Comprehensive pan-cancer analysis reveals that C5orf34 regulates the proliferation and mortality of lung cancer.

The gene C5orf34 exhibits evolutionary conservation among mammals, and emerging evidence suggests its potential involvement in tumor development; however, comprehensive investigations of this gene are lacking. This study aims to elucidate the functional attributes and underlying mechanisms of C5orf34 in cancer. To evaluate its clinical predictive value, we conducted an analysis of the pan-cancerous expression, clinical data, mutation, and methylation data of C5orf34. Additionally, we investigated the correlation between C5orf34 and tumor mutant load (TMB), immune cell infiltration, and microsatellite instability (MSI) through relevant analyses. Furthermore, immunohistochemical (IHC) staining was employed to validate clinical samples, while knockdown and overexpression experiments and transcriptome RNA sequencing were utilized to examine the impact of C5orf34 on LUAD cells. According to our study, C5orf34 exhibits high expression levels in the majority of malignant tumors. The upregulation of C5orf34 is governed by DNA copy number alterations and methylation patterns, and it is closely associated with patients' survival prognosis and immune characteristics, thereby holding significant clinical implications. Furthermore, IHC staining analysis, cellular experiments, and transcriptome RNA sequencing have provided evidence supporting the role of C5orf34 in modulating the cell cycle to promote LUAD proliferation, migration, and invasion. This highlights its potential as a promising therapeutic target. The findings of this investigation suggest that C5orf34 may serve as a valuable biomarker for various tumor types and represent a potential target for immunotherapy, particularly in relation to the proliferation, migration, and apoptosis of LUAD cells.

Mechanism of salidroside regulating autophagy based on network pharmacology and molecular docking.

Salidroside is a natural product of phenols with a wide range of pharmacological functions, but whether it plays a role in regulating autophagy is unclear. We systematically investigated the regulatory effect and molecular mechanism of salidroside on autophagy through network pharmacology, which provided a theoretical basis for subsequent experimental research. First, the target genes of salidroside were obtained using the Chinese Medicine System Pharmacology Database and Analysis Platform, and the target genes were converted into standardized gene names using the Uniprot website. At the same time, autophagy-related genes were collected from GeneCards, and preliminary handling of data to obtain intersecting genes. Then, the String website was used to construct a protein-protein interaction network, and to perform the Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. To observe the specific molecular mechanism by which salidroside regulates autophagy, we constructed a drug component-target genes-autophagy network. Finally, we performed molecular docking to verify the possible binding conformation between salidroside and the candidate target. By searching the database and analyzing the data, we found that 113 target genes in salidroside interact with autophagy. Salidroside regulate autophagy in relation to a number of important oncogenes and signaling pathways. Molecular docking confirmed that salidroside has high affinity with mTOR, SIRT1, and AKT1. Through network pharmacology combined with molecular docking-validated research methods, we revealed the underlying mechanism of salidroside regulation of autophagy. This study not only provides new systematic insights into the underlying mechanism of salidroside in autophagy, but also provides new ideas for network approaches for autophagy-related research.

E-Protein Inhibition in ILC2 Development Shapes the Function of Mature ILC2s during Allergic Airway Inflammation.

E-protein transcription factors limit group 2 innate lymphoid cell (ILC2) development while promoting T cell differentiation from common lymphoid progenitors. Inhibitors of DNA binding (ID) proteins block E-protein DNA binding in common lymphoid progenitors to allow ILC2 development. However, whether E-proteins influence ILC2 function upon maturity and activation remains unclear. Mice that overexpress ID1 under control of the thymus-restricted proximal Lck promoter (ID1tg/WT) have a large pool of primarily thymus-derived ILC2s in the periphery that develop in the absence of E-protein activity. We used these mice to investigate how the absence of E-protein activity affects ILC2 function and the genomic landscape in response to house dust mite (HDM) allergens. ID1tg/WT mice had increased KLRG1- ILC2s in the lung compared with wild-type (WT; ID1WT/WT) mice in response to HDM, but ID1tg/WT ILC2s had an impaired capacity to produce type 2 cytokines. Analysis of WT ILC2 accessible chromatin suggested that AP-1 and C/EBP transcription factors but not E-proteins were associated with ILC2 inflammatory gene programs. Instead, E-protein binding sites were enriched at functional genes in ILC2s during development that were later dynamically regulated in allergic lung inflammation, including genes that control ILC2 response to cytokines and interactions with T cells. Finally, ILC2s from ID1tg/WT compared with WT mice had fewer regions of open chromatin near functional genes that were enriched for AP-1 factor binding sites following HDM treatment. These data show that E-proteins shape the chromatin landscape during ILC2 development to dictate the functional capacity of mature ILC2s during allergic inflammation in the lung.

Short-term exposure to extreme temperature and outpatient visits for respiratory diseases among children in the northern city of China: a time-series study.

BACKGROUND: Although studies have indicated that extreme temperature is strongly associated with respiratory diseases, there is a dearth of studies focused on children, especially in China. We aimed to explore the association between extreme temperature and children's outpatient visits for respiratory diseases and seasonal modification effects in Harbin, China. METHODS: A distributed lag nonlinear model (DLNM) was used to explore the effect of extreme temperature on daily outpatient visits for respiratory diseases among children, as well as lag effects and seasonal modification effects. RESULTS: Extremely low temperatures were defined as the 1st percentile and 2.5th percentile of temperature. Extremely high temperatures were defined as the 97.5th percentile and 99th percentile of temperature. At extremely high temperatures, both 26 °C (97.5th) and 27 °C (99th) showed adverse effects at lag 0-6 days, with relative risks (RRs) of 1.34 [95% confidence interval (CI): 1.21-1.48] and 1.38 (95% CI: 1.24-1.53), respectively. However, at extremely low temperatures, both - 26 °C (1st) and - 23 °C (2.5th) showed protective effects on children's outpatient visits for respiratory diseases at lag 0-10 days, with RRs of 0.86 (95% CI: 0.76-0.97) and 0.85 (95% CI: 0.75-0.95), respectively. We also found seasonal modification effects, with the association being stronger in the warm season than in the cold season at extremely high temperatures. CONCLUSIONS: Our study indicated that extremely hot temperatures increase the risk of children's outpatient visits for respiratory diseases. Efforts to reduce the exposure of children to extremely high temperatures could potentially alleviate the burden of pediatric respiratory diseases, especially during the warm season.

Epidemiological survey and risk factor analysis of high-risk human papillomavirus in women in Longgang District, Shenzhen.

Objective: The objective of this study was to assess the prevalence of high-risk HPV infection in married women in Longgang District, Shenzhen, and to analyze the distribution of HPV subtypes across different age groups while identifying risk factors associated with HPV infection. Methods: 1. From January 2018 to December 2020, 209,627 married women in Longgang District were selected as study subjects, using high-risk HPV testing as the primary screening means. HPV 16 or 18 positive directly referred to colposcopy, other types positive continued liquid-based thin-layer cytology (TCT) examination, if ≥ ASCUS, referred to colposcopy, and biopsy if necessary. 2. 210 female patients who came to our hospital for HPV testing from January 2018 to December 2020 were used for the study, including 130 HPV-positive patients and 80 HPV-negative patients. The risk factors of HPV infection were studied by questionnaire. Results: The HPV infection rate in 2018 was 13.17%, including LSIL 6.87%, HSIL 3.57%, the single type infection rate was 79.83%, top5 monotypes were 52, 53, 16, 58, 81, multiple types infection rate was 20.17%, top5 multiple types were 52/ 53, 52/68, 16/52 52/58, 52/81; 2019 HPV positivity rate was 10.23%, including LSIL 5.98%, HSIL 5.81%, the monotypic infection rate was 82.5%, top5 monotypic were: 52, 16, 58, 51, 53, multi heavy sex infection rate was 17.5%, top5 multi typic were: 52/53, 52/58, 52/68, 16/52, 51/52; HPV positive rate in 2020 was 11.28%, including LSIL 6 %, HSIL 4.84%, monotypic infection rate was 79.89%, top5 monotypic were: 52, 16, 53, 58, 51, multiheavy category infection rate was 20.11%, top5 multitypic were: 52/58, 16/52, 52/68, 52/53, 51/52. 30-50 years old is the high prevalence age of HPV susceptibility, followed by 50-60 years old, and HPV52 is the most common type. 2. 210 female patients were surveyed by filling out questionnaires: Smoking history, age at first sex, age at first pregnancy, abortion, number of sexual partners, contraceptive method, bleeding during intercourse, cervicitis, vaginitis, sleeping habits, and mental status totaling 11 factors were significant between infected and control (P < .05). Dichotomous logistic regression analysis with these 11 factors as independent variables and HPV infection as dependent variable revealed that abortion (OR=2.117, 95% CI: 1.337-3.354), number of sexual partners (OR=2.562, 95% CI: 1.222-5.373), cervicitis (OR=2.873, 95% CI: 1.407-5.868), vaginitis (OR=2.413, 95% CI: 1.158-5.026) staying up late (OR=2.408, 95% CI: 1.134-5.115) and mental status (OR=3.139, 95% CI: 1.470-6.703) were six factors that were risk factors for HPV infection. Conclusion: The common HPV infection types among women in Longgang district were mainly 52, 16, 58, 53, and 51, with a predominance of a single type of infection. The positive rate and pathogenicity of HPV 52 were higher than HPV 16. Women aged 30-60 years should be included in priority screening for cervical lesions. The six factors of miscarriage, number of sexual partners, cervicitis, vaginitis, staying up late, and mental status were risk factors for HPV infection occurrence.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Kiwifruit Peel Extract Improves the Alterations in Lipid Metabolism in High-fat Diet-fed Model Rats.

Previous studies have demonstrated that the kiwifruit peel, which is usually discarded by consumers and factories, has the highest polyphenol content among all parts of the kiwifruit. To maximize the utilization of these waste resources, the aim of this study was to examine the regulatory effects of polyphenols extracted from kiwifruit peel (KPE) on lipid metabolism and investigate their underlying mechanisms. Thirty-two male Sprague‒Dawley rats were divided into four groups: those fed a normal diet, those fed a high-fat (HF) diet, and those fed a HF diet with a low dose of KPE solution (50 mg/kg) or a high dose of KPE (100 mg/kg) by gavage. The findings of the study revealed that KPE effectively reduced body weight gain and the increases in triglycerides and total cholesterol in serum induced by the HF diet (HFD). Additionally, KPE supplementation led to a significant decrease in hepatic fat accumulation, potentially by increasing hepatic oxidation abilities. Hepatic lipidomics demonstrated that KPE influenced various metabolic pathways, including linoleic acid metabolism, steroid biosynthesis, and the biosynthesis of unsaturated fatty acids in HFD-induced rats, which were associated with the downregulation of FATP2, ACC, FAS, GPAT, DGTA1, DGTA2, and PPARγ expression as well as the upregulation of AMPK, PGC-1α, CPT-1, and PPARα expression. These findings suggest that KPE has considerable regulatory effects in rats with dyslipidaemia, which may provide supporting information for the reuse of kiwifruit peel.

Expression and functional analysis of fam76b in zebrafish.

FAM76B is nuclear speckle-localized protein with a molecular weight of 39 kDa. The amino sequence of FAM76B protein is highly conserved among species, suggesting that FAM76B has important biological functions. However, the biological function of FAM76B is currently still unclear. To explore the biological function of FAM76B, we firstly used zebrafish as the experimental model to study the distribution and expression level of Fam76b. The results indicated that fam76b is highly expressed in hematopoiesis and immune systems of zebrafish by real-time quantitative PCR, in situ hybridization and Tg(fam76b: eGFP) transgenic zebrafish. Then, the fam76b gene was knocked out by CRISPR/Cas9 in zebrafish and fam76b rescue in fam76b-/- zebrafish was performed using the TOL2 transposable system. fam76b gene knockout zebrafish exhibit reduced thymus, excessive inflammatory response, and increased mortality. FAM76B was further found to be involved in regulating the development of hematopoiesis and immune system, and participate in the process of inflammatory response. Our findings in the study lay the groundwork for elucidating the function of the new molecule Fam76b and provide new insights into the development of zebrafish hematopoietic and immune system.

From waste to wealth: Innovations in organic solid waste composting.

Organic solid waste (OSW) is not only a major source of environmental contamination, but also a vast store of useful materials due to its high concentration of biodegradable components that can be recycled. Composting has been proposed as an effective strategy for recycling OSW back into the soil in light of the necessity of a sustainable and circular economy. In addition, unconventional composting methods such as membrane-covered aerobic composting and vermicomposting have been reported more effective than traditional composting in improving soil biodiversity and promoting plant growth. This review investigates the current advancements and potential trends of using widely available OSW to produce fertilizers. At the same time, this review highlights the crucial role of additives such as microbial agents and biochar in the control of harmful substances in composting. Composting of OSW should include a complete strategy and a methodical way of thinking that can allow product development and decision optimization through interdisciplinary integration and data-driven methodologies. Future research will likely concentrate on the potential in controlling emerging pollutants, evolution of microbial communities, biochemical composition conversion, and the micro properties of different gases and membranes. Additionally, screening of functional bacteria with stable performance and exploration of advanced analytical methods for compost products are important for understanding the intrinsic mechanisms of pollutant degradation.

Diagnostic performance analysis of the Integrated Care for Older People (ICOPE) screening tool for identifying decline in intrinsic capacity.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of an individual's positive attributes. The World Health Organization (WHO) recommends a two-step approach to assess IC decline among older people. The first step involves the used of the integrated care for older people (ICOPE) screening tool to identify potential issues, and the second step involves using detailed assessments for confirmation. This study aimed to assess the diagnostic performance of the ICOPE screening tool as a simple preliminary screening to identify IC decline among community-dwelling older people, which has been rarely reported in China. METHODS: This cross-sectional study included 228 community-dwelling older individuals aged ≥ 75 (mean age, 84.0 ± 4.4 years; 131 [57.5%] females) who completed the IC evaluation according to the WHO IC assessment pathway. The diagnostic performance of the ICOPE screening tool was calculated using a 2 × 2 table and a receiver operating characteristic curve. RESULTS: The proportion of possible IC decline identified by the ICOPE screening tool was 79.4%, whereas the actual IC decline assessed by the detailed assessment was 73.2%, mainly in locomotion. The ICOPE screening tool showed sensitivity and specificity of 94.6% and 62.3%, respectively, with an overall diagnostic accuracy of 86.0%. The diagnostic effectiveness of the ICOPE screening tool was 0.91 (95% confidence interval: 0.87-0.95, p = 0.020). Except for the sensory dimension, the sensitivity of the ICOPE screening tool for diagnosing impairments in each dimension of the IC was the highest in the cognition domain (100%) and the lowest in the vitality domain (51.3%), whereas the specificity was the highest in vitality (94.7%) and the lowest in cognition (55.6%). CONCLUSIONS: The ICOPE screening tool exhibits high sensitivity and can be used as an IC screening tool in community-dwelling older people. However, further improvements are needed in the vitality dimension of the ICOPE screening tool to enhance its sensitivity in identifying individuals at risk of malnutrition.

The Effect of Diabetes Management Shared Care Clinic on Glycated Hemoglobin A1c Compliance and Self-Management Abilities in Patients with Type 2 Diabetes Mellitus.

Objective: We aim to evaluate the impact of diabetes management shared care clinic (DMSCC) on glycated hemoglobin A1c (HbA1c) compliance and self-management abilities in patients with type 2 diabetes mellitus (T2DM). Methods: This study was a prospective cohort study of patients with T2DM participating in the DMSCC. At baseline and after management, the HbA1c levels were measured, the HbA1c compliance rate were calculated, and the Summary of Diabetes Self-Care Activities-6 (SDSCA-6), Diabetes Empowerment Scale-DAWN Short Form (DES-DSF), and Problem Areas in Diabetes Scale-Five-item Short Form (PAID-5) were completed. These pre- and post-management data were compared. Results: A total of 124 eligible patients were enrolled. After the diabetes management of DMSCC, the average HbA1c decreased and the HbA1c compliance rate increased significantly (P < 0.01). SDSCA-6 showed significant improvement in physical activity, glycemic monitoring, smoking (P < 0.01), and taking medication (P < 0.05). DES-DSF suggested a greater willingness to try to effectively treat diabetes (P < 0.05). PAID-5 indicated significant improvement in diabetes-related emotional distress. Conclusion: DMSCC can help patients with T2DM reduce HbA1c, increase HbA1c compliance, improve diabetes self-management behaviors, empowerment, and diabetes-related emotional distress and serve as an effective exploration and practice of diabetes self-management education and support.

Fate of antibiotic resistance genes in cultivation substrate and its association with bacterial communities throughout commercial production of Agaricus bisporus.

Animal manure is an important raw material for Agaricus bisporus production; however, it is also a reservoir for antibiotic residues, antibiotic resistance genes (ARGs), and antibiotic-resistant bacteria. Little is known about the influence of the commercial cultivation of A. bisporus on the dynamics of ARGs and the underlying mechanisms that cause their variations. In this study, we investigated the fate of 285 ARGs, 10 mobile genetic elements, and seven major categories of antibiotic residues in substrate and mushroom samples at different production phases. The results showed that commercial substrate preparation, particularly the pasteurization phase, was highly efficient in removing ARGs from the substrate. We further found that mycelium proliferation of A. bisporus contributed significantly to the removal of ARGs from the substrate and casing soil. The bacterial community is the key driver of changes in ARGs during the commercial cultivation of A. bisporus, which explained 46.67% of the variation in ARGs. Our results indicate that, despite the addition of animal manure, the risk of ARG dissemination to fruiting bodies and the environment is low. We propose that bioremediation by specific edible fungi might be a novel and promising method for scavenging antimicrobial resistance contamination from soil environment.

Comparison of the predictive value of intrinsic capacity and comorbidity on adverse health outcome in community-dwelling older adults.

OBJECTIVES: To compare the predictive value of intrinsic capacity (IC) and comorbidity on all-cause mortality and falls. METHODS: This prospective cohort study included 220 older adults (84.0±4.4 years) followed for 3 years in a community in Beijing. The methodology recommended by the World Health Organization was used to assess IC, and comorbidity was assessed by the Cumulative Illness Rating Scale for Geriatrics. RESULTS: The areas under the characteristic curve of IC and comorbidity were 0.78 vs. 0.67 (p=0.033), respectively, in predicting all-cause mortality, and 0.69 vs. 0.61 in predicting falls (p=0.032). The vitality domain impairment (odds ratio [OR]=3.28, p=0.013), and cognition domain impairment (OR=3.97, p=0.004) were significantly associated with all-cause mortality. Locomotion domain impairment (OR=2.35, p=0.010) was associated with higher fall risk. CONCLUSION: IC might be a better predictor than comorbidity in community-dwelling older adults, in which the vitality, locomotion and cognition domains should be given more attention.

Effect of food matrix on rapid detection of Vibrio parahaemolyticus in aquatic products based on toxR gene.

Vibrio parahaemolyticus has become an important public threat to human health. Rapid and robust pathogen diagnostics are necessary for monitoring its outbreak and spreading. Herein, we report an assay for the detection of V. parahaemolyticus based on recombinase aided amplification (RAA) combined with lateral flow dipstick (LFD), namely RAA-LFD. The RAA-LFD took 20 min at 36~38 â„ƒ, and showed excellent specificity. It detected as low as 6.4 fg/µL of V. parahaemolyticus in genomic DNA, or 7.4 CFU/g spiked food samples with 4 h of enrichment. The limit of detection in shrimp (Litopenaeus Vannamei), fish (Carassius auratus), clam (Ruditapes philippinarum) evidenced that sensitivity was considerably affected by the food matrix. The presence of food matrix reduced the sensitivity of spiked food samples by 10 ~ 100 times. In the filed samples detection, RAA-LFD method showed good coincidence with GB4789.7-2013 method and PCR method at rates of 90.6% and 94.1%, respectively. RAA-LFD has high accuracy and sensitivity for the detection of V. parahaemolyticus, which can serve as a model tool to meet the growing need for point-of-care diagnosis of V. parahaemolyticus.

Production of Reactive Oxygen Species via Nanobubble Water Improves Radish Seed Water Absorption and the Expression of Aquaporin Genes.

Nanobubbles (NBs) stimulate seed germination; however, the mechanism of the promotion effect of NBs remains unclear. The impact of NBs on seed water absorption was investigated; we subsequently studied the genes associated with the response of radish seeds to NB water and used RNA sequencing to generate their expression profiles, especially those of aquaporin genes. NB water significantly promoted germination. The times at which 50% of the germinating seeds achieved germination (T50) for the submerged radish seeds in NB and control water were 11.6 and 17.4 h, respectively. NB water-germinated radish seeds showed a water uptake rate coefficient that was 15% higher than that of those germinated in control water. Through GO enrichment and cluster analyses, it was evident that NB water significantly increased the level of expression of the genes associated with the following activities: oxidoreductase, peroxidase, and antioxidant. Our results demonstrated that NB water increases the water uptake rate of radish seeds via two mechanisms. The NB water-produced exogenous hydroxyl radical (•OH) increases the seed coat's water permeability and enhances cell wall loosening, and NB water increases the aquaporin gene expression level of radish seeds.

Connexin32 ameliorates epithelial-to-mesenchymal-transition in diabetic renal tubular via inhibiting NOX4.

Renal tubulointerstitial fibrosis (RIF), characterized by epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs), is the main cause of diabetic renal fibrosis. Oxidative stress plays a pivotal role in the development of diabetic RIF. Connexin32 (Cx32), prominently expressed in renal TECs, has emerged as an important player in the regulation of oxidative stress. However, the role of Cx32 in diabetic RIF has not been explored yet. Here, we showed that adenovirus-mediated Cx32 overexpression suppressed EMT to ameliorate RIF and renal function in STZ-induced diabetic mice, while knockout (KO) of Cx32 exacerbated RIF in diabetic mice. Moreover, overexpression of Cx32 inhibited EMT and the production of extra cellular matrix (ECM) in high glucose (HG) induced NRK-52E cells, whereas knockdown of Cx32 showed the opposite effects. Furthermore, we showed that NOX4, the main source of ROS in renal tubular, was down-regulated by Cx32. Mechanistically, Cx32 down-regulated the expression of PKC alpha in a carboxyl-terminal-dependent manner, thereby inhibiting the phosphorylation at Thr147 of p22phox triggered by PKC alpha, which ultimately repressed the formation of the p22phox-NOX4 complex to reduce the protein level of NOX4. Thus, we establish Cx32 as a novel target and confirm the protection mechanism in RIF.

Sialic acid-based strategies for the prevention and treatment of Helicobacter pylori infection: Emerging trends in food industry.

Approximately 50% of the world population is infected with Helicobacter pylori. Antibiotics are widely used for H. pylori infection treatment but there are drawbacks, e.g., the emergence of antibiotic-resistant bacteria. Sialic acids are a family of acylated derivatives of a nine-carbon carboxylated monosaccharide. Because sialic acid of the host cells is vital to H. pylori pathogenesis, sialic acid-guided therapies have been proposed for the prevention and treatment of H. pylori infection, including anti-adhesive therapy and site-specific delivery. This review aims to shed light on the prospects of sialic acid-based strategies in the food industry for developing functional foods with potent anti-H. pylori activity. In this work, progress on the identification of sialic acid-containing components as anti-adhesive agents against H. pylori is reviewed. The current applications of sialic acid-based delivery systems in eradicating H. pylori are discussed, including microspheres, beads, hydrogels, and nanoparticles. The challenges and future perspectives of sialic acid-guided strategies and the possibility of their applications in food industry are highlighted. Antibiotic resistance is still a major challenge and the sialic acid-based technologies have tremendous potential to be utilized to develop functional foods that hold promise to be a future trend for preventing or treating H. pylori infection.

Nano-silica embedded polydimethylsiloxane on interdigitated sensor as adhesive polymer for detecting lung cancer mutation.

Non-small cell lung cancer (NSCLC) incited by epidermal growth factor receptor (EGFR) mutation makes up ∼85% of lung cancer diagnosed and death cases worldwide. The presented study introduced an alternative approach in detecting EGFR mutation using nano-silica integrated with polydimethylsiloxane (PDMS) polymer on interdigitated electrode (IDE) sensor. A 400 µm gap-sized aluminum IDE was modified with nano-polymer layer, which was made up of silica nanoparticles and PDMS polymer. IDE and PDMS-coated IDE (PDMS/IDE) were imaged using electron microscopes that reveals its smooth and ideal sensor morphology. The nano-silica-integrated PDMS/IDE surface was immobilized with EGFR probe and target to specify the lung cancer detection. The sensor specificity was justified through the insignificant current readouts with one-base mismatch and noncomplementary targets. The sensitivity of nano-silica-integrated PDMS/IDE was examined with mutant target spiked in human serum, where the resulting current affirms the detection of EGFR mutation. Based on the slope of the calibration curve, the sensitivity of nano-silica-integrated PDMS/IDE was 2.24E-9 A M-1 . The sensor recognizes EGFR mutation lowest at 1 aM complementary mutant target; however, the detection limit obtained based on 3σ calculation is 10 aM with regression value of 0.97.

Characterization of zygotic genome activation-dependent maternal mRNA clearance in mouse.

An important event of the maternal-to-zygotic transition (MZT) in animal embryos is the elimination of a subset of the maternal transcripts that accumulated during oogenesis. In both invertebrates and vertebrates, a maternally encoded mRNA decay pathway (M-decay) acts before zygotic genome activation (ZGA) while a second pathway, which requires zygotic transcription, subsequently clears additional mRNAs (Z-decay). To date the mechanisms that activate the Z-decay pathway in mammalian early embryos have not been investigated. Here, we identify murine maternal transcripts that are degraded after ZGA and show that inhibition of de novo transcription stabilizes these mRNAs in mouse embryos. We show that YAP1-TEAD4 transcription factor-mediated transcription is essential for Z-decay in mouse embryos and that TEAD4-triggered zygotic expression of terminal uridylyltransferases TUT4 and TUT7 and mRNA 3'-oligouridylation direct Z-decay. Components of the M-decay pathway, including BTG4 and the CCR4-NOT deadenylase, continue to function in Z-decay but require reinforcement from the zygotic factors for timely removal of maternal mRNAs. A long 3'-UTR and active translation confer resistance of Z-decay transcripts to M-decay during oocyte meiotic maturation. The Z-decay pathway is required for mouse embryo development beyond the four-cell stage and contributes to the developmental competence of preimplantation embryos.

ILC Differentiation in the Thymus.

The thymus provides a microenvironment conducive to the differentiation of innate lymphoid cells (ILCs), supplying IL-7 as well as Notch ligands. Early T cell precursors also express a number of obligatory transcription factors essential for ILC differentiation. Therefore, the thymus could be a powerhouse for ILC production. However, coordinated regulation by transcription factors and T cell receptor signaling events ensure that T cell production is the dominating output of the thymus. One group of the key regulators are the basic helix-loop-helix E protein transcription factors and their inhibitors, Id proteins. When E protein activities are downregulated, T cell development is blocked and massive ILC2 production occurs in the thymus. Normally, the thymus indeed generates a small number of ILCs, mostly group 2 ILCs (ILC2s). It has been shown in vitro that ILC2s can be differentiated from multipotent early T cell progenitors (ETPs) as well as committed T cell precursors. Moreover, thymus-derived ILC precursors have been found in the blood of adult mice. They then home to peripheral tissues and undergo differentiation into distinct ILC subsets. These ILC precursors may replenish tissue ILC pools in steady state or on demand in pathophysiological conditions. Collectively, emerging evidence suggests that the thymus plays an underappreciated role in ILC homeostasis.