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Sarcodon mushrooms are esteemed as a rare and highly valuable resource for both culinary and medicinal purposes. Ancient medical classics have documented their beneficial effects on conditions such as indigestion, loss of appetite, and neurological disorders. Modern phytochemical research into their secondary metabolites has led to the discovery of numerous bioactive compounds with significant biological activities. Despite notable achievements in the study of the chemical composition and bioactivity of Sarcodon mushrooms, a comprehensive understanding of these findings has been lacking. This review provides an exhaustive summary of the advancements in the phytochemistry of Sarcodon mushrooms, as well as the biological and pharmacological activities of the isolated compounds and crude extracts derived from Sarcodon over the past nine decades. A total of 100 secondary metabolites isolated from these mushrooms have been classified into five major categories based on their chemical structures, which exhibit bioactivities such as anti-tumour, neurotrophic, and neuroprotective, antioxidant, anti-inflammatory, antimicrobial, and hypoglycaemic properties. The aim of this study is to establish a scientific foundation for future research in drug discovery, biotechnological development, and the exploration of functional foods involving Sarcodon mushrooms.

Abstract Background Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis–gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome. Results The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts. Conclusion These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association. Highlights 1 Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. 2 Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. 3 Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients. Graphical abstract

Abstract Within the framework of braneworld holography, we construct a quantum charged black hole localized on a three-dimensional anti-de Sitter (AdS) brane that intersects the asymptotic boundary of the four-dimensional AdS spacetime at the conformal defects and incorporates quantum backreaction effects from the conformal field theory (CFT) on the brane. This quantum charged black hole is an exact solution of the semiclassical gravitational equation corresponding to a theory with higher curvature gravity and nonminimally coupled nonlinear gauge field. In the framework of double holography, we investigate the thermodynamics of the quantum charged black hole from three perspectives: a pure bulk perspective, in which four-dimensional classical Einstein gravity couples to Maxwell electrodynamics and a codimension-one tensional brane; a brane perspective, where semiclassical higher curvature gravity is subject to quantum backreaction from the holographic CFT on the brane, yielding a quantum charged black hole; and a boundary perspective, where the defect CFT is coupled to a boundary CFT at the asymptotic boundary and the degrees of freedom for defect quantum conformal matter is considered. In so doing, we obtain doubly holographic formulations of both the first law of thermodynamics and the Smarr (energy) relations for the quantum charged black holes.

Abstract Background This study aims to construct a clinical prediction model and create a visual line chart depicting the risk of acute kidney injury (AKI) following resuscitation in cardiac arrest (CA) patients. Additionally, the study aims to validate the clinical predictive accuracy of the developed model. Methods Data were retrieved from the Dryad database, and publicly shared data were downloaded. This retrospective cohort study included 347 successfully resuscitated patients post-cardiac arrest from the Dryad database. Demographic and clinical data of patients in the database, along with their renal function during hospitalization, were included. Through data analysis, the study aimed to explore the relevant influencing factors of acute kidney injury (AKI) in patients after cardiopulmonary resuscitation. The study constructed a line chart prediction model using multivariate logistic regression analysis with post-resuscitation shock status (Post-resuscitation shock refers to the condition where, following successful cardiopulmonary resuscitation after cardiac arrest, some patients develop cardiogenic shock.), C reactive protein (CRP), Lactate dehydrogenase (LDH), and Alkaline phosphatase (ALP) identified as predictive factors. The predictive efficiency of the fitted model was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results Multivariate logistic regression analysis showed that post-resuscitation shock status, CRP, LDH, and PAL were the influencing factors of AKI after resuscitation in CA patients. The calibration curve test indicated that the prediction model was well-calibrated, and the results of the Decision Curve Analysis (DCA) demonstrated the clinical utility of the model constructed in this study. Conclusion Post-resuscitation shock status, CRP, LDH, and ALPare the influencing factors for AKI after resuscitation in CA patients. The clinical prediction model constructed based on the above indicators has good clinical discriminability and practicality.

Abstract Background Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening. Methods This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated. Results A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p

Abstract Mitochondria, responsible for cellular energy synthesis and signal transduction, intricately regulate diverse metabolic processes, mediating fundamental biological phenomena such as cell growth, aging, and apoptosis. Tumor invasion and metastasis, key characteristics of malignancies, significantly impact patient prognosis. Tumor cells frequently exhibit metabolic abnormalities in mitochondria, including alterations in metabolic dynamics and changes in the expression of relevant metabolic genes and associated signal transduction pathways. Recent investigations unveil further insights into mitochondrial metabolic abnormalities, revealing their active involvement in tumor cell proliferation, resistance to chemotherapy, and a crucial role in tumor cell invasion and metastasis. This paper comprehensively outlines the latest research advancements in mitochondrial structure and metabolic function. Emphasis is placed on summarizing the role of mitochondrial metabolic abnormalities in tumor invasion and metastasis, including alterations in the mitochondrial genome (mutations), activation of mitochondrial-to-nuclear signaling, and dynamics within the mitochondria, all intricately linked to the processes of tumor invasion and metastasis. In conclusion, the paper discusses unresolved scientific questions in this field, aiming to provide a theoretical foundation and novel perspectives for developing innovative strategies targeting tumor invasion and metastasis based on mitochondrial biology. Graphical Abstract

Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells (RGCs). Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes, which may affect RGCs in retinal degenerative diseases. The NLRP3 inflammasome was a protein complex that, upon activation, produces caspase-1, mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases. Upregulated autophagy could inhibit NLRP3 inflammasome activation, while inhibited autophagy can promote NLRP3 inflammasome activation, which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina. The activated NLRP3 inflammasome could further inhibit autophagy, thus forming a vicious cycle that accelerated the damage and death of RGCs. This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration, providing a new perspective and direction for the treatment of retinal diseases.

Abstract Background HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. Methods Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. Results A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p

Highlights A systematic review of recent advances of microrobots applied in the musculoskeletal system with an emphasis on design strategies of microrobotic systems for tissue regeneration. The fabrication, motion and control, and image-guided delivery of microrobots in the musculoskeletal system are reviewed based on the up-to-date works. Prospects and challenges for future clinical translation of microrobots in the musculoskeletal system and regenerative medicine are discussed.

Abstract Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and the current therapeutic strategies including antiplatelet medication or intervene surgery are reported to not clinically benefit the patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted for the potential treatment of critical PAD. Aiming for transcellular delivery of VEGF-encoding plasmid DNA (pDNA), we proposed to elaborate intriguing virus-like DNA condensates, wherein the supercoiled rigid micrometer-scaled plasmid DNA (pDNA) could be regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process with the aid of cationic block copolymer poly(ethylene glycol)-polylysine at an extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking was proposed between the polylysine segments with the aim of stabilizing these intriguing toroidal condensates. Pertaining to the critical hindlimb ischemia, our proposed toroidal VEGF-encoding pDNA condensates demonstrated high levels of VEGF expression at the dosage sites, which consequently contributed to the neo-vasculature (the particularly abundant formation of micro-vessels in the injected hindlimb), preventing the hindlimb ischemia from causing necrosis at the extremities. Moreover, excellent safety profiles have been demonstrated by our proposed toroidal condensates, as opposed to the apparent immunogenicity of the naked pDNA. Hence, our proposed virus-like DNA condensates herald potentials as gene therapy platform in persistent expressions of the therapeutic proteins, and might consequently be highlighted in the management of a variety of intractable diseases.

Abstract Diffuse solar radiation (DSR) plays a critical role in renewable energy utilization and efficient agricultural production. However, there is a scarcity of high-precision, long-term, and spatially continuous datasets for DSR in the world, and particularly in China. To address this gap, a 41-year (1982–2022) daily diffuse solar radiation dataset (CHDSR) is constructed with a spatial resolution of 10 km, based on a new ensemble model that combines the clear-sky irradiance estimated by the REST2 model and a machine-learning technique using precise cloud information derived from reanalysis data. Validation against ground-based measurements indicates strong performance of the new hybrid model, with a correlation coefficient, root mean square error and mean bias error (MBE) of 0.94, 13.9 W m−2 and −0.49 W m−2, respectively. The CHDSR dataset shows good spatial and temporal continuity over the time horizon from 1982 to 2022, with a multi-year mean value of 74.51 W m−2. This dataset is now freely available on figshare to the potential benefit of any analytical work in solar energy, agriculture, climate change, etc ( https://doi.org/10.6084/m9.figshare.21763223.v3 ).

Abstract Background Extralobar pulmonary sequestration is located outside the lung parenchyma and is covered by a separated pleural sac, which comprises approximately 25% of all pulmonary sequestration. Case presentation This article reported one case of an extralobar pulmonary sequestration originated from the mesoesophagus, which was recognized and excised during a lung resection. Histologic examination revealed an ectopic lung tissue with hyperplasia of bronchioles, which was accord with an extralobar pulmonary sequestration. Conclusions CT angiogram, ultrasound and MRI can be used to clarify the diagnosis and detect the abnormal feeding arteries of extralobar pulmonary sequestration. Carefulness should be taken while dissecting and ligating the potential feeding arteries. Endovascular occlusion might be an alternative option to surgery.

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

AIM: To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin (AST). METHODS: ICR mice were intraperitoneally injected NaIO3, CY-09, AST successively and divided into 5 groups, including the control, NaIO3, NaIO3+CY-09, NaIO3+AST, and NaIO3+CY-09+AST groups. Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry, enzyme linked immunosorbent assay (ELISA), and Western blotting. Retinal pigment epithelium cell line (ARPE-19 cells) and mouse photoreceptor cells line (661W cells) were also treated with NaIO3, CY-09, and AST successively. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay. Apoptosis was analyzed by flow cytometry. Changes in autophagosome morphology were observed by transmission electron microscopy. Quantitative polymerase chain reaction (qPCR) was used to detect NLRP3 and caspase-1. NLRP3, caspase-1, cleaved caspase-1, p62, Beclin-1, and LC3 protein levels were measured by Western blotting. IL-1β and IL-18 were measured by ELISA. RESULTS: Compared with the control group, the activity of NaIO3-treated 661W cells decreased within 24 and 48h, apoptosis increased, NLRP3, caspase-1, IL-1β and IL-18 levels increased, and autophagy-related protein levels increased (P

Foodborne pathogens are one of the important factors affecting food safety. Efficient and rapid detection technology of foodborne pathogens is particularly important to ensure food safety. Among the rapid detection methods of foodborne pathogens, molecular biology technology has been widely used because of its advantages of strong specificity, high accuracy, and fast detection speed. This paper introduces the application of various molecular biological techniques in the rapid detection of foodborne pathogens, including polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), nuclear acid sequence-based amplification (NAS-BA), recombinase polymerase amplification (PRA), recombinase-aided isothermal amplification (RAA), and gene chip (GC). The application status, application scope and existing problems of these technologies are also analyzed and summarized to provide theoretical reference for the rapid detection of foodborne pathogens in the future.

The exposure of ethanol increases the risk of head and neck inflammation and tumor progression. However, limited studies have investigated the composition and functionality of laryngeal microbiota under ethanol exposure. We established an ethanol-exposed mouse model to investigate the changes in composition and function of laryngeal microbiota using Metagenomic shotgun sequencing. In the middle and late stages of the experiment, the laryngeal microbiota of mice exposed to ethanol exhibited obvious distinguished from that of the control group on principal-coordinate analysis (PCoA) plots. Among the highly abundant species, Salmonella enterica and Mycobacterium marinum were likely to be most impacted. Our findings indicated that the exposure to ethanol significantly increased their abundance in larynxes in mice of the same age, which has been confirmed through FISH experiments. Among the species-related functions and genes, metabolism is most severely affected by ethanol. The difference was most obvious in the second month of the experiment, which may be alleviated later because the animal established tolerance. Notable enrichments concerning energy, amino acid, and carbohydrate metabolic pathways occurred during the second month under ethanol exposure. Finally, based on the correlation between species and functional variations, a network was established to investigate relationships among microbiota, functional pathways, and related genes affected by ethanol. Our data first demonstrated the continuous changes of abundance, function and their interrelationship of laryngeal microbiota under ethanol exposure by Metagenomic shotgun sequencing. Importance: Ethanol may participate in the inflammation and tumor progression by affecting the composition of the laryngeal microbiota. Here, we applied the metagenomic shotgun sequencing instead of 16 S rRNA sequencing method to identify the laryngeal microbiota under ethanol exposure. Salmonella enterica and Mycobacterium marinum are two dominant species that may play a role in the reconstruction of the laryngeal microenvironment, as their local abundance increases following exposure to ethanol. The metabolic function is most evidently impacted, and several potential metabolic pathways could be associated with alterations in microbiota composition. These findings could help us better understand the impact of prolonged ethanol exposure on the microbial composition and functionality in the larynx.

As people live longer, the burden of aging-related brain diseases, especially dementia, is increasing. Brain aging increases the risk of cognitive impairment, which manifests as a progressive loss of neuron function caused by the impairment of synaptic plasticity via disrupting lipid homeostasis. Therefore, supplemental dietary lipids have the potential to prevent brain aging. This review summarizes the important roles of dietary lipids in brain function from both structure and mechanism perspectives. Epidemiological and animal studies have provided evidence of the functions of polyunsaturated fatty acids (PUFAs) in brain health. The results of interventions indicate that phospholipids—including phosphatidylcholine, phosphatidylserine, and plasmalogen—are efficient in alleviating cognitive impairment during aging, with plasmalogen exhibiting higher efficacy than phosphatidylserine. Plasmalogen is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of neurons. Future research should determine the dose-dependent effects of plasmalogen in alleviating brain-aging diseases and should develop extraction and storage procedures for its clinical application.

Abstract This study aimed to perform the first external validation of the modified Child-Turcotte-Pugh score based on plasma ammonia (aCTP) and compare it with other risk scoring systems to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. We retrospectively reviewed 473 patients from three cohorts between January 2016 and June 2022 and compared the aCTP score with the Child-Turcotte-Pugh (CTP) score, albumin-bilirubin (ALBI), model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) in predicting transplant-free survival by the concordance index (C-index), area under the receiver operating characteristic curve, calibration plot, and decision curve analysis (DCA) curve. The median follow-up time was 29 months, during which a total of 62 (20.74%) patients died or underwent liver transplantation. The survival curves for the three aCTP grades differed significantly. Patients with aCTP grade C had a shorter expected lifespan than patients with aCTP grades A and B (P

Abstract Background To compare the application of conventional MRI analysis and MRI-based radiomics to identify the circumferential resection margin (CRM) status of rectal cancer (RC). Methods A cohort of 301 RC patients with 66 CRM invloved status and 235 CRM non-involved status were enrolled in this retrospective study between September 2017 and August 2022. Conventional MRI characteristics included gender, age, diameter, distance to anus, MRI-based T/N phase, CEA, and CA 19 − 9, then the relevant logistic model (Logistic-cMRI) was built. MRI-based radiomics of rectal cancer and mesorectal fascia were calculated after volume of interest segmentation, and the logistic model of rectal cancer radiomics (Logistic-rcRadio) and mesorectal fascia radiomics (Logistic-mfRadio) were constructed. And the combined nomogram (nomo-cMRI/rcRadio/mfRadio) containing conventional MRI characteristics, radiomics of rectal cancer and mesorectal fascia was developed. The receiver operator characteristic curve (ROC) was delineated and the area under curve (AUC) was calculated the efficiency of models. Results The AUC of Logistic-cMRI was 0.864 (95%CI, 0.820 to 0.901). The AUC of Logistic-rcRadio was 0.883 (95%CI, 0.832 to 0.928) in the training set and 0.725 (95%CI, 0.616 to 0.826) in the testing set. The AUCs of Logistic-mfRadio was 0.891 (95%CI, 0.838 to 0.936) in the training set and 0.820 (95%CI, 0.725 to 0.905) in the testing set. The AUCs of nomo-cMRI/rcRadio/mfRadio were the highest in both the training set of 0.942 (95%CI, 0.901 to 0.969) and the testing set of 0.909 (95%CI, 0.830 to 0.959). Conclusion MRI-based radiomics of rectal cancer and mesorectal fascia showed similar efficacy in predicting the CRM status of RC. The combined nomogram performed better in assessment.

Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

Abstract Background Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Abstract In cold areas, the steel fiber reinforced rubber concrete (SFRRC) pavement is exposed to natural environment and experiences varying degrees of damage from freezing and thawing. This can have a serious impact on the normal usage and safe operation of the pavement structure. This research examines the impact of varying rubber concentrations on multiple variables, such as the rate of mass reduction, relative dynamic modulus of elasticity, compressive strength, and thickness of the damage layer (H f) during freeze–thaw (F-T) durability testing conducted on SFRRC. Furthermore, an analysis is conducted to determine the degradation pattern exhibited by SFRRC. The internal structure evolution and pore structure characteristics of SFRRC were examined using scanning electron microscopy and mercury intrusion porosimetry techniques, which revealed the underlying damage mechanism in SFRRC during F-T cycles. The results suggest that the addition of an appropriate amount of rubber can effectively enhance the frost resistance of SFRRC in water. A gradual improvement in the frost resistance of SFRRC is observed when increasing the rubber content from 0 to 10%. The optimal frost resistance is observed in SFRRC with 10% rubber content. However, when the rubber content reaches 15%, SFRRC exhibits significant degradation and lower level of resistance to freezing compared to SFRRC without rubber. Microcracks form within SFRRC due to the freezing–thawing forces experienced during the experiment, resulting in the development of a damage layer that extends from the surface to the interior. The compressive strength of the damaged layer significantly decreases as H f increases. The addition of appropriate rubber in SFRRC improves its pore structure, leading to an increased proportion of harmless or less harmful pores and a reduction in average pore size, thereby significantly enhancing its frost resistance.

Abstract Background Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. Methods To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. Results Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). Conclusions Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity. Graphical Abstract

Abstract Using a curved carbon-fiber plate (CFP) in running shoes may offer notable performance benefit over flat plates, yet there is a lack of research exploring the influence of CFP geometry on internal foot loading during running. The objective of this study was to investigate the effects of CFP mechanical characteristics on forefoot biomechanics in terms of plantar pressure, bone stress distribution, and contact force transmission during a simulated impact peak moment in forefoot strike running. We employed a finite element model of the foot-shoe system, wherein various CFP configurations, including three stiffnesses (stiff, stiffer, and stiffest) and two shapes (flat plate (FCFP) and curved plate (CCFP)), were integrated into the shoe sole. Comparing the shoes with no CFP (NCFP) to those with CFP, we consistently observed a reduction in peak forefoot plantar pressure with increasing CFP stiffness. This decrease in pressure was even more notable in a CCFP demonstrating a further reduction in peak pressure ranging from 5.51 to 12.62%, compared to FCFP models. Both FCFP and CCFP designs had a negligible impact on reducing the maximum stress experienced by the 2nd and 3rd metatarsals. However, they greatly influenced the stress distribution in other metatarsal bones. These CFP designs seem to optimize the load transfer pathway, enabling a more uniform force transmission by mainly reducing contact force on the medial columns (the first three rays, measuring 0.333 times body weight for FCFP and 0.335 for CCFP in stiffest condition, compared to 0.373 in NCFP). We concluded that employing a curved CFP in running shoes could be more beneficial from an injury prevention perspective by inducing less peak pressure under the metatarsal heads while not worsening their stress state compared to flat plates.

Objective The resurrections of ancient landslide deposits are one of the primary geological hazards in the Qinghai-Tibet Plateau and surrounding areas of China and pose significant safety threats to major transportation and water conservancy projects under construction in western China. Therefore, it is crucial to investigate the formation and evolution mechanism of ancient landslides and evaluate the stability of their deposits. This research can provide theoretical support for the early recognition and prevention of the resurrection of ancient landslide deposits. Methods The ancient landslide deposits in Jiangdingya, Zhouqu County, Gansu Province, have experienced local resurrection several times in the past decade, creating severe threats to the lives and property of local people by blocking the Bailong River. To determine the morphology and structural characteristics of the ancient Jiangdingya landslide deposits, this study utilized field investigations and unmanned aerial vehicle (UAV) tilt photography. Based on this, the evolution mechanism and dynamic process of the landslide were analysed, and the stability of the deposits was qualitatively evaluated using InSAR deformation data. Results The results show that the ancient landslide at Jiangdingya is a typical large-scale earthquake landslide, with its sliding body located in a downslope position in three directions, forming a multilevel stepped deposit shape. The dynamic process of an ancient landslide under seismic loads can be divided into several stages, including vibration and cracking in the upper-middle part, shearing and landslide initiation in the front edge locking segment, tearing and landslide acceleration in the rear edge, obstruction and landslide deceleration in the front edge, and stabilization. Conclusion Due to the overall downwards movement of the ancient landslide under seismic loads, there are a large number of intact rock masses in the upper deposits, which are relatively stable. However, the middle and lower deposits are mostly composed of weak structures such as fault fracture zones and fragmented rock masses, which have poor stability and are highly likely to resurrect in the future. This study provides important insights into the formation and evolution of ancient landslides and the evaluation of their stability, which can help prevent future landslides and protect local communities.

Abstract Long non-coding RNAs (lncRNAs) and cancer stem cells (CSCs) are crucial for the growth, migration, recurrence, and medication resistance of tumors. However, the impact of lncRNAs related to stemness on the outcome and tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC) is still unclear. In this study, we aimed to predict the outcome and TIME of ccRCC by constructing a stem related lncRNAs (SRlncRNAs) signature. We firstly downloaded ccRCC patients’ clinical data and RNA sequencing data from UCSC and TCGA databases, and abtained the differentially expressed lncRNAs highly correlated with stem index in ccRCC through gene expression differential analysis and Pearson correlation analysis. Then, we selected suitable SRlncRNAs for constructing a prognostic signature of ccRCC patients by LASSO Cox regression. Further, we used nomogram and Kaplan Meier curves to evaluate the SRlncRNA signature for the prognose in ccRCC. At last, we used ssGSEA and GSVA to evaluate the correlation between the SRlncRNAs signature and TIME in ccRCC. Finally, We obtained a signtaure based on six SRlncRNAs, which are correlated with TIME and can effectively predict the ccRCC patients’ prognosis. The SRlncRNAs signature may be a noval prognostic indicator in ccRCC.

Abstract Background Segmenting liver vessels from contrast-enhanced computed tomography images is essential for diagnosing liver diseases, planning surgeries and delivering radiotherapy. Nevertheless, identifying vessels is a challenging task due to the tiny cross-sectional areas occupied by vessels, which has posed great challenges for vessel segmentation, such as limited features to be learned and difficult to construct high-quality as well as large-volume data. Methods We present an approach that only requires a few labeled vessels but delivers significantly improved results. Our model starts with vessel enhancement by fading out liver intensity and generates candidate vessels by a classifier fed with a large number of image filters. Afterwards, the initial segmentation is refined using Markov random fields. Results In experiments on the well-known dataset 3D-IRCADb, the averaged Dice coefficient is lifted to 0.63, and the mean sensitivity is increased to 0.71. These results are significantly better than those obtained from existing machine-learning approaches and comparable to those generated from deep-learning models. Conclusion Sophisticated integration of a large number of filters is able to pinpoint effective features from liver images that are sufficient to distinguish vessels from other liver tissues under a scarcity of large-volume labeled data. The study can shed light on medical image segmentation, especially for those without sufficient data.

Abstract Background It has been proposed that inflammation plays a role in the development of sarcopenia. This study aimed to investigate the links of complete blood cell count (CBC) parameters and CBC-derived inflammatory indicators with sarcopenia and mortality. Methods Data pertaining to sarcopenia were extracted from the 1999–2006 National Health and Nutrition Examination Survey (NHANES), and mortality events were ascertained through the National Death Index up to December 31, 2019. The CBC-derived inflammatory indicators assessed in this study included the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte to lymphocyte ratio (NMLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII). The prognostic significance of these CBC-derived inflammatory indicators was evaluated using the random survival forests (RSF) analysis. Results The study encompassed a cohort of 12,689 individuals, among whom 1,725 were diagnosed with sarcopenia. Among individuals with sarcopenia, 782 experienced all-cause mortality, and 195 succumbed to cardiovascular causes. Following adjustment for confounding variables, it was observed that elevated levels of NLR, dNLR, NMLR, SIRI, and SII were associated with an increased prevalence of sarcopenia. Among participants with sarcopenia, those in the highest quartile of NLR (HR = 1.336 [1.095–1.631]), dNLR (HR = 1.274 [1.046–1.550]), MLR (HR = 1.619 [1.290–2.032]), NMLR (HR = 1.390 [1.132–1.707]), and SIRI (HR = 1.501 [1.210–1.862]) exhibited an elevated risk of all-cause mortality compared to those in the lowest quartile of these inflammation-derived indicators. These associations were similarly observed in cardiovascular mortality (HR = 1.874 [1.169–3.003] for MLR, HR = 1.838 [1.175–2.878] for SIRI). The RSF analysis indicated that MLR exhibited the highest predictive power for both all-cause and cardiovascular mortality among individuals with sarcopenia. Conclusions Our findings underscore the association between CBC-derived inflammatory indicators and mortality in adults with sarcopenia. Of note, MLR emerged as the most robust predictor of all-cause and cardiovascular mortality in this population.

With the construction of the Three Gorges Reservoir dam, frequent reservoir landslide events have been recorded. In recent years, multi-row stabilizing piles (MRSPs) have been used to stabilize massive reservoir landslides in China. In this study, two centrifuge model tests were carried out to study the unreinforced and MRSP-reinforced slopes subjected to reservoir water level (RWL) operation, using the Taping landslide as a prototype. The results indicate that the RWL rising can provide lateral support within the submerged zone and then produce the inward seepage force, eventually strengthening the slope stability. However, a rapid RWL drawdown may induce outward seepage forces and a sudden debuttressing effect, consequently reducing the effective soil normal stress and triggering partial pre-failure within the RWL fluctuation zone. Furthermore, partial deformation and subsequent soil structure damage generate excess pore water pressures, ultimately leading to the overall failure of the reservoir landslide. This study also reveals that a rapid increase in the downslope driving force due to RWL drawdown significantly intensifies the lateral earth pressures exerted on the MRSPs. Conversely, the MRSPs possess a considerable reinforcement effect on the reservoir landslide, transforming the overall failure into a partial deformation and failure situated above and in front of the MRSPs. The mechanical transfer behavior observed in the MRSPs demonstrates a progressive alteration in relation to RWL fluctuations. As the RWL rises, the mechanical states among MRSPs exhibit a growing imbalance. The shear force transfer factor (i.e. the ratio of shear forces on pile of the nth row to that of the first row) increases significantly with the RWL drawdown. This indicates that the mechanical states among MRSPs tend toward an enhanced equilibrium. The insights gained from this study contribute to a more comprehensive understanding of the failure mechanisms of reservoir landslides and the mechanical behavior of MRSPs in reservoir banks.

Abstract The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1β, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques.

Abstract Background Class III peroxidase (POD) enzymes play vital roles in plant development, hormone signaling, and stress responses. Despite extensive research on POD families in various plant species, the knowledge regarding the POD family in Chinese pear (Pyrus bretschenedri) is notably limited. Results We systematically characterized 113 POD family genes, designated as PbPOD1 to PbPOD113 based on their chromosomal locations. Phylogenetic analysis categorized these genes into seven distinct subfamilies (I to VII). The segmental duplication events were identified as a prevalent mechanism driving the expansion of the POD gene family. Microsynteny analysis, involving comparisons with Pyrus bretschenedri, Fragaria vesca, Prunus avium, Prunus mume and Prunus persica, highlighted the conservation of duplicated POD regions and their persistence through purifying selection during the evolutionary process. The expression patterns of PbPOD genes were performed across various plant organs and diverse fruit development stages using transcriptomic data. Furthermore, we identified stress-related cis-acting elements within the promoters of PbPOD genes, underscoring their involvement in hormonal and environmental stress responses. Notably, qRT-PCR analyses revealed distinctive expression patterns of PbPOD genes in response to melatonin (MEL), salicylic acid (SA), abscisic acid (ABA), and methyl jasmonate (MeJA), reflecting their responsiveness to abiotic stress and their role in fruit growth and development. Conclusions In this study, we investigated the potential functions and evolutionary dynamics of PbPOD genes in Pyrus bretschenedri, positioning them as promising candidates for further research and valuable indicators for enhancing fruit quality through molecular breeding strategies.

ABSTRACTPreparing regular time series optical remote sensing data is a difficult task due to the influences of frequently cloudy and rainy days. The irregular data and their forms severely limit the data’s ability to be analyzed and modeled for vegetation classification. However, how irregular time series data affect vegetation classification in deep learning models is poorly understood. To address these questions, this research preprocessed the 2019–2021 time series of Sentinel-2 in both unequal and equal intervals, and transformed them into an image through recurrence plot for each pixel. The initial one-dimension time series (1DTS) and recurrence plot data were then used as input data for three deep learning methods (i.e. Conv1D model based on one-dimensional convolution, GoogLeNet model based on two-dimensional convolution, and CGNet model which fused Conv1D and GoogLeNet) for vegetation classification, respectively. The class separability of the features generated by each model was evaluated and the importance of spectral and temporal features was further examined through gradient backpropagation. The equal-interval time series data significantly improved the classification accuracy with 0.04, 0.13, and 0.09 for Conv1D, GoogLeNet, and CGNet, respectively. The CGNet achieved the highest classification accuracy, indicating that the information from 1DTS and recurrence plot can be a good complementary for vegetation classification. The importance of spectral bands and time showed that the Sentinel-2 red edge-1 spectral band played a critical role in the identification of eucalyptus, loquat, and honey pomelo, but the importance order of bands varied in different vegetation types in GoogLeNet. The time importance varied across different vegetation types but is similar in these deep learning models. This study quantified the impacts of organizational form (1DTS and recurrence plot) of time series data on different models. This research is valuable for us to choose appropriate data structures and efficient deep learning models for vegetation classification.

Abstract The theory and technology of rock bolting are fundamental research topics for strata control in civil and mining engineering. Rebar bolts are commonly used for roadway primary support in underground coal mine. To adapt to deep resource mining, a new left threaded rebar bolt has been developed. Compared to conventional rebar bolts, the result of installation test showed that the new bolt reduced of 41.5% and 57.9% in stirring resistance force and torque, respectively. In laboratory pullout tests, PVC and aluminum sleeves were used to simulate weak and medium strength surrounding rocks. The average peak pullout force, displacement at the peak load and energy absorption increased by 27%, 107% and 108%, respectively, using PVC sleeve; and increased by 113%, 109% and 212%, respectively, using aluminum sleeve. Field tests were conducted under soft coal, hard coal and medium strength rock geo-conditions. Different borehole depths were selected to precisely calculate the average anchorage performance of the new bolt. Results showed that the average peak pullout force of the new bolt increased by 37%, 38% and 28%, respectively, under different surrounding rock conditions. Moreover, based on on-site test results, the pullout curves in field-testing were summarised and classified into 6 different patterns, which were discussed from a viewpoint of causality mechanism. The research findings validate that the newly developed bolt has better anchorage performance compared to conventional rebar bolts, making it a new anchorage material for deep resource mining.

In order to solve the problems of low absorption efficiency and small frequency range of traditional terahertz (THz) detectors, a broadband terahertz metasurface pyroelectric detector was proposed by combining a dual metasurface absorption array structure with the LiTaO3 pyroelectric detector. The optimization method of MATLAB and CST co-simulation was used to optimize the metasurface structure on demand. ANSYS was used to simulate and analyze the pyroelectric detector, and the influence of characteristic parameters such as sensitive layer and adiabatic layer on the temperature change rate and response current of terahertz pyroelectric detector was obtained. The results show that the use of metasurface array structure improves the detection performance of the whole THz band, and the average pyroelectric current output of the stool-type pyroelectric detector under given conditions is 31.52 pA. The use of metasurface as an absorption structure can make the pyroelectric detector have continuous and efficient wave absorption characteristics, which provides some reference for the design of broadband terahertz detectors.

Abstract Background The growth and development of organism were dependent on the effect of genetic, environment, and their interaction. In recent decades, lots of candidate additive genetic markers and genes had been detected by using genome-widely association study (GWAS). However, restricted to computing power and practical tool, the interactive effect of markers and genes were not revealed clearly. And utilization of these interactive markers is difficult in the breeding and prediction, such as genome selection (GS). Results Through the Power-FDR curve, the GbyE algorithm can detect more significant genetic loci at different levels of genetic correlation and heritability, especially at low heritability levels. The additive effect of GbyE exhibits high significance on certain chromosomes, while the interactive effect detects more significant sites on other chromosomes, which were not detected in the first two parts. In prediction accuracy testing, in most cases of heritability and genetic correlation, the majority of prediction accuracy of GbyE is significantly higher than that of the mean method, regardless of whether the rrBLUP model or BGLR model is used for statistics. The GbyE algorithm improves the prediction accuracy of the three Bayesian models BRR, BayesA, and BayesLASSO using information from genetic by environmental interaction (G × E) and increases the prediction accuracy by 9.4%, 9.1%, and 11%, respectively, relative to the Mean value method. The GbyE algorithm is significantly superior to the mean method in the absence of a single environment, regardless of the combination of heritability and genetic correlation, especially in the case of high genetic correlation and heritability. Conclusions Therefore, this study constructed a new genotype design model program (GbyE) for GWAS and GS using Kronecker product. which was able to clearly estimate the additive and interactive effects separately. The results showed that GbyE can provide higher statistical power for the GWAS and more prediction accuracy of the GS models. In addition, GbyE gives varying degrees of improvement of prediction accuracy in three Bayesian models (BRR, BayesA, and BayesCpi). Whatever the phenotype were missed in the single environment or multiple environments, the GbyE also makes better prediction for inference population set. This study helps us understand the interactive relationship between genomic and environment in the complex traits. The GbyE source code is available at the GitHub website ( https://github.com/liu-xinrui/GbyE ).

Abstract Background The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. Methods We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. Results For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01–1.23) and 1.78 (1.38–2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14–1.39) and 1.57 (1.36–1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with β of 0.09 (95% CI 0.04–0.14) and 0.57 (95% CI 0.35–0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. Conclusions High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness.

Mesenchymal stem cell derived exosomes (MSC-Exos) demonstrate beneficial effects on wound healing via anti-inflammatory and angiogenic properties. Chitosan (CS) exhibits excellent biocompatibility and accelerates cellular migration, adhesion, and proliferation. The ions released from bioactive glass (BG) and titanium dioxide (TiO2) nanoparticles exhibit sustained angiogenic and antibacterial potency. In this study, CMCS-CEBT hydrogel was synthesized from exosomes encapsulated carboxymethyl chitosan (CMCS), chitosan nanoparticles (CS-NPs), BG, and TiO2 nanoparticles for a preliminary evaluation of its impacts on the treatment of full-thickness skin defects, diabetic wounds, and burn skin injury due to burns. In vitro analysis indicated that the hydrogel exhibits excellent cell compatibility, stimulates endothelial cell adhesion and proliferation, and presents anti-inflammatory, angiogenic, and antibacterial activities. In vivo, the composite hydrogel dressing accelerated a wound healing acceleration effect, stimulated angiogenesis, and increased collagen deposition and the expression of anti-inflammatory factors. This innovative composite hydrogel dressing as a potential clinical therapy, utilizing bioactive materials, holds promise as a potential clinical therapy that aims to facilitate the regeneration of acute and chronically damaged skin tissue.

In the development of new electrochemical concepts for the fabrication of high-energy-density batteries, fluoride-ion batteries (FIBs) have emerged as one of the valid candidates for the next generation electrochemical energy storage technologies, showing the potential to match or even surpass the current lithium-ion batteries (LIBs) in terms of energy density, safety without dendritic grains, and elimination of dependence on scarce lithium and cobalt resources. However, the development of FIBs is still in its infancy and their performance is far from satisfactory, with issues such as the lower fluoride-ion conductivity of the electrolytes and the reversibility of the electrodes hindering their commercialization. Previous reviews have mainly focused on inorganic solid electrolytes with a brief emphasis on the development of various fluoride-ion conductors and their ion-conducting properties. Therefore, this review summarizes the current developments in various electrolytes, a systematic overview of the current progress for various fluoride-ion electrolytes is presented by beginning with the history, structure and classification of FIBs, ion-transport mechanisms are briefly discussed. Recent advances in different classes of fluoride-ion electrolytes are described. The methods for optimizing the ionic conductivity characteristics of the fluoride-ion electrolytes are highlighted. Finally, an outlook on the future research direction of FIBs is given by highlighting some critical issues, challenges and prospects of fluoride-ion electrolytes.

Competitive diving is a popular sport that attracts numerous participants worldwide; unfortunately, competitive divers experience a notable frequency of injuries during training and competition. Despite this, injuries in diving often received less attention compared to those in other aquatic sports. The purpose of this study was to conduct a systematic review to update the scientific evidence on injury incidence in competitive divers to offer insights into the prevalent injury patterns and help develop injury prevention strategies. This involved analyzing injury data collected from the Injury Surveillance Programme (ISP) across various levels of competition events and assessing case reports involving a wide spectrum of diving injuries. Four online bibliographical databases were consulted: Google Scholar, PubMed, Scops, and Web of Science from their inception until December 6, 2023.819 studies were initially identified, and 15 studies were finally included in this review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines and PRISMA in Exercise, Rehabilitation, Sport Medicine, and Sport Science (PERSiST) were followed. Two independent reviewers evaluated the methodological quality of the studies. The majority of diving injuries are concentrated on the upper body/trunk, including the shoulder, spine, hand/wrist, head/face, and neck, with overuse injury being a main contribution. Regarding diving incidence, the actual injury rate in competitive athletes could be even higher than currently reported, primarily due to limitations in implementing injury surveillance protocol for diving athletes. The latest injury data for diving in big competition events is absent, and there is a strong expectation for more new injury surveillance data to be published in the future. Additionally, the specific injury pattern, prevention strategy, and rehabilitation training plan for diving injury are severely deficient in the current literature.

Anaerobic digestion (AD) plays a significant role in renewable energy recovery. Upgrading AD from thermophilic (50–57 °C) to mesophilic (30–38 °C) conditions to enhance process stability and reduce energy input remains challenging due to the high sensitivity of thermophilic microbiomes to temperature fluctuations. Here we compare the effects of two decreasing-temperature modes from 55 to 35 °C on cell viability, microbial dynamics, and interspecies interactions. A sharp transition (ST) is a one-step transition by 20 °C d−1, while a mild transition (MT) is a stepwise transition by 1 °C d−1. We find a greater decrease in methane production with ST (88.8%) compared to MT (38.9%) during the transition period. ST mode overproduced reactive oxygen species by 1.6-fold, increased membrane permeability by 2.2-fold, and downregulated microbial energy metabolism by 25.1%, leading to increased apoptosis of anaerobes by 1.9-fold and release of intracellular substances by 2.9-fold, further constraining methanogenesis. The higher (1.6 vs. 1.1 copies per gyrA) metabolic activity of acetate-dependent methanogenesis implied more efficient methane production in a steady mesophilic, MT-mediated system. Metagenomic binning and network analyses indicated that ST induced dysbiosis in keystone species and greatly enhanced microbial functional redundancy, causing loss of microbial syntrophic interactions and redundant metabolic pathways. In contrast, the greater microbial interconnections (average degrees 44.9 vs. 22.1) in MT at a steady mesophilic state suggested that MT could better maintain necessary system functionality and stability through microbial syntrophy or specialized pathways. Adopting MT to transform thermophilic digesters into mesophilic digesters is feasible and could potentially enhance the further optimization and broader application of practical anaerobic engineering.

BackgroundStudies on the relationships between diseases of the urinary system and human plasma proteomes have identified several potential biomarkers. However, none of these studies have elucidated the causal relationships between plasma proteins and urolithiasis.ObjectiveThe objective of the study was to investigate the potential risks of plasma metabolites in urolithiasis using a two-sample Mendelian randomization (MR) study.MethodsA total of 1,400 metabolites were identified in the most comprehensive genome-wide association study (GWAS) of plasma metabolomics in a European population to date, and single-nucleotide polymorphisms (SNPs) were used as the instrumental variables for the plasma metabolites. The European GWAS data for urinary calculi included 482,123 case samples and 6,223 control samples (ebi-a-GCST90018935). The associations between the plasma metabolites and risk of urolithiasis were evaluated by inverse variance weighting (IVW) and supplemented by sensitivity analyses of the MR-Egger and MR-PRESSO tests.ResultsFor the first time, we found a causal relationship between two plasma metabolites (p < 1.03 × 10−4) and urolithiasis (p < 0.05). The chemical 4-hydroxychlorothalonil, which is an intermediate product of the pesticide hydroxychlorothalonil, could promote urolithiasis (odds ratio (OR) = 1.12) as a risk factor. Moreover, 1-stearoyl-2-arachidonoyl-GPC, which is an important component of phospholipid metabolism in the human body, can inhibit urolithiasis (OR = 0.94).Conclusions Our results suggest that blood metabolites can be used as blood markers and drug targets in the prevention, diagnosis, and treatment of urolithiasis; furthermore, our results can provide a basis for policy makers to formulate prevention and treatment policies for urolithiasis.

Predicting carbon dioxide emissions is crucial for addressing climate change and achieving environmental sustainability. Accurate emission forecasts provide policymakers with a basis for evaluating the effectiveness of policies, facilitating the design and implementation of emission reduction strategies, and helping businesses adjust their operations to adapt to market changes. Various methods, such as statistical models, machine learning, and grey prediction models, have been widely used in carbon dioxide emission prediction. However, existing research often lacks comparative analysis with other forecasting techniques. This paper constructs a new Discrete Fractional Accumulation Grey Gompertz Model (DFAGGM(1,1) based on grey system theory and provides a detailed solution process. The Whale Optimization Algorithm (WOA) is used to find the hyperparameters in the model. By comparing it with five benchmark models, the effectiveness of DFAGGM(1,1) in predicting carbon dioxide emissions data for China and the United States is validated.

Pathogenic microorganisms with antibiotic resistance genes (ARGs) pose a serious threat to public health and soil ecology. Although new drugs and available antibacterial materials can kill ARG carriers but accidentally kill beneficial microorganisms. Therefore, the rapid enrichment and separation of ARGs and their carriers from soil is becoming an important strategy for controlling the diffusion of ARGs. Hydroxamate siderophore (HDS) has gained widespread attentions for its involvement in trace element transfer among microorganisms in the soil environment, we thus explored an in-situ trapping-enrichment method for ARGs and their carriers via a small molecular HDS secreted by Pseudomonas fluorescens HMP01. In this study, we demonstrate that HDS significantly in-situ traps and enriches certain ARGs, including chloramphenicol, MLS, rifamycin, and tetracycline resistance genes in the soil environment. The enrichment efficiencies were 1473-fold, 38-fold, 17-fold, and 5-fold, respectively, higher than those in the control group. Specifically, the primary enriched ARGs were rpoB, mphL, catB2, and tetA(60), and Bacillus, Rhizobium, Rossellomorea, and Agrobacterium were hosts for these ARGs. This enrichment was caused by the upregulation of chemotaxis genes (e.g., cheW, cheC, and cheD) and rapid biofilm formation within the enriched bacterial population. Notably, representative ARGs such as cat, macB, and rpoB were significantly reduced by 36%, 85.7%, and 72%, respectively, in the paddy soil after HDS enrichment. Our research sheds light on the potential application of siderophore as a rapping agent for the eco-friendly reduction of ARGs and their carriers in soil environments.

BackgroundBrain network dysfunction has been characterized by resting-state electroencephalography (EEG) and magnetic resonance imaging (MRI) in the prodromal stage. This study aimed to identify multi-modal electrophysiological and neuroimaging biomarkers for differential diagnosis in synucleinopathies and phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD).MethodsWe enrolled 35 patients with multiple system atrophy (MSA), 32 with Parkinson's disease (PD), 30 with iRBD and 30 matched healthy controls (HC). Power spectral density (PSD) was calculated in different frequency bands. EEG functional connectivity (FC) was calculated using the weighted Phase Lag Index (wPLI) after source localization. Significant network disruptions were further confirmed by MRI FC analysis.ResultsQuantitative EEG analysis demonstrated that delta and theta power spectral density significantly differed among MSA, PD and HC. The increased PSD was correlated with cognitive decline and olfactory dysfunction in PD. Band-specific FC profiles were observed in theta, alpha, and gamma bands. The hypoconnected alpha network significantly correlated with motor dysfunction, while the gamma FC distinguished PD from MSA. By integrating EEG and MRI network analyses, we found that FC between the olfactory cortex and dorsolateral prefrontal cortex was significantly different between MSA and PD. A multimodal discriminative model for MSA and PD, integrating spectral and FC attributes of EEG and MRI, yielded an area under the receiver operating characteristic curve of 0.900. Simultaneously, we found the FC abnormalities were more prominent than spectral features in iRBD indicating prodromal dysfunction. The decreased FC between the angular gyrus and striatum was identified in α-synucleinopathies. This hypoconnectivity was associated with dopaminergic degeneration in iRBD examined by dopamine transporter imaging.DiscussionOur study demonstrated EEG spectral and functional profiles in prodromal and clinical-defined synucleinopathies. Multimodal EEG and MRI provided a novel approach to discriminate MSA and PD, and monitor neurodegenerative progression in the preclinical phase.

Purpose: To assess the accuracy of Raman spectroscopy in distinguishing between patients with leukemia and healthy individuals. Method: PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases were searched for relevant articles published from inception of the respective database to November 1, 2023. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), were calculated along with their corresponding 95 % confidence intervals (CI). A summary comprehensive receiver operating characteristic curve (SROC) was constructed and the area under the curve (AUC) was calculated. The degree of heterogeneity was tested and analyzed. Results: Fifteen groups of original studies from 13 articles were included. The pooled SEN and SPE were 0.93 (95 % CI, [0.92 –0.93]) and 0.91(95 % CI, [0.90–0.92]), respectively. The DOR was 613.01 (95 %CI, [270.79–1387.75]), and the AUC was 0.99. The Deeks’ funnel plot asymmetry test indicated no significant publication bias among the included studies (bias coefficient, 40.80; P = 0.13 < 0.10). The meta-regression analysis findings indicated that the observed heterogeneity could be attributed to variations in sample categories and Raman spectroscopy techniques. Conclusion: We confirmed that Raman spectroscopy has good accuracy in differentiating patients with leukemia from healthy individuals, and may become a means of leukemia screening in clinical practice. In the case of analysis based on live cells using surface-enhanced Raman spectroscopy (SERS) improved diagnostic efficacy was observed.

BackgroundThe purpose of this study was to investigate the diagnostic value of IL-17 detection in bronchoalveolar lavage fluid (BALF) and plasma samples from nonneutropenic patients with invasive pulmonary aspergillosis.MethodsWe retrospectively collected data on non-neutropenic patients who were suspected to have IPA admitted to the Third Affiliated Hospital of Soochow University between March 2020 to January 2023. IL-17 and GM were measured using enzyme-linked immunosorbent assays.ResultsA total of 281 patients were enrolled in this study, of which 62 had proven or probable IPA and the remaining 219 patients were controls. The plasma and BALF IL-17 levels were significantly higher in the IPA group compared with the control group. The plasma GM, plasma IL17, BALF GM, and BALF IL17 assays had sensitivities of 56.5%, 72.6%, 68.7%, and 81.2%, respectively, and specificities of 87.7%, 69.4%, 91.9%, and 72.6%, respectively. The sensitivity of IL17 in plasma and BALF was higher than that of GM. Plasma GM in combination with IL-17 increases the sensitivity but does not decrease the diagnostic specificity of GM testing. The diagnostic sensitivity and specificity of BALF GM combined with IL-17 for IPA in non-neutropenic patients were greater than 80% and there was a significant increase in sensitivity compared with BALF GM.ConclusionsPlasma and BALF IL-17 levels were significantly higher in non-neutropenic patients with IPA. The sensitivity of plasma and BLAF IL-17 for diagnosing IPA in non-neutropenic patients was superior to that of GM. Combined detection of lavage fluid GM and IL17 significantly improves the diagnosis of IPA in non-neutropenic patients. The combined detection of GM and IL-17 in plasma also contributes to the diagnosis of IPA in patients who cannot tolerate invasive procedures.

The rhizosphere hosts diverse microbes crucial for plant growth. This is because plant roots secrete organic compounds, thereby enriching the rhizosphere with essential nutrients. Biochar improves soil quality, while nano-biochar shows promise in contaminant adsorption. Its production from biochar is easily achievable through top-down methodologies including hydrothermal synthesis, ball-milling, sonication, and centrifugation. The advantages of employing nano-biochar are evident in several aspects. Nano-biochar exhibits enhanced properties such as greater surface area, increased porosity, and greater reactivity compared to bulk-biochar. This enhanced surface area allows for greater adsorption capacity, enabling nano-biochar to effectively immobilize contaminants in the environment. In this review, detailed interactions and applications of nano-biochar are summarized. Nano-biochar interacts with contaminants in the rhizosphere by electrostatic interaction, cation-π interactions and redox reactions, influencing soil microbial communities and plant resilience. Nano-biochar can adsorb contaminants from the rhizosphere, such as heavy metals and organic pollutants. Thus, it helps alleviate abiotic stresses, improves nutrient availability, and supports plant growth. Furthermore, the mechanistic processes of surface oxidation, mineral dissolution, organic matter release, and mechanical fragmentation in biochar are discussed, culminating in biochar ageing and nano-biochar formation, which creates a conducive environment for microorganisms. This review examines nano-biochar-rhizosphere interactions, highlighting their effects on plant-soil dynamics and resilience. Future research should address synthesis scalability and safety concerns to unlock nano-biochar's potential in sustainable agriculture and environmental management.

Abstract Background Lysine methyltransferase 2D (KMT2D) mediates mono‐methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D‐mediated H3K4me1 mark modulates gene expression in triple‐negative breast cancer (TNBC) progression is unresolved. Methods and Results We recognized Y‐box‐binding protein 1 (YBX1) as a “reader” of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP‐seq and RNA‐seq data indicated that YBX1 was co‐localized with KMT2D‐mediated H3K4me1 in the promoter regions of c‐Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c‐Myc and SENP1 in a KMT2D‐dependent manner. Conclusion Our results suggest that KMT2D‐mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c‐Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D‐H3K4me1‐YBX1 axis for TNBC treatment. Highlights YBX1 is a KMT2D‐mediated H3K4me1‐binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1. KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c‐Myc and SENP1 expression in vitro and in vivo. YBX1 is colocalized with H3K4me1 in the c‐Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients.