A Keggin Al13 -Montmorillonite Modified Separator Retards the Polysulfide Shuttling and Accelerates Li-Ion Transfer in Li-S Batteries.

The commercialization of Li-S batteries as a promising energy system is terribly impeded by the issues of the shuttle effect and Li dendrite. Keggin Al13 -pillared montmorillonite (AlMMT), used as the modified film of the separator together with super-P and poly (vinylidene fluoride) (PVDF), has a good chemical affinity to lithium polysulfide (LiPS) to retard the polysulfide shuttling, excellent electrolyte wettability, and a stable structure, which can improve the rate capability and cycling stability of Li-S batteries. Density function theory (DFT) calculations reveal the strong adsorption ability of AlMMT for LiPS. Consequently, the modified film allows Li-S batteries to reach 902 mAh g-1 at 0.2C after 200 cycles and 625 mAh g-1 at 1C after 1000 cycles. More importantly, a high reversible areal capacity of 4.04 mAh cm-2 can be realized under a high sulfur loading of 6.10 mg cm-2 . Combining the merits of rich resources of montmorillonite, prominent performance, simple operation and cost-effectiveness together, this work exploits a new route for viable Li-S batteries for applications.

Enoxaparin attenuates pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome by inhibiting oncostatin M expression.

BACKGROUND AND AIMS: The definitive treatment for pyrrolizidine alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS) is not available. The effectiveness of anticoagulation therapy remains controversial. The efficacy of low molecular weight heparin (LMWH) should be investigated in patients and animal models, and the underlying mechanism should be explored. METHODS: The prognosis of patients with PAs-HSOS who received anticoagulation therapy was retrospectively analysed. The effect of enoxaparin on the liver injury was determined in animal models of monocrotaline (MCT)-induced HSOS was determined, and the underlying mechanism was investigated using a murine model. RESULTS: The cumulative survival rate of patients with PAs-induced HSOS was 60.00% and 90.90% in the non-anticoagulation group and anticoagulation group. Enoxaparin attenuated liver injury effectively in a rat model of MCT-induced HSOS. Additionally, the improvement of severe liver injury was observed in MCT-treated mice after the administration of enoxaparin (40 mg/kg). The alleviation of liver injury was observed in mice with hepatocyte-specific deletion of oncostatin M (Osm△Hep ). In MCT-treated mice administrated with enoxaparin, no significant differences in liver injury were observed between Osm△Hep mice and Osmflox/flox mice. Additionally, adenovirus-mediated overexpression of Osm resulted in severe liver injury in MCT-induced mice after the administration of enoxaparin. CONCLUSIONS: LMWH attenuated severe liver injury in patients with PAs-Induced HSOS and animal models of MCT-induced HSOS, which provides a rationale for the application of anticoagulation therapy.

Association between healthy lifestyle factors and health-related quality of life among Chinese adolescents: the moderating role of gender.

BACKGROUND: To examine the associations of the independent and combined healthy lifestyle factors with health-related quality of life (HRQOL) in adolescents, and to test the moderating role of gender. METHODS: This cross-sectional study included 5125 adolescents aged between 11 and 20 years. They provided self-reported data on six healthy lifestyle factors, including never smoking, never drinking, good sleep quality, sufficient sleep duration, appropriate Internet use, and adequate physical activity. Adolescents' HRQOL was evaluated using the Pediatric Quality of Life Inventory version 4.0. Linear regression models were conducted to explore the association of individual and combined healthy lifestyle factors with adolescents' HRQOL. We further performed stratified analyses and likelihood ratio test to explore the moderating role of gender in these associations. RESULTS: Of the included adolescents, the proportions with 0-2, 3, 4, and 5-6 healthy lifestyle factors were 13.6%, 26.4%, 44.3%, and 15.7%, respectively. Compared to adolescents with composite healthy lifestyle scores of 0-2, those with scores of 3, 4, or 5-6 had significantly higher HRQOL scores across all dimensions, summary scales, and total scale in both unadjusted and adjusted models. Specifically, adolescents with 5-6 healthy lifestyle factors had a total scale score that was 19.03 (95%CI: 17.76 to 20.30) points higher than their counterparts who only had 0-2 healthy lifestyle factors. Significant dose-response patterns were also observed in aforementioned associations. Gender was a significant moderator in the associations between composite healthy lifestyle groups and HRQOL scores, except for the social functioning dimension. CONCLUSIONS: Our results confirmed that combined healthy lifestyle factors were associated with improved HRQOL among adolescents, with a stronger association observed in girls. These findings underscore the necessity for education and healthcare authorities to design health-promoting strategies that encourage multiple healthy lifestyle factors in adolescents, with the objective of enhancing their overall health outcomes.

A multicenter study on efficacy of dual-target neoadjuvant therapy for HER2-positive breast cancer and a consistent analysis of efficacy evaluation of neoadjuvant therapy by Miller-Payne and RCB pathological evaluation systems (CSBrS-026).

Objective: The aim of this study was to investigate the factors influencing pathological complete response (pCR) rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab (H) + pertuzumab (P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden (RCB) systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2 (HER2)+ breast cancer was analyzed. Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery (CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry (IHC) 3+/hormone receptor (HR)-, IHC3+/HR+, IHC2+ in situ hybridization (ISH)+/HR- and IHC2+ ISH+/HR+ groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed. Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals; 18,853 (24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target (H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate (P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0% (κ=0.717, P<0.001). Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+ breast cancer.

Associations of excessive screen time and early screen exposure with health-related quality of life and behavioral problems among children attending preschools.

BACKGROUND: Both excessive screen time and early screen exposure have been linked to children's health outcomes, but few studies considered these two exposures simultaneously. The aim of this study was to explore the independent and interactive associations of excessive screen time and early screen exposure with health-related quality of life (HRQOL) and behavioral problems among Chinese children attending preschools. METHODS: A cross-sectional study of 4985 children aged between 3 and 6 years was conducted in Chengdu, China. Each parent has finished an online questionnaire regarding their children's screen use, HRQOL, and behavioral problems. Children with screen time over 1 h/day were considered as having excessive screen time. Early screen exposure was defined if the children had started using screen-based media before the age of 2 years. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0), while behavioral problems were confirmed with the 48-item Conners' Parent Rating Scale (CPRS-48). RESULTS: Of the 4985 children (2593 boys and 2392 girls) included, the mean age was 4.6 (SD: 1.0) years. After adjustment for confounders and early screen exposure, excessive screen time was significantly associated with worse HRQOL scores in all dimensions and summary scales, as well as each type of behavioral problems (all p values < 0.05). We also found that compared to children with later initiation of screen exposure, those with screen use before the age of 2 years had significantly lower emotional functioning score (ß: - 2.13, 95%CI: - 3.17, - 1.09) and psychosocial health summary score (ß: - 0.82, 95%CI: - 1.54, - 0.10) of HRQOL, as well as higher risks of conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, and hyperactivity index, which were independent of excessive screen use. Furthermore, there were significant interactive effects of excessive screen time and early screen exposure on emotional functioning domain of HRQOL scores and conduct problems. CONCLUSION: Excessive screen time and early screen exposure are two independent and interactive factors to children's HRQOL and behavioral problems. Our findings support current guidelines to limit screen exposure in children. Appropriate screen use may represent an important intervention target to improve children's HRQOL and reduce their behavioral problems.

Combination of probiotics with different functions alleviate DSS-induced colitis by regulating intestinal microbiota, IL-10, and barrier function.

The potential of probiotics for treating ulcerative colitis (UC) has attracted increasing attention. However, more studies are still needed to guide physicians on the proper selection and use of probiotics. Here, we propose that combination of multiple probiotics with different functions can reduce intestinal inflammation. In this study, the effects of probiotics (Lactobacillus reuteri, Bacillus coagulans, Bifidobacterium longum, and Clostridium butyricum) on the physiology and histopathology of colon were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. The combined species, as well as the species individually, were tested and compared with sulfasalazine (SASP) and two Chinese herbal therapies. Results show that the functions of the four probiotic strains were different in regulating intestinal immunity and barrier function. The four-species probiotic cocktail was more effective than the species individually and anti-inflammatory drugs in repairing the dysbiosis of mucosal microbial ecology and reducing intestinal inflammation. The multi-strain probiotic mixture increased the proportion of beneficial bacteria and decreased the proportion of pro-inflammatory bacteria in the colonic mucosa. In addition, probiotic mixture significantly enhanced the expression of IL-10 and intestinal barrier function. These results suggest that a combination of multiple probiotics with different functions has synergistic effects and can restore the balance of interactions between microorganisms and immunological niches.

Clinicopathological analysis of early-stage breast cancer patients that meet indications for BRCA1/2 genetic testing.

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2 (BRCA1/2) genetic testing in China. METHODS: Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology, genetic/familial high-risk assessment: Breast and ovarian (Version 2. 2019), a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center, Peking University First Hospital between January 2008 and December 2016. Clinicopathological characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. RESULTS: A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group, accounting for 34.7% of all breast cancer patients treated in Breast Disease Center, Peking University First Hospital during the study period. Compared with breast cancer patients without indications for BRCA genetic testing, the overall survival (OS) and disease-free survival (DFS) of patients with indications were not significantly different. In the study group, patients with premenopausal status, high T stage, lymph node positive, estrogen receptor (ER) negative, Ki-67>20% and presence of a vascular tumor thrombus had worse prognosis. There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications. CONCLUSIONS: Single-center data showed that more than 30% of patients with early-stage breast cancer had indications for BRCA genetic testing. There was no prognostic difference in patients with or without indications for BRCA genetic testing. Premenopausal status, high T stage, lymph node positive, ER negative, Ki-67>20%, and presence of a vascular tumor thrombus were associated with poor prognosis.

Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet-Induced Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice.

Postfermented Pu-erh tea (PE) protects against metabolic syndrome (MS), but little is known regarding its underlying mechanisms. Animal experiments were performed to determine whether the gut microbiota mediated the improvement in diet-induced MS by PE and its main active components (PEAC). We confirmed that PE altered the body composition and energy efficiency, attenuated metabolic endotoxemia and systemic and multiple-tissue inflammation, and improved the glucose and lipid metabolism disorder in high-fat diet (HFD)-fed mice via multiple pathways. Notably, PE promoted the lipid oxidation and browning of white adipose tissue (WAT) in HFD-fed mice. Polyphenols and caffeine (CAF) played critical roles in improving these parameters. Meanwhile, PE remodeled the disrupted intestinal homeostasis that was induced by the HFD. Many metabolic changes observed in the mice were significantly correlated with alterations in specific gut bacteria. Akkermansia muciniphila and Faecalibacterium prausnitzii were speculated to be the key gut bacterial links between the PEAC treatment and MS at the genus and species levels. Interestingly, A. muciniphila administration altered body composition and energy efficiency, promoted the browning of WAT, and improved the lipid and glucose metabolism disorder in the HFD-fed mice, whereas F. prausnitzii administration reduced the HFD-induced liver and intestinal inflammatory responses. In summary, polyphenol- and CAF-rich PE improved diet-induced MS, and this effect was associated with a remodeling of the gut microbiota.

Probiotics-fermented Massa Medicata Fermentata ameliorates weaning stress in piglets related to improving intestinal homeostasis.

Weaning stress has serious negative effects on piglets' health and the swine industry. Probiotics-fermented Chinese herbal medicines are potential feed additives to ameliorate weaning stress. In this study, the effects of probiotics-fermented Massa Medicata Fermentata (MMFP) on intestinal homeostasis were evaluated in weaning piglets. Dietary supplementation with MMFP promoted the development of the intestinal structure and elevated the concentrations of lactic acid and short-chain fatty acids (SCFAs) in the intestinal contents and antioxidant capacities in serum. MMFP reduced the levels of inflammatory factors in the intestinal mucosa. Microbial community analysis demonstrated that MMFP led to the selective and progressive enrichment of lactic acid- and SCFA-producing bacteria along the gastrointestinal tract, in particular, OTUs corresponding to Lactobacillus, Streptococcus, Acetitomaculum, Roseburia, and Eubacterium xylanophilum group, while MMFP reduced the relative abundance of pathogenic bacteria. On the contrary, antibiotics had negative effects on intestinal histology and increased the relative abundance of pro-inflammatory bacterium, such as Marvinbryantia, Peptococcus, Turicibacter, and Blautia. Correlation analysis reflected that the bacteria enriched in MMFP group were positively correlated with enhanced intestinal homeostasis, which suggested that dietary supplementation with MMFP enhanced host intestinal homeostasis by modulating the composition of gut microbiota and the levels of beneficial SCFAs, thus ameliorating weaning stress in piglets.

A Sensor Based on LiCl/NaA Zeolite Composites for Effective Humidity Sensing.

LiCl/NaA zeolite composites were successfully prepared by doping 1 wt%, 2 wt%, 5 wt%, and 8 wt% of LiCl into NaA zeolite. The humidity sensing properties of LiCl/NaA composites were investigated among 11% 95% relative humidity (RH). The LiCl/NaA composites exhibited better humidity sensing properties than pure NaA zeolite. The sensor made by 2 wt% Li-doped NaA zeolite possesses the best linearly in the whole RH. These results demonstrate that the LiCl/NaA composites have the potential application in humidity sensing.

Metabolic adaptation to the aqueous leaf extract of Moringa oleifera Lam.-supplemented diet is related to the modulation of gut microbiota in mice.

The aqueous leaf extract of Moringa oleifera Lam. (LM-A) is reported to have many health beneficial bioactivities and no obvious toxicity, but have mild adverse effects. Little is known about the mechanism of these reported adverse effects. Notably, there has been no report about the influence of LM-A on intestinal microecology. In this study, animal experiments were performed to explore the relationships between metabolic adaptation to an LM-A-supplemented diet and gut microbiota changes. After 8-week feeding with normal chow diet, the body weight of mice entered a stable period, and one of the group received daily doses of 750-mg/kg body weight LM-A by gavage for 4 weeks (assigned as LM); the other group received the vehicle (assigned as NCD). The liver weight to body weight ratio was enhanced, and the ceca were enlarged in the LM group compared with the NCD group. LM-A-supplemented-diet mice elicited a uniform metabolic adaptation, including slightly influenced fasting glucose and blood lipid profiles, significantly reduced liver triglycerides content, enhanced serum lipopolysaccharide level, activated inflammatory responses in the intestine and liver, compromised gut barrier function, and broken intestinal homeostasis. Many metabolic changes in mice were significantly correlated with altered specific gut bacteria. Changes in Firmicutes, Eubacterium rectale/Clostridium coccoides group, Faecalibacterium prausnitzii, Akkermansia muciniphila, segmented filamentous bacteria, Enterococcus spp., and Sutterella spp. may play an important role in the process of host metabolic adaptation to LM-A administration. Our research provides an explanation of the adverse effects of LM-A administration on normal adult individuals in the perspective of microecology.

Extracellular Biocoordinated Zinc Nanofibers Inhibit Malignant Characteristics of Cancer Cell.

Inhibition of the heat shock proteins (HSPs) has been considered to be one of the promising strategies for cancer treatment. However, developing highly effective HSP inhibitors remains a challenge. Recent studies on the evolutionarily distinct functions between intracellular and extracellular HSPs (eHSPs) trigger a new direction with eHSPs as chemotherapeutic targets. Herein, the first engineered eHSP nanoinhibitor with high effectiveness is reported. The zinc-aspartic acid nanofibers have specific binding ability to eHSP90, which induces a decrease in the level of the tumor marker-gelatinases, consequently resulting in downregulation of the tumor-promoting inflammation nuclear factor-kappa B signaling, and finally inhibiting cancer cell proliferation, migration, and invasion; while they are harmless to normal cells. Our findings highlight the potential for cancer treatment by altering the key determinants that shape its ability to adapt and evolve using novel nanomaterials.

Causal associations between severe mental illness and sepsis: a Mendelian randomization study.

Objective: SMI (severe mental illness) has been identified as a risk factor for sepsis in observational studies; however, the causal association between them has yet to be firmly established. We conducted MR (mendelian randomization) to unveil the causal relationship between SMI and sepsis as well as sepsis mortality. Methods: GWAS (Genome-wide association) data for major depression and schizophrenia were selected as exposure. GWAS data for sepsis and sepsis mortality were selected as outcome. Genetic variants significantly associated with the exposure (P value<1x10-6) were selected as instruments. We primarily employed the IVW (inverse-variance weighted) method for analysis. Furthermore, we employed Cochrane's Q test to assess heterogeneity and the MR-Egger intercept test to identify horizontal pleiotropy. Results: We selected 108 SNPs (single nucleotide polymorphism) used to predict major depression and 260 SNPs that predicted schizophrenia. Genetically predicted major depression was suggestively linked to a higher sepsis risk (OR=1.13, 95%CI 1.02-1.26, P=0.023). In contrast, MR analysis did not find an association between schizophrenia and sepsis risk (OR=1.00, 95%CI 0.97-1.04, P=0.811). Furthermore, no significant causal evidence was found for genetically predicted SMI in sepsis mortality. Moreover, no heterogeneity and horizontal pleiotropy were detected. Conclusion: Our research revealed a suggestive association between genetically predicted major depression and an elevated risk of sepsis in individuals of European ancestry. This finding can serve as a reminder for clinicians to consider the possibility of subsequent infection and sepsis in depressive patients, which may help reduce the incidence of sepsis in individuals with depression.

SARS-CoV-2 Neutralization Assays Used in Clinical Trials: A Narrative Review.

Since the emergence of COVID-19, extensive research efforts have been undertaken to accelerate the development of multiple types of vaccines to combat the pandemic. These include inactivated, recombinant subunit, viral vector, and nucleic acid vaccines. In the development of these diverse vaccines, appropriate methods to assess vaccine immunogenicity are essential in both preclinical and clinical studies. Among the biomarkers used in vaccine evaluation, the neutralizing antibody level serves as a pivotal indicator for assessing vaccine efficacy. Neutralizing antibody detection methods can mainly be classified into three types: the conventional virus neutralization test, pseudovirus neutralization test, and surrogate virus neutralization test. Importantly, standardization of these assays is critical for their application to yield results that are comparable across different laboratories. The development and use of international or regional standards would facilitate assay standardization and facilitate comparisons of the immune responses induced by different vaccines. In this comprehensive review, we discuss the principles, advantages, limitations, and application of different SARS-CoV-2 neutralization assays in vaccine clinical trials. This will provide guidance for the development and evaluation of COVID-19 vaccines.

Lung single-cell RNA profiling reveals response of pulmonary capillary to sepsis-induced acute lung injury.

Background: Sepsis-induced acute lung injury (ALI) poses a significant threat to human health. Endothelial cells, especially pulmonary capillaries, are the primary barriers against sepsis in the lungs. Therefore, investigating endothelial cell function is essential to understand the pathophysiological processes of sepsis-induced ALI. Methods: We downloaded single-cell RNA-seq expression data from GEO with accession number GSE207651. The mice underwent cecal ligation and puncture (CLP) surgery, and lung tissue samples were collected at 0, 24, and 48 h. The cells were annotated using the CellMarker database and FindAllMarkers functions. GO enrichment analyses were performed using the Metascape software. Gene set enrichment Analysis (GSEA) and variation Analysis (GSVA) were performed to identify differential signaling pathways. Differential expression genes were collected with the "FindMarkers" function. The R package AUCell was used to score individual cells for pathway activities. The Cellchat package was used to explore intracellular communication. Results: Granulocytes increased significantly as the duration of endotoxemia increased. However, the number of T cells, NK cells, and B cells declined. Pulmonary capillary cells were grouped into three sub-clusters. Capillary-3 cells were enriched in the sham group, but declined sharply in the CLP.24 group. Capillary-1 cells peaked in the CLP.24 group, while Capillary-2 cells were enriched in the CLP.48 group. Furthermore, we found that Cd74+ Capillary-3 cells mainly participated in immune interactions. Plat+ Capillary-1 and Clec1a+ Capillary-2 are involved in various physiological processes. Regarding cell-cell interactions, Plat+ Capillary-1 plays the most critical role in granulocyte adherence to capillaries during ALI. Cd74+ Capillary cells expressing high levels of major histocompatibility complex (MHC) and mainly interacted with Cd8a+ T cells in the sham group. Conclusion: Plat+ capillaries are involved in the innate immune response through their interaction with neutrophils via ICAM-1 adhesion during endotoxemia, while Cd74+ capillaries epxressed high level of MHC proteins play a role in adaptive immune response through their interaction with T cells. However, it remains unclear whether the function of Cd74+ capillaries leans towards immunity or tolerance, and further studies are needed to confirm this.

Metabolome and microbiome analyses of the anti-fatigue mechanism of Acanthopanax senticosus leaves.

Acanthopanax senticosus leaves, widely used as a vegetable and tea, are reported to be beneficial in treating neurological disorders. At present, their anti-fatigue effect remains to be established. In this study, we analyzed the composition of the extracts from A. senticosus leaves and confirmed their antioxidant and anti-inflammatory properties at the cellular level. In mice subjected to exhaustive running on a treadmill, supplementation with A. senticosus leaf extracts enhanced exercise performance and alleviated fatigue via the reversal of exercise-induced 5-HT elevation, metabolic waste accumulation, organ damage, and glucose metabolism-related gene expression. The collective findings from microbiome and metabolomic analyses indicate that A. senticosus leaf extracts increase α-diversity, regulate microbial composition, and reverse exercise-mediated disruption of carbohydrate, creatine, amino acid, and trimethylamine metabolism. This study provides preliminary evidence for the utility of A. senticosus leaves as a promising anti-fatigue food and offers insights into the underlying mechanism.

Portulaca oleracea L. polysaccharide alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal homeostasis.

Portulaca oleracea L. (purslane) is a vegetable that contains a variety of active compounds with nutritional properties and has the potential to treat ulcerative colitis (UC). However, the mechanisms underlying the effects of Portulaca oleracea L. polysaccharide (POP) in alleviating UC remain unclear. In this study, we prepared an aqueous extract of purslane and separated a fraction with molecular weight >10 kDa using membrane separation. This fraction was used to isolate POP. The effect of POP on gut microbiota and colon transcriptome in dextran sulfate sodium-induced UC model mice was evaluated. POP treatment reduced inflammation and oxidative stress imbalance in UC mice. In addition, POP improved the intestinal barrier and regulated intestinal homeostasis. Importantly, POP was found to regulate gut microbiota, maintain the levels of retinol and short-chain fatty acids in the gut, promote the proliferation and differentiation of B cells in the colon, and increase the expression of immunoglobulin A. These results provide novel insights into the role of POP in regulating intestinal homeostasis, which should guide further development of POP as a functional food.

Internet addiction and health-related quality of life in adolescents: The mediating role of sleep disturbance.

BACKGROUND: Internet addiction (IA) has emerged as a recognized risk factor associated with impaired health-related quality of life (HRQOL) in adolescents. However, the role of sleep disturbance in this association remains unclear. This study aimed to investigate the association of IA with HRQOL in Chinese adolescents and to evaluate the potential mediating role of sleep disturbance. METHODS: A cross-sectional study was conducted among adolescents attending six randomly selected middle schools in Guangzhou, China. Adolescents self-reported their internet use using the Young Diagnostic Questionnaire. HRQOL and sleep disturbance were assessed by the Pediatric Quality of Life Inventory version 4.0 and the Pittsburgh Sleep Quality Index, respectively. Multivariate linear regression analysis was employed to assess the association between IA and HRQOL. Baron and Kenny's causal steps method was used to examine the possible mediating role of sleep disturbance. RESULTS: Of the 6473 adolescents included, 23.5% had maladaptive internet use (MIU) and 16.6% had pathological internet use (PIU). Compared to adolescents with adaptive internet use (AIU), those with IA had significantly lower scores across all HRQOL dimensions and summary scales. Mediation analysis revealed that sleep disturbance was a significant mediator. Specifically, sleep disturbance mediated 34.55% of the effects of MIU and 34.06% of the effects of PIU on the HRQOL total scale score , respectively. CONCLUSIONS: IA was associated with poorer HRQOL, indicating the needs of preventing IA in Chinese adolescents. Additionally, our findings underscored the importance of enhancing sleep quality to mitigate the adverse impact of IA on adolescents' well-being.

Crystal structure of the superfamily 1 helicase from Tomato mosaic virus.

The genomes of the Tomato mosaic virus and many other plant and animal positive-strand RNA viruses of agronomic and medical importance encode superfamily 1 helicases. Although helicases play important roles in viral replication, the crystal structures of viral superfamily 1 helicases have not been determined. Here, we report the crystal structure of a fragment (S666 to Q1116) of the replication protein from Tomato mosaic virus. The structure reveals a novel N-terminal domain tightly associated with a helicase core. The helicase core contains two RecA-like α/ß domains without any of the accessory domain insertions that are found in other superfamily 1 helicases. The N-terminal domain contains a flexible loop, a long α-helix, and an antiparallel six-stranded ß-sheet. On the basis of the structure, we constructed deletion mutants of the S666-to-Q1116 fragment and performed split-ubiquitin-based interaction assays in Saccharomyces cerevisiae with TOM1 and ARL8, host proteins that are essential for tomato mosaic virus RNA replication. The results suggested that both TOM1 and ARL8 interact with the long α-helix in the N-terminal domain and that TOM1 also interacts with the helicase core. Prediction of secondary structures in other viral superfamily 1 helicases and comparison of those structures with the S666-to-Q1116 structure suggested that these helicases have a similar fold. Our results provide a structural basis of viral superfamily 1 helicases.

Efficient soluble expression of secreted matrix metalloproteinase 26 in Brevibacillus choshinensis.

Matrix metalloproteinase 26 (MMP-26) is a novel member of the matrix metalloproteinase family with minimal domain constitution and unknown physiological function. The three-dimensional (3D) structure of the enzyme also remains to be deciphered. Previous studies show that MMP-26 may be expressed in Escherichia coli (E. coli) as inclusion bodies and re-natured with catalytic activity. However, the low re-naturation rate of this method limits its usage in structural studies. In this paper, we tried to clone, express and purify the pro form and catalytic form of MMP-26 (ProMMP-26 and CatMMP-26) in several widely used expression vectors and express the recombinant MMP-26 proteins in E. coli cells. These constructs resulted in insoluble expressions or soluble expressions of MMP-26 with little catalytic activity. We then used Brevibacillus choshinensis (B. choshinensis) as the host system for the soluble and active expression of MMP-26. The enzyme was secreted in soluble form in the supernatant of cell culture medium and purified via a two-step purification process that included Ni(2+) affinity chromatography followed by gel filtration. The yields of purified ProMMP-26 and CatMMP-26 were 12 and 18mg/L, respectively, with high purity and homogeneity. Both ProMMP-26 and CatMMP-26 showed gelatin zymography activity and the purified CatMMP-26 had high enzymatic activity against DQ-gelatin substrate. The large-scale soluble and active protein production for future structural studies of MMP-26 is thus feasible using the B. choshinensis host system.