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Objective: To elucidate the small molecule peptides in Shanxi vinegar and further explore their potential mechanism of action against cardiovascular and other related diseases. Methods: The small molecule peptides of Shanxi vinegar were analyzed using ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The targets and pathways of small molecule peptides were predicted via Genecards, Drugbank 5.0, DAVID, and other databases. The "component-target-signaling pathway-disease" network was constructed using Cytoscape software. Autodock Dock 1.5.6 and Pymol 2.2.0 were used to perform molecular docking between the core targets of Shanxi vinegar and the components. Results: A total of 41 small molecule peptide compounds were identified by UPLC-Q-TOF-MS/MS, which including 27 cyclic dipeptides, 10 linear dipeptides, and 4 tripeptides. The "component-target-signaling pathway-disease" network, contributing to the health-promoting effects on cardiovascular and obesity, encompasses 14 active components and 109 drug targets. A total of 59 pathways were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking results demonstrated favorable binding interactions between the core targets (F2, MAPK1, MMP9, VCAM1) and the corresponding active components Cyclo (Leu-Pro), Val-Val, Pro-Phe, Cyclo (His-Pro) in Shanxi vinegar, which preliminarily confirming the accuracy of the network pharmacology prediction. Conclusion: Shanxi vinegar might prevent and regulate cardiovascular diseases and obesity through multiple components, targets and pathways.

Abstract We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P 30 ng/mL) and deficient groups (

Obesity and type 2 diabetes are widespread throughout the world, especially in developed countries. Starch is an important part of human staple food, the modulating of starch digestibility is conducive to reducing postprandial blood glucose levels and alleviating the chronic disease caused by high caloric intake. The digestion properties of starch are correlated with its structural features, including crystallization, amylose/amylopectin ratio, non-starch components, etc. Among the modified methods applied to regulate starch digestibility, non-thermal processing techniques (NTPT) receive extensive attention due to the characteristics of safety, environmental friendliness and high efficiency. The influence and mechanism of NTPT on the digestion properties of starch are discussed in this review, including ultrasounds, high pressure, γ-irradiation, etc. NTPT induces the alternation of morphological and structural characteristics of native starch, changing their sensitivity to enzymes. The effects of NTPT on the digestibility of starch are highly related to the processing parameters and structure characteristics of native starch. The review shows that NTPT is an effective way to modulate the digestion properties of starch and prevent people from suffering from chronic diseases such as obesity and type 2 diabetes.

Abstract. Background:. Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors. Methods:. The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25–70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020. Results:. The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy. Conclusions:. We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Genome-scale metabolic models (GEMs) have been widely employed to predict microorganism behaviors. However, GEMs only consider stoichiometric constraints, leading to a linear increase in simulated growth and product yields as substrate uptake rates rise. This divergence from experimental measurements prompted the creation of enzyme-constrained models (ecModels) for various species, successfully enhancing chemical production. Building upon studies that allocate macromolecule resources, we developed a Python-based workflow (ECMpy) that constructs an enzyme-constrained model. This involves directly imposing an enzyme amount constraint in GEM and accounting for protein subunit composition in reactions. However, this procedure demands manual collection of enzyme kinetic parameter information and subunit composition details, making it rather user-unfriendly. In this work, we've enhanced the ECMpy toolbox to version 2.0, broadening its scope to automatically generate ecGEMs for a wider array of organisms. ECMpy 2.0 automates the retrieval of enzyme kinetic parameters and employs machine learning for predicting these parameters, which significantly enhances parameter coverage. Additionally, ECMpy 2.0 introduces common analytical and visualization features for ecModels, rendering computational results more user accessible. Furthermore, ECMpy 2.0 seamlessly integrates three published algorithms that exploit ecModels to uncover potential targets for metabolic engineering. ECMpy 2.0 is available at https://github.com/tibbdc/ECMpy or as a pip package (https://pypi.org/project/ECMpy/).

Abstract This paper introduces the efficient medical-images-aimed segment anything model (EMedSAM), addressing the high computational demands and limited adaptability of using SAM for medical image segmentation tasks. We present a novel, compact image encoder, DD-TinyViT, designed to enhance segmentation efficiency through an innovative parameter tuning method called med-adapter. The lightweight DD-TinyViT encoder is derived from the well-known ViT-H using a decoupled distillation approach.The segmentation and recognition capabilities of EMedSAM for specific structures are improved by med-adapter, which dynamically adjusts the model parameters specifically for medical imaging. We conducted extensive testing on EMedSAM using the public FLARE 2022 dataset and datasets from the First Hospital of Zhejiang University School of Medicine. The results demonstrate that our model outperforms existing state-of-the-art models in both multi-organ and lung segmentation tasks.

Abstract Background and aim Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. Methods A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. Results In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. Conclusion The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.

Illicit discharges into sewer systems are a widespread concern within China's urban drainage management. They can result in unforeseen environmental contamination and deterioration in the performance of wastewater treatment plants. Consequently, pinpointing the origin of unauthorized discharges in the sewer network is crucial. This study aims to evaluate an integrative method that employs numerical modeling and statistical analysis to determine the locations and characteristics of illicit discharges. The Storm Water Management Model (SWMM) was employed to track water quality variations within the sewer network and examine the concentration profiles of exogenous pollutants under a range of scenarios. The identification technique employed Bayesian inference fused with the Markov chain Monte Carlo sampling method, enabling the estimation of probability distributions for the position of the suspected source, the discharge magnitude, and the commencement of the event. Specifically, the cases involving continuous release and multiple sources were examined. For single-point source identification, where all three parameters are unknown, concentration profiles from two monitoring sites in the path of pollutant transport and dispersion are necessary and sufficient to characterize the pollution source. For the identification of multiple sources, the proposed SWMM-Bayesian strategy with improved sampling is applied, which significantly improves the accuracy. HIGHLIGHTS Identifying pollution sources can be applied for both instantaneous and continuous discharge scenarios.; To characterize a single pollution source, data from two monitoring sites along the pollutant's path are necessary and sufficient.; The strategic placement of monitoring sites and improved sampling enhance the effectiveness and precision of the Bayesian-SWMM approach for identifying multiple unauthorized discharge sources.;

Abstract Tin-lead halide perovskites with a bandgap near 1.2 electron-volt hold great promise for thin-film photovoltaics. However, the film quality of solution-processed Sn-Pb perovskites is compromised by the asynchronous crystallization behavior between Sn and Pb components, where the crystallization of Sn-based perovskites tends to occur faster than that of Pb. Here we show that the rapid crystallization of Sn is rooted in its stereochemically active lone pair, which impedes coordination between the metal ion and Lewis base ligands in the perovskite precursor. From this perspective, we introduce a noncovalent binding agent targeting the open metal site of coordinatively unsaturated Sn(II) solvates, thereby synchronizing crystallization kinetics and homogenizing Sn-Pb alloying. The resultant single-junction Sn-Pb perovskite solar cells achieve a certified power conversion efficiency of 24.13 per cent. The encapsulated device retains 90 per cent of the initial efficiency after 795 h of maximum power point operation under simulated one-sun illumination.

Abstract Background H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. Results Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. Conclusions Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract

Abstract Background Iron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press–strain loop (LV-PSL). Methods Sixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL

Abstract Background Low back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients’ mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients. Methods This is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (

Abstract Background COVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children. Methods This study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection. Results Among the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P

Abstract To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.

Abstract Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier’s intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy. Graphical Abstract

The confined aquifer dewatering for long-deep excavations usually encounters challenges due to complicated geotechnical conditions, large excavation sizes, and high hydraulic pressures. To propose the most efficient scheme of confined aquifer dewatering for long-deep excavations, dewatering optimizations were performed using the simulation–optimization method. An open cut tunnel of the Jiangyin-Jingjiang Yangtze River Tunnel Project was taken as an example. The methods of finite element and linear programming (LP) were combined to optimize the dewatering process. A three-dimensional finite element model was developed. After simulating the pumping tests, hydraulic conductivity was inverted. Then, necessary parameters in the LP method were determined by simulating dewatering with each pumping well, and various LP models were developed based on some important influence factors such as dewatering sequence, considered pumping wells, and pumping rate limitation. Finally, the optimal pumping rates were solved and applied to the numerical model, with induced drawdown and ground settlement computed for comparison. The results indicate that the optimization can significantly reduce the required wells in the original design. Dewatering in the deepest zone exhibits the highest efficiency for long-deep excavations with gradually varying depths. For the dewatering sequence from the shallowest to the deepest zone, more pumping wells are required but less energy is consumed. Higher quantity and more advantageous locations of pumping wells in the LP model usually result in lower total pumping rate, drawdown, and ground settlement. If more pumping wells are considered in the deepest zone, pumping rate limitation of single well will only slightly increase the total pumping rate, number of required pumping wells, drawdown, and ground settlement.

Abstract Background Childbirth pain is a physiological phenomenon during the delivery process, the intense pain of childbirth could bring harmful effects to pregnant women and their babies. Assessment of childbirth pain is the first step in childbirth pain intervention. Some pain assessment scales have shortcomings such as interfering in the birthing process and affecting pain perception during delivery, while the Rating Scale of Pain Expression during Childbirth (ESVADOPA) could be used as an auxiliary scale to compensate for these shortcomings. The purpose of this study was to introduce the ESVADOPA and adapt it among Chinese pregnant women to check on the psychometric properties of the translated version of ESVADOPA. Methods A new translation model based on Brislin’s classical back translation model was used to translate and cross-cultural adapt the ESVADOPA. During June 2021 and June 2022, pregnant women at Shandong Provincial Hospital Affiliated to Shandong First Medical University were invited. In the stage of translation and cross-culturally adaptation, 18 midwives and 30 pregnant women were invited to participate in the first round of pre-experiment. And in the second round of pre-experiment, 15 midwives and 20 pregnant women were invited to participate. The Chinese version of ESVADOPA was tested on a group of pregnant women (N = 487). Construct validity was evaluated by exploratory factor analysis, confirmatory factor analysis and criterion-related validity. Reliability was assessed by Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability and Guttman split-half reliability. Results The item statistical analysis and construct validity resulted in six items and one factor that explained 61.064% of the total variance. Confirmatory factor analysis showed that the data fit the one-factor structure. Criterion-related validity indicated that the scale is significantly and positively correlated with the Numeric Rating Scale (NRS). Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability, and Guttman split-half reliability of the Chinese version of ESVADOPA were 0.868, 0.896, 0.845, 0.842, respectively. Conclusion The Chinese version of the ESVADOPA with good reliability and validity data could be used to assess the pain rating of pregnant women during childbirth without interfering in the birthing process.

Abstract Legumes acquire nitrogen-fixing ability by forming root nodules. Transferring this capability to more crops could reduce our reliance on nitrogen fertilizers, thereby decreasing environmental pollution and agricultural production costs. Nodule organogenesis is complex, and a comprehensive transcriptomic atlas is crucial for understanding the underlying molecular events. Here, we utilized spatial transcriptomics to investigate the development of nodules in the model legume, Lotus japonicus. Our investigation has identified the developmental trajectories of two critical regions within the nodule: the infection zone and peripheral tissues. We reveal the underlying biological processes and provide gene sets to achieve symbiosis and material exchange, two essential aspects of nodulation. Among the candidate regulatory genes, we illustrate that LjNLP3, a transcription factor belonging to the NIN-LIKE PROTEIN family, orchestrates the transition of nodules from the differentiation to maturation. In summary, our research advances our understanding of nodule organogenesis and provides valuable data for developing symbiotic nitrogen-fixing crops.

Abstract Although multiple myeloma (MM) responds well to immunotherapeutic treatment, certain portions of MM are still unresponsive or relapse after immunotherapy. Other immune molecules are needed for the immunotherapy of MM. Here, we revealed that leukocyte immunoglobulin-like receptor B4 (LILRB4) was highly expressed in multiple myeloma cell lines and patient samples and that the expression of LILRB4 was adversely correlated with the overall survival of MM patients. Knockdown of LILRB4 efficiently delayed the growth of MM cells both in vitro and in vivo. Mechanistically, IKZF1 transactivated LILRB4 expression to trigger the downstream of STAT3-PFKFB1 pathways to support MM cell proliferation. Blockade of LILRB4 signaling by blocking antibodies can effectively inhibit MM progression. Our data show that targeting LILRB4 is potentially an additional therapeutic strategy for the immunotherapeutic treatment of MM.

Abstract Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17–2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.

Abstract Objective Diabetic foot ulcer (DFU) is a common and debilitating complication of diabetes that is associated with an increased risk of lower-limb amputation and a reduced life expectancy. Tibial cortex transverse transport (TTT) has become a newly alternative surgical method to facilitate ulcer healing and prevent lower limb amputation. Herein, we investigated the efficacy of TTT in treating DFU and changes of serum omentin-1 and irisin levels. Methods This study prospectively recruited 52 consecutive patients with DFU who were treated with TTT. The follow-up was performed weekly during the first 12 weeks postoperatively and every 3 months until 1 year after TTT. The serum levels of vascular endothelial growth factor (VEGF), omentin-1, and irisin in DFU patients undergoing TTT were determined by ELISA methods on the preoperative 1st day, postoperative 2nd week and 4th week. Results The wound healing rate was 92.3% (48/52) at the 1-year follow-up. The visual analog scale (VAS) pain scores of patients showed a significant reduction at the 4th week after TTT (p

Abstract The effect of the place-based policies on sustainable development has received substantial attention in economic research. In China, the industrial transformation and upgrading exemplary zone policy is a prominent example of such policies, as it targets old industrial and resource-based cities. The paper provides an early assessment of the policy’s capability to reduce carbon emissions. Specifically, we use data from old industrial and resource-based cities for the period of 2012–2019 and apply the difference-in-differences method to examine the policy’s influence on total carbon emissions and intensity. The results show that the policy can effectively reduce carbon emissions through reducing energy consumption, promoting urban green innovation and tertiary industry agglomeration. Compared to resource-based cities, cities with a low level of economic development and central, western cities, this impact is more notable in old industrial cities, cities with a high level of economic development and eastern cities. Additional analysis reveals that the policy has beneficial spatial radiation impacts on the nearby cities as well. In the meanwhile, the strategy may have a synergy effect on reducing carbon emissions and pollution. The results of this study may have an impact on how nations implement place-based policies and reduce carbon emissions.

Abstract Large language models (LLMs) are seen to have tremendous potential in advancing medical diagnosis recently, particularly in dermatological diagnosis, which is a very important task as skin and subcutaneous diseases rank high among the leading contributors to the global burden of nonfatal diseases. Here we present SkinGPT-4, which is an interactive dermatology diagnostic system based on multimodal large language models. We have aligned a pre-trained vision transformer with an LLM named Llama-2-13b-chat by collecting an extensive collection of skin disease images (comprising 52,929 publicly available and proprietary images) along with clinical concepts and doctors’ notes, and designing a two-step training strategy. We have quantitatively evaluated SkinGPT-4 on 150 real-life cases with board-certified dermatologists. With SkinGPT-4, users could upload their own skin photos for diagnosis, and the system could autonomously evaluate the images, identify the characteristics and categories of the skin conditions, perform in-depth analysis, and provide interactive treatment recommendations.

Abstract Background This study aimed to explore the associations between triglyceride glucose (TyG) index-related obesity indices and periodontitis within the American population. Methods This cross-sectional investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) for 2009–2014. The association between the TyG–waist-to-height ratio (TyG-WHtR), TyG–weight-adjusted-waist index (TyG-WWI), TyG–waist circumference (TyG-WC), or TyG–body mass index (TyG-BMI) and periodontitis was investigated utilizing multivariable logistic regression model, subgroup, and dose-response curve analyses. Results This study enrolled 4,808 adult participants. Except for TyG-BMI, which did not exhibit a relationship with periodontitis, TyG-WHtR, [odds ratio (OR) (95% confidence interval (CI))] = 2.83 [1.58–5.10], P = 0.002], TyG-WWI [OR (95% CI) = 7.50 (3.06–18.34), P

Developing highly active oxygen evolution reaction (OER) electrocatalysts with robust durability is essential in producing high-purity hydrogen through water electrolysis. Layered double hydroxide (LDH) based catalysts have demonstrated efficient catalytic performance toward the relatively sluggish OER. By considering the promotion effect of phosphate (Pi) on proton transfer, herein, a facile phosphate acid (PA) surface-neutralization strategy is developed to in-situ construct NiCo-LDH/NiCoPi hetero-sheets toward OER catalysis. OER activity of NiCo-LDH is significantly boosted due to the proton promotion effect and the electronic modulation effect of NiCoPi. As a result, the facilely prepared NiCo-LDH/NiCoPi catalyst displays superior OER catalytic activity with a low overpotential of 300 mV to deliver 100 mA cm−2 OER and a Tafel slope of 73 mV dec−1. Furthermore, no visible activity decay is detected after a 200-h continuous OER operation. The present work, therefore, provides a promising strategy to exploit robust OER electrocatalysts for commercial water electrolysers.

Background: Drug-induced liver injury (DILI) is a leading cause of drug development failures during clinical trials and post-market introduction. Current biomarkers, such as ALT and AST, lack the necessary specificity and sensitivity needed for accurate detection. Exosomes, which protect LncRNAs from RNase degradation, could provide reliable and easily accessible options for biomarkers. Materials and methods: RNA-sequencing was used to identify differentially expressed LncRNAs (DE-LncRNAs), followed by isolation of LncRNAs from plasma exosomes in this study. Exosome characterization was conducted by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). Bioinformatics analysis included functional enrichment and co-expression network analysis. Five rat models were established, and quantitative real-time PCR was used to verify the specificity and sensitivity of two candidate exosomal LncRNAs. Results: The APAP-induced hepatocellular injury model was successfully established for RNA-sequencing, leading to the identification of several differentially expressed exosomal LncRNAs. Eight upregulated exosomal DE-LncRNAs were selected for validation. Among them, NONRATT018001.2 (p

BackgroundCoal workers' pneumoconiosis (CWP) is a serious occupational lung disease and one of the prescript occupational diseases in China. Epithelial-mesenchymal transition (EMT) is involved in the diffuse fibrosis of lung tissue of pneumoconiosis patients, and its mechanism may be related to the polarization of macrophages regulated by let-7c.ObjectiveTo investigate the effect of let-7c on the regulation of macrophage polarization in EMT in rats induced by coal dust exposure with different content of free SiO2.MethodsSD rats were randomly divided into a control group, a 5% SiO2 group, a 30% SiO2 group, and a 99.9% SiO2 group, with 16 rats in each group. The rats in each group were tracheally titrated with 100 μL of 20 mg·mL−1 suspension (5% SiO2, 30% SiO2, and 99.9% SiO2) or normal saline, respectively. Alveolar lavage fluid was collected at the ends of the 1st month and the 3rd month. The relative expression levels of M1 or M2 markers, CD86 or CD206, in alveolar macrophages (AMs) were detected by immunofluorescence. The inflammation and fibrosis of lung tissue were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), E-cadherin, and vimentin were detected by Western blotting. The expression levels of let-7c and c/EBP-δ genes were detected by real-time fluorescence quantitative PCR.ResultsThe HE and Masson staining results showed that compared with the control group, the degree of pulmonary fibrosis in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased with the increase of dust exposure time. Compared with the control group, the expressions of CD86 and CD206 in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased at the end of the 1st month (F=330.904, 146.801, P

Abstract Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

Computer-aided diagnosis systems play a crucial role in the diagnosis and early detection of breast cancer. However, most current methods focus primarily on the dual-view analysis of a single breast, thereby neglecting the potentially valuable information between bilateral mammograms. In this paper, we propose a Four-View Correlation and Contrastive Joint Learning Network (FV-Net) for the classification of bilateral mammogram images. Specifically, FV-Net focuses on extracting and matching features across the four views of bilateral mammograms while maximizing both their similarities and dissimilarities. Through the Cross-Mammogram Dual-Pathway Attention Module, feature matching between bilateral mammogram views is achieved, capturing the consistency and complementary features across mammograms and effectively reducing feature misalignment. In the reconstituted feature maps derived from bilateral mammograms, the Bilateral-Mammogram Contrastive Joint Learning module performs associative contrastive learning on positive and negative sample pairs within each local region. This aims to maximize the correlation between similar local features and enhance the differentiation between dissimilar features across the bilateral mammogram representations. Our experimental results on a test set comprising 20% of the combined Mini-DDSM and Vindr-mamo datasets, as well as on the INbreast dataset, show that our model exhibits superior performance in breast cancer classification compared to competing methods.

Abstract Despite widespread agreement in the scholarly community about the significance of academic title structure on research output, research on the underlying mechanisms remains insufficient. Social contribution and research resources were selected as mediating variables, panel data of the materials science and engineering discipline of 30 Chinese universities from 2016 to 2020 were chosen as the research samples, and a fixed-effects model was subsequently applied to conduct a chain mediating effect test. The results showed: (1) Both the proportion of national-level talents and that of senior titles can promote research output, with the former having a much greater effect, while the proportion of associate senior titles has an indistinctive negative correlation with research output. (2) Both the proportion of national-level talents and that of senior titles can significantly enhance research output through the chain mediating effect of social contribution and research resources, with national-level talents having a stronger ability to make social contributions and obtain research resources. (3) Social contribution is more effective than research resources in enhancing research output. Based on the findings, it is recommended to improve policies for introducing high-end talents and to increase support for researchers with associate senior titles. Furthermore, it is advisable to establish a research evaluation system based on social influence, guiding researchers to obtain research resources and enhance research output through social contributions.

Abstract Background This study developed a nomogram model using CT-based delta-radiomics features and clinical factors to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). Methods The study retrospectively analyzed 232 ESCC patients who underwent pretreatment and post-treatment CT scans. Patients were divided into training (n = 186) and validation (n = 46) sets through fivefold cross-validation. 837 radiomics features were extracted from regions of interest (ROIs) delineations on CT images before and after nCRT to calculate delta values. The LASSO algorithm selected delta-radiomics features (DRF) based on classification performance. Logistic regression constructed a nomogram incorporating DRFs and clinical factors. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses evaluated nomogram performance for predicting pCR. Results No significant differences existed between the training and validation datasets. The 4-feature delta-radiomics signature (DRS) demonstrated good predictive accuracy for pCR, with α-binormal-based and empirical AUCs of 0.871 and 0.869. T-stage (p = 0.001) and differentiation degree (p = 0.018) were independent predictors of pCR. The nomogram combined the DRS and clinical factors improved the classification performance in the training dataset (AUCαbin = 0.933 and AUCemp = 0.941). The validation set showed similar performance with AUCs of 0.958 and 0.962. Conclusions The CT-based delta-radiomics nomogram model with clinical factors provided high predictive accuracy for pCR in ESCC patients after nCRT.

ObjectiveTo explore the status of knowledge graph-based research into breast cancer microenvironment and to predict future research hotspots. MethodsThe literature related to breast cancer microenvironment in recent 20 years was retrieved from CNKI and Web of Science Core Collection database and analyzed with CiteSpace and VOSviewer. ResultsA total of 825 Chinese articles and 16,221 English articles were retrieved. Visual analysis showed that research focus has gradually shifted from cellular research to molecular research and drug innovation. Cancer stem cells, PD-1, PD-L1, immune checkpoint inhibitors, and nanoparticles are the main subjects of interest in research on breast cancer microenvironment, and the United States has the largest number of studies on breast cancer microenvironment, followed by China and Italy. ConclusionCurrent research mainly focuses on tumor stemness, immunotherapy, and nanodelivery. Owing to deepening research in this field, the targeting of the breast cancer microenvironment for the prevention of tumor development and metastasis and improvement of tumor prognosis has emerged as a new research direction.

Abstract Background The occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China. Methods This was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0—31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs. Results A total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration. Conclusions The current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.

Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute ischemic stroke (AIS) who are ineligible for acute revascularization therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment. Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks (D29), 8 weeks (D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to posttreatment. The secondary outcomes are as follows: D29 change of simplified Fugl-Meyer score from baseline to posttreatment; proportion of participants whose D29 NIHSS scores decreased by four or more points from baseline D90 proportion of subjects with mRS score of 0–2 (inclusive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebrovascular events. Safety endpoint includes mortality within 90 days; proportion of subjects with adverse events/serious adverse events within 90 days. Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expenditures globally and, in turn, benefiting a broader population of stroke patients.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies. Methods This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified. Results High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68+CXCL10+PD-L1+) and diminished CD8+ T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077–2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207–5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p

Spores are the main dormant forms of some bacteria under harsh environment conditions, which are widely distributed in nature. Bacterial spores have a rigid structure, which helps resist to environmental stresses such as heat and ultraviolet radiation. At present, it is difficult to inactivate bacterial spores by the conventional sterilization methods used in the food industry. Therefore, bacterial spores are one of the most important factors influencing the food safety. In recent years, the application of non-thermal processing technologies in killing spores has received great deal of attention. Cold plasma is a novel non-thermal physical sterilization technology, which has a broad application prospect in the food industry due to its various advantages such as high bactericidal efficiency, low energy consumption, and secondary pollution-free. In this paper, the application of cold plasma in the inactivation of bacterial spores in foods is reviewed, and the underlying mechanisms are also summarized in detail. Moreover, the effects of diverse factors on cold plasma-induced spores inactivation are analyzed, and the future research direction is also prospected. This article provides important theoretical basis for the practical application of cold plasma in food safety and quality control.

Biosynthesis of atypical angucyclines involves unique oxidative B-ring cleavage and rearrangement reactions, which are catalyzed by AlpJ-family oxygenases, including AlpJ, JadG, and GilOII. Prior investigations established the essential requirement for FADH2/FMNH2 as cofactors when utilizing the quinone intermediate dehydrorabelomycin as a substrate. In this study, we unveil a previously unrecognized facet of these enzymes as cofactor-independent oxygenases when employing the hydroquinone intermediate CR1 as a substrate. The enzymes autonomously drive oxidative ring cleavage and rearrangement reactions of CR1, yielding products identical to those observed in cofactor-dependent reactions of AlpJ-family oxygenases. Furthermore, the AlpJ- and JadG-catalyzed reactions of CR1 could be quenched by superoxide dismutase, supporting a catalytic mechanism wherein the substrate CR1 reductively activates molecular oxygen, generating a substrate radical and the superoxide anion O2•−. Our findings illuminate a substrate-controlled catalytic mechanism of AlpJ-family oxygenases, expanding the realm of cofactor-independent oxygenases. Notably, AlpJ-family oxygenases stand as a pioneering example of enzymes capable of catalyzing oxidative reactions in either an FADH2/FMNH2-dependent or cofactor-independent manner.

Abstract Background The study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification. Methods We retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion. Results A total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O’Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems. Conclusion Parotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1–2 vs. 3–4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O’Brien staging systems.

Abstract Variations in chromosome number are occasionally observed among oomycetes, a group that includes many plant pathogens, but the emergence of such variations and their effects on genome and virulence evolution remain ambiguous. We generated complete telomere-to-telomere genome assemblies for Phytophthora sojae, Globisporangium ultimum, Pythium oligandrum, and G. spinosum. Reconstructing the karyotype of the most recent common ancestor in Peronosporales revealed that frequent chromosome fusion and fission drove changes in chromosome number. Centromeres enriched with Copia-like transposons may contribute to chromosome fusion and fission events. Chromosome fusion facilitated the emergence of pathogenicity genes and their adaptive evolution. Effectors tended to duplicate in the sub-telomere regions of fused chromosomes, which exhibited evolutionary features distinct to the non-fused chromosomes. By integrating ancestral genomic dynamics and structural predictions, we have identified secreted Ankyrin repeat-containing proteins (ANKs) as a novel class of effectors in P. sojae. Phylogenetic analysis and experiments further revealed that ANK is a specifically expanded effector family in oomycetes. These results revealed chromosome dynamics in oomycete plant pathogens, and provided novel insights into karyotype and effector evolution.

Abstract Biochar is widely used for sediment remediation owing to its excellent adsorption properties and low carbon footprint. However, the impacts of biochar capping on phosphorus (P) bioavailability and mobility in the sediment are little known. In this study, the P mobilization processes in sediments capped with biochar were investigated by combining advanced high-resolution sampling techniques and microbiome analysis. The results showed that biochar is a double-edged sword for the sediment P release, depending on the application dosage and the capping time. In the short term (30 days), 2-cm biochar capping decreased the release flux of soluble reactive phosphorus (SRP) by 73.1%, whereas the 1-cm biochar capping significantly increased the release flux of SRP by 51.0%. After aging of biochar (80 days), the resupply capacity of sediment P was improved, resulting in increases of more than 33.7% and 121.5% in the release fluxes of SRP in the 1-cm and 2-cm capping groups, respectively, compared to the control group. Chemisorption played a pivotal role in regulating the levels of SRP, particularly during the short-term capping period. And more biochar can provide more adsorption sites on P. The P mobilization increase could be attributed to P desorption from biochar after biochar aging. Furthermore, biochar capping intensified the microbial-mediated iron reduction and organic matter decomposition, which enhanced P mobility. Our study highlights the importance of biochar application dosage and the capping time in sediment remediation, providing a scientific basis for the optimization of biochar capping techniques. Graphical Abstract

Highlights Recent progress on the applications of 2D materials in perovskite solar cells is discussed from the views of bottom interfaces, top interfaces, and electrodes. The roles of van der Waals heterojunction in enhancing the performance of perovskite solar cells are highlighted. The future directions and challenges in development of 2D materials-based perovskite solar cells are provided.

Abstract Background The incidence of spontaneous abortion (SA), which affects approximately 15–20% of pregnancies, is the most common complication of early pregnancy. Pathogenic copy number variations (CNVs) are recognized as potential genetic causes of SA. However, CNVs of variants of uncertain significance (VOUS) have been identified in products of conceptions (POCs), and their correlation with SA remains uncertain. Results Of 189 spontaneous abortion cases, trisomy 16 was the most common numerical chromosome abnormality, followed by monosomy X. CNVs most often occurred on chromosomes 4 and 8. Gene Ontology and signaling pathway analysis revealed significant enrichment of genes related to nervous system development, transmembrane transport, cell adhesion, and structural components of chromatin. Furthermore, genes within the VOUS CNVs were screened by integrating human placental expression profiles, PhyloP scores, and Residual Variance Intolerance Score (RVIS) percentiles to identify potential candidate genes associated with spontaneous abortion. Fourteen potential candidate genes (LZTR1, TSHZ1, AMIGO2, H1-4, H2BC4, H2AC7, H3C8, H4C3, H3C6, PHKG2, PRR14, RNF40, SRCAP, ZNF629) were identified. Variations in LZTR1, TSHZ1, and H4C3 may contribute to embryonic lethality. Conclusions CNV sequencing (CNV-seq) analysis is an effective technique for detecting chromosomal abnormalities in POCs and identifying potential candidate genes for SA.

Abstract Marine resources are rich. In recent years, more and more people have paid attention to the development of blue food. Fish protein is one of the essential biomolecules in blue food. It is a natural emulsifier because of its natural, nontoxic, easily obtained, degradable, and good surface activity. The research and application of fish protein as an emulsifier were reviewed in this paper. The emulsifying mechanism of fish protein was discussed. The emulsifying property of fish protein was affected by natural factors (source and protein concentration) and processing environment (ion strength, temperature, and pH). The emulsifying property of fish protein was improved by ultrasound, high pressure, microgel, complexation, glycosylation, and enzyme cross‐linking. It was pointed out that future research of fish protein applications should focus on the problems of shortening the gap between laboratory and commercial; stable emulsion of fish protein is difficult to preserve and single loading. It provides a reference for the development of fish protein emulsifiers.

Abstract Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

Background: Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others. Aims: To investigate the role of TSLP in the pathogenesis of psoriasis. Study Design: In vitro and in vivo study. Methods: To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4+ T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4+ T cells. Conclusion: These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.

Underground hydrogen storage (UHS) and compressed air energy storage (CAES) are two viable large-scale energy storage technologies for mitigating the intermittency of wind and solar power. Therefore, it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes. This study employs a multi-physical coupling model to compare the operations of CAES and UHS, integrating gas thermodynamics within caverns, thermal conduction, and mechanical deformation around rock caverns. Gas thermodynamic responses are validated using additional simulations and the field test data. Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes. Hydrogen reaches higher temperature and pressure following gas charging stage compared to air, and the ideal gas assumption may lead to overestimation of gas temperature and pressure. Unlike steel lining of CAES, the sealing layer (fibre-reinforced plastic FRP) in UHS is prone to deformation but can effectively mitigates stress in the sealing layer. In CAES, the first principal stress on the surface of the sealing layer and concrete lining is tensile stress, whereas UHS exhibits compressive stress in the same areas. Our present research can provide references for the selection of energy storage methods.

The lateral response of combined pile-raft foundations (CPRFs) adjacent to tunnel excavation is a challenging problem owing to the complexity of the pile-raft connections. In current engineering practices, the impact of these connections on the lateral performance of CPRFs is frequently overlooked, despite their importance. To address this issue, this study conducted three-dimensional finite element analyses to evaluate the contribution of pile-raft connections to the tunnelling-induced lateral performance of CPRFs in saturated clay. In the analysis, both passive and active loading at the pile head could be considered by varying the tunnel depth. Several parameter studies, such as relative pile-raft modulus, pile embedded modulus, pile embedded depths, and pile shaft skin friction, were conducted to determine the optimal design parameters for CPRFs. The results indicate that pile-raft connections significantly affect the tunnelling-induced deflections and bending moments of pile groups. Inspired by the results, a simplified design method, the pile-raft connection coefficient Kc was proposed. Additionally, the pile-head restraint percentage was established to make a relationship with the pile-raft connection coefficient in order to assess the pile-raft connection and guide the pile-raft design. In this paper, the recommended range value of Kc is 10–200 and the range value of pile-head restraint percentage is 24%–42%.

In the present work, seven Mg-Zn-Ag alloys with the nominal composition of Mg96-xZnxAg4 (x = 17, 20, 23, 26, 29, 32, 35 in at.%) were prepared by induction melting and single-roller melt-spinning. The X-ray diffraction (XRD) analyses indicate the metallic glasses with three composition of Mg73Zn23Ag4, Mg70Zn26Ag4, and Mg67Zn29Ag4 were obtained successfully. The differential scanning calorimetry (DSC) measurement was used to obtain the characteristic temperature of Mg-Zn-Ag metallic glasses for the glass-forming ability analysis. The maximum glass transition temperature (Trg) was found to be 0.525 with a composition close to Mg67Zn29Ag4, which results in the best glass-forming ability. Moreover, the immersion test in simulated body fluid (SBF) demonstrate the relative homogeneous corrosion behavior of the Mg-Zn-Ag metallic glasses. The corrosion rate of Mg-Zn-Ag metallic glasses in SBF solution decreases with the increase of Zn content. The sample Mg67Zn29Ag4 has the lowest corrosion rate of 0.19 mm/yr, which could meet the clinical application requirement well. The in vitro cell experiments show that the Madin-Darby canine kidney (MDCK) cells cultured in sample Mg67Zn29Ag4 and its extraction medium have higher activity. However, the Mg-Zn-Ag metallic glasses exhibit obvious inhibitory effect on human rhabdomyosarcoma (RD) tumor cells. The present investigations on the glass-forming ability, corrosion behavior, cytocompatibility and tumor inhibition function of the Mg-Zn-Ag based metallic glass could reveal their biomedical application possibility.