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Objective: Machine learning (ML) has been widely used to detect and evaluate major depressive disorder (MDD) using neuroimaging data, i.e., resting-state functional magnetic resonance (rs-fMRI). However, the diagnostic efficiency is unknown. The aim of the study is to conduct an updated meta-analysis to evaluate the diagnostic performance of ML based on rs‑fMRI data for MDD. Methods: English databases were searched for relevant studies. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the methodological quality of the included studies. A random‑effects meta‑analytic model was implemented to investigate the diagnostic efficiency, including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Regression meta-analysis and subgroup analysis were performed to investigate the cause of heterogeneity. Results: Thirty-one studies were included in this meta-analysis. The pooled sensitivity, specificity, DOR, and AUC with 95% confidence intervals were 0.80 (0.75, 0.83), 0.83 (0.74, 0.82), 14.00 (9, 22.00), and 0.86 (0.83, 0.89), respectively. There were significant heterogeneity among the included studies. The meta-regression showed that the leave-one-out cross-validation（loocv）: (sensitivity: p100: (sensitivity: p100:sensitivity:0.71, specificity: 0.72,n<100:sensitivity:0.81, specificity: 0.79), the different levels of disease evaluated by Hamilton Depression Rating Scale （HDRS） (mild vs moderate vs severe: sensitivity:0.52 vs 0.86 vs 0.89, specificity:0.62 vs 0.78 vs 0.82) ， the depression scales in the same symptom, (BDI vs HDRS/HAMD: sensitivity:0.86 vs 0.87, specificity: 0.78 vs 0.80),and the features(graph vs functional connectivity: sensitivity:0.84 vs 0.86,specificity:0.76 vs 0.78) selected might be the causes of heterogeneity. Conclusion: ML showed high accuracy for the automatic diagnosis of MDD. Future studies are warranted to promote the potential use of those classification algorithms to clinical settings.

Curcumin has been proven to have a weight-loss effect in a menopausal rat model induced by ovariectomy. However, the effects of curcumin on gut microfloral communities of ovariectomized (OVX) rats remains unclear. Here, we used high-throughput 16S rDNA sequencing to explore the effects of curcumin on microbial diversity in the gut of OVX rats. Female Wistar rats were subjected to either ovariectomy or a sham operation (SHAM group). The OVX rats were treated with vehicle (OVX group) or curcumin (CUR group) by oral gavage. After 12-week treatments, the weights of the bodies and uteri of rats were recorded, the levels of estradiol in the serum were assayed by electrochemiluminescence immunoassay (ECLIA). Then, the fragments encompassing V3–V4 16S rDNA hypervariable regions were PCR amplified from fecal samples, and the PCR products of V3–V4 were sequenced on an Illumina MiSeq for characterization of the gut microbiota. Our results showed that, compared to rats in the SHAM group, rats in the OVX group had more weight gain and lower levels of estradiol in the serum, and curcumin could cause significant weight loss in OVX rats but did not increase the levels of estradiol. Sequencing results revealed the presence of 1120, 1114, and 1119 operational taxonomic units (OTUs) found in the SHAM, OVX, and CUR groups, respectively. The percentage of shared OTUs was 86.1603%. Gut microbiota of rats from the SHAM or CUR group had higher levels of biodiversity and unevenness estimations than those from the OVX group. At the phyla level, compared to rats in SHAM group, rats in the OVX group had a higher ratio of phyla Firmicutes and Bacteroidetes in the gut; at the genus level, four differential gut microbiota (Incertae_Sedis, Anaerovorax, Anaerotruncus, and Helicobacter) between SHAM and OVX groups were found, whereas seven differential gut microbiota (Serratia, Anaerotruncus, Shewanella, Pseudomonas, Papillibacter, Exiguobacterium, and Helicobacter) between OVX and CUR groups were found. In conclusion, estrogen deficiency induced by ovariectomy caused changes in the distribution and structure of intestinal microflora in rats, and curcumin could partially reverse changes in the diversity of gut microbiota.

The Datong pluton, the largest early Palaeozoic granitoid in the Western Kunlun Orogenic Belt (WKOB) in NW China, is a typical appinite-granite complex. It consists of diorites, quartz diorites, monzodiorites, quartz monzodiorites, monzonites, quartz monzonites, syenites, granodiorites and monzogranites. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) zircon U–Pb dating yielded crystallization ages of 459 ± 3 Ma for the quartz monzonites and 452 ± 5 Ma for the monzogranites (Late Ordovician). The rocks possess a wide range of SiO2 (56.0–73.4 wt %), MgO (0.17–4.55 wt %) and Mg no. (25–60), with high K2O (2.83–5.29 wt %) contents, exhibiting high-K calc-alkaline to shoshonitic traits. They are characterized by enrichments in large-ion lithophile elements (LILEs) and light rare Earth elements (LREEs), as well as depletions in high-field-strength elements (HFSEs). The rocks have initial 87Sr/86Sr ratios of 0.7086–0.7185, negative εNd(t) values of –3.72 to –1.79 and εHf(t) values vary from –1.6 to +4.7. These features are modelled to show that they were most likely derived from an enriched lithospheric mantle source and that fractional crystallization with minor crustal contamination was involved in their petrogenetic process. Considering the distribution and chronology of the Palaeozoic intrusions – such as Kegang, Bulong, Qiukesu, Yierba, North Kudi, Dongbake, Buya, Ayilixi and Warengzilafu granitoid plutons with ages of c. 420–530 Ma – in conjunction with the Palaeozoic metamorphic overprinting in the WKOB, we propose a divergent double-subduction model to explain the destruction of the Proto-Tethys Ocean and suggest that the Datong pluton was likely emplaced in a post-collisional setting following the termination of subduction in response to slab break-off.

Different studies have consistently demonstrated a positive correlation between chronic pain and cognitive changes. This study aimed to explore the genetic factors underlying the relationship between chronic pain and cognitive traits, and to investigate whether an inherent causal connection exists between them. The genetic contributions of chronic multi-site pain and eight cognitive traits were investigated based on Genome-wide association studies (GWAS) data. Linkage disequilibrium score regression (LDSC) was employed to assess the genetic correlations between each pair of traits. The shared genetic components of these traits were investigated by identifying single nucleotide polymorphisms (SNPs) with pleiotropic effects using the Cross Phenotype Association (CPASSOC) method. Furthermore, enrichment analysis and transcriptome-wide association studies (TWAS) were performed to characterize the significant associations between genetic traits. The latent causal variable model (LCV) was employed to explore the potential causal relationship between both traits. A significant negative genetic correlation was found between chronic pain and several cognitive functions, particularly intelligence (rg = -0. 11,  = 7.77 × 10 ). CPASSOC identified 150 pleiotropic loci. A co-localization analysis was conducted, which identified 20 loci exhibiting pleiotropic effects at the same genomic position. The LCV analysis indicated no causal relationship between both traits. The present work contributed to an enhanced understanding of the complex genetic interplay between cognitive function and chronic pain.

The increasing prevalence of aquatic sports presents significant public health concerns due to the risk of infections from waterborne pathogens. Conventional detection methods are often labor intensive, rely on sophisticated laboratory instrumentation, and are inadequate for meeting the urgent demand for onsite, point-of-care testing (POCT). This study reports the development and validation of an integrated POCT platform. The system incorporates three core modules: (1) an instrument-free, syringe-actuated device for simple nucleic acid extraction; (2) a PMMA microfluidic chip enabling uniform sample distribution to multiple reaction chambers via manual centrifugation; and (3) a visual, pH indicator-based loop-mediated isothermal amplification (LAMP) assay. The primers and reaction chemistries were systematically optimized for pathogens, including Staphylococcus aureus and Shigella flexneri . The developed platform enables a sample-to-answer workflow in approximately 60 min, with an analytical limit of detection of 10–100 copies per reaction. Notably, the microfluidic chip platform showed enhanced performance compared to conventional tube-based assays in both sensitivity and stability, particularly yielding more robust results for low-titer samples. Furthermore, the simplified extraction method achieved a recovery efficiency for gram-negative bacteria comparable to that of commercial kits, while noting differences in efficiency for gram-positive strains. The integrated platform exhibited high specificity and robustness against interferents in simulated contaminated water. This work demonstrates a user-friendly, cost-effective, and fully integrated platform for the visual detection of multiple pathogens, requiring only a portable heating module for its entire operation. The platform not only offers a viable technical solution for onsite safety monitoring in aquatic sports but also validates the concept of “backend compensation”: a well-designed detection module can help offset the performance loss from simplified frontend sample preparation. This philosophy provides valuable insights for developing reliable POCT systems destined for real-world, resource-limited settings.

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by synovitis and cartilage destruction. The active compound, icariin (ICA), derived from the herb Epimedium, exhibits potent anti-inflammatory properties. However, its clinical utility is limited by its water insolubility, poor permeability, and low bioavailability. To address these challenges, we developed a multifunctional drug delivery system—adipose-derived stem cells-exosomes (ADSCs-EXO)-ICA to target active macrophages in synovial tissue and modulate macrophage polarization from M1 to M2. High-performance liquid chromatography analysis confirmed a 92.4 ± 0.008% loading efficiency for ADSCs-EXO-ICA. In vitro studies utilizing cellular immunofluorescence (IF) and flow cytometry demonstrated significant inhibition of M1 macrophage proliferation by ADSCs-EXO-ICA. Enzyme-linked immunosorbent assay, cellular transcriptomics, and real-time quantitative PCR indicated that ADSCs-EXO-ICA promotes an M1-to-M2 phenotypic transition by reducing glycolysis through the inhibition of the ERK/HIF-1α/GLUT1 pathway. In vivo, ADSCs-EXO-ICA effectively accumulated in the joints. Pharmacodynamic assessments revealed that ADSCs-EXO-ICA decreased cytokine levels and mitigated arthritis symptoms in collagen-induced arthritis (CIA) rats. Histological analysis and micro computed tomography confirmed that ADSCs-EXO-ICA markedly ameliorated synovitis and preserved cartilage. Further in vivo studies indicated that ADSCs-EXO-ICA suppresses arthritis by promoting an M1-to-M2 switch and suppressing glycolysis. Western blotting supported the therapeutic efficacy of ADSCs-EXO-ICA in RA, confirming its role in modulating macrophage function through energy metabolism regulation. Thus, this study not only introduces a drug delivery system that significantly enhances the anti-RA efficacy of ADSCs-EXO-ICA but also elucidates its mechanism of action in macrophage function inhibition. Graphical abstract

The North China Craton underwent extensive lithospheric thinning and crustal reworking during the Mesozoic, challenging classic views of craton stability. This period marks a transition from tectonic quiescence to widespread reactivation, but timing and magnitude remain poorly constrained. Here we reconstruct crustal thickness evolution along the southern margin of the North China Craton using strontium to yttrium and lanthanum to ytterbium ratios, plus neodymium isotopic data from granitoids. Thickening began in the Jurassic and peaked around 130 Ma, when crustal thickness exceeded 70 km and palaeoelevation surpassed 5 km, forming a plateau comparable to the Tibetan Plateau. After ~128 Ma, thickness and elevation decreased to 30–40 km and <3 km by 125–110 Ma. These shifts parallel sedimentary, structural and geophysical evidence. We interpret this evolution as two stages: initial thickening from North China–Yangtze collision, followed by extensional collapse and lithospheric thinning likely driven by Paleo-Pacific plate rollback. The North China Craton underwent two distinct crustal stages, characterized by thickening due to Mesozoic collision, followed by extensional collapse and lithospheric thinning likely driven by PaleoPacific plate rollback, according to a crustal thickness reconstruction using Sr/Y and La/Yb ratios as well as εNd isotopic data of granitoids.

Osteoclasts are the only multinucleated cells in vivo responsible for bone resorption and are vital for regulating bone remodeling and maintaining bone mass. The RAW264.7 cell line is widely used to study osteoclastic differentiation and biological molecular mechanism. However, protocols for inducing osteoclast formation in RAW264.7 cells vary considerably between laboratories, hindering the replication of results. Therefore, we tested the influence of culture conditions on osteoclast differentiation, including cell density and receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations with or without macrophage colony-stimulating factors (M-CSF). Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the morphology of osteoclasts. qPCR was used to detect gene expression of osteoclast-specific gene marker cathepsin K (CTSK), osteoclast transcription factors c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). The bone resorption function was evaluated by a scanning electron microscope (SEM). RANKL treatment increased multinucleated osteoclasts formation and increased CTSK, c-Fos and NFATc1 gene expression. Compared with RANKL treatment, M-CSF significantly decreased multinucleated osteoclasts formation, reduced CTSK gene expression and had little effect on c-Fos and NFATc1 gene expression. Concerning bone resorption activity, RANKL treatment increased bone resorption pits on bovine bone slices. Significantly higher levels of osteoclastogenesis were observed with RAW264.7-cell density of 2×10 4 cells/well in 24-well plates. Our results suggest that the addition of 50 ng/ml M-CSF has no positive effect on osteoclastogenesis. RANKL treatment and cell density contribute to osteoclast formation, and the optimal conditions are beneficial when exploring osteoclast function and mechanism.

The existence of chronic pain increases susceptibility to virus and is now widely acknowledged as a prominent feature recognized as a major manifestation of long-term coronavirus disease 2019 (COVID-19) infection. Given the ongoing COVID-19 pandemic, it is imperative to explore the genetic associations between chronic pain and predisposition to COVID-19. We conducted genetic analysis at the single nucleotide polymorphism (SNP), gene, and molecular levels using summary statistics of genome-wide association study (GWAS) and analyzed the drug targets by summary data-based Mendelian randomization analysis (SMR) to alleviate the multi-site chronic pain in COVID-19. Additionally, we performed a latent causal variable (LCV) method to investigate the causal relationship between chronic pain and susceptibility to COVID-19. The cross-trait meta-analysis identified 19 significant SNPs shared between COVID-19 and chronic pain. Coloc analysis indicated that the posterior probability of association (PPH4) for three loci was above 70% in both critical COVID-19 and COVID-19, with the corresponding top three SNPs being rs13135092, rs7588831, and rs13135092. A total of 482 significant overlapped genes were detected from MAGMA and CPASSOC results. Additionally, the gene ANAPC4 was identified as a potential drug target for treating chronic pain (P=7.66E-05) in COVID-19 (P=8.23E-03). Tissue enrichment analysis highlighted that the amygdala (P=7.81E-04) and prefrontal cortex (P=8.19E-05) as pivotal in regulating chronic pain of critical COVID-19. KEGG pathway enrichment further revealed the enrichment of pleiotropic genes in both COVID-19 (P=3.20E-03,Padjust=4.77E-02,hsa05171) and neurotrophic pathways (P=9.03E-04,Padjust =2.55E-02,hsa04621). Finally, the latent causal variable (LCV) model was applied to find the genetic component of critical COVID-19 was causal for multi-site chronic pain (P=0.015), with a genetic causality proportion (GCP) of was 0.60. In this study, we identified several functional genes and underscored the pivotal role of the inflammatory system in the correlation between the paired traits. Notably, heat shock proteins emerged as potential objective biomarkers for chronic pain symptoms in individuals with COVID-19. Additionally, the ubiquitin system might play a role in mediating the impact of COVID-19 on chronic pain. These findings contribute to a more comprehensive understanding of the pleiotropy between COVID-19 and chronic pain, offering insights for therapeutic trials.

This study aims to investigate the composition and function of the gut microbiome in long-term depression using an 8-week chronic unpredictable mild stress (CUMS) rat model. Animals were sacrificed after either 4 weeks or 8 weeks under CUMS to mimic long-term depression in humans. The gut microbiome was analyzed to identify potential depression-related gut microbes, and the fecal metabolome was analyzed to detect their functional metabolites. The correlations between altered gut microbes and metabolites in the long-term depression rats were explored. The crucial metabolic pathways related to long-term depression were uncovered through enrichment analysis based on these gut microbes and metabolites. The microbial composition of long-term depression (8-week CUMS) showed decreased species richness indices and different profiles compared with the control group and the 4-week CUMS group, characterized by disturbance of Alistipes indistinctus, Bacteroides ovatus, and Alistipes senegalensis at the species level. Additionally, long-term depression was associated with disturbances in fecal metabolomics. D-pinitol was the only increased metabolite in the 8-week CUMS group among the top 10 differential metabolites, while the top 3 decreased metabolites in the long-term depression rats included indoxyl sulfate, trimethylaminen-oxide, and 3 alpha,7 alpha-dihydroxy-12-oxocholanoic acid. The disordered fecal metabolomics in the long-term depression rats mainly involved the biosynthesis of pantothenate, CoA, valine, leucine and isoleucine. Our findings suggest that the gut microbiome may participate in the long-term development of depression, and the mechanism may be related to the regulation of gut metabolism.