cm) were collected around a Pb-Zn smelter in Yunnan Province, and six heavy metals (Pb, Cd, Zn, As, Cu, and Hg) and pH were analyzed to assess heavy metal status, ecological risk, and probabilistic health risk. The results revealed that the average contents of six heavy metals (Pb:4413.93 mg·kg-1, Cd:6.89 mg·kg-1, Zn:1672.76 mg·kg-1, As:44.45 mg·kg-1, Cu:47.61 mg·kg-1, and Hg:0.21 mg·kg-1) were higher than their background values in Yunnan Province. Cd had the highest mean geo-accumulation index (Igeo) of 0.24, the highest mean pollution index (Pi) of 30.42, and the greatest average ecological risk index (Er) of 1312.60, indicating that Cd was the primary enriched and highest-ecological risk pollutant. The mean hazard index (HI) through exposure to six HMs was 2.42E-01 and 9.36E-01 for adults and children, respectively, with 36.63% of HI values for children exceeding the risk threshold of 1. Moreover, the mean total cancer risks (TCR) were 6.98E-05 and 5.93E-04 for adults and children, respectively, with 86.85% of TCR values for children exceeding the guideline value of 1E-04. The probabilistic health risk assessment suggested that Cd and As were the main contributors for the non-carcinogenic risks and carcinogenic risks. This work will provide scientific reference for the precise risk management and effective remediation strategy of soil heavy metal pollution in this study area.

How do inpatients' costs, length of stay, and quality of care vary across age groups after a new case-based payment reform in China? An interrupted time series analysis.

CONTEXT: A patient classification-based payment system called diagnosis-intervention packet (DIP) was piloted in a large city in southeast China in 2018. OBJECTIVE: This study evaluates the impact of DIP payment reform on total costs, out-of-pocket (OOP) payments, length of stay (LOS), and quality of care in hospitalised patients of different age. METHODS: An interrupted time series model was employed to examine the monthly trend changes of outcome variables before and after the DIP reform in adult patients, who were stratified into a younger (18-64 years) and an older group (≥ 65 years), further stratified into young-old (65-79 years) and oldest-old (≥ 80 years) groups. RESULTS: The adjusted monthly trend of costs per case significantly increased in the older adults (0.5%, P = 0.002) and oldest-old group (0.6%, P = 0.015). The adjusted monthly trend of average LOS decreased in the younger and young-old groups (monthly slope change: -0.058 days, P = 0.035; -0.025 days, P = 0.024, respectively), and increased in the oldest-old group (monthly slope change: 0.107 days, P = 0.030) significantly. The changes of adjusted monthly trends of in-hospital mortality rate were not significant in all age groups. CONCLUSION: Implementation of the DIP payment reform associated with increase in total costs per case in the older and oldest-old groups, and reduction in LOS in the younger and young-old groups without deteriorating quality of care.

[Comparison and health risk assessment of mineral elements in stems and leaves of Dendrobium officinale cultivated with conventional method and mycorrhizal fungi].

This study aims to analyze the variation of the content of mineral elements in stems and leaves of Dendrobium officinale cultivated with conventional method and mycorrhizal fungi, which is expected to lay a basis for safety of stems and leaves of D. officinale. A total of 7 samples from Jiangsu, Fujian, Shanghai, and Zhejiang were collected, which were then cultivated with conventional method and mycorrhizal fungi, separately. The content of 17 mineral elements in stems and leaves was measured by inductively coupled plasma-mass spectrometry(ICP-MS), and the content changes of the mineral elements were analyzed. The health risks of Pb, Cd, Hg, and As in stems were assessed by target hazard quotient(THQ). The results showed that the content of polluting elements in stems and leaves of D. officinale was low, and the content in the plants cultivated with mycorrhizal fungi was reduced. The content of K, Ca, Mg, and P was high in stems and leaves of the species, suggesting that cultivation with mycorrhizal fungi improved the content of other elements irregularly. According to the THQ, the safety risk of stems of D. officinale cultivated with either conventional method or mycorrhizal fungi was low, particularly the D. officinale cultivated mycorrhizal fungi. The results indicated that cultivation with mycorrhizal fungi influenced the element content in stems and leaves of D. officinale. It is necessary to study the culture substrate, processing technology, and the mechanism of the increase or decrease in mineral elements of D. officinale in the future.

Construction Land Expansion of Resource-Based Cities in China: Spatiotemporal Characteristics and Driving Factors.

Studying construction land expansion (CLE) characteristics and driving factors in resource-based cities (RBCs) is important to promote efficient land use and maintain ecological equilibrium in RBCs. This study explores the CLE and its driving factors in RBCs. The results indicated that (1) the CLE in RBCs became increasingly obvious, and the number of cities with expansion areas exceeding 20 km2 increased from 29 to 86. In RBCs in different regions, CLE in eastern, central, and western regions was obvious, while CLE in the northeast region decelerated. The order of CLE degree at different stages of RBCs was mature, growing, regenerative, and declining. (2) Single factors such as gross domestic product, fixed-asset investment, and secondary industry added value, playing a major role. This differs from the dominant role of population and urbanization in existing research. This occurred because population growth is slow, the urbanization rate is low, population contraction prominently occurs, and economic development exhibits notable path dependence in RBCs. (3) Interaction-factor detection demonstrated that the force of two-factor interaction was greater than that of a single factor, and the interactions of total population with fixed-asset investment and economic development level strongly drove CLE in RBCs.

[Ecological Risk Assessment of Microplastics Occurring in Surface Water of Terrestrial Water Systems across China].

To assess the ecological risk of microplastics (MPs) occurring in the surface water of terrestrial water systems across China, this study obtained relevant literature and data by searching keywords including microplastics, urban, and river on websites such as Science Direct and Web of Science. We constructed an evaluation method of ecological risk characterization ratio (RCR) based on chemical hazard data, as well as data of MPs abundance and polymer proportion originating in studies from 2017 to 2021 that covered 33 water bodies in 15 provinces. The results showed that the average abundance of MPs in natural water bodies in China reached (3604.2±5926.4) n·m-3, and the average abundance of MPs in urban water bodies was (7722.6±9505.7) n·m-3. The corresponding average RCR of natural water bodies was 22.09±45.2, and the average RCR of urban water bodies was 15.67±34.8. Therefore, according to the value of RCR, the ecological risk could be rated as four levels. Of these, no significant risk (RCR ≤ 1) was found in 17 water bodies, accounting for 42.5%; low ecological risks (RCR 1-10) were found in 12 water bodies (30%); medium ecological risks (RCR 10-100) were found in 9 water bodies (22.5%); and high ecological risks (RCR>100) were found in 2 water bodies (5%). Data analysis showed a significant correlation between MPs abundance and RCR values in natural water bodies (R2=0.875, P<0.01), though not in urban water bodies. This suggested that the high abundance of MPs could not precisely indicate a high degree of ecological risk in the area. In addition, RCR values were observed to be positively correlated with the watershed area (R2=0.864, P<0.01), and MPs abundance was correlated with GDP (R2=0.679, P<0.05) and watershed resident population (R2=0.922, P<0.05). This study provides baseline data for evaluating the ecological risk of MPs and a feasible method for evaluating the ecological risk of MPs in surface water of terrestrial water systems.

Polymeric Nanohybrids Engineered by Chitosan Nanoparticles and Antimicrobial Peptides as Novel Antimicrobials in Food Biopreservatives: Risk Assessment and Anti-Foodborne Pathogen Escherichia coli O157:H7 Infection by Immune Regulation.

Polymeric nanomaterials (APs) are gaining attention as promising clinical antimicrobials with rapidly increasing antibiotic resistance. Infections by zoonotic enterohemorrhagic Escherichia coli are a severe global threat to public health. Chitosan nanoparticles-microcin J25 (CNM), a class of APs engineered by bioactive peptides and chitosan nanoparticles, can be used as a novel antimicrobial agent against bacterial infections. However, the risk assessment of CNM on animal health or its potential immune modulation to treat serotype E. coli O157:H7 infection impacts in vivo are not well understood. Herein, our findings in mouse models uncovered that oral administration of low levels of CNM significantly increased the body weight and made beneficial effects on the lifespan or clinical signs, accompanied by a significant improvement in gut health, including enhancing the intestinal barrier, immune modulation, and changes in gut microbiota compositions or metabolites. However, high concentrations of CNM induced serious adverse effects, negatively improving intestinal health targets. Anti-infective results proved that oral 0.1% CNM enhances host defense against E. coli O157:H7 infection by improving immune functions and modulating the Th1/Th2 balance. In summary, these findings uncover an instrumental link between the dosage and toxicity risk, suggesting that APs need to be comprehensively assessed for risk before application as safe and reliable food preservatives or therapeutic agents. In addition, CNM as a promising AP may markedly enhance host immunity and therapeutic effects by oral administration.

A large geographic-scale characterization of organochlorine pesticides (OCPs) in surface sediments and multiple aquatic foods of inland freshwater aquaculture ponds in China: Co-occurrence, source and risk assessment.

Inland freshwater aquaculture ponds (IFAPs) represent the key component of the global lentic freshwater environment and are increasingly important for global aquaculture production, yet the occurrence of organochlorine pesticides (OCPs) in these pond systems remains largely unknown. Here, we characterized the residual concentrations of 19 individual OCPs in sediments and in cultured fish and crustacean species (crabs, shrimp, crayfish and lobster), which were on-spot sampled from the IFAPs at a large region-scale in China. The total OCP levels in sediments varied dramatically between regions. Crabs presented the greatest OCP contamination among the studied species. Dichlorodiphenyltrichloroethanes (DDTs) was the dominating contaminant in sediments and crabs and its stable degradation products 4,4'-DDE and 4,4'-DDD were co-occurrent between these two compartments. The diagnostic ratio analysis indicated fresh inputs of DDTs, lindane and aldrin in multiple regions, which may be resulted from agricultural soil erosion, surface runoff and local anthropogenic activities. Ecological impacts of these pesticides could be expected at some sites due to their levels in sediments above the risk level. Risk assessment based on the OCP levels corrected by the cooking loss revealed that daily consumption of the IFAPs-derived aquatic foods may pose carcinogenic risks in humans.

Ongoing Clinical Trials in Aging-Related Tissue Fibrosis and New Findings Related to AhR Pathways.

Fibrosis is a pathological manifestation of wound healing that replaces dead/damaged tissue with collagen-rich scar tissue to maintain homeostasis, and complications from fibrosis contribute to nearly half of all deaths in the industrialized world. Ageing is closely associated with a progressive decline in organ function, and the prevalence of tissue fibrosis dramatically increases with age. Despite the heavy clinical and economic burden of organ fibrosis as the population ages, to date, there is a paucity of therapeutic strategies that are specifically designed to slow fibrosis. Aryl hydrocarbon receptor (AhR) is an environment-sensing transcription factor that exacerbates aging phenotypes in different tissues that has been brought back into the spotlight again with economic development since AhR could interact with persistent organic pollutants derived from incomplete waste combustion. In addition, gut microbiota dysbiosis plays a pivotal role in the pathogenesis of numerous diseases, and microbiota-associated tryptophan metabolites are dedicated contributors to fibrogenesis by acting as AhR ligands. Therefore, a better understanding of the effects of tryptophan metabolites on fibrosis modulation through AhR may facilitate the exploitation of new therapeutic avenues for patients with organ fibrosis. In this review, we primarily focus on how tryptophan-derived metabolites are involved in renal fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis and cardiac fibrosis. Moreover, a series of ongoing clinical trials are highlighted.