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Abstract The deformation law of pipelines crossing landslide areas is an important prerequisite for the scientific design of pipelines. Most current studies find it difficult to simulate the real stress and strain state of pipelines on site. This study conducted two centrifuge model tests to observe pipeline failure indicators (deformation, stress, strain) and slope failure indicators (crack width, soil pressure, landslide displacement) in response to changes in acceleration. The experimental findings align with the results obtained from numerical simulations. The findings indicate that slope failure with high moisture content is more serious. At a moisture content of 15%, the slope has a maximum displacement of 70 mm in close reach to the buried pipeline. The pipeline has a “bimodal distribution” of strain along its axial length. The largest amount of deformation occurs at a distance of L/4 from the center of the pipeline, and the deformation value is 9000 με. Moreover, the maximum deformation in the mid-span is 21 mm, which corresponds to the result accumulated from the numerical simulation. Thus, the pipeline needs to improve the disaster prevention capabilities at the mid-span and L/4 of the pipeline.

Abstract Photoacoustic tomography offers a powerful tool to visualize biologically relevant molecules and understand processes within living systems at high resolution in deep tissue, facilitated by the conversion of incident photons into low-scattering acoustic waves through non-radiative relaxation. Although current endogenous and exogenous photoacoustic contrast agents effectively enable molecular imaging within deep tissues, their broad absorption spectra in the visible to near-infrared (NIR) range limit photoacoustic multiplexed imaging. Here, we exploit the distinct ultrasharp NIR absorption peaks of lanthanides to engineer a series of NIR photoacoustic nanocrystals. This engineering involves precise host and dopant material composition, yielding nanocrystals with sharply peaked photoacoustic absorption spectra (~3.2 nm width) and a ~10-fold enhancement in NIR optical absorption for efficient deep tissue imaging. By combining photoacoustic tomography with these engineered nanocrystals, we demonstrate photoacoustic multiplexed differential imaging with substantially decreased background signals and enhanced precision and contrast.

Abstract Background Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. Methods The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. Results In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: − 0.43, − 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: − 0.61, − 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: − 0.69, − 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. Conclusions This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission. Graphical Abstract

Abstract Background The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. Methods The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. Results In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37–13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38–0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01–0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92–7.59) and 13.63 (95% CI: 9.44–18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73–2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09–0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00–0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32–8.32) and 10.00 (95% CI: 6.09–14.05), respectively. Conclusions The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection. Graphical Abstract

Abstract Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

Abstract Background Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Purpose To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. Methods BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1β. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. Results BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/β-catenin signaling, regardless of IL-1β presence or duration of exposure. This inhibition of the Wnt/β-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. Conclusions PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/β-catenin signaling, irrespective of inflammatory conditions.

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract Background Compared to traditional thoracotomy, transapical transcatheter aortic valve implantation (TAVI) surgery offers reduced trauma and faster recovery, fostering the adoption of enhanced recovery after surgery (ERAS) protocols in cardiac surgery. Despite these advancements, postoperative pain management has received insufficient attention. The potential effects of multi-mode analgesia, including ultrasound-guided serratus anterior plane block (SAPB), on postoperative pain and early quality of recovery have not been widely studied, lacking comprehensive prospective evidence. Therefore, this study aims to investigate the impact of SAPB combined with general anesthesia on early recovery quality and analgesic efficacy in transapical TAVI patients. Methods This prospective, randomized controlled study will enroll 70 patients undergoing transapical TAVI, randomly allocated to either the SAPB group or the control group. The primary outcome, assessed using Quality of Recovery-40 (QOR-40) scale, focuses on the quality of recovery at 24 h and 48 h postoperatively. Secondary outcomes include the visual analog scale (VAS) pain scores at rest and during coughing at 6 h, 12 h, 24 h, and 48 h after surgery, frequency of patient-controlled analgesia (PCA) utilization at 24 h and 48 h, opioid consumption at 24 h and 48 h, time and frequency of rescue analgesia and severe pain at 24 h and 48 h, incidence of nausea and vomiting at 48 h after surgery, and dosage of antiemetic drugs. Discussion The purpose of our study is to evaluate the effects of ultrasound-guided SAPB combined with general anesthesia on postoperative early quality of recovery and analgesia in transapical TAVI patients. The results obtained may provide valuable insight for the implementation of multi-mode analgesia and enhanced ERAS in this specific patient population. Trial registration China Clinical Trial Register ChiCTR2300068584. Registered on 24 February 2023.

Abstract Background Off-pump coronary artery bypass grafting (OPCABG) presents distinct hemodynamic characteristics, yet the relationship between intraoperative hypotension and short-term adverse outcomes remains clear. Our study aims to investigate association between intraoperative hypotension and postoperative acute kidney injury (AKI), mortality and length of stay in OPCABG patients. Methods Retrospective data of 494 patients underwent OPCABG from January 2016 to July 2023 were collected. We analyzed the relationship between intraoperative various hypotension absolute values (MAP > 75, 65 65 mmHg emerges as a significant independent protective factor for AKI in OPCABG and IOH is related to length of hospital stay. Proactive intervention targeting intraoperative hypotension may provide a potential opportunity to reduce postoperative renal injury and hospital stay. Trial registration ChiCTR2400082518. Registered 31 March 2024. https://www.chictr.org.cn/bin/project/edit?pid=225349 .

Abstract Objectives Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low‐dose computed tomography (LDCT) screening for the high‐risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real‐world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick‐slice LDCT scanning. Methods A total of 29 296 subjects who underwent low‐dose thick‐slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low‐dose thin‐slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. Results The positive rate of LDCT screening in the thin‐slice scanning group was significantly higher than that in the thick‐slice scanning group (20.1% vs. 14.4%, p

With the rise of computing power networks, a novel infrastructure centered around computational power has emerged as a key driver in the development of the information economy. Data, recognized as a crucial production factor in the digital era, serves as a vital pillar for constructing new development paradigms. The data factor market, acting as the link between data and computational power networks, is particularly critical. Its robust operation directly affects the sustainable development of computational power networks and is provided with crucial support for the information economy system. Therefore, the data products were treated as the focal point, while the processes involved in the data factor market and the inherent connections among these components were introduced. Subsequently, the existing work on three key aspects of the data factor market was studied, including data value, data pricing, and data transactions. Regarding data value assessment, key aspects such as relative data value evaluation were discussed, introducing indicator systems, indicator weights, and value indices. For data asset value assessment, traditional methods such as the cost method, income method, and market method were discussed, as well as emerging methods based on machine learning. In terms of data pricing models, existing methods were categorized into two main types: pricing for dataset products and pricing for data service products. Seven pricing methods were summarized, and the advantages, disadvantages, and applicable scenarios of each method were further analyzed. Regarding data transaction systems, the applications of centralized and distributed architectures in the data trading market were analyzed from the perspective of system architecture. The current status and prospects of both on-exchange and over-the-counter trading modes were then introduced.

Abstract Background and aims The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. Method The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan–Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25–1.45, P

Purpose – Adopting adaptive behavior has become a basic measure for farmers because the increasingly severe climate change is affecting agricultural production. Perception is a critical first step in adopting adaptive behaviors. Livelihood resilience represents a farmer's ability to adapt to climate change. Therefore, this article aims to explore the impact of livelihood resilience and climate change perception on the climate change adaptation behavior of farmers in the Qinling Mountains region of China. Design/methodology/approach – In this study, 443 micro-survey data of farmers are obtained through one-on-one interviews with farmers. The Logit model and Poisson regression model are used to empirically examine the impact of farmers' livelihood resilience and climate change perception on their climate change adaptation behaviors. Findings – It was found that 86.68% of farmers adopt adaptive behaviors to reduce the risks of facing climate change. Farmers' perception of extreme weather has a significant positive impact on their adaptive behavior under climate change. The resilience of farmers' livelihoods and their perception of rainfall have a significant positive impact on the intensity of their adaptive behavior under climate change. Climate change adaptation behaviors are also different for farmers with different levels of livelihood resilience. Originality/value – Based on the results, policy recommendations are proposed to improve farmers' perception of climate change, enhance the sustainability of farmers' adaptive behavior to climate change, strengthen emergency management and infrastructure construction and adjust and upgrade farmers' livelihood models.

This study focuses on the pretreatment and characterization of natural fibers from the bamboo shoot shell (BSS) of Phyllostachys heterocycla to determine their suitability as biorefining materials. The discarded bamboo shoot shell was used as a source of fibers, which were analyzed for their physical, chemical, and microstructure properties. Fourier transform infrared spectroscopy, X-ray diffraction spectra, and scanning electron microscopy confirmed that a mixture of sodium hydroxide immersion plus high-pressure steam treatment allowed the cellulose structure to be disrupted, providing more adsorption sites for cellulases. Gas chromatography mass spectrometry (GC-MS) also showed that the pretreatment exposed the internal structure of the fibers and that high-mass silicon compounds were present in the eluted solution. After adding the cellulase produced by Trichoderma viride and Aspergillus niger, the reducing sugar yield was increased by 268% and 251%, compared to unpretreated BSS fibers. This strategy may apply to many industries, especially biorefining and lignocellulose biotransformation technology.

Abstract With the large-scale construction of oil and gas pipelines, the safety issues of long-distance buried pipelines in the service and construction have become increasingly prominent. The complex geological and topographical conditions of the special zone will put forwards extremely high requirements on pipe trench laying backfill materials and construction technology. For example, pipelines are inevitable to cross the active fault, while the trench backfilled with soil has limitations in protecting them from failure under the active fault displacement caused by the earthquake. Therefore, it is necessary to study the pipe–soil interaction mechanism, determine the stress state of the pipeline and propose a new backfilling material that can protect the pipeline from failure. Foam concrete (FC) provides a new choice to backfill the buried pipeline trench due to its high-homogeneity, lightweight, controllable-strength, and self-compacting. To further determine the applicability of the FC, the pipe-FC interaction mechanism is studied. Then, a FE model of the FC-pipeline-soil interaction system is established by Abaqus to quantitatively analyze the applicability of the FC based on the experimental data of the mechanical performance of the FC. It proves that using FC as trench backfill material has a noticeable protective effect on the pipeline under the earthquake-induced displacement of the normal fault. Furthermore, FC has a better protective effect on the pipeline subjected to compressive than tensile. Therefore, the reference for applying FC in trench backfilling of pipelines crossing normal fault is provided.

Abstract Background Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. Methods This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. Results The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index

Abstract Background Sarcopenic obesity (SO) in nursing home residents is rarely studied. We aimed to evaluate and compare the prevalence and consistency of different SO diagnostic methods and to investigate which criterion demonstrated a stronger association with instrumental activities of daily living (IADL) disability. Methods We consecutively recruited older adults aged ≥ 60 years, residing in 15 nursing homes in Zigong City, China. Sarcopenia obesity was defined according to the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity criteria (SOESPEN), recommending skeletal muscle mass (SMM) adjusted by body weight (SMM/W) to identify low muscle mass. Further, we adapted ESPEN criteria (SOESPEN−M) by employing SMM adjusted by body mass index (SMM/BMI). Results We included 832 participants (median age 73.0 years, 296 women). The prevalence of SOESPEN and SOESPEN−M was 43.5% and 45.3%, respectively. SOESPEN showed good consistency with SOESPEN−M (Cohen’s kappa = 0.759). More than one-third of participants in the normal weight group were diagnosed with SOESPEN or SOESPEN−M. Even within the underweight group, the prevalence of SOESPEN and SOESPEN−M was 8.9% and 22.2%, respectively. Participants with IADL disability had significantly lower SMM/W and SMM/BMI, but higher fat mass percentage of body weight (FM%) than participants without IADL disability. After full adjustment for potential confounders, SOESPEN−M (OR 1.68, 95% CI 1.21 to 2.32), but not SOESPEN (OR 1.28, 95% CI 0.93 to 1.75), remained significantly associated with IADL disability. Conclusions Both SOESPEN and SOESPEN−M showed a high prevalence among nursing home residents, even among individuals with underweight or normal weight. While SOESPEN had a good consistency with SOESPEN−M, only SOESPEN−M was independently associated with IADL disability. Screening and diagnosis of SO should be conducted in nursing home residents irrespective of BMI.

Abstract Background This study aimed to evaluate the efficacy of radiomics signatures derived from polyenergetic images (PEIs) and virtual monoenergetic images (VMIs) obtained through dual-layer spectral detector CT (DLCT). Moreover, it sought to develop a clinical-radiomics nomogram based on DLCT for predicting cancer stage (early stage: stage I-II, advanced stage: stage III-IV) in pancreatic ductal adenocarcinoma (PDAC). Methods A total of 173 patients histopathologically diagnosed with PDAC and who underwent contrast-enhanced DLCT were enrolled in this study. Among them, 49 were in the early stage, and 124 were in the advanced stage. Patients were randomly categorized into training (n = 122) and test (n = 51) cohorts at a 7:3 ratio. Radiomics features were extracted from PEIs and 40-keV VMIs were reconstructed at both arterial and portal venous phases. Radiomics signatures were constructed based on both PEIs and 40-keV VMIs. A radiomics nomogram was developed by integrating the 40-keV VMI-based radiomics signature with selected clinical predictors. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves analysis (DCA). Results The PEI-based radiomics signature demonstrated satisfactory diagnostic efficacy, with the areas under the ROC curves (AUCs) of 0.92 in both the training and test cohorts. The optimal radiomics signature was based on 40-keV VMIs, with AUCs of 0.96 and 0.94 in the training and test cohorts. The nomogram, which integrated a 40-keV VMI-based radiomics signature with two clinical parameters (tumour diameter and normalized iodine density at the portal venous phase), demonstrated promising calibration and discrimination in both the training and test cohorts (0.97 and 0.91, respectively). DCA indicated that the clinical-radiomics nomogram provided the most significant clinical benefit. Conclusions The radiomics signature derived from 40-keV VMI and the clinical-radiomics nomogram based on DLCT both exhibited exceptional performance in distinguishing early from advanced stages in PDAC, aiding clinical decision-making for patients with this condition.

Abstract Background Frailty not only affects disease survival but also impacts the long-term function and quality life of all adults diagnosed with and/or treated for cancer.The American Heart Association has introduced Life’s Essential 8 (LE8) as a novel metric for assessing cardiovascular health. Currently, LE8’s application in evaluating the frailty of cancer survivors remains unreported. This research seeks to explore the connection between LE8 scores and frailty levels in cancer survivors across the United States, thereby addressing a significant void in existing studies. Methods This study analyzed data from cancer survivors enrolled in the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2005 to 2018, providing a comprehensive dataset. Multivariable logistic regression models were used to examine the linkage between LE8 rankings and frailty condition in cancer survivors. Furthermore, the study delved deeper into this correlation using restricted cubic spline (RCS) curves and subgroup analyses. Results In the fully adjusted model, an increased LE8 level was closely associated with a reduced odds ratio of frailty among cancer survivors, with an OR of 0.95 (95% CI: 0.94–0.96, p

Explosive welding (EW) with an interlayer is considered a suitable technology for producing Al/Nb layered composite, but the fundamental process behaviors of this method remain insufficient discussion. Here, contrast EW experiments respectively using 1060Al and Ag sheets as the interlayers were carried out to prepare 2A14Al/Nb composites, and the complex interfacial phenomena and the underlying mechanisms were thoroughly examined by advanced characterizations and theoretical analyses. The microstructure results indicated that the interlayer materials had significant influence on the bonding morphologies, but the defects of the two composites shared the same geometry and distribution characteristics. Combining the microstructures and thermodynamic history, the formation mechanisms of the different defects were revealed. The 2A14Al/Ag/Nb and 2A14Al/1060Al/Nb composites had the advantages of no intermetallic compounds and few defects, respectively, but the latter showed a higher bond strength, suggesting that the geometric defects had more negative effects on mechanical properties than intermetallic compounds. The multi-view EBSD data provided insights into the intricate grain evolutions induced by the EW process, including equiaxed 2A14Al grains and columnar 1060Al grains at the 2A14Al/1060Al interface, and nanoscale Al3Nb grains at the 1060Al/Nb interface. Finally, the correlations between the grain structures and mechanical properties were established by nanoindentation tests.

Abstract Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.

Objective To detect the expressions of X-box binding protein 1 unspliced （xbp1u） and X-box binding protein 1 spliced （xbp1s） mRNA in peripheral blood CD19+B cells of patients with lupus nephritis （LN） and healthy subjects and explore the clinical significance of XBP1 in LN patients. Methods The expression levels of xbp1u and xbp1s in peripheral blood CD19+B cells of 65 LN patients and 30 healthy controls were detected by real-time polymerase chain reaction （RT-PCR）. And the ratio of CD19−CD138+plasma cells/CD19+B cells in peripheral blood was detected by flow cytometry. Results The expression level of xbp1u mRNA in CD19+B cells of active LN group （0.078±0.034） was higher than that in control group（0.035±0.011）（P＜0.05） and in stable group（0.049±0.016）（P＜0.05）. The expression level of xbp1s mRNA in CD19+B cells of active LN group（0.076±0.037）was higher than that in control group（0.022±0.010）（P＜0.05） and stable group（0.043±0.017）（P＜0.05）. The ratio of CD19−CD138+ plasma cells /CD19+B cells in LN group（0.059±0.024）was significantly higher than that in control group （P＜0.01） and stable group （0.073±0.036）（P＜0.05）; XBP1 expression in LN patients was correlated positively with the ratio of CD19−CD138+ plasma cells/CD19+B cells （r value = 0.138 & 0.036）, positively with anti-ds-DNA antibody and systemic lupus erythematosus disease activity index（SLEDAI）score （r value = 0.417 & 0.058） and negatively with hemoglobin and complement C3 （r value = −0.559 & −0.219）. Conclusion The expressions of xbp1u and xbp1s mRNA in peripheral blood mononuclear cells of LN patients in active group are higher than those in healthy group. Both are correlated positively with SLEDAI score and anti-DS DNA antibody. The expression of XBP1 is up-regulated in B cells of LN patients and it is significantly correlated with plasma cells. It implies that XBP1 may participate in the pathogenesis of LN through promoting the differentiation of B cells.

Abstract The application of network formulaology and network pharmacology has significantly advanced the scientific understanding of traditional Chinese medicine (TCM) treatment mechanisms in disease. The field of herbal biology is experiencing a surge in data generation. However, researchers are encountering challenges due to the fragmented nature of the data and the reliance on programming tools for data analysis. We have developed TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. TCMNPAS incorporates multiple resources and offers a range of functions designed for automated analysis implementation, including prescription mining, molecular docking, network pharmacology analysis, and visualization. These functions enable researchers to analyze and obtain core herbs and core formulas from herbal prescription data through prescription mining. Additionally, TCMNPAS facilitates virtual screening of active compounds in TCM and its formulas through batch molecular docking, allowing for the rapid construction and analysis of networks associated with “herb-compound-target-pathway” and disease targets. Built upon the integrated analysis concept of network formulaology and network pharmacology, TCMNPAS enables quick point-and-click completion of network-based association analysis, spanning from core formula mining from clinical data to the exploration of therapeutic targets for disease treatment. TCMNPAS serves as a powerful platform for uncovering the combinatorial rules and mechanism of TCM formulas holistically. We distribute TCMNPAS within an open-source R package at GitHub ( https://github.com/yangpluszhu/tcmnpas ), and the project is freely available at http://54.223.75.62:3838/ .

Abstract Esophageal squamous cell carcinoma (ESCC) remains an important health concern in developing countries. Patients with advanced ESCC have a poor prognosis and survival rate, and achieving early diagnosis remains a challenge. Metabolic biomarkers are gradually gaining attention as early diagnostic biomarkers. Hence, this multicenter study comprehensively evaluated metabolism dysregulation in ESCC through an integrated research strategy to identify key metabolite biomarkers of ESCC. First, the metabolic profiles were examined in tissue and serum samples from the discovery cohort (n = 162; ESCC patients, n = 81; healthy volunteers, n = 81), and ESCC tissue-induced metabolite alterations were observed in the serum. Afterward, RNA sequencing of tissue samples (n = 46) was performed, followed by an integrated analysis of metabolomics and transcriptomics. The potential biomarkers for ESCC were further identified by censoring gene-metabolite regulatory networks. The diagnostic value of the identified biomarkers was validated in a validation cohort (n = 220), and the biological function was verified. A total of 457 dysregulated metabolites were identified in the serum, of which 36 were induced by tumor tissues. The integrated analyses revealed significant alterations in the purine salvage pathway, wherein the abundance of hypoxanthine/xanthine exhibited a positive correlation with HPRT1 expression and tumor size. A diagnostic model was developed using two purine salvage–associated metabolites. This model could accurately discriminate patients with ESCC from normal individuals, with an area under the curve (AUC) (95% confidence interval (CI): 0.680–0.843) of 0.765 in the external cohort. Hypoxanthine and HPRT1 exerted a synergistic effect in terms of promoting ESCC progression. These findings are anticipated to provide valuable support in developing novel diagnostic approaches for early ESCC and enhance our comprehension of the metabolic mechanisms underlying this disease.

Abstract Background The caregiver burden frequently experienced by family members tending to advanced cancer patients significantly impacts their psychological well-being and quality of life (QoL). Although family resilience might function as a mitigating factor in this relationship, its specific role remains to be elucidated. This study aims to probe the mediating effect of psychological distress on the relationship between caregiver burden and QoL, as well as the moderating effect of family resilience. Methods A cross-sectional study was conducted between June 2020 and March 2021 in five tertiary hospitals in China. Data were collected on caregiver burden, family resilience, psychological distress (including anxiety and depression), and QoL. Moderated mediation analysis was performed. Results Data analysis included 290 caregivers. It confirmed the mediating role of psychological distress in the caregiver burden-QoL relationship (P

Objective Icotinib has been approved for adjuvant treatment of stage II–IIIA non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations in China, yet the long-term costs and outcomes of this strategy are unknown. Thus, we examined the cost effectiveness of adjuvant icotinib, compared with adjuvant chemotherapy, for the treatment of resected stage II–IIIA EGFR-mutated NSCLC.Design We performed a cost-effectiveness analysis from the perspective of the Chinese healthcare system, comparing 2-year adjuvant icotinib with four cycles of adjuvant chemotherapy. Costs and quality-adjusted life years (QALYs) were estimated using a Markov model. Model inputs were obtained from local data and literature. The influence of model parameters and assumptions was explored in sensitivity analyses. All costs are expressed in 2022 US dollars, and costs and QALYs were discounted at a rate of 5% per year. The willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product.Setting The Chinese healthcare system perspective.Participants A hypothetical Chinese cohort of patients with resected stage II–IIIA EGFR-mutated NSCLC.Interventions Icotinib versus chemotherapy.Primary outcome measure Costs, QALYs, incremental cost-effectiveness ratio.Results The incremental cost per QALY gained with the use of 2-year icotinib, from the Chinese healthcare system perspective, was $3440.66 compared with adjuvant chemotherapy. At a WTP threshold of $40 500, adjuvant icotinib was the optimal treatment in over 99% of replications. The interpretation of the results was insensitive to model and input assumptions.Conclusions Compared with adjuvant chemotherapy, adjuvant icotinib may be a cost-effective treatment for resected stage II–IIIA EGFR-mutated NSCLC as the WTP threshold is set at $40 500 per QALY.

BackgroundThe aim of this study was to investigate the relationship between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) and all-cause mortality in adults with metabolic syndrome (MeS) and explore the mediating role of oxidative stress.MethodsThis study included 6131 adults with MeS from the National Health and Nutrition Examination Survey (NHANES). The relationships between TyG index and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines (RCS) Fine-Gray competing risk model. In addition, mediation analysis was used to test the indirect effect of oxidative stress indicators.ResultsOver a median 106-month follow-up, a total of 357 CVD and 1292 all-cause deaths were recorded. After multivariate adjustment, there was a J-type relationship between TyG index and CVD and all-cause mortality, with optimal inflection point of 9.13 and 8.92. After the threshold point, TyG index was positively associated with CVD (HR: 4.21, 95%CI: 1.82, 9.78) and all-cause mortality(HR: 2.93, 95%CI: 2.05, 4.18). Even using non-cardiovascular mortality as a competitive risk, the Fine-Gray model also illustrated that the cumulative CVD mortality incidence was higher in MeS with TyG index >9.13 (Fine-Gray P< 0.01). Mediation analysis revealed that biomarkers of oxidative stress, including gamma-glutamyl transferase and uric acid, collectively mediated 10.53% of the association between the TyG index and CVD mortality, and 8.44% of the association with all-cause mortality (P < 0.05).ConclusionIn the cohort study, TyG index was found to have a J-shaped association with CVD mortality and all-cause mortality in MeS population and oxidative stress may play a key mediating role in this relationship.

Objectives To evaluate changes in health outcomes between years 2 and 3 after discharge following COVID-19 and to identify risk factors for poor health 3-year post-discharge.Design This is a multicentre observational cohort study.Setting This study was conducted in two centres from Wuhan, China.Participants Eligibility screening has been performed in 3988 discharged laboratory-confirmed adult COVID-19 patients. Exclusion criteria were refusal to participate, inability to contact and death before follow-up. The WHO COVID-19 guidelines on defining disease severity were adopted.Results 1594 patients participated in the 1-year, 2-year and 3-year follow-ups, including 796 (49.9%) male patients, and 422 (26.5%) patients were classified in the severe disease group. 3 years after discharge, 182 (11.4%) patients still complained of at least one symptom. The most common symptoms were fatigue, myalgia, chest tightness, cough, anxiety, shortness of breath and expectoration. Fatigue or myalgia, the most common symptom cluster, frequently coexisted with chest symptoms and anxiety. Symptom persistence between years 2 and 3 was reported in 70 patients (4.4%) for which intensive care unit (ICU) admission was a risk factor (p=0.038). Of the 1586 patients who completed the chronic obstructive pulmonary disease assessment test (CAT), 97 (6.1%) scored ≥10, with older age being associated with CAT ≥10 (p=0.007).Conclusions Between years 2 and 3 after SARS-CoV-2 infection, most patients returned to an asymptomatic state, and only a few were still symptomatic. ICU admission was a risk factor for symptom persistence.

As a low-toxicity metal, aluminum has garnered increasing attention in relation to its impact on the human body; however, the specific mechanism of action remains unclear. To bridge this knowledge gap and facilitate practical applications, this study took 8-week-old ICR mice as the research object to study the effects of dietary addition of aluminum potassium sulfate on intestinal flora structure and liver. As the concentration of aluminum increased, it inhibited mice weight growth rate and significantly altered the composition of white blood cells in their bloodstream. Histological examination revealed liver inflammation through HE staining sections. The oxidative stress markers MDA increased, GSH-PX and CAT decreased significantly. And liver function index MAO increased, TC and ALP decreased first and then increased. Moreover, there was a significant increase in pro-inflammatory factor TNF-α content. Further 16S rRNA sequencing analysis demonstrated substantial changes in both composition and structure of mouse intestinal microbiota induced by aluminum exposure; microbial phenotype prediction indicated that aluminum-induced oxidative stress promoted an increase in abundance of oxidation-resistant microbial types. Alterations in gut flora structure also influenced the liver via the gut-liver axis. These findings lay a foundation for further research on the regulation and interaction of aluminum on intestinal flora.

Summary: Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18–25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive fat deposition in hepatocytes and a major cause of end-stage liver disease. Autophagy is a metabolic pathway responsible for degrading cytoplasmic products and damaged organelles, playing a pivotal role in maintaining the homeostasis and functionality of hepatocytes. Recent studies have shown that pharmacological intervention to activate or restore autophagy provides benefits for liver function recovery by promoting the clearance of lipid droplets (LDs) in hepatocytes, decreasing the production of pro-inflammatory factors, and inhibiting activated hepatic stellate cells (HSCs), thus improving liver fibrosis and slowing down the progression of NAFLD. This article summarizes the physiological process of autophagy, elucidates the close relationship between NAFLD and autophagy, and discusses the effects of drugs on autophagy and signaling pathways from the perspectives of hepatocytes, kupffer cells (KCs), and HSCs to provide assistance in the clinical management of NAFLD.

Background and aimMetabolic-associated fatty liver disease (MAFLD) has gradually become one of the main health concerns regarding liver diseases. Postmenopausal women represent a high-risk group for MAFLD; therefore, it is of great importance to identify and intervene with patients at risk at an early stage. This study established a predictive nomogram model of MAFLD in postmenopausal women and to enhance the clinical utility of the new model, the researchers limited variables to simple clinical and laboratory indicators that are readily obtainable.MethodsData of 942 postmenopausal women from January 2023 to October 2023 were retrospectively collected and divided into two groups according to the collection time: the training group (676 cases) and the validation group (226 cases). Significant indicators independently related to MAFLD were identified through univariate logistic regression and stepwise regression, and the MAFLD prediction nomogram was established. The C-index and calibration curve were used to quantify the nomogram performance, and the model was evaluated by measuring the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).ResultsOf 37 variables, 11 predictors were identified, including occupation (worker), body mass index, waist-to-hip ratio, number of abortions, anxiety, hypertension, hyperlipidemia, diabetes, hyperuricemia, and diet (meat and processed meat). The C-index of the training group predicting the related risk factors was 0.827 (95% confidence interval [CI] 0.794–0.860). The C-index of the validation group was 0.787 (95% CI 0.728–0.846). Calibration curves 1 and 2 (BS1000 times) were close to the diagonal, showing a good agreement between the predicted probability and the actual incidence in the two groups. The AUC of the training group was 0.827, the sensitivity was 0.784, and the specificity was 0.735. The AUC of the validation group was 0.787, the sensitivity was 0.674, and the specificity was 0.772. The DCA curve showed that the nomogram had a good net benefit in predicting MAFLD in postmenopausal women.ConclusionsA predictive nomogram for MAFLD in postmenopausal women was established and verified, which can assist clinicians in evaluating the risk of MAFLD at an early stage.

ObjectiveEpidemics are sudden and rapidly spreading. Hospitals in underdeveloped areas are particularly vulnerable in case of an outbreak. This paper aims to assess the epidemic risk state and its change trend of hospitals in different epidemic stages, identify the key factors affecting hospital epidemic risk change, provide priority reference for hospital epidemic risk control, and enhance the hospital's ability to respond to sudden epidemics.MethodsBased on Grounded theory, the epidemic risk indicators that affect hospital safety are summarized. The concept of epidemic risk state and its random state space is proposed according to Markov chain theory. The impact of each indicator on the random risk state and its change is comprehensively assessed from two aspects: risk occurrence probability and risk loss. Finally, the assessment of the hospital epidemic risk state and its change at different stages is achieved.ResultsThe stable risk states of public hospitals in underdeveloped areas in non-epidemic stage t0, early epidemic stage t1, and outbreak stage t2 are P^t0(Sn)={0.142,0.546,0.220,0.093}, P^t1(Sn)={0.025,0.364,0.254,0.357}, and P^t2(Sn)={0.020,0.241,0.191,0.548}, respectively. In non-epidemic stage, the key factor in improving the hospital epidemic risk state is emergency funding. In early epidemic stage, the key factors in improving the hospital epidemic risk state are the training of medical staff in epidemic prevention skills and the management of public health. In outbreak state, the key factor in improving the hospital epidemic risk state is the training of medical staff in epidemic prevention skills and psychological awareness.ConclusionThis paper proposes the concept of epidemic risk state, providing an effective assessment method for the epidemic risk state and its change trend in public hospitals. According to the assessment, public hospitals in underdeveloped areas in different epidemic stages should adopt different risk control strategies to improve their current risk state. Blind risk control is inefficient and may even cause the epidemic risk to transition toward a more dangerous state.

Background: With the popularity of the internet, short videos have become an indispensable tool to obtain health information. However, avoiding health disinformation owing to the openness of the Internet is difficult for users. Disinformation may endanger the health and lives of users. Objective: With a focus on the process of identifying short videos' health disinformation and the factors affecting the accuracy of identification, this study aimed to investigate the identification methods, coping strategies, and the impact of short videos’ health disinformation on undergraduate nursing students. The findings will provide guidance to users on obtaining high-quality and healthy information, in addition to reducing health risks. Methods: Semi-structured in-depth interviews were conducted with 22 undergraduate nursing students in October 2022, and data were collected for collation and content analyses. Results: The techniques used to identify short videos that include health disinformation as well as how undergraduate nursing students perceived these videos' features are among the study's findings. The failure factors in identification, coping paths, and adverse impacts of short videos on health disinformation were analyzed. The platform, the material itself, and the students' individual characteristics all have an impact on their identifying behavior. Conclusions: Medical students continue to face many obstacles in identifying and responding to health disinformation through short videos. Preventing and stopping health disinformation not only requires individual efforts to improve health literacy and maintain rational thinking, it also requires the joint efforts of short video producers, relevant departments, and platforms.

Background: Infantile hemangioma (IH) is a common vascular tumor in female infants, which can lead to aesthetic issues and facial scarring. This study aimed to investigate the inhibitory effects and underlying mechanisms of 755 nm long-pulsed alexandrite laser on IH. Methods: Hemangioma endothelial cells (HemECs) were exposed to 755 nm long-pulsed alexandrite laser to evaluate its impact on cell proliferation and apoptosis. A patient-derived xenograft model was established to assess the inhibitory effects of laser treatment on IH in vivo. Results: In vitro, 755 nm long-pulsed alexandrite laser effectively suppressed the proliferation of HemECs and induced cell apoptosis. Laser treatment significantly inhibited the volume and weight of tumors, accompanied by significant downregulation of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) expression levels in both hemangioma cells and tumors. Additionally, laser treatment resulted in the conversion of VEGFA165a to VEGFA165b. TUNEL staining demonstrated increased apoptosis in tumor cells after laser treatment, along with upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. Conclusion: In addition to the principle of selective photothermal decomposition, modulation of the VEGF/PI3K/Akt axis may serve as a potential mechanism for IH treatment using a long pulse-width 755 nm laser. This sheds valuable light on the molecular mechanisms underlying IH pathogenesis and potential therapeutic targets while providing a theoretical basis for the safe and efficient management of proliferative IH using laser therapy.

3D bioprinting technology, a subset of 3D printing technology, is currently witnessing widespread utilization in tissue repair and regeneration endeavors. In particular, light-based 3D bioprinting technology has garnered significant interest and favor. Central to its successful implementation lies the judicious selection of photosensitive polymers. Moreover, by fine-tuning parameters such as light irradiation time, choice of photoinitiators and crosslinkers, and their concentrations, the properties of the scaffolds can be tailored to suit the specific requirements of the targeted tissue repair sites. In this comprehensive review, we provide an overview of commonly utilized bio-inks suitable for light-based 3D bioprinting, delving into the distinctive characteristics of each material. Furthermore, we delineate strategies for bio-ink selection tailored to diverse repair locations, alongside methods for optimizing printing parameters. Ultimately, we present a coherent synthesis aimed at enhancing the practical application of light-based 3D bioprinting technology in tissue engineering, while also addressing current challenges and future prospects.

The drawback of low strength of 304 stainless steel could be overcome by fabricating gradient nanostructures (GNS). However, deformation-induced martensite results in magnetic generation and plasticity degradation. In this work, a single austenitic GNS 304 stainless steel is fabricated by first creating a dual-phase GNS through the ultrasonic surface rolling process (USRP), followed by rapid induction heating. The yield strength of the single austenite GNS (520 MPa) is 1.68 times higher than that of the homogeneous coarse-grained structure (310 MP) without sacrificing plasticity (elongation of 65 %). Quantitative calculations indicate that fine grain, dislocation, twinning, and back-stress strengthening contribute to the strength increment by 30 %, 17.5 %, 23.4 %, and 29.1 %, respectively. Coarse-grained regions deform mainly through FCC-HCP-BCC martensitic transformation, whereas the subsurface layer forms stacking faults and twins due to increased stacking fault energy caused by the reduction in grain size. At the topmost layer, the stress required to activate dislocations is lower than that for twinning. Under high-stress conditions, martensite forms along the nanograin boundaries via a phase transition from FCC to BCC. Consequently, the excellent plasticity of the single austenite GNS stems from the synergistic effects of high back-stress hardening, TRIP and TWIP effect.

Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.

Abstract Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation.

Abstract Coffee, a widely consumed beverage, has shown benefits for human health but lacks sufficient basic and clinical evidence to fully understand its impacts and mechanisms. Here, we conducted a cross‐sectional observational study of coffee consumption and a 1‐month clinical trial in humans. We found that coffee consumption significantly reshaped the immune system and metabolism, including reduced levels of inflammatory factors and a reduced frequency of senescent T cells. The frequency of senescent T cells and the levels of the senescence‐associated secretory phenotype were lower in both long‐term coffee consumers and new coffee consumers than in coffee nondrinking subjects, suggesting that coffee has anti‐immunosenescence effects. Moreover, coffee consumption downregulated the activities of the The Janus kinase/signal transduction and activator of transcription (JAK/STAT) and mitogen‐activated protein kinases (MAPK) signaling pathways and reduced systemic proinflammatory cytokine levels. Mechanistically, coffee‐associated metabolites, such as 1‐methylxanthine, 3‐methylxanthine, paraxanthine, and ceramide, reduced the frequency of senescent CD4+CD57+ T cells in vitro. Finally, in vivo, coffee intake alleviated inflammation and immunosenescence in imiquimod‐induced psoriasis‐like mice. Our results provide novel evidence of the anti‐inflammatory and anti‐immunosenescence effects of coffee, suggesting that coffee consumption could be considered a healthy habit.

Abstract Elasticity, featured by a recoverable strain, refers to the ability that materials can return to their original shapes after deformation. Typically, the elastic strains of most metals are well‐known 0.2%. In shape memory alloys and high entropy alloys, the elastic strains can be several percent, as called superelasticity, which are all triggered by external stresses. A superelasticity induced by magnetic field, termed as magneto‐superelasticity, is extremely important for contactless work of materials and for developing brand‐new large stroke actuators and high efficiency energy transducers. In magnetic shape memory alloys, the twin boundary motion driven by magnetic field can output a strain of several percent. However, this strain is unrecoverable when removing the magnetic field and hence it is not magneto‐superelasticity. Here, a giant magneto‐superelasticity of 5% in a Ni34Co8Cu8Mn36Ga14 single crystal is reported by introducing arrays of ordered dislocations to form preferentially oriented martensitic variants during the magnetically induced reverse martensitic transformation. This work provides an opportunity to achieve high performance in functional materials by defect engineering.

Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell Fe3O4@TiO2 nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form Fe3O4@TiO2@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy. Laser confocal microscopy and flow cytometry results demonstrate that FTV nanoparticles are specifically recognized and phagocytosed by Panc-2 cells. In vivo experiments reveal that ultrasound-triggered TiO2 SDT can induce tumor immunogenic cell death (ICD) and recruit T-cell infiltration within the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs). Furthermore, ultrasound loosens the dense fibrous stroma surrounding the pancreatic tumor and increases vascular density, facilitating immune therapeutic efficiency. In summary, our study demonstrates that FTV nanoparticles hold great promise for synergistic SDT and immunotherapy in pancreatic cancer.

BackgroundMalnutrition is strongly correlated with worsened treatment outcomes, reduced standard of living, and heightened mortality rates among individuals with cancer. Our research explores how the Geriatric Nutritional Risk Index (GNRI), a measure of nutritional status, relates to all-cause mortality, cancer-specific, and non-cancer mortality among middle-aged and older adult cancer patients.MethodsWe enrolled 3,253 participants aged 40 and above who were diagnosed with cancer. The data was obtained from the National Health and Nutrition Examination Survey (NHANES) dataset covering the period from 2001 to 2018, with a median follow-up duration of 83 months. According to the GNRI levels, patients in the study were classified into two distinct groups: the group with a low GNRI (

BackgroundThe prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients.MethodsA total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms.ResultsPatients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25–7.72; p

Epiphyas postvittana, commonly known as the light brown apple moth (LBAM), is native to Australia and has a restricted global distribution. Its polyphagous nature and the recent surge in interceptions have emphasized the need for focused risk assessments to guide effective measures to curb the entry of this pest into new countries. This study aimed to perform a detailed global invasion risk assessment using an optimized MaxEnt model that incorporated 19 bioclimatic variables and elevation. The predictive outcomes underscored the significance of key variables, specifically the minimum temperature of the coldest month (bio6), precipitation of the driest month (bio14), and precipitation of the coldest quarter (bio19), in shaping the potential geographical distribution of LBAM. Regions beyond the existing range, including the southeastern United States, southern Brazil, eastern Argentina, Uruguay, southern Chile, and various Western European countries, were identified as susceptible to invasion and establishment by LBAM. An increase in suitability was observed above 45°N and 40°S under future climate scenario. With respect to climate change, LBAM would expand its potential range in Western Europe and the United States, especially under SSP5-8.5, in the 2050s. An upward trend in the latitudinal suitability gradient for LBAM in mid-high latitude areas implies that amid changing climate conditions, LBAM may find favorable habitats in these regions. For countries and regions with invasion risk, it is imperative to implement corresponding inspections and quarantine measures to thwart the introduction of LBAM, particularly in countries with established trade ties with invaded regions.

Summary: Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5′,8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.