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Abstract Signal transduction across biological membranes enables cells to detect and respond to diverse chemical or physical signals, and replicating these complex biological processes through synthetic methods is of significant interest in synthetic biology. Here we present an artificial signal transduction system using oriented cholesterol-tagged triplex DNA (TD) as synthetic receptors to transmit and amplify signals across lipid bilayer membranes through H+-mediated TD conformational transitions from duplex to triplex. An auxiliary sequence, complementary to the third strand of the TD, ensures a controlled and preferred outward orientation of cholesterol-tagged TD on membranes. Upon external H+ stimuli, the conformational change triggers the translocation of the third strand from the outer to the inner membrane leaflet, resulting in effective transmembrane signal transduction. This mechanism enables fluorescence resonance energy transfer (FRET), selective photocleavage, catalytic signal amplification, and logic gate modulation within vesicles. Our findings demonstrate that these TD-based receptors mimic the functional dynamics of natural G protein-coupled receptors (GPCRs), providing a foundation for advanced applications in biosensing, cell signaling modulation, and targeted drug delivery systems.

Abstract Background Patient satisfaction is a powerful predictor of an individual's mental health, according to previous research. However, there has not been a thorough study on the relationship between depression and overall medical service satisfaction (OMSS) in middle-aged and older adults. Moreover, little is known about how different Internet-using patterns affect this relationship. Methods We selected 4,523 participants from the China Family Panel Studies (CFPS) 2020 dataset who were aged 45 and older. The relationship between OMSS and depression was examined using logistic regression analysis, distinct Internet-using patterns were investigated using latent class analysis, and the moderating effects of these patterns were examined using SPSS PROCESS macro analysis. Results The results showed OMSS was negatively related to depression in middle-aged and older adults (β = -0.181, p

Abstract Methods Web of Science, Cochrane library and PubMed were systematically searched up to January 2024 to identify studies examining the impact of financial incentives on diabetes management in patients. Studies were evaluated based on the robustness of their methodology, participant numbers, and quality scores. The Cochrane risk-of-bias tool was applied for randomized controlled trials, while the Newcastle–Ottawa Scale was used for non-randomized controlled trials to assess study quality. Due to the heterogeneity of the included studies, a narrative synthesis approach was utilized. Results In the study, we included 12 published research studies. Five studies investigated the influence of financial incentives on patient behavior, all demonstrating a significant positive impact on behaviors such as blood glucose monitoring, medication adherence, and physical activity. 10 studies analyzed the impact of financial incentives on HbA1c levels in diabetes patients. Among them, 5 studies reported that financial incentives could improve HbA1c levels through longitudinal historical comparisons. The other 5 studies did not find significant improvements compared to the control group. Three studies explored long-term effects, two studies targeting the adolescent population had no impact, and one study targeting adults had a positive impact. Conclusions In summary, this review found that financial incentives can positively influence patient behavior and enhance compliance, but their impact on HbA1c levels is inconsistent. Financial incentives may help adult patients maintain behavior even after the withdrawal of incentives.

Lung cancer accounts for the highest proportion of cancer deaths in the world and poses a great threat to human health. About 30% to 40% of non-small cell lung cancer (NSCLC) is caused by point mutations, exon insertion and exon deletion of the epidermal growth factor receptor (EGFR). In addition to the common exon 19 deletion mutation and exon 21 L858R mutation, exon 18 G719X mutation, exon 21 L861Q mutation and exon 20 S768I mutation are the most important rare mutations. At present, the diagnostic methods for major rare mutations are mainly next-generation sequencing (NGS), digital polymerase chain reaction (dPCR), droplet digital PCR (ddPCR), etc. Regarding the targeted therapy of G719X/L861Q/S768I mutant NSCLC, the first generation EGFR-tyrosine kinase inhibitors (TKIs) have poor efficacy, while the second and third generation EGFR-TKIs have similar efficacy. The novel third generation EGFR-TKIs and combination therapy show a good therapeutic prospect. This article summarized the progress in the diagnosis and targeted therapy of G719X/L861Q/S768I mutant NSCLC, so as to provide reference for subsequent clinical drug use and research.

Abstract Background It was reported that either shorter programmed intermittent epidural bolus (PIEB) intervals or high-speed bolus can produce more extensive epidural spread. We hypothesized that a combination of shortened time interval and increased speed of epidural bolus might further improve analgesic effect and therefore reduce the hourly volume for epidural labour analgesia. Methods This double-blind dose-finding study used a biased coin up-and-down sequential allocation method to determine the 90% effective bolus volume of ropivacaine combined with sufentanil while using the push pump at a rate of 400 mL/hr and interval of 30 min to provide effective analgesia without breakthrough pain. We used 0.1% ropivacaine with 0.4 µg/mL sufentanil, with bolus volumes ranging from 3 to 6 mL. The first patient was assigned a volume of 3 mL, and the remaining volumes were assigned according to the biased coin-up-and-down method. Results The estimated 90% effective volume (EV90) of ropivacaine combined with sufentanil for epidural labour analgesia at a time interval of 30 min was 4.88 mL (95% confidence interval 4.83–5.38). Conclusions The optimum bolus volume of ropivacaine with sufentanil while using push pump at a time interval of 30 min is approximately 5 mL. It could probably further reduce the hourly bolus volume for epidural labour analgesia.

While plastic water bottles are known to potentially release various volatile organic compounds (VOCs) when exposed to light, existing knowledge in this field remains limited. In this study, we systematically examined the composition, yield, and toxicity of VOCs released from six plastic containers obtained from different continents under UV-A and solar irradiation. After light exposure, all containers released VOCs, including alkanes, alkenes, alcohols, aldehydes, carboxylic acids, aromatics, etc. The 1#, 3#, 4#, 5#, and 6# containers exhibited 35, 32, 19, 24 and 37 species of VOCs, respectively. Specifically, the 2# container released 28 and 32 series of VOCs after 1-day (short-term) and 7-day (long-term) UV-A irradiation, respectively, compared to 30 and 32 species under solar irradiation. Over half of the VOCs identified were oxidized compounds alongside various short-chain hydrocarbons. Significant differences in VOC compositions among the containers were observed, potentially originating from light-induced aging and degradation of the polyethylene terephthalate structure in the containers. Toxicological predictions unveiled distinctive toxic characteristics of VOCs from each container. For example, among the various VOCs produced by the 2# container, straight-chain alkanes like n-hexadecane (544-76-3) were identified as the most toxic compounds. After long-term irradiation, the yield of these toxic VOCs from the 2# container ranged from 0.11 ng/g to 0.79 ng/g. Considering the small mass of a single bottle, the volatilization of VOCs from an individual container would be insignificant. Even after prolonged exposure to light, the potential health risks associated with inhaling VOCs when opening and drinking bottled water appear manageable.

In order to improve the quality of whole wheat steamed bread, in this paper, stone-ground whole wheat flour with low-temperature and low-speed milling was selected, and the natural pigment of pumpkin flour was utilized to study the effect of the addition of pumpkin flour on the whole wheat flour-wheat flour mixture, and the effects of the addition of whole wheat flour, the addition of pumpkin flour, the addition of yeast, and the fermentation time on the sensory, specific volume, and chromaticity of the whole wheat steamed bread. On this basis, the sensory score was used as the response value, and the Box-Behnken experiment was used to optimize to obtain the optimal formulation of whole wheat steamed bread and the nutritional characteristics of whole wheat steamed bread were analyzed. The results showed that the influence of each factor on the sensory scores of whole wheat steamed bread was in descending order: the amount of whole wheat flour added, the amount of yeast added, and the amount of pumpkin flour added. The optimal formulation of whole wheat steamed bread was 55% wheat flour, 45% whole wheat flour, 10% pumpkin flour, 2% yeast, and fermentation time 40 min. The sensory score of whole wheat steamed bread prepared under this formulation was 97.23, which was similar to the predicted value of 97.81. The moisture content of pumpkin whole wheat steamed bread under the optimal formulation was 44.86%, the polyphenol content was 5.47 mg/g, and the flavonoid content was 2.57 mg/g. The steamed bread under the formulation had a golden color, and prominent aroma, fluffy and tasty, and possessed the unique flavors of pumpkin and whole wheat. It provides a useful reference for the deep processing and comprehensive utilization of pumpkins.

Purpose To assess whether gray-scale ultrasound (US) based radiomic features can help distinguish HER2 expressions (ie, HER2-overexpressing, HER2-low-expressing, and HER2-zero-expressing) in breast cancer. Materials and Methods This retrospective study encompassed female breast cancer patients who underwent US examinations at two distinct centers from February 2021 to July 2023. Tumor segmentation and radiomic feature extraction were performed on grayscale US images. Decision Tree analysis was employed to simultaneously evaluate feature importance, and the Least Absolute Shrinkage and Selection Operator technique was utilized for feature selection to construct the radiomic signature. The Area Under the Curve (AUC) of the Receiver Operating Characteristic curve was employed to assess the performance of the radiomic features. Multivariate logistic regression was used to identify independent predictors for distinguishing HER2 expression in the dataset. Results The training set comprised 292 patients from Center 1 (median, 51 years; interquartile range [IQR]: 45-61), while the external validation set included 131 patients from Center 2 (median, 51 years; IQR: 45-62). In the external validation dataset, the radiomic features achieved AUC of 0.76 for distinguishing between HER2-low and positive tumors versus HER2-zero tumors. The AUC for differentiating HER2-low (1+) from HER2-zero tumors was 0.74, and for distinguishing HER2-low (2+) from HER2-zero tumors, the AUC was 0.77. In the multivariate analysis assessing HER2-low and HER2-positive versus HER2-zero tumors, internal echoes (P = .029) and margins (P

Abstract Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long‐term safety of GLP‐1 RAs remains insufficiently studied. This study aimed to provide real‐world evidence on potential adverse outcomes associated with GLP‐1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. Methods We conducted a retrospective cohort study involving 7746 T2D patients on GLP‐1 RAs in Shenzhen, China. They were compared with 124 371 metformin‐only users and 36 146 insulin‐only users, forming two therapy control groups. GLP‐1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP‐1 RAs use. Results Compared with metformin‐only users, GLP‐1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24–3.24), acute nephritis (3.20, 2.17–4.70), kidney failure (3.73, 2.74–5.08), thyroid cancer (2.25, 1.23–4.10), and thyroid dysfunction (1.27, 1.00–1.63), respectively; Similar results were also found when compared with insulin‐only users. Importantly, long‐term (≥12 months) GLP‐1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. Conclusion Compared with traditional T2D treatments, GLP‐1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP‐1 RAs. Further validation is crucial across diverse populations.

IntroductionThe Asian elephant (Elephas maximus) is a giant herbivore classified as an endangered wildlife species by the International Union for Conservation of Threatened Species.This study aims to investigate and compare the core gut microbiota of captive Asian elephants from three different locations in Yunnan Province, China, to explore the impact of environmental and husbandry factors on microbial diversity.MethodsWe collected fecal samples from 29 captive Asian elephants from three locations and performed full-length 16S rRNA gene sequencing. Microbial diversity was assessed using alpha diversity (Chao1 and Shannon indexes) and beta diversity (Bray-Curtis and Euclidean distance metrics). Principal coordinate analysis (PCoA) was used to visualize microbial variation among groups.ResultsAlpha diversity analysis showed that the microbial diversity in the Yexianggu group was higher than that in the other groups. Bray-Curtis and Euclidean metrics revealed significant differences among the microbial communities. Bacteroidetes and Firmicutes, which are key cellulose-degrading bacteria, were the dominant phyla in all groups. Synergistaceae was the most abundant family in the Menghai group, while Lachnospiraceae and Pirellulaceae were more abundant in the Yexianggu and Yuantongshan groups, respectively. Genus p-1008-a5-gut-group was more abundant in Yexianggu, and Prevotella was predominant in Menghai.DiscussionThese results indicate that habitat and husbandry practices significantly influence the gut microbiota of captive Asian elephants. The identification of bacterial species such as Lactobacillus fermentum, Clostridium neonatale, Enterococcus mundtii, Klebsiella huaxiensis, Corynebacterium nasicanis, and Streptococcus equinus highlights the potential role of specific microbes in maintaining host-microbial interactions. Promoting microbial diversity through improved captive conditions could enhance the health of these endangered animals.

PurposeTo analyze the application of ‘instrument and equipment surface cleaning and disinfection’ in hospitals based on standardization and the management of cleaning and disinfection information systems.MethodsEmployees and all cleaning and disinfected instruments and equipment from 56 inpatient departments in our hospital were selected as the subjects of observation. The period before the intervention (January 2023) was designated as the control group, while the period after the intervention (July 2023) was designated as the study group. In the control group, the instruments and equipment under routine management were disinfected. The research team applied the Failure Mode and Effects Analysis (FMEA) method to clean and disinfect the surfaces of instruments and equipment on the basis of standardization and cleaning and disinfection information system management. Employees’ theoretical knowledge points and operational skill scores before and after the intervention were compared and evaluated. The changes in the risk priority coefficient (RPN) values of high-risk factors were analyzed. Fifty-six clinical medical staff from 56 inpatient departments in the hospital were selected to evaluate the clinical satisfaction of the cleaning and disinfection management of instruments and equipment before and after the intervention, and the clinical satisfaction of the two groups was compared.ResultsThe scores of theoretical knowledge and operational skills of the staff in the research group were significantly higher than those in the control group. The passing rates of theoretical knowledge and operational skills in the control group and the research group were 44.64 and 94.64% respectively, and 55.36 and 96.43%, respectively. The qualified rate of theoretical knowledge and operational skills of staff in the study group was significantly higher than that in the control group (p

Background: Allergic rhinitis (AR) is a global health issue affecting millions of individuals worldwide. Pyroptosis has emerged as a major player in the development of AR, and targeting its inhibition with specific drugs holds promise for AR treatment. However, a comprehensive understanding of the precise mechanisms underlying pyroptosis in AR remains to be explored, warranting further investigation. Objective: This study aims to elucidate the roles of HMGB1, Sphk1, and HDAC4 in regulating human nasal epithelial cell (hNEC) pyroptosis and AR. Methods: An in vitro AR cell culture model and an in vivo AR mouse model were established. Western blot, ELISA, histological staining, and flow cytometry were utilized to confirm the gene and protein expression. The interactions among Sphk1, HDAC4, and HMGB1 were validated through ChIP, Co-IP, and Dual-luciferase assay. Results and conclusion: We identified that the expression levels of Sphk1, HMGB1, and inflammasome components, including IL-18, and IL-1β were elevated in AR patients and mouse models. Knockdown of Sphk1 inhibited hNEC pyroptosis induced by dust mite allergen. Overexpression of HDAC4 suppressed HMGB1-mediated pyroptosis in hNECs. In addition, HDAC4 was found to mediate the transcriptional regulation of HMGB1 via MEF2C, a transcription factor. Additionally, Sphk1 was shown to interact with CaMKII-δ, promoting the phosphorylation of HDAC4 and inhibiting its cytoplasmic translocation. Knockdown of HDAC4 reversed the effect of Sphk1 knockdown on pyroptosis. These discoveries offer a glimpse into the molecular mechanisms underlying AR and suggest potential therapeutic targets for the treatment of this condition.

Background: The elevated long-term cardiovascular disease (CVD) risks associated with pneumonia have been observed among inpatients, yet the risks associated with outpatients are less understood. Methods: We used register-based data and a matched cohort design, including 98,354 pneumonia inpatients and 44,486 outpatients, as well as a 5-fold number of matched healthy controls. Associations between pneumonia presentation (in inpatient and outpatient settings) and long-term CVD risks were measured by rate difference and hazard ratio (HR) using Poisson and Cox regressions in a time-dependent manner. Results: During a maximum follow-up period of 5.7 years of ischemic heart disease (IHD), heart failure (HF), and stroke were documented among pneumonia inpatients.Relative to healthy controls, pneumonia patients showed increased risks of IHD, HF, and stroke. Women and young inpatients demonstrated stronger associations of CVD with pneumonia; inpatients aged 60 years or older showed the highest excessive CVD risks. Conclusions: Pneumonia demanding outpatient and inpatient cares are intermediate-term and long-term risk factors of incident CVDs respectively, underscoring the need to plan setting-specific and time-dependent CVD-preventive cares following pneumonia presentation.

Abstract Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.

Abstract Background Mucosal-associated invariant T (MAIT) cells have been reported to regulate tumor immunity. However, the immune characteristics of MAIT cells in non-small cell lung cancer (NSCLC) and their correlation with the treatment efficacy of immune checkpoint inhibitors (ICIs) remain unclear. Patients and methods In this study, we performed single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence assays to determine the proportion and characteristics of CD8+MAIT cells in patients with metastatic NSCLC who did and did not respond to anti-PD-1 therapy. Survival analyses were employed to determine the effects of MAIT proportion and C-X-C chemokine receptor 6 (CXCR6) expression on the prognosis of patients with advanced NSCLC. Results The proportion of activated and proliferating CD8+MAIT cells were significantly higher in responders-derived peripheral blood mononuclear cells (PBMCs) and lung tissues before anti-PD-1 therapy, with enhanced expression of cytotoxicity-related genes including CCL4, KLRG1, PRF1, NCR3, NKG7, GZMB, and KLRK1. The responders’ peripheral and tumor-infiltrating CD8+MAIT cells showed an upregulated CXCR6 expression. Similarly, CXCR6+CD8+MAIT cells from responders showed higher expression of cytotoxicity-related genes, such as CST7, GNLY, KLRG1, NKG7, and PRF1. Patients with ≥15.1% CD8+MAIT cells to CD8+T cells ratio and ≥35.9% CXCR6+CD8+MAIT cells to CD8+MAIT cells ratio in peripheral blood showed better progression-free survival (PFS) after immunotherapy. The role of CD8+MAIT cells in lung cancer immunotherapy was potentially mediated by classical/non-classical monocytes through the CXCL16-CXCR6 axis. Conclusion CD8+MAIT cells are a potential predictive biomarker for patients with NSCLC responding to anti-PD-1 therapy. The correlation between CD8+MAIT cells and immunotherapy sensitivity may be ascribed to high CXCR6 expression.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract Background This study investigates the relationship between triglyceride-glucose (TyG) index trajectories and the results of ablation in patients with stage 3D atrial fibrillation (AF). Methods A retrospective cohort study was carried out on patients who underwent AF Radiofrequency Catheter Ablation (RFCA) at the Cardiology Department of the Fourth Affiliated Hospital of Zhejiang University and Taizhou Hospital of Zhejiang Province from January 2016 to December 2022. The main clinical endpoint was determined as the occurrence of atrial arrhythmia for at least 30 s following a 3-month period after ablation. Using a latent class trajectory model, different trajectory groups were identified based on TyG levels. The relationship between TyG trajectory and the outcome of AF recurrence in patients was assessed through Kaplan-Meier survival curve analysis and multivariable Cox proportional hazards regression model. Results The study included 997 participants, with an average age of 63.21 ± 9.84 years, of whom 630 were males (63.19%). The mean follow-up period for the participants was 30.43 ± 17.75 months, during which 200 individuals experienced AF recurrence. Utilizing the minimum Bayesian Information Criterion (BIC) and the maximum Entropy principle, TyG levels post-AF RFCA were divided into three groups: Locus 1 low-low group (n = 791), Locus 2 low-high-low group (n = 14), and Locus 3 high-high group (n = 192). Significant differences in survival rates among the different trajectories were observed through the Kaplan-Meier curve (P

Abstract BackgroundHypertension is highly prevalent among patients undergoing hemodialysis, with a significant proportion experiencing poorly controlled blood pressure (BP). Digital BP management in this population has been underused. ObjectiveThis study aimed to explore the efficacy of a web-based home BP monitoring (HBPM) program in improving predialysis BP control and enhancing knowledge, perception, and adherence to HBPM among patients with hypertension undergoing hemodialysis. MethodsA multicenter, open-label, randomized controlled trial was conducted at 2 hemodialysis units. Patients were randomly allocated in a 1:1 ratio to either the web-based HBPM program as the intervention group or to usual care as the control group over a 6-month period. The primary outcomes were the predialysis BP control rate, defined as less than 140/90 mm Hg, and the predialysis systolic and diastolic BP, assessed from baseline to the 6-month follow-up. Secondary outcomes included patient knowledge, perception, and adherence to HBPM, evaluated using the HBPM Knowledge Questionnaire, HBPM Perception Scale, and HBPM Adherence Scale, respectively. A generalized estimating equations analysis was used to analyze the primary outcomes in the intention-to-treat analysis. ResultsOf the 165 patients enrolled in the program (n=84, 50.9% in the web-based HBPM group and n=81, 49.1% in the control group), 145 (87.9%) completed the follow-up assessment. During the follow-up period, 11 instances of hypotension occurred in 9 patients in the web-based HBPM group, compared to 15 instances in 14 patients in the control group. The predialysis BP control rate increased from 30% (25/84) to 48% (40/84) in the web-based HBPM group after the 6-month intervention, whereas in the control group, it decreased from 37% (30/81) to 25% (20/81; χ22PPt163PPt163PPt163Pt163Pt163P ConclusionsThe implementation of a web-based HBPM program can enhance predialysis BP control and the knowledge, perception, and adherence to HBPM among patients undergoing hemodialysis. This web-based HBPM program should be promoted in appropriate clinical settings.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored. Method: We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated. Results: Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence. Conclusions: This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.

PurposePotentially inappropriate prescribing (PIP) is commonly encountered in older adults; yet, there is limited information on the occurrence of PIP among older adults with hypertension. This study aims to determine and compare the prevalence of PIP and its association with comorbidities in older adult outpatients with hypertension across hospitals and community health centers (CHCs).MethodsThis 3-year (2015–2017) repeated cross-sectional study used electronic medical records from Shenzhen, China, involving 62 hospitals and 678 primary medical institutions. PIP was defined using the 2019 Beers Criteria. Older adults (≥65 years) with hypertension and at least one outpatient prescription were included. Modified Poisson regression analysis was used to assess the association between chronic comorbidities, healthcare settings, and PIP.ResultsThe prevalence of PIP in old adult outpatients with hypertension in 2015, 2016, and 2017 was 46.32%, 46.98%, and 46.58% in hospitals, with a sample size of 38,411, 46,235, and 50,495, respectively, and 29.14%, 26.66%, and 29.84% in CHCs, with a sample size of 26,876, 29,434, and 34,775 respectively. The top four most popular PIP in hospitals and CHCs was proton-pump inhibitors (PPIs), diuretics, benzodiazepines, and non-cyclooxygenase-selective non-steroidal anti-inflammatory drugs (NSAIDs), respectively. PIP was most associated with chronic gastrointestinal disease (adjusted prevalence ratio = 1.54, 95% confidence interval [CI] = 1.50–1.59) and mental and behavioral disorders (adjusted prevalence ratio = 1.49, 95% CI = 1.46–1.53) in hospitals and with mental and behavioral disorders (adjusted prevalence ratio = 1.99; 95% CI = 1.95–2.03) and musculoskeletal system and connective tissue disorders (adjusted prevalence ratio = 1.33; 95% CI = 1.31–1.36) in CHCs. The prevalence of PIP was significantly higher in hospital settings than in CHCs (adjusted prevalence ratio = 1.65; 95% CI = 1.63–1.66).ConclusionAmong older adult outpatients with hypertension in Shenzhen, PIP was more prevalent in hospitals than in CHCs. The comorbidities most strongly associated with PIP were chronic gastrointestinal disease and mental and behavioral disorders in hospitals and mental and behavioral disorders in CHCs. Clinical pharmacy integration needs to be considered to reduce inappropriate prescribing in this vulnerable population.

Background: The differentiation between benign and malignant breast tumors extends beyond morphological structures to encompass functional alterations within the nodules. The combination of photoacoustic (PA) imaging and radiomics unveils functional insights and intricate details that are imperceptible to the naked eye. Purpose: This study aims to assess the efficacy of PA imaging in breast cancer radiomics, focusing on the impact of peritumoral region size on radiomic model accuracy. Materials and methods: From January 2022 to November 2023, data were collected from 358 patients with breast nodules, diagnosed via PA/US examination and classified as BI-RADS 3–5. The study used the largest lesion dimension in PA images to define the region of interest, expanded by 2 mm, 5 mm, and 8 mm, for extracting radiomic features. Techniques from statistics and machine learning were applied for feature selection, and logistic regression classifiers were used to build radiomic models. These models integrated both intratumoral and peritumoral data, with logistic regressions identifying key predictive features. Results: The developed nomogram, combining 5 mm peritumoral data with intratumoral and clinical features, showed superior diagnostic performance, achieving an AUC of 0.950 in the training cohort and 0.899 in validation. This model outperformed those based solely on clinical features or other radiomic methods, with the 5 mm peritumoral region proving most effective in identifying malignant nodules. Conclusion: This research demonstrates the significant potential of PA imaging in breast cancer radiomics, especially the advantage of integrating 5 mm peritumoral with intratumoral features. This approach not only surpasses models based on clinical data but also underscores the importance of comprehensive radiomic analysis in accurately characterizing breast nodules.

Key Clinical Message Permanent pacemaker implantation is the main treatment of symptomatic bradyarrhythmia, which has been widely used. Lead implantation is a critical step. When the lead malfunctions and needs to be replaced, extraction or abandonment of the primary lead (in whole or in part) should be determined according to the situation.

Ivosidenib, an isocitrate dehydrogenase 1 (IDH1) inhibitor, has demonstrated clinical benefits in a pivotal study (AG120-C-001) in patients with IDH1-mutated (mIDH1) acute myeloid leukemia (AML). A registry study (CS3010-101: NCT04176393) was conducted to assess the pharmacokinetic (PK) characteristics, safety, and efficacy of ivosidenib in Chinese patients with relapsed or refractory (R/R) mIDH1 AML. Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression. Ten subjects underwent intensive PK/progressive disease (PD) assessments. All subjects had the clinical response assessed at screening, every 28 days through month 12, and then every 56 days. Between November 12, 2019, and April 2, 2021, 30 patients were enrolled; 26 (86.7%) had de novo AML and 18 (60.0%) were transfusion-dependent at baseline. Following single and repeated doses of ivosidenib, median time to maximum plasma concentration (Tmax) was 4.0 and 2.0 hours, respectively. The inter-individual variability of pharmacokinetic exposure was moderate to high (coefficient of variation [CV], 25%–53%). No obvious accumulation was observed after repeated doses at cycle 2 day 1. Regarding the clinical response, the CR + CRh rate was 36.7% (95% confidence interval [CI]: 19.9%–56.1%), the median duration of CR + CRh was 19.7 months (95% CI: 2.9 months–not reached [NR]), and median duration of response (DoR) was 14.3 months (95% CI: 6.4 months–NR). Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months, as compared with primary data cutoff, and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.

Shallow purple soils (Entisols) were widely distributed in hilly areas of southwest China and were easily subjected to drought due to the weak soil water retention capacity, which largely reduced the crop productivity. However, the impact of solum thickness on ecological traits and water use strategies of crops remain poorly understood under the shallow Entisol environment. In this study, water use patterns and physiological adaptation of maize with different solum thicknesses were investigated to ascertain the optimum solum thickness based on an in-situ experiment. Isotopic (2H and 18O) tracing technique was used to investigate the water sources for maize growth in sloping croplands with solum of 20 cm (C1), 40 cm (C2), 60 cm (C3), 80 cm (C4), 100 cm (C5) thickness. The morphological and physiological characteristics were also discussed under different soil moisture regimes. The results showed the soil water storage capacity significantly increased with solum thickness. The isotopes of xylem water in shallow solum (≦40 cm) were more enriched, indicating more contributions from the bottom soil water, especially under dry regimes (62.3% for C1, 42.8% for C2, at Jul. 09). The water sources utilized by maize in the treatments with solum thickness greater than 60 cm were relatively evenly distributed throughout the soil profile (mean 19.3%, 19.6% and 17.6%, respectively, in the 0–10 cm, 10–20 cm, 20–40 cm soil layer), and the water niche breadth increased with the solum thickness. Maize in shallow solum (≦40 cm) had lower biomass and higher specific leaf area (SLA) to reduce transpiration rate and improved water use efficiency (WUEi) (highest for C1, P60 cm) had significantly higher yields than in shallower solum (P

Adeno-associated virus (AAV) is a relatively safe and efficient vector for gene therapy. However, due to its 4.7-kb limit of cargo, SpCas9-mediated base editors cannot be packaged into a single AAV vector, which hinders their clinical application. The development of efficient miniature base editors becomes an urgent need. Un1Cas12f1 is a class II V-F-type CRISPR-Cas protein with only 529 amino acids. Although Un1Cas12f1 has been engineered to be a base editor in mammalian cells, the base-editing efficiency is less than 10%, which limits its therapeutic applications. Here, we developed hypercompact and high-efficiency base editors by engineering Un1Cas12f1, fusing non-specific DNA binding protein Sso7d, and truncating single guide RNA (sgRNA), termed STUminiBEs. We demonstrated robust A-to-G conversion (54% on average) by STUminiABEs or C-to-T conversion (45% on average) by STUminiCBEs. We packaged STUminiCBEs into AAVs and successfully introduced a premature stop codon on the PCSK9 gene in mammalian cells. In sum, STUminiBEs are efficient miniature base editors and could readily be packaged into AAVs for biological research or biomedical applications.

Abstract Objectives Emerging evidence suggests a potential relationship between body composition and short-term prognosis of ulcerative colitis (UC). Early and accurate assessment of rapid remission based on conventional therapy via abdominal computed tomography (CT) images has rarely been investigated. This study aimed to build a prediction model using CT-based body composition parameters for UC risk stratification. Methods In total, 138 patients with abdominal CT images were enrolled. Eleven quantitative parameters related to body composition involving skeletal muscle mass, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured and calculated using a semi-automated segmentation method. A prediction model was established with significant parameters using a multivariable logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate prediction performance. Subgroup analyses were implemented to evaluate the diagnostic efficiency of the prediction model between different disease locations, centers, and CT scanners. The Delong test was used for statistical comparison of ROC curves. Results VAT density, SAT density, gender, and visceral obesity were significantly statistically different between remission and invalidation groups (all p 0.05). Conclusions The predicting model constructed with CT-based body composition parameters is a potential non-invasive approach for short-term prognosis identification and risk stratification. Additionally, VAT density was an independent predictor for escalating therapeutic regimens in UC cohorts. Critical relevance statement The CT images were used for evaluating body composition and risk stratification of ulcerative colitis patients, and a potential non-invasive prediction model was constructed to identify non-responders with conventional therapy for making therapeutic regimens timely and accurately. Key points • CT-based prediction models help divide patients into invalidation and remission groups in UC. • Results of the subgroup analysis confirmed the stability of the prediction model with a high AUC (all > 0.820). • The visceral adipose tissue density was an independent predictor of bad short-term prognosis in UC. Graphical Abstract

Abstract Background The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250–300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. Results Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. Conclusion While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.

Abstract Investigations into the aerodynamic properties of vertical sound barriers exposed to high-speed operations employ computational fluid dynamics. The primary focus of this research is to evaluate the influence of train speed and the distance (D) from the track centerline under various operating conditions. The findings elucidate a marked elevation in the aerodynamic effect amplitude on sound barriers as train speeds increase. In single-train passages, the aerodynamic effect amplitude manifests a direct relationship with the square of the train speed. When two trains pass each other, the aerodynamic amplitude intensifies due to an additional aerodynamic increment on the sound barrier. This increment exhibits an approximate quadratic correlation with the retrograde train speed. Notably, the impact of high-speed trains on sound barrier aerodynamics surpasses that of low-speed trains, and this discrepancy amplifies with larger speed differentials between trains. Moreover, the train-induced aerodynamic effect diminishes significantly with greater distance (D), with occurrences of pressure coefficient (C P) exceeding the standard thresholds during dual-train passages. This study culminates in the formulation of universal equations for quantifying the influence of train speed and distance (D) on sound barrier aerodynamic characteristics across various operational scenarios.

Abstract Immune checkpoint inhibitors have transformed the treatment landscape of non-small cell lung cancer (NSCLC). However, accurately identifying patients who will benefit from immunotherapy remains a challenge. This study aimed to discover potential biomarkers for predicting immunotherapy response in NSCLC patients. Single-cell mass cytometry (CyTOF) was utilized to analyze immune cell subsets in peripheral blood mononuclear cells (PBMCs) obtained from NSCLC patients before and 12 weeks after single-agent immunotherapy. The CyTOF findings were subsequently validated using flow cytometry and multiplex immunohistochemistry/immunofluorescence in PBMCs and tumor tissues, respectively. RNA sequencing (RNA-seq) was performed to elucidate the underlying mechanisms. In the CyTOF cohort (n = 20), a high frequency of CD57+CD8+ T cells in PBMCs was associated with durable clinical benefit from immunotherapy in NSCLC patients (p = 0.034). This association was further confirmed in an independent cohort using flow cytometry (n = 27; p

ABSTRACT Aims/Introduction This study investigated the roles of voltage‐dependent anion channel 1‐related differentially expressed genes (VRDEGs) in diabetic nephropathy (DN). Materials and Methods We downloaded two datasets from patients with DN, namely, GSE30122 and GSE30529, from the Gene Expression Omnibus database. VRDEGs associated with DN were obtained from the intersection of voltage‐dependent anion channel 1‐related genes from the GeneCards database, and differentially expressed genes were screened according to group (DN/healthy) in the two datasets. The enriched pathways of the VRDEGs were analyzed. Hub genes were selected using a protein–protein interaction network, and their predictive value was verified through receiver operating characteristic curve analysis. The CIBERSORTx software examined hub genes and immune cell infiltration associations. The protein expression of hub genes was verified through immunohistochemistry in 16‐week‐old db/db mice for experimentation as a model of type 2 DN. Finally, potential drugs targeting hub genes that inhibit DN development were identified. Results A total of 57 VRDEGs were identified. The two datasets showed high expression of the PI3K, Notch, transforming growth factor‐β, interleukin‐10 and interleukin‐17 pathways in DN. Five hub genes (ITGAM, B2M, LYZ, C3 and CASP1) associated with DN were identified and verified. Immunohistochemistry showed that the five hub genes were highly expressed in db/db mice, compared with db/m mice. The infiltration of immune cells was significantly correlated with the five hub genes. Conclusions Five hub genes were significantly correlated with immune cell infiltration and might be crucial to DN development. This study provides insight into the mechanisms involved in the pathogenesis of DN.

Rapid urbanization during the past decades have turned southeastern coastal China from traditional brick settlements into concrete forests. However, studies in Putian Plain reveal that apart from the physical appearances, local popular religion welcomed repercussions in these decades, even during the pandemic years. This paper looks at contemporary ritual practices and points out how social, cultural and ecological system of a unique ritual alliance system (Qijing) actives. Through practicing a ritualized everyday life, local communities managed to maintain certain indolence in different political and economic circumstances and achieve cultural resilience through various challenges brought by urbanization.

Abstract Background Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT‐determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)‐determined skeletal muscle mass and quality at L1 are associated with mortality in initial‐dialysis patients. Methods This 3‐year multicentric retrospective study included initial‐dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2/m2] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex‐specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all‐cause mortality. The outcomes were all‐cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. Results A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P 0.05). Low L1 SMD (n = 280, 57.73%) was diagnosed based on the optimal cutoff value (

Noise suppression is an important part of microseismic monitoring technology. Signal and noise can be separated by denoising and filtering to improve the subsequent analysis. In this paper, we propose a new denoising method based on convolutional blind denoising network (CBDNet). The method is partially modified for image denoising network CBDNet to make it suitable for one–dimensional data denoising. At present, most of the existing filtering methods are proposed for the Gaussian white noise denoising. In contrast, the proposed method also learns the wind noise, construction noise, traffic noise and mixed noise through the strategy of residual learning. The full convolution subnetwork is used to estimate the noise level, which significantly improves the signal-to-noise ratio and its performance of removing the correlated noise. The model is trained with different types of real noise and random noise. The denoising result is evaluated by corresponding indexes and compared with other denoising methods. The results show that the proposed method has better denoising performance than traditional methods, and it has a superior noise suppression level for oil well construction noise and mixed noise. The proposed method can suppress the interference of time–frequency overlapped end to end and still have noise suppression and event detection capability even if the signal is superimposed on other types of noise.

In this study, the combined combustion characteristics and gaseous product emissions of coal slime and corn stover were compared at different blending ratios. The TG-DTG curves indicate that the optimal performance is achieved when the corn straw blending ratio is 20%. Furthermore, the TG-FTIR coupling results demonstrated an increase in gas species as the blending ratio increased. The composition analysis of ash samples formed at various combustion temperatures using XRD and XRF indicated that a portion of KCl in the fuel was released as volatile matter, while another part reacted with Al2O3 and SiO2 components in the slime to form silica–aluminate compounds and other substances. Notably, interactions between the components of slime and potassium elements in corn stover primarily occurred within the temperature range of 800–1000 °C. These findings contribute to a comprehensive understanding of biomass and coal co-firing combustion chemistry, offering potential applications for enhancing energy efficiency and reducing emissions in industrial processes.

This study examined the synergistic effects of combining Rhodiola rosea (RHO) and caffeine (CAF) supplementation on muscle endurance and explosiveness in SD rats and human subjects, encompassing individuals without prior exercise training experience and seasoned aerobic athletes. Male SD rats and healthy human volunteers were randomly divided into four groups: CAF, RHO, CAF + RHO, and a control group (CTR). Nutritional supplements were administered throughout the training period, and pre-and post-measurement data were collected. In both the rat model and human subjects, the RHO+CAF group demonstrated significantly greater effects compared to the use of RHO or CAF supplements individually. Rats in the RHO+CAF group demonstrated extended running and swimming times and an increase in erythropoietin (EPO) mRNA expression in comparison to the CTR. Blood parameters, such as serum EPO levels, were enhanced in the CAF + RHO group, while blood urea nitrogen (BUN) and lactate (LA) levels significantly decreased in both the RHO and CAF + RHO groups. Hepatic and muscle glycogen contents were also higher in these groups. The gene expression analysis in rats demonstrated an elevation in the mRNA levels of glucose transporter-4 (GLUT-4), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), Monocarboxylate transporter 1 (MCT-1), and Heme Oxygenase-1 (HO-1) in both the RHO and RHO+CAF groups. For individuals without prior aerobic training experience, the RHO+CAF group showed significant improvements compared to the CTR group in maximal oxygen consumption (VO2max), 5 km run, countermovement jump (CMJ), standing long jump, and 30 m sprint. For individuals with years of aerobic training experience, the RHO+CAF group exhibited enhanced performance in the 5 km run, CMJ, and standing long jump compared to the CTR group. In conclusion, the continuous 30 days supplementation of RHO, combined with a single dose of CAF, demonstrated superior effects on muscle endurance and explosiveness in both animal and human studies when compared to the use of RHO or CAF individually.

BackgroundTelomere length is closely linked to the aging phenotype, where cellular aging results in the production of a cascade of cell factors and the senescence-associated secretory phenotype (SASP), leading to an inflammatory response. The presence of inflammation plays a crucial role in the formation of intracranial aneurysms. Nevertheless, the relationship between telomere length and intracranial aneurysms remains unclear. This study aims to explore the causal connection between telomere length and intracranial aneurysms through the utilization of Mendelian randomization (MR) analysis.MethodsData on telomere length were obtained from the genome-wide association studies conducted on the UK Biobank, comprising a total of 472,174 participants. Data on intracranial aneurysms were obtained from the summary dataset of the Global Genome-wide Association Study (GWAS) conducted by the International Stroke Genetics Consortium. The dataset consisted of 7,495 cases and 71,934 controls, all of European descent. Initially, the linkage disequilibrium score was used to investigate the connection between telomere length and intracranial aneurysms. Subsequently, a bidirectional MR was conducted using two-sample analysis to assess whether there is a causal connection between telomere length and intracranial aneurysm risk. The results were analyzed utilizing five MR methods, with the inverse variance weighted method serving as the main methodology. In addition, we did various analyses to evaluate the presence of heterogeneity, pleiotropy, and sensitivity in the study results. A reverse MR analysis was conducted to investigate potential reverse causal links.ResultsIn the forward MR analysis, it was observed that both the inverse variance-weighted and weighted median analyses implied a potential causal relationship between longer telomere length and a decreased incidence of intracranial aneurysms (IVW: OR = 0.66, 95% CI: 0.47–0.92, p = 1.49 × 10−2). There was no heterogeneity or horizontal pleiotropy. The findings were verified to be robust through the utilization of leave-one-out analysis. The use of reverse MR analysis did not establish a potential causal link between the occurrence of intracranial aneurysms and telomere length.ConclusionThere may exist a potential correlation between longer telomere length and a decreased likelihood of intracranial aneurysms within the European population. The present study offers novel insights into the correlation between telomere length and intracranial aneurysms. Additional research is required to clarify the underlying mechanisms and validate our discoveries in diverse populations.

Abstract Background Lipopolysaccharide (LPS)-induced dysfunction of pancreatic β-cells leads to impaired insulin (INS) secretion. Astragalus polysaccharide (APS) is a bioactive heteropolysaccharide extracted from Astragalus membranaceus and is a popular Chinese herbal medicine. This study aimed to elucidate the mechanisms by which APS affects INS secretion from β-cells under LPS stress. Methods Rat insulinoma (INS-1) cells were treated with LPS at a low, medium, or high concentration of APS. Glucose-stimulated insulin secretion (GSIS) was evaluated using an enzyme-linked immunosorbent assay (ELISA). Transcriptome sequencing was used to assess genome-wide gene expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the signaling pathways affected by APS. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) was performed to evaluate the gene expression of glucose transporter 2 (GLUT2), glucokinase (GCK), pancreatic duodenal homeobox-1 (PDX-1), and INS. Western blot analysis was used to detect the protein expression of phosphorylated protein kinase B (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), total mTOR (t-mTOR), and GLUT2. Results LPS decreased GLUT2, GCK, PDX-1, and INS expression and reduced GSIS. These LPS-induced decreases in gene expression and GSIS were restored by APS treatment. In addition, transcriptome sequencing in combination with KEGG enrichment analysis revealed changes in the INS signaling pathway following APS treatment. LPS decreased p-Akt and p-mTOR expression, which was restored by APS treatment. The restorative effects of APS on GSIS as well as on the expression of GLUT2, GCK, PDX-1, and INS were abolished by treatment with the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin (RPM). Conclusions APS restored GSIS in LPS-stimulated pancreatic β-cells by activating the Akt/mTOR/GLUT2 signaling pathway.

Deep-ultraviolet (DUV) disinfection technology provides an expeditious and efficient way to suppress the transmission of coronavirus disease 2019 (COVID-19). However, the influences of viral variants (Delta and Omicron) and low temperatures on the DUV virucidal efficacy are still unknown. Here, we developed a reliable and uniform planar light source comprised of 275-nm light-emitting diodes (LEDs) to investigate the effects of these two unknown factors and delineated the principle behind different disinfection performances. We found the lethal effect of DUV at the same radiation dose was reduced by the cryogenic environment, and a negative-U large-relaxation model was used to explain the difference in view of the photoelectronic nature. The chances were higher in the cryogenic environment for the capture of excited electrons within active genetic molecules back to the initial photo-ionised positions. Additionally, the variant of Omicron required a significantly higher DUV dose to achieve the same virucidal efficacy, and this was thanks to the genetic and proteinic characteristics of the Omicron. The findings in this study are important for human society using DUV disinfection in cold conditions (e.g., the food cold chain logistics and the open air in winter), and the relevant DUV disinfection suggestion against COVID-19 is provided.

Abstract Objectives To appraise effective predictors for infection in patients with decompensated cirrhosis (DC) by using XGBoost algorithm in a retrospective case-control study. Methods Clinical data were retrospectively collected from 6,648 patients with DC admitted to five tertiary hospitals. Indicators with significant differences were determined by univariate analysis and least absolute contraction and selection operator (LASSO) regression. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed infection risk prediction model with simple-tree XGBoost model. Finally, the simple-tree XGBoost model is compared with the traditional logical regression (LR) model. Performances of models were evaluated by area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. Results Six features, including total bilirubin, blood sodium, albumin, prothrombin activity, white blood cell count, and neutrophils to lymphocytes ratio were selected as predictors for infection in patients with DC. Simple-tree XGBoost model conducted by these features can predict infection risk accurately with an AUROC of 0.971, sensitivity of 0.915, and specificity of 0.900 in training set. The performance of simple-tree XGBoost model is better than that of traditional LR model in training set, internal verification set, and external feature set (P

Hyperuricemia (HUA) may lead to myocardial cell damage, thereby promoting the occurrence and adverse outcomes of heart diseases. In this review, we discuss the latest clinical research progress, and explore the impact of HUA on myocardial damage-related diseases such as myocardial infarction, arrhythmias, and heart failure. We also combined recent findings from basic research to analyze potential mechanisms linking HUA with myocardial injury. In different pathological models (such as direct action of high uric acid on myocardial cells or combined with myocardial ischemia-reperfusion model), HUA may cause damage by activating the NOD-like receptor protein 3 inflammasome-induced inflammatory response, interfering with cardiac cell energy metabolism, affecting antioxidant defense systems, and stimulating reactive oxygen species production to enhance the oxidative stress response, ultimately resulting in decreased cardiac function. Additionally, we discuss the impact of lowering uric acid intervention therapy and potential safety issues that may arise. However, as the mechanism underlying HUA-induced myocardial injury is poorly defined, further research is warranted to aid in the development novel therapeutic strategies for HUA-related cardiovascular diseases.

This paper experimentally investigates the performance of piezoelectric force actuators. Using the same encapsulated piezoelectric stack, an inertial-type actuator and a frame-type actuator are constructed for performance comparison. The experimental results are also used to validate the recently established actuator models, whilst the mechanical and piezoelectrical parameters of the models are experimentally identified. The performance of the actuators is described by the transmitted force(s) and input power flow from the actuators to the base structure with reference to the same electrical input voltage to the stack. The validation is deemed successful due to the strong agreement observed between the measured and predicted actuator performances. Additionally, it is discovered that the frame-type actuator has the capacity to produce significantly higher transmitted forces and input power flow to the base structure compared to the inertial-type actuator. The mechanism underlying the performance disparity between these two types of actuators is also examined. This paper clarifies the mechanism, shedding light on the design and optimization of piezoelectric actuators.

Abstract Bronchopulmonary dysplasia (BPD) is a chronic, devastating disease primarily occurring in premature infants. To date, intervention strategies to prevent or treat BPD are limited. We aimed to determine the effects of umbilical cord blood‐derived exosomes (UCB‐EXOs) from healthy term pregnancies on hyperoxia‐induced lung injury and to identify potential targets for BPD intervention. A mouse model of hyperoxia‐induced lung injury was created by exposing neonatal mice to hyperoxia after birth until the 14th day post birth. Age‐matched neonatal mice were exposed to normoxia as the control. Hyperoxia‐induced lung injury mice were intraperitoneally injected with UCB‐EXO or vehicle daily for 3 days, starting on day 4 post birth. Human umbilical vein endothelial cells (HUVECs) were insulted with hyperoxia to establish an in vitro model of BPD to investigate angiogenesis dysfunction. Our results showed that UCB‐EXO alleviated lung injuries in hyperoxia‐insulted mice by reducing histopathological grade and collagen contents in the lung tissues. UCB‐EXO also promoted vascular growth and increased miR‐185‐5p levels in the lungs of hyperoxia‐insulted mice. Additionally, we found that UCB‐EXO elevated miR‐185‐5p levels in HUVECs. MiR‐185‐5p overexpression inhibited cell apoptosis, whereas promoted cell migration in HUVECs exposed to hyperoxia. The luciferase reporter assay results revealed that miR‐185‐5p directly targeted cyclin‐dependent kinase 6 (CDK6), which was downregulated in the lungs of hyperoxia‐insulted mice. Together, these data suggest that UCB‐EXO from healthy term pregnancies protect against hyperoxia‐induced lung injuries via promoting neonatal pulmonary angiogenesis partially by elevating miR‐185‐5p.

Cervical cancer (CC) remains one of the most common and deadly malignancies among women worldwide, with exceptionally high morbidity and mortality rates. The aberrant activation of the hedgehog pathway is intimately associated with tumor development and progression. Nevertheless, the potential therapeutic targets within the hedgehog pathway in CC have yet to be clearly identified. In this study, we conducted an in-depth investigation of hedgehog pathway-related genes in CC, integrating single-cell sequencing data and spatial transcriptomics. Utilizing a comprehensive scoring algorithm, we identified that myofibroblasts within CC tissue exhibit a highly enriched hedgehog pathway. Our analysis of the myofibroblast development process revealed that MYH9 plays a crucial role. Further exploration using spatial transcriptome data allowed us to delve into the role of MYH9 in myofibroblasts. We discovered that MYH9-negative and MYH9-positive myofibroblasts display distinct profiles. Validation using extensive transcriptome data demonstrated that a high infiltration of MYH9-positive myofibroblasts is a risk factor for CC patients, significantly impacting prognosis and immunotherapeutic efficacy. Our study provides unique insights into the relationship between CC and the hedgehog pathway, offering new directions for cancer treatment strategies.

Abstract With high spatio‐temporal resolution geostationary hyperspectral infrared sounder (GeoHIS) observations, monitoring, and predicting rapidly changing weather events are expected to be improved with continuous information of 3D weather cube. However, due to the nature of radiation, clouds prevent an adequate retrieval of atmospheric thermodynamic information under clear‐sky conditions due to large uncertainties in the current radiative transfer model. Removing cloud effects from GeoHIS sub‐footprint is an alternative approach for enhancing clear radiance generation. Such cloud removal can be achieved through the optimal cloud‐clearing (OCC) method, which usually relies on the assumption of atmospheric spatial homogeneity. With high temporal resolution observations from GeoHIS, cloud removal can also be achieved through OCC but using the assumption of temporal homogeneity. This concept was demonstrated using 15‐min Geostationary Interferometric Infrared Sounder (GIIRS) observations. The longwave GIIRS clear radiances under partially cloud cover can be effectively produced with observation errors less than 0.02 ± 0.86 K and 0.04 ± 0.77 K for 11 and 12 μm, respectively.

Most clinically non-functioning pituitary tumour arise from gonadotroph cells. However, clinically functional pituitary gonadotroph adenoma is rare. Here we report a female case who presented with menstrual disturbances, however further workup demonstrated a pituitary microadenoma with elevated FSH and oestradiol level. Transsphenoidal resection was performed and the surgical histopathology confirmed pituitary gonadotroph adenoma. Postoperatively, improvement in both symptoms and hormonal profile were observed. Interestingly, the initially enlarged and polycystic ovaries became within normal range around eight months after the surgery. We suggest functional gonadotroph adenoma should be considered in the presence of gynaecological disorder with persistently elevated oestradiol and FSH levels.