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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.

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

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 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.

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.

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 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.

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.

T5 is a siphophage that has been extensively studied by structural and biochemical methods. However, the complete in situ structures of T5 before and after DNA ejection remain unknown. In this study, we used cryo-electron microscopy (cryo-EM) to determine the structures of mature T5 (a laboratory-adapted, fiberless T5 mutant) and urea-treated empty T5 (lacking the tip complex) at near-atomic resolutions. Atomic models of the head, connector complex, tail tube, and tail tip were built for mature T5, and atomic models of the connector complex, comprising the portal protein pb7, adaptor protein p144, and tail terminator protein p142, were built for urea-treated empty T5. Our findings revealed that the aforementioned proteins did not undergo global conformational changes before and after DNA ejection, indicating that these structural features were conserved among most myophages and siphophages. The present study elucidates the underlying mechanisms of siphophage infection and DNA ejection.

The motor protein prestin, found in the inner ear’s outer hair cells (OHCs), is responsible for high sensitivity and sharp frequency selectivity in mammalian hearing. Some studies have suggested that prestin could be a serological biomarker for cochlear damage, as OHCs are highly vulnerable to damage from various sources. However, the reported data are inconsistent and lack appropriate negative controls. To investigate whether prestin can be used as a serological biomarker for cochlear damage or stress, we measured prestin quantities in the bloodstreams of mice using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that rapidly kill OHCs. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect prestin specifically. The ELISA kit that could detect the prestin protein from cochlear homogenates failed to detect prestin in the bloodstream, despite there being significant damage to OHCs in the cochleae. Furthermore, the optical densities of the serum samples, which correlate to prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice using ELISA.

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 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.

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.

Abstract Bronchopulmonary dysplasia (BPD) is characterized by abnormal development of the blood vessels and alveoli in lungs, which largely occurs in premature infants. Exosomes (EXO) from very preterm infants (VPI) with BPD (BPD-EXO) impair angiogenic activities of human umbilical vein endothelial cells (HUVECs) via EXO-miRNAs cargo. This study aimed to determine whether and how BPD-EXO affect the development of BPD in a mouse model. We showed that treating BPD mice with BPD-EXO chronically and irreversibly aggravated lung injury. BPD-EXO up-regulated 139 and down-regulated 735 genes in the mouse lung tissue. These differentially expressed genes were enriched to the MAPK pathway (e.g., Fgf9 and Cacna2d3), which is critical to angiogenesis and vascular remodeling. BPD-EXO suppressed expression of Fgf9 and Cacna2d3 in HUVECs and inhibited migration, tube formation, and increased cell apoptosis in HUVECs. These data demonstrate that BPD-EXO aggravate lung injury in BPD mice and impair lung angiogenesis, plausibly leading to adverse outcomes of VPI with BPD. These data also suggest that BPD-EXO could serve as promising targets for predicting and treating BPD.

Maize (Zea mays L.) is one of the three major food crops and an important source of carbohydrates for maintaining food security around the world. Plant height (H), stem diameter (SD), leaf area index (LAI) and dry matter (DM) are important growth parameters that influence maize production. However, the combined effect of temperature and light on maize growth is rarely considered in crop growth models. Ten maize growth models based on the modified logistic growth equation (Mlog) and the Mitscherlich growth equation (Mit) were proposed to simulate the H, SD, LAI and DM of maize under different mulching practices based on experimental data from 2015–2018. Either the accumulative growing degree-days (AGDD), helio thermal units (HTU), photothermal units (PTU) or photoperiod thermal units (PPTU, first proposed here) was used as a single driving factor in the models; or AGDD was combined with either accumulative actual solar hours (ASS), accumulative photoperiod response (APR, first proposed here) or accumulative maximum possible sunshine hours (ADL) as the dual driving factors in the models. The model performances were evaluated using seven statistical indicators and a global performance index. The results showed that the three mulching practices significantly increased the maize growth rates and the maximum values of the growth curves compared with non-mulching. Among the four single factor-driven models, the overall performance of the MlogPTU Model was the best, followed by the MlogAGDD Model. The MlogPPTU Model was better than the MlogAGDD Model in simulating SD and LAI. Among the 10 models, the overall performance of the MlogAGDD–APR Model was the best, followed by the MlogAGDD–ASS Model. Specifically, the MlogAGDD–APR Model performed the best in simulating H and LAI, while the MlogAGDD–ADL and MlogAGDD–ASS models performed the best in simulating SD and DM, respectively. In conclusion, the modified logistic growth equations with AGDD and either APR, ASS or ADL as the dual driving factors outperformed the commonly used modified logistic growth model with AGDD as a single driving factor in simulating maize growth.

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.

To improve the accuracy of microseismic inversion, seismic anisotropy and moment tensor source should be carefully considered in the forward modelling stage. In this study, 3D microseismic anisotropy wave forward modelling with a moment tensor source was proposed. The modelling was carried out based on a rotated-staggered-grid (RSG) scheme. In contrast to staggered-grids, the RSG scheme defines the velocity components and densities at the same grid, as do the stress components and elastic parameters. Therefore, the elastic moduli do not need to be interpolated. In addition, the detailed formulation and implementation of moment-tensor source loaded on the RSG was presented by equating the source to the stress increments. Meanwhile, the RSG-based 3D wave equation forward modelling was performed in parallel using compute unified device architecture (CUDA) programming on a graphics processing unit (GPU) to improve its efficiency. Numerical simulations including homogeneous and anisotropic models were carried out using the method proposed in this paper, and compared with other methods to prove the reliability of this method. Furthermore, the high efficiency of the proposed approach was evaluated. The results show that the computational efficiency of proposed method can be improved by about two orders of magnitude compared with traditional central processing unit (CPU) computing methods. It could not only help the analysis of microseismic full wavefield records, but also provide support for passive source inversion, including location and focal mechanism inversion, and velocities inversion.

BackgroundCerebral cavernous malformation (CCM) is a rare disease associated with a latent risk of intracranial hemorrhage. However, due to limited evidence, the safety of recommending intravenous tissue plasminogen activators for patients with acute stroke and CCM remains uncertain.MethodsOur study identified five patients with acute stroke and CCM treated between 2017 and 2023 across two hospitals. A comprehensive literature review was conducted, incorporating three similar case reports and two retrospective studies.ResultsAmong 30 patients reviewed, three exhibited symptomatic intracranial hemorrhage, two of whom were women. Additionally, three patients presented with calcification in their CCM, with two experiencing symptomatic intracranial hemorrhage.ConclusionThe observed incidence of symptomatic intracranial hemorrhage following intravenous tissue plasminogen activator administration appears to be elevated in patients with CCM. Therefore, before thrombolysis, a thorough evaluation of personalized risk–benefit ratios is crucial. Furthermore, conducting further research involving multiple centers and larger sample sizes is imperative to advance our understanding in this area, especially in identifying hemorrhage risk factors.

Aboveground biomass (AGB) is a crucial physiological parameter for monitoring crop growth, assessing nutrient status, and predicting yield. Texture features (TFs) derived from remote sensing images have been proven to be crucial for estimating crops AGB, which can effectively address the issue of low accuracy in AGB estimation solely based on spectral information. TFs exhibit sensitivity to the size of the moving window and directional parameters, resulting in a substantial impact on AGB estimation. However, few studies systematically assessed the effects of moving window and directional parameters for TFs extraction on rice AGB estimation. To this end, this study used Unmanned aerial vehicles (UAVs) to acquire multispectral imagery during crucial growth stages of rice and evaluated the performance of TFs derived with different grey level co-occurrence matrix (GLCM) parameters by random forest (RF) regression model. Meanwhile, we analyzed the importance of TFs under the optimal parameter settings. The results indicated that: (1) the appropriate window size for extracting TFs varies with the growth stages of rice plant, wherein a small-scale window demonstrates advantages during the early growth stages, while the opposite holds during the later growth stages; (2) TFs derived from 45° direction represent the optimal choice for estimating rice AGB. During the four crucial growth stages, this selection improved performance in AGB estimation with R2 = 0.76 to 0.83 and rRMSE = 13.62% to 21.33%. Furthermore, the estimation accuracy for the entire growth season is R2 =0.84 and rRMSE =21.07%. However, there is no consensus regarding the selection of the worst TFs computation direction; (3) Correlation (Cor), Mean, and Homogeneity (Hom) from the first principal component image reflecting internal information of rice plant and Contrast (Con), Dissimilarity (Dis), and Second Moment (SM) from the second principal component image expressing edge texture are more important to estimate rice AGB among the whole growth stages; and (4) Considering the optimal parameters, the accuracy of texture-based AGB estimation slightly outperforms the estimation accuracy based on spectral reflectance alone. In summary, the present study can help researchers confident use of GLCM-based TFs to enhance the estimation accuracy of physiological and biochemical parameters of crops.

Objective Peritoneal dialysis-related peritonitis (PDRP) presents a significant challenge for nephrologists. Continuous intraperitoneal cefazolin and ceftazidime are recommended for the treatment of peritonitis. However, some pharmacokinetic studies have shown that doses of 15–20 mg/kg/d may not achieve sufficient therapeutic levels. In this study, we investigated the pharmacokinetics of ceftazidime and cefazolin in patients with continuous ambulatory peritoneal dialysis-related peritonitis and compared the pharmacokinetic characteristics between traditional and modified treatment groups.Methods From February 2017 to December 2019, 42 PDRP patients (17 males, 25 females; mean age: 50.7 ± 12.1 years; mean body weight: 60.9 ± 11.8 kg) were recruited for the study, all participants were anuric. Twenty patients were enrolled in the traditional group and treated with cefazolin (1.0 g) and ceftazidime (1.0 g) via intraperitoneal administration once daily for 14 days. Twenty-two patients were enrolled in the modified group and received the same dose of antibiotics twice daily for the initial five days, followed by once daily for the subsequent nine days. Serum and dialysate samples were collected after days 1, 2, 3, 5, 7, 10, and 14 and analyzed via liquid chromatography-mass spectrometry.Results In the traditional group, the highest and lowest serum concentrations of ceftazidime were 35.9 and 21.7 µg/mL, respectively. The highest concentration of cefazolin was 54.6 µg/mL on day 5 and the lowest concentration was 30.4 µg/mL on day 1. In the modified group, the highest and lowest serum concentrations of ceftazidime were 102.2 and 54.8 µg/mL, respectively. The highest concentration of cefazolin was 141.7 µg/mL and the lowest concentration was 79.8 µg/mL. All antibiotic concentrations were above the minimum inhibitory concentration (MIC) level (8 µg/mL of ceftazidime and 2 µg/mL of cefazolin) throughout the treatment period. However, on day 1, the concentration of ceftazidime in the third bag of dialysate effluent from the traditional group fell below the MIC level. Despite remaining above the MIC, cefazolin concentration was consistently lower in the third bag of dialysate effluent from the traditional group throughout the treatment period.Conclusions Intraperitoneal administration of cefazolin and ceftazidime at a dose of 1 g twice daily for 5 days and then once daily for the rest of the treatment period ensured adequate therapeutic levels of antibiotics for treating anuric PDRP patients.

Introduction We explored the relationship and the predictive value of serum fibroblast growth factor 21 (FGF21) with all-cause mortality, major adverse cardiovascular events (MACEs) and pneumonia in hemodialysis (HD) patients.Methods A total of 388 Chinese HD patients from two HD centers were finally enrolled in this prospective cohort study (registration number: ChiCTR 1900028249) between January 2018 and December 2018. Serum FGF21 was detected. Patients were followed up with a median period of 47 months to record the MACEs and pneumonia until death or 31 December 2022.Results The incidence of all-cause mortality, MACEs and pneumonia in HD patients were 20.6%, 29.6%, and 34.8%, respectively. The optimal cutoffs for FGF21 to predict all-cause mortality, MACEs and pneumonia were 437.57 pg/mL, 216.99 pg/mL and 112.79 pg/mL. Multivariate Cox regression analyses showed that FGF21, as a categorical variable, was an independent predictor for all-cause mortality, MACEs and pneumonia (HR, 3.357, 95% CI, 2.128–5.295, p

IntroductionTraumatic brain injury (TBI) seriously affects the quality of human health and the prognosis of the patient, but the epidemiological characteristics of TBI can vary among populations. Numerous changes have occurred in the epidemiological characteristics of individuals with TBI in the fast-paced city of Shenzhen, China. However, little is known about these characteristics. This study aimed to investigate the changes in TBI epidemiology, help clinicians improve medical treatment.MethodsIn this retrospective cross-sectional analysis, we collected the data of 4,229 patients with TBI admitted to 20 hospitals in Shenzhen in 2017. We collected data on age, gender, cause and severity of the injury, eventual diagnosis, time from injury to admission in a neurosurgery department, and patient outcomes. Two neurosurgeons simultaneously collected the data. We compared these results with a similar study conducted in Shenzhen during the period from 1994 to 2003 to clarify and explain the changes in the epidemiological characteristics of TBI.ResultsThe majority of respondents were men [2,830 (66.9%)]. The mean age was 32.5 ± 21.4 years. The youngest patient was less than 1 year old, and the oldest patient was 101 years old. A total of 3,947 (93.3%) patients had a favorable outcome, 219 (5.2%) had an unfavorable outcome, and 63 (1.5%) died. The predominant external cause was falls (1,779 [42.1%]); this was the most common cause of TBI in children and older adults. Riders of electric bicycles (423 [29.0%]) were the most vulnerable to traffic accident-related injuries. Time greater than 50 h from injury to admission to a neurosurgical department had a significant effect on prognosis (p

The aim of this study was to examine the characteristics and prognosis of patients with myelodysplastic syndrome (MDS) accompanied by TP53 abnormalities and explore potential prognostic factors and treatment responses. This retrospective analysis included 95 patients with MDS and TP53 abnormalities and 173 patients with MDS without TP53 abnormalities at the Fujian Medical University Union Hospital between January 2016 and June 2023. Among patients with TP53 abnormalities, 26 (27.4%) developed AML during the disease course, with a median transformation time of 5.7 months. Complex karyotypes were observed in 73.1% of patients, and the proportions of -5 or del(5q), -7 or del(7q), +8, and -20 or del(20q) were 81.8%, 54.5%, 30.7%, and 25.0%, respectively. These patients exhibited poor survival, with a median overall survival (OS) of 7.3 months, and had 1- and 2-year OS rates of 42.2% and 21.5%, respectively. The complete response rates for azacitidine monotherapy, venetoclax combined with azacitidine, decitabine monotherapy, and decitabine combined with low-dose chemotherapy were 9.1%, 41.7%, 37.5%, and 33.3%, respectively. Long-term survival was similar among the four treatment groups. Patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) had a median OS of 21.3 months, which trended to be longer than that of patients who did not undergo allo-HSCT (5.6 months; P = 0.1449). Patients with pulmonary infection at diagnosis experienced worse OS than those without pulmonary infection (2.3 months vs. 15.4 months; P < 0.0001). Moreover, 61.9% of patients with pulmonary infection had immune dysfunction, with a ratio of CD4+ to CD8+ T lymphocytes below two. Pulmonary infections and complex karyotypes were independent adverse prognostic factors for OS. In conclusion, TP53 abnormalities in patients with MDS were frequently accompanied by complex karyotypes, and treatments based on hypomethylating agents or venetoclax have limited efficacy. Pulmonary infections associated with immune dysfunction is associated with poor prognosis.