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Abstract Background Deoxynivalenol (DON) is a mycotoxin that severely pollutes feed ingredients, and methods for reducing DON toxicity have become a significant research direction. Chlorogenic acid (CGA) is an active polyphenol found in some plants, which has anti-inflammatory and antioxidant properties and a protective effect on animal intestinal health. The effects of CGA on DON-induced pyroptosis in the intestinal porcine epithelial cell line-J2 (IPEC-J2) and its potential mechanism were explored in this study. Results IPEC-J2 cells viability and membrane integrity were inversely correlated with DON concentration. Compared to those in the group treated with DON alone at 2,500 ng/mL, pretreatment with 80 μmol/L CGA for 4 h significantly improved cell viability (P

Abstract Methane (CH4) photocatalytic upgrading to value-added chemicals, especially C2 products, is significant yet challenging due to sluggish energy/mass transfer and insufficient chemical driven-force in single photochemical process. Herein, we realize solar-driven CH4 oxidation to ethanol (C2H5OH) on crystalline carbon nitride (CCN) modified with Cu9S5 and Cu single atoms (Cu9S5/Cu-CCN). The integration of photothermal effect and photocatalysis overcomes CH4-to-C2H5OH conversion bottlenecks, with Cu9S5 as a hotspot to convert solar-energy to heat. In-situ characterizations demonstrate that Cu single atoms play as electron acceptor for O2 reduction to ·OOH/ · OH, while Cu9S5 acts as hole acceptor and site for CH4 adsorption, C − H activation, and C − C coupling. Theoretical calculations demonstrate that Cu9S5/Cu-CCN reduces C − C coupling energy barrier by stabilizing ·CH3 and ·CH2O. Impressively, C2H5OH productivity reaches 549.7 μmol g–1 h–1, with selectivity of 94.8% and apparent quantum efficiency of 0.9% (420 nm). This work provides a sustainable avenue for CH4 conversion to value-added chemcials.

This research aims to study the effect of magnetic nanoparticles of Fe3O4 (MNP Fe3O4) containing gambogic acid (GA-MNP Fe3O4) on colorectal cancer (CRC). MNP Fe3O4 enhanced the antitumor effect of GA by inhibiting the malignant behavior of CRC cells. RORB was a target of GA, and GA activated RORB expression to inhibit metastasis of CRC. Knockdown of RORB impaired the effect of GA-MNP Fe3O4 on CRC metastasis. EMILIN1 was a target of RORB, and RORB promoted transcription of EMILIN1. Overexpression of EMILIN1 reversed the effect of knockdown of RORB on GA-MNP Fe3O4 and inhibited metastasis in CRC. These findings revealed that MNP Fe3O4 enhanced the antitumor effect of GA and activated RORB to promote EMILIN1 transcription and inhibit CRC metastasis.

Abstract Urban greening can reduce concentrations of particulate matter (PM). However, most of the PM is deposited temporarily on foliage and can be removed by precipitation. Due to the unpredictability and randomness of natural rain and the complexity of environmental conditions, the effect of rainfall on PM removal from foliage is usually examined using simulated rain. The aim of this study was to compare the effects of natural and simulated rain on washing off PM deposited on the foliage of seventeen plant species (evergreen/deciduous trees and shrubs, herbaceous plants). Regardless of the PM fraction studied, simulated rain washed off a larger fraction of the PM than natural rain. A novel finding is the differential role played by various plant characteristics in determining the effectiveness of PM wash off under natural and simulated rain conditions, with their influence being more pronounced under natural rainfall. The type of rainfall and PM size fraction influenced the effectiveness of the PM wash-off from different plant groups. Natural rain was more effective at removing PM from evergreen trees, while simulated rainfall was more effective at removing PM from deciduous shrubs and herbaceous plants. The results obtained from this study suggest that simulated rain does not reflect the effects of natural precipitation on the processes removing PM from leaves, and therefore should not be used to explain phenomena that occur in realistic conditions.

Abstract Oxide ceramic electrolytes (OCEs) have great potential for solid-state lithium metal (Li0) battery applications because, in theory, their high elastic modulus provides better resistance to Li0 dendrite growth. However, in practice, OCEs can hardly survive critical current densities higher than 1 mA/cm2. Key issues that contribute to the breakdown of OCEs include Li0 penetration promoted by grain boundaries (GBs), uncontrolled side reactions at electrode-OCE interfaces, and, equally importantly, defects evolution (e.g., void growth and crack propagation) that leads to local current concentration and mechanical failure inside and on OCEs. Here, taking advantage of a dynamically crosslinked aprotic polymer with non-covalent –CH3⋯CF3 bonds, we developed a plastic ceramic electrolyte (PCE) by hybridizing the polymer framework with ionically conductive ceramics. Using in-situ synchrotron X-ray technique and Cryogenic transmission electron microscopy (Cryo-TEM), we uncover that the PCE exhibits self-healing/repairing capability through a two-step dynamic defects removal mechanism. This significantly suppresses the generation of hotspots for Li0 penetration and chemomechanical degradations, resulting in durability beyond 2000 hours in Li0-Li0 cells at 1 mA/cm2. Furthermore, by introducing a polyacrylate buffer layer between PCE and Li0-anode, long cycle life >3600 cycles was achieved when paired with a 4.2 V zero-strain cathode, all under near-zero stack pressure.

Abstract Tibetan sheep are indigenous to the Qinghai-Xizang Plateau. Owing to the harsh hypoxic environment in this plateau, the hemoglobin (Hb) protein in Tibetan sheep has undergone adaptive changes over time. Hb is primarily responsible for transporting O2 and CO2 between the lungs and other tissues of the body. The α subunit of Hb, encoded by the HBA gene, is a crucial component of the protein. However, whether variations in the HBA gene sequence affect the adaptation of Tibetan sheep to high-altitude hypoxia remains unclear. In this study, we sequenced the HBA gene and identified three single nucleotide polymorphisms (SNPs). These SNPs were genotyped in Tibetan and Hu sheep using Kompetitive Allele-Specific PCR (KASP). The results showed that the frequencies of the AT genotype and H1H2 haplotype were higher in Tibetan sheep than in Hu sheep. Individuals with the AT genotype exhibited higher P50 levels, whereas those with the H1H2 haplotype exhibited lower PO2 and SaO2 levels. The higher P50 levels indicated that O2 was more readily released from oxygenated Hb into the tissues, with the lower PO2 and SaO2 levels facilitating this process. These findings indicate that variations in the HBA gene sequence contribute to enhancing O2 transfer efficiency in Tibetan sheep.

Abstract Background The surgical procedure of vertebral column decancellation (VCD) has been increasingly performed in orthopaedic surgery for those with spinal deformity. To investigate the results of single-segment VCD performed at different vertebra for correcting thoracolumbar kyphosis in ankylosing spondylitis (AS) and to guide the osteotomy strategy. Methods Eighty-six AS patients (77 males, 9 females) having thoracolumbar kyphosis underwent single-segment VCD (ranging from T12 to L3) between January 2016 and September 2019 were enrolled and divided into four groups according to the osteotomy vertebra: T12 in 9 cases (Group A), L1 in 15 cases (Group B), L2 in 47 cases (Group C), and L3 in 15 cases (Group D). Demographics, operational data, radiological and clinical data were compared among the four groups. Results All patients had significant improvements in spinopelvic alignments and health-related quality of life after correction surgeries. Having the similar demographics, patients in the group C obtained the maximum local kyphosis and global kyphosis correction of 45.05° ± 9.07° (P

Abstract Salt bladders, specialized structures on the surface of quinoa leaves, secrete Na+ to mitigate the effects of the plant from abiotic stresses, particularly salt exposure. Understanding the development of these structures is crucial for elucidating quinoa’s salt tolerance mechanisms. In this study, we employed transmission electron microscopy to detail cellular differentiation across the developmental stages of quinoa salt bladders. To further explore the developmental trajectory and underlying molecular mechanisms, we conducted single-cell RNA sequencing on quinoa protoplasts derived from young leaves. This allowed us to construct a cellular atlas, identifying 13 distinct cell clusters. Through pseudotime analysis, we mapped the developmental pathways of salt bladders and identified regulatory factors involved in cell fate decisions. GO and KEGG enrichment analyses, as well as experimental results, revealed the impacts of salt stress and the deprivation of sulfur and nitrogen on the development of quinoa salt bladders. Analysis of the transcription factor interaction network in pre-stalk cells (pre-SC), stalk cells (SC), and epidermal bladder cells (EBCs) indicated that TCP5, YAB5, NAC078, SCL8, GT-3B, and T1P17.40 play crucial roles in EBC development. Based on our findings, we developed an informative model elucidating salt bladder formation. This study provides a vital resource for mapping quinoa leaf cells and contributes to our understanding of its salt tolerance mechanisms.

Abstract Background In recent years, the hypervirulent and carbapenem-resistant Klebsiella pneumoniae has been increasingly reported worldwide. The objective of this study was to compare the antibiotic resistance and virulence profiles of carbapenem-resistant hypervirulent K.pneumoniae (CR-hvKP) and hypervirulent carbapenem-resistant K.pneumoniae (hv-CRKP) and identify the prevailing strain in clinical settings. Methods In this study, hv-CRKP or CR-hvKP were identified based on the results of whole-genome analysis (WGS), multilocus sequence typing (MLST) and the antimicrobial susceptibility testing. We then compared antibiotic resistance and virulence profiles between CR-hvKP and hv-CRKP through the antimicrobial susceptibility testing and a series of virulence experiments including biofilm formation ability detection method, the resistance test against human serum, siderophore production test, neutrophil phagocytosis assay and Galleria mellonella infection model. Additionally, pathway enrichment analysis was conducted to assess the effect of SNPs on the phenotype. Results In this study, we categorized 17.4% of hypervirulent and carbapenem-resistant K. pneumoniae strains as CR-hvKP and 82.6% as hv-CRKP. Among them, 84.2% (16/19) of CR-hvKP strains harboring carbapenemase genes exhibited lower imipenem and meropenem MIC values compared to hv-CRKP strains. The virulence potential of hv-CRKP and CR-hvKP was confirmed by using virulence experiments in vitro and in vivo, showing that virulence of the CR-hvKP strains was comparable to that of hv-CRKP strains. Notably, the 90 hv-CRKP strains were classified into 3 different ST types and 8 capsule types, each showing varying degrees of resistance and virulence. We observed that subclonal replacement was within the predominant hv-CRKP clone, with the ST11-KL64 strain, characterized by high-level resistance and virulence emerging as the currently prevailing subclone, replacing ST11-KL47. KEGG enrichment analysis showed that pathways associated with the citrate cycle (TCA cycle), glycolysis/gluconeogenesis, glutathione metabolism, two-component regulatory system, and folate metabolism were significantly enriched among the group expressing different levels of capsular polysaccharides. Conclusions The hv-CRKP strains exhibited a greater survival advantage in the hospital environment than CR-hvKP strains. Notably, the ST11-KL64 hv-CRKP strain which displayed a high level of resistance and hypervirulence, warrants the most clinical vigilance. Clinical trial number Not applicable.

Abstract Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and a primary cause of end-stage renal disease (ESRD). Increasing studies suggest that immune cells are involved in regulating renal inflammation, which contributes to the progression of DKD. Compared with conventional methods, single-cell sequencing technology is more developed technique that has advantages in resolving cellular heterogeneity, parallel multi-omics studies, and discovering new cell types. ScRNA-seq helps researchers to analyze specifically gene expressions, signaling pathways, intercellular communication as well as their regulations in various immune cells of kidney biopsy and urine samples. It is still challenging to investigate the function of each cell type in the pathophysiology of kidney due to its complex and heterogeneous structure and function. Here, we discuss the application of single-cell transcriptomics in the field of DKD and highlight several recent studies that explore the important role of immune cells including macrophage, T cells, B cells etc. in DKD through scRNA-seq analyses. Through combing the researches of scRNA-seq on immune cells in DKD, this review provides novel perspectives on the pathogenesis and immune therapeutic strategy for DKD.

Abstract The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further analysis showed that chondrocytes might communicate with immune cells via the MIF, TNFSF9, SPP1 and CCL4L2 signaling pathways. In addition, we found that invading endothelial cells might interact with chondrocytes through the COL4A1, CXCL12, VEGFA and SEMA3E signaling pathways. Our results reveal the cellular complexity and phenotypic characteristics of NP tissues at single-cell resolution, which will contribute to the in-depth investigation of preventative and regenerative strategies for IVDD.

Abstract Background Olfactory function is closely related to mood and the endocrine system. However, the role of olfactory function in bipolar disorder combined with metabolic syndrome remains unclear. The purpose of this study was to explore the associations among olfactory function, tumor necrosis factor alpha (TNF-α), and metabolic syndrome and its components in patients with bipolar disorder. Methods Ninety-six bipolar disorder patients were divided into two groups with and without metabolic syndrome. We also included 46 healthy controls. Olfactory function was assessed using the Sniffin’ Sticks test. Blood samples were collected to measure metabolic indicators and serum TNF-α levels. Results Significant differences in olfactory function were found among the three groups. Compared with the healthy controls, the bipolar disorder without metabolic syndrome group showed poorer olfactory identification ability (P

Abstract Background Post-stroke stress can trigger instant survival but its influence on long-term ischemic stroke outcomes remains controversial. Thus, we sought to explore the associations of acute post-stroke stress evidenced by endocrine and metabolic changes, with long-term ischemic stroke outcomes. Methods Admissions for acute ischemic stroke within seven days of onset were prospectively recruited to determine acute endocrine and metabolic variations measured by thyroid parameters and the stress hyperglycemia ratio (SHR). Long-term ischemic stroke prognoses were followed up for one year, with the primary outcome being a modified Rankin Scale score of 3 to 6. Results A total of 887 patients were enrolled, of which 535 reached the final one-year followed up at a poor prognosis rate of 29.3%. Patients with poor outcomes were observed to have lower levels of free triiodothyronine (fT3) and higher levels of SHR on admission. Medium values (fT3, 4.4 mmol/L; SHR, 8 nmol/L) were used to divide patients into four gradient stress degrees. Larger acute endocrine and metabolic variations (fT3

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to the pro-tumor effect of M2-like TAMs, M1-like TAMs account for a small proportion and have anti-tumor effects. Since TAMs can switch from one type to another, reprogramming TAMs may be an important treatment for HCC therapy. However, the mechanisms of phenotypic switch and reprogramming TAMs are still obscure. In this study, we analyzed differential genes in normal macrophages and TAMs, and found that loss of MANF in TAMs accompanied by high levels of downstream genes negatively regulated by MANF. MANF reprogrammed TAMs into M1 phenotype. Meanwhile, loss of MANF promoted HCC progression in HCC patients and mice HCC model, especially tumor neovascularization. Additionally, macrophages with MANF supplement suppressed HCC progression in mice, suggesting MANF supplement in macrophage was an effective treatment for HCC. Mechanistically, MANF enhanced the HSF1–HSP70-1 interaction, restricted HSF1 in the cytoplasm of macrophages, and decreased both mRNA and protein levels of HSP70-1, which in turn led to reprogramming TAMs, and suppressing neovascularization of HCC. Our study contributes to the exploration the mechanism of TAMs reprogramming, which may provide insights for future therapeutic exploitation of HCC neovascularization.

Abstract In situ electrochemistry on micron and submicron-sized individual particles and thin layers is a valuable, emerging tool for process understanding and optimization in a variety of scientific and technological fields such as material science, process technology, analytical chemistry, and environmental sciences. Electrochemical characterization and manipulation coupled with soft X-ray spectromicroscopy helps identify, quantify, and optimize processes in complex systems such as those with high heterogeneity in the spatial and/or temporal domain. Here we present a novel platform optimized for in situ electrochemistry with variable liquid electrolyte flow in soft X-ray scanning transmission X-ray microscopes (STXM). With four channels for fluid control and a modular design, it is suited for a wealth of experimental conditions. We demonstrate its capabilities by proving the reversible oxidation and reduction of individual microbial biofilm structures formed by microaerophilic Fe(II)-oxidizing bacteria, also known as twisted stalks. We show spectromicroscopically the heterogeneity of the redox activity on the submicron scale. Examples are also provided of electrochemical modification of liquid electrolyte species (Fe(II) and Fe(III) cyanides), and in situ studies of electrodeposited copper nanoparticles as CO2 reduction electrocatalysts under reaction conditions.

Abstract Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

Abstract Exposure to adverse life events is linked to somatic disorders. The study aims to evaluate the association between adverse events at varying life stages and the risk of chronic kidney disease (CKD), a condition affecting about 10% population worldwide. This prospective cohort study included 140,997 participants from the UK Biobank. Using survey items related to childhood maltreatment, adulthood adversity and catastrophic trauma, we performed latent class analysis to summarize five distinct patterns of exposure to adverse life events, namely “low-level exposure”, “childhood exposure”, “adulthood exposure”, “sexual abuse” and “child-to-adulthood exposure”. We used Cox proportional hazard regression to evaluate the association of patterns of exposure to adverse life events with CKD, regression-based mediation analysis to decompose the total effect, and gene-environment-wide interaction study (GEWIS) to identify interactions between genetic loci and adverse life events. During a median follow-up of 5.98 years, 2734 cases of incident CKD were identified. Compared with the “low-level exposure” pattern, “child-to-adulthood exposure” was associated with increased risk of CKD (hazard ratio 1.37, 95% CI 1.14 to 1.65). BMI, smoking and hypertension mediated 11.45%, 9.79%, and 4.50% of this total effect, respectively. Other patterns did not show significant results. GEWIS and subsequent analyses indicated that the magnitude of the association between adverse life events and CKD differed according to genetic polymorphisms, and identified potential underlying pathways (e.g., interleukin 1 receptor activity). These findings underscore the importance of incorporating an individual’s psychological encounters and genetic profiles into the precision prevention of CKD.

Abstract Background Intraspinal cysticercosis, usually with serious neurological deterioration, is rarely diagnosed because its clinical manifestations are nonspecific, and most physicians might not be familiar with its imaging features. Case presentation A 50-year-old woman presented with a 2-month history of increasing pain in her right buttock, rectal tenesmus and uncontrolled micturition. Intradural extramedullary cystic lesion was found, and the characteristic MRI findings of a living cysticercus and a dying cysticercus were presented simultaneously. Finally, the giant intraspinal cysticercus was treated by surgery and antiparasitic treatment. Conclusions This case emphasizes that the characteristic imaging findings of different cysticercus cysts as well as the detailed personal history usually provide useful diagnostic clues. Cerebrospinal fluid analysis may aid in confirming the diagnosis.

The observability of underground engineering, such as coal mining, is extremely limited, which makes it difficult to obtain reliable pre-analysis basis for many complex engineering problems. Especially in face of new engineering environment brought about by deep conditions and high-intensity mining, the applicability of the existing theoretical system and technical solutions is facing severe challenges. Based on the technical characteristics of the digital era, a digital rock mechanics solution that integrates data laws, mechanical logic and engineering experience is proposed. The solution makes full use of the objective characteristics of real engineering laws contained in engineering data, and gives a specific mode of underlying integration among theoretical achievements, engineering experience and data law mining. Through the non-damaged inference of mechanical parameters of coal specimens, the feasibility of the above technical path is verified, and the data mining and utilization with both reliability and interpretability are realized. Furthermore, a digital rock mechanics theoretical system with rock physical properties, geological structure and spatial stress as the basic elements is established, and a general operation mode of digital rock mechanics underground engineering with the steps of “engineering sketch, physical knowledge embedding, professional knowledge integration, decision generation” is proposed. The reliability of the digital rock mechanics solution is verified by the application in complex engineering, which provides a practical implementation path for the digital transformation and intelligent upgrading of underground engineering such as coal mining.

Abstract Aliphatic diols such as ethylene and propylene glycol are the key products in the chemical industry for manufacturing polymers. The synthesis of these molecules usually implies sequential processes, including epoxidation of olefins using hydrogen peroxide or oxygen with subsequent hydrolysis to glycols. Direct hydroxylation of olefins by cheap and green oxidants is an economically attractive and environmentally friendly route for the synthesis of diols. Here, we report a photocatalytic reaction for the dihydroxylation of ethylene and propylene to their glycols at room temperature using water as the oxidant. The photocatalyst contains Pd clusters stabilized by sub-nanometric polyoxometalate with TiO2 as the host material. Under light irradiation, it results in production rates of ethylene glycol and propylene glycols of 146.8 mmol·gPd −1·h−1 and 28.6 mmol·gPd −1·h−1 with liquid-phase selectivities of 63.3 % and 80.0 %, respectively. Meanwhile, green hydrogen derived from water is produced as another valuable product. Combined spectroscopy investigation suggests that the reaction proceeds via π-bonded adsorption of olefins over Pd clusters with hydroxylation by hydroxyl radicals formed by photocatalytic dissociation of water.

Abstract Although perovskite solar cells (PSCs) are promising next generation photovoltaics, the production of PSCs might be hampered by complex and inefficient procedures. This Review outlines important advances in materials and methods for the cost-effective manufacturing of PSCs, including precursor synthesis, selection criteria for precursors based on chemistry, additive engineering, and deposition techniques. The goal of these technologies is not only to improve the performance and stability of PSCs, but also to significantly reduce their manufacturing costs. These advances are critical to the commercialization of PSCs, in terms of making them viable and cost-effective.

Abstract Background Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. Results In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. Conclusions This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Abstract Background Postoperative refracture of osteoporotic compression fractures in the elderly due to underlying illnesses is a complicated matter involving several variables. A multidisciplinary approach involving orthopedics, geriatrics, endocrinology, and rehabilitation medicine is necessary for an investigation of these issues. investigating the impact of older patients’ underlying medical conditions on the refracture of osteoporotic compression fractures following surgery. Methods A retrospective analysis was conducted on 2383 patients between August 2013 and August 2023. 550 patients with comorbid geriatric underlying diseases were screened, 183 patients underwent refractories, and 367 patients were classified as non-refractories. The patients were then divided into two groups: those undergoing refractories and those not, and the underlying diseases of the patients in both groups were examined using ROC curves and unifactorial and multifactorial logistic regression analyses. Results Among the patients gathered, the frequency of re-fracture was 33.3%. A statistically significant difference was observed when re-fracture was linked to patients with long-term alcohol consumption, operated vertebrae ≤ 1, hypertension, COPD, diabetes mellitus, stroke sequelae, conservative treatment of coronary heart disease, trauma, mental abnormality, scoliosis, and chronic renal disease. Having hypertension decreased the risk of re-fracture (P = 0.018, OR = 0.548), while alcohol intake ≥ 10years (P = 0.003, OR = 2.165), mental abnormality (P

Currently, many countries and regions worldwide face the challenge of declining population growth due to persistently low rates of female reproduction. Since 2017, China's birth rate has hit historic lows and continued to decline, with the death rate now equaling the birth rate. Concerns have emerged regarding the potential impact of environmental contaminants on reproductive health, including pregnancy loss. Endocrine-disrupting chemicals (EDCs) like phthalate esters (PAEs), bisphenol A (BPA), triclosan (TCS), and perfluoroalkyl substances (PFASs) have raised attention due to their adverse effects on biological systems. While China's 14th Five-Year Plan (2021–2025) for national economic and social development included the treatment of emerging pollutants, including EDCs, there are currently no national appraisal standards or regulatory frameworks for EDCs and their mixtures. Addressing the risk of EDC mixtures is an urgent matter that needs consideration from China's perspective in the near future. In this Perspective, we delve into the link between EDC mixture exposure and pregnancy loss in China. Our focus areas include establishing a comprehensive national plan targeting reproductive-aged women across diverse urban and rural areas, understanding common EDC combinations in women and their surrounding environment, exploring the relationship between EDCs and pregnancy loss via epidemiology, and reconsidering the safety of EDCs, particularly in mixtures and low-dose scenarios. We envision that this study could aid in creating preventive strategies and interventions to alleviate potential risks induced by EDC exposure during pregnancy in China.

Abstract Corynespora cassiicola is a highly diverse fungal pathogen that commonly occurs in tropical, subtropical, and greenhouse environments worldwide. In this study, the isolates were identified as C. cassiicola, and the optimum growth and sporulation were studied. The phenotypic characteristics of C. cassiicola, concerning 950 different growth conditions, were tested using Biolog PM plates 1–10. In addition, the strain of C. cassiicola DWZ from tobacco hosts was sequenced for the using Illumina PE150 and Pacbio technologies. The host resistance of tobacco Yunyan 87 with different maturity levels was investigated. In addition, the resistance evaluation of 10 common tobacco varieties was investigated. The results showed that C. cassiicola metabolized 89.47% of the tested carbon source, 100% of the nitrogen source, 100% of the phosphorus source, and 97.14% of the sulfur source. It can adapt to a variety of different osmotic pressure and pH environments, and has good decarboxylase and deaminase activities. The optimum conditions for pathogen growth and sporulation were 25–30 °C, and the growth was better on AEA and OA medium. The total length of the genome was 45.9 Mbp, the GC content was 51.23%, and a total of 13,061 protein-coding genes, 202 non-coding RNAs and 2801 and repeat sequences were predicted. Mature leaves were more susceptible than proper mature and immature leaves, and the average diameter of diseased spots reached 17.74 mm at 12 days. None of the tested ten cultivars exhibited obvious resistance to Corynespora leaf spot of tobacco, whereby all disease spot diameters reached > 10 mm and > 30 mm when at 5 and 10 days after inoculation, respectively. The phenotypic characteristics, genomic analysis of C. cassiicola and the cultivar resistance assessment of this pathogen have increased our understanding of Corynespora leaf spot of tobacco.

Abstract Millimeter-Wave (MMW) imaging is a promising technique for contactless security inspection. However, the high cost of requisite large-scale antenna arrays hinders its widespread application in high-throughput scenarios. Here, we report a large-scale single-shot MMW imaging framework, achieving low-cost high-fidelity security inspection. We first analyzed the statistical ranking of each array element through 1934 full-sampled MMW echoes. The highest-ranked elements are preferentially selected based on the ranking, building the experimentally optimal sparse sampling strategy that reduces antenna array cost by one order of magnitude. Additionally, we derived an untrained interpretable learning scheme, realizing robust and accurate MMW image reconstruction from sparsely sampled echoes. Last, we developed a neural network for automatic object detection, and experimentally demonstrated successful detection of concealed centimeter-sized targets using 10% sparse array, whereas all the other contemporary approaches failed at such a low sampling ratio. With the strong detection ability and order-of-magnitude cost reduction, we anticipate that this technique provides a practical way for large-scale single-shot MMW imaging.

Abstract Stroke, the second leading cause of death and disability, causes massive cell death in the brain followed by secondary inflammatory injury initiated by disease associated molecular patterns released from dead cells. Nonetheless, the evidence regarding the causal relationship between inflammatory cytokines and stroke subtypes is obscure. To leverage large scale genetic association data to investigate the interplay between circulating cytokines and stroke, we adopted a two-sample bi-directional Mendelian randomization (MR) analysis. Firstly, we performed a forward MR analysis to examine the associations of genetically determined 31 cytokines with 6 stroke subtypes. Secondly, we conducted a reverse MR analysis to check the associations of 6 stroke subtypes with 31 cytokines. In the forward MR analysis, genetic evidence suggests that 21 cytokines were significantly associated with certain stroke subtype risk with |β| ranging from 1.90 × 10−4 to 0.74. In the reverse MR analysis, our results found that five stroke subtypes (intracerebral hemorrhage (ICH), large artery atherosclerosis ischemic stroke (LAAS), lacunar stroke (LS), cardioembolic ischemic stroke (CEI), small-vessel ischemic stroke (SV)) caused significantly changes in 16 cytokines with |β| ranging from 1.08 × 10−4 to 0.69. In particular, those five stroke subtypes were statistically significantly associated with C-reactive protein (CRP). In addition, ICH, LAAS, LS and SV were significantly correlated with vascular endothelial growth factor (VEGF), while LAAS, LS, CEI and SV were significantly related to fibroblast growth factor (FGF). Moreover, integrated bi-directional MR analysis, these factors (IL-3Rα, IL-6R, IL-6Rα, IL-1Ra, insulin-like growth factor-1(IGF-1), IL-12Rβ2) can be used as predictors of some specific stroke subtypes. As well as, IL-16 and C–C motif chemokine receptor 7 (CCR7) can be used as prognostic factors of stroke. Our findings prognostic identify potential pharmacological opportunities, including perturbation of circulating cytokines for both predicting stroke risk and post stroke treatment effects. As we conducted a comprehensive search and analysis of stroke subtype and cytokines in the existing publicly available GWAS database, the results have good population-generalizability.

Abstract Background Generalized anxiety (GA) is showing a high prevalence among adolescents nowadays; investigations on influencing factors and potential mechanisms are important to inform intervention development. The present two-wave study investigated the ways in which family functioning predicted GA six months later among adolescents, by considering the mediating role of self-identity and cognitive flexibility. Methods Adolescents were recruited from 27 randomly selected classes in two secondary schools in Chongqing and Fujian Province, China. Survey questionnaires assessing family functioning, self-identity, cognitive flexibility and GA were obtained from 1223 adolescents (M age = 13.14, SD = 1.35) at two time points of the 6-month interval. Results The association between family functioning (T1) and GA (T2) was significant (r= -0.152, p

Abstract Immune evasion is one of the critical hallmarks of malignant tumors, especially non-small cell lung cancer (NSCLC). Emerging findings have illustrated the roles of N6-methyladenosine (m6A) on NSCLC immune evasion. Here, this study investigated the function and underlying mechanism of m6A reader YTH domain family protein 3 (YTHDF3) on NSCLC immune evasion. YTHDF3 was found to be highly expressed in NSCLC tissue and act as an independent prognostic factor for overall survival. Functionally, up-regulation of YTHDF3 impaired the CD8+ T antitumor activity to deteriorate NSCLC immune evasion, while YTHDF3 silencing recovered the CD8+ T antitumor activity to inhibit immune evasion. Besides, YTHDF3 up-regulation reduced the apoptosis of NSCLC cells. Mechanistically, PD-L1 acted as the downstream target for YTHDF3, and YTHDF3 could upregulate the transcription stability of PD-L1 mRNA. Overall, YTHDF3 targeted PD-L1 to promote NSCLC immune evasion partially through escaping effector cell cytotoxicity CD8+ T mediated killing and antitumor immunity. In summary, this study provides an essential insight for m6A modification on CD8+ T cell-mediated antitumor immunity in NSCLC, which might inspire an innovation for lung cancer tumor immunotherapy.

Objective: This study evaluated the antihypertensive properties of leaf extracts of Prosopis africana (PA) in vitro and in hypertensive rats. Methods: Ethanol (ELPA) and differential solvent fractions [ethyl-acetate (EAPA), butanol (BLPA), and aqueous (ALPA)] were prepared using standard protocols. Hypertension was induced in female albino Wistar rats intraperitoneally using cyclosporine (25 mg/kg/day) while extracts were administered via oral route. Forty female rats were grouped into 5 (n = 8). Group 1 received 2 ml distilled water, Group 2: (cyclosporine + 2 ml distilled water); Group 3: cyclosporine + captopril (10 mg/kg/day); Group 4: cyclosporine + 1000 mg/kg ELPA and Group 5: cyclosporine + 1500 mg/kg ELPA. The blood pressure of anesthetized rats was measured using LabScribe coupled to a Lab-Trax-4/24T, and the activities of angiotensin-converting enzyme (ACE), arginase, phosphodiesterase-5 (PDE-5), acetylcholinesterase (AChE) and adenosine deaminase (ADA) were evaluated using standard methods. Results: All the fractions exerted significantly (p < 0.05) higher ACE inhibitory effect (ELPA = 64.36 ± 0.50%; EAPA = 86.31 ± 0.60%; BLPA= 85.28 ± 2.30 % ; ALPA= 82.27 ± 2.10 % ) than the reference, lisinopril (40.22±0.50 % ); while the butanol fraction (67.05±0.40 % ) showed higher PDE-5 inhibition than the reference, sildenafil (23.06±0.70 % ). Administration of cyclosporine caused notable (p < 0.05) elevation of systolic/diastolic blood (131.00 ± 1.22/93.25 ± 1.49 mmHg) pressure plus elevated heart rate when in comparison with the normotensive rats (106.25 ± 1.65/85.25 ± 1.18 mmHg). Treatment of hypertensive rats with ELPA significantly reduced elevated activities of ACE, PDE-5, AChE, and arginase to values that are not significantly (p < 0.05) different from those of the rats treated with the reference drug. Conclusion: This result could validate the use of P. africana as an antihypertensive agent in folklore.

In the evolving landscape of the digital era, edge computing emerges as an essential paradigm, especially critical for low-latency, real-time applications and Internet of Things (IoT) environments. Despite its advantages, edge computing faces severe limitations in storage capabilities and is fraught with reliability issues due to its resource-constrained nature and exposure to challenging conditions. To address these challenges, this work presents a tailored storage mechanism for edge computing, focusing on space efficiency and data reliability. Our method comprises three key steps: relation factorization, column clustering, and erasure encoding with compression. We successfully reduce the required storage space by deconstructing complex database tables and optimizing data organization within these sub-tables. We further add a layer of reliability through erasure encoding. Comprehensive experiments on TPC-H datasets substantiate our approach, demonstrating storage savings of up to 38.35% and time efficiency improvements by 3.96x in certain cases. Furthermore, our clustering technique shows a potential for additional storage reduction up to 40.41%.

ABSTRACTGenerating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.

The incidence and mortality of chronic kidney disease (CKD) are increasing globally. Studies have demonstrated the significance of genetic risk factors in the progression of CKD. Telomerase reverse transcriptase (TERT) may be implicated in the development of CKD. This study aimed to investigate the correlation between TERT gene variants and susceptibility to CKD in the Chinese population. A total of 507 patients with CKD and 510 healthy controls were recruited for this case-control study. Four candidate loci were identified using the MassARRAY platform. Logistic regression analysis was employed to assess the association between TERT gene variants and the risk of CKD. The false positive reporting probability (FPRP) method was utilized to evaluate the validity of statistically significant associations. The multifactorial dimensionality reduction (MDR) method was used to evaluate the interaction between SNPs and the risk of CKD. Furthermore, discrepancies in the clinical features of subjects with diverse genotypes were evaluated using one-way analysis of variance (ANOVA). Our findings revealed a correlation between rs2735940 and rs4635969 and an increased risk of CKD. Stratification analysis indicated that rs4635969 was related to an increased risk of CKD in different subgroups (age ≤ 50 years and male). MDR analysis indicated that the two-site model (rs2735940 and rs4635969) was the best prediction model. Furthermore, the rs2735940 GG genotype was found to be linked to an increased level of microalbuminuria (MAU) in patients with CKD. Our study is the first to reveal a connection between TERT gene variants and susceptibility to CKD, providing new insights into the field of nephrology.

ABSTRACTLand use/cover change is a major cause of ecological degradation. Reliable LUCC data are essential for evaluating habitat quality. The current method of surface cover classification based on the convolutional neural networks (CNNs) is usually a local spatial operation using a regular convolutional kernel, which ignores the correlation between adjacent image elements. This paper proposes a combination network with two branches, branch 1 uses the K-nearest neighbor clustering algorithm to construct superpixels and then uses the data transformation module to construct a graph attention network (GAT); branch 2 constructs the CNN using attention and residual modules to obtain the spatial and higher-order semantic information of the images. Finally, the features are fused using weighted fusion, and a classification map with less point noise and greater consistency with the real surface coverage is obtained. The classification results of this network are better than those of the other competitive methods. In addition, the urbanization of Sanya has resulted in significant habitat degradation. A good fit ([Formula: see text] in 2020 = 0.639) between habitat quality (HQ) and natural and socioeconomic factors was observed in Sanya. Natural factors are more relevant to HQ than socioeconomic factors and vary spatially.

BackgroundThe Albumin-Bilirubin (ALBI) score and grade are widely used to stratify patients with primary biliary cholangitis (PBC) into different disease statuses and risk levels. Recent studies have increasingly highlighted the role of gut microbiota in autoimmune liver diseases. This study aimed to investigate the differences in gut microbiota among PBC patients with varying ALBI grades.MethodsClinical data and stool samples were collected from outpatient and inpatient PBC patients between 2019 and 2022. Gut microbiota profiles were obtained using 16S rDNA sequencing of stool samples. We analyzed alpha diversity, beta diversity, LEfSe analysis and pathway function prediction. Additionally, various machine learning methods—including random forest (RF), lasso, gradient boosting machine (GBM) and support vector machine (SVM)—were employed to identify key features and to build and validate predictive models using bootstrap techniques.ResultsClinical characteristics of ALBI grade 1 patients were comparatively better than those of ALBI grade 2 and 3 patients, including multiple laboratory indices. Gut microbiota analysis revealed that species richness and balance were higher in ALBI grade 1 patients. Both the comparison of the most abundant genera and the linear discriminant analysis (LDA) in LEfSe demonstrated that Lachnospira had a higher abundance and better discriminative ability in ALBI grade 1. Pathway function prediction indicated that sulfur metabolism was upregulated in higher ALBI grades. Furthermore, RF identified 10 specific genera, which were then used to build and validate models for discriminating PBC patients according to their ALBI grades. All three models, developed using different machine learning methods, demonstrated good discrimination ability (mean AUC 0.75–0.80).ConclusionThis study highlights significant differences in gut microbiota profiles among PBC patients with different ALBI grades. The increased abundance of Lachnospira and upregulation of sulfur metabolism pathways are notable in patients with lower ALBI grades. The machine learning models developed based on gut microbiota features offer promising tools for discriminating between PBC patients with varying disease severities, which could enhance the precision of treatment strategies.

Abstract Ferroptosis is known to mediate the pathogenesis of chemotherapeutic drug‐induced acute kidney injury (AKI); however, leveraging the benefits of ferroptosis‐based treatments for nephroprotection remains challenging. Here, ultrasmall nanodots, denoted as FerroD, comprising the amphiphilic conjugate (tetraphenylethylene‐L‐serine‐deferoxamine, TPE‐lys‐Ser‐DFO (TSD)) and entrapped ferrostatin‐1 are designed. After being internalized through kidney injury molecule‐1‐mediated endocytosis, FerroD can simultaneously remove the overloaded iron ions and eliminate the overproduction of lipid peroxides by the coordination‐disassembly mechanisms, which collectively confer prominent inhibition efficiency of ferroptosis. In cisplatin (CDDP)‐induced AKI mice, FerroD equipped with dual anti‐ferroptotic ability can provide long‐term nephroprotective effects. This study may shed new light on the design and clinical translation of therapeutics targeting ferroptosis for various ferroptosis‐related kidney diseases.

Vitamin D deficiency has emerged as a significant concern in public health due to its potential association with various metabolic disorders. This study aimed to investigate the relationship between serum vitamin D levels and the susceptibility to hyperlipidemia among adults. Using a multi-stage sampling approach, we recruited a cohort of 2072 eligible individuals aged over 18 years. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured alongside glucolipid metabolic markers, and comprehensive demographic and physical data were collected. The cohort exhibited a hyperlipidemia prevalence of 42.18%, with 19.88% demonstrating vitamin D deficiency. Notably, 23.68% of individuals with vitamin D deficiency also presented hyperlipidemia. Statistical analysis revealed a significantly higher prevalence of hyperlipidemia among those with vitamin D deficiency compared to those with sufficient levels (23.68% vs. 17.11%, P < 0.05). After adjusting for various factors including age, geographical region, exercise status, BMI, fasting glucose level, and blood pressure, lower serum 25(OH)D concentrations were found to significantly increase the risk of hyperlipidemia (Odds Ratio [OR] = 1.41; 95% CI: 1.057, 1.885; P < 0.05). Further stratification of the hyperlipidemic cohort revealed that vitamin D deficiency was associated with 1.459- and 1.578-times higher risks for total cholesterol and triglyceride abnormalities, respectively, compared to those with sufficient vitamin D levels. Moreover, each 10 ng/mL decrease in serum vitamin D level corresponded to an increased risk of total cholesterol (OR = 0.82; 95% CI: 0.728, 0.974; P < 0.05) and triglyceride abnormalities (OR = 0.79; 95% CI: 0.678, 0.927; P < 0.05). However, there were no significant differences observed between vitamin D-sufficient and−deficient groups regarding Low-Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) abnormalities. These findings underscore the potential role of serum vitamin D deficiency as an independent risk factor contributing to the elevated prevalence of hyperlipidemia in the adult population.

Abstract The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS‐induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD+ biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury‐exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD+ metabolism proves effective in relieving liver injury‐aggravated experimental colitis. Mechanistically, the NAD+ salvage pathway regulates gut ILC2s in a cell‐intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease‐UC interplay, identifying a metabolic target for innovative treatments in liver injury‐complicated colitis.

Employee turnover has a negative impact on business profitability. To tackle this issue, we can utilize computational advancements to forecast attrition and minimize expenses. We employed an HR Analytics dataset to investigate the feasibility of using these predictive models in decision support systems. We developed an ensemble of gradient-based decision trees that accurately predicted employee turnover and performed better than other sophisticated techniques. This approach demonstrates exceptional performance in handling structured and imbalanced data, effectively capturing intricate patterns. Gradient-based decision trees provide scalable solutions that effectively balance predictive accuracy and computational efficiency, making them well-suited for strategic business analysis. The importance of our findings lies in their ability to offer dependable insights for making well-informed decisions in business settings.

Objetivo: Analizar sistemáticamente la seguridad y la eficacia de la ablación por radiofrecuencia en pacientes con osteoartritis de rodilla y evaluar la calidad metodológica de los estudios publicados. Método: Mediante una búsqueda en las bases de datos PubMed, EMBASE y CENTRAL, recuperamos y recopilamos los ensayos aleatorizados controlados relevantes publicados hasta el 26 de junio de 2023. Resultados: Se incluyeron 13 ensayos aleatorizados controlados que involucraron a 865 pacientes. En comparación con el grupo control, el grupo de ablación por radiofrecuencia registró una reducción significativa en la puntuación de dolor a 1-2 semanas, 4 semanas, 12 semanas y 24 semanas del tratamiento, con una diferencia media estandarizada de −1.24 (intervalo de confianza del 95% [IC95%]: −1.99 a −0.49; p = 0.001; I2 = 91%), de −0.76 (IC95%: −1.27 a −0.26; p = 0.003; I2 = 76%), de −1.70 (IC95%: −2.56 a − 0.83; p = 0.0001%; I2 = 2.94%) y de – 2.26 (IC95%: −3.49 a −1.04; p = 0.0003; I2 = 95%), respectivamente. Conclusiones: La ablación por radiofrecuencia como tratamiento adyuvante muestra potencial en el tratamiento de pacientes con osteoartritis de rodilla. Este método puede convertirse en la principal estrategia terapéutica para estos pacientes.

Purpose – Under the high-speed operating conditions, the effects of wheelset elastic deformation on the wheel rail dynamic forces will become more notable compared to the low-speed condition. In order to meet different analysis requirements and selecting appropriate models to analyzing the wheel rail interaction, it is crucial to understand the influence of wheelset flexibility on the wheel-rail dynamics under different speeds and track excitations condition. Design/methodology/approach – The wheel rail contact points solving method and vehicle dynamics equations considering wheelset flexibility in the trajectory body coordinate system were investigated in this paper. As for the wheel-rail contact forces, which is a particular force element in vehicle multibody system, a method for calculating the Jacobian matrix of the wheel-rail contact force is proposed to better couple the wheel-rail contact force calculation with the vehicle dynamics response calculation. Based on the flexible wheelset modeling approach in this paper, two vehicle dynamic models considering the wheelset as both elastic and rigid bodies are established, two kinds of track excitations, namely normal measured track irregularities and short-wave irregularities are used, wheel-rail geometric contact characteristic and wheel-rail contact forces in both time and frequency domains are compared with the two models in order to study the influence of flexible wheelset rotation effect on wheel rail contact force. Findings – Under normal track irregularity excitations, the amplitudes of vertical, longitudinal and lateral forces computed by the flexible wheelset model are smaller than those of the rigid wheelset model, and the virtual penetration and equivalent contact patch are also slightly smaller. For the flexible wheelset model, the wheel rail longitudinal and lateral creepages will also decrease. The higher the vehicle speed, the larger the differences in wheel-rail forces computed by the flexible and rigid wheelset model. Under track short-wave irregularity excitations, the vertical force amplitude computed by the flexible wheelset is also smaller than that of the rigid wheelset. However, unlike the excitation case of measured track irregularity, under short-wave excitations, for the speed within the range of 200 to 350 km/h, the difference in the amplitude of the vertical force between the flexible and rigid wheelset models gradually decreases as the speed increase. This is partly due to the contribution of wheelset’s elastic vibration under short-wave excitations. For low-frequency wheel-rail force analysis problems at speeds of 350 km/h and above, as well as high-frequency wheel-rail interaction analysis problems under various speed conditions, the flexible wheelset model will give results agrees better with the reality. Originality/value – This study provides reference for the modeling method of the flexible wheelset and the coupling method of wheel-rail contact force to the vehicle multibody dynamics system. Furthermore, by comparative research, the influence of wheelset flexibility and rotation on wheel-rail dynamic behavior are obtained, which is useful to the application scope of rigid and flexible wheelset models.

Underground engineering often passes through water-rich fractured rock masses, which are prone to fracture and instability under the long-term coupling of in-situ stress field and pore water (P-W) pressure, ultimately threatening the stability of underground structures. In order to explore the mechanical properties of rocks under H-M coupling, the corresponding damage constitutive (D-C) model has become the focus of attention. Considering the inadequacy of the current research on rock strength parameters, energy evolution characteristics and D-C model under H-M coupling, the mechanical properties of typical sandstone samples are discussed based on laboratory tests. The results show that the variation of characteristic stresses of sandstone under H-M coupling conforms to the normalized attenuation equation and Mohr-Coulomb (M−C) criterion. The P-W pressure mechanism of sandstone exhibits a dynamic change from softening effect to H-M fracturing effect. The closure stress is mainly provided by cohesive strength, while the initiation stress, damage stress, and peak stress are jointly dominated by cohesive strength and friction strength. In addition, residual stress is attributed to the friction strength formed by the bite of the fracture surface. Subsequently, the energy evolution characteristics of sandstone under H-M coupling were studied, and it was found that P-W pressure weakened the energy storage capacity and energy dissipation capacity of sandstone, and H-M fracturing was an important factor in reducing its energy storage efficiency. Finally, combined with energy dissipation theory and statistical damage theory, two types of D-C models considering P-W pressure are proposed accordingly, and the model parameters can be determined by four methods. The application results indicate that the proposed and modified D-C models have high reliability, and can characterize the mechanical behavior of sandstone under H-M coupling, overcome the inconvenience of existing D-C models due to excessive mechanical parameters, and can be applied to the full-range stress–strain process. The results are conducive to revealing the deformation and damage mechanisms of rocks under H-M coupling, and can provide theoretical guidance for related engineering problems.

Despite the advancements in alternative fuels and energy sources, there continues to be a significant global dependence on oil production and extraction. A substantial volume of oilfield-produced water (OPW) is generated during the production and extraction processes of oil fields. Recurrent OPW treatments encountered significant challenges in addressing this particular type of wastewater. Advanced oxidation processes (AOPs) are regarded as a promising alternative approach for the degradation of recalcitrant organic compounds in the OPW. This review focuses on the characterization of OPW. The treatment of organic pollutants in wastewater using AOPs, such as ozonation, Fenton oxidation-based processes, heterogeneous photocatalysis, and persulfate oxidation, is comprehensively reviewed in terms of their efficiency for pollutant degradation. The primary challenges in this field and the future directions for development are proposed, with the aim of providing a valuable reference for achieving highly effective treatment of OPW. HIGHLIGHTS Characteristics of oilfield-produced water were analyzed.; Treatment of oilfield-produced water using advanced oxidation processes was discussed.; Recommendation and future research are proposed.;

BackgroundThe substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. ObjectiveTo calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. MethodsUsing a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. ResultsOverall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). ConclusionHeat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.

Abstract Background About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response. Methods This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal. Results PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy. Conclusion PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

2319 aluminum alloy parts was prepared by wire arc additive manufacturing technology. The corrosion properties of additively manufactured 2319 aluminum alloy and 2219 aluminum alloy sheets were systematically investigated by electrochemical tests and localized corrosion tests. The results of electrochemical tests showed that the 2219 aluminum alloy sheet has a lower corrosion current density than the additively manufactured 2319 aluminum alloy. Localized corrosion test results indicated that the additively manufactured 2319 aluminum alloy exhibited a higher intergranular corrosion depth and more severe corrosion morphology than the 2219 aluminum alloy sheet. This suggests that the 2219 aluminum alloy sheet has higher corrosion resistance than the additively manufactured 2319 aluminum alloy. The poor corrosion resistance of additively manufactured 2319 aluminum alloy could be attributed to the formation of a coarse continuous Al2Cu phase along the grain boundary. Based on this, heat treatment was used to dissolve the Al2Cu, which can effectively improve the corrosion resistance of additively manufactured 2319 aluminum alloy to the same level as that of the 2219 aluminum alloy sheet.

An enclosed microgroove is a vital surface microstructure that is difficult to prepare on the surfaces of difficult-to-machine electrically conductive materials using conventional methods. Electrical discharge machining (EDM) is suitable for this task. It is obtained primarily through layer-by-layer scanning EDM with micro-column electrodes or reciprocating EDM with foil electrodes. However, owing to the small cross-sectional size of the electrodes, a stable machining process is challenging to achieve, which seriously reduces the machining efficiency. To solve these problems, this study proposed ultrasonic vibration-assisted EDM using a laminated electrode possessed strong anti-interference properties for enclosed microgrooves. The effects of ultrasonic vibration on the EDM of microgrooves with single foil and laminated electrodes were investigated. The results show that ultrasonic vibration could improve the machining efficiency of the two types of electrodes and significantly improve the profile quality of the microgrooves prepared using laminated electrodes. When the amplitude was 3 μm and the frequency was 30 kHz, the bottom sidewall corner radius of microgrooves machined by brass foils in laminated electrodes was 28 μm, the width, depth, and roughness of microgrooves machined by copper foils in laminated electrodes were approximately 78 μm, 229 μm and 0.7 μm, the material removal rate was 0.0072 mm3/min. Based on the optimized parameters, inverted “convex” microgrooves with fine consistency were successfully prepared using laminated electrodes on Ti–6Al–4V alloy surfaces. The machining time was reduced by 40% for each microgroove compared with using the single foil electrode. This study provides a new method for preparing complex microgrooves.

Abstract Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-β-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-β-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy. Graphical Abstract

Background: Reactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction. Materials and methods: Human UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H2O2 in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining. Results: UCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H2O2. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological NPCs. 4D-LFQ proteomics and western blotting further revealed that UCMSC-exos up-regulated the levels of the mitochondrial protein, mitochondrial transcription factor A (TFAM), in H2O2-induced NPCs. High-throughput sequencing and qRT-PCR uncovered that UCMSC-exos down-regulated the levels of miR-194-5p, a potential negative regulator of TFAM, induced by H2O2. Finally, in vivo results showed that UCMSC-exos injection improved the histopathological structure and enhanced the expression levels of COL2A1 and TFAM in the rat IVDD model. Conclusions: Our findings suggest that UCMSC-exos promote ECM synthesis, relieve mitochondrial oxidative stress, and attenuate mitochondrial dysfunction in vitro and in vivo, thereby effectively treating IVDD. The translational potential of this article: This study provides solid experimental data support for the therapeutic effects of UCMSC-exos on IVDD, suggesting that UCMSC-exos will be a promising nanotherapy for IVDD.