Diosmetin-7-O-ß-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Association of weight change with all-cause and cause-specific mortality: an age-stratified analysis.

BACKGROUND: The associations of weight change with all-cause and cause-specific mortality stratified by age remains unclear. We evaluated the age-stratified (< 65 vs ≥ 65 years) associations of weight change with all-cause and cause-specific mortality in a large sample of Chinese adults. METHODS: Our cohort study included 746,991 adults aged at least 45 years from the Shenzhen Healthcare Big Data Cohort in China. BMI change were categorized as change within 5% (stable), decrease by 5% to 10%, decrease by > 10%, increase by 5% to 10%, and increase by > 10%. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, non-communicable disease, cardiovascular disease (CVD), and cancer mortality according to BMI change, with adjustment for potential confounders. RESULTS: During a median follow-up of 2.2 years (2,330,180 person-years), there were 10,197 deaths. A notable interaction emerged between weight change and age. For participants ≥ 65 years, compared with stable BMI, more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.69, 95% CI: 1.54-1.86), non-communicable disease mortality (HR: 1.67, 95% CI: 1.52-1.84), CVD mortality (HR: 1.55, 95% CI: 1.34-1.80), and cancer mortality (HR: 1.59, 95% CI: 1.33-1.92). Similar patterns of results for 5% to 10% decrease in BMI were observed. More than a 10% increase in BMI was associated with increased risk of all-cause mortality (HR: 1.13, 95% CI: 1.04-1.24), non-communicable disease mortality (HR: 1.14, 95% CI: 1.04-1.25), and CVD mortality (HR: 1.27, 95% CI: 1.12-1.44). For participants < 65 years, only more than a 10% decrease in BMI was associated with higher risk of all-cause mortality (HR: 1.41, 95% CI: 1.12-1.77), non-communicable disease mortality (HR: 1.43, 95% CI: 1.13-1.81), and cancer mortality (HR: 1.79, 95% CI: 1.29-2.47). CONCLUSIONS: Weight loss and excessive weight gain were associated with increased risks of mortality among older adults, while only excessive weight loss was associated with increased risks of mortality among middle-aged adults.

Using syringe filtration after lab-scale adsorption processes potentially overestimates PFAS adsorption removal efficiency from non-conventional irrigation water.

The adsorption process, known for its cost-effectiveness and high efficiency, has been extensively investigated at the laboratory scale for removing per- and polyfluoroalkyl substances (PFAS) from non-conventional irrigation water. However, a syringe filtration step is commonly used when quantifying PFAS removal during this adsorption process, potentially leading to PFAS retention onto the filters and an overestimate of adsorption removal efficiency. Here, we assessed the retention of three prevalent PFAS (i.e., perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], and perfluorobutanoic acid [PFBA]) on six syringe filters. When filtering distilled deionized water spiked with 1 µg/L and 100 µg/L of each PFAS, we observed the highest and lowest PFAS recovery percentages by mixed cellulose ester (MCE) (0.20 µm, 25 mm; 97 ± 11%, 101 ± 4.8%) and polytetrafluoroethylene (0.45 µm, 13 mm; 61 ± 37%, 80 ± 28%), respectively. Under the initial concentration of 1 µg/L and 100 µg/L, PFOS had recovery percentages of 55 ± 25% and 68 ± 24%, significantly lower than 96 ± 12% and 99 ± 5% for PFOA and 95 ± 8% and 97 ± 4% for PFBA, highlighting the importance of PFAS functional groups. PFAS recovery percentage increased with filtration volume in the order of 80 ± 28% (1 mL) < 85 ± 21% (5 mL) < 90 ± 18% (10 mL). Using MCE to filter treated municipal wastewater spiked with 1 µg/L and 100 µg/L of each PFAS, we found recovery percentages >90% for all three PFAS. Our study underscores the significance of syringe filter selection and potential overestimate of PFAS removal efficacy by the lab-scale adsorption processes.

Facilely Achieving Near-Infrared-II J-Aggregates through Molecular Bending on a Donor-Acceptor Fluorophore for High-Performance Tumor Phototheranostics.

Constructing J-aggregated organic dyes represents a promising strategy for obtaining biomedical second near-infrared (NIR-II) emissive materials, as they exhibit red-shifted spectroscopic properties upon assembly into nanoparticles (NPs) in aqueous environments. However, currently available NIR-II J-aggregates primarily rely on specific molecular backbones with intricate design strategies and are susceptible to fluorescence quenching during assembly. A facile approach for constructing bright NIR-II J-aggregates using prevalent donor-acceptor (D-A) molecules is still lacking. In this study, we present a facile method that transforms D-A molecules into J-aggregates by simply bending the molecule through introducing a methyl group, enabling high-performance NIR-II phototheranostics. The TAA-BT-CN molecule exhibits hypsochromic-shift absorption upon forming H-aggregated NPs, while the designed mTAA-BT-CN with a bent structure demonstrates a bathochromic shift of over 100 nm in absorption upon forming J-aggregated NPs, leading to much enhanced NIR-II emission beyond 1100 nm. With respect to its H-aggregated counterpart with the aggregation-caused quenching (ACQ) phenomenon, the J-aggregated mTAA-BT-CN NPs exhibit a 7-fold increase in NIR-II fluorescence owing to their aggregation-induced emission (AIE) property as well as efficient generation of heat and reactive oxygen species under 808 nm light excitation. Finally, the mTAA-BT-CN NPs are employed for whole-body blood vessel imaging using NIR-II technology as well as imaging-guided tumor phototherapies. This study will facilitate the flourishing advancement of J-aggregates based on prevalent D-A-type molecules.

Responsiveness of anti-VEGF treatment for polypoidal choroidal vasculopathy based on aqueous humour proteomics: A preliminary study.

OBJECTIVES: Patients with polypoidal choroidal vasculopathy (PCV) exhibit variability in response to anti-VEGF therapy. This study aimed to analyse the aqueous humour proteomic profiles of PCV patients and provide preliminary insights for the identification of biomarkers associated with anti-VEGF drug responsiveness. METHODS: PCV patients who were treatment-naïve or untreated for more than 3 months were prospectively recruited from two hospitals in Beijing and Tianjin. Based on the relative changes in central macular thickness (ΔCMT/baseline-CMT) before and after anti-VEGF treatment, the PCV patients were divided into a good response (GR) group (≤-25%) and a poor response (PR) group (>-25%). Aqueous humour proteomics was performed by the Data-independent Acquisition-Mass Spectrometry (DIA-MS) method, and differentially expressed proteins (DEPs) analysis between the different PCV groups and the control group was conducted. Key DEPs were selected for preliminary validation in the aqueous humour using the Luminex method retrospectively. RESULTS: A total of 31 PCV patients (31 eyes) were included, 13 in the GR group and 18 in the PR group. A total of 414 DEPs were identified, including 36 significantly upregulated proteins, such as G protein regulatory factor 10 (RGS10), podocin (PODN) and epidermal growth factor (EGF), and 32 downregulated proteins, including RAB11FIP4 (Rab11 family-interacting protein 4), α-synuclein (SNCA), haemoglobin subunit δ (HBD) and interleukin 6 (IL6). Compared to the cataract control group (10 eyes), 134 proteins were significantly upregulated, and 72 were downregulated. KEGG pathway enrichment analysis revealed that the GR and PR groups differ in terms of cell communication, and cell signal transduction. Protein-protein interaction analysis revealed interactions between EGF and various DEPs. Validation of aqueous humour proteins using the Luminex method revealed that changes in the levels of EGF were associated with the anti-VEGF treatment response in PCV patients. CONCLUSIONS: PCV patients with good or poor anti-VEGF responses exhibit distinct aqueous humour proteomic profiles. Aqueous EGF may serve as a biomarker for the 'precise treatment' of PCV.

Pre-transplantation levels of lysine (K)-specific methyltransferase 2A (KMT2A) partial tandem duplications can predict relapse of acute myeloid leukemia patients following haploidentical donor hematopoietic stem cell transplantation.

We aimed to identify dynamic changes of lysine (K)-specific methyltransferase 2A partial tandem duplications (KMT2A-PTD) before and after haploidentical donor hematopoietic stem cell transplantation (HID HSCT) and explore the prognostic value of pre-transplantation levels of KMT2A-PTD in acute myeloid leukemia (AML) receiving HID HSCT. Consecutive 64 AML patients with KMT2A-PTD positivity at diagnosis receiving HID HSCT were included in this study. Patients with KMT2A-PTD ≥1% before HSCT had a slower decrease of KMT2A-PTD after HID HSCT. Patients with KMT2A-PTD ≥1% before HID HSCT had a higher cumulative incidence of relapse (36.4%, 95% confidence interval [CI]: 6.3%-66.5%) at 2 years after HSCT than those with KMT2A-PTD <1% (7.5%, 95% CI: 0.3%-14.7%, P = .010). In multivariable analysis, KMT2A-PTD ≥1% before HID HSCT was the only independent risk factor for relapse (hazard ratio [HR]: 4.90; 95% CI: 1.22-19.59; P = .025). Thus, pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.

A Biocompatible, Highly Sensitive, and Non-Enzymatic Glucose Electrochemical Sensor Based on a Copper-Cysteamine (Cu-Cy)/Chitosan-Modified Electrode.

A biocompatible, highly sensitive, and enzyme-free glucose electrochemical sensor was developed based on a copper-cysteamine (Cu-Cy)-modified electrode. The catalytically active biocompatible material Cu-Cy was immobilized on the electrode surface by the natural polymer chitosan (CTS). The electrochemical characterization and glucose response of the Cu-Cy/CTS/glassy carbon electrode (GCE) were investigated by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and constant potential amperometry. The significant electrocatalytic activity of Cu-Cy to the oxidation of glucose in an alkaline environment was revealed. Several crucial parameters, including the number of scanning cycles for electrode activation, applied potential, and the contents of Cu-Cy and chitosan, were investigated to understand their impact on the sensor's response. The proposed sensing platform exhibited linear ranges of 2.7 µM to 1.3 mM and 1.3 mM to 7.7 mM for glucose detection, coupled with high sensitivity (588.28 and 124.42 µA·mM-1·cm-2), and commendable selectivity and stability. Moreover, a Cu-Cy/CTS-modified screen-printed electrode (SPE) was further developed for portable direct detection of glucose in real samples.

Dapagliflozin suppressed gastric cancer growth via regulating OTUD5 mediated YAP1 deubiquitination.

Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.

Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics.

Nicotine is widely recognized as the primary contributor to tobacco dependence. Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area (VTA) neurons, and accumulating evidence suggests that glia play prominent roles in nicotine addiction. However, VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration. Here, a male mouse model of nicotine self-administration was established and the timing of three critical phases (pre-addiction, addicting, and post-addiction phase) was characterized. Single-nucleus RNA sequencing (snRNA-seq) in the VTA at each phase was performed to comprehensively classify specific cell subtypes. Adaptive changes occurred during the addicting and post-addiction phases, with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacted the transcription in each cell subtype. Furthermore, significant transcriptional changes in energy metabolism-related genes were observed, accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration. The results provide insights into mechanisms underlying the progression of nicotine addiction, serving as important resource for identifying potential molecular targets for nicotine cessation.

Hepatocellular carcinoma-specific epigenetic checkpoints bidirectionally regulate the antitumor immunity of CD4 + T cells.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with significant global health implications. The role of CD4+ T cells, particularly conventional CD4+ T cells (Tconvs), in HCC progression remains unexplored. Furthermore, epigenetic factors are crucial in immune regulation, yet their specific role in HCC-infiltrating Tconv cells remains elusive. This study elucidates the role of MATR3, an epigenetic regulator, in modulating Tconv activity and immune evasion within the HCC microenvironment. Reanalysis of the scRNA-seq data revealed that early activation of CD4+ T cells is crucial for establishing an antitumor immune response. In vivo and in vitro experiments revealed that Tconv enhances cDC1-induced CD8+ T-cell activation. Screening identified MATR3 as a critical regulator of Tconv function, which is necessary for antitumour activity but harmful when overexpressed. Excessive MATR3 expression exacerbates Tconv exhaustion and impairs function by recruiting the SWI/SNF complex to relax chromatin in the TOX promoter region, leading to aberrant transcriptional changes. In summary, MATR3 is an HCC-specific epigenetic checkpoint that bidirectionally regulates Tconv antitumour immunity, suggesting new therapeutic strategies targeting epigenetic regulators to enhance antitumour immunity in HCC.

MATR3 promotes liver cancer progression by suppressing DHX58-mediated type I interferon response.

MATR3 is a nuclear matrix protein implicated in various cancers; however, its specific role in tumor progression remains unclear. The study utilized the TCGA database to reveal that MATR3 expression is upregulated in liver cancer and is correlated with poor prognosis. Functionally, MATR3 promoted liver cancer cell proliferation and metastasis. Comprehensive RNA sequencing analysis showed that MATR3 significantly affected the type I IFN signaling pathway and DHX58 is a downstream target of MATR3. Further experiments showed that MATR3 bound to DHX58 mRNA through its RRM structural domain and recruited YTHDF2, an m6A reader, leading to degradation of DHX58 mRNA and suppression of the type I IFN signaling pathway. The knockout of MATR3 in liver cancer cells triggered a natural immune response that stimulated CD8+ T cells to eliminate liver cancer cells. This study demonstrated that MATR3 downregulates type I IFN signaling in liver cancer cells through m6A modification and inhibits immune cell infiltration within tumors. These findings expand our understanding of the role of MATR3 in liver cancer.

A single dose of recombinant adenoviral vector rabies vaccine expressing two copies of glycoprotein protects mice from lethal virus challenge.

INTRODUCTION: Rabies is a fatal infectious disease, that poses a major public health threat in developing countries. With an annual death toll of approximately 59,000, more than half of which are children, an urgent need exists for a safe, affordable, and effective preventive measure against rabies virus infection. METHODOLOGY: A recombinant rabies vaccine called Ad5-dRVG was constructed by introducing two copies of the rabies virus glycoprotein into a human adenoviral vector. Virus-neutralizing assays and virus challenge experiments were employed to evaluate the Ad5-dRVG vaccine. RESULTS: Our findings demonstrate that a single dose of Ad5-dRVG, administered either intramuscularly or orally, elicited significantly stronger immune responses than Ad5-RVG. Moreover, both vaccines provided complete protection in mice. Notably, the vaccine exhibited remarkable efficacy even at low doses, suggesting potential cost reduction in production. CONCLUSIONS: The development of the Ad5-dRVG recombinant rabies vaccine represents a significant advancement in rabies prevention. Its enhanced immunogenicity, demonstrated efficacy and potential cost savings make it a promising candidate for widespread use.

Pogostemon cablin essential oil as feed additive promotes the repair of the rumen epithelial barrier in heat-stressed beef cattle.

Pogostemon cablin essential oil (PEO), extracted from P. cablin, has anti-oxidant, anti-inflammatory, and anti-stress properties, as well as the ability to improve gastrointestinal digestion. This study aims to evaluate the effects of PEO on the performance, rumen epithelial morphology, and barrier function in heat-stressed beef cattle. Thirty-six male Jingjiang cattle at 18 months old were randomly assigned into four groups and fed a diet containing PEO at 0 (control), 50, 100, or 150 mg/kg in the feed concentrate (n = 9). All experimental cattle were fed under high temperature and humidity in summer for 60 days. The results indicated that 50 mg/kg of PEO treatment enhanced the average daily gain of beef cattle compared with the control group (P = 0.032). All PEO treatments reduced the diamine oxidase activity (P = 0.004) and malondialdehyde content (P = 0.008) in serum. In addition, the content of 70 kDa heat shock protein in the 100 mg/kg group was increased, and the activity of glutathione peroxidase and total antioxidant capacity in both 100 mg/kg and 150 mg/kg groups were enhanced compared to the control group (P < 0.05). More importantly, PEO treatment with 50 mg/kg enhanced the mRNA relative expressions of occludin in ruminal epithelia but decreased the mRNA relative expressions of c-Jun N-terminal kinase, P38 mitogen-activated protein kinases, caspase-3, Beclin1 (P < 0.05), and extremely significant declined the mRNA relative expressions of extracellular regulated protein kinases and ubiquitin-binding protein in contrast to the control group (P < 0.01). These findings indicated that dietary PEO supplementation might be favorable to improve growth performance and repairing damaged rumen epithelium of heat-stressed cattle by down-regulating the mitogen-activated protein kinase signaling pathway.

Effective Synthesis of C20-epi-Isothiocyanato-Salinomycin and Its Thiourea Derivatives as Potential Anticancer Agents.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, Hela, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner.

Long-Term Outcomes of Esophageal Squamous Neoplasia with Muscularis Mucosa Involvement after Endoscopic Submucosal Dissection.

Ambiguity exists over treatment and surveillance strategies after endoscopic submucosal dissection (ESD) for esophageal squamous cell neoplasia (ESCN) with unfavorable histologic features. This study investigated the long-term outcomes of ESD in high-risk ESCN patients. We retrospectively included early ESCN patients treated with ESD at two medical centers in Taiwan between August 2010 and December 2023. Demographic, endoscopic and pathological data were collected. Among 146 patients (mean age 59.17 years) with 183 lesions, 73 (50%) had a history of head and neck cancer (HNC). En bloc and R0 resections were achieved in 100% and 95.6% of the lesions, respectively. The 5-year overall survival (OS), disease-specific survival (DSS) and local recurrence rates were 42.7%, 94.7% and 11%. R0 resections were significantly associated with recurrence in a univariate analysis (HR: 0.19, 95% CI: 0.06-0.66, p = 0.008). Alcohol abstinence was independently associated with lower recurrence (HR: 0.34, 95% CI: 0.16-0.73, p = 0.006). Patients with pT1a-MM (muscularis mucosa invasion) had comparable OS (p = 0.82), DSS (p = 0.617) and recurrence (p = 0.63) rates to those with pT1a-EP/LPM (epithelium/lamina propria invasion). The long-term outcomes of ESCN patients after ESD for expanded indications were satisfactory. ESD could be considered in selected ESCN patients involving the muscularis mucosa, notably among high-risk HNC patients.

ALDH1A1 promotes immune escape of tumor cells through ZBTB7B-glycolysis pathway.

The primary impediment to the success of immunotherapy lies in the immune evasion orchestrated by tumors, contributing to the suboptimal overall response rates observed. Despite this recognition, the intricacies of the underlying mechanisms remain incompletely understood. Through preliminary detection of clinical patient tissues, we have found that ALDH1A1 was a key gene for the prognosis of cancer patients and tumor glycolysis. In vitro experiments and tumor formation in nude mice suggested that targeting ALDH1A1 could inhibit tumor growth. Through further analysis of xenograft tumor models in immune-normal mice and flow cytometry, we found that deficiency in ALDH1A1 could promote immune system suppression of tumors in vivo. Specifically, RNA-seq analysis, combined with qPCR and western blot, identified the transcription factor ZBTB7B as downstream of ALDH1A1. The binding sites of the transcription factor ZBTB7B on the LDHA promoter region, which is responsible for regulating the rate-limiting enzyme gene LDHA in glycolysis, were determined using luciferase reporter gene detection and Chip-qPCR, respectively. In addition, the increased SUMOylation of ZBTB7B stabilized its transcriptional activity. Further in vivo and in vitro experiments confirmed that the combination of targeting ALDH1A1 and ZBTB7B with immune checkpoint inhibitors could synergistically inhibit tumors in vivo. Finally, after conducting additional verification of patient tissue and clinical data, we have confirmed the potential translational value of targeting ALDH1A1 and ZBTB7B for tumor immunotherapy. These results emphasize the potential translational significance of targeting ALDH1A1 and ZBTB7B in the realm of tumor immunotherapy. The convergence of ALDH1A1 inhibition and immune checkpoint blockade, particularly with PD-L1/PD-1 mAb, presents a compelling avenue for curtailing tumor immune escape.

Effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women: a meta-analysis.

BACKGROUND: The bone status of postmenopausal women is worsening. In fact, postmenopausal period is the high incidence stage of osteoporosis and falls. Notably, a recent study has pointed out that exercise can improve bone health in postmenopausal women. However, the effect of Tai Chi exercise on postmenopausal women is controversial. Therefore, a meta-analysis was designed to analyze the effect of Tai Chi exercise on bone health and fall prevention in postmenopausal women. METHODS: The researches on Tai Chi improving the bone health of postmenopausal women before August 31, 2023 were collected from Chinese and English databases, such as PubMed, Embase, and Web of Science, etc. The risk of bias of the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials. Besides, R software 4.3.1 was employed to analyze the effect sizes in the meta-analysis to summarize the impact of Tai Chi on vertebral bone mineral density, serum calcium, clinical balance scores, the number of falls, total falls, and health status scores in postmenopausal women. RESULTS: There were 12 studies eventually included in this meta-analysis. A total of 1,272 postmenopausal women were involved, including 628 in the experimental group (intervention with Tai Chi exercise) and 644 in the control group (without any intervention). Briefly, postmenopausal women practicing Tai Chi presented a significant increase in vertebral bone density [standardized mean difference (SMD) = 0.37, 95% confidence interval (CI) (0.04-0.71), P = 0.03] and health status score [SMD = 0.25, 95% CI (0.01-0.49), P = 0.04]. In contrast, there were no significant differences for postmenopausal women between the two groups in terms of serum calcium [SMD = -0.01, 95% CI (-0.39, 0.36), P = 0.77], clinical balance [SMD = 0.17, 95% CI (-0.01, 0.46), P = 0.23], number of falls [SMD = -0.61, 95% CI (-1.24, 0.02), P = 0.06] and total falls [odds ratio = 0.35, 95% CI (0.11-1.12), P = 0.07]. CONCLUSION: Tai Chi exercise can improve the bone mineral density of postmenopausal women, thereby maintaining bone health. Hence, Tai Chi exercise is necessary to prevent osteoporosis.

Clinical characteristics and risk stratification for late-onset herpes zoster following allogeneic hematopoietic stem cell transplantation.

The incidence of herpes zoster (HZ) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is significantly higher than that of the general public. Although routine antiviral prophylaxis is recommended, late-onset HZ has been highlighted, yet limited information is known about its clinical features and predictors. Here, we conducted a retrospective nested case-control study to identify patients with late-onset HZ, defined as a diagnosis of HZ after 1 year of transplantation, among allo-HSCT recipients between 2012 and 2017 at Peking University People's Hospital. Three controls were matched for each patient. A total of 201 patients developed late-onset HZ. Age over 20 years, absence of neutrophil engraftment by 14 days, mental disorders, immunosuppressant use at 1 year, and a peripheral CD4+/CD8+ ratio ≥0.5 at 1 year were independent risk factors, among which the CD4+/CD8+ ratio demonstrated good discriminative power for predicting late-onset HZ. For patients with a CD4+/CD8+ ratio <0.5, patient age, neutrophil engraftment time, mental disorders, and immunosuppressant use were potential risk factors. A stratification algorithm was accordingly established, classifying the transplant recipients into three risk groups. Whether the algorithm could facilitate the administration of posttransplant antiviral prophylaxis merits further validation.

Research on the castor oil pressing extraction mechanism based on multi-physics coupling simulation.

Castor oil has been widely used in various fields due to its properties, leading to large attention for its extraction mechanism. To research the castor oil extraction mechanism during pressing, a self-developed uniaxial compression device combined with an in situ observation is established. The effects of pressure, loading speed, and creep time are investigated, and a finite element model coupling with multi-physics is established for castor oil pressing extraction, verified by the seed cake experimental compression strain matching with numerical simulation under the same condition. Simulation results indicated that the pressing oil extraction process can be divided into two stages, Darcy's speed shows the first sharp decreasing stage and the second gradual increasing stage during porosity and pressure interaction. In the first stage, porosity is dominant on Darcy's speed. With porosity decreasing, the pressure effect on Darcy's speed exceeds porosity in the second stage. With seed thickness increasing, Darcy's speed first increases and then decreases. With loading speed increasing, Darcy's speed increases. Darcy's speed decreases constantly with creep time increasing. This study can provide basic theoretical and practical guidance for oil extraction.

Plasma SCUBE2 as a novel biomarker associates with survival outcomes in patients with sepsis-associated acute kidney injury.

BACKGROUND: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. METHODS: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. RESULTS: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. CONCLUSIONS: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.