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Abstract. Background:. The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups. Methods:. A total of 2,968,462 participants aged 35–75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014–2019) were included. Cox proportional hazard models and Fine–Gray subdistribution hazard models were used to estimate associations between LDL-C categories (

Abstract Background In recent years, transcatheter aortic valve implantation (TAVI) has become a widely used treatment for low-risk elderly patients. As an alternative to TAVI via the femoral artery, transapical TAVI (TA-TAVI) is a better surgical choice for patients with severe vascular diseases. The J-Valve assists doctors in completing valve implantation easily using its positioning locator device, which prevents the self-leaflet from approaching the sinus wall. This function acts as coronary artery protection to avoid coronary occlusion. However, the clinical prognosis of J-Valve implantation for patients with aortic valve stenosis and low coronary openings is unclear. Methods A retrospective analysis was performed on 30 patients with aortic stenosis (AS) and coronary openings measuring ≤ 10 mm in height. All patients underwent TA-TAVI with J-Valve implantation. Patients were screened using preoperative computed tomography three-dimensional imaging of the aortic root, and the safety and efficacy of the procedure were evaluated. The collected indexes included patients’ general data, cardiac function, preoperative imaging parameters, intraoperative data and postoperative short-term prognosis. Results Of the 30 patients in the study successfully underwent TA-TAVI and J-Valve implantation. Two patients required temporary cardiopulmonary bypass assistance during the operation due to heart failure. The implant success rate was 100%, and there were no deaths within 30 days postoperatively. No patients experienced intraoperative or postoperative coronary artery occlusion. Postoperative echocardiography, physiological state and laboratory test results indicated that all patients recovered well. The electrocardiograms remained normal after TA-TAVI, and heart function improved within 30 days. Conclusion Transapical TAVI with J-Valve implantation is a safe and effective treatment option for patients with AS and a low coronary artery opening. Preoperative coronary artery evaluation and the locators of the J-Valve are crucial in preventing coronary artery occlusion. This treatment regimen provides beneficial outcomes and warrants further multi-centre clinical research in the future.

Abstract The present study investigates the efficacy of newly developed Zr-based metal–organic frameworks, specifically MIP-206, and its amine-modified counterpart, MIP-206-NH2, for the re-covery of antimony (Sb) from both synthetic and actual mining wastewater. Batch method studies were employed to examine the effect of waste media pH, Sb concentration, process kinetics, and the performance of the regeneration solution. MIP-206-NH2 exhibited impressive separation capabilities, achieving 102.18 mg/g and 63.23 mg/g for Sb (V) and Sb (III), respectively. In contrast, the pristine MIP-206 reached maximum values of 26.26 mg/g for Sb (V) and 16.95 mg/g for Sb (III). The separation process was well-described by the Langmuir equation, and the kinetics followed the pseudo-second-order model. Although the amine modification resulted in a decrease in the surface area of MIP-206 from 1345.21 to 1169.86 m2/g, SEM and XRD analyses confirmed that the structural integrity of MIP-206-NH2 remained unchanged. In terms of reusability, MIP-206-NH2 maintained up to 90% of its separation performance over 9 cycles, while MIP-206 demonstrated effectiveness for 7 cycles. The regeneration solution exhibited a capacity of approximately 0.63 mol/L for Sb (V) and 0.71 mol/L for Sb (III). Furthermore, MIP-206 and MIP-206-NH2 demonstrated successful application in selectively separating Sb from real mining wastewater.

ABSTRACT: Adequate energy supply is a crucial factor for maintaining the production performance in cows during the early lactation period. Adding fatty acids (FA) to diets can improve energy supply, and the effect could be related to the chain length and degree of saturation of those FA. This study was conducted to evaluate the effect of different ratios of palmitic acid (C16:0) to oleic acid (cis-9 C18:1) on the production performance, nutrient digestibility, blood metabolites, and milk FA profile in early lactation dairy cows. Seventy-two multiparous Holstein cows (63.5 ± 2.61 days in milk) blocked by parity (2.39 ± 0.20), body weight (668.3 ± 20.1 kg), body condition score (3.29 ± 0.06), and milk yield (47.9 ± 1.63 kg) were used in a completely randomized design. Cows were divided into 3 groups with 24 cows in each group. Cows in the 3 treatment groups were provided iso-energy and iso-nitrogen diets, but the C16:0 to cis-9 C18:1 ratios were different: (1) 90.9% C16:0 + 9.1% cis-9 C18:1 (90.9:9.1); (2) 79.5% C16:0 + 20.5% cis-9 C18:1 (79.5:20.5); and (3) 72.7% C16:0 + 27.3% cis-9 C18:1 (72.7:27.3). Fatty acids were added at 1.3% on a dry matter basis. Although the dry matter intake fat-corrected milk yield and energy-corrected milk yield were not affected, the milk yield, milk protein yield, and feed efficiency increased linearly with increasing cis-9 C18:1 ratio. The milk protein percentage and milk fat yield did not differ among treatments, whereas the milk fat percentage tended to decrease linearly with the increasing cis-9 C18:1 ratio. The lactose yield increased linearly and lactose percentage tended to increase linearly with increasing cis-9 C18:1 ratio, but the percentage of milk total solids and somatic cell count decreased linearly. Although body condition scores were not affected by treatments, body weight loss decreased linearly with increasing cis-9 C18:1 ratio. The effect of treatment on nutrient digestibility was limited, except for a linear increase in ether extract and neutral detergent fiber digestibility with increasing cis-9 C18:1 ratio. There was a linear increase in the concentration of plasma glucose, but the triglyceride and nonesterified FA concentrations decreased linearly with increasing cis-9 C18:1 ratio. As the cis-9 C18:1 ratio increased, the concentration of de novo FA decreased quadratically, but the mixed and preformed fatty acids increased linearly. In conclusion, increasing cis-9 C18:1 ratio could increase production performance and decrease body weight loss by increasing nutrient digestibility, and the ratio that had the most powerful beneficial effect on early lactation cows was 72.7:27.3 (C16:0 to cis-9 C18:1).

Introduction: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. Objectives: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. Methods: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Results: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Conclusions: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Background: Medulloblastoma (MB) is a malignant pediatric central nervous system tumor that is prone to leptomeningeal metastasis. Currently, apart from magnetic resonance imaging and cerebrospinal fluid (CSF) cytology, there are no reliable biomarkers for MB progression. Cytokines are key proteins in signaling pathways in the tumor microenvironment and are closely related to tumor recurrence and progression. This study aimed to investigate the CSF cytokine profile in pediatric patients with MB to identify biomarkers of tumor progression and metastasis. Methods: In total, 10 patients were recruited for this study. Five patients had nonmetastatic MB and five had metastatic MB. A cytokine antibody array was used to detect the expression of 120 cytokines in the CSF, and differentially expressed cytokines were screened by integrated bioinformatics analysis. Results: Twenty-seven cytokines were upregulated in patients with MB compared to control individuals. Of these, eight were upregulated by > 1.5-fold (CCL2, BMP-4, beta-NGF, FGF-7, IL-12p40, eotaxin-2, M-CSF, and NT-4). Twelve cytokines were differentially expressed between patients with metastatic MB and nonmetastatic (nine cytokines were upregulated and three were downregulated). Among them, NAP-2, MIP-1α, MIP-1β, IGFBP-1, IGFBP-2 and IGFBP-3 were upregulated by more than two-fold. Gene Ontology analysis revealed that the upregulated cytokines were enriched mainly in “epithelial cell proliferation” and “chemotaxis,” and the Kyoto Encyclopedia of Genes and Genomes analysis indicated the enrichment of the “MAPK,” “PI3K-Akt,” and “Ras” signaling pathways. Conclusions: The present study investigated cytokine profiles in the CSF of pediatric patients with MB. Our results suggest that these differentially expressed cytokines may serve as novel markers for detecting MB, especially for assessing the risk of progression and metastasis.

Microplastics and antibiotics are emerging contaminants in agricultural soil that can have negative effects on crops. However, limited research has been conducted on the effects of the polypropylene (PP) microplastic and sulfamethoxazole (SMX) co-exposure on crops, specifically regarding the impact of PP microplastics on SMX uptake and transport in crops. In this study, hydroponic experiments were carried out using lettuce (Lactuca sativa L.), PP microplastics (1.0 g L−1), and SMX (0.5 mg L−1 or 2.5 mg L−1) to investigate the individual and co-exposure effects of PP microplastics and SMX on Lettuce growth, explore the uptake and translocation of SMX in lettuce and elucidate the underlying mechanism of PP microplastic impact on SMX uptake. Results demonstrated that co-exposure to 1.0 g L−1 of PP microplastics and 0.5 mg L−1 of SMX resulted in an enhanced toxic effect. However, no intensified toxic effect on the lettuce was observed when 1.0 g L−1 PP microplastics were added in the presence of 2.5 mg L−1 SMX, indicating that the SMX dominated the toxic effect on lettuce at high concentrations. Additionally, the study found that the water absorption process controlled by the aquaporin and transpiration contributed to the uptake and translocation of SMX in lettuce. When exposed to PP microplastics, no impact was observed on the aquaporin contents of the lettuce while the transpiration rate was significantly decreased by 31.6 % - 44.2 % resulting from microplastics adhered to the root surface. Therefore, in the presence of 2.5 mg L−1 SMX, the SMX uptake in the lettuce root was inhibited by 35.9 % (P < 0.05) when exposed to 1.0 g L−1 PP microplastic. This work deepens our understanding of the behaviour of microplastics and antibiotics in the terrestrial environment.

ObjectiveCerebrospinal fluid biomarkers are challenging to use for diagnosing mild cognitive impairment (MCI) in large populations, and there is an urgent need for new blood biomarkers. The aim of this study is to investigate whether astrocyte activation is correlated with hippocampal atrophy, and to assess the potential of glial fibrillary acidic protein (GFAP) as a biomarker for diagnosing MCI among community-dwelling older individuals.MethodsThis cross-sectional study included 107 older adults. The levels of GFAP in serum were measured, and the volumetric assessment of gray matter within hippocampal subregions was conducted using Voxel-Based Morphometry (VBM). The relationship between hippocampal subregion volume and blood biomarkers were analyzed using partial correlation. The effectiveness of blood biomarkers in differentiating MCI was assessed using a receiver operating characteristic (ROC) curve.ResultsWe found that serum GFAP levels were significantly elevated in the MCI group compared to the cognitively normal (CN) group. Additionally, individuals with MCI exhibited a reduction gray matter volume in specific hippocampal subregions. Notably, the right dentate gyrus (DG) and right cornu ammonis (CA) subregions were found to be effective for distinguishing MCI patients from CN individuals. Serum levels of GFAP demonstrate a sensitivity of 65.9% and a specificity of 75.6% in differentiating patients with MCI from CN individuals.ConclusionSpecific atrophy within hippocampal subregions has been observed in the brains of community-dwelling elderly individuals. Elevated levels of circulating GFAP may serve as a sensitive peripheral biomarker indicative of hippocampal-specific cognitive alterations in patients with MCI.

The reported electrocaloric (EC) effect in ferroelectrics is poised for application in the next generation of solid-state refrigeration technology, exhibiting substantial developmental potential. This study introduces a novel and efficient EC effect strategy in (1–x)Pb(Lu1/2Nb1/2)O3-xPbTiO3 (PLN-xPT) ceramics for low electric-field-driven devices. Phase-field simulations provide fundamental insights into thermally induced continuous phase transitions, guiding subsequent experimental investigations. A comprehensive composition/temperature-driven phase evolution diagram is constructed, elucidating the sequential transformation from ferroelectric (FE) to antiferroelectric (AFE) and finally to paraelectric (PE) phases for x=0.10−0.18 components. Direct measurements of EC performance highlight x=0.16 as an outstanding performer, exhibiting remarkable properties, including an adiabatic temperature change (ΔT) of 3.03 ​K, EC strength (ΔT/ΔE) of 0.08 ​K ​cm kV−1, and a temperature span (Tspan) of 31 ​°C. The superior EC effect performance is attributed to the temperature-induced FE to AFE transition at low electric fields and diffusion phase transition behavior contributing to the wide Tspan. This work provides valuable insights into developing high-performance EC effect across broad temperature ranges through the strategic design of continuous phase transitions, offering a simplified and economical approach for advancing ecofriendly and efficient solid-state cooling technologies.

Olfactory receptors are seven-transmembrane G-protein-coupled receptors on the cell surface. Over the past few decades, evidence has been mounting that olfactory receptors are not unique to the nose and that their ectopic existence plays an integral role in extranasal diseases. Coupled with the discovery of many natural or synthetic odor-compound ligands, new roles of ecnomotopic olfactory receptors regulating blood glucose, obesity, blood pressure, and other metabolism-related diseases are emerging. Many well-known scientific journals have called for attention to extranasal functions of ecnomotopic olfactory receptors. Thus, the prospect of ecnomotopic olfactory receptors in drug target research has been greatly underestimated. Here, we have provided an overview for the role of ecnomotopic olfactory receptors in metabolic diseases, focusing on their effects on various metabolic tissues, and discussed the possible molecular biological and pathophysiological mechanisms, which provide the basis for drug development and clinical application targeting the function of ecnomotopic olfactory receptors via literature machine learning and screening.

Myricaria laxiflora is an endangered shrub plant with remarkable tolerance to waterlogging stress, however, little attention has been paid to understanding the underlying mechanisms. Here, physiological and transcriptomic approaches were applied to uncover the physiological and molecular reconfigurations in the stem of M. laxiflora in response to waterlogging stress. The accumulation of the contents of H2O2 and malonaldehyde (MDA) alongside increased activities of enzymes for scavenging the reactive oxygen species (ROS) in the stem of M. laxiflora were observed under waterlogging stress. The principal component analysis (PCA) of transcriptomes from five different timepoints uncovered PC1 counted for 17.3 % of total variations and separated the treated and non-treated samples. A total of 8714 genes in the stem of M. laxiflora were identified as differentially expressed genes (DEGs) under waterlogging stress, which could be assigned into two different subgroups with distinct gene expression patterns and biological functions. The DEGs involved in glycolysis were generally upregulated, whereas opposite results were observed for nitrogen uptake and the assimilation pathway. The contents of abscisic acid (ABA) and jasmonic acid (JA) were sharply decreased alongside the decreased mRNA levels of the genes involved in corresponding synthesis pathways upon waterlogging stress. A network centered by eight key transcription factors has been constructed, which uncovered the inhibited cell division processes in the stem of M. laxiflora upon waterlogging stress. Taken together, the obtained results showed that glycolysis, nitrogen metabolism and meristem activities played an important role in the stem of M. laxiflora in response to waterlogging stress.

Summary: Energy crops play a vital role in meeting future energy and chemical demands while addressing climate change. However, the idealization of low-carbon workflows and careful consideration of cost-benefit equations are crucial for their more sustainable implementation. Here, we propose tobacco as a promising energy crop because of its exceptional water solubility, mainly attributed to a high proportion of water-soluble carbohydrates and nitrogen, less lignocellulose, and the presence of acids. We then designed a strategy that maximizes biomass conversion into bio-based products while minimizing energy and material inputs. By autoclaving tobacco leaves in water, we obtained a nutrient-rich medium capable of supporting the growth of microorganisms and the production of bioproducts without the need for extensive pretreatment, hydrolysis, or additional supplements. Additionally, cultivating tobacco on barren lands can generate sufficient biomass to produce approximately 573 billion gallons of ethanol per year. This approach also leads to a reduction of greenhouse gas emissions by approximately 76% compared to traditional corn stover during biorefinery processes. Therefore, our study presents a novel and direct strategy that could significantly contribute to the goal of reducing carbon emissions and global sustainable development compared to traditional methods.

Microplastics (MPs) have been detected in various human tissues. However, whether MPs can accumulate within tumors and how they affect the tumor immune microenvironment (TIME) and therapeutic responses remains unclear. This study aimed to determine the presence of MPs in tumors and their potential effects on the TIME. Sixty-one tumor samples were collected for analysis. The presence of MPs in tumors was qualitatively and quantitatively assessed using pyrolysis-gas chromatography-mass spectrometry. MPs were detected in 26 of the samples examined. Three types of MPs were identified: polystyrene, polyvinyl chloride, and polyethylene. In lung, gastric, colorectal, and cervical tumors, the MP detection rates were 80 %, 40 %, 50 %, and 17 % (7.1–545.9 ng/g), respectively. MPs were detected in 70 % of pancreatic tumors (18.4–427.1 ng/g) but not detected in esophageal tumors. In pancreatic cancer, the MP-infiltrated TIME exhibited a reduction in CD8+ T, natural killer, and dendritic cell counts, accompanied by substantial neutrophil infiltration. This study illustrates the potential presence of MPs in diverse tumors; varying adhesive affinities were observed among different tumor types. MPs may lead to a more adverse TIME in pancreatic tumors. Further investigations are warranted to assess whether MPs promote tumor progression and affect the efficacy of immunotherapy

Abstract Cd contamination, especially in farmland soil, can pose serious threats to human health as well as ecological security. Stabilization is an important strategy for agricultural soil Cd remediation. In this study, a Cd-resistant strain (Cupriavidus B-7) was isolated and loaded onto cow manure (CDB), rice straw (RSB) and pine wood biochar (PB) to investigate its effects on Cd stabilization by a 60-day pot experiment. Results indicated that the Cupriavidus B-7-loaded biochar (labelled as CDBB, PBB and RSBB) reduced the CaCl2-extractable Cd by 43.06–59.78%, which was significantly superior to individual applications of Cupriavidus B-7 and biochar. Likewise, the soil physicochemical properties, urease, catalase and phosphatase activities were improved, indicating improved soil health. Consequently, dry weights of pakchoi’s shoot and root were increased by 938.9–1230.9% and 149.1–281.2%, respectively, by applying CDBB, PBB and RSBB. Meanwhile, the Cd accumulation in pakchoi shoots decreased by 38.06–50.75%. Notably, the RSBB exhibited an optimal performance on pakchoi growth promotion and Cd accumulation alleviation. The structural equation model indicated the synergistic effect on pakchoi growth promotion and Cd accumulation decreased between biochar and Cupriavidus B-7. Our research provides some new insights into the development of strategies for green and sustainable remediation of Cd-contaminated soil. Graphical Abstract

Abstract The image classification task of porcelain fragments is of great significance for the digital preservation of cultural heritage. However, common issues are encountered in the image processing of porcelain fragments, including the low computation speed, decreased accuracy due to the uneven distribution of sample categories, and model instability. This study proposes a novel Capsule Network model, referred to as LBCapsNet, which is suitable for the extraction of features from images of porcelain artifacts fragments. A bottleneck-like channel transformation module denoted by ChannelTrans, which resides between the convolutional layer and the PrimaryCaps layer, was first designed. This module is used to reduce the computational complexity and enhance the processing speed when dealing with intricate porcelain images. The MF-R loss function was then proposed by incorporating focal loss into the original loss function. This allows to address the issue of imbalanced distribution of ceramic shard samples and reduce the classification errors, which leads to faster convergence with smoother trend. Finally, an adaptive dynamic routing mechanism is designed with a dynamic learning rate to enhance the overall stability of the classification process. The experimental results obtained on public datasets, such as MNIST, Fashion- MNIST, CIFAR10, FMD and DTD as well as porcelain fragments dataset, demonstrate that LBCapsNet achieves high classification accuracy with faster and more stable computation compared with existing methods. Furthermore, the ability of LBCapsNet to process special textures can provide technical support for the digital preservation and restoration of cultural heritage.

Mitochondria are highly dynamic organelles that constantly change their morphology to adapt to the cellular environment through fission and fusion, which is critical for a cell to maintain normal cellular functions. Despite the significance of this process in the development and pathogenicity of the rice blast fungus Magnaporthe oryzae, the underlying mechanism remains largely elusive. Here, we identified and characterized a mitochondrial outer membrane translocase, MoTom20, in M. oryzae. Targeted gene deletion revealed that MoTom20 plays an important role in vegetative growth, conidiogenesis, penetration, and infectious growth of M. oryzae. The growth rate, conidial production, appressorium turgor, and pathogenicity are decreased in the ΔMotom20 mutant compared with the wild-type and complemented strains. Further analysis revealed that MoTom20 localizes in mitochondrion and plays a key role in regulating mitochondrial fission and fusion balance, which is critical for infectious growth. Finally, we found that MoTom20 is involved in fatty-acid utilization, and its yeast homolog ScTom20 is able to rescue the defects of ΔMotom20 in mitochondrial morphology and pathogenicity. Overall, our data demonstrate that MoTom20 is a key regulator for mitochondrial morphology maintenance, which is important for infectious growth of the rice blast fungus M. oryzae. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

Abstract With the increasing application of renewable energy sources (RESs), more and more grid‐connected voltage‐source converters (VSCs) in the grid need to operate in a “grid‐forming” manner. However, when large disturbances occur in the grid, grid‐connected converters may lose synchronization and cause the current to exceed set limits. To ensure the stable and safe operation of VSC during large disturbances and to improve the power supply capacity during voltage dips of RES, this paper proposes an emergency control method that takes into account the virtual synchronous generator (VSG) current limit and transient stability based on a large‐signal mathematical model of the VSG during fault and normal states. The method divides the operation area of the VSG into non‐emergency area and emergency area. If the operating point is in the non‐emergency region after a fault, only the active power reference value is changed to avoid current exceeding the limit and transient instability; if the operating point is in the emergency region, the current exceeding the limit and transient instability are avoided by changing the active power reference value and adding in the virtual impedance. Finally, the effectiveness of the proposed control strategy is verified by simulation.

Abstract Analgesia and sedation are important treatment strategies in the intensive care unit (ICU). Due to the opioid crisis, opioid-sparing medications become the focus of clinical studies. Ketamine and its isomers (mainly esketamine) are intravenous anesthetics that possess sedative, analgesic, and anesthetic effects, which have recently attracted the attention of critical care physicians. However, the application of ketamine/esketamine in ICU is limited and inexperienced. Experts from the Critical Care Medicine Professional Committee of the Chinese Research Hospital Association drafted this consensus based on the current clinical evidence to provide recommendations for the application of ketamine/esketamine in different fields of critical care, including sepsis and septic shock, endotracheal intubation, neurocritical care, respiratory critical care, post cardiac surgery care, burn and depression in ICU. Meanwhile, this expert consensus also appeals for more high-quality clinical trials to facilitate more reasonable guidelines in this area.

Abstract Background Calamus tetradactylus, a species primarily distributed in Vietnam, Laos, and southern China, is highly valued for its utilization as a small-diameter rattan material. While its physical and mechanical properties have been extensively studied, the genomic characteristics of C. tetradactylus remain largely unexplored. Results To gain a better understanding of its chloroplast genomic features and evolutionary relationships, we conducted sequencing and assembly of the chloroplast genome of C. tetradactylus. The complete chloroplast genome exhibited the typical highly conserved quartile structure, with specific variable regions identified in the single-copy region (like psbF-psbE, π = 0.10327, ndhF-rpl32, π = 0.10195), as well as genes such as trnT-GGU (π = 0.05764) and ycf1 (π = 0.03345) and others. We propose that these regions and genes hold potential as markers for species identification. Furthermore, phylogenetic analysis revealed that C. tetradactylus formed a distinct clade within the phylogenetic tree, alongside other Calamus species, and C. tetradactylus was most closely related to C. walkeri, providing support for the monophyly of the genus. Conclusion The analysis of the chloroplast genome conducted in this study provides valuable insights that can contribute to the improvement of rattan breeding programs and facilitate sustainable development in the future.

Abstract Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.

Abstract Hepatocellular carcinoma (HCC) remains a formidable malignancy that significantly impacts human health, and the early diagnosis of HCC holds paramount importance. Therefore, it is imperative to develop an efficacious signature for the early diagnosis of HCC. In this study, we aimed to develop early HCC predictors (eHCC-pred) using machine learning-based methods and compare their performance with existing methods. The enhancements and advancements of eHCC-pred encompassed the following: (i) utilization of a substantial number of samples, including an increased representation of cirrhosis tissues without HCC (CwoHCC) samples for model training and augmented numbers of HCC and CwoHCC samples for model validation; (ii) incorporation of two feature selection methods, namely minimum redundancy maximum relevance and maximum relevance maximum distance, along with the inclusion of eight machine learning-based methods; (iii) improvement in the accuracy of early HCC identification, elevating it from 78.15 to 97% using identical independent datasets; and (iv) establishment of a user-friendly web server. The eHCC-pred is freely accessible at http://www.dulab.com.cn/eHCC-pred/ . Our approach, eHCC-pred, is anticipated to be robustly employed at the individual level for facilitating early HCC diagnosis in clinical practice, surpassing currently available state-of-the-art techniques.

Abstract For the porous‐membrane‐based osmotic energy generator, the potential synergistic enhancement mechanism of various key parameters is still controversial, especially because optimizing the trade‐off between permeability and selectivity is still a challenge. Here, to construct a permeability and selectivity synergistically enhanced osmotic energy generator, the two‐dimensional porous membranes with tunable charge density are prepared by inserting sulfonated polyether sulfone into graphene oxide. Influences of charge density and pore size on the ion transport are explored, and the ionic behaviors in the channel are calculated by numerical simulations. The mechanism of ion transport in the process is studied in depth, and the fundamental principles of energy conversion are revealed. The results demonstrate that charge density and pore size should be matched to construct the optimal ion channel. This collaborative enhancement strategy of permeability and selectivity has significantly improved the output power in osmotic energy generation; compared to the pure graphene oxide membrane, the composite membrane presents almost 20 times improvement.

BackgroundAortic regurgitation (AR) may lead to right ventricular dysfunction (RVD), but the prognostic value of RVD in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear. Our goal was to evaluate the clinical implications, predictors and prognostic significance of RVD in patients with pure AR after TAVR.MethodsIn this multicentre prospective study, patients undergoing TAVR were included between January 2019 and April 2021. The patients were divided into four groups according to the results of transthoracic echocardiography pre- and post-TAVR. The primary end point was 2-year all-cause mortality.ResultsA total of 648 patients were divided into four groups: 325 patients (54.3%) in the no RVD group; 106 patients (17.7%) in the new-onset RVD group; 73 patients (12.2%) in the normalized RVD group; and 94 patients (15.7%) in the residual RVD group. At the 2-year follow-up, there were significant differences in all-cause mortality among the four groups (5.2%, 12.3%, 11.0% and 17.0%, respectively; p

BackgroundThe prevalence of venous thromboembolism (VTE) is high in patients with cancer and can often present as the first symptom of malignancy. Cancer-associated VTE is one of the most important risk factors contributing to cancer mortality, making its prevention and treatment critical for patients with lung cancer.MethodsWe systematically searched for observational studies that estimated the prevalence of VTE in patients with lung cancer. A comprehensive search of electronic databases, including PubMed, EMBASE and Cochrane Library, was systematically conducted from database inception through January 21, 2022. The qualities of included studies were assessed in three domains, including patient selection, comparison, and results. Random effects meta-analyses of the prevalence of VTE in lung cancer were conducted using the metaprop procedure. Chi-square test and I2 value were used to evaluate study heterogeneity.ResultsThirty-five studies involving 742,156 patients were considered eligible for this study. The pooled prevalence of VTE among patients with lung cancer was 5% (95% CI: 0.043–0.056, P = 0.000). The regional prevalence of VTE was 7% (95% CI: 0.06–0.08; I2 = 99.2%) in North America, 8% (95% CI: 0.06–0.10; I2 = 97.6%) in Asia, 6% (95% CI: 0.04–0.09; I2 = 95.9%) in Europe and 11% (95% CI: 0.07–0.15) in Australasia.ConclusionsThe prevalence of lung cancer-related VTE is high and region-specific. These results of this review emphasize the importance of understanding the incidence of lung cancer-related VTE and provide argue for VTE screening of patients with lung cancer.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022306400).

Objective: Inflammation plays an important role in the transformation of pulmonary nodules (PNs) from benign to malignant. Prediction of benignancy and malignancy of PNs is still lacking efficacy methods. Although Mayo or Brock model have been widely applied in clinical practices, their application conditions are limited. This study aims to construct a diagnostic model of PNs by machine learning using inflammation-related biological markers (IRBMs). Methods: Inflammatory related genes (IRGs) were first extracted from GSE135304 chip data. Then, differentially expressed genes (DEGs) and infiltrating immune cells were screened between malignant pulmonary nodules (MN) and benign pulmonary nodule (BN). Correlation analysis was performed on DEGs and infiltrating immune cells. Molecular modules of IRGs were identified through Consistency cluster analysis. Subsequently, IRBMs in IRGs modules were filtered through Weighted gene co-expression network analysis (WGCNA). An optimal diagnostic model was established using machine learning methods. Finally, external dataset GSE108375 was used to verify this result. Results: 4 hub IRGs and 3 immune cells showed significantly difference between MN and BN, C1 and C2 module, namely PRTN3, ELANE, NFKB1 and CTLA4, T cells CD4 naïve, NK cells activated and Monocytes. IRBMs were screened from black module and yellowgreen module through WGCNA analysis. The Support vector machines (SVM) was identified as the optimal model with the Area Under Curve (AUC) was 0.753. A nomogram was established based on 5 hub IRBMs, namely HS.137078, KLC3, C13ORF15, STOM and KCTD13. Finally, external dataset GSE108375 verified this result, with the AUC was 0.718. Conclusion: SVM model established by 5 hub IRBMs was able to effectively identify MN or BN. Accumulating inflammation and immune dysfunction were important to the transformation from BN to MN.

BackgroundUndifferentiated small round-cell sarcomas (uSRCSs) are a subgroup of sarcomas that are difficult to diagnose. Some uSRCSs have specific gene re-arrangements, but others do not. Currently, there is no specific treatments for advanced uSRCSs, and its treatment is largely based on general experience with sarcomas, which includes chemotherapy, targeted therapy, and immunotherapy. In this article, we report a patient with uSRCS who responded to treatment with anti-VEGF inhibitor surufatinib and anti-PD-1 inhibitor camrelizumab after progression on first-line chemotherapy, second-line anlotinib combined with immunotherapy, and third-line chemotherapy.Case descriptionIn July 2020, a 37-year-old female patient was diagnosed with advanced uSRCS. Results for the Ewing sarcoma RNA binding protein 1 and Wilms tumor suppressor (EWSR1/WT1) fusion gene were negative. The patient was also negative with BCOR (BCL6 co-repressor) and CIC (capicua transcriptional repressor) fusion gene. The next-generation sequencing results revealed point mutations on Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), Transcription Factor Binding To IGHM Enhancer 3 (TFE3), Mucin 16 (MUC16), and AXL (Axl, also called UFO, ARK, and Tyro7, is part of a family of receptor tyrosine kinases). The patient received 4 cycles of the Ifosfamide and epirubicin hydrochloride regimen, and her best objective response was stable disease. On November 3, 2020, a computed tomography (CT) scan revealed progressive disease (PD). Two cycles of camrelizumab (a programmed death-1 inhibitor) plus anlotinib (an anti- vascular endothelial growth factor drug) were administered, but PD was again observed. Thus, a regimen of gemcitabine plus docetaxel was adopted. Unfortunately, the disease progressed once again after two cycles of the treatment. On February 4, 2021, the patient began to receive targeted therapy with surufatinib combined with camrelizumab. A CT scan showed that the tumor achieved a partial response. As of April 2023, the patient had a progression-free survival time of 26 months.ConclusionsSurufatinib in combination with camrelizumab could be effective in the treatment of advanced uSRCSs.

Problems, such as toxic side effects and drug resistance of chemoradiotherapy, target therapy and immunotherapy accompanying the current anti-cancer treatments, have become bottlenecks limiting the clinical benefit for patients. Therefore, it is urgent to find promising anti-cancer strategies with higher efficacy and lesser side effects. Baicalein, a flavonoid component derived from the Chinese medicine scutellaria baicalensis, has been widely studied for its remarkable anti-cancer activity in multiple types of malignancies both at the molecular and cellular levels. Baicalein exerts its anti-tumor effects by inhibiting angiogenesis, invasion and migration, inducing cell apoptosis and cell cycle arrest, as well as regulating cell autophagy, metabolism, the tumor microenvironment and cancer stem cells with no obvious toxic side effects. The role of classic signaling pathways, such as PI3K/AKT/mTOR, MAPK, AMPK, Wnt/β-catenin, JAK/STAT3, MMP-2/-9, have been highlighted as the major targets for baicalein exerting its anti-malignant potential. Besides, baicalein can regulate the relevant non-coding RNAs, such as lncRNAs, miRNAs and circ-RNAs, to inhibit tumorigenesis and progression. In addition to the mentioned commonalities, baicalein shows some specific anti-tumor characteristics in some specific cancer types. Moreover, the preclinical studies of the combination of baicalein and chemoradiotherapy pave the way ahead for developing baicalein as an adjunct treatment with chemoradiotherapy. Our aim is to summary the role of baicalein in different types of cancer with its mechanisms based on in vitro and in vivo experiments, hoping providing proof for baicalein serving as an effective and safe compound for cancer treatment in clinic in the future.

Plasmodesmata are transmembrane channels embedded within the cell wall that can facilitate the intercellular communication in plants. Plasmodesmata callose-binding (PDCB) protein that associates with the plasmodesmata contributes to cell wall extension. Given that the elongation of cotton fiber cells correlates with the dynamics of the cell wall, this protein can be related to the cotton fiber elongation. This study sought to identify PDCB family members within the Gossypium. hirsutum genome and to elucidate their expression profiles. A total of 45 distinct family members were observed through the identification and screening processes. The analysis of their physicochemical properties revealed the similarity in the amino acid composition and molecular weight across most members. The phylogenetic analysis facilitated the construction of an evolutionary tree, categorizing these members into five groups mainly distributed on 20 chromosomes. The fine mapping results facilitated a tissue-specific examination of group V, revealing that the expression level of GhPDCB9 peaked five days after flowering. The VIGS experiments resulted in a marked decrease in the gene expression level and a significant reduction in the mature fiber length, averaging a shortening of 1.43–4.77 mm. The results indicated that GhPDCB9 played a pivotal role in the cotton fiber development and served as a candidate for enhancing cotton yield.

Background: The paper was to investigate the clinical relevance of oxidative stress (OS) and inflammation-associated target in coronary artery lesions (CALs) associated with Kawasaki disease (KD). Methods: The data of clinical from 455 sufferers diagnosed with KD between February 2021 and June 2023 were gathered and fell into two groups: CAL and NCAL. The regression analysis was conducted to search independent covariates for CALs related to OS and inflammation. The predictive nomogram was structured according to these risk factors. The properties of the model were estimated using calibration and receiver operating characteristic curves. Results: The levels of CRP, IL-6, PLT count, ESR, ox-HDL, MDA, and PLR were dramatically more elevate, interestingly, HDL and SOD were low in the CAL group. Ascension of CRP, IL-6, ESR, ox-HDL, MDA, and PLR, and diminution of HDL and SOD were considered as independent risk factors. The nomogram constructed using these factors demonstrated a satisfactory calibration degree and discriminatory power, with an area under the curve of 0.812. In the verification set, the area under the curve was found to be 0.799. Conclusion: The model was established according to 8 OS and inflammation- associated risk factors bound up with CALs in sufferers with KD, and maybe a usable approach for early diagnosis of CALs in KD.

PurposeThis systematic review and meta-analysis of clinical observational studies aims to clarify the correlation between the intake levels of fruits and vegetables and non-alcoholic fatty liver disease (NAFLD).Materials and methodsPubMed, Embase, Web of Science, and the Cochrane Library were searched for studies on the association between vegetable or fruit intake with the risk of NAFLD from the foundation of each database up until September 2023. The relative risk (OR) and the 95% confidence interval (CI) were pooled for both the highest and lowest consumption levels of vegetables and fruits to explore their association with the incidence of NAFLD.ResultsThe meta-analysis encompassed 11 studies with a total of 493,682 patients. A higher consumption of vegetables (OR = 0.78, 95% CI = 0.67–0.91) and fruits (OR = 0.88, 95% CI = 0.83–0.93) was found to have a negative correlation with the risk of NAFLD, denoting an inverse association. This correlation, however, varied among different ethnic groups and gender.ConclusionsOur results indicate that increased consumption of vegetables and fruits is associated with a reduced likelihood of developing NAFLD.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier: CRD42023460430.

ObjectiveNumerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation.MethodsWe conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis.ResultsMR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae.ConclusionMetformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.

BackgroundAccording to data from the World Health Organization (WHO), there is a significant public health issue regarding the increasing number of individuals affected by obesity and overweight on an annual basis. Therefore, it is imperative to urgently identify interventions that can effectively control and improve this condition. Baduanjin, as a medium-intensity exercise, appears a suitable approach for weight reduction among individuals with obesity. This paper aimed to provide a systematic review and meta-analysis of the efficacy of Baduanjin in addressing obesity and overweight, with the ultimate goal of assisting individuals with obesity in finding an effective, safe, and engaging method for weight reduction.MethodsWe conducted a comprehensive search of multiple databases including PubMed, Cochrane Library, Web of Science, Embase, The China National Knowledge Infrastructure (CNKI), The Chinese Scientific Journal Database (VIP), The Chinese Biomedical Literature Database (CBM), and WanFang Database to identify relevant articles published from the inception of each database until September 2023. Specifically, we focused on randomized controlled trials (RCTs) investigating the effects of Baduanjin on weight reduction. Data from these studies were extracted and analyzed using appropriate statistical methods. In cases where there was no significant heterogeneity (I2 < 50%, p > 0.1), we employed a fixed effects model for data synthesis; otherwise, a random effects model was selected. Funnel plots were used to assess publication bias, and the mean difference (MD) was reported as an indicator of treatment group differences.ResultsA total of 420 participants were included in 10 studies. The MD results of the experimental group when compared with the control group were −3.69 (95%CI = −4.97 to −2.40, p < 0.001) for body weight (BW), −5.42 (95%CI = −6.56 to −4.28, p < 0.001) for body mass index (BMI), −1.36 (95%CI = −1.76 to −0.96, p < 0.001) for waist circumference (WC), −3.40 (95%CI = −4.43 to −2.37, p < 0.001) for hip circumference (HC), and −0.03 (95%CI = −0.04 to −0.02, p > 0.1) for the waist-to-hip ratio (WHR). All of the values in the experimental group showed significant difference. The results of the Egger’s test (t = 1.43, p = 0.190) suggest that there was no substantial bias present within the data analysis process. The safety profile revealed no adverse events reported across all 10 studies.ConclusionBaduanjin could be effective in reducing weight, and the practice of Baduanjin has the potential to regulate BW, BMI, WC, HC, and WHR. However, further well-designed RCTs are still necessary to provide more robust evidence in the future.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024513789.

ABSTRACT This study aims to elucidate additional mutation loci associated with fluoroquinolone (FQ) resistance and evaluate the discriminatory capacity of mutation loci and allele mutation frequencies in identifying FQ-resistant Mycobacterium tuberculosis (MTB) isolates. A random selection of isolates was extracted from an ongoing collection. Drug resistance was determined using the resazurin microtiter assay (REMA) as the gold standard. Mutation loci and the burden of mutations in the quinolone resistance-determining region (QRDR) were elucidated through whole-genome sequencing (WGS). Novel amino acid mutations, namely, G520D and G520T, were identified in the gyrB and associated with FQ resistance. In the context of distinguishing FQ-resistant isolates, the AUC for the QRDR mutation frequency burden (0.969) surpassed that of the mutation locus (0.929), and this difference was statistically significant (P = 0.03). Furthermore, using the resistance mutation locus as a reference, setting the QRDR mutation frequency burden threshold at 1.31% resulted in a 3.60% increase in the accuracy of classifying FQ-resistant isolates (NRI = 3.60%, P < 0.001). The QRDR mutation frequency burden appears to offer superior diagnostic efficacy in discriminating FQ-resistant isolates compared to qualitative detection of mutant loci.IMPORTANCEFluoroquinolone (FQ) drugs are recommended as second-line drugs for the treatment of multidrug-resistant tuberculosis. With the massive use of FQ drugs in the clinical treatment of tuberculosis (TB), there is an increasing rate of drug resistance to FQ drugs. In this study, we identified and demonstrated novel amino acid mutations associated with FQ resistance in Mycobacterium tuberculosis (MTB), and we quantified the mutation sites and identified the quinolone resistance-determining region (QRDR) mutation frequency burden as a novel diagnostic method for FQ resistance. We hope that the results of this study will provide data support and a theoretical basis for the rapid diagnosis of FQ-resistant MTB.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

In this article, a novel robust adaptive neural network tracking control scheme is presented for a class of uncertain nonlinear systems with quantized inputs and full state constraints. A tan-type barrier Lyaponov function is proposed to constrain all states, and the unknown nonlinear function term in virtual control is approximated by radial basis function neural network(RBFNN). The uncertainty term and disturbance term in the system are dealt with by robust scheme. Under the proposed quantized tracking control scheme, the communication load of the system is reduced, the boundedness of all signals in the closed-loop system is verified, the full state constraints are satisfied. Simulation results are presented to illustrate the effectiveness of the proposed adaptive control scheme.

Abstract Asthma exacerbations caused by respiratory viral infections are a serious global health problem. Impaired antiviral immunity is thought to contribute to the pathogenesis, but the underlying mechanisms remain understudied. Here using mouse models we find that Cullin5 (CUL5), a key component of Cullin-RING E3 ubiquitin ligase 5, is upregulated and associated with increased neutrophil count and influenza-induced exacerbations of house dust mite-induced asthma. By contrast, CUL5 deficiency mitigates neutrophilic lung inflammation and asthma exacerbations by augmenting IFN-β production. Mechanistically, following thymic stromal lymphopoietin stimulation, CUL5 interacts with O-GlcNAc transferase (OGT) and induces Lys48-linked polyubiquitination of OGT, blocking the effect of OGT on mitochondrial antiviral-signaling protein O-GlcNAcylation and RIG-I signaling activation. Our results thus suggest that, in mouse models, pre-existing allergic injury induces CUL5 expression, impairing antiviral immunity and promoting neutrophilic inflammation for asthma exacerbations. Targeting of the CUL5/IFN-β signaling axis may thereby serve as a possible therapy for treating asthma exacerbations.

Abstract Purpose To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. Methods This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. Results The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. Conclusion GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.

In the realm of parallel and distributed computation, All-gather operation, a process where each node in a distributed system gathers data from all others, is pivotal. This operation underpins various high-performance computing (HPC) applications, notably in distributed deep learning (DL), by enabling model and hybrid parallelisms. Although optical interconnection networks promise unmatched bandwidth and reliability for data transfers between distributed nodes, most current All-gather algorithms remain optimized for electrical interconnects, leading to suboptimal performance in optical contexts. This paper proposes “OpTree”, an advanced scheme distinctly designed for All-gather operation in optical interconnect systems. OpTree constructs an optimal $m$ -ary tree that minimizes communication time by determining the optimal number of communication stages. A comprehensive comparison between OpTree’s communication steps and existing All-gather algorithms is provided. Theoretical insights reveal that OpTree substantially curtails communication steps within optical interconnects. Constraints imposed by OpTree on optical communication are also elaborated. Empirical evaluations, through rigorous simulations, establish that: 1) OpTree is effective in generating an optimal m-ary tree for minimizing communication time. 2) For a 1024-node optical ring system, OpTree cuts communication time by 72.97%, 93.15%, and 86.32% against WRHT, Ring, and Neighbor Exchange (NE) schemes, respectively, tested over different message sizes. 3) With varying node counts, the reductions stand at 42.27%, 92.74%, and 85.49% against the same counterparts. 4) As the number of wavelengths increases, communication time further diminishes.

Abstract Purpose Patients with advanced non-small cell lung cancer (NSCLC) mostly receive essential routine care and support from informal caregivers, who usually experience poorer health-related quality of life (HRQoL). The study aimed to evaluate the HRQoL and its predictors among informal caregivers of patients with advanced NSCLC in China. Methods We interviewed the adult caregiver population of patients with advanced NSCLC (stage IIIB~IV) in nine tertiary hospitals from multiple provinces in China between November 2020 and June 2021. The EQ-5D-5L instrument measured the HRQoL of caregivers, as analyzed by employing descriptive analysis, univariate analysis, Tobit regression, and multivariate logistic regression, and investigated the important influencing factors further. Results A valid sample of 553 caregivers was analyzed. The mean EQ-5D-5L utility score of caregivers was 0.92 (SD = 0.14). Caregivers reported the greatest problems in mental health, with 45.39% reporting slight, moderate, severe, or extreme anxiety/depression. The potential influencing factors of HRQoL in caregivers included patients' age and cancer histology, relationship with the patients, and daily caregiving hours. Compared to other caregivers, patients' spouses had the lowest HRQoL. In addition, over six hours of caregiving per day was associated with lower HRQoL in caregivers of patients with advanced NSCLC. Conclusions The HRQoL of caregivers for patients with advanced NSCLC was investigated for the first time in China. The informal caregivers experience decreased HRQoL, with anxiety /depression problems being reported the most. The findings of this study would provide extensive information on the HRQoL of advanced NSCLC patients' caregivers for future health-promoting self-care.

Abstract Background Wu Mei Pills (WMP) is a traditional Chinese medication that exhibits considerable anti-inflammatory effects. While WMP has been documented for its efficacy in treating RA, its mechanism of action on the condition remains unestablished. Methods The chemical composition of WMP was analyzed through UPLC-MS. Next, the enzyme-linked immunosorbent assay, cell scratch, Transwell, and Western blotting techniques were used to investigate its intrinsic mechanism. Lastly, the effect of WMP in inhibiting RA was explored by applying it to CIA rats. Result UPLC-MS analysis detected 181 compounds in WMP. RA-FLS migration and invasion mechanisms were significantly hindered by serum containing WMP (2%, 8%). Moreover, WMP (0.5 g/kg, 2 g/kg) restricted arthritis and immune organ indices in CIA rats with type II collagen-induced rheumatoid arthritis by blocking TLR4-NF-κB inflammatory pathway activation. Conclusions WMP is valuable in mitigating the course of RA through inhibiting the classical TLR4-NF-κB inflammatory pathway and reducing the secretion of inflammatory factors in the serum of RA-FLS and CIA rats. Moreover, it regulates the dynamic balance of MMP-2/TIMP-2, MMP-9/TIMP-1, modulates the mechanism of RA-FLS invasion, and safeguards articular cartilage tissues in RA.

In response to the rapid increase in world population and subsequent demands for food, edible insects represent an alternative food source for humans that is rich in proteins, amino acids and minerals. Entomophagy is a tradition in many countries including China and Thailand, and edible insects have attracted a lot of attention in Western World due to their suitable nutrient composition, high mineral content (e.g., Fe, Zn, Ca, Mg) and potential use as a supplement in human diet. In this study, we surveyed mineral content in seven insect orders and 67 species of mass produced and wild-harvested edible insects. The total content of essential elements in edible insects was very high in Tenebrio molitor, Bombyx mori, and Zonocerus variegatus. The heavy metal content (summarized for eight species) was below the maximum limit allowed for safe consumption. Sustainable supply of minerals derived from insect biomass is complicated due to the high variations of mineral content in insects and the potential of its change due to processing.

The vertical launch of shipborne depth charge can greatly improve platform adaptability and combat effectiveness, which is of great significance in improving the combat capability of ships. This paper took a vertical cold launch depth charge as the prototype and set up a vertical launch trajectory calculation model of depth charge according to the vertical launch kinematics and dynamics equations. Based on this model, the paper considered the projectile mass, total impulse, initial muzzle velocity, turning height, terminal angle of attack, pitch angle at the end of turning, lift coefficient, drag coefficient, and other influence factors and calculated and analyzed the influence of shipborne depth charge range. The results show that: 1) The range is positively correlated with the total impulse, initial muzzle velocity, turning height, terminal angle of attack, and lift coefficient, while it is negatively correlated with the projectile mass, pitch angle at the end of turning, and drag coefficient; 2) the projectile mass, total impulse, initial muzzle velocity, and pitch angle at the end of turning have great influence on the depth charge range, while the terminal angle of attack, lift coefficient, and drag coefficient have relatively little influence on the depth charge range. In addition, the turning height has almost no influence on the depth charge range. The simulation results can provide a reference for the overall vertical launch and trajectory design of the depth charge.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

The in-plane folding wing is one of the important research directions in the field of morphing or bionic aircraft, showing the unique application value of enhancing aircraft maneuverability and gust resistance. This article provides a structural realization of an in-plane folding wing and an aeroelasticity modeling method for the folding process of the wing. By approximating the change in structural properties in each time step, a method for calculating the structural transient response expressed in recursive form is obtained. On this basis, an aeroelasticity model of the wing is developed by coupling with the aerodynamic model using the unsteady panel/viscous vortex particle hybrid method. A wind-tunnel test is implemented to demonstrate the controllable morphing capability of the wing under aerodynamic loads and to validate the reliability of the wing loads predicted by the method in this paper. The results of the gust simulation show that the gust scale has a significant effect on the response of both the open- and closed-loop systems. When the gust alleviation controller is enabled, the peak bending moment at the wing root can be reduced by 5.5%∼47.3% according to different gust scales.

Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer with limited treatment options. Parishin A, a natural compound derived from Gastrodia elata, possesses multiple therapeutic properties. However, its effects on OSCC remain unexplored. Purpose: This study explores the anti-cancer potential of Parishin A on OSCC and its mechanisms. Methods: OSCC cell lines YD-10B and Ca9-22 were treated with varying Parishin A concentrations. Cell viability was detected using the CCK-8 assay, and colony formation was evaluated in agarose gel. Migration and invasion ability were assessed through wound healing and Matrigel invasion assays. The protein expression levels involved in the PI3K/AKT/mTOR signaling pathway and epithelial–mesenchymal transition (EMT) markers were examined via Western blotting. Results: Parishin A inhibited OSCC cell viability in both dose- and time-dependent manners, with significant reductions at 20, 40, 60, and 80 μM, without affecting normal human gingival fibroblasts. Colony formation decreased substantially at ≥40 μM higher Parishin A concentrations in a dose-dependent manner. Also, migration and invasion assays showed significant suppression by Parishin A treatment concentration ≥40 μM in a dose-dependent manner, as evidenced by decreased wound closure and invasion. Western blot analyses revealed increased E-cadherin levels and decreased N-cadherin and vimentin levels, suggesting EMT inhibition. Parishin A also decreased the phosphorylation levels of PI3K, AKT, and mTOR. Conclusion: Collectively, these findings support the potential of Parishin A as an anti-OSCC agent.

Background: Transcatheter aortic valve replacement (TAVR) is a challenge for patients with aortic regurgitation (AR) and a large annulus. Our goal was to evaluate the clinical outcomes and predictors of transapical TAVR in AR patients with a large annulus and noncalcification and the feasibility and safety of 3-dimensional printing (3DP) in the preprocedural simulation. Methods: Patients with a large annulus (diameter >29 mm) were enrolled and divided into the simulation (n = 43) and the nonsimulation group (n = 82). Surgeons used the specific 3DP model of the simulation group to simulate the main steps before the procedure and to refit the transcatheter heart valve (THV) according to the simulated results. Results: The average annular diameter of the overall cohort was 29.8 ± 0.7 mm. Compared with the nonsimulation group, the simulation group used a higher proportion of extra oversizing for THVs (97.6% vs. 85.4%, p = 0.013), and the coaxiality performance was better (9.7 ± 3.9° vs. 12.7 ± 3.8°, p < 0.001). Both THV displacement and ≥ mild paravalvular leakage (PVL) occurred only in the nonsimulation group (9.8% vs. 0, p < 0.001; 9.8% vs. 0, p < 0.001). Multivariate regression analysis showed that extra oversizing, coaxial angle and annulus diameter were independent predictors of THV displacement and ≥ mild PVL, respectively. Conclusions: Based on 3DP guidance, transapical TAVR using extra oversizing was safe and feasible for patients with noncalcified AR with a large annulus. Extra oversizing and coaxial angle were predictors of postprocedural THV displacement and ≥ mild PVL in such patients.

The use of Generally Recognized as Safe (GRAS)-grade microbial cell factories to produce recombinant protein-based nutritional products is a promising trend in developing food and health supplements. In this study, GRAS-grade Kluyveromyces marxianus was employed to express recombinant human heavy-chain ferritin (rhFTH), achieving a yield of 11 g/L in a 5 L fermenter, marking the highest yield reported for ferritin nanoparticle proteins to our knowledge. The rhFTH formed 12 nm spherical nanocages capable of ferroxidase activity, which involves converting Fe2+ to Fe3+ for storage. The rhFTH-containing yeast cell lysates promoted cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β)) and enhanced locomotion, pharyngeal pumping frequency, egg-laying capacity, and lifespan under heat and oxidative stress in the RAW264.7 mouse cell line and the C. elegans model, respectively, whereas yeast cell lysate alone had no such effects. These findings suggest that rhFTH boosts immunity, holding promise for developing ferritin-based food and nutritional products and suggesting its adjuvant potential for clinical applications of ferritin-based nanomedicine. The high-yield production of ferritin nanoparticles in K. marxianus offers a valuable source of ferritin for the development of ferritin-based products.

Objective: Given the significant impact of long-term traditional Chinese medicine (TCM) treatment on the prognosis of patients with non-small cell lung cancer (NSCLC), we aimed to develop nomograms, with or without consideration of TCM treatment duration, to accurately predict the overall survival (OS) of patients with stage IIIB/IV NSCLC treated with TCM. Methods: Nomograms were developed from a training cohort comprised of 292 patients diagnosed with NSCLC, using univariate and multivariate Cox regression analyses to screen for various prognostic factors with and without TCM treatment. The nomograms were evaluated using the concordance index (C-index), calibration curve, and decision curve analysis (DCA), after which they were validated, using the bootstrap self-sampling method for internal validation, and a validation cohort comprised of 175 patients for external validation. Bootstrap validation is a resampling technique that involves randomly selecting and replacing data from the original dataset to make statistical inferences, thereby circumventing the issue of sample reduction that can arise from cross-validation. Results: We identified seven significant prognostic factors for OS. For nomogram A (excluding TCM treatment time), the C-indexes (95 % confidence interval [CI]) were 0.674 (0.635–0.712) and 0.660 (0.596–0.724) for the training and validation cohorts, respectively. For nomogram B (including TCM treatment time), the C-indices (95 % CI) were 0.846 (0.822–0.870) and 0.783 (0.730–0.894), for the training and validation cohorts, respectively, indicating that nomogram B was superior to nomogram A. Both the calibration curves and DCA results exhibited favorable clinical concordance and usefulness. Conclusion: The nomogram B yielded precise prognostic predictions for patients with advanced NSCLC treated with TCM.