Proteomic insights from extracellular vesicles into the molecular mechanisms of health effects induced by Per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFASs) can induce a range of adverse health effects, with the precise molecular mechanisms remaining elusive. Extracellular vesicles (EVs) have demonstrated their potential to elucidate unknown molecular mechanisms. Building upon the close alignment of their biological functions with the observed health effects of PFASs, this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs. Through rat exposure experiments and proteomics technology, it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs, leading to changes in related pathways. These changes encompass various biological processes, including proteasome activity, immune response, cytoskeletal organization, oxidative stress, cell signaling, and nervous system function. Particularly noteworthy is the uncovering of the activation of the proteasome pathway, highlighting significant key contributing proteins. These novel findings provide a new perspective for exploring the molecular mechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers. Additionally, comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.

In Situ Imaging of Cellular Inflammatory Response to Antibiotic Exposure with a DNAzyme Nanorobot.

Antibiotic-induced inflammation involves the release of myeloperoxidase (MPO), an enzyme whose expression in tissues is associated with the inflammatory pathway. However, existing methods for detecting MPO in cells are limited. In this study, a DNAzyme nanorobot was developed using a scaffold of gold nanoparticles (AuNPs) decorated with functional DNAzyme strands and their fluorophore-labeled substrate strands. The DNAzyme remains inactive due to a self-assembled hairpin structure, with a phosphorothioate (PT) modification inserted into the stem domain. When MPO is present, it triggers a halogenation process that generates hypochlorous acid (HClO). HClO specifically catalyzes the cleavage of the PT-site, releasing free DNAzyme strands to cleave their substrates and generating an increasing fluorescent signal. The detection limit for MPO and its primary product, HClO, were determined to be 0.038 µg/mL and 0.013 µM, respectively. The DNAzyme nanorobot can be readily introduced into cells and function autonomously to differentiate increased MPO/HClO levels caused by antibiotics. This approach was applied to image RAW264.7 cells exposed to four prevalent antibiotics found in the environment (phorbol 12-myristate 13-acetate, erythromycin, penicillin, and tetracycline) as well as antibiotic production wastewater. This nanorobot offers novel strategies for monitoring inflammation to evaluate the health impacts of antibiotic exposure.

Clinical profile analysis of SARS-CoV-2 community infections during periods with omicron BA.2, BA.4/5, and XBB dominance in Hong Kong: a prospective cohort study.

BACKGROUND: Existing studies on SARS-CoV-2 infection have mainly focused on severe clinical outcomes; understanding of the clinical severity profile of general community infections is poor. We aimed to assess and compare the clinical profiles of infections with SARS-CoV-2 omicron (B.1.1.529) subvariants in a representative community cohort in Hong Kong during periods of BA.2, BA.4/5, and XBB dominance. METHODS: In this prospective cohort study in Hong Kong, a representative community cohort of individuals aged at least 5 years were recruited by random-digit dialling and underwent weekly rapid antigen testing for SARS-CoV-2, irrespective of symptoms, during three periods from March 1, 2022, to Oct 31, 2023, in which the BA.2, BA.4/5, or XBB subvariants were dominant. We analysed the likelihood of symptoms, as well as the patterns, severity, and duration of symptoms and their associations with participant demographics and vaccination and infection histories. FINDINGS: 1126 (11·0%) of 10 279 participants in the BA.2 period, 830 (6·6%) of 12 588 in the BA.4/5 period, and 633 (11·1%) of 5690 during the XBB period tested positive for SARS-CoV-2 infection on rapid antigen tests. Community infections were generally mild, with asymptomatic infections comprising 22·0-25·0% of infections. No hospitalisations or deaths occurred as a direct result of SARS-CoV-2 infection during the study period. Compared with children aged 5-17 years, a higher likelihood of being symptomatic on infection was found for adults aged 18-59 years during the period of BA.2 dominance and adults aged 60 years or older during XBB dominance. Most (>90·0%) participants with symptomatic infections reported respiratory and systemic symptoms. Up-to-date vaccination with a regimen containing the BNT162b2 vaccine, compared with those without an up-to-date vaccine, was associated with a reduced likelihood of symptoms on infection during the period of BA.2 dominance and of severe symptoms causing substantial disturbance to daily life (grade 3 symptoms) during periods of BA.2 and BA.4/5 dominance, whereas no association was observed during the period of XBB dominance. Previous SARS-CoV-2 infection was associated with a reduced likelihood of symptoms on infection during BA.4/5 and XBB dominance and of severe symptoms during XBB dominance. Reports of severe symptoms increased over the three periods, from 236 (27·7%) of 852 symptomatic participants during BA.2 dominance to 176 (37·1%) of 475 during XBB dominance. The duration of symptoms was longest in the BA.2 period (median 10·0 days [95% CI 9·0-10·0]) and similar in the other two periods (8·0 [8·0-9·0] during BA.4/5 dominance and 8·0 [8·0-9·0] during XBB dominance). A symptom duration of 60 days or longer was reported only during the period of BA.2 dominance, in six (0·7%) of 824 infections. INTERPRETATION: SARS-CoV-2 infections were generally mild, but not increasingly so, along the evolution of omicron subvariants in this highly vaccinated population. About a third of participants with symptomatic infections reported that the symptoms severely affected daily life even if they were not admitted to hospital, resulting in morbidity, absence from work or school due to illness, productivity loss, and increased medicoeconomic burden. A gradual reduction in the association of vaccines and increase in the association of previous infection with the symptom profile, possibly reflecting the effects of immune escape and waning, were observed over the study period. FUNDING: Henry Fok Foundation and Hong Kong Health Bureau.

The individualized optimal pillow height and neck support design for side sleepers.

An optimal pillow effectively increases sleep quality and prevents cervical symptoms. However, the influence of body dimension on optimal pillow design or selection strategy has not been clarified quantitatively. This study aims to investigate the individualized optimal pillow height and neck support for side sleepers. Nine healthy subjects were recruited and laid laterally on foam-latex pillow with four height levels (8 cm, 10 cm, 12 cm, 14 cm) and with/without neck support, respectively. Healthiness was evaluated using cervical spine morphology (measured by motion capturing system) and musculoskeletal internal force (simulated by a multi-body model). Comfortability was evaluated by a deviation standardized overall comfort rating. Individualized pillow height was identified by Hφ (calculated by the subject's shoulder width and absolute pillow height). Correlation analysis and linear mixed model were performed between C1-T1 slope and Hφ. A paired-t test was performed on the cervical curve and comfort score comparisons between neck support pillow and flat pillow. The C1-T1 slope of the cervical curve showed statistically significant correlation to Hφ and was well predicted by Hφ through linear relation (R2 = 0.80 for flat pillow, R2 = 0.82 for neck support pillow). The correlation between comfort score and Hφ was moderate or weak. Medium individualized height pillow (Hφ 9.74-11.76 cm) with neck support showed a cervical curve closest to natural standing and the lowest musculoskeletal internal force. Sub-low individualized height pillow (Hφ 11.76-13.78 cm) with neck support showed the highest average comfort score. For side sleepers, cervical curve morphology and optimal individualized pillow height are well predicted by Hφ. Comfortability perception is not sensitive to Hφ. Sub-low individualized height pillow showed the best comfortability and relatively good healthiness. Medium individualized height pillow with neck support showed the best healthiness.

Emerging Chemicals in China: Historical Development, Current Situation, and Future Outlook.

There has been a widespread international consensus to enhance the regulation of emerging chemicals in the 21st century. The substantial implementation work conducted over the past two decades has established a strong foundation for the control of emerging chemicals across the world. Nevertheless, distinct challenges confront countries and regions due to the ever-evolving diverse national conditions. China, as a developing nation and a major consumer of chemicals, is encountering particularly severe hurdles. This Perspective presents an overview encompassing the historical progression, current circumstances, and challenges confronted by China with regard to emerging chemicals. The central goal of these efforts is to prioritize the control of emerging chemicals and actively establish a monitoring mechanism. Additionally, it is necessary to develop a multistakeholder environmental risk prevention and control system. Ultimately, comprehensive efforts to enhance green substitution practices and active engagement of governance initiatives will be required.

Percutaneous Penetration and Dermal Exposure Risk Assessment of UV Absorbents in Sunscreens and Isolation Cosmetics.

Ultraviolet absorbents (UVs) make up a group of industrial chemicals that is used in various consumer products and industrial applications. Due to their extensive production and usage, UVs have been detected in multiple environmental matrixes. Recently, UVs have garnered significant attention because of their probable adverse impacts on human health and the environment. This study examines UVs levels in sunscreens and isolation cosmetics and further assesses human exposure to UVs through the application of cosmetics. The total concentrations of nine UVs in 87 sunscreen and isolation cosmetic products ranged from 75.5 to 4.25 × 104 ng/g. Among them, 2-(2-hydroxy-5-methyl-phenyl)benzotriazole (UV-P) and 2-hydroxy-4-(octoxy)benzophenone (UV-531) had the highest concentrations. Use of the EpiSkin model indicated rapid absorption and strong dermal penetration by UV-328 following 36 h of exposure with a cumulative absorption rate of 41.8% ± 2.82%. Other congeners are expected to be distributed in the dermal tissue and donor fluid. Furthermore, this study explored potential mechanisms implicating skin biochemical barriers in the metabolism and transport of UVs. The potential of UVs to act as substrates and inhibitors of P450 enzymes was assessed, and their metabolites were predicted. Molecular docking simulations demonstrated that UVs can significantly interact and bind with three transport proteins in skin: MDR1, OATP2B1, and OATP3A1. Daily UVs exposure through the skin was assessed, revealing that dermal absorption levels of UV-P in sunscreen sprays (4.66 × 103 ng/(kg bw day)) and sunscreens (6.01 × 103 ng/(kg bw day)) were close to or exceeded the reference dose (RfD) and therefore require more attention.

Supplementation with Akkermansia muciniphila improved intestinal barrier and immunity in Zebrafish (Danio rerio).

Akkermansia muciniphila (Akk), a second-generation probiotic known for its ability to regulate intestinal function in mammals, is not yet fully understood in the context of aquaculture. This study aims to investigate the effects of different forms of Akk on intestinal barrier function and immune response in zebrafish (Danio rerio) under high-fat diet conditions. The experimental groups included a control group, a high-fat diet group, an Akk group, and a group receiving various concentrations of pasteurized Akkermansia muciniphila (P-Akk) along with a high-fat diet. Evaluation methods included histological examination with hematoxylin and eosin staining, ultrastructural analysis using transmission electron microscopy, real-time fluorescence quantitative analysis, and transcriptome sequencing technology. The results showed that both the Akk and P-Akk groups exhibited a significant increase in villi number and length compared to the high-fat group. Furthermore the expression levels of claudin, claudin-2, occludin A, occludin B, and other genes were significantly upregulated, while the expression levels of intestinal proinflammatory factors genes and proteins were significantly downregulated. Compared to the high-fat group, the Akk group showed a more complete and well-preserved nucleus, mitochondria, and tight junction structures. Additionally, the morphology of intestinal epithelial microvilli in the medium and high concentration Akk group was complete and dense. The expressions of tlr2 and nf-κb were upregulated, while the expressions of myd88 and nod2 were downregulated in the medium- and high-concentration Akk groups. Akk may improve immune dysfunction in high-fat fed zebrafish through the TLR2/NF-κB signaling pathway, which requires further study. Transcriptome analysis revealed significant upregulation of the immune-related gene pigr, significant downregulation of stat3, and significant upregulation of the intercellular adhesion molecule f11r. In conclusion, dietary Akk supplementation alleviated intestinal barrier damage and immune dysfunction in high-fat zebrafish. This study provides important insights into the potential use of Akk in fish and lays the foundation for further studies on its role in fish immunity.

Occurrence and Ecological Risk Assessment of Highly Toxic Halogenated Byproducts during Chlorination Decolorization of Textile Printing and Dyeing Wastewater.

Textile printing and dyeing wastewater is a substantial source of highly toxic halogenated pollutants because of the chlorination decolorization. However, information on the occurrence and fate of the highly toxic halogenated byproducts, which are produced by chlorination decolorization of the textile printing and dyeing wastewater, is very limited. In this study, the occurrence of six categories of halogenated byproducts (haloacetic acids (HAAs), haloacetonitriles (HANs), N-nitrosamines (NAs), trihalomethanes, halogenated ketones, and halonitromethanes) was investigated along the full-scale treatment processes of textile printing and dyeing wastewater treatment plants. Furthermore, the ecological risk of the halogenated byproducts was evaluated. The results showed that the total concentration of halogenated byproducts increased significantly after chlorination. Large amounts of HAAs (average 122.1 µg/L), HANs (average 80.9 µg/L), THMs (average 48.3 µg/L), and NAs (average 2314.3 ng/L) were found in the chlorinated textile wastewater, and the results showed that the generations of HANs and NAs were positively correlated with the BIX and ß/α index, indicating that the HANs and NAs might form from the microbial metabolites. In addition, HAAs and HANs exhibited high ecological risk quotients (>1), suggesting their high potential ecological risk. The results also demonstrated that most halogenated byproducts could be effectively removed by reverse osmosis treatment processes except NAs, with a lower removal rate of 18%. This study is believed to provide an important theoretical basis for controlling and reducing the ecological risks of halogenated byproducts in textile printing and dyeing wastewater effluents.

Heat stress induces a three-phase thermoregulatory response in different hot and humid environments in rats.

As global warming intensifies, heat waves occur more frequently around the world. Heat stress from hot and humid environments poses a significant threat to human health. It can cause a significant increase in core body temperature (CBT), and even lead to life-threatening heat stroke. Extremely high CBT is considered the most important clinical symptom and prognostic indicator of heat stroke. To study it, we implanted temperature-monitoring capsules into the abdominal cavities of rats to measure their CBT values. The rats were then exposed to different hot and humid environments to monitor the resultant changes in their CBTs. The results showed that heat stress could induce a three-phase thermoregulatory response in rats under different conditions. A temperature plateau was observed as part of the three-phase thermoregulatory response, at a similar CBT across different conditions. The duration of this plateau can reflect the thermotolerance of rats in hot and humid environments. The third stage of the three-phase thermoregulatory response reflects the pathogenesis of heat stroke, which may present the key stage of heat injury. Moreover, a certain range of humidity did not affect the thermoregulatory responses of rats, but exerted a significant impact once a certain threshold was reached. In this study, the CBTs of the rats in different environments were monitored to characterize their thermoregulatory responses under heat stress. In particular, the discovery of the plateau phase and humidity threshold may help to better understand the effects of high temperature and humidity conditions on living organisms.

Molecular designing of potential environmentally friendly PFAS based on deep learning and generative models.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used across a spectrum of industrial and consumer goods. Nonetheless, their persistent nature and tendency to accumulate in biological systems pose substantial environmental and health threats. Consequently, striking a balance between maximizing product efficiency and minimizing environmental and health risks by tailoring the molecular structure of PFAS has become a pivotal challenge in the fields of environmental chemistry and sustainable development. To address this issue, a computational workflow was proposed for designing an environmentally friendly PFAS by incorporating deep learning (DL) and molecular generative models. The hybrid DL architecture MolHGT+ based on heterogeneous graph neural network with transformer-like attention was applied to predict the surface tension, bioaccumulation, and hepatotoxicity of the molecules. Through virtual screening of the PFAS master database using MolHGT+, the findings indicate that incorporating the siloxane group and betaine fragment can effectively decrease both the bioaccumulation and hepatotoxicity of PFAS while preserving low surface tension. In addition, molecular generative models were employed to create a structurally diverse pool of novel PFASs with the aforementioned hit molecules serving as the initial template structures. Overall, our study presents a promising AI-driven method for advancing the development of environmentally friendly PFAS.

The effect of anthropogenic activities on the behavior of novel brominated flame retardants in surface soil of Northern China urbanized zone.

Novel brominated flame retardants (NBFRs) have emerged as an alternative to traditional brominated flame retardants (BFRs) and may pose risks to the environment and human health. However, the distribution pattern of NBFRs in urbanized zones and their association with multiple socioeconomic variables have not been adequately explored. Herein, seven NBFRs were investigated in surface soil samples from Tianjin, China, a typical urbanized area. The ∑7NBFRs ranged from n.d. to 101 ng/g, dry weight (dw) (mean: 12.6 ± 17.6 ng/g dw), which exhibited a relatively elevated level compared to NBFRs in soils from other regions worldwide. Decabromodiphenylethane (DBDPE) was the main contaminant, and its concentration ranged from 0.378 to 99 ng/g, dry weight (dw) (mean: 11.4 ± 17.0 ng/g dw), accounting for 81 % of the ∑7NBFRs. Notably, NBFRs exhibited peak concentrations within residential zones, significantly surpassing those recorded in the remaining four regions (green, farmland, water environment and other) (p < 0.05). Furthermore, the concentration of NBFRs in the soil of the Binhai New District within Tianjin was the highest, significantly exceeding that of other administrative areas, which was closely related to the intensive industrial activities in this region. The above results indicate that human activities are a key factor affecting the concentration of NBFRs in the soil. Moreover, a variety of statistical methods were employed to investigate the correlation between socioeconomic variables and the distribution of NBFRs. The concentration of NBFRs showed a significant correlation with population density and the gross domestic product (GDP) (p < 0.05), and the incorporation of administrative regional planning into structural equation models demonstrated an indirect influence on the spatial distribution of NBFRs concentration, mediated by its impact on population density. These results emphasize the association between NBFRs contamination and the degree of urbanization, thereby providing valuable insights for assessing the exposure risk of NBFRs among urban residents.

Hydrological interactions between surface water and groundwater in ancient manmade village tank cascade systems (VTCSs) in the dry zone of Sri Lanka.

Sri Lanka, a tropical island, confronts climate-driven water scarcity and is of great concern to building climate-resilient water management to achieve UN SDGs 6 and 13. This study explores the dynamic interaction between surface water (SW) and groundwater (GW) in the dry zone of Sri Lanka, employing a multi-tracer of dual stable isotopes (18O and 2H) and chloride. Two basins, Mahakanadarawa (MK) basin with numerous village tanks and tank cascade systems (VTCSs/TCSs) and Kawudulla (KW) basin serving as a control with a lack of tanks, were selected in this study. Results show that the presence or absence of TCSs emerges as a pivotal factor influencing regional water dynamics. Water quality (TDS and Cl-) in natural waters between the two basins was significantly different (ANOVA: p < 0.05) in both seasons. Statistically uniform dissolved mineral content in tanks and shallow groundwater in the MK basin contrasted with significant regional deviation in the KW basin. ANOVA and Tukey tests showed significant seasonal differences (p < 0.05) in mean values of ẟ2H and ẟ18O compositions of shallow groundwater and tank water within the MK basin, while non-significance in the KW basin. Isotopic mass balance calculations revealed that tank water mixing in the shallow groundwater (fT: mixed Tank water mass fraction) ranged from 0.9 % to 77.8 % across the MK basin depending on the regional soil characteristics. Lack of tank-aquifer interconnection observed in the shallow soil in rock knob plain results in groundwater depletion while enhanced interconnections within alluvial sediment regions encourage stable and pollution-resistant shallow groundwater bodies. The consistency of the groundwater flow system in TCS regions throughout the year ensures a stable water supply, highlighting the vital synergy between TCSs and regional groundwaters in these arid regions. These results shed insights for policymakers and water managers to implement effective conservation strategies for rehabilitation and restoring these ancient VTCSs/TCSs.

Exposure Assessment of Benzotriazole Ultraviolet Absorbers in Plastic Sports Field Dust and Indoor Dust: Are Plastic Sports Fields High Exposure Scenarios?

Benzotriazole ultraviolet absorbers (BUVs), as emerging contaminants of extensive use, especially in plastic sports fields, have aroused increasing concern due to their potential human and environmental impacts. However, BUV exposure from plastic sports field dust is still unknown. This study compared BUVs in plastic sports field dust and indoor dust for the first time. The order of the geometric mean concentrations of the total BUVs (ΣBUVs) in plastic sports field dust was indoor badminton courts (11023 ng g-1) > basketball courts (4777 ng g-1) > plastic tracks (3779 ng g-1) > synthetic turf (1920 ng g-1) > tennis courts (689 ng g-1). The geometric mean concentrations of ΣBUVs in indoor dust (1150 ng g-1) were lower than those in most plastic sports field dust. The dominant BUV was 2-hydroxy-4-(octyloxy)benzophenone (UV-531) in plastic sports field dust, while 2,2'-methylenebis[4-(1,1,3,3-tetramethylbutyl)-6-2H-benzotriazole-2-yl)phenol] (UV-360) was the dominant BUV in indoor dust. Releases from plastic track materials, sneaker soles, and friction between them might be important BUV sources in plastic track dust. The average estimated daily intakes of ΣBUVs from plastic sports field dust for general exercisers were lower than those from indoor dust, but those for exercisers with long time or professional athletes might be higher, potentially posing health risks.

A rolling-mode triboelectric nanogenerator with multi-tunnel grating electrodes and opposite-charge-enhancement for wave energy harvesting.

In light of the crucial role of marine ecosystems and the escalating environmental conservation challenges, it is essential to conduct marine monitoring to help implement targeted environmental protection measures efficiently. Energy harvesting technologies, particularly triboelectric nanogenerators (TENGs), have great potential for prolonging the lifespan and enhancing the reliability of sensors in remote areas. However, the high internal resistance, low current, and friction-induced abrasion issues of TENGs limit their performance in practical applications. This work presents a rolling mode triboelectric nanogenerator that utilizes multi-tunnel grating electrodes and the opposite-charge-enhancement mechanism to harvest wave energy efficiently. The device achieves significant instantaneous and root mean square power density of 185.4 W/(m3·Hz) and 10.92 W/(m3·Hz), respectively. By utilizing stacked devices and an exclusively designed power management module, a self-powered ocean sensing system including computing and long-range wireless communication (0.8 km) capabilities was developed. Laboratory and in-situ ocean tests were conducted to assess and validate the system. This work offers a potential solution for the challenging deployment of marine self-powered sensing nodes.

Versatile plant genome engineering using anti-CRISPR-Cas12a systems.

CRISPR-Cas12a genome engineering systems have been widely used in plant research and crop breeding. To date, the performance and use of anti-CRISPR-Cas12a systems have not been fully established in plants. Here, we conduct in silico analysis to identify putative anti-CRISPR systems for Cas12a. These putative anti-CRISPR proteins, along with known anti-CRISPR proteins, are assessed for their ability to inhibit Cas12a cleavage activity in vivo and in planta. Among all anti-CRISPR proteins tested, AcrVA1 shows robust inhibition of Mb2Cas12a and LbCas12a in E. coli. Further tests show that AcrVA1 inhibits LbCas12a mediated genome editing in rice protoplasts and stable transgenic lines. Impressively, co-expression of AcrVA1 mitigates off-target effects by CRISPR-LbCas12a, as revealed by whole genome sequencing. In addition, transgenic plants expressing AcrVA1 exhibit different levels of inhibition to LbCas12a mediated genome editing, representing a novel way of fine-tuning genome editing efficiency. By controlling temporal and spatial expression of AcrVA1, we show that inducible and tissue specific genome editing can be achieved in plants. Furthermore, we demonstrate that AcrVA1 also inhibits LbCas12a-based CRISPR activation (CRISPRa) and based on this principle we build logic gates to turn on and off target genes in plant cells. Together, we have established an efficient anti-CRISPR-Cas12a system in plants and demonstrate its versatile applications in mitigating off-target effects, fine-tuning genome editing efficiency, achieving spatial-temporal control of genome editing, and generating synthetic logic gates for controlling target gene expression in plant cells.

Drivers of change behind the spatial distribution and fate of typical trace organic pollutants in fresh waste leachate across China.

There have been growing concerns regarding the health and environmental impacts of trace organic pollutants (TOPs). However, fresh leachate from municipal solid waste (MSW) has been overlooked as a potential reservoir of TOPs. Therefore, we investigated 90 legacy and emerging TOPs in fresh leachate from 14 provinces and municipalities in China. Additionally, the fate and final discharge impacts of TOPs in 14 leachate treatment systems were analyzed. The results revealed that the detection rate of 90 TOPs was over 50 % in all samples. Notably, polychlorinated biphenyls, banned for 40 years, were frequently detected in fresh leachate. The concentration of pseudo-persistent TOPs (105-107 ng/L) is significantly higher than that of persistent TOPs (102-104 ng/L). Spatial distribution patterns of TOPs in fresh leachate suggest that economy, population, climate, and policies impact TOPs discharge from MSW. For example, economically developed and densely populated areas displayed higher TOPs concentrations, whereas warmer climates facilitate TOPs leaching from MSW. We confirmed that waste classification policies were a key driver of the decline in multiple TOPs in leachate. Mass balance analysis shows that the final effluent and sludge from current dominant leachate treatment systems contain refractory TOPs, especially perfluoroalkyl acids, which must be prioritized for control. This paper was the first comprehensive investigation of multiple TOPs in fresh leachate at a large geographic scale. The factors affecting the occurrence, spatial distribution, and fate of TOPs in fresh leachate were revealed. It provides a valuable reference for the establishment of policies for the management of TOPs in MSW and the associated leachate.

Heat acclimation with probiotics-based ORS supplementation alleviates heat stroke-induced multiple organ dysfunction via improving intestinal thermotolerance and modulating gut microbiota in rats.

Heat stroke (HS) is a critical condition with extremely high mortality. Heat acclimation (HA) is widely recognized as the best measure to prevent and protect against HS. Preventive administration of oral rehydration salts III (ORSIII) and probiotics have been reported to sustain intestinal function in cases of HS. This study established a rat model of HA that was treated with probiotics-based ORS (ORSP) during consecutive 21-day HA training. The results showed that HA with ORSP could attenuate HS-induced hyperthermia by regulating thermoregulatory response. We also found that HA with ORSP could significantly alleviate HS-induced multiple organ injuries. The expression levels of a series of heat-shock proteins (HSPs), including HSP90, HSP70, HSP60, and HSP40, were significantly up-regulated from the HA training. The increases in intestinal fatty acid binding protein (I-FABP) and D-Lactate typically seen during HS were decreased through HA. The representative TJ proteins including ZO-1, E-cadherin, and JAM-1 were found to be significantly down-regulated by HS, but sustained following HA. The ultrastructure of TJ was examined by TEM, which confirmed its protective effect on the intestinal barrier protection following HA. We also demonstrated that HA raised the intestinal levels of beneficial bacteria Lactobacillus and lowered those of the harmful bacteria Streptococcus through 16S rRNA gene sequencing. These findings suggest that HA with ORSP was proven to improve intestinal thermotolerance and the levels of protective gut microbiota against HS.

Characteristics of disinfection byproducts from dissolved organic matter during chlor(am)ination of source water in Tibetan Plateau, China.

The Tibetan Plateau, a typical high-altitude area, is less affected by human activities such as industrial development, and the external pollution to water sources is extremely low. Then it is also an important source of water samples for exploring the molecular characteristics of precursors in the dissolved organic matter (DOM) of disinfection byproducts (DBPs) in drinking water. Research data on DBPs in drinking water on the Tibet Plateau remains insufficient, leading to uncertainty about DBP contamination in the area. This study explores the formation potential of 35 typical DBPs, including 6 trihalomethanes (THMs), 9 haloacetic acids (HAAs), 2 halogenated ketones (HKs), 9 nitrosamines (NAs), and 9 aromatic DBPs, during chlorination and chloramination of typical source water samples in the Tibet Plateau of China. Moreover, in order to further investigate the characteristics of the generation of DBPs, the molecular composition of DOM in the collected water samples was characterized by Fourier transform ion cyclotron resonance mass spectrometry. The findings reveal that, for chlorination and chloramination, the average concentration of the five classes of DBPs was ranked as follows (chlorination, chloramination): HAAs (268.1 µg/L, 54.2 µg/L) > THMs (44.0 µg/L, 2.0 µg/L) > HKs (0.7 µg/L, 1.8 µg/L) > NAs (26.5 ng/L, 74.6 ng/L) > Aromatics (20.4 ng/L, 19.5 ng/L). The dominant compounds in THMs, HAAs, and NAs are trichloromethane, dichloroacetic acid, trichloroacetic acid, and nitrosopyrrolidine, respectively. This study highlights a significant positive correlation between DBP generation and UV254, SUV254, and the double bond equivalents of DOM in the source water. It systematically elucidates DOM molecular composition characteristics and DBP formation potential in high-altitude water sources, shedding light on key factors influencing DBP generation at the molecular level in high-altitude areas.

Correlation of FBXO45 Expression Levels with Cancer Severity by ZEB1 Ubiquitin in Non-Small-Cell Lung Cancer.

The early diagnostic methods for non-small-cell lung cancer (NSCLC) are limited, lacking effective biomarkers, and the late stage surgery is difficult and has a high recurrence rate. We investigated whether the effects of FBXO45 in arcinogenesis and metastasis of NSCLC. The up-regulation of FBXO45 expression in NSCLC patients or cell lines were observed. FBXO45 gene promoted metastasis and Warburg effect, and reduced ferroptosis of NSCLC. FBXO45 induced ZEB1 expression to promote Warburg effect and reduced ferroptosis of NSCLC. Sh-FBXO45 reduced cancer growth of NSCLC in mice model. FBXO45 decreased the ubiquitination of ZEB1, leading to increased expression of ZEB1, which in turn promoted the Warburg effect and reduced ferroptosis in NSCLC. In vivo imaging, Sh-FBXO45 also reduced ZEB1 expression levels of lung tissue in mice model. FBXO45 in NSCLC through activating the Warburg effect, and the inhibition of ferroptosis of NSCLC by the suppression of ZEB1 ubiquitin, FBXO45 may be a potential therapeutic strategy for NSCLC.