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In order to obtain a green and efficient preparation process for carboxymethyl porous starch, carboxymethyl porous starch was prepared by mechanical activation solid phase etherification method, where enzymatically hydrolyzed porous cassava starch was used as raw material, sodium chloroacetate as etherifying agent, and sodium hydroxide as catalyst. Single-factor experiments were conducted to explore the effects of various factors on the degree of substitution (DS) of carboxymethyl porous starch, and the application of carboxymethyl porous starch in soy sauce was discussed. The results showed that the optimal process conditions for the preparation of carboxymethyl porous starch by mechanical activation and solid phase synthesis method were as follows: The molar ratio of porous starch to sodium chloroacetate was 1:1, the mass fraction of sodium hydroxide was 18.8%, the ball milling time was 1.5 h, and the reaction temperature was 50℃. Under these conditions, the highest DS of carboxymethyl porous starch obtained was up to 0.2532. Furthermore, the carboxymethylation reaction of porous starch was confirmed by infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). With the increase of DS of carboxymethyl porous starch, its cold water solubility, water absorption, and adsorption of lemon yellow increased. When DS was 0.2532, the cold water solubility of carboxymethyl porous starch reached 64.94%, the water absorption rate reached 180.73%, and the adsorption amount of lemon yellow reached 2.5086 mg·g−1. The powder soy sauce prepared by carboxymethyl porous starch has better solubility, lower moisture absorption, and higher content of amino acid nitrogen, and is closer to the original soy sauce compared to those prepared by cassava starch and porous starch. Therefore, the mechanical activation and solid phase etherification method can effectively prepare carboxymethyl porous starch, which is simple to operate, environmentally friendly, and highly substitutive, providing a scientific basis for the development and utilization of porous starch.

Abstract The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included. Overall pathologic complete response (pCR) rate of 56%. Sequencing of ddAC vs CbT first showed no difference in pCR rate (ddAC 55% vs. CbT 58%, p = 0.77). However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, p = 0.03), with cytopenias most frequent (ddAC 59% vs. CbT 31%, p = 0.001). ddAC in a modified KN522 regimen is safe, tolerable, and effective. Efficacy is comparable regardless of chemotherapy sequencing, but ddAC first is significantly associated with higher rates of treatment delays and cytopenias.

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Abstract In recent years, single-cell analyses have revealed the heterogeneity of the tumour microenvironment (TME) at the genomic, transcriptomic, and proteomic levels, further improving our understanding of the mechanisms of tumour development. Single-cell RNA sequencing (scRNA-seq) technology allow analysis of the transcriptome at the single-cell level and have unprecedented potential for exploration of the characteristics involved in tumour development and progression. These techniques allow analysis of transcript sequences at higher resolution, thereby increasing our understanding of the diversity of cells found in the tumour microenvironment and how these cells interact in complex tumour tissue. Although scRNA-seq has emerged as an important tool for studying the tumour microenvironment in recent years, it cannot be used to analyse spatial information for cells. In this regard, spatial transcriptomics (ST) approaches allow researchers to understand the functions of individual cells in complex multicellular organisms by understanding their physical location in tissue sections. In particular, in related research on tumour heterogeneity, ST is an excellent complementary approach to scRNA-seq, constituting a new method for further exploration of tumour heterogeneity, and this approach can also provide unprecedented insight into the development of treatments for pancreatic cancer (PC). In this review, based on the methods of scRNA-seq and ST analyses, research progress on the tumour microenvironment and treatment of pancreatic cancer is further explained.

Abstract Post-diagnosis weight gain is common in early-stage breast cancer and is associated with increased risk of recurrence and mortality. Intentional weight loss is difficult to maintain, and digital lifestyle interventions may provide a scalable approach to address this challenge. In this prospective single-arm study (ClinicalTrials.gov NCT04753268; February 15, 2021), key eligibility criteria included: stage I–III breast cancer, body mass index (BMI) ≥ 27.5 kg/m2, and completion of cancer treatment ≥6 months before study enrollment. Participants were provided with a behavioral change mobile application (Noom®). The primary endpoint was a change in self-reported weight from baseline to 26 weeks. Secondary endpoints included engagement, changes in physical activity, dietary patterns, and patient-reported outcomes (PRO). In total, 31 patients were enrolled (mean age 56.8 ± 9.9, mean baseline BMI 33.5 kg/m2 ± 6.5). The mean weight change was −4.8 kg ( ± 4.4, P

Objective:. Pancreatic cancer is one of the most aggressive malignancies, a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making. Methods:. A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature. Furthermore, the most pivotal gene in the signature was identified. The potential mechanism of the core gene function was revealed through GSEA, CIBERSORT, ESTIMATE, immunophenoscore (IPS) algorithm, single-cell analysis, and functional experiment. Results:. An immune-related prognostic signature and associated nomogram were constructed and validated. Among the genes constituting the signature, interleukin 1 receptor type II (IL1R2) was identified as the gene occupying the most paramount position in the risk signature. Meanwhile, knockdown of IL1R2 significantly inhibited the proliferation, invasion, and migration ability of pancreatic cancer cells. Additionally, high IL1R2 expression was associated with reduced CD8+ T cell infiltration in pancreatic cancer microenvironment, which may be due to high programmed cell death-ligand-1 (PD-L1) expression in cancer cells. Finally, the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy. Conclusion:. In conclusion, our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer, as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.

Single-atom catalysts (SACs) have unique advantages over traditional nanoparticle-based catalysts. They are promising for various green energy technology applications. However, single atoms with high surface energy are prone to aggregation. Common SACs are often limited to low loadings of catalytically active sites, resulting in inadequate catalytic performance. In this context, high-loading SACs (HL-SACs) are much more desirable. The increased density of active sites also creates unique synergistic effects, bringing beneficial catalytic properties. This short review article summarizes recent advances in HL-SACS. We first review new synthesis methods to obtain HL-SACs. Then, we highlight studies discussing the effects of increased metal mass loadings on catalytic performances in terms of activity, selectivity, and stability. Last, we present our views on key research areas to move this field forward. We hope this review can drive the development of high-performance HL-SACs to realize their practical applications.

BackgroundAdvanced age is a primary risk factor for adverse COVID-19 outcomes, potentially attributed to immunosenescence and dysregulated inflammatory responses. In the post-pandemic era, with containment measures lifted, the elderly remain particularly susceptible, highlighting the need for intensified focus on immune health management.MethodsA total of 281 elderly patients were enrolled in this study and categorized based on their clinical status at the time of admission into three groups: non-severe (n = 212), severe survivors (n = 49), and severe non-survivors (n = 20). Binary logistic regression analysis was employed to identify independent risk factors associated with disease severity and in-hospital outcomes. The diagnostic performance of risk factors was assessed using the receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis and log-rank test were utilized to compare the 30-day survival rates. Furthermore, the transcriptomic data of CD4+ T cells were extracted from Gene Expression Omnibus (GEO) database. Gene Set Enrichment Analysis (GSEA) was applied to reveal biological processes and pathways involved.ResultsIn the comparison between severe and non-severe COVID-19 cases, significant elevations were observed in the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and Serum Amyloid A (SAA) levels, concurrent with a notable reduction in CD8+ T cells, CD4+ T cells, natural killer (NK) cells, and monocytes (all p < 0.05). CD4+ T cells (OR: 0.997 [0.995-1.000], p

BackgroundHepatocellular carcinoma (HCC) is a common malignancy worldwide, and its development is closely related to abnormalities in iron metabolism. This study aims to systematically analyze changes in iron metabolism in the tumor microenvironment of HCC using single-cell sequencing technology, and investigate the potential mechanisms by which iron metabolism regulation affects the survival of liver cancer patients.Materials and methodsSingle-cell sequencing data from hepatocellular carcinoma patients were obtained from the GEO database. By iron metabolism genomic scoring, we assessed differences in iron metabolism levels in hepatocellular carcinoma samples. By cell communication analysis as well as GO and KEGG enrichment analysis, we determined the functional role of iron metabolism in different cell types. We used survival analysis and Kaplan-Meier curves to assess the impact of iron metabolism levels on patient prognosis. In addition, we identified and analyzed the expression profile of the GLRX3 gene, investigated its key regulatory role in iron metabolism, and validated its clinical value as a prognostic marker. Finally, we explored the effect of GLRX3 on hepatocellular carcinoma phenotype by in vitro experiments such as PCR, transwell, CCK8, and wound healing assay.ResultsBioinformatics results and experimental validation confirmed the dysregulation of iron metabolism in the development of hepatocellular carcinoma, revealing iron’s regulatory influence across various cell types. Additionally, GLRX3 was identified as a key regulatory factor in iron metabolism, and the mechanism by which GLRX3 regulates tumor cell proliferation and immune evasion was determined. Furthermore, experiments verified GLRX3’s role in facilitating tumor cell proliferation and invasion.ConclusionThis study highlights the critical role of iron metabolism in the progression of hepatocellular carcinoma, particularly the regulatory mechanism of the GLRX3 gene in tumor cell proliferation and immune evasion. Iron metabolism abnormalities are not only drivers of liver cancer development but also key indicators of patient prognosis.

ObjectiveTo construct a hierarchical management system for specialist nurses based on Patricia Benner’s theory, and evaluate its implement effect, so as to provide reference for the hierarchical management of specialist nurses.MethodsLiterature retrieval, semi-structured interview and Delphi method were conducted for initially formulation of the draft of hierarchical management system for specialist nurses. Forty-three specialist nurses and 14 nursing managers were selected for the study, using a non-randomized controlled experimental study design, and at the end of the study, the job satisfaction, job engagement, job exuberance, advice behaviors and nursing managers’ overall job satisfaction of specialist nurses were compared before and after the hierarchical management.ResultsThis study constructed a hierarchical management system for specialist nurses. The differences in specialist nurses’ job satisfaction, job engagement, job exuberance and constructive behaviors before and after hierarchical management were statistically significant (p

BackgroundHerbal products have long been utilized as remedies for various disease conditions, including infections. This study investigates the therapeutic mechanism of a traditional Chinese herbal combination in treating high-risk HPV infections.MethodsThe herbal formula was prepared using common herbs: dry Millettia speciosa, Guanzhong (a spermatophyte), Sarsaparilla, White Fruit, and Cockscomb Flower. Eight female patients diagnosed with high-risk HPV were enrolled from January to September 2023 at Shenzhen Hospital of Beijing University of Traditional Chinese Medicine. Cervicovaginal secretions were collected before and after treatment with the herbal remedy and analyzed using non-targeted metabolomics techniques. In vitro studies were conducted using HeLa cells to determine the optimal effective concentration of the remedy, assessed via the CCK8 method. The proliferation and migration of HeLa cells were evaluated using Transwell assays. Quantitative PCR was employed to measure mRNA levels of endothelial-to-mesenchymal transition (EndMT) markers, including VE-Cadherin, eNOS, α-SMA, and Snail.ResultsIn vivo, significant alterations in cervicovaginal secretion metabolites post-treatment were observed through PCA, OPLS-DA, and volcano plot analyses. KEGG enrichment analysis highlighted crucial signaling pathways such as arginine and proline metabolism, purine metabolism, glycerophospholipid metabolism, and phenylalanine metabolism, indicating the herbal combination’s systemic effects on patients. In vitro experiments demonstrated a dose-dependent reduction in HeLa cell proliferation and migration, confirmed by scratch and Transwell assays. Additionally, qPCR analysis revealed down-regulation of α-SMA and Snail, and up-regulation of VE-Cadherin and eNOS, suggesting inhibition of EndMT in HeLa cells.ConclusionThe traditional Chinese herbal combination modulates key metabolic pathways in vivo and inhibits EndMT in vitro, while reducing HeLa cell proliferation and migration. These findings highlight its potential as a therapeutic approach for managing HPV infections, bridging traditional practices with scientific research.

Background: Codonopsis pilosula is a traditional herb widely used in Asian countries. As regulatory institutions increasingly acknowledge its medicinal and food-related characteristics, the attention from scholars is expected to increase rapidly. However, an overview and reports on research focus on this promising herb are currently lacking. Therefore, the objective of this study was to fill this knowledge gap by conducting a systematic review of relevant literature to explore the developing history and research focus on C. pilosula. This research is of significant importance in gaining a deeper understanding of the potential benefits and application areas of C. pilosula. Method: The output, institutions, countries, authors, highly cited publications, frontier focus and funding agencies of C. pilosula were analyzed using VOSviewer, CiteSpace, and COOC software. Results: The development of C. pilosula experienced 3 stages: initial stage (1979–2002), fast stage (2003–2012), and explosive stage (2013-present), with each stage showing linear growth. Worldwide attention from 1292 institutions in 27 countries have been paid, with China leading in output and collaboration. Lanzhou University in China contributed most publications with Fangdi Hu as a core specialist facilitating collaborations in agricultural and pharmacological research. A stable cooperation network has formed among researchers from different fields, focusing on pharmacological activity, chemical constituents, quality control, and medication rules. The research focus updated timely with new scientific frontiers occur. Medication rules, data mining, molecular docking, traditional Chinese medicine, gut microbiota, and polysaccharide are frontier focus presently and in the near future. Significant attention and funding have been provided by the national and local government of Gansu province in China. Conclusion: Research on C. pilosula is thriving, particularly in China, with a promising future in traditional Chinese medicine and pharmacology. This study provides valuable insights for future research directions and contributes to the effective development of C. pilosula.

Ecological changes have been observed to promote rates of lineage diversification, yet the precise roles of ecological factors, species evolution, and environmental variability in driving species diversity remain research hot spots. The association between ecological change and lineage diversification, particularly with regard to the size of the time scale, remains poorly understood. To explore whether ecological change facilitates species evolution, we focused on the unique family Paeoniaceae, which encompasses both herbaceous and woody taxa, to investigate the evolutionary rates. As a unique family characterized by a single genus of angiosperms and comprising various climatic types, the ecological niche changes of Paeoniaceae are closely associated with the evolution, making it an ideal model for conducting association analysis. In this study, we integrated the molecular fragments and ecological factors to explore the relationship between species evolution and niche changes in Paeoniaceae. The phylogenetic tree revealed that Paeoniaceae forms a sister relationship with Penthoraceae, Haloragidaceae, Iteaceae, Crassulaceae, and Saxifragaceae, constituting an independent clade based on the positive selection of molecular fragments including two protein-coding genes and eight non-coding regions. The divergence time was estimated to be between 102 and 116 Mya (Million years ago). The phylogenetic tree within Paeonia revealed a clear division into three groups: sections of Paeonia, Moutan, and Onaepia with high support values for each branch based on the ten positive selection of molecular fragments. The rapid rate of evolution observed in Paeonia, about 0-5 Mya. In addition, ecological niche modeling showed that the potential distributions for Paeonia expanded from middle Asia to eastern Asia, and from central North America to the Northern part of North America during the Last Glacial Maximum (LGM) to Mid Holocene (MID) period. This suggests that Paeonia continuously adapted to changing ecological environments over time. Compared to the rate of climatic niche divergence and lineage diversification, the ecological niche of Paeonia underwent significant changes during the period of 3-11 Mya, occurring 5 Mya earlier than the period of evolutionary rate change. These findings offer comprehensive insights into the relationship between niche change and the evolution of species, providing valuable perspectives for further ecological cultivation efforts.

The home range utilization of primates reflects their behavioral and ecological strategies to adapt to their environment. However, little is known about the home range behavior of endemic gibbons (Nomascus hainanus) found in a secondary tropical forest of Hainan Island, China. Knowledge of their ranging patterns could contribute to scientific evaluations of the survival risk of this species under habitat conversion. In this study, we analyzed the home range utilization patterns and the seasonal variation of a group of Hainan gibbons in secondary tropical forests in the Bawangling area of National Park of Hainan Tropical Rainforest, using infrared cameras and direct observations. The results show that the annual home area of the gibbon group was 137.4 ha, with no significant difference between the wet and dry seasons. The feeding hotspots of Hainan gibbons are more scattered in the rainy season and more concentrated in the dry season, but not for sleeping hotspots. The relatively small home range suggests that secondary forests may not represent low-quality habitats and thus have a supporting role for the Hainan gibbon population. The widely distributed range of feeding hotspots in the rainy season may be related to the abundance of fruit resources in this season, while gibbons reduce their travel distance and energy expenditure when food is scarce in the dry season. Overall, our findings provide insights into the ecological flexibility of gibbons to seasonal variations in food resources and highlight the conservation value of secondary forests for gibbon populations.

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

BackgroundPatients with Alzheimer’s disease (AD) often exhibit characteristic clinical manifestations, particularly neuropsychiatric symptoms. Previous studies have shown that white matter hyperintensity (WMH) is strongly associated with AD progression, as well as neuropsychiatric symptoms. The purpose of this study was to investigate the clinical and neuropsychological characteristics of AD patients with WMH.MethodsThis retrospective study involved 104 18-fluorodeoxyglucose-positron emission computed tomography (18FDG-PET-CT)-defined AD patients treated at Tianjin Huanhu Hospital from January 2010 to December 2022. Cranial magnetic resonance imaging (MRI) provided semi-quantitative data on brain structure and WMH. Collect and analyze patient clinical data. Neuropsychological assessments were used to evaluate cognitive function and psychobehavioral traits.ResultsAmong the 104 patients, 66 were in the WMH group (63.5%) and 38 in the non-white matter hyperintensity (non-WMH) group (36.5%). There were no significant differences in gender, age, age of onset, education, BMI, smoking, drinking, diabetes, coronary heart disease, dementia family history, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) between the two groups. The WMH group showed higher rates of hypertension, homocysteine (Hcy) levels, NPI, and CDR scores as compared to the non-WMH group (p

BackgroundRNA editing, especially A-to-I editing sites, is a common RNA modification critical for stem cell differentiation, muscle development, and disease occurrence. Unveiling comprehensive RNA A-to-I editing events associated with myogenesis of the skeletal muscle satellite cells (MuSCs) is essential for extending our knowledge of the mechanism underpinning muscle development.ResultsA total of 9,632 RNA editing sites (RESs) were screened in the myoblasts (GM), myocytes (DM1), and myotubes (DM5) samples. Among these sites, 4,559 A-to-I edits were classified and further analyzed. There were 3,266 A-to-I sites in the protein-coding region, out of which 113 missense sites recoded protein. Notably, five A-to-I sites in the 3′ UTR of four genes (TRAF6, NALF1, SLC38A1, ENSCHIG00000019092) altered their targeted miRNAs. Furthermore, a total of 370 A-to-I sites with different editing levels were detected, including FBN1, MYH10, GSK3B, CSNK1D, and PRKACB genes. These genes were predominantly enriched in the cytoskeleton in muscle cells, the hippo signaling pathway, and the tight junction. Furthermore, we identified 14 hub genes (TUFM, GSK3B, JAK2, RPSA, YARS1, CDH2, PRKACB, RUNX1, NOTCH2, CDC23, VCP, FBN1, RARS1, MEF2C) that potentially related to muscle development. Additionally, 123 stage-specific A-to-I editing sites were identified, with 43 sites in GM, 25 in DM1, and 55 in DM5 samples. These stage-specific edited genes significantly enriched essential biological pathways, including the cell cycle, oocyte meiosis, motor proteins, and hedgehog signaling pathway.ConclusionWe systematically identified the RNA editing events in proliferating and differentiating goat MuSCs, which was crucial for expanding our understanding of the regulatory mechanisms of muscle development.

ABSTRACT Background Despite numerous studies confirming the association between insulin resistance (IR) and macrophage polarization, there is a lack of bibliometric analysis in this area. Therefore, our objective is to conduct a comprehensive analysis of published literature and identify potential future research trends using bibliometrics. Method Publications on the topic of macrophage polarization in IR were gathered from the Web of Science Core Collection database (WoSCC) spanning the years 1999–2023. Bibliometric analysis and visualization were conducted using VOSviewers, CiteSpace, the R package “bibliometrix” and Tableau Public. Result A total of 3435 articles published between 1999 and 2023 were included in the analysis. These articles originated from 75 countries, with the United States and China leading in contributions. The top five research institutions are the University of California, San Diego, Harvard University, the University of Michigan, Shanghai Jiao Tong University, and Huazhong University of Science and Technology. In this research domain, Diabetes is the most frequently published journal, and the Journal of Clinical Investigation is the most co‐cited. Among the 19,398 authors contributing to these publications, Lumeng CN. not only authored the most papers but also received the highest number of co‐citations. “Insulin resistance” emerges as a primary keyword in the analysis of emerging research hotspots. Conclusion For the first time, bibliometric methods have been employed to conduct a comprehensive summary of papers relevant to macrophage polarization in IR. This study aims to identify the current research direction and future research hotspots, offering valuable guidance and insights for scholars in the field.

BackgroundClinical rotation practicum provides NQNs with more opportunities to learn their professional knowledge and develop basic nursing skills. ICU is often used as one of the clinical practicum departments for NQNs. Nursing shortages have been particularly felt in ICU. Due to the characteristic fast-paced working environments, high acuity of patient care, and technical complexities of an ICU. The experience of NQNs is highly stressful and challenging in these settings, which hinders their professional development and impacts patient care.AimsThe study aimed to systematically review and synthesis the findings of qualitative studies exploring experience of NQNs in ICU rotation, to provide a basis for enhancing the quality of clinical nursing.MethodsNine databases were systematically searched for relevant publications from inception until February 2024. All qualitative studies in English and Chinese that explored the experience of NQNs in ICU rotation were collected. Two independent reviewers selected the studies and used The Joanna Briggs Institute Critical Appraisal Tool to evaluate the quality of the studies. Meta-synthesis was performed to integrate the results.ResultsA total of 13 studies revealed five descriptive themes and 14 sub-themes: ICU readiness, physical and psychological stress, positive self-perception, developing relationships, and ICU reflections.ConclusionStandardized training in ICU, the working ability of NQNs is exercised and their professional quality is improved. However, it is also adversely affected by various stressors. The appropriate guidance and monitoring should be given by hospital managers, so as to promote the development of NQNs and enhance the quality of clinical nursing.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42023475257.

BackgroundCodonopsis pilosula (Campanulaceae) is a traditional herbal plant that is widely used in China, and the drought stress during the seedling stage directly affects the quality, ultimately impacting its yield. However, the molecular mechanisms underlying the drought resistance of C. pilosula seedlings remain unclear.MethodHerein, we conducted extensive comparative transcriptome and physiological studies on two distinct C. pilosula cultivar (G1 and W1) seedlings subjected to a 4-day drought treatment.ResultsOur findings revealed that cultivar G1 exhibited enhanced retention of proline and chlorophyll, alongside a marked elevation in peroxidase activity, coupled with diminished levels of malondialdehyde and reduced leaf relative electrolyte leakage compared with cultivar W1. This suggested that cultivar G1 had relatively higher protective enzyme activity and ROS quenching capacity. We discerned a total of 21,535 expressed genes and identified 4,192 differentially expressed genes (DEGs) by RNA sequencing (RNA-seq). Our analysis revealed that 1,764 DEGs unique to G1 underwent thorough annotation and functional categorization utilizing diverse databases. Under drought conditions, the DEGs in G1 were predominantly linked to starch and sucrose metabolic pathways, plant hormone signaling, and glutathione metabolism. Notably, the drought-responsive genes in G1 were heavily implicated in hormonal modulation, such as ABA receptor3-like gene (PYL9), regulation by transcription factors (KAN4, BHLH80, ERF1B), and orchestration of drought-responsive gene expression. These results suggest that cultivar G1 possesses stronger stress tolerance and can better adapt to drought growing conditions. The congruence between qRT-PCR validation and RNA-seq data for 15 DEGs further substantiated our findings.ConclusionOur research provides novel insights into the physiological adaptations of C. pilosula to arid conditions and lays the groundwork for the development of new, drought-tolerant C. pilosula cultivars.

Objectives To appraise the quality of clinical practice guidelines (CPGs) and expert consensus statements on rehabilitation for patients with COVID-19, summarise recommendations of rehabilitation assessments and interventions and evaluate the heterogeneity of the recommendations.Design Systematic review.Data sources PubMed and Embase databases and five online guideline repositories: The National Guideline Clearinghouse, Guidelines International Network, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence and WHO were searched from their inception to August 2024. In addition, we reviewed reference lists of eligible citations and searched the grey literature on the relevant websites.Eligibility criteria for selecting studies We included CPGs and expert consensus statements which provided information about rehabilitation of patients with COVID-19. To be eligible, the CPGs and expert consensus statements were issued in English by a nationally or internationally recognised government authority, medical/academic society or organisation. If there were multiple versions of the guidelines, we included the latest one. The translations, interpretations and abstracts of guidelines were excluded.Data extraction and synthesis All recommendations on rehabilitation assessments and interventions for COVID-19 were extracted and summarised. Two reviewers independently evaluated the methodological quality with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and two other reviewers assessed the reporting quality using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement of included CPGs and expert consensus statements. We used the Measurement Scale of Rate of Agreement to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements.Results A total of 31 CPGs and expert consensus statements were included. 14 guidelines provided recommendations for rehabilitation assessments. At the early, development, critical and recovery stages of COVID-19, the most frequently recommended were exercise therapy (25.8%, 35.5%, 25.8% and 58.1%, respectively). According to AGREE II, 17 included guidelines were assessed as low methodological quality (35%–56%), 10 guidelines were rated as moderate quality (46%– 62%) and four had high quality (69%–79%). Among 31 eligible guidelines, the reporting rate of 22 items in the RIGHT checklist ranged from 10% to 100%. The included guidelines were consistent with the reference guidelines (80%–100%). Only one guideline existed minor (60%–80%) disagreements in respiratory muscle training relative to the reference guideline.Conclusions Rehabilitation assessments and interventions should be implemented consistently throughout the entire process of COVID-19. The recommendations should be tailored to each stage of COVID-19. The methodological and reporting qualities of several guidelines remain suboptimal. Therefore, developers should adhere strictly to the AGREE II standard and RIGHT checklist to formulate and publish CPGs and expert consensus statements with high quality.PROSPERO registration number CRD42020190761.

Background: Sivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS. Methods: A retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO2), the ratio of PaO2 to the fraction of inspired oxygen (PaO2/FiO2), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia. Results: In the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, P

Abstract Intercropping, a widely adopted agricultural practice worldwide, aims to increase crop yield, enhance plant nutrient uptake, and optimize the utilization of natural resources, contributing to sustainable farming practices on a global scale. However, the underlying changes in soil physio-chemical characteristics and enzymatic activities, which contribute to crop yield and nutrient uptake in the intercropping systems are largely unknown. Consequently, a two-year (2021–2022) field experiment was conducted on the maize/soybean intercropping practices with/without nitrogen (N) fertilization (i.e., N0; 0 N kg ha−1 and N1; 225 N kg ha−1 for maize and 100 N kg ha−1 for soybean ) to know whether such cropping system can improve the nutrients uptake and crop yields, soil physio-chemical characteristics, and soil enzymes, which ultimately results in enhanced crop yield. The results revealed that maize intercropping treatments (i.e., N0MI and N1MI) had higher crop yield, biomass dry matter, and 1000-grain weight of maize than mono-cropping treatments (i.e., N0MM, and N1MM). Nonetheless, these parameters were optimized in N1MI treatments in both years. For instance, N1MI produced the maximum grain yield (10,105 and 11,705 kg ha−1), biomass dry matter (13,893 and 14,093 kg ha−1), and 1000-grain weight (420 and 449 g) of maize in the year 2021 and 2022, respectively. Conversely, soybean intercropping treatments (i.e., N0SI and N1SI) reduced such yield parameters for soybean. Also, the land equivalent ratio (LER) and land equivalent ratio for N fertilization (LERN) values were always greater than 1, showing the intercropping system’s benefits in terms of yield and improved resource usage. Moreover, maize intercropping treatments (i.e., N0MI and N1MI) and soybean intercropping treatments (i.e., N0SI and N1SI) significantly (p

Abstract Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

Abstract Pralsetinib, a potent and selective inhibitor of oncogenic RET fusion and RET mutant proteins, is a substrate of the drug metabolizing enzyme CYP3A4 and a substrate of the efflux transporter P‐gp based on in vitro data. Therefore, its pharmacokinetics (PKs) may be affected by co‐administration of potent CYP3A4 inhibitors and inducers, P‐gp inhibitors, and combined CYP3A4 and P‐gp inhibitors. With the frequent overlap between CYP3A4 and P‐gp substrates/inhibitors, pralsetinib is a challenging and representative example of the need to more quantitatively characterize transporter‐enzyme interplay. A physiologically‐based PK (PBPK) model for pralsetinib was developed to understand the victim drug–drug interaction (DDI) risk for pralsetinib. The key parameters driving the magnitude of pralsetinib DDIs, the P‐gp intrinsic clearance and the fraction metabolized by CYP3A4, were determined from PBPK simulations that best captured observed DDIs from three clinical studies. Sensitivity analyses and scenario simulations were also conducted to ensure these key parameters were determined with sound mechanistic rationale based on current knowledge, including the worst‐case scenarios. The verified pralsetinib PBPK model was then applied to predict the effect of other inhibitors and inducers on the PKs of pralsetinib. This work highlights the challenges in understanding DDIs when enzyme‐transporter interplay occurs, and demonstrates an important strategy for differentiating enzyme/transporter contributions to enable PBPK predictions for untested scenarios and to inform labeling.

Abstract Background The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. Methods PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. Results Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. Conclusions The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

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

Abstract Background Sensory impairment in older adults is associated with cognitive decline, elevated depressive symptoms, and low levels of life satisfaction. However, these relationships are usually investigated separately and in pairs. This study examined these relationships comprehensively, for the first time. Methods The analysis included 5,658 community-dwelling older adults from the China Health and Retirement Longitudinal Study (aged 50 to 108 years, 52.1% male) who completed the Jorm Informant Questionnaire Cognitive Decline in the Elderly and the Center for Epidemiological Studies-Depression-short form. A questionnaire was used to collect information on hearing, visual status, and life satisfaction. Structural equation modelling was used to examine the direct and indirect relationships between these variables. Results Self-reported hearing and vision problems are directly associated with cognitive decline and elevated depressive symptoms. In addition, hearing and vision problems are indirectly related to cognitive decline through elevated depressive symptoms. Although hearing and vision problems had no direct effect on life satisfaction, they were indirectly associated with life satisfaction through cognitive decline and depressive symptoms. Conclusions This study provides the first epidemiological evidence of the comprehensive relationships between hearing and vision problems, cognitive decline, depressive symptoms, and life satisfaction. When older adults report hearing and/or vision problems, clinicians and caregivers should be aware of the concurrence of declined cognition, elevated depressive symptoms, and compensated life satisfaction. Future studies should examine the causal relationships and potential mechanisms of these relationships.

id="st1" To explore which pattern recognition receptors (PRRs) play a key role in the development of hand, foot, and mouth disease (HFMD) by analyzing PRR-associated genes. id="st2" We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells (PBMCs) infected with enterovirus 71 (EV-A71) which were derived from patients with HFMD of different severities and at different stages. A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates. Subsequently, ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes, specifically, BST2, IRF7, 1FI16, TRIM21, MX1, and DDX58. id="st3" Compared with those at the recovery stage, the expression levels of BST2 (P=0.027), IFI16 (P=0.016), MX1 (P=0.046) and DDX58 (P=0.008) in the acute stage of infection were significantly upregulated, while no significant difference in the expression levels of IRF7 (P=0.495) and TRIM21 (P=0.071) was found between different stages of the disease. The expression levels of BST2, IRF7, IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens, and BST2, IRF7, IFI16 and MX1 expression levels were significantly lower in coxsackie B virus (COXB) positive patients than the negative patients. Expression levels of one or more of BST2, IRF7, IFI16, TRIM21, MX1 and DDX58 genes were correlated with PCT levels, various white blood cell counts, and serum antibody levels that reflect disease course of HFMD. Aspartate aminotransferase was correlated with BST2, MX1 and DDX58 expression levels. id="st4" PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.

Abstract Dazomet is a dry powder formulation that releases toxic gas containing methyl isothiocyanate, which controls soil-borne pests and weeds, improving crop yields when applied to moist soils. To explore the efficacy of dazomet fumigation in the cultivation of the perennial herb Codonopsis pilosula, four typical cultivars (G1, G2, W1 and TCK) in Gansu Province were selected for seedling cultivation after soil fumigation (F) by dazomet, and non-fumigated soil was used as a control (CK). The experiments took 2 years to complete. The functional diversity of the soil enzymes and microorganisms, seedling emergence and physiological characteristics, and the quality and yield of Codonopsis seedlings and Radix were assessed. The results showed that the seed emergence rate, seedling re-green rate and several antioxidant enzymatic activities improved in the treatments involving soil fumigation with dazomet, and membrane lipid peroxidation in the seedlings decreased. On average, compared with those of the respective controls, the root viability and yield of the seedlings of the tested cultivars also increased by 34.87% and 42.4%, respectively, and the incidence of root rot in the seedlings was reduced by 83.9%, compared with their respective controls. After harvest, the yield increased by 23.9%, the incidence of root rot decreased by 61.3%, increase in yield and a 61.3% reduction in incidence, and the medicinal materials were determined to be safe and residue-free. The effects of fumigation were cultivar-specific and were especially prominent in G2. Therefore, soil fumigation with dazomet could improve the quality and productivity of Codonopsis pilosula seedlings. Taken together, these findings suggest that when herbs are bred by seedling transplantation, especially cultivars of good quality but poor resistance or species with rare germplasm resources, soil fumigation provides a way to improve cultivation effectiveness and, more importantly, ensures the probability of successfully breeding the species.

Abstract Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy. Graphical Abstract

Facing the massive amount of risk management data for deep foundation pit excavation (DFPE) construction, how to store and utilize these data to prevent the occurrence of risk events is an urgent problem that needs to be solved. The goal of this research is to build an ontology knowledge base aimed at standardizing and formalizing risk knowledge in the field of DFPE construction risk. The ontology knowledge base can promote construction risk identification and reduce the occurrence of risk events. A six-step method was applied to define the ontology classes and class hierarchy, determine objects and related data attributes. Ontology instances were created to further evaluate the integrity, correctness and consistency of the developed knowledge base. The case studies showed that through the formalization of knowledge and establishment of rule libraries, rule reasoning could intelligently identify potential risk events and provide risk prevention measures. This research contributed a new perspective to resolve problems of access and integration knowledge and information in DFPE risk management work. By structuring and standardizing knowledge and information, the ontology-based risk knowledge base can facilitate knowledge transfer, sharing and reuse among different project participants. The ontology knowledge base can provide decision support for managers to protect the on-site workers, building structures and the surrounding environments.

The recycling of coal gangue has considerable potential to produce secondary environmental hazards, which significantly influence the high-end application of coal gangue in practical engineering. The present study investigates the effects of activation treatment on the physical, chemical properties and leaching behavior of coal gangue. The mineral composition, micro-pore structure and element leaching were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Thermogravimetry Analysis (TG), Low-Temperature Nitrogen Adsorption (LTNA) and Inductively Coupled Plasma (ICP). The results indicate that kaolinite and pyrite in coal gangue experienced reconstruction after 600 °C during thermal activation. The density of thermally activated coal gangue is increased with the calcination temperature as well as the alkalinity (from 4.8–7.1) due to the burning of organic and the oxidation of pyrite. The calcination treatment induced the reduction in macropore volume (>50 nm), and enhancement in mesopore (

This study aims to investigate the risk factors for infection and mortality associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospitalized children, with the goal of providing valuable insights for the prevention and treatment of these bacterial infections. A retrospective case-control study was conducted, including 153 cases of carbapenem-sensitive K. pneumoniae infection in children and 49 cases of CRKP infection. Among the CRKP cases, 40 children survived and nine died. Logistic regression analysis was used to screen the risk factors for CRKP infection in children, establish a predictive model, and analyze the factors associated with mortality in CRKP-infected children. The results of the multivariate regression analysis showed that hematopoietic malignancies (OR = 28.272, 95% CI: 2.430–328.889), respiratory tract infections (OR = 0.173, 95% CI: 0.047–0.641), mechanical ventilation (OR = 3.002, 95% CI: 1.117–8.071), number of antibiotic agents (OR = 1.491, 95% CI: 1.177–1.889), WBC (OR = 0.849, 95% CI: 0.779–0.926), and neutrophil count (OR = 0.779, 95% CI: 0.677–0.896) were identified as significant factors associated with CRKP infection in children. Specifically, CRKP-infected children with a history of multiple hospitalizations within the past three months, blood stream infections, and decreased WBC and lymphocyte counts should be monitored closely due to poor prognosis. Underlying hematopoietic malignancies in children, non-respiratory tract infections, mechanical ventilation after admission, and use of multiple antibiotics without significant increase in white blood cell and neutrophil counts are major factors influencing CRKP infection. Particularly, CRKP-infected children with blood stream infections and no significant increase in neutrophil count should be closely monitored for potential severity of illness.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

IntroductionThe quality of traditional Chinese medicine is based on the content of their secondary metabolites, which vary with habitat adaptation and ecological factors. This study focuses on Lonicera japonica Flos (LJF), a key traditional herbal medicine, and aims to evaluate how ecological factors impact its quality.MethodsWe developed a new evaluation method combining high-performance liquid chromatography (HPLC) fingerprinting technology and MaxEnt models to assess the effects of ecological factors on LJF quality. The MaxEnt model was used to predict suitable habitats for current and future scenarios, while HPLC was employed to analyze the contents of key compounds. We also used ArcGIS for spatial analysis to create a quality zoning map.ResultsThe analysis identified 21 common chromatographic peaks, with significant variations in the contents of Hyperoside, Rutin, Chlorogenic acid, Cynaroside, and Isochlorogenic acid A across different habitats. Key environmental variables influencing LJF distribution were identified, including temperature, precipitation, and elevation. The current suitable habitats primarily include regions south of the Yangtze River. Under future climate scenarios, suitable areas are expected to shift, with notable expansions in southern Gansu, southeastern Tibet, and southern Liaoning. The spatial distribution maps revealed that high-quality LJF is predominantly found in central and southern Hebei, northern Henan, central Shandong, central Sichuan, southern Guangdong, and Taiwan.DiscussionThe study indicates that suitable growth areas can promote the accumulation of certain secondary metabolites in plants, as the accumulation of these metabolites varies. The results underscore the necessity of optimizing quality based on cultivation practices. The integration of HPLC fingerprinting technology and the MaxEnt model provides valuable insights for the conservation and cultivation of herbal resources, offering a new perspective on evaluating the impact of ecological factors on the quality of traditional Chinese medicines.

Soil temperature is one of the important environmental factors for the underground parts of plants. It is important to detect soil temperature in agricultural production. Acoustic waves serve as effective carriers of soil information, providing a reliable means to detect soil physical properties. In order to detect the temperature of sandy loam soil based on acoustic technology, this study extends the application of Wyllie model to the temperature measurement of sandy loam soil. The relationship between soil temperature and acoustic velocity is explored. A model of soil moisture content-soil temperature-acoustic velocity (MTV) for temperature measurement in sandy loam soil is proposed by extending the temperature–velocity of sound relationship with the introduction of a variable empirical coefficient related to soil moisture β(θ). In order to determine the parameters of proposed model, a pulsed acoustic velocity detection system was built in this paper. The influence of temperature on the acoustic velocity in sandy loam soil was analyzed through experiments. Based on the experimental results, the key parameters of the MTV model are refined. Finally, a validation experiment was carried out on sandy loam soil. The maximum estimation error of soil temperature based on the MTV model for sandy loam soil temperature estimation is 8.55 %. The results indicate that the MTV model proposed in this study can be used for temperature estimation in sandy loam soil, providing a theoretical basis for the development of acoustic soil physical information detection sensors.

BackgroundThis study aims to evaluate the efficacy and complications of endovascular treatment for hemorrhage caused by ruptured internal carotid artery pseudoaneurysms following radiotherapy in nasopharyngeal carcinoma (NPC) patients.MethodsThis study retrospectively analyzed NPC patients who underwent endovascular treatment for ruptured internal carotid artery pseudoaneurysm hemorrhage after radiotherapy at Zhongshan People's Hospital from January 2016 to December 2022. The study aims to assess the postoperative hemostasis rate, postoperative rebleeding rate, complication rate, and 1-year postoperative survival rate.ResultsDuring the study period, 36 patients underwent endovascular treatment, of which 24 patients underwent embolization of the internal carotid artery and 12 patients underwent stenting of the internal carotid artery. The procedure success rate was 100%. The rebleeding rate at 1 year after the procedure was 5.6% (2/36, one patient with stent placement and one patient with coil embolization), and the complication rate was 11.1% (4/36, four patients with coil embolization patients). Two patients developed large-area cerebral infarction after the procedure, and two patients had different degrees of neurological impairment after the procedure. The 1-year survival rate was 91.7% (33/36).ConclusionRuptured internal carotid artery pseudoaneurysm hemorrhage after radiotherapy is rare but life-threatening. Endovascular treatment with coil occlusion or stenting reconstruction of the internal carotid artery provides immediate hemostasis and elimination of the pseudoaneurysm with a low rate of recurrence, which may be effective in reducing patient mortality.

In recent times, a notable increase in the leverage ratios among numerous households across China has been witnessed, culminating in heightened household financial vulnerability. Concurrently, the sphere of digital inclusive finance has witnessed rapid advancement, establishing itself as a crucial mechanism for Chinese households to counteract financial risk shocks. This research article meticulously constructs an ordered regression model, anchored in micro-level data from household surveys, to delve into the influence and operative mechanisms of digital inclusive finance on the vulnerability of household finances. Empirical findings from this study robustly indicate that the evolution of digital inclusive finance significantly mitigates the household financial vulnerability. A thorough mechanism analysis reveals that digital inclusive finance primarily curtails household financial vulnerability through several avenues: it notably enhances financial literacy, augments the income derived from household financial assets, and elevates contributions to commercial insurance. Intriguingly, a heterogeneity analysis underscores that the impact of digital inclusive finance is more pronounced in reducing financial vulnerability amongst households registered in rural areas and those with lower income levels. This article contributes to the expansion of the theoretical framework concerning household financial vulnerability, offering insightful guidance and policy implications for addressing financial vulnerability concerns and forestalling macro-financial risks.

IntroductionThis study explores the impact of Building Information Modelling (BIM) staff on construction project performance, with a focus on the roles of the Unified Theory of Acceptance and Use of Technology (UTAUT) and Task-Technology Fit (TTF). The research aims to understand how BIM personnel attributes influence project outcomes and how these effects are mediated by TTF and moderated by UTAUT.MethodsPartial Least Squares Structural Equation Modelling (PLS-SEM) was employed to analyze the data, allowing for the examination of complex interactions between BIM staff attributes, project characteristics, and outcomes. This method is particularly suited for handling smaller sample sizes and non-normal data distributions.ResultsThe analysis revealed that BIM staff attributes—such as team size, expertise, training, and experience—significantly influence construction project performance. Key performance areas affected include design efficiency, error reduction, and adherence to schedules and budgets. TTF emerged as a critical mediator, enhancing performance metrics like stakeholder satisfaction and cost management. UTAUT further moderated the relationship between BIM staff, TTF, and project performance, highlighting the importance of technology acceptance and use within BIM contexts.DiscussionThe findings emphasize the need for organizations to strategically allocate BIM staff and invest in their professional development to optimize project outcomes. Recommendations include fostering supportive organizational structures and promoting a culture of collaboration and innovation to enhance project resilience and performance, particularly in the face of disruptive events. Future research should expand to diverse project types and scales, investigate emerging technologies, and consider cultural factors through cross-cultural studies. Longitudinal studies and cost-benefit analyses of BIM training and technology adoption are also suggested to provide deeper insights and inform strategic decision-making.

Abstracts: With the gradual development of urban construction, more high-rise buildings with deep foundations are been constructed near tunnel groups. Analyzing how tunnels and surrounding strata respond to diverse construction strategies and challenging conditions during the excavation is crucial. This examination is instrumental in safeguarding infrastructure and minimizing construction expense. This paper explores the deformation response of structures and ground caused by irregular deep foundation pits that are excavated in structural strata adjacent to a tunnel groups (

BackgroundAccumulating evidence has linked dyslipidemia during pregnancy to the risk of delivering infants born either large for gestational age (LGA) or small for gestational age (SGA). However, the effects of the vitamin D status on these relationships require further investigation. This study investigated whether the relationship between lipid profiles and the risk of LGA or SGA was influenced by vitamin D levels during the second trimester.MethodsMaternal lipid profile levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and vitamin D levels, were measured in a cohort of 6,499 pregnant women during the second trimester. Multivariate regression models and subgroup analyses were employed to evaluate the potential associations between maternal lipid profiles, vitamin D levels, and the risk of LGA or SGA.ResultsThe prevalence of SGA infants was 9.8% (n=635), whereas that of LGA infants was 6.9% (n=447). Maternal TG levels were found to be positively associated with the risk of LGA (odds ratio [OR] = 1.41, 95% confidence interval [CI]:1.17–1.70), whereas a negative association was observed between maternal TG, TC, LDL-C levels, and risk of SGA. Additionally, mothers with higher HDL-C levels were less likely to give birth to an LGA infant (OR=0.58, 95% CI:0.39–0.85). Importantly, associations between TG, TC, LDL-c, and SGA as well as between TG and LGA were primarily observed among pregnant women with insufficient vitamin D levels. As for HDL-C, the risk of LGA was lower in mothers with sufficient vitamin D (OR = 0.42, 95% CI:0.18–0.98) compared to those with insufficient vitamin D (OR = 0.65, 95% CI:0.42–0.99).ConclusionVitamin D status during the second trimester exerts a modifying effect on the association between lipid profiles and the risk of LGA and SGA infants.

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury.Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury.Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

BackgroundGlycosyltransferase-associated genes play a crucial role in hepatocellular carcinoma (HCC) pathogenesis. This study investigates their impact on the tumor microenvironment and molecular mechanisms, offering insights into innovative immunotherapeutic strategies for HCC.MethodsWe utilized cutting-edge single-cell and spatial transcriptomics to examine HCC heterogeneity. Four single-cell scoring techniques were employed to evaluate glycosyltransferase genes. Spatial transcriptomic findings were validated, and bulk RNA-seq analysis was conducted to identify prognostic glycosyltransferase-related genes and potential immunotherapeutic targets. MGAT1’s role was further explored through various functional assays.ResultsOur analysis revealed diverse cell subpopulations in HCC with distinct glycosyltransferase gene activities, particularly in macrophages. Key glycosyltransferase genes specific to macrophages were identified. Temporal analysis illustrated macrophage evolution during tumor progression, while spatial transcriptomics highlighted reduced expression of these genes in core tumor macrophages. Integrating scRNA-seq, bulk RNA-seq, and spatial transcriptomics, MGAT1 emerged as a promising therapeutic target, showing significant potential in HCC immunotherapy.ConclusionThis comprehensive study delves into glycosyltransferase-associated genes in HCC, elucidating their critical roles in cellular dynamics and immune cell interactions. Our findings open new avenues for immunotherapeutic interventions and personalized HCC management, pushing the boundaries of HCC immunotherapy.

This study explores the impact of the proportion of students with special educational needs (SEN) on Chinese middle school teachers’ job stress, satisfaction, and exhaustion, amid increasing emphasis on inclusive education. The research hypothesizes that a higher proportion of SEN students may lead to increased job stress, decreased job satisfaction, and heightened job exhaustion. This study utilized data from the China Education Panel Survey, and Structural equation modeling was used for data analysis. The study found a significant negative association between the proportion of SEN students and teacher job satisfaction (β = −0.09, p 0.05) and job exhaustion (β = −0.08, p > 0.05). However, there was an indirect positive impact of the proportion of SEN students on job exhaustion via job satisfaction (β = 0.05, p

BackgroundImmune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors.MethodsThe genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites.ResultsOur investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002–1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873–0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002–1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer.ConclusionThis MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.

Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis were used to characterize the nonvolatile compounds of broken green tea and explore the effect of isolated scenting on metabolic profile and taste quality of broken green tea in this research. A total of 236 nonvolatile compounds were identified and 13 compounds were believed to be the key characteristic taste compounds of scented broken green tea. Meanwhile, the optimal isolated scenting time of broken green tea was determined to be 10 h based on the sensory evaluation and PLS results. The contents and types of flavonoids, organic acids and catechins lead to the difference of taste quality at different scenting times. Overall, these findings provided a theoretical basis for scenting to improve the taste of broken green tea, and provide a new idea for improving the taste of broken green tea.

Abstract Aqueous zinc‐ion batteries (ZIBs) have attracted extensive interest for the next‐generation batteries, which, however, are facing great challenges due to the poor reversibility of zinc (Zn) anodes and side reactions of water decomposition. Herein, we demonstrated a strategy that the solvation sheath of Zn ions could be facilely regulated by supramolecular coordination chemistry by adding small amounts of cyclodextrins (CDs) and, hence, inhibited the side reactions and side products, widened the electrochemical window, facilitated the homogenous deposition of Zn ions, refined the Zn grains, and enhanced the stability of Zn anodes. Importantly, we demonstrated that compared with α‐ and β‐CD, the γ‐CD showed the best regulation effect of the solvation sheath of Zn ions either at the same molar ratio or at the same mass concentration, which could be ascribed to their difference in supramolecular coordination chemistry and the strongest interaction of γ‐CD with Zn ions. As a result, with γ‐CD, the Zn//Zn symmetric cells showed ultrahigh stability with a cycling lifespan of over 2400 h at a current density of 1 mA/cm2. These results highlight the regulation of solvation sheath by supramolecular coordination chemistry for highly stable Zn anodes and pave a new way to realize high‐performance ZIBs.