Salt Effects on the Mechanical Properties of Ionic Conductive Polymer: A Molecular Dynamics Study.

Functional polymers can be used as electrolyte and binder materials in solid-state batteries. This often requires performance targets in terms of both the transport and mechanical properties. In this work, a model ionic conductive polymer system, i.e., poly(ethylene oxide)-LiTFSI, was used to study the impact of salt concentrations on mechanical properties, including different types of elastic moduli and the viscoelasticity with both nonequilibrium and equilibrium molecular dynamics simulations. We found an encouragingly good agreement between experiments and simulations regarding Young's modulus, bulk modulus, and viscosity. In addition, we identified an intermediate salt concentration at which the system shows high ionic conductivity, high Young's modulus, and short elastic restoration time. Therefore, this study laid the groundwork for investigating ionic conductive polymer binders with self-healing functionality from molecular dynamics simulations.

Nickel-Doped Decatungstate as a Robust Photocatalyst for Violet Light-Triggered Redox Coupling Conversion of Alcohol and Water to Aldehyde/Ketone and Hydrogen.

The effective coupling of photoinduced alcohol oxidation and water reduction may economically produce hydrogen (H2) from water, which is of great significance in solving the current energy crisis. This study discloses that decatungstate (DT) and especially Ni2+ions-doped DTs are active for the photoreaction of benzyl alcohol with H2O, and under 48 h of violet light illumination, the best 1%Ni-DT yields ca. 86.1% benzoic acid and a 4.65 h-1 H2 generation efficiency (turnover frequency, TOF). Also, 1%Ni-DT is efficient for the photoredox coupling reaction of aliphatic and especially aromatic primary/secondary alcohols with water. A series of characterizations support that the doubled-reduced H2DT produced from the photoreaction plays a key role in water reduction to H2, which is accelerated by the doped Ni2+. In particular, it and the derived Ni3+ may construct a Z-type catalyst for water overall splitting, thereby hoisting the acid yield and H2 amount in the later stage of the photoreaction.

Preoperative CECT-Based Multitask Model Predicts Peritoneal Recurrence and Disease-Free Survival in Advanced Ovarian Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: Peritoneal recurrence is the predominant pattern of recurrence in advanced ovarian cancer (AOC) and portends a dismal prognosis. Accurate prediction of peritoneal recurrence and disease-free survival (DFS) is crucial to identify patients who might benefit from intensive treatment. We aimed to develop a predictive model for peritoneal recurrence and prognosis in AOC. METHODS: In this retrospective multi-institution study of 515 patients, an end-to-end multi-task convolutional neural network (MCNN) comprising a segmentation convolutional neural network (CNN) and a classification CNN was developed and tested using preoperative CT images, and MCNN-score was generated to indicate the peritoneal recurrence and DFS status in patients with AOC. We evaluated the accuracy of the model for automatic segmentation and predict prognosis. RESULTS: The MCNN achieved promising segmentation performances with a mean Dice coefficient of 84.3% (range: 78.8%-87.0%). The MCNN was able to predict peritoneal recurrence in the training (AUC 0.87; 95% CI 0.82-0.90), internal test (0.88; 0.85-0.92), and external test set (0.82; 0.78-0.86). Similarly, MCNN demonstrated consistently high accuracy in predicting recurrence, with an AUC of 0.85; 95% CI 0.82-0.88, 0.83; 95% CI 0.80-0.86, and 0.85; 95% CI 0.83-0.88. For patients with a high MCNN-score of recurrence, it was associated with poorer DFS with P < 0.0001 and hazard ratios of 0.1964 (95% CI: 0.1439-0.2680), 0.3249 (95% CI: 0.1896-0.5565), and 0.3458 (95% CI: 0.2582-0.4632). CONCLUSION: The MCNN approach demonstrated high performance in predicting peritoneal recurrence and DFS in patients with AOC.

Asiaticoside promoted ferroptosis and suppressed immune escape in gastric cancer cells by downregulating the Wnt/ß-catenin pathway.

BACKGROUND: Our previous study has revealed that asiaticoside (AC) promotes endoplasmic reticulum stress and antagonizes proliferation and migration of gastric cancer (GC) via miR-635/HMGA1 axis. However, the effect and mechanism of AC on other progressions of GC, such as ferroptosis and immune escape, are still unknown. METHODS: AGS and HGC27 cells were incubated with 1, 2 and 4 µM of AC for 24 h. Mice xenografted with AGS cells were intragastrically injected with AC. The effect and mechanism of AC on GC were determined by the measurement of the ferrous iron level, the ROS level and the glutathione peroxidase (GSH) content, flow cytometry, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and western blotting assays. RESULTS: AC increased the Fe2+ level and the ROS level, but decreased the expression of GPX4 and SLC7A11 and the GSH level. Besides, AC enhanced the percent of CD8+ T cells and the IFN-γ concentration, but reduced the PD-L1 expression and the IL-10 level. Mechanically, AC downregulated the relative levels of ß-catenin, active-ß-catenin, p-GSK3ß/GSK3ß, cyclin D1 and c-Myc in GC cells, which were rescued with the application of LiCl (an activator of Wnt/ß-catenin pathway) in AGS cells. Moreover, activation of Wnt/ß-catenin pathway by LiCl or the ß-catenin overexpression inverted the effect of AC on ferroptosis and immune escape in GC cells. In vivo, AC treatment declined the tumor size and weight, the level of GPX4, SLC7A11, PD-L1 and IFN-γ, and the expression of Wnt/ß-catenin pathway. CONCLUSION: AC enhanced ferroptosis and repressed immune escape by downregulating the Wnt/ß-catenin signaling in GC.

Association between periodontitis and dental caries: a systematic review and meta-analysis.

OBJECTIVES: Recent evidence suggested a link between periodontitis (PD) and dental caries, but the trends and nature of this association remained unclear. The overall aim of this study was to critically assess the correlation of two disorders. METHODS: A comprehensive search was conducted within the PUBMED and EMBASE databases including grey literatures up to July 5th, 2023. The Newcastle-Ottawa scale was used to qualitatively evaluate the risk of bias. RESULTS: Overall, 18 studies were included. In terms of caries risk in PD patients, the prevalence of caries was increased by PD (OR = 1.57, 95%CI:1.20-2.07), both in crown (OR = 1.03, 95%CI:1.01-1.05) and root caries (OR = 2.10, 95%CI:1.03-4.29). Odds of caries were also raised by PD severity (OR moderate = 1.38, 95%CI:1.15-1.66; OR severe = 2.14, 95%CI:1.74-2.64). Besides, patients with PD exhibited a higher mean number of decayed, missing and filled teeth (DMFT) and decayed and filled root teeth (DFR) [weighted mean difference (WMD)DMFT = 0.87, 95%CI: -0.03-1.76; WMDDFR = 1.13, 95%CI: 0.48-1.78]. Likewise, patients with caries had an elevated risk of PD (OR = 1.79, 95%CI:1.36-2.35). However, Streptococcus mutans, one of the main pathogens of caries, was negatively correlated with several main pathogens of periodontitis. CONCLUSIONS: This study indicated a positive correlation between dental caries and periodontitis clinically, while the two disease-associated pathogens were antagonistic. CLINICAL RELEVANCE: Further research, including clinical cohort studies and mechanisms of pathogens interaction is needed on this link for better prevention and treatment of PD and caries. In addition, innovative prevention strategies need to be developed and incorporated in dental practices to prevent these two highly prevalent oral diseases.

Environmental specificity of karst cave habitats evidenced by diverse symbiotic bacteria in Opiliones.

BACKGROUND: Karst caves serve as natural laboratories, providing organisms with extreme and constant conditions that promote isolation, resulting in a genetic relationship and living environment that is significantly different from those outside the cave. However, research on cave creatures, especially Opiliones, remains scarce, with most studies focused on water, soil, and cave sediments. RESULTS: The structure of symbiotic bacteria in different caves were compared, revealing significant differences. Based on the alpha and beta diversity, symbiotic bacteria abundance and diversity in the cave were similar, but the structure of symbiotic bacteria differed inside and outside the cave. Microorganisms in the cave play an important role in material cycling and energy flow, particularly in the nitrogen cycle. Although microbial diversity varies inside and outside the cave, Opiliones in Beijing caves and Hainan Island exhibited a strong similarity, indicating that the two environments share commonalities. CONCLUSIONS: The karst cave environment possesses high microbial diversity and there are noticeable differences among different caves. Different habitats lead to significant differences in the symbiotic bacteria in Opiliones inside and outside the cave, and cave microorganisms have made efforts to adapt to extreme environments. The similarity in symbiotic bacteria community structure suggests a potential similarity in host environments, providing an explanation for the appearance of Sinonychia martensi in caves in the north.

How peer relationships affect academic achievement among junior high school students: The chain mediating roles of learning motivation and learning engagement.

BACKGROUND: Despite the recognition of the impact of peer relationships, learning motivation, and learning engagement on academic achievement, there is still a gap in understanding the specific mechanisms through which peer relationships impact academic achievement via learning motivation and learning engagement. METHODS: This study aims to investigate how peer relationships affect junior high school students' academic achievement through the chain mediating roles of learning motivation and learning engagement, employing the self-system model of motivational development as the theoretical framework. In January 2024, 717 participants were selected from two middle schools in eastern China (mean age = 13.49 years, SD = 0.5). The data analysis in this study was performed using the structural equation model (SEM) in AMOS 24.0 and SPSS 24.0. RESULTS: The results showed that peer relationships were directly and significantly related to junior high school students' academic achievement, and that peer relationships were indirectly and positively related to junior high school students' academic achievement via learning motivation and learning engagement respectively. The results also revealed a significant indirect and positive relationship between peer relationships and junior high school students' academic achievement, mediated by the sequential mediating roles of learning motivation and learning engagement. Moreover, the path "peer relationship→learning motivation→academic achievement" has the strongest indirect effect. CONCLUSION: For junior high school students to achieve academic success, the appropriate interventions should be implemented to improve peer relationships, learning motivation, and learning engagement.

Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS.

Osteosarcoma, a prevalent primary malignant bone tumor, often presents with lung metastases, severely impacting patient survival rates. Extracellular vesicles, particularly exosomes, play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions. However, the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure, with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown. This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site. This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate (MARCKS) expression. Addressing this phenomenon, in this study we employ cationic bovine serum albumin (CBSA) to form nanoparticles (CBSA-anta-194/215) via electrostatic interaction with antagomir-miR-194/215. These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles (anta-194/215@Exo) targeting osteosarcoma lung metastatic sites. Intervention with bioengineered exosome mimetics (anta-194/215@Exo) not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing mice. These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS, making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

Structural characterization and immune modulation activities of Chinese Angelica polysaccharide (CAP) and selenizing CAP (sCAP) on dendritic cells.

sCAP was obtained by the nitrate­sodium selenite method. SEM, molecular weight evaluation, monosaccharide composition, FT-IR and NMR of sCAP were carried out. Compared with CAP, sCAP had a relatively smooth and lamellar sheet morphology with edge folds on the surface, presented molecular weights in range of 0.90-97.08 KDa, and was mainly composed of GalA, Ara and Gal. sCAP had both α and ß configurations of the pyranose ring, the characteristic vibrational peak of Se-O-C and the signal of galacturonic acid residue. The phagocytic activity of immature BMDCs, the expression of CD40, CD80, CD86, and MHCII on BMDCs were detected by flow cytometry, the ability of sCAP-treated BMDCs to stimulate the proliferation of allogeneic lymphocytes, presentation of antigens, cytokines in the supernatants and the protein in MyD88/NF-κB signaling pathway were detected. The results showed that the phagocytic activity of immature BMDCs was significantly enhanced when sCAP was at 3.92-1.96 µg·mL-1. The levels of IL-6, TGF-ß1, INF-γ, and TNF-α were significantly elevated, IL-1ß and MIP-1α were significantly reduced. These results indicate that sCAP could be as a new immunopotentiator by increasing MyD88/NF-κB signaling pathway. This study provides a reference for the research and development of new dosage forms of polysaccharide.

Seroepidemiology of pertussis in Huzhou: A population-based, cross-sectional study.

PURPOSE: The resurgence of pertussis has occurred around the world. However, the epidemiological profiles of pertussis cannot be well understood by current diseases surveillance. This study was designed to understand the seroepidemiological characteristics of pertussis infection in the general population of Huzhou City, evaluate the prevalence infection of pertussis in the population, and offer insights to inform adjustments in pertussis prevention and control strategies. METHODS: From September to October 2023, a cross-sectional serosurvey was conducted in Huzhou City, involving 1015 permanent residents. Serum samples were collected from the study subjects, and pertussis toxin IgG antibodies (Anti-PT-IgG) were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The analysis included the geometric mean concentration (GMC) of Anti-PT-IgG, rates of GMC≥40IU/mL, ≥100IU/mL, and <5IU/mL. Stratified comparisons were made based on age, vaccination history, and human categories. RESULTS: Among the 1015 surveyed individuals, the geometric mean concentration (GMC) of Anti-PT-IgG was 10.52 (95% CI: 9.96-11.11) IU/mL, with a recent infection rate of 1.58%, a serum positivity rate of 11.43%, and a proportion with <5IU/mL of 40.49%. Among 357 children with clear vaccination history, susceptibility decreased with an increasing number of vaccine doses (Z = -6.793, P < 0.001). The concentration of Anti-PT-IgG exhibited a significant post-vaccination decline over time (Z = -5.143, P < 0.001). In women of childbearing age, the GMC of Anti-PT-IgG was 7.71 (95% CI: 6.90-8.62) IU/mL, with no significant difference in susceptibility among different age groups (χ2 = 0.545, P = 0.909). The annual pertussis infection rate in individuals aged ≥3 years was 9321 (95%CI: 3336-16039) per 100,000, with peak infection rates in the 20-29, 40-49, and 5-9 age groups at 34363 (95%CI: 6327-66918) per 100,000, 22307.72 (95%CI: 1380-47442) per 100,000, and 18020(95%CI: 1093-37266) per 100,000, respectively. CONCLUSIONS: In 2023, the actual pertussis infection rate in the population of Huzhou City was relatively high. Vaccine-induced antibodies exhibit a rapid decay, and the estimated serum infection rate increases rapidly from post-school age, peaking in the 20-29 age group. It is recommended to enhance pertussis monitoring in adolescents and adults and refine vaccine immunization strategies.

An interpretable machine learning model for predicting 28-day mortality in patients with sepsis-associated liver injury.

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction.

Himalayas is barrier for transportation of light-absorbing particles from South Asia to inner Third Pole.

Through a comprehensive investigation into the historical profiles of black carbon derived from ice cores, the spatial distributions of light-absorbing impurities in snowpit samples, and carbon isotopic compositions of black carbon in snowpit samples of the Third Pole, we have identified that due to barriers of the Himalayas and remove of wet deposition, local sources rather than those from seriously the polluted South Asia are main contributors of light-absorbing impurities in the inner part of the Third Pole. Therefore, reducing emissions from residents of the Third Pole themselves is a more effective way of protecting the glaciers of the inner Third Pole in terms of reducing concentrations of light-absorbing particles in the atmosphere and on glaciers.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Emodin inhibits respiratory syncytial virus entry by interactions with fusion protein.

Introduction: Respiratory syncytial virus (RSV) fusion (F) protein is essential for facilitating virus entry into host cells, providing a hopeful path for combating viral diseases. However, F protein inhibitors can rapidly select for viral resistance. Thus, discovering new inhibitors of F-protein is necessary to enrich the RSV drug development pipeline. Methods: In this study, we screen 25 bioactive compounds from Chinese herbal medicines that exhibit a strong binding to the RSV-F protein using surface plasmon resonance. Results: After screening, we found emodin could strongly bind to RSV-F protein, and could effectively curb RSV infection. Further investigations certificated that emodin specifically disrupts the attachment and internalization phases of RSV infection by targeting the RSV-F protein. In vivo studies with mice infected with RSV demonstrated that emodin effectively reduces lung pathology. This therapeutic effect is attributed to emodin's capacity to diminish pro-inflammatory cytokine production and reduce viral load in the lungs. Discussion: In conclusion, our findings provide initial insights into the mechanism by which emodin counters RSV infection via engagement with the RSV-F protein, establishing it as a viable contender for the development of novel therapeutic agents aimed at RSV.

Assessing the aging and environmental implications of polyethylene mulch films in agricultural land.

Polyethylene mulch films (MFs) are widely employed in agricultural land to enhance crop yield and quality, but the MF residue causes significant environmental concerns. To promote the sustainable application of MFs, it is essential to assess their fate throughout their service life and understand the underlying degradation mechanisms. In this study, surface-exposed and soil-buried MFs were separately collected from agricultural land in Inner Mongolia, China. The variations in aging performance and corresponding property alterations of MF were thoroughly examined. The results indicated that sunlight exposure considerably hastens MF degradation, whereas buried MFs experience a more moderate aging process due to the inhibitory effects of the dark and anaerobic environment on oxidation. Surface cracking was observed in MF-Light samples as a result of photodegradation, while chemical and moisture interactions with soil caused partial perforation in MF-Soil samples. Relative to the pristine MF, the oxidation, unsaturation, and hydroxylation levels of MF-Light increased to 0.88, 0.35, and 0.73, respectively, with corresponding values for MF-Soil at 0.44, 0.13, and 0.24. The generated oxygen-containing functional groups lead to a decrease in contact angles of MF-Light and MF-Soil, enhancing their hydrophilicity. The aging process of MFs led to a decline in mechanical properties, posing challenges for recycling. Moreover, nearly all phthalate esters (PAEs) were released from MFs, regardless of sunlight exposure or soil burial. The use of MFs also impacted the abundance of soil microbial communities. Specifically, the selected polyethylene MF enriched Actinobacteriota by 75%, while reducing Chloroflexi and Firmicutes by 27% and 45%, respectively.

Characterization and evaluation of actinomycete from the Protaetia brevitarsis Larva Frass.

Protaetia brevitarsis larvae (PBL) are soil insects important for the soil organic carbon cycle, and PBL frass not only contains a large amount of humic acid but also affects the diversity, novelty, and potential functions of actinomycetes. Here, we characterized and assessed the actinomycete. The operational taxonomic unit (OTU) data showed that 90% of the actinomycetes cannot be annotated to species, and pure culture and genome analysis showed that 35% of the strains had the potential to be new species, indicating the novelty of PBL frass actinomycetes. Additionally, genome annotation showed that many gene clusters related to antifungal, antibacterial and insecticidal compound synthesis were identified, and confrontation culture confirmed the antifungal activities of the actinomycetes against soil-borne plant pathogenic fungi. The incubation experiment results showed that all isolates were able to thrive on media composed of straw powder and alkaline lignin. These results indicated that PBL hindgut-enriched actinomycetes could survive in soil by using the residual lignocellulose organic matter from plant residues, and the antibiotics produced not only give them a competitive advantage among soil microflora but also have a certain inhibitory effect on plant diseases and pests. This study suggests that the application of PBL frass can not only supplement soil humic acid but also potentially affect the soil microbiota of cultivated land, which is beneficial for the healthy growth of crops.

Kaempferol efficacy in metabolic diseases: Molecular mechanisms of action in diabetes mellitus, obesity, non-alcoholic fatty liver disease, steatohepatitis, and atherosclerosis.

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.

Diversity and Functionality of Bacteria Associated with Different Tissues of Spider Heteropoda venatoria Revealed through Integration of High-Throughput Sequencing and Culturomics Approaches.

Spiders host a diverse range of bacteria in their guts and other tissues, which have been found to play a significant role in their fitness. This study aimed to investigate the community diversity and functional characteristics of spider-associated bacteria in four tissues of Heteropoda venatoria using HTS of the 16S rRNA gene and culturomics technologies, as well as the functional verification of the isolated strains. The results of HTS showed that the spider-associated bacteria in different tissues belonged to 34 phyla, 72 classes, 170 orders, 277 families, and 458 genera. Bacillus was found to be the most abundant bacteria in the venom gland, silk gland, and ovary, while Stenotrophomonas, Acinetobacter, and Sphingomonas were dominant in the gut microbiota. Based on the amplicon sequencing results, 21 distinct cultivation conditions were developed using culturomics to isolate bacteria from the ovary, gut, venom gland, and silk gland. A total of 119 bacterial strains, representing 4 phyla and 25 genera, with Bacillus and Serratia as the dominant genera, were isolated. Five strains exhibited high efficiency in degrading pesticides in the in vitro experiments. Out of the 119 isolates, 28 exhibited antibacterial activity against at least one of the tested bacterial strains, including the pathogenic bacteria Staphylococcus aureus, Acinetobacter baumanii, and Enterococcus faecalis. The study also identified three strains, GL312, PL211, and PL316, which exhibited significant cytotoxicity against MGC-803. The crude extract from the fermentation broth of strain PL316 was found to effectively induce apoptosis in MGC-803 cells. Overall, this study offers a comprehensive understanding of the bacterial community structure associated with H. venatoria. It also provides valuable insights into discovering novel antitumor natural products for gastric cancer and xenobiotic-degrading bacteria of spiders.

Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease.

Mouse models of autosomal dominant polycystic kidney disease (ADPKD) show that intact primary cilia are required for cyst growth following the inactivation of polycystin-1. The signaling pathways underlying this process, termed cilia-dependent cyst activation (CDCA), remain unknown. Using translating ribosome affinity purification RNASeq on mouse kidneys with polycystin-1 and cilia inactivation before cyst formation, we identify the differential 'CDCA pattern' translatome specifically dysregulated in kidney tubule cells destined to form cysts. From this, Glis2 emerges as a candidate functional effector of polycystin signaling and CDCA. In vitro changes in Glis2 expression mirror the polycystin- and cilia-dependent changes observed in kidney tissue, validating Glis2 as a cell culture-based indicator of polycystin function related to cyst formation. Inactivation of Glis2 suppresses polycystic kidney disease in mouse models of ADPKD, and pharmacological targeting of Glis2 with antisense oligonucleotides slows disease progression. Glis2 transcript and protein is a functional target of CDCA and a potential therapeutic target for treating ADPKD.

Leveraging Janus Substrates as a Confined "Interfacial Reactor" to Synthesize Ultrapermeable Polyamide Nanofilms.

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.