Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice.

BACKGROUND: Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. RESULTS: In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin-CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. CONCLUSIONS: In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice.

Prognostic factors and novel prediction models for overall survival of patients with submandibular gland cancer: A population-based retrospective cohort study.

Background: Accurately predicting the survival rate of submandibular gland cancer (SGC) is of significant importance for guiding treatment decision-making and improving patient outcomes. This study was aimed to identify the independent prognostic factors of overall survival (OS) in SGC patients, and develop novel prediction models to aid clinicians in predicting the survival probability. Materials and methods: Patients diagnosed with primary SGC after the year 2010 were extracted from SEER database and then randomly allocated into training and test samples in a 7:3 ratio. Uni- and multi-variable COX analyses were employed using the training sample to ascertain independent prognostic factors for OS. Subsequently, graphic and online dynamic nomograms were established basing on the independent prognostic factors. We utilized C-index, calibration curve, receiver operating characteristic (ROC) curve, and area under ROC curve (AUC) value to evaluate the discrimination capacity and the consistency between predicted and actual survival. Results: A total of 527 SGC patients were included (369 assigned to training group and 158 assigned to test group). The multivariable COX analysis showed that age, sex, marital status, tumor histology, summary stage, metastases to bone, and tumor size were independently associated with OS. Novel graphical and online dynamic (URL: https://yangxg1209.shinyapps.io/overall_survival_submandibular_gland_tumor/) nomograms were established. The C-indices (training: 0.77, 95%CI 0.71-0.84; test: 0.77, 95%CI 0.68-0.85) indicate favorable discrimination ability of the model, and the calibration curves demonstrated favorable consistency between the predicted and actual survival rates. Conclusions: Our study identified the independent prognostic factors influencing OS in patients with SGC, and successfully established and validated novel nomograms, which provide accurate prediction of survival rates and allows for personalized risk assessment.

Transcription factor OsSHR2 regulates rice architecture and yield per plant in response to nitrogen.

MAIN CONCLUSION: Mutation of OsSHR2 adversely impacted root and shoot growth and impaired plant response to N conditions, further reducing the yield per plant. Nitrogen (N) is a crucial factor that regulates the plant architecture. There is still a lack of research on it. In our study, it was observed that the knockout of the SHORTROOT 2 (OsSHR2) which was induced by N deficiency, can significantly affect the regulation of plant architecture response to N in rice. Under N deficiency, the mutation of OsSHR2 significantly reduced root growth, and impaired the sensitivity of the root meristem length to N deficiency. The mutants were found to have approximately a 15% reduction in plant height compared to wild type. But mutants showed a significant increase in tillering at post-heading stage, approximately 26% more than the wild type, particularly in high N conditions. In addition, due to reduced seed setting rate and 1000-grain weight, mutant yield was significantly decreased by approximately 33% under low N fertilizer supply. The mutation also changed the distribution of N between the vegetative and reproductive organs. Our findings suggest that the transcription factor OsSHR2 plays a regulatory role in the response of plant architecture and yield per plant to N in rice.

Insight into effect of polyethylene microplastic on nitrogen removal in moving bed biofilm reactor: Focusing on microbial community and species interactions.

Microplastics (MPs) pollution has emerged as a global concern, and wastewater treatment plants (WWTPs) are one of the potential sources of MPs in the environment. However, the effect of polyethylene MPs (PE) on nitrogen (N) removal in moving bed biofilm reactor (MBBR) remains unclear. We hypothesized that PE would affect N removal in MBBR by influencing its microbial community. In this study, we investigated the impacts of different PE concentrations (100, 500, and 1000 µg/L) on N removal, enzyme activities, and microbial community in MBBR. Folin-phenol and anthrone colorimetric methods, oxidative stress and enzyme activity tests, and high-throughput sequencing combined with bioinformation analysis were used to decipher the potential mechanisms. The results demonstrated that 1000 µg/L PE had the greatest effect on NH4+-N and TN removal, with a decrease of 33.5 % and 35.2 %, and nitrifying and denitrifying enzyme activities were restrained by 29.5-39.6 % and 24.6-47.4 %. Polysaccharide and protein contents were enhanced by PE, except for 1000 µg/L PE, which decreased protein content by 65.4 mg/g VSS. The positive links of species interactions under 1000 µg/L PE exposure was 52.07 %, higher than under 500 µg/L (51.05 %) and 100 µg/L PE (50.35 %). Relative abundance of some metabolism pathways like carbohydrate metabolism and energy metabolism were restrained by 0.07-0.11 % and 0.27-0.4 %. Moreover, the total abundance of nitrification and denitrification genes both decreased under PE exposure. Overall, PE reduced N removal by affecting microbial community structure and species interactions, inhibiting some key metabolic pathways, and suppressing key enzyme activity and functional gene abundance. This paper provides new insights into assessing the risk of MPs to WWTPs, contributing to ensuring the health of aquatic ecosystems.

Disseminated Talaromyces marneffei infection initially presenting as cutaneous and subcutaneous lesion in an HIV-Negative renal transplant recipient: a case report and literature review.

BACKGROUND: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding. CASE PRESENTATION: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment. CONCLUSIONS: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population.

Ciprofloxacin affects nutrient removal in manganese ore-based constructed wetlands: Adaptive responses of macrophytes and microbes.

Ciprofloxacin (CIP) has received considerable attention in recent decades due to its high ecological risk. However, little is known about the potential response of macrophytes and microbes to varying levels of CIP exposure in constructed wetlands. Therefore, lab-scale manganese ore-based tidal flow constructed wetlands (MO-TFCWs) were operated to evaluate the responses of macrophytes and microbes to CIP over the long term. The results indicated that total nitrogen removal improved from 79.93% to 87.06% as CIP rose from 0 to 4 mg L-1. The chlorophyll content and antioxidant enzyme activities in macrophytes were enhanced under CIP exposure, but plant growth was not inhibited. Importantly, CIP exposure caused a marked evolution of the substrate microbial community, with increased microbial diversity, expanded niche breadth and enhanced cooperation among the top 50 genera, compared to the control (no CIP). Co-occurrence network also indicated that microorganisms may be more inclined to co-operate than compete. The abundance of the keystone bacterium (involved in nitrogen transformation) norank_f__A0839 increased from 0.746% to 3.405%. The null model revealed drift processes (83.33%) dominated the community assembly with no CIP and 4 mg L-1 CIP. Functional predictions indicated that microbial carbon metabolism, electron transfer and ATP metabolism activities were enhanced under prolonged CIP exposure, which may contribute to nitrogen removal. This study provides valuable insights that will help achieve stable nitrogen removal from wastewater containing antibiotic in MO-TFCWs.

Porcine lung tissue slices: a culture model for PRCV infection and innate immune response investigations.

Respiratory coronaviruses (RCoVs) significantly threaten human health, necessitating the development of an ex vivo respiratory culture system for investigating RCoVs infection. Here, we successfully generated a porcine precision-cut lung slices (PCLSs) culture system, containing all resident lung cell types in their natural arrangement. Next, this culture system was inoculated with a porcine respiratory coronavirus (PRCV), exhibiting clinical features akin to humans who were infected by SARS-CoV-2. The results demonstrated that PRCV efficiently infected and replicated within PCLSs, targeting ciliated cells in the bronchioles, terminal bronchioles, respiratory bronchioles, and pulmonary alveoli. Additionally, through RNA-Seq analysis of the innate immune response in PCLSs following PRCV infection, expression levels of interferons, inflammatory cytokines and IFN stimulated genes were significantly upregulated. This ex vivo model may not only offer new insights into PRCV infection in the porcine respiratory tract but also serve as a valuable tool for studying human respiratory CoVs infection.

Spatiotemporal drivers of urban water pollution: Assessment of 102 cities across the Yangtze River Basin.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

From stem cells to pancreatic ß-cells: strategies, applications, and potential treatments for diabetes.

Loss and functional failure of pancreatic ß-cells results in disruption of glucose homeostasis and progression of diabetes. Although whole pancreas or pancreatic islet transplantation serves as a promising approach for ß-cell replenishment and diabetes therapy, the severe scarcity of donor islets makes it unattainable for most diabetic patients. Stem cells, particularly induced pluripotent stem cells (iPSCs), are promising for the treatment of diabetes owing to their self-renewal capacity and ability to differentiate into functional ß-cells. In this review, we first introduce the development of functional ß-cells and their heterogeneity and then turn to highlight recent advances in the generation of ß-cells from stem cells and their potential applications in disease modeling, drug discovery and clinical therapy. Finally, we have discussed the current challenges in developing stem cell-based therapeutic strategies for improving the treatment of diabetes. Although some significant technical hurdles remain, stem cells offer great hope for patients with diabetes and will certainly transform future clinical practice.

Identification of Molecular Subtype and Prognostic Signature for Prostate Adenocarcinoma based on Neutrophil Extracellular Traps.

Background: Prostate adenocarcinoma (PRAD) is one of the most common cancers in male. Increasing evidences pointed out that Neutrophil Extracellular Traps (NETs) play an important role in tumor angiogenesis, tumor metastasis and drug resistance. However, limited systematic studies regarding the role of NETs in PRAD have been performed. Identification of biomarkers based on NETs might facilitate risk stratification which help optimizing the clinical strategies. Methods: NETs-related genes with differential expressions were identified between PRAD and adjacent normal tissues in TCGA-PRAD dataset. Consensus cluster analysis was performed to determine the PRAD subtypes based on the different-expressed NETs-related genes. The difference of pathway enrichment, infiltrating immune cell and genomic mutation were also evaluated between subtypes. LASSO cox regression analysis was conducted to construct a NETs-related prognostic signature. Result: We identified 19 NETs related genes with differential expressions between PRAD and adjacent normal tissue in TCGA-PRAD dataset. Two significant subtypes were identified based on these 19 genes by consensus cluster analysis, namely subtype 1 and subtype 2. Significant differences in prognosis, immune infiltration and tumor mutation burden were observed in subtypes. LASSO Cox regression analysis identified a NETs-associated prognostic signature including 13 genes, and this signature had a good performance in predicting the progression-free survival of PRAD patients. Further integrated analysis indicated that MMP9 mostly expressed in Mono/Macrophage cells might play a role in regulating NETs formation via neutrophil activation in PRAD. Conclusion: To sum up, the current study identified two NETs-related molecular subtypes and based on which constructed a prognostic signature for PRAD.

New insights into substrates shaped nutrients removal, species interactions and community assembly mechanisms in tidal flow constructed wetlands treating low carbon-to-nitrogen rural wastewater.

A limited understanding of microbial interactions and community assembly mechanisms in constructed wetlands (CWs), particularly with different substrates, has hampered the establishment of ecological connections between micro-level interactions and macro-level wetland performance. In this study, CWs with distinct substrates (zeolite, CW_A; manganese ore, CW_B) were constructed to investigate the nutrient removal efficiency, microbial interactions, metabolic mechanisms, and ecological assembly for treating rural sewage with a low carbon-to-nitrogen ratio. CW_B showed higher removal of ammonia nitrogen and total nitrogen by about 1.75-6.75 % and 3.42-5.18 %, respectively, compared to CW_A. Candidatus_Competibacter (denitrifying glycogen-accumulating bacteria) was the dominant microbial genus in CW_A, whereas unclassified_f_Blastocatellaceae (involved in carbon and nitrogen transformation) dominated in CW_B. The null model revealed that stochastic processes (drift) dominated community assembly in both CWs; however, deterministic selection accounted for a higher proportion in CW_B. Compared to those in CW_A, the interactions between microbes in CW_B were more complex, with more key microbes involved in carbon, nitrogen, and phosphorus conversion; the synergistic cooperation of functional bacteria facilitated simultaneous nitrification-denitrification. Manganese ores favour biofilm formation, increase the activity of the electron transport system, and enhance ammonia oxidation and nitrate reduction. These results elucidated the ecological patterns exhibited by microbes under different substrate conditions thereby contributing to our understanding of how substrates shape distinct microcosms in CW systems. This study provides valuable insights for guiding the future construction and management of CWs.

Association of anemia with all-cause mortality in Chinese centenarians: a prospective cohort study.

OBJECTIVES: This study aimed to examine the relationship between anemia and all-cause mortality in Chinese centenarians. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We included 1002 Chinese centenarians from the China Hainan Centenarian Cohort Study (CHCCS) MEASUREMENTS: Standard procedures were followed to perform blood analysis, home interviews, and physical examinations. Anemia was defined as a hemoglobin level of less than 130 g/L for men and less than 120 g/L for women. RESULTS: During the 9-year follow-up period, a total of 929 (92.7%) deaths were identified. Cox proportional hazards regression models revealed that anemia (hazard ratio [HR] 1.289, 95% confidence interval [CI]: 1.117-1.489) was significantly associated with all-cause mortality. There was an apparent dose-response relationship between anemia and all-cause mortality. Centenarians with severe anemia had approximately 1.6 times higher likelihood of all-cause mortality than those without anemia (HR 1.662; 95% CI: 1.154-2.394). CONCLUSION: Anemia is associated with an increased risk of all-cause mortality in Chinese centenarians. Further research will be needed to collect more comprehensive data on the etiology of anemia and causes of death in centenarians.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

First Specific Detection of Mammalian Orthoreovirus from Goats Using TaqMan Real-Time RT-PCR Technology.

Mammalian orthoreovirus (MRV) infections are ubiquitous in multiple mammalian species including humans, and mainly causes gastroenteritis and respiratory disease. In this study, we developed a rapid and sensitive TaqMan qRT-PCR method for MRV detection based on the primers and probe designed within the conserved L1 gene. The qRT-PCR assay was evaluated for its sensitivity, specificity, efficiency and reproducibility. It was found that the detection sensitivity was equivalent to 10 DNA copies/µL, and the standard curves had a linear correlation of R2 = 0.998 with an amplification efficiency of 99.6%. The inter- and intra-assay coefficients of variation (CV%) were in the range of 0.29% to 2.16% and 1.60% to 3.60%, respectively. The primer sets specifically amplified their respective MRV segments and had the highest detection sensitivities of 100.25 TCID50/mL with amplification efficiencies of 99.5% (R2 = 0.999). qRT-PCR was used for MRV detection from samples of sheep, goats, and calves from four regions in China, and the overall MRV prevalence was 8.2% (35/429), whereas 17/429 (4.0%) were detected by RT-PCR and 14/429 (3.3%) by virus isolation. The qRT-PCR assay showed significantly higher sensitivity than RT-PCR and virus isolation. Results from an epidemiological survey indicated that the positive rate of MRV in rectal swabs from sheep and goats tested in Shaanxi, Jiangsu, and Xinjiang were 9/80 (11.3%), 12/93 (12.9%) and 14/128 (10.9%), respectively. In goats and sheep, MRV prevalence was obviously associated with season and age, with a high positive rate of more than 8% during September to April and approximately 13% in small ruminant animals under two months of age. This is the first instance of MRV infection in sheep and goats in China, thus broadening our knowledge of MRV hosts. Consequently, primer optimization for qRT-PCR should not only prioritize amplification efficiency and specificity, but also sensitivity. This assay will contribute to more accurate and rapid MRV monitoring by epidemiological investigation, viral load, and vaccination efficacy.

The glycosylation sites in RBD of spike protein attenuate the immunogenicity of PEDV AH2012/12.

Porcine epidemic diarrhea (PED) is a highly contagious swine intestinal disease caused by PED virus (PEDV). Vaccination is a promising strategy to prevent and control PED. Previous studies have confirmed that glycosylation could regulate the immunogenicity of viral antigens. In this study, we constructed three recombinant PEDVs which removed the glycosylation sites in RBD. Viral infection assays revealed that similar replication characteristics between the recombinant viruses and parental PEDV. Although animal challenging study demonstrated that the glycosylation sites in RBD do not affect the pathogenicity of PEDV, we found that removing the glycosylation sites on the RBD regions could promote the IgG and neutralization titer in vivo, suggesting deglycosylation in RBD could enhance the immunogenicity of PEDV. These findings demonstrated that removal of the glycosylation sites in RBD is a promising method to develop PEDV vaccines.

Microplastics shaped performance, microbial ecology and community assembly in simultaneous nitrification, denitrification and phosphorus removal process.

The widespread use of microplastics (MPs) has led to an increase in their discharge to wastewater treatment plants. However, the knowledge of impact of MPs on macro-performance and micro-ecology in simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) systems is limited, hampering the understanding of potential risks posed by MPs. This study firstly comprehensively investigated the performance, species interactions, and community assembly under polystyrene (PS) and polyvinyl chloride (PVC) exposure in SNDPR systems. The results showed under PS (1, 10 mg/L) and PVC (1, 10 mg/L) exposure, total nitrogen removal was reduced by 3.38-10.15 %. PS and PVC restrained the specific rates of nitrite and nitrate reduction (SNIRR, SNRR), as well as the activities of nitrite and nitrate reductase enzymes (NIR, NR). The specific ammonia oxidation rate (SAOR) and activity of ammonia oxidase enzyme (AMO) were reduced only at 10 mg/L PVC. PS and PVC enhanced the size of co-occurrence networks, niche breadth, and number of key species while decreasing microbial cooperation by 5.85-13.48 %. Heterogeneous selection dominated microbial community assembly, and PS and PVC strengthened the contribution of stochastic processes. PICRUSt prediction further revealed some important pathways were blocked by PS and PVC. Together, the reduced TN removal under PS and PVC exposure can be attributed to the inhibition of SAOR, SNRR, and SNIRR, the restrained activities of NIR, NR, and AMO, the changes in species interactions and community assembly mechanisms, and the suppression of some essential metabolic pathways. This paper offers a new perspective on comprehending the effects of MPs on SNDPR systems.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

Machine learning assisted combined systems of wastewater treatment plants with constructed wetlands optimal decision-making.

This study proposed an efficient framework for optimizing the design and operation of combined systems of wastewater treatment plants (WWTP) and constructed wetlands (CW). The framework coupled a WWTP model with a CW model and used a multi-objective evolutionary algorithm to identify trade-offs between energy consumption, effluent quality, and construction cost. Compared to traditional design and management approaches, the framework achieved a 27 % reduction in WWTP energy consumption or a 44 % reduction in CW cost while meeting strict effluent discharge limits for Chinese WWTP. The framework also identified feasible decision variable ranges and demonstrated the impact of different optimization strategies on system performance. Furthermore, the contributions of WWTP and CW in pollutant degradation were analyzed. Overall, the proposed framework offers a highly efficient and cost-effective solution for optimizing the design and operation of a combined WWTP and CW system.

The HEAT repeat protein HPO-27 is a lysosome fission factor.

Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impairs animal development and longevity. Thus, HPO-27 and MROH1 act as self-assembling scission factors to maintain lysosomal homeostasis and function.

The mechanism of curcumin to protect mouse ovaries from oxidative damage by regulating AMPK/mTOR mediated autophagy.

BACKGROUND: Oxidative stress is considered the main cause of granulosa cell apoptosis in ovarian disease. Curcumin has various biological roles, but its potential role in protecting granulosa cells from oxidative damage remains unidentified. PURPOSE: The study revealed the protective effect of curcumin on granulosa cell survival under oxidative stress, and explored its mode of action. STUDY DESIGN: The protective effect of curcumin on oxidative stress-induced ovarian cell apoptosis was evaluated in vivo and in vitro, and the role of autophagy and AMPK/mTOR signaling pathway in this process was also demonstrated. METHODS: First, mice were injected to 3-nitropropionic acid (3-NPA, 20 mg/kg/day) for 14 consecutive days to establish the ovarian oxidative stress model, at same time, curcumin (50, 100, 200 mg/kg/day) was given orally. Thereafter, functional changes, cell apoptosis, and autophagy in ovarian tissue were evaluated by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, western blotting, TUNEL assays, and transmission electron microscopy. Finally, oxidative stress model of granulosa cells was established with H2O2in vitro and treated with curcumin. The underlying mechanisms of curcumin to protect the apoptosis under oxidative stress in vitro were determined using western blotting and TUNEL assays. RESULTS: In our study, after curcumin treatment, the mouse ovarian function disorder under 3-nitropropionic acid-induced oxidative stress recovered significantly, and ovarian cell apoptosis decreased. H2O2 induced granulosa cell apoptosis in vitro, and curcumin antagonized this process. Autophagy contributes to tissue and cell survival under stress. We therefore examined the role of autophagy in this process. According to the in vivo and in vitro results, curcumin restored autophagy under oxidative stress. The autophagy inhibitor (chloroquine) exhibited the same effect as curcumin, whereas the autophagy activator (rapamycin) antagonized the effect of curcumin. In addition, the study found that the AMPK/mTOR pathway plays a crucial role in curcumin- mediated autophagy to protect against oxidative stress-induced apoptosis. CONCLUSION: Our findings for the first time systematically revealed a new mechanism through which curcumin protects ovarian granulosa cells from oxidative stress-induced damage through AMPK/mTOR-mediated autophagy and suggested that it can be a new therapeutic direction for female ovarian diseases.