Investigation of spatiotemporal distribution and formation mechanisms of ozone pollution in eastern Chinese cities applying convolutional neural network.

Severe ground-level ozone (O3) pollution over major Chinese cities has become one of the most challenging problems, which have deleterious effects on human health and the sustainability of society. This study explored the spatiotemporal distribution characteristics of ground-level O3 and its precursors based on conventional pollutant and meteorological monitoring data in Zhejiang Province from 2016 to 2021. Then, a high-performance convolutional neural network (CNN) model was established by expanding the moment and the concentration variations to general factors. Finally, the response mechanism of O3 to the variation with crucial influencing factors is explored by controlling variables and interpolating target variables. The results indicated that the annual average MDA8-90th concentrations in Zhejiang Province are higher in the northern and lower in the southern. When the wind direction (WD) ranges from east to southwest and the wind speed (WS) ranges between 2 and 3 m/sec, higher O3 concentration prone to occur. At different temperatures (T), the O3 concentration showed a trend of first increasing and subsequently decreasing with increasing NO2 concentration, peaks at the NO2 concentration around 0.02 mg/m3. The sensitivity of NO2 to O3 formation is not easily affected by temperature, barometric pressure and dew point temperature. Additionally, there is a minimum [Formula: see text] at each temperature when the NO2 concentration is 0.03 mg/m3, and this minimum [Formula: see text] decreases with increasing temperature. The study explores the response mechanism of O3 with the change of driving variables, which can provide a scientific foundation and methodological support for the targeted management of O3 pollution.

Optimized administration of human embryonic stem cell-derived immunity-and-matrix regulatory cells for mouse lung injury and fibrosis.

BACKGROUND: Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. METHODS: To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. RESULTS: Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. CONCLUSION: Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.

Expected Eight-Week Prenatal Versus Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-To-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-label, Randomized Controlled Trial.

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

Evaluating the spatiotemporal land ecological changes in the Yangtze-to-Huaihe Water Diversion Project area.

As a fundamental component of human existence, land is inextricably linked to human development, and its ecological functions are closely associated with multiple sustainable development goals. This paper presents a framework for constructing and optimizing ecological function space, with the Yangtze-to-Huaihe Water Diversion Project area serving as a case study. A comprehensive land ecological index system is established, encompassing natural foundation, land degradation, land production, ecological structure, and ecological protection. An identity-discrepancy-contrary connection method is employed to investigate changes in regional land ecological functions before (2013) and during (2017, 2020, and 2022) the project's construction based on remote sensing data. The results indicated that the mean values of the land ecological index for each period were 0.1883, 0.1981, 0.2253, and 0.1370, respectively. The study calculated the connection, differences, and contradictions in the land ecological impacts across the counties, revealing a gradual decrease in differences and a growing prominence of contradictions. The land ecology of the Yangtze-to-Huaihe Water Diversion Project area is affected by the project construction, particularly within the construction area, showing an overall improvement. Most counties exhibited a trend of ecological improvement compared to the land ecology before the project's construction. However, after the project implementation, most districts demonstrated a trend of ecological deterioration. As the distance from the construction canal increases, the characteristics of each section and stage vary, generally exhibiting an exponential decrease in the land ecological index. The study highlighted the significance of enhancing the land ecological pattern, improving water quality, increasing water supply along the project, and alleviating groundwater overexploitation. The study can serve as a reference for land ecological protection and restoration in water transfer areas and river basins worldwide.

Sacituzumab govitecan in HR+HER2- metastatic breast cancer: the randomized phase 3 EVER-132-002 trial.

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+HER2-) metastatic breast cancer (mBC) in the global TROPiCS-02 study. TROPiCS-02 enrolled few Asian patients. Here we report results of SG in Asian patients with HR+HER2- mBC from the EVER-132-002 study. Patients were randomized to SG (n = 166) or chemotherapy (n = 165). The primary endpoint was met: PFS was improved with SG versus chemotherapy (hazard ratio of 0.67, 95% confidence interval 0.52-0.87; P = 0.0028; median 4.3 versus 4.2 months). OS also improved with SG versus chemotherapy (hazard ratio of 0.64, 95% confidence interval 0.47-0.88; P = 0.0061; median 21.0 versus 15.3 months). The most common grade ≥3 treatment-emergent adverse events were neutropenia, leukopenia and anemia. SG demonstrated significant and clinically meaningful improvement in PFS and OS versus chemotherapy, with a manageable safety profile consistent with prior studies. SG represents a promising treatment option for Asian patients with HR+HER2- mBC (ClinicalTrials.gov identifier no. NCT04639986 ).

Prediction of preoperative lymph-vascular space invasion and survival outcomes of cervical squamous cell carcinoma by utilizing 18F-FDG PET/CT imaging at early stage.

OBJECTIVE: To establish nomograms for predicting preoperative lymph-vascular space invasion (LVSI) and survival outcomes of cervical squamous cell carcinoma (CSCC) based on PET/CT radiomics. METHODS: One hundred and twenty-three patients with CSCC and LVSI status were enrolled retrospectively. Independent predictors of LVSI were identified through clinicopathological factors and PET/CT metabolic parameters. We extracted 1316 features from PET and CT volume of interest, respectively. Additionally, four models (PET-RS: radiomic signature of PET only; CT-RS: radiomic signature of CT only; PET/CT-RS + clinical data; PET/CT-RS: radiomic signature of PET and CT) were established to predict LVSI status. Calculation of radiomics scores of PET/CT was executed for assessment of the survival outcomes, followed by development of nomograms with radiomics (NR) or without radiomics (NWR). RESULTS: One hundred and twenty-three patients with pathologically confirmed CSCC had been categorized into two sets (training and testing sets). It was found that only maximum standardized uptake value (SUVmax) and squamous cell carcinoma antigen were independent predictors of LVSI. Meanwhile, the PET/CT-RS + clinical data outperformed the other three models in the training set [area under the curve (AUC): 0.91 vs. 0.861 vs. 0.81 vs. 0.814] and the testing set (AUC: 0.885 vs. 0.857 vs. 0.783 vs. 0.798). Additionally, SUVmax and LVSI had been demonstrated to be independent prognostic indicators for progression-free survival and overall survival. Decision curve analysis and calibration curve indicated that NRs were superior to NWRs. The survival outcomes were assessed. CONCLUSION: PET/CT-based radiomic signature nomogram enables a new method for preoperative prediction of LVSI and survival prognosis for patients with CSCC.

HyperArc radiotherapy for recurrent synovial sarcoma of infratemporal fossa: a rare case report and review of the literature.

Background: Synovial sarcoma (SS), a malignant and uncommon soft tissue sarcoma, typically manifests in the extremities and trunk. However, its occurrence in the infratemporal fossa (ITF) of the head and neck is exceedingly rare. Patients afflicted with SS in this anatomical region pose considerable challenges, as radical surgery is often difficult to undertake, leading to a high rate of postoperative recurrence. Moreover, it is often difficult to effectively control the tumor when the cancer relapses. Much of our understanding regarding SS of ITF stems from limited case reports, with a lack of established clinical guidelines for its management. There exists a significant clinical need for effective therapeutic approaches. Case Description: This case report documents a patient with SS of ITF, experiencing repeated recurrences despite undergoing multiple surgeries and chemotherapy treatments. The patient underwent HyperArc (HA) radiotherapy (RT) in conjunction with concurrent chemotherapy utilizing cisplatin, resulting in a remarkable 3-year follow-up period devoid of recurrence. Conclusions: The primary objective of this case report is to disseminate knowledge regarding this rare manifestation of SS of ITF, detailing the successful treatment strategy employed. In this case, we employed a comprehensive treatment strategy involving concurrent chemoradiotherapy based on HA. Our findings demonstrate that this approach was effective in achieving disease control and improving patient outcomes.

Rapid genome-wide profiling of DNA methylation and genetic variation using guide positioning sequencing (GPS).

Whole-genome bisulfite sequencing (WGBS) has been extensively utilized for DNA methylation profiling over the past decade. However, it has shown limitations in terms of high costs and inefficiencies. The productivity and accuracy of DNA methylation detection rely critically on the optimization of methodologies and the continuous refinements of related sequencing platforms. Here, we describe a detailed protocol of guide positioning sequencing (GPS), a bisulfite-based, location-specific sequencing technology designed for comprehensive DNA methylation characterization across the genome. The fundamental principle of GPS lies in the substitution of dCTP with 5-methyl-dCTP (5 mC) at the 3'-end of DNA fragments by T4 DNA polymerase, which protects cytosines from bisulfite conversion to preserve the integrity of the base composition. This alteration allows the 3'-end to independently facilitate genetic variation profiling and guides the 5'-end, enriched with methylation information, to align more rapidly to the reference genome. Hence, GPS enables the concurrent detection of both genetic and epigenetic variations. Additionally, we provide an accessible description of the data processing, specifically involving certain software and scripts. Overall, the entire GPS procedure can be completed within a maximum of 15 days, starting with a low initial DNA input of 100-500 ng, followed by 4-5 days for library construction, 8-10 days for high-throughput sequencing (HTS) and data analysis, which can greatly facilitate the promotion and application of DNA methylation detection, especially for the rapid clinical diagnosis of diverse disease pathologies associated with concurrent genetic and epigenetic variations.

Study on risk factors of impaired fasting glucose and development of a prediction model based on Extreme Gradient Boosting algorithm.

Objective: The aim of this study was to develop and validate a machine learning-based model to predict the development of impaired fasting glucose (IFG) in middle-aged and older elderly people over a 5-year period using data from a cohort study. Methods: This study was a retrospective cohort study. The study population was 1855 participants who underwent consecutive physical examinations at the First Affiliated Hospital of Soochow University between 2018 and 2022.The dataset included medical history, physical examination, and biochemical index test results. The cohort was randomly divided into a training dataset and a validation dataset in a ratio of 8:2. The machine learning algorithms used in this study include Extreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), Naive Bayes, Decision Trees (DT), and traditional Logistic Regression (LR). Feature selection, parameter optimization, and model construction were performed in the training set, while the validation set was used to evaluate the predictive performance of the models. The performance of these models is evaluated by an area under the receiver operating characteristic (ROC) curves (AUC), calibration curves and decision curve analysis (DCA). To interpret the best-performing model, the Shapley Additive exPlanation (SHAP) Plots was used in this study. Results: The training/validation dataset consists of 1,855 individuals from the First Affiliated Hospital of Soochow University, yielded significant variables following selection by the Boruta algorithm and logistic multivariate regression analysis. These significant variables included systolic blood pressure (SBP), fatty liver, waist circumference (WC) and serum creatinine (Scr). The XGBoost model outperformed the other models, demonstrating an AUC of 0.7391 in the validation set. Conclusions: The XGBoost model was composed of SBP, fatty liver, WC and Scr may assist doctors with the early identification of IFG in middle-aged and elderly people.

Ultrasound-Guided Glucocorticoid Injection as a Treatment for Rotator Cuff Calcific Tendinopathy: A Case Report.

Rotator cuff calcific tendinopathy (RCCT) is a common disorder of the rotator cuff causing shoulder pain and dysfunction. RCCT is characterized by calcium deposition on and around the tendons of the rotator cuff muscles. Treatment is typically conservative, consisting of anti-inflammatory drugs (NSAIDs) and physical therapy, although certain patients require more invasive treatment. If first-line treatments do not resolve the pain, second-line treatments such as glucocorticoid injections, extracorporeal shock wave therapy (ESWT), barbotage, and surgery may be considered; however, there is no gold standard treatment for these refractory cases. In this case study, a 36-year-old female patient with confirmed RCCT achieved symptom remission with ultrasound-guided methylprednisolone injection followed by adjunctive physical therapy. Ultrasonography enabled precise, targeted delivery of steroids to the calcified lesions, with near 100% resolution of deposits on repeat radiography. With additional physical therapy, the patient was completely pain-free with a full range of motion and the ability to perform daily activities. This case report demonstrates that ultrasound-guided glucocorticoid injection can be an efficacious treatment option for refractory cases of RCCT.

Forsythoside A mitigates osteoarthritis and inhibits chondrocyte senescence by promoting mitophagy and suppressing NLRP3 inflammasome via the Nrf2 pathway.

BACKGROUND: Chondrocyte senescence and inflammation are hallmarks of osteoarthritis (OA). Forsythiaside A (FTA), a phenylethanol glycoside isolated from air-dried fruits of Forsythia, has been reported to have significant anti-inflammatory and antioxidant properties. However, its protective effects against OA have not been elucidated. PURPOSE: We explored the therapeutic efficacy of FTA in inhibiting chondrocyte senescence and inflammation during OA, as well as the potential underlying mechanisms. STUDY DESIGN: This study aimed to investigate the novel mechanism of FTA in alleviating OA in both cell and animal models. METHODS: The protective effect of FTA against tert­butyl hydroperoxide-induced chondrocyte damage was assessed, and the effects of FTA on cartilage aging and OA progression were evaluated using a medial meniscus (DMM)-induced knee OA mouse model. The regulatory effects of FTA on the NLRP3 Inflammasome, mitophagy, and the PKC/Nrf2 pathway were also explored. RESULTS: In vitro, FTA improved mitochondrial function, enhanced mitophagy, suppressed NLRP3 inflammasome activation, and inhibited chondrocyte senescence; however, these chondroprotective effects were partially reversed after mitophagy inhibition, NLRP3 inflammasome activation, and Nrf2 pathway inhibition. Furthermore, we found that FTA directly interacts with Nrf2 and enhances its phosphorylation by protein kinase C (PKC). In vivo, FTA attenuated the pathological signs of knee OA in a DMM-model mouse model, which was partially reversed by ML385. CONCLUSION: FTA inhibited chondrocyte senescence and OA progression by activating the PKC-Nrf2 pathway. Thus, FTA is a potential novel therapeutic agent for OA.

Superficial ice and deep blaze: A defense strategy of the skin.

It's crucial for skin to establish efficient defense strategies. Liu et al. reveal that the transcription factor ZNF750 recruits the histone demethylase KDM1A to silence pattern recognition receptors in the outer epidermis, making their expression limited to deeper, undifferentiated keratinocytes to address threats penetrating the skin.

Phase I/II study of BMS-986156 with ipilimumab or nivolumab with or without stereotactic ablative radiotherapy in patients with advanced solid malignancies.

BACKGROUND: BMS-986156 is an agonist of the glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) and promotes increased effector T-cell activation. Combined anti-GITR, anti-programmed death-1, anti-cytotoxic T-lymphocyte-associated protein 4 antibodies and radiotherapy improve tumor control in preclinical studies. Herein we describe the results of the safety and efficacy of BMS-986156+ipilimumab or nivolumab with/without stereotactic ablative radiotherapy (SABR) in patients with advanced solid cancers (NCT04021043). METHODS: This open-label, multigroup, single-center phase I/II study enrolled patients with histologically-confirmed stage IV solid cancers resistant to standard treatments. Group 1 (G1, n=20) received four cycles of ipilimumab (3 mg/kg) plus BMS-986156 (30 mg as dose level 1 (L1) or 100 mg as dose level 2 (L2)), every 3 weeks (Q3W). Group 2 (G2, n=10) received four cycles of ipilimumab (3 mg/kg) plus BMS-986156 (dose as determined in G1, Q3W) with SABR (50 Gy/4 fx or 60-70 Gy/10 fx to liver/lung lesions. Group 3 (G3, n=20) received four cycles of nivolumab (480 mg) plus BMS-986156 (30 mg), every 4 weeks with SABR. Maintenance nivolumab could be given up to 2 years. Tumor responses were assessed every 1-3 months until progression, using immune-related response criteria. RESULTS: 50 patients were enrolled between 10/2019 and 12/2021. Patients received a median of 3 (IQR 2-4.25) initial treatment cycles. 100 mg BMS-986156 with ipilimumab was tolerated well. Five discontinued BMS-986156 with ipilimumab due to treatment-related adverse events (TRAEs), with three in G1/L1, one in G1/L2 and one in G2, respectively. 22 patients (44%) experienced Grade 1-3 TRAEs (6, 4, 5, 7 patients for G1/L1, G1/L2, G2, G3). Six (12%) had Grade 3 TRAEs (2, 2, 1, 1 for G1/L1, G1/L2, G2, G3), with elevated alanine aminotransferase (n=3, in G1/L2, G2 and G3) and aspartate aminotransferase (n=2, in G2 and G3) being the most common. There was no Grade 4-5 TRAEs. Overall, 19/39 (48.7%) patients eligible for efficacy analysis had stable disease and 3 (7.7%) achieved a partial response. Out-of-field (abscopal) disease control rate (ACR) and out-of-field (abscopal) response rate (ARR) were 38.5% and 7.7%, respectively, with the highest ACR (50%, 9/18) and ARR (11.1%, 2/18) in G3. CONCLUSIONS: BMS-986156 was well-tolerated with ipilimumab, nivolumab, with or without SABR. Outcomes were encouraging in this population, as more than half of patients had stable disease/partial response.

MIR937 amplification potentiates ovarian cancer progression by attenuating FBXO16 inhibition on ULK1-mediated autophagy.

High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological cancer. Genetic studies have revealed gene copy number alterations (CNAs) frequently occurred in HGSOC pathogenesis, however the function and mechanism of CNAs for microRNAs are still not fully understood. Here, we show the dependence on gene copy number amplification of MIR937 that enhances cell autophagy and dictates HGSOC proliferative activity. Data mining of TCGA database revealed MIR937 amplification is correlated with increased MIR937 expression and cell proliferation of HGSOC. Deletion of MIR937 in HGSOC cells led to impaired autophagy and retarded cell proliferation, and the extent for its inhibitory effects scaled with the degree of MIR937 copy loss. Rescue assay confirmed miR-937-5p, a mature product of MIR937, was sufficient to restore its oncogenic function. Mechanistically, MIR937 amplification raised the expression of miR-937-5p, enhanced its binding to 3' UTR of FBXO16 transcript, and thereby restricting FBXO16 degradative effects on ULK1. Our results demonstrate that MIR937 amplification augments cell autophagy and proliferation, and suggest an alternative strategy of MIR937/FBXO16/ULK1 targeting for HGSOC treatment.

Strain-dependent glutathionylation of fibronectin fibers impacts mechano-chemical behavior and primes an integrin switch.

The extracellular matrix (ECM) is a protein polymer network that physically supports cells within a tissue. It acts as an important physical and biochemical stimulus directing cell behaviors. For fibronectin (Fn), a predominant component of the ECM, these physical and biochemical activities are inextricably linked as physical forces trigger conformational changes that impact its biochemical activity. Here, we analyze whether oxidative post-translational modifications, specifically glutathionylation, alter Fn's mechano-chemical characteristics through stretch-dependent protein modification. ECM post-translational modifications represent a potential for time- or stimulus-dependent changes in ECM structure-function relationships that could persist over time with potentially significant impacts on cell and tissue behaviors. In this study, we show evidence that glutathionylation of Fn ECM fibers is stretch-dependent and alters Fn fiber mechanical properties with implications on the selectivity of engaging integrin receptors. These data demonstrate the existence of multimodal post-translational modification mechanisms within the ECM with high relevance to the microenvironmental regulation of downstream cell behaviors.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer.

BACKGROUND: Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer. AIM: To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research. METHODS: We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins. RESULTS: XJZ mainly regulates IL6, PTGS2, CCL2, MMP9, MMP2, HMOX1, and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6, PTGS2, MMP9, MMP2, and CCL2, and an increase in the mRNA expression of HOMX1. XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein. CONCLUSION: XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Effects of breast-fed infants-derived Limosilactobacillus reuteri and Bifidobacterium breve ameliorate DSS-induced colitis in mice.

Studies have shown that breastfeeding can reduce the risk and severity of inflammatory bowel disease (IBD) in children and adults. Probiotics in breast milk have also been isolated and their effects on IBD have been studied. However, based on current evidence, the exact efficacy and mechanisms of probiotics in the treatment of IBD cannot be determined. In this study, Bifidobacterium breve FPHC4024 (BB FPHC4024) and Limosilactobacillus reuteri FPHC2951 (LR FPHC2951) were isolated from feces of exclusively breastfed healthy infants and administered by gavage to dextran sulfate sodium (DSS)-induced IBD mice. The results showed that LR FPHC2951 improved the symptoms of DSS-induced IBD, increased the expression of interleukin (IL)-10 mRNA and upregulated the abundance of Verrucomicrobiaceae Akkermansia. Combined with Kyoto Encyclopedia of Genes and Genomes (KEGG)-based Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) function prediction results, we hypothesized that LR FPHC2951 improved DSS-induced colitis symptoms in mice by increasing of IL-10 mRNA, altering the structure of intestinal flora, and reducing proinflammatory pathways and enhancing pathways associated with anti-inflammatory and intestinal protection.

Nuclear envelope budding inhibition slows down progerin-induced aging process.

Progerin causes Hutchinson-Gilford progeria syndrome (HGPS), but how progerin accelerates aging is still an interesting question. Here, we provide evidence linking nuclear envelope (NE) budding and accelerated aging. Mechanistically, progerin disrupts nuclear lamina to induce NE budding in concert with lamin A/C, resulting in transport of chromatin into the cytoplasm where it is removed via autophagy, whereas emerin antagonizes this process. Primary cells from both HGPS patients and mouse models express progerin and display NE budding and chromatin loss, and ectopically expressing progerin in cells can mimic this process. More excitingly, we screen a NE budding inhibitor chaetocin by high-throughput screening, which can dramatically sequester progerin from the NE and prevent this NE budding through sustaining ERK1/2 activation. Chaetocin alleviates NE budding-induced chromatin loss and ameliorates HGPS defects in cells and mice and significantly extends lifespan of HGPS mice. Collectively, we propose that progerin-induced NE budding participates in the induction of progeria, highlight the roles of chaetocin and sustained ERK1/2 activation in anti-aging, and provide a distinct avenue for treating HGPS.

Unveiling the Dynamic Mechanism of SARS-CoV-2 Entry Host Cells at the Single-Particle Level.

Understanding the dynamic features of severe acute respiratory coronavirus 2 (SARS-CoV-2) binding to the cell membrane and entry cells is crucial for comprehending viral pathogenesis and transmission and facilitating the development of effective drugs against COVID-19. Herein, we employed atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) to study the binding dynamics between the virus and cell membrane. Our findings revealed that the Omicron variant of SARS-CoV-2 virus-like particles (VLPs) exhibited a slightly stronger affinity for the angiotensin-converting enzyme-2 (ACE2) receptor compared with the Delta variant and was significantly higher than the wild-type (WT). Using a real-time force-tracing technique, we quantified the dynamic parameters for a single SARS-CoV-2 VLP entry into cells, showing that approximately 200 ms and 60 pN are required. The parameters aligned with the analysis obtained from coarse-grained molecular dynamics (CGMD) simulations. Additionally, the Omicron variant invades cells at a higher entry cell speed, smaller force, and higher probability. Furthermore, single-particle fluorescence tracking visually demonstrated clathrin-dependent endocytosis for SARS-CoV-2 entry into A549 cells. The dynamic features of endocytosis provide valuable insights into the SARS-CoV-2 entry mechanism and possible intervention strategies targeting the viral infection process.

Stability, Inheritance, Cross-Resistance, and Fitness Cost of Resistance to λ-Cyhalothrin in Cydia pomonella.

Insecticides are commonly utilized in agriculture and forestry for pest control, but their dispersal can pose hazards to humans and environment. Understanding resistance, inheritance patterns, and fitness costs can help manage resistance. A λ-cyhalothrin-resistant population (LCR) of Cydia pomonella, a global pest of pome fruits and walnuts, was obtained through selective insecticide breeding for 15 generations, showing stable moderate resistance (23.85-fold). This population was cross-resistant to deltamethrin (4.26-fold) but not to ß-cypermethrin, chlorantraniliprole, chlorpyrifos, and avermectin. Genetic analysis revealed the resistance was autosomal, incompletely dominant, and controlled by multiple genes. Increased activity of glutathione S-transferases and cytochrome P450 monooxygenases (P450s) played a primary role in resistance, with specific genes up-regulated in LCR, and exhibited significant expression in midgut. LCR also exhibited fitness costs, including delays in development, reduced fecundity, and slower population growth. These findings contribute to understanding λ-cyhalothrin resistance in C. pomonella and can guide resistance management strategies.