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Abstract Crohn’s disease (CD) is a chronic inflammatory autoimmune disease of unknown etiology. To identify new targets related to the initiation of CD, we screened a pair of twins with CD, which is a rare phenomenon in the Chinese population, for genetic susceptibility factors. Whole-exome sequencing (WES) of these patients revealed a mutation in their SERPINB4 gene. Therefore, we studied a wider clinical cohort of patients with CD or ulcerous colitis (UC), healthy individuals, and those with a family history of CD for this mutation by Sanger sequencing. The single-nucleotide difference in the SERPINB4 gene, which was unique to the twin patients with CD, led to the substitution of lysine by a glutamic acid residue. Functional analysis indicated that this mutation of SERPINB4 inhibited the proliferation, colony formation, wound healing, and migration of intestinal epithelial cells (IECs). Furthermore, mutation of SERPINB4 induced apoptosis and activated apoptosis-related proteins in IECs, and a caspase inhibitor significantly reduced these effects. Transcriptome sequencing revealed that the expression of genes encoding proinflammatory proteins (IL1B, IL6, IL17, IL24, CCL2, and CXCR2) and key proteins in the immune response (S100A9, MMP3, and MYC) was significantly upregulated during SERPINB4 mutant-induced apoptosis. Thus, the heterozygous SERPINB4 gene mutation causes the dysfunction of IECs, which would disrupt the intestinal epithelial barrier and contribute to the development of intestinal inflammation. The activation of SERPINB4 might represent a novel therapeutic target for inflammatory bowel disease.

Abstract Background Diabetes characterized by chronic hyperglycemia, has become a serious hazard to human health in the recent decades. Previous research suggests that asprosin may contribute to the development of diabetes by regulating glucose homeostasis, appetite, insulin secretion, and insulin sensitivity. Although some studies have shown that asprosin levels are higher in patients with diabetes than in healthy individuals, the association between asprosin levels and diabetes remains controversial. Aim This meta-analysis aimed to assess asprosin levels in patients with diabetes and in healthy individuals. Methods We searched the following electronic databases: Web of Science, ScienceDirect, PubMed, and Willy. The title or abstract uses the following search term: “diabetes” is used in combination with the term “asprosin.” The meta-analysis results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Results Fourteen articles were included in this meta-analysis. In our meta-analysis, the asprosin level in patients with diabetes was significantly higher than that in healthy controls (SMD: 0.95, 95% CI [0.66, 1.24]). Moreover, there was a significant difference in the asprosin levels between patients with diabetes without complication and those with complication (SMD: 0.81, 95% CI [0.33, 1.29]). Conclusions This systematic review is the first to evaluate the relationship between asprosin levels and diabetes. The asprosin levels were significantly higher in patients with diabetes. Clinical trial number Not applicable.

Abstract Background Non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), is influenced by tumor-immune interactions. M2 macrophages play a significant role in the tumor microenvironment. This study explores the role of MRO, an M2 macrophage-associated gene, in NSCLC, focusing on immune infiltration, prognostic significance, and therapeutic potential. Methods NSCLC samples from The Cancer Genome Atlas (TCGA) were analyzed using the CIBERSORT algorithm to quantify immune cell compositions. Differential gene expression and correlation studies examined MRO’s association with M2 macrophages. Univariate Cox regression and Kaplan–Meier analyses assessed prognostic significance. Single-cell RNA sequencing data from TISCH2 evaluated MRO expression in different cell types. The ESTIMATE algorithm analyzed correlations between MRO expression and immune scores, while TIDE and Submap analyses predicted immunotherapy responses. Results MRO was highly expressed in NSCLC, particularly in LUAD and LUSC, and associated with M2 macrophages. MRO correlated with key immune pathways, including TNFα signaling via NFκB, inflammatory response, and IL6 JAK STAT3 signaling. High MRO expression correlated with poorer overall survival (OS) and disease-specific survival (DSS). Single-cell analysis confirmed MRO expression in macrophages. The ESTIMATE algorithm showed positive correlations between MRO expression and immune scores. TIDE and Submap analyses suggested low MRO expression in LUSC patients might predict better immunotherapy responses. Conclusions MRO is a critical M2 macrophage-associated gene in NSCLC, influencing immune infiltration and prognosis. It may serve as a biomarker for prognostication and a target for therapeutic intervention in NSCLC.

Deep rocks encountered in underground engineering are frequently in complex in situ environments and experience both excavation disturbance during construction and cyclic loading throughout the long-term operation. Understanding the fatigue behavior of excavation-disturbed rocks in complex stress environments is critical for assessing the long-term stability of deep rock structures. Hence, an experimental method has been developed to capture the fatigue damage process of rocks while considering the in situ environment and excavation disturbance. Using this method, a series of triaxial fatigue damage experiments were conducted on Jinping deep marble samples from various in situ environments of 100 m, 1000 m, 1800 m, and 2400 m to better understand the variation in fatigue characteristics at different depths. With increasing depth, the samples experienced more cycles and greater fatigue deformation before failure. Further insights were gained into the fatigue damage behavior in terms of stiffness degradation, energy dissipation and irreversible strain accumulation. A decrease in the elastic modulus and an increase in the dissipated energy and irreversible strain exhibit an evolution pattern of initial→stabilization→acceleration, reflecting the nonlinear fatigue process that occurs inside marble. With increasing depth, marble samples have longer fatigue lives but exhibit more significant stiffness loss, energy dissipation and irrecoverable deformation accumulation; thus, evaluating the instability of deep rock structures solely using fatigue life alone is inadequate. Moreover, the previously reported inverted S-shaped evolution of fatigue damage was observed, and it was found that an increase in depth leads to an earlier onset of the accelerated fatigue damage stage with greater dominance of fatigue failure. Based on the nonlinear strain, loading cycle variable and fatigue life, a highly accurate nonlinear fatigue model was developed to describe the complete inverted S-shaped evolution pattern of fatigue damage, which demonstrated excellent practical implications for the theoretical characterization of anisotropic fatigue damage in disturbed Jinping marble.

ABSTRACT Objective Percutaneous pedicle screw fixation (PPSF) technique requires a very precise entry point of the Jamshidi needle, which leads to repeated adjustments, damaging the pedicle and increasing radiation exposure. This study was designed to propose an improved percutaneous pedicle screw fixation technique‐trajectory dynamic adjustment (TDA) technique, and evaluate its feasibility and assess the clinical outcomes. Method A total of 445 patients with lumbar spondylolisthesis or lumbar spinal stenosis associated with instability from June 2017 to May 2022 were included in the retrospective study. They were randomly separated into two groups. Two hundred thirty‐one patients underwent TDA technique (TDA group). Two hundred fourteen patients underwent traditional PPSF technique (PPSF group). All patients underwent postoperative CT to assess the accuracy of screw placement, superior facet joint violation (FJV). The evaluated clinical outcomes were needle insertion time, radiation exposure, blood loss, hospital stay, the Japanese Orthopedic Association (JOA) score, the Visual Analogue Scale (VAS) scores for lower back pain (LBP), and leg pain, lumbar interbody fusion rate, and postoperative complications. The independent‐sample t test and paired t‐test were used for continuous data. The contingency table and Mann–Whitney U test were used for categorical data. Results The time of the insertion in TDA group was significantly lower than that in PPSF group (p 0.05). Overall, there was no significant difference in the proportion of clinically acceptable screws between the two groups (p > 0.05). In addition, the lateral screw misplacement in TDA group was higher. Moreover, FJV rate was significantly lower than that in PPSF group (p 0.05). Conclusion Compared to traditional PPSF technique, TDA technique is a safer and more effective procedure which has shorter surgical time, lower radiation exposure, and lower facet joint violation rate.

Abstract Backgound Preformed metal crowns (PMCs) and zirconia crowns (ZCs) are commonly used for the treatment of primary molar caries. However, there have been no reports on factors influencing parental awareness, willingness to use these treatments, and the associated discomfort after crown placement in children.This study is the first to report factors influencing preformed crowns, providing a reference for the prevention and treatment of deciduous carious teeth. Methods Parents whose children’s posterior caries were restored with preformed crowns at Shenzhen Children’s Hospital from October 2021 to October 2023 were recruited. A questionnaire gathered data on multiple variables, including basic information about the participants, their oral health behaviors, and their attitudes toward oral health. Results Approximately two-thirds of the surveyed parents were aware of preformed metal crowns (PMCs) (67.8%), whereas over half were hardly aware of prefabricated zirconia crowns (ZCs) (59.6%). In terms of discomfort symptoms, 105 (76.7%) and 102 (76.1%) cases were reported after PMC and ZC placement respectively; however, there was no statistically significant difference between the two groups (P > 0.05). Among the surveyed parents, 19 (8.7%) expressed that they could not accept the PMC color, whereas all could accept the ZC color, and the difference was statistically significant (P

Abstract Advanced biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) have poor prognoses and limited treatment options. Here, we conducted this first-in-class phase II study to evaluate the efficacy and safety of SHR-1701, a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor-beta (TGF-β), combined with famitinib, a multi-targeted receptor tyrosine kinase inhibitor, in patients with advanced BTC or PDAC who failed previous standard treatment (trial registration: ChiCTR2000037927). Among 51 enrolled patients, the BTC cohort showed an objective response rate (ORR) of 28% (including 2 complete responses) and a disease control rate (DCR) of 80%, with a median progression-free survival (mPFS) of 5.1 months and a median overall survival (mOS) of 16.0 months. In the PDAC cohort, the ORR was 15% (2 complete responses), with a DCR of 60%, and the mPFS and mOS were 2.1 months and 5.3 months, respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 29.4% of patients, with no grade 5 TRAEs reported. Exploratory analyses revealed that primary tumor resection history, peripheral blood immunophenotype changes, and distinct immune-metabolic profiles were associated with treatment benefits. An immune/metabolism score integrating the features of six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts, allowing for the selection of patients most likely to experience positive outcomes from this therapy regimen. In conclusion, our study provides proof-of-concept data supporting the potential of SHR-1701 plus famitinib as an effective and safe subsequent-line therapy for refractory BTC and PDAC, highlighting the promise of targeting PD-L1, TGF-β, and angiogenesis pathways simultaneously.

Globally elevated temperatures during the Cretaceous extreme greenhouse climate interval were punctuated by the Valanginian cooling event, which was characterized by a positive carbon isotope excursion, global cooling, and a glacial event approximately at 135 Ma. Disentangling ocean temperature and continental ice volume trends enables us to better understand climate fluctuations over deep time. We investigated the ocean temperature–ice sheet dynamics of glaciation events that occurred in the Cretaceous greenhouse world. New clumped isotope and δ18O data from sites in the Tethyan Ocean show that seawater temperatures decreased by 5–6 °C, consistent with the development of glacial periods, and maximum ice volumes about half the size of present-day Antarctica. This cooling event provides a counter-example to other Mesozoic climate transitions driven by changes in atmospheric greenhouse gas contents. Our results emphasize the importance of quantitatively reconstructing continental ice volume, providing further support for exploring deep-time Earth climate dynamics.

Abstract Background Retinitis pigmentosa is a neurodegenerative disease with major pathologies of photoreceptor apoptosis and immune imbalance. Mesenchymal stem cells (MSCs) have been approved for clinical application for treating various immune-related or neurodegenerative diseases. The objective of this research was to investigate the mechanisms underlying the safeguarding effects of MSC-derived exosomes in a retinal degenerative disease model. Methods Interferon gamma-stimulated exosomes (IFNγ-Exos) secreted from MSCs were isolated, purified, and injected into the vitreous body of RCS rats on postnatal day (P) 21. Morphological and functional changes in the retina were examined at P28, P35, P42, and P49 in Royal College of Surgeons (RCS) rats. The mechanism was explored using high-throughput sequencing technology and confirmed in vitro. Results Treatment with IFNγ-Exo produced better protective effects on photoreceptors and improved visual function in RCS rats. IFNγ-Exo significantly suppressed the activated microglia and inhibited the inflammatory responses in the retina of RCS rats, which was also confirmed in the lipopolysaccharide-activated microglia cell line BV2. Furthermore, through tRNA-derived small RNA (tsRNA) sequencing, we found that IFNγ-Exos from MSCs contained higher levels of Other-1_17-tRNA-Phe-GAA-1-M3, Other-6_23-tRNA-Lys-TTT-3, and TRF-57:75-GLN-CGG-2-m2 than native exosomes, which mainly regulated inflammatory and immune-related pathways, including the mTOR signaling pathway and EGFR tyrosine kinase inhibitor resistance. Conclusions IFNγ stimulation enhanced the neuroprotective effects of MSC-derived exosomes on photoreceptors of the degenerative retina, which may be mediated by immune regulatory tsRNAs acting on microglia. In conclusion, IFNγ-Exo is a promising nanotherapeutic agent for the treatment of retinitis pigmentosa. Graphical Abstract

In this study, we proposed a multi-source approach for mapping local-scale population density of England. Specifically, we mapped both the working and daytime population densities by integrating the multi-source data such as residential population density, point-of-interest density, point-of-interest category mix, and nighttime light intensity. It is demonstrated that combining remote sensing and social sensing data provides a plausible way to map annual working or daytime population densities. In this paper, we trained models with England-wide data and subsequently tested these models with Wales-wide data. In addition, we further tested the models with England-wide data at a higher level of spatial granularity. Particularly, the random forest and convolutional neural network models were adopted to map population density. The estimated results and validation suggest that the three built models have high prediction accuracies at the local authority district level. It is shown that the convolutional neural network models have the greatest prediction accuracies at the local authority district level though they are most time-consuming. The models trained with the data at the local authority district level are less appropriately applicable to test data at a higher level of spatial granularity. The proposed multi-source approach performs well in mapping local-scale population density. It indicates that combining remote sensing and social sensing data is advantageous to mapping socioeconomic variables.

Abstract Gas therapy has emerged as a promising approach for treating cancer, with gases like NO, H2S, and CO showing positive effects. Among these, NO is considered a key gas molecule with significant potential in stopping cancer progression. However, due to its high reactivity and short half-life, delivering NO directly to tumors is crucial for enhancing cancer treatment. NO-driven nanomedicines (NONs) have been developed to effectively deliver NO donors to tumors, showing great progress in recent years. This review provides an overview of the latest advancements in NO-based cancer nanotherapeutics. It discusses the types of NO donors used in current research, the mechanisms of action behind NO therapy for cancer, and the different delivery systems for NO donors in nanotherapeutics. It also explores the potential of combining NO donors with other treatments for enhanced cancer therapy. Finally, it examines the future prospects and challenges of using NONs in clinical settings for cancer treatment. Graphical Abstract

Moringa oleifera is a perennial medicinal and edible plant, and polyphenols as one of its main active ingredients. This study reviews the current status of development of the polyphenol types and contents of different parts, polyphenol extraction methods, polyphenol efficacy, and polyphenol applications of Moringa oleifera. Additionally, the current research on the antioxidant, anti-inflammatory, antibacterial, antiviral, anticancer, and hypoglycemic properties of polyphenols from Moringa oleifera is critically examined. The aim of this review is to provide a theoretical basis as well as new insights into the future research and applications of Moringa oleifera polyphenols.

Abstract Aims This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country‐specific economic strata. Methods This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio‐demographic Index (SDI) levels. Through age‐period‐cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. Results Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all‐age prevalence and YLDs increased over the 30 year span, age‐standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was −0.26% and −0.25%, respectively. Conclusions This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

Abstract Background Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. Methods This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. Results In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host’s inflammatory reaction. Conclusions XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis. Graphical Abstract

Abstract Background The Clinical Dementia Rating (CDR) scale allows to detect the presence of dementia and to assess its severity, however its evaluation requires a significant time (45 min). We evaluated the agreement between two methods of collection of the CDR: face-to-face interview or based on the information available in the patient’s medical record. Methods The CLIMER study was conducted among patients attending a memory center. The CDR scale was evaluated during face-to-face interviews between neuropsychologists and patients and their caregivers and based on blind analysis of the information of the patients’ medical record by neuropsychologists. The agreement of the CDR sum of boxes (CDR-SB), the 5-point scale CDR and the different domains of the CDR evaluated between the different methods was measured using intraclass correlation (ICC) coefficient, Bland and Altman method, and linearly weighted Kappa. Results The study included 139 patients (means ± SD age 80.1 ± 6, 58.3% women, 71.9% with dementia). The ICC for the CDR-SB score assessed by face-to-face and with all the information available in the patient’s medical record was 0.95 (95% CI: 0.93–0.97). The mean difference between the CDR-SB score assessed by face-to-face and with the medical record was 0.098 ± 1.036, and 92.4% of the patients lay within the 95% limits of agreement. The ICC for the 5-point scale CDR assessed by face-to-face and with the patient’s medical record was 0.92 (95% CI: 0.88–0.95) when all the available information of the patient’s medical record was used. The linear weighted Kappa coefficients was 0.79 (95% CI: 0.68–0.91) for the 5-point scale CDR comparison between the two evaluation methods. The analysis by domain of the CDR showed ICC ranging from 0.65 to 0.91 depending of the domains and the methods of evaluation. Conclusion This study showed an excellent level of agreement of the evaluation of the CDR- SB and the 5-point scale CDR when using all the information of the patient’s medical record compared to the face-to-face interview. Trial registration https//clinicaltrials.gov/ct2/show/NCT04763941 Registration Date 02/17/2021.

The interaction between microorganisms, proteins, and lipids plays a critical role in the odor production of fish. To explore the specific impact of the interaction between lipids and microorganisms on the overall odor of grouper, this study excluded the influence of proteins and assessed lipid (POV and TBARS) and microbial characteristics (biofilm mass and ATP content) in lipid solutions. The Results showed that microbial growth and lipid oxidation mutually promote each other. Lipidomics analysis identified 44 differential lipids, and microbial diversity analysis pinpointed five key microorganisms (Carnobacterium, Pseudomonas, Gluconacetobacter, Vagococcus, and Shewanella). Furthermore, 20 key volatile compounds (VOCs) related to odor changes in the grouper lipid solution were identified using HS-SPME-GC–MS. Correlation network analysis revealed potential microbial and lipid contributions to VOC categories, including alcohols, aldehydes, ketones, and nitrogen- and sulfur-containing compounds. This study provides new insights into the roles of microorganisms and lipids in flavor formation, offering valuable knowledge for improving seafood quality control.

Abstract The virulent bacteria‐induced host immune response dominates the occurrence and progression of periodontal diseases because of the roles of individual virulence factors from these pathogens in the initiation and spread of inflammation. Outer membrane vesicles (OMVs) as a pathogenic entity have recently attracted great attention as messenger bridges between bacteria and host tissues. Herein, the novel role of OMVs derived from Fusobacterium nucleatum in the occurrence of periodontitis is dissected. In a rat periodontitis model, it is found that OMVs derived from F. nucleatum caused deterioration of periodontitis by enhancing inflammation of the periodontium and absorption of alveolar bone, which is almost equivalent to the effect of F. nucleatum itself. Furthermore, that OMVs can independently induce periodontitis is shown. The pathogenicity of OMVs is attributed to multiple pathogenic components identified by omics. After entering human periodontal ligament stem cells (hPDLSCs) by endocytosis, OMVs activated NLRP3 inflammasomes and impaired the mineralization of hPDLSCs through NF‐κB (p65) signaling, leading to the final injury of the periodontium and damage of alveolar bone in periodontitis. These results provide a new understanding of OMVs derived from pathogens and cues for the prevention of periodontitis.

In modern highway construction, asphalt pavement is a widely used structural form, which is easily affected by various external conditions, among which the temperature effect is the most significant. In this paper, the cohesion model is used to simulate the structural cracks of asphalt pavement, the finite element method is used to simulate the asphalt concrete pavement model, and the temperature field simulation model of the pavement is established by using ABAQUS software, with the help of which the spatial distribution of stresses under different temperature conditions is deeply explored, and then the crack extension law during the process of temperature change is systematically investigated, and the effect of the temperature load on the degree of damage to the asphalt pavement is also studied. With the temperature change, the pavement surface layer is affected the most, and the soil base layer is affected the least. The higher the external temperature, the larger the crack expansion width inside the pavement structure, and the faster the corresponding expansion rate. The fatigue damage rate of the pavement structure is accelerated along with the increase of temperature. The research results can provide a theoretical basis for improving the high temperature performance of asphalt pavement.

Sjögren’s disease (SjD) is a chronic autoimmune disease, in which the immune system targets exocrine glands and leads to dryness symptoms. There is an increasing need to develop novel therapeutic approach as the treatment plan has not been changed in the past decade. However, findings in mouse model may not be directly applied in patients, given the substantial differences of immune system between human and mice. In the present study, using antigens derived from human salivary A-253 cells, we established experimental Sjögren’s syndrome (ESS) in mice with human immune system (HIS). HIS-ESS mice exhibited key features of human disease, including salivary hypofunction, increased serum levels of autoantibodies and tissue destruction in the salivary glands. Phenotypic analysis revealed enhanced effector B and T cell subsets, including Th1, Th17 and T follicular helper (Tfh) cells in HIS-ESS mice, while multiplex imaging analysis suggested enlarged B cell follicles and expanded memory B cells. IL-17 neutralization therapy significantly ameliorated disease pathology at both acute and chronic stages, in which B cells were mainly affected, to the less extent Th1 and Tfh cells in HIS-ESS mice. Together, HIS-ESS mouse model highly recapitulated SjD features and immunopathogenesis, which may serve as a useful tool in drug screening and pre-clinical studies.

Spinal cord injury (SCI) is a severe event that occurs in the central nervous system (CNS). Long noncoding RNAs (lncRNAs) have already been proven to play key roles in different diseases of the CNS. Nevertheless, the roles of messenger RNAs (mRNAs) and lncRNAs one week after SCI remain to be elucidated. We established a rat model of SCI and examined the differential levels of mRNAs and lncRNAs, and then, the differentially expressed mRNAs (DE mRNAs) and lncRNAs (DE lncRNAs) were investigated. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DE lncRNAs and mRNAs were subsequently carried out to explore crucial biological processes and signaling pathways. Moreover, we constructed protein–protein interaction (PPI) networks, the STRING database, and identified the 10 high degree core nodes. We also established a co-expression network by calculating the correlation between lncRNA expression profile and mRNA expression profile. The identified DE lncRNAs and DE mRNAs may potentially be critical targets for the diagnosis and treatment of SCI in the future. Abbreviations: SCI: spinal cord injury; CNS: central nervous system; YLDs: years of life lived with disability; lncRNAs: long noncoding RNAs; mRNAs: messenger RNAs; DE: differentially expressed; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: gene set enrichment analysis; RIN: Renewable Identification Number; PCA: principal component analysis; PPI: protein–protein interaction; MF, molecular function; BP: biological process; CC: cellular component; MCODE: molecular complex detection

How to reduce the quality loss of aquatic products during storage is a topic worth exploring. This study proposed a method combining orthogonal dual-frequency ultrasound-assisted treatment (20 kHz vertically, 40 kHz horizontally, 400 W) with bioactive coating (Melissa officinalis L. essential oil-carboxymethyl chitosan-locust bean gum) and discussed the effects of this combined treatment on the quality, lipid, and protein of large yellow croaker during cold storage (4 °C). The results showed that both ultrasound-assisted treatment (US) and bioactive coating (CMCS) significantly inhibited microbial growth and quality deterioration in the fish, with the combined treatment group (US+CMCS) showing the best effect. The shelf life of large yellow croaker in the control group (CK) was 6 d, while the shelf life for US, CMCS, and US+CMCS treatments was 12 d, 12 d, and 18 d, respectively. Additionally, the combined treatment inhibited lipid oxidation and effectively delayed the oxidative degradation of protein in the large yellow croaker during cold storage. Therefore, the method of orthogonal dual-frequency ultrasound-assisted treatment (20 kHz vertically, 40 kHz horizontally, 400 W) combined with bioactive coating (Melissa officinalis L. essential oil-carboxymethyl chitosan-locust bean gum) proposed in this study was a promising approach for the preservation of aquatic products during storage.

Objective Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice.Materials and methods A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours.Results Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1β) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1β/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1β. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1β/IL-6 levels were reversed.Conclusions These results indicated that gut microbiota might affect host’s inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. ‘Limosilactobacillus-3-OMDP-IL-1β/IL-6’ might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.

Inappropriate slaughter methods can lead to differences in fish quality. In the past few years, few studies have focused on the effects of different slaughter methods on the postmortem effects of tilapia, especially the cold storage of tilapia after slaughter. The aim of this study was to investigate the effects of different slaughter methods on the biochemical characteristics and quality changes of tilapia during cold storage. In terms of blood and plasma parameters, the CS sample had lower levels of lactate dehydrogenase (LDH), cortisol (COR), and glucose (GLU) than the other samples. The results of K-value and FAAs showed that CS and ASCN groups were beneficial to prolong the freshness life of tilapia during cold storage. The texture properties of CS group were better. In summary, group CS is more conducive to prolonging the fresh life of refrigerated tilapia and is a recommended method of slaughter.

Abstract Cultural heritage is an important contributor to sustainable urban development, and its conservation is considered a global task. Previous research has primarily focused on the conservation of heritage buildings within architectural contexts and world heritage sites within geographical contexts. However, there is a notable gap in conservation of green cultural heritage (GCH) within a landscape-based framework. This study used the extended theory of planned behavior to explore the factors and pathways that influence the public's behavioral intentions toward GCH conservation. Based on 1075 questionnaires collected in Tokyo, Japan, the hypotheses of the newly constructed theoretical model were tested using partial least squares structural equation modeling. The results show that perceived behavioral control has the greatest positive influence on citizens' GCH conservation intentions and behaviors, while social norms do not influence people's behavioral intention to conserve. In the extended factors, the environmental awareness which including heritage awareness and cultural attachment, significantly influences public attitudes towards conservation. Additionally, environmental perception, including perceived usefulness and perceived quality, significantly affects the public's conservation intentions and behaviors, respectively. Our findings have implications for local governments and policymakers to enhance public participation in GCH, as well as some several new theoretical interests for further studies.

Abstract Predicting the dynamic mechanical characteristics of rocks during freeze–thaw cycles (FTC) is crucial for comprehending the damage process of FTC and averting disasters in rock engineering in cold climates. Nevertheless, the conventional mathematical regression approach has constraints in accurately forecasting the dynamic compressive strength (DCS) of rocks under these circumstances. Hence, this study presents an optimized approach by merging the Coati Optimization Algorithm (COA) with Random Forest (RF) to offer a reliable solution for nondestructive prediction of DCS of rocks in cold locations. Initially, a database of the DCS of rocks after a series of FTC was constructed, and these data were obtained by performing the Split Hopkinson Pressure Bar Test on rocks after FTC. The main influencing factors of the test can be summarized into 10, and PCA was employed to decrease the number of dimensions in the dataset, and the microtests were used to explain the mechanism of the main influencing factors. Additionally, the Backpropagation Neural Network and RF are used to construct the prediction model of DCS of rock, and six optimization techniques were employed for optimizing the hyperparameters of the model. Ultimately, the 12 hybrid prediction models underwent a thorough and unbiased evaluation utilizing a range of evaluation indicators. The outcomes of the research concluded that the COA-RF model is most recommended for application in engineering practice, and it achieved the highest score of 10 in the combined score of the training and testing phases, with the lowest RMSE (4.570,8.769), the lowest MAE (3.155,5.653), the lowest MAPE (0.028,0.050), the highest R 2 (0.983,0.94).

Abstract In order to explore the damage characteristics and crack development laws of hard rock under laser irradiation, laser irradiation experiments on sandstone were conducted considering the interaction of three laser parameters: spot diameter, laser power, and irradiation time. Subsequently, uniaxial compression experiments were conducted on sandstone samples before and after laser irradiation. In addition, based on the maximum principal stress intensity criterion and finite element software, laser induced fracturing sandstone simulation experiments were conducted. Research has found that: Laser irradiation significantly reduces the uniaxial compressive strength of sandstone, with a maximum reduction of about 88.9%, and is also accompanied by a significant decrease in elastic modulus. The degree of sandstone damage escalates with increasing laser power and irradiation time, alongside a reduction in spot diameter. Strong correlations were observed between the strength reduction rate and crack metrics like opening, area, and depth, enabling the establishment of a high-precision regression model. Cracks originate internally within sandstone, initially extending diagonally upwards toward the specimen’s surface before propagating outward. These findings elucidate the mechanisms behind sandstone’s strength reduction and crack propagation under laser irradiation, providing some insights for the practical application of laser rock breaking technology in engineering.

Abstract Background Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. Methods We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999–2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. Results In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value

Abstract Rapid urbanization has resulted in the substantial population growth in metropolitan areas. However, existing research on population change of the cities predominantly draws on grid statistical data at the administrative level, overlooking the intra-urban variegation of population change. Particularly, there is a lack of attention given to the spatio-temporal change of population across different urban forms and functions. This paper therefore fills in the lacuna by clarifying the spatio-temporal characteristics of population growth in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 2000 to 2020 through the methods of local climate zone (LCZ) scheme and urban–rural gradients. The results showed that: (1) High population density was observed in the compact high-rise (LCZ 1) areas, with a noticeable decline along urban–rural gradients. (2) The city centers of GBA experienced the most significant population growth, while certain urban fringes and rural areas witnessed significant population shrinkage. (3) The rate of growth tended to slow down after 2010, but the uneven development of population-based urbanization was also noticeable, as urbanization and industrialization varied across different LCZ types and cities in GBA. This paper therefore contributes to a deeper understanding of population change and urbanization by clarifying their spatio-temporal contingences at landscape level.

BackgroundPolycystic ovary syndrome (PCOS), a common endocrine disorder, affects women of reproductive age, and its adverse consequences affect women throughout their lifespan, from adolescence to postmenopause. The prevalence of depression is much higher in women with PCOS than in healthy controls. Thus, it is recommended that depressive syndrome be screened routinely in all patients with PCOS at diagnosis. To date, no comprehensive bibliometric analysis has been conducted in this field. Therefore, we conducted a bibliometric analysis to describe the current status, trends, and hotspots of PCOS research related to depression.Materials and methodsUsing data retrieved from the Web of Science (WoS) Core Collection database from 1993 to 2024, bibliometric analyses were performed using WoS and CiteSpace software.ResultsSince the first paper was published in 1993, studies related to PCOS and depression have remained rare in the following decade. Since the establishment of the Rotterdam criteria in 2003, research on the etiology, pathogenesis, and treatment of PCOS with depressive syndrome has entered a booming period. The United States and Australia indisputably took leading positions in this area, with the most outstanding institutions in the world being the University of Pennsylvania and Monash University. Although achievements have flourished since 2003, the exact pathogenesis of PCOS remains uncertain owing to its heterogeneity. New research is rapidly increasing to fill these gaps and to push forward the goal of improving the quality of life in women with PCOS and depression. Along with progress in research, the world's leading societies organize conferences every 5 years to update guidelines for the assessment and management of PCOS. “Oxidative stress,” “inflammation,” “obstructive sleep apnea,” “gut microbiota,” and “single nucleotide polymorphism” appeared as new hotspots in the recent 5 years.ConclusionA bibliometric analysis was performed to describe the trends and hotspots of research in women with PCOS and depression to attract the attention of more researchers to this topic.Systematic Review Registrationhttps://www.webofscience.com/wos/woscc/basic-search.

A variety of polyphenols in walnut green husk have shown physiological benefits, but their primary hypoglycemic active ingredients remain unclear. We report the extraction of walnut green husk polyphenols (WGHP) and their hypoglycemic effects in vitro. WGHP was extracted using ultrasound-assisted ethanol extraction, with optimization via response surface methodology resulting in 88.0 ± 0.1 % purity after D101 macroporous resin purification. WGHP effectively inhibited α-glucosidase and α-amylase, with IC50 values of 3.42 μg/mL and 2.56 mg/mL, respectively. It also increased glycogen synthesis in insulin-resistant HepG2 cells and enhanced glucose consumption in 3T3-L1 and insulin-resistant HepG2 cells. Screening six α-glucosidase ligands from WGHP using affinity ultrafiltration and UPLC-MS/MS, combined with molecular docking, identified hydrogen bonds and binding energies between the ligands and the enzyme. These results highlight the hypoglycemic potential of walnut green husk polyphenols and provide a basis for future therapeutic research.

Abstract 2D layered semiconductors have attracted considerable attention for beyond‐Si complementary metal‐oxide‐semiconductor (CMOS) technologies. They can be prepared into ultrathin channel materials toward ultrascaled device architectures, including double‐gate field‐effect‐transistors (DGFETs). This work presents an experimental analysis of DGFETs constructed from chemical vapor deposition (CVD)‐grown monolayer (1L) molybdenum disulfide (MoS2) with atomic layer deposition (ALD) of hafnium oxide (HfO2) high‐k gate dielectrics (top and bottom). This extends beyond previous studies of DGFETs based mostly on exfoliated (few‐nm thick) MoS2 flakes, and advances toward large‐area wafer‐scale processing. Here, significant improvements in performance are obtained with DGFETs (i.e., improvements in ON/OFF ratio, ON‐state current, sub‐threshold swing, etc.) compared to single top‐gate FETs. In addition to multi‐gate device architectures (e.g., DGFETs), the scaling of the equivalent oxide thickness (EOT) is crucial toward improved electrostatics required for next‐generation transistors. However, the impact of EOT scaling on the characteristics of CVD‐grown MoS2 DGFETs remains largely unexplored. Thus, this work studies the impact of EOT scaling on subthreshold swing (SS) and gate hysteresis using current–voltage (I–V) measurements with varying sweep rates. The experimental analysis and results elucidate the basic mechanisms responsible for improvements in CVD‐grown 1L‐MoS2 DGFETs compared to standard top‐gate FETs.

PurposeThis meta-analysis aimed to evaluate the diagnostic efficacy of dual-energy computed tomography (DECT) in detecting cervical lymph node metastasis among papillary thyroid cancer (PTC) patients.MethodsA comprehensive search across PubMed, Embase, and Web of Science databases was conducted to identify pertinent publications up to May 2024. This search focused on studies examining the diagnostic accuracy of DECT in detecting cervical lymph node metastases in PTC patients. We employed a bivariate random-effects model to calculate pooled sensitivity and specificity of DECT. The degree of heterogeneity in the studies was quantified using the I2 statistic. Furthermore, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was utilized to evaluate the methodological quality of the included studies.ResultsThis meta-analysis encompassed 14 articles, collectively involving 1,615 patients. The pooled sensitivity, specificity, and AUC for DECT in detecting cervical lymph node metastases in PTC patients were 0.81 (95% CI: 0.76–0.85), 0.86 (95% CI: 0.80–0.91), and 0.89 (95% CI: 0.86–0.92), respectively. According to Fagan’s nomogram, for DECT, with a pre-test probability of 50%, the post-test probability was calculated as 85% for a positive result and 18% for a negative result. Deeks’ funnel plot asymmetry test showed no significant publication bias was observed for DECT (p = 0.28).ConclusionOur meta-analysis indicates that DECT demonstrates superior sensitivity and specificity in cervical lymph node metastasis among PTC patients. To corroborate these findings and evaluate their clinical applicability, further prospective studies are necessary.

BackgroundGastric intestinal metaplasia is a common pathological feature in patients with Helicobacter pylori (H. pylori) infection. Rabeprazole was widely used as the first-line regimen for H. pylori infectious treatment. The objective of this study is to explore the mechanism of rabeprazole in gastric intestinal metaplasia treatment.MethodsReal-time PCR, Western blotting (WB) and ROS analysis were conducted to confirm that rabeprazole could induce ferroptosis to suppress gastric intestinal metaplasia. Cellular fraction, luciferase and chromatin immunoprecipitation (ChIP) were used to identify the mechanism underlying rabeprazole modulated ferroptosis.ResultsHerein, we found rabeprazole treatment led to inhibit CDX2 and MUC2 expression, alleviating gastric intestinal metaplasia, which was attributed to enhanced ferroptosis characterized by decreased GPX4 expression. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) could reverse decreased CDX2 and MUC2 expression caused by rabeprazole. Mechanically, Rabeprazole could inhibit CREB phosphorylation and nuclear translocation, which further decreased the binding of CREB to GPX4 promoter, reducing GPX4 transactivity. Moreover, endogenous PKA interacted with CREB, and this interaction was drastically destroyed in response to rabeprazole treatment. Most importantly, enhanced ferroptosis was observed in H. pylori-infected gastric intestinal metaplasia in comparison to HC control.ConclusionThese findings suggested that rabeprazole induced ferroptosis to reduce CDX2 expression in gastric epithelial cells through PKA/CREB cascade signaling, implying that targeting ferroptosis could be a promising strategy in improving gastric intestinal metaplasia during H. pylori-infected patients.

This study investigated the impact of multi-frequency ultrasound-assisted (20/28/40 kHz) thawing (MUAT) at different power levels (195, 220, 245, and 270 W, respectively) on the flesh quality and protein stability of large yellow croakers. Compared with flowing water thawing (FWT) and the other MUAT sample, flesh quality results indicated that the MUAT-220 W significantly reduced (p

Abstracts: Several pre-cooling methods for bok choi were used, such as natural convection pre-cooling (NCPC), strong wind pre-cooling (SWPC), vacuum pre-cooling (VPC), cold water pre-cooling (CWPC), electrolyzed water pre-cooling (EWPC), and fluid ice pre-cooling (FIPC), in order to determine the most suitable precooling method. It was found that VPC reduced the respiration rate, inhibited the increase of malondialdehyde (MDA) and relative electrolyte leakage, and significantly decreased the total bacterial count. This may be due to the rapid decompression process during vacuum pre-cooling, which disrupts the microbial structure and has a certain sterilizing effect. Bok choi pre-cooled by VPC had the best color, hardness value, chlorophyll, titratable acid (TA) content, vitamin C (VC) content, total phenolic (TP) content, soluble sugar content, superoxide dismutase (SOD) activity, ascorbate peroxidase (APX) activity, and catalase (CAT) activity. Therefore, the most suitable pre-cooling method for bok choi among the above pre-cooling methods was the VPC method.

Pakchoi seedlings (Brassica chinensis L.) is susceptible to damage and spoilage during harvest and transport, leading to significant quality deterioration and financial losses. This study explored the use of ammonium glycyrrhizinate (AG) to address these issues. AG self-assembles into macromolecules at room temperature, blocking stomata and regulating respiration rates in Pakchoi seedlings. Additionally, it disrupts bacterial cell biofilm and inhibits its synthesis. While AG has been used in medicine, its application in the food industry remains limited. The study found that incorporating AG in Pakchoi seedlings preserves water content and total soluble solids (TSS), while preventing declines in catalase (CAT), Vitamin C (VC), and chlorophyll during storage. AG also reduced malondialdehyde (MDA) levels and maintained peroxidase (POD) and superoxide dismutase (SOD) activities. At a concentration of 4.25 g L−1, AG enhanced radical scavenging ability and extended the shelf life of Pakchoi seedlings by inhibiting bacteria and postponing senescence.

Study region: Xiangjiang River Basin (XRB) in subtropical China. Study focus: Vegetation changes have a substantial impact on the water cycle in watersheds. However, the responses of hydrological processes to vegetation changes in subtropical regions have not yet been thoroughly clarified. The primary objectives of this study were to quantify the sensitivity of hydrological variables to vegetation changes and to elucidate the contributions of vegetation greening and climatic changes to alterations in hydrological variables in the Xiangjiang River Basin (XRB). New hydrological insights for the region: Evapotranspiration (ET) exhibits a significant positive sensitivity to alterations in Leaf Area Index (LAI) in the XRB, while soil water storage (SW) and flow depth (Q) showed a significant negative sensitivity to LAI changes. Changes in LAI primarily result in increased ET and reduced SW and Q, while increased in precipitation leads to augmented ET, SW, and Q. Alterations in potential evapotranspiration have been associated with heightened ET and reduced SW and Q. From the perspective of relative contributions, LAI predominantly influences alterations in ET within the XRB; P and PET are the primary driver of shifts in SW; and P chiefly governs the variations in Q. Our results highlight the important impact of vegetation changes on hydrological variables in subtropical watersheds.