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Background and Purpose: The field of hydrogen medicine has garnered extensive attention since Professor Ohsawa established that low concentrations of hydrogen (2%-4%) exert antioxidant effects. The present study aimed to evaluate the therapeutic effect of molecular hydrogen in a CUMS rat model., Methods: A total of 40 SD rats were randomly divided into a control group, a model group, a hydrogen group, and a positive drug group. Four weeks post-modeling, hydrogen inhalation and other treatments were administered. Behavioral, biochemical, and immunohistochemical evaluations were performed after treatment., Results: Hydrogen inhalation alleviated depressive behavior and hippocampal neuronal damage in CUMS rats, as well as restored the levels of neurotransmitters, inflammatory factors, and oxidative stress. Moreover, it maintained mitochondrial homeostasis and up-regulated the expression of PGC-1α, PINK1, and Parkin., Conclusions: The results collectively indicated that hydrogen significantly attenuated CUMS-induced depressive-like behavior and monoamine neurotransmitter deficiency, as well as protected the brain from oxidative stress and inflammatory damage and effectively preserved mitochondrial homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Erxian decoction (EXD) is an empirical formula for treating cardiovascular disease, our previous work has shown that EXD could improve the cardiovascular structure and function in ovariectomized (OVX) rats, but its pharmacological mechanism is still unclear., Materials and Methods: Network pharmacology was utilized to assess the key active components and central targets of EXD in treating postmenopausal cardiovascular disease. Then, an OVX rat model was established, HE staining and transmission electron microscope were utilized to observe myocardial tissue morphology, TUNEL staining was utilized to detect cardiomyocyte apoptosis, western blot, and ELISA were used to confirm efficacy and pathway of EXD., Results: The network pharmacology prediction results showed that 129 common targets were identified by intersecting EXD targets and postmenopausal cardiovascular disease targets, including AKT1, TNF, IL-6, IL-1β, PTGS2 and other core targets, apoptosis, PI3K/AKT, and other signaling pathways may be closely related to postmenopausal cardiovascular disease. After ovariectomy, the myocardial tissue of rats was damaged, the expression level of PI3K/AKT pathway-related molecules in the myocardial tissue were decreased, the apoptosis index of cardiomyocytes was increased, and the levels of inflammatory factors (TNF-α, IL-6, and IL-1β) were enhanced. EXD intervention could improve myocardial tissue injury, EXD could up-regulate the protein expression of PI3K and p-AKT in myocardial tissue, and thereby prevent myocardial cell apoptosis. At the same time, EXD downregulated the levels of inflammatory factors in serum of ovariectomized rats., Conclusion: EXD may prevent myocardial tissue damage through induction of the PI3K/AKT signaling pathway, thereby reducing cardiomyocyte apoptosis and inflammation. EXD may be a potential drug for the treatment of postmenopausal cardiovascular disease.

Observational studies suggest a link between osteoarthritis (OA) and frailty, but the shared genetic architecture and causal relationships remain unclear. We analyzed X-ray and 18 F-FDG PET/CT images in frail and non-frail individuals and conducted genetic correlation analyses using Linkage Disequilibrium Score Regression (LDSC) based on recent Genome-Wide Association Studies (GWAS) for OA and frailty. We identified pleiotropic single-nucleotide polymorphisms (SNPs) through Cross-Phenotype Association (CPASSOC) and Colocalization (COLOC) analyses and investigated genetic overlaps using Multi-marker Analysis of GenoMic Annotation (MAGMA). Transcriptome-wide association studies (TWAS) were conducted to analyze pleiotropic gene expression, and Mendelian Randomization (MR) was used to assess causal relationships between OA and frailty. Frail individuals showed more severe OA on X-ray (67% vs. 31%, P ≤ 0.01) and higher SUVmax on 18 F-FDG PET/CT (4.1 vs. 3.6, P < 0.05) compared to non-frail individuals. Genetic correlation between frailty and OA was significant (rg = 0.532, P = 4.230E-88). Cross-trait analyses identified 42 genomic loci and 138 genes shared between the conditions. COLOC analysis revealed 2 pleiotropic loci, while TWAS identified 27 significant shared genetic expressions in whole blood and musculoskeletal tissue. Bidirectional MR indicated that OA increases the risk of frailty (IVW: beta: 0.13, P = 1.52E-08) and vice versa (IVW: beta: 0.73, P = 1.66E-04). Frail individuals exhibit more severe imaging features of OA. The shared genetic basis between OA and frailty suggests an intrinsic link, providing new insights into the relationship between these conditions., Competing Interests: The authors declared that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (AJNMMI Copyright © 2024.)

Background: Associations between thyroid diseases and psychiatric disorders have been mainly described before. However, the genetic mechanism behind hypothyroidism and psychiatric disorders remains unexplained., Methods: We examined the genetic architecture of hypothyroidism and 8 psychiatric disorders. Firstly, the global and local genetic relationship between the paired traits was explored. Secondly, cross-trait analysis was performed to investigate the genomic loci and genes between psychiatric disorders and hypothyroidism. Thirdly, the significant expression of these genes and the causal relationships were investigated. Lastly, enrichment analysis was conducted on these genes to explore their biological mechanisms., Results: We observed significant positive genetic correlations between psychiatric disorders and hypothyroidism. The cross-trait meta-analysis identified 62 shared genetic loci between hypothyroidism and psychiatric disorders. The colocalization analysis additionally revealed 15 potential pleiotropic loci with a posterior probabilities.H4 (PP·H4) value >0.7. We also found 2308 genes shared between both traits, which were highly enriched in biological pathways such as immune cell differentiation and autoimmune diseases, as well as in tissue structures like the frontal cortex and cerebral cortex. Especially, many pleiotropic genes were significantly expressed for multiple pairwise traits, such as BCL11B, RERE, and SUOX. Lastly, the Latent causal variable model (LCV) analysis did not find any causal components in the genetic structure between them., Limitations: The limitations of this study include that the conclusions were drawn from a European population., Conclusions: These findings not only deepens our understanding of their biological mechanisms but also has significant implications for the intervention and treatment of these diseases., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Activated macrophages are key effector cells and specific markers in patients with rheumatoid arthritis (RA). Cysteine cathepsin B (CTS-B) is highly expressed in macrophages and positively associated with RA activity and severity. This study aims to evaluate an activity-based multi-modality diagnostic agent, 68 Ga-BMX2, which targets CTS-B to visualize the arthritis activity and evaluate the treatment efficacy. A CTS-B activity-based probe, BMX2, was labeled efficiently with 68 Ga to produce 68 Ga-BMX2 for fluorescent and positron emission tomography (PET) multi-modality imaging. The affinity and specificity of BMX2 binding with the CTS-B enzyme in macrophages were determined by radioactive experiment using RAW 264.7 cell lines, with CA074 and BMX5 as the inhibitors to test the specificity of the binding. Then, PET and fluorescence imaging were acquired on collagen-induced arthritis (CIA) mice. Additionally, the treatment monitoring capability of 68 Ga-BMX2 PET/CT imaging was tested with methotrexate (MTX). RAW 264.7 macrophage cells showed significant uptake of 68 Ga-BMX2. The binding of BMX2 with CTS-B in RAW 264.7 macrophage cells is time-dependent and could be blocked by CA074 and BMX5. In vivo optical and PET imaging showed high signals in the right hind arthritis in CIA mice from 68 Ga-BMX2 and BMX2 accumulated for at least 120 h. Additionally, 68 Ga-BMX2 signals were significantly reduced in the MTX-treated CIA mice compared to the control group. The 68 Ga-BMX2, a radioactive and fluorescent dual-modality diagnostic agent targeting CTS-B, demonstrated a practical approach for CIA PET and fluorescence imaging. The 68 Ga-BMX2 multimodality imaging could significantly monitor the treatment response in the CIA mice., Competing Interests: The authors declared that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (AJNMMI Copyright © 2024.)

Abnormal macrophage polarization is one of the common pathological bases of various inflammatory diseases. The current research focus involves targeting macrophages to remodel their phenotype as a treatment approach for inflammatory diseases. Notably, exosomes can be delivered to specific types of cells or tissues or inflammatory area to realize targeted drug delivery. Although icariin (ICA) exhibits regulatory potential in macrophage polarization, the practical application of ICA is impeded by its water insolubility, poor permeability, and low bioavailability. Exploiting the inherent advantages of exosomes as natural drug carriers, we introduce a novel drug delivery system-adipose-derived stem cells-exosomes (ADSCs-EXO)-ICA. High-performance liquid chromatography analysis confirmed a loading rate of 92.7 ± 0.01 % for ADSCs-EXO-ICA, indicating the successful incorporation of ICA. As demonstrated by cell counting kit-8 assays, ADSCs-EXO exerted a significantly higher promotion effect on macrophage proliferation. The subsequent experimental results revealed the superior anti-inflammatory effect of ADSCs-EXO-ICA compared to individual treatments with EXO or ICA in the lipopolysaccharide + interferon-gamma-induced M1 inflammation model. Additionally, results from enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and western blot analyses revealed that ADSCs-EXO-ICA effectively inhibited macrophage polarization toward the M1-type and concurrently promoted polarization toward the M2-type. The underlying mechanism involved the modulation of macrophage polarization through inhibition of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factor-kappa B signaling pathway, thereby mitigating inflammation. These findings underscore the potential therapeutic value of ADSCs-EXO-ICA as a novel intervention for inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

Background: This study aims to explore the genetic architecture shared between Attention-Deficit/Hyperactivity Disorder (ADHD) and risk behavior., Methods: Based on the latest large-scale Genome-wide association studies (GWAS), we firstly employed Linkage disequilibrium score regression (LDSC) and Local Analysis of Variant Association (LAVA) to investigate the genetic correlation between risk behavior and ADHD. Then, we conducted cross-trait analysis to identified the Pleiotropic loci. Finally, bidirectional Mendelian randomization analysis (MR) was applied to examine the causal relationship., Results: We found a significant positive genetic correlation between ADHD and risk-taking behavior (rg = 0.351, p = 6.50E-37). The cross-trait meta-analysis identified 27 significant SNPs shared between ADHD and risk behavior. The most significant locus, located near the CADM2 gene on chromosome 3, had been identified associated with this two trait (pADHD = 3.07E-05 and prisk-taking behavior = 2.47E-30). The same situation can also be observed near the FOXP2 gene on chromosome 7 (rs8180817, pmeta = 5.72E-21). We found CCDC171 gene and other genes played a significant role in ADHD and risk behavior in mRNA level. Bidirectional MR analysis found a causal relationship between them., Limitation: The majority of our data sources were of European origin, which may limit the generalizability of our findings to other ethnic populations., Conclusion: This article reveals in depth the shared genetic structure between ADHD and risk-taking behavior, finding a significant positive genetic correlation between ADHD and risk-taking behavior. Providing insights for the future treatment and management of these two traits., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Noninvasively and accurately predicting the epidermal growth factor receptor (EGFR) mutation status is a clinically vital problem. Moreover, further identifying the most suspicious area related to the EGFR mutation status can guide the biopsy to avoid false negatives. Deep learning methods based on computed tomography (CT) images may improve the noninvasive prediction of EGFR mutation status and potentially help clinicians guide biopsies by visual methods. Inspired by the potential inherent links between EGFR mutation status and invasiveness information, we hypothesized that the predictive performance of a deep learning network can be improved through extra utilization of the invasiveness information. Here, we created a novel explainable transformer network for EGFR classification named gated multiple instance learning transformer (GMILT) by integrating multi-instance learning and discriminative weakly supervised feature learning. Pathological invasiveness information was first introduced into the multitask model as embeddings. GMILT was trained and validated on a total of 512 patients with adenocarcinoma and tested on three datasets (the internal test dataset, the external test dataset, and The Cancer Imaging Archive (TCIA) public dataset). The performance (area under the curve (AUC) =0.772 on the internal test dataset) of GMILT exceeded that of previously published methods and radiomics-based methods (i.e., random forest and support vector machine) and attained a preferable generalization ability (AUC =0.856 in the TCIA test dataset and AUC =0.756 in the external dataset). A diameter-based subgroup analysis further verified the efficiency of our model (most of the AUCs exceeded 0.772) to noninvasively predict EGFR mutation status from computed tomography (CT) images. In addition, because our method also identified the "core area" of the most suspicious area related to the EGFR mutation status, it has the potential ability to guide biopsies.

Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication, developing and designing antidotes with superior detoxification capacity and revealing their underlying mechanisms remains a major challenge. Therefore, we developed the first next-generation probiotic E. coli 1917 -pSK18a-MT that delivers metallothionein (MT) to overcome Cd-induced liver injury in C57BL/6 mice by utilizing bacterial surface display technology. The results demonstrate that E. coli 1917 -pSK18a-MT could efficiently express MT without altering the growth and probiotic properties of the strain. Moreover, we found that E. coli 1917 -pSK18a-MT ameliorated Cd contamination-induced hepatic steatosis, inflammatory cell infiltration, and liver fibrosis by decreasing the expression of aminotransferases along with inflammatory factors. Activation of the Nrf2-Keap1 signaling pathway also further illustrated the hepatoprotective effects of the engineered bacteria. Finally, we showed that E. coli 1917 -pSK18a-MT improved the colonic barrier function impaired by Cd induction and ameliorated intestinal flora dysbiosis in Cd-poisoned mice by increasing the relative abundance of the Verrucomicrobiota. These data revealed that the combination of E. coli 1917 and MT both alleviated Cd-induced liver injury to a greater extent and restored the integrity of colonic epithelial tissues and bacterial dysbiosis.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Liu, Zhang, Ye, Yi, Fan, Zhao and Liu.)

Ion mobility spectrometry (IMS) has a promising application prospect in food surveillance. However, due to the complexity of food matrix and trace levels of pesticide residues, the effective and rapid detection of pesticides by IMS has been a challenge, especially when using electrospray ionization (ESI) as an ion source. In this study, low-temperature partitioning with dispersive solid-phase extraction (LTP-dSPE) was explored and compared with conventional procedures. Both methods were validated for the quantification of eight pesticides in apples, obtaining a limit of detection (LOD) of 0.02-0.12 mg/kg for LTP-dSPE and 0.02-0.09 mg/kg for conventional solid-phase extraction (SPE), lower than those usually stipulated by government legislation in food matrices. For LTP-dSPE, the matrx effect (ME) ranged from -16.3 to -68.6 %, lower than that for the SPE method, ranging from -70.0 to -92.9 %. The results showed satisfactory efficiency and precision, with recovery values ranging from 67.9 to 115.4 % for LTP-dSPE and from 62.0 to 114.8 % for conventional SPE, with relative standard deviations below 13.0 %. Notably, the proposed LTP-dSPE/ESI-IMS has been shown to be more cost-effective, easier to use, more environment-friendly, more accessible, and, most importantly, less matrix effect than the conventional method, thereby being suitably applicable to a wide range of food safety applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Observational studies have reported high comorbidity between obesity and severe COVID-19. The aim of this study is to explore whether genetic factors are involved in the co-occurrence of the two traits. Based on the available genome-wide association studies (GWAS) summary statistics, we explored the genetic correlation and performed cross-trait meta-analysis (CPASSOC) and colocalization analysis (COLOC) to detect pleiotropic single nucleotide polymorphisms (SNPs). At the genetic level, we obtained genes detected by Functional mapping and annotation (FUMA) and the Multi-marker Analysis of GenoMic Annotation (MAGMA). Potential functional genes were further investigated by summary-data-based Mendelian randomization (SMR). Finally, the casualty was identiied using the latent causal variable model (LCV). A significant positive genetic correlation was revealed between obesity and COVID-19. We found 331 shared genetic SNPs by CPASSOC and 13 shared risk loci by COLOC. At the genetic level, We obtained 3546 pleiotropic genes, among which 107 genes were found to be significantly expressed by SMR. Lastly, we observed these genes were mainly enriched in immune pathways and signaling transduction. These indings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Fan and Liu.)

A method for the rapid and simultaneous determination of carbendazim and thiabendazole residues by electrospray ionization-ion mobility spectrometry (ESI-IMS) combined with a metal ion-assisted technique was developed and validated in different fruit matrices. The metal ion assisted strategy was performed instead of tedious pre-separation procedures to overcome the limitation of low resolution of IMS. Four transition metal cations, Co(II), Ni(II), Cu(II), and Zn(II), were screened and their interactions with carbendazim and thiabendazole were investigated. The injection flow rate and metal ion concentration were optimized. The Cu(II) assisted approach helped to achieve well-separated peaks with a peak-to-peak resolution of 3.61. This method was then applied to detect carbendazim and thiabendazole simultaneously in apples, pears, bananas, and mangoes. The limit of detection (LOD) were 0.03 mg kg -1 and 0.13 mg kg -1 for carbendazim and thiabendazole, respectively, while spiked recoveries were 61.5-122.0% and 83.5-119.8%, respectively, with RSDs less than 13.9%. These satisfactory evaluation parameters indicated that the approach was capable of performing quantitative analysis of multi-pesticide residues. In addition, the feasibility of using metal ion assisted-ESI-IMS for the simultaneous detection also was theoretically demonstrated through molecular electrostatic potential analysis and binding energy calculation based on density functional theory (DFT). Both experimental and theoretical results revealed the effectiveness of the metal ion assisted strategy in improving the resolution of ESI-IMS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Observational research and medical trials have suggested a connection between gut microbiota and glioblastoma, but it remains unclear if the relationship is causal. Method: A two-sample Mendelian randomization (MR) study was conducted by employing data from the MiBioGen consortium's largest genome-wide association study (n=18340) and the FinnGen consortium R8 release information (162 cases and 256,583 controls). Inverse variance weighted (IVW), weighted median estimator (WME), weighted model, MR-Egger, simple mode, and MR-PRESSO were used to determine the causal relationship between gut microbiota and glioblastoma. Reverse MR analysis was also performed on bacteria identified as causally related to glioblastoma. Results: Seven causal relationships were identified between genetic liability in the gut microbiota and glioblastoma, involving various bacterial families and genera. No significant causal effect was found on gut microbiota from glioblastoma, and no significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was observed. Conclusion: A two-sample MR analysis reveals a causal association between the gut microbiota and glioblastoma, highlighting the need for more investigation to comprehend the processes behind this association., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Postmenopausal osteoporosis (PMOP) has increased in prevalence in recent years, thus researchers have evaluated alternative medicine therapies. Fructus Ligustri Lucidi (FLL) can inhibit bone loss, and ferroptosis serves an important role in osteoporosis. Therefore, the present study assessed the presence of ferroptosis in PMOP and whether FLL could inhibit ferroptosis to improve bone microstructure in ovariectomized rats. Ovariectomized rats were treated with FLL (1.56 g/kg/day) for 12 weeks. Micro-CT was performed to evaluate the bone microstructure and bone mineral density. Western blotting and reverse transcription-quantitative PCR were performed to assess the relative expression levels of proteins and mRNA. Subsequently, malondialdehyde (MDA) and Fe 2+ assay kits were used to quantify the MDA and Fe 2+ content, respectively. The results demonstrated that ovariectomy (OVX) resulted in iron overload and the accumulation of lipid peroxide. Furthermore, the expression of key factors that inhibited ferroptosis, glutathione peroxidase 4 and solute carrier family 7 member 11 was significantly downregulated in ovariectomized rats, which was significantly reversed by FLL treatment. Furthermore, bone formation was assessed using the expression of osteogenesis-related genes, runt-related transcription factor 2 and osterix, which revealed significantly higher levels in FLL-treated rats compared with ovariectomized rats. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also significantly recovered following FLL treatment. In the present study, OVX of postmenopausal osteoporotic rats was found to induce ferroptosis by enhancing lipid peroxidation and Fe 2+ levels. FLL significantly suppressed ferroptosis, protected the osteogenic ability of ovariectomized rats and promoted the Nrf2/HO-1 signaling pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Li et al.)

Cognitive impairment is a significant concern in aging populations. This study utilized Mendelian randomization analysis to explore the impact of dietary habits and macro-nutrients on cortical structure. A bidirectional Mendelian randomization approach was employed, incorporating large-scale genetic data on dietary habits and brain cortical structure. The results did not reveal significant causal relationships between dietary factors and overall cortical structure and thickness. However, specific dietary factors showed associations with cortical structure in certain regions. For instance, fat intake affected six cortical regions, while milk, protein, fruits, and water were associated with changes in specific regions. Reverse analysis suggested that cortical thickness influenced the consumption of alcohol, carbohydrates, coffee, and fish. These findings contribute to understanding the potential mechanisms underlying the role of dietary factors in cognitive function changes and provide evidence supporting the existence of the gut-brain axis.

The aim of this study is to investigate the pathological changes in cardiac function, blood pressure, blood lipids and bone metabolism in ovariectomized (OVX) rats, as well as the intervention effect of Guizhi Longgu Muli decoction (GZLM). Bilateral oophorectomy was used to establish an OVX menopausal model. Four groups of rats were randomly selected: Sham surgery group, OVX group, estradiol (0.018g/L) and GZLM group (20g/kg). Cardiac function was assessed using ultrasound, blood pressure was measured using the tail cuff method. The oxidase method was used to determine the total cholesterol (TC) and triglycerides in serum. Direct measurement of high-density lipoprotein and low-density lipoprotein levels (LDL-C). Hematoxylin eosin staining and electron microscopy examination of myocardial structure. Microscopic CT was used to determine the bone microstructure. GZLM improved pathological cardiac changes and reduced the LVIDs, LVVols and LVVold. There was a decrease in systolic pressure, diastolic pressure and mean blood pressure in GZLM group. A decrease in serum TC and LDL-C levels was observed in the GZLM group. The BMD, BV/TV, Tb.Th, Tb.N of GZLM group raised, while Tb.SP and SMI significantly decreased or decreased. GZLM may have the effect of improving abnormal cardiac structure and function, promoting bone metabolism in OVX rats.

Importance: The clinical manifestations and effects on the brain of the SARS-CoV-2 Omicron variant in the acute postinfection phase remain unclear., Objective: To investigate the pathophysiological mechanisms underlying clinical symptoms and changes to gray matter and subcortical nuclei among male patients after Omicron infection and to provide an imaging basis for early detection and intervention., Design, Setting, and Participants: In this cohort study, a total of 207 men underwent health screening magnetic resonance imaging scans between August 28 and September 18, 2022; among them, 98 provided complete imaging and neuropsychiatric data. Sixty-one participants with Omicron infection were reevaluated after infection (January 6 to 14, 2023). Neuropsychiatric data, clinical symptoms, and magnetic resonance imaging data were collected in the acute post-Omicron period, and their clinical symptoms were followed up after 3 months. Gray matter indexes and subcortical nuclear volumes were analyzed. Associations between changes in gray matter and neuropsychiatric data were evaluated with correlation analyses., Exposures: Gray matter thickness and subcortical nuclear volume change data were compared before and after Omicron infection., Main Outcomes and Measures: The gray matter indexes and subcutaneous nuclear volume were generated from the 3-dimensional magnetization-prepared rapid acquisition gradient echo and were calculated with imaging software., Results: Ninety-eight men underwent complete baseline data collection; of these, 61 (mean [SD] age, 43.1 [9.9] years) voluntarily enrolled in post-Omicron follow-up and 17 (mean [SD] age, 43.5 [10.0] years) voluntarily enrolled in 3-month follow-up. Compared with pre-Omicron measures, Beck Anxiety Inventory scores were significantly increased (median, 4.50 [IQR, 1.00-7.00] to 4.00 [IQR, 2.00-9.75]; P = .006) and depressive distress scores were significantly decreased (median, 18.00 [IQR, 16.00-20.22] to 16.00 [IQR, 15.00-19.00]; P = .003) at the acute post-Omicron follow-up. Fever, headache, fatigue, myalgia, cough, and dyspnea were the main symptoms during the post-Omicron follow-up; among the participants in the 3-month follow-up, fever (11 [64.7%] vs 2 [11.8%]; P = .01), myalgia (10 [58.8%] vs 3 (17.6%]; P = .04), and cough (12 [70.6%] vs 4 [23.5%]; P = .02) were significantly improved. The gray matter thickness in the left precuneus (mean [SD], 2.7 [0.3] to 2.6 [0.2] mm; P < .001) and right lateral occipital region (mean [SD], 2.8 [0.2] to 2.7 [0.2] and 2.5 [0.2] to 2.5 [0.2] mm; P < .001 for both) and the ratio of the right hippocampus volume to the total intracranial volume (mean [SD]. 0.003 [0.0003] to 0.003 [0.0002]; P = .04) were significantly reduced in the post-Omicron follow-up. The febrile group had reduced sulcus depth of the right inferior parietal region compared with the nonfebrile group (mean [SD], 3.9 [2.3] to 4.8 [1.1]; P = .048. In the post-Omicron period, the thickness of the left precuneus was negatively correlated with the Beck Anxiety Inventory scores (r = -0.39; P = .002; false discovery rate P = .02), and the ratio of the right hippocampus to the total intracranial volume was positively correlated with the Word Fluency Test scores (r = 0.34; P = .007)., Conclusions and Relevance: In this cohort study of male patients infected with the Omicron variant, the duration of symptoms in multiple systems after infection was short. Changes in gray matter thickness and subcortical nuclear volume injury were observed in the post-Omicron period. These findings provide new insights into the emotional and cognitive mechanisms of an Omicron infection, demonstrate its association with alterations to the nervous system, and verify an imaging basis for early detection and intervention of neurological sequelae.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system. However, whether and how cortical changes occur in NMOSD with normal-appearing brain tissue, or whether any cortical changes correlate with clinical characteristics, is not completely clear. The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age, sex, and educational background from December 2020 to February 2022. A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness, sulcal depth, and gyrification index. Analysis showed that cortical thickness in the bilateral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants. Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes, those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus, superior parietal cortex, and pericalcarine cortex. Correlation analysis indicated that cortical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale. These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue, and that the degree of thinning is correlated with clinical disability and cognitive function. These findings will help improve our understanding of the imaging characteristics in NMOSD and their potential clinical significance., Competing Interests: None

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 imaging (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. Substantial heterogeneity was observed among the studies included. The meta-regression showed that the leave-one-out cross-validation (loocv) (sensitivity: p  < 0.01, specificity: p  < 0.001), graph theory (sensitivity: p  < 0.05, specificity: p  < 0.01), n  > 100 (sensitivity: p  < 0.001, specificity: p  < 0.001), simens equipment (sensitivity: p  < 0.01, specificity: p  < 0.001), 3.0T field strength (Sensitivity: p  < 0.001, specificity: p  = 0.04), and Beck Depression Inventory (BDI) (sensitivity: p  = 0.04, specificity: p  = 0.06) might be the sources of heterogeneity. Furthermore, the subgroup analysis showed that the sample size ( n  > 100: sensitivity: 0.71, specificity: 0.72, n  < 100: sensitivity: 0.81, specificity: 0.79), the different levels of disease evaluated by the Hamilton Depression Rating Scale (HDRS/HAMD) (mild vs. moderate vs. severe: sensitivity: 0.52 vs. 0.86 vs. 0.89, specificity: 0.62 vs. 0.78 vs. 0.82, respectively), the depression scales in patients with comparable levels of severity. (BDI vs. HDRS/HAMD: sensitivity: 0.86 vs. 0.87, specificity: 0.78 vs. 0.80, respectively), and the features (graph vs. functional connectivity: sensitivity: 0.84 vs. 0.86, specificity: 0.76 vs. 0.78, respectively) 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 these classification algorithms in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhao, Yi and Liu.)

Background : Brain imaging results in sleep deprived patients showed structural changes in the cerebral cortex; however, the reasons for this phenomenon need to be further explored. Methods : This MR study evaluated causal associations between morningness, ease of getting up, insomnia, long sleep, short sleep, and the cortex structure. Results : At the functional level, morningness increased the surface area (SA) of cuneus with global weighted (beta(b) (95% CI): 32.63 (10.35, 54.90), p = 0.004). Short sleep increased SA of the lateral occipital with global weighted (b (95% CI): 394.37(107.89, 680.85), p = 0.007. Short sleep reduced cortical thickness (TH) of paracentral with global weighted (OR (95% CI): -0.11 (-0.19, -0.03), p = 0.006). Short sleep reduced TH of parahippocampal with global weighted (b (95% CI): -0.25 (-0.42, -0.07), p = 0.006). No pleiotropy was detected. However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and the five types of sleep traits met the threshold. Conclusions : Our results potentially show evidence of a higher risk association between neuropsychiatric disorders and not only paracentral and parahippocampal brain areas atrophy, but also an increase in the middle temporal zone. Our findings shed light on the associations of cortical structure with the occurrence of five types of sleep traits.

Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. Recent studies have demonstrated that DIO reduces bone loss. This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. Raw reads were filtered to remove chimera sequences. Operational taxonomic units (OTUs) were clustered in the filtered reads. A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. LEfSe analysis was conducted to evaluate the specific GM of the three groups. The GM functions were analyzed using the KEGG and CAZy databases. After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. DIO treatment improved the bone microstructure and structural parameters of rat tibias. Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. The percentage of common OTUs was 41.2%. Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia&#95;idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids&#95;uniformis, Bacteroids&#95;xylanisolvens. The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the most effective measures to control the coronavirus disease 2019 (COVID-19) pandemic. However, there is still lack of an ideal detection platform capable of high sample throughput, portability, and multiplicity. Herein, by combining Hive-Chip (capillary microarray) and reverse transcriptional loop-mediated isothermal amplification (RT-LAMP), we developed an iPad-controlled, high-throughput (48 samples at one run), portable (smaller than a backpack), multiplex (monitoring 8 gene fragments in one reaction), and real-time detection platform for SARS-CoV-2 detection. This platform is composed of a portable Hi ve-Chip device ( Hi Cube; 32.7 × 29.7 × 20 cm, 5 kg), custom-designed software, and optimized Hive-Chips. RT-LAMP primers targeting seven SARS-CoV-2 genes (S, E, M, N, ORF1ab, ORF3a, and ORF7a) and one positive control (human RNase P) were designed and prefixed in the Hive-Chip. On-chip RT-LAMP showed that the limit of detection (LOD) of SARS-CoV-2 synthetic RNAs is 1 copy/μL, and there is no cross-reaction among different target genes. The platform was validated by 100 clinical samples of SARS-CoV-2, and the results were highly consistent with those of the traditional real-time PCR assay. In addition, on-chip detection of 6 other respiratory pathogens showed no cross-reactivity. Overall, our platform has great potential for fast, accurate, and on-site detection of SARS-CoV-2.

Vigorous-intensity leisure-time physical activity, such as marathon, has become increasingly popular, but its effect on immune functions and health is poorly understood. Here, we performed scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) after a bout of symptom-limited cardiopulmonary exercise (CPX) test or marathon. Time-series single-cell analysis revealed the detailed series of landscapes of immune cells in response to short and long vigorous-intensity activities. Reduction of effective T cells was observed with the cell migration and motility pathways enriched in circulation following marathon. Baseline values of PBMCs abundance were reached around 1 h after CPX and 24 h following marathon, but longer time was required for expression recovery of cytotoxicity genes. The ratio of effector/naive T cells was found to change uniformly among the participants and could serve as a better indicator for exercise intensity than the CD4+/CD8+ T cell ratio. Moreover, we identified time-dependent monocyte state transitions after marathon., Competing Interests: Authors declare that they have no competing interests., (© 2023 The Author(s).)

A sufficient intake of folic acid is essential during pregnancy, but several genetic polymorphisms reduce its absorption, threaten the lives of pregnant women and cause congenital disabilities in newborns. Traditional laboratory detection of genetic variants related to folic acid metabolism is time-consuming and labor-intensive. Microfluidics-based molecular diagnosis integrates sample pre-processing and nucleic acid amplification on-chip to achieve rapid, sensitive, high-throughput, and automated detection. Here, we developed a fully integrated microfluidic system for the detection of genetic polymorphisms related to folic acid metabolism in a "sample in-answer out" style. The system consists of nucleic acid extraction and amplification modules. During nucleic acid extraction, blood cells are lysed, and DNA is captured and eluted through a silica-gel membrane. After that, multiple gene loci are detected using loop-mediated isothermal amplification (LAMP) and the color of the reaction chamber indicates whether genetic mutations are present. The experimental results demonstrate that the system can accurately detect gene polymorphisms associated with folic acid metabolism in blood samples with high sensitivity and no cross-contamination between chambers. The blood samples of five patients were tested for mutant alleles on this system, and the test results were consistent with qPCR and DNA sequencing observations. The operation is fully automated, and the detection is completed in approximately 70 minutes. The proposed system has great potential in prenatal diagnosis and other types of nucleic acid detection.

Objective: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Li, Cheng, Liu, Zhao, Liu, Chen, Sun, Zhai, Wu, Yan, Sun and Zhang.)

Introduction: Dairy products have long been regarded as a controversial nutrient for the skin. However, a clear demonstration of donkey milk (DM) on skincare is required., Methods: In this study, spectrum and chemical component analyses were applied to DM. Then, the effects of DM on UVB-induced skin barrier damage and melanin pigmentation were first evaluated in vitro and in vivo . Cell survival, animal models, and expression of filaggrin (FLG) were determined to confirm the effect of DM on UVB-induced skin barrier damage. Melanogenesis and tyrosinase (TYR) activity were assessed after UVB irradiation to clarify the effect of DM on whitening activities. Further, a network pharmacology method was applied to study the interaction between DM ingredients and UVB-induced skin injury. Meanwhile, an analysis of the melanogenesis molecular target network was developed and validated to predict the melanogenesis regulators in DM., Results: DM was rich in cholesterols, fatty acids, vitamins and amino acids. The results of evaluation of whitening activities in vitro and in vivo indicated that DM had a potent inhibitory effect on melanin synthesis. The results of effects of DM on UVB‑induced skin barrier damage indicated that DM inhibited UVB-induced injury and restored skin barrier function via up-regulation expression of FLG (filaggrin). The pharmacological network of DM showed that DM regulated steroid biosynthesis and fatty acid metabolism in keratinocytes and 64 melanin targets which the main contributing role of DM might target melanogenesis, cell adhesion molecules (CAMs), and Tumor necrosis factor (TNF) pathway., Discussion: These results highlight the potential use of DM as a promising agent for whitening and anti-photoaging applications., Competing Interests: FL and YF were employed by Dong-E-E-Jiao Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RD declared a shared affiliation with the authors LX, AL, HH, YC, JT, and LL to the handling editor at the time of review., (Copyright © 2023 Li, He, Chen, Liao, Tang, Li, Fan, Li, and Xiong.)

Ethnopharmacological Relevance: Er-Xian decoction (EXD) is a traditional Chinese medicine (TCM) formula used to treat osteoporosis (OP). However, the anti-OP mechanism of EXD has not yet been fully elucidated., Aim of the Study: The study aimed to verify the anti-OP effect of EXD and to explore its underlying mechanism., Methods: The anti-OP targets and mechanisms of EXD were predicted by network pharmacological analysis. Then, an ovariectomized (OVX) rat model was established to validate the key anti-OP mechanism of EXD. Firstly, the therapeutic effect of EXD on OP was confirmed using micro-CT bone analysis, pathological observation, and ELISA detection. Secondly, serum metabolites related to key biological processes were detected using an automatic biochemical analyzer and GC-MS. Finally, ELISA, qRT-PCR, and western blot were utilized to further explore the potential key anti-OP pathway of EXD., Results: A total of 159 anti-OP targets of EXD were identified. Functional annotation revealed that OP treatment using EXD was associated with lipid metabolism, fatty acid (FA) metabolism, and PI3K/AKT signaling pathway. Experimental studies confirmed that EXD ameliorated ovariectomy-induced bone loss and bone microstructure deterioration. EXD treatment also upregulated the level of serum estrogen and downregulated the level of OC, PⅠNP, CTX-1, TC, and LDL-C. Besides, principal component analysis (PCA) and heat map of serum FAs distinguished OVX rats from the SHAM and EXD groups. Serum concentrations of important n-3 FAs, including C20:3N3, C20:5N3, and C22:5N3, were significantly increased in the EXD group. The increased stearoyl-CoA desaturase 1 (SCD1) index 1 and index 2 in the OVX group were reversed by EXD administration. Additionally, EXD reversed the decreased serum IGF1 level and tibia IGF1R, PI3K, and AKT expression in OVX rats., Conclusion: EXD ameliorated ovariectomy-induced bone loss by modulating lipid metabolism, FA metabolism, and IGF1/PI3K/AKT pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and purpose: Long COVID with regard to the neurological system deserves more attention, as a surge of treated patients are being discharged from the hospital. As the dynamic changes in white matter after two years remain unknown, this characteristic was the focus of this study. Methods: We investigated 17 recovered COVID-19 patients at two years after discharge. Diffusion tensor imaging, neurite orientation dispersion and density imaging were performed to identify white matter integrity and changes from one to two years after discharge. Data for 13 revisited healthy controls were collected as a reference. Subscales of the Wechsler Intelligence scale were used to assess cognitive function. Repeated-measures ANOVA was used to detect longitudinal changes in 17 recovered COVID-19 patients and 13 healthy controls after one-year follow-up. Correlations between diffusion metrics, cognitive function, and other clinical characteristics (i.e., inflammatory factors) were also analyzed. Results: Longitudinal analysis showed the recovery trends of large-scale brain regions, with small-scale brain region deterioration from one year to two years after SARS-CoV-2 infection. However, persistent white matter abnormalities were noted at two years after discharge. Longitudinal changes of cognitive function showed no group difference. But cross-sectional cognitive difference between recovered COVID-19 patients and revisited HCs was detected. Inflammation levels in the acute stage correlated positively with white matter abnormalities and negatively with cognitive function. Moreover, the more abnormal the white matter was at two years, the greater was the cognitive deficit present. Conclusion: Recovered COVID-19 patients showed longitudinal recovery trends of white matter. But also had persistent white matter abnormalities at two years after discharge. Inflammation levels in the acute stage may be considered predictors of cognition and white matter integrity, and the white matter microstructure acts as a biomarker of cognitive function in recovered COVID-19 patients. These findings provide an objective basis for early clinical intervention., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The long-term effects of COVID-19 on brain structure remain unclear. A prospective study was conducted to explore the changes in brain structure in COVID-19 survivors at one and two years after discharge (COVID-19 one , COVID-19 two ). The difference in gray matter volume (GMV) was analyzed using the voxel-based morphometry method, and correlation analyses were conducted. The dynamic changes in clinical sequelae varied. The GMVs in the cerebellum and vermis were reduced in COVID-19 one and COVID-19 two , positively correlated with lymphocyte count, and negatively correlated with neutrophil count, neutrophil/lymphocyte ratio (COVID-19 one ), and systemic immune-inflammation index (COVID-19 two ). The decreased GMVs in the left middle frontal gyrus, inferior frontal gyrus of the operculum, right middle temporal gyrus, and inferior temporal gyrus returned to normal in COVID-19 two . The decreased GMV in the left frontal lobe was negatively correlated with the Athens Insomnia Scale (AIS). The GMV in the left temporal lobe was aggravated in COVID-19 two and positively correlated with C-reactive protein. In conclusion, GMV recovery coexisted with injury, which was associated with AIS and inflammatory factors. This may shed some light on the dynamic changes in brain structure and the possible predictors that may be related to GMV changes in COVID-19 two ., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

The purpose of this study is to determine whether preoperative 6-minute walk test (6MWT) is associated with prolonged postoperative hospitalization in high risk patients with severe tricuspid regurgitation (TR) after transcatheter tricuspid valve replacement (TTVR). Forty-one patients with severe TR who underwent TTVR and discharged between September 2018 and April 2021 were enrolled in this study. Patients were divided into 2 groups according to whether the postoperative hospital stay was >10 days and patients' data were retrospectively collected. 6MWT was performed before operation. Twenty-one patients were in the control group (≤10 days) and 20 patients were in the prolonged postoperative stay (PPS) group (>10 days). 6MWT distance was significantly decreased in PPS group (192.70 ± 62.34 vs 274.57 ± 52.09 m, P < .05). PPS group had more patients with severe liver disease (50.00% vs 19.05%, P < .05), higher systolic pulmonary artery pressure (45.05 ± 9.28 vs 35.57 ± 8.91 mm Hg, P < .05) and longer procedure time (159.85 ± 56.61 vs 124.43 ± 31.67 min, P < .05). Multivariable logistic regression analysis found 6MWT <267 m was an independent risk factor with the odds ratio of 10.95 (1.66-72.39, P < .05) for prolonged postoperative hospitalization in patients who received TTVR. In the present study, we identified that preoperative decreased 6MWT distance was an independent risk factor for prolonged hospitalization in high risk TR patients after TTVR., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study is aimed at predicting and contrasting the mechanisms of artemisinin (ARS), dihydroartemisinin (DHA), artesunate (ART), artemether (ARM), and arteether (ARE) in the treatment of osteoporosis (OP) using network pharmacology and molecular docking., Methods: The targets of ARS, DHA, ART, ARM, and ARE were obtained from the SwissTargetPrediction. The targets related to OP were obtained from the TTD, DrugBank, Genecards, and DisGeNet databases. Then, the anti-OP targets of ARS, DHA, ART, ARM, and ARE were obtained and compared using the Venn diagram. Afterward, the protein-protein interaction (PPI) networks were built using the STRING database, and Cytoscape was used to select hub targets. Moreover, molecular docking validated the binding association between five molecules and hub targets. Finally, GO enrichment and KEGG pathway enrichment were conducted using the DAVID database. The common pathways of five molecules were analysed., Results: A total of 28, 37, 36, 27, and 33 anti-OP targets of ARS, DHA, ART, ARM, and ARE were acquired. EGFR, EGFR, CASP3, MAPK8, and CASP3 act as the top 1 anti-OP targets of ARS, DHA, ART, ARM, and ARE, respectively. MAPK14 is the common target of five molecules. All five molecules can bind well with these hubs and common targets. Meanwhile, functional annotation showed that MAPK, Serotonergic synapse, AMPK, prolactin, and prolactin signaling pathways are the top 1 anti-OP pathway of ARS, DHA, ART, ARM, and ARE, respectively. IL-17 signaling pathway and prolactin signaling pathway are common anti-OP pathways of five molecules. Besides, GO enrichment showed five biological processes and three molecular functions are common anti-OP mechanisms of five molecules., Conclusion: ARS, DHA, ART, ARM and ARE can treat OP through multi-targets and multi pathways, respectively. All five molecules can treat OP by targeting MAPK14 and acting on the IL-17 and prolactin signaling pathways., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Yujie Ma et al.)

Aims: Abnormal changes in cardiac function have been reported in menopausal women, but there are few clinical studies on this topic. Erxian decoction (EXD) is a classic prescription that is widely used in the treatment of female menopausal diseases. The purpose of this study was to investigate the dynamic evolution of cardiac function and glucose and lipid metabolism in ovariectomized (OVX) rats and the intervention effect of EXD., Materials and Methods: The OVX climacteric rat model was established by bilateral ovariectomy. After successful modeling, the rats were randomly divided into four groups: the sham operation (SHAM) group (equal volumes of purified water), OVX group (equal volumes of purified water), estradiol (E 2 ) group (1.8 × 10 -4  g/kg), and EXD group (9 g/kg). Each group of rats was treated for 16 weeks. At the 4 th , 8 th , 12 th , and 16 th weeks after treatment, the cardiac function of the rats in each group was evaluated by ultrasound. The coaxial method was used to measure blood pressure (BP). Serum endothelin-1 (ET-1) and angiotensin-2 (Ang II) levels were determined by the enzyme-linked immunosorbent assay (ELISA). The strip method was used to measure fasting blood glucose (FBG). The serum total cholesterol (TC) and triglyceride (TG) levels of rats were measured with the oxidase method. Direct methods were used to measure serum high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. At week 16 of dosing, serum E 2 levels were determined by E 2 radioimmunoassay. The myocardium and uterus of the rats in each group were stained with HE (hematoxylin-eosin). The ultrastructure of the rat myocardium was observed by electron microscopy., Results: After the 16 th week of treatment, the serum E 2 level decreased ( P < 0.05), and the uterus was atrophied in OVX rats. The cardiac ejection fraction (EF%) decreased at 4 weeks after treatment, and systolic and diastolic function decreased after 12 weeks. After the 16 th week, the EF%, which reflects the "pump" function of the heart, decreased significantly ( P < 0.05 or P < 0.01). At the 4 th , 8 th , 12 th , and 16 th weeks of treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean pressure (MBP) of the rats in the OVX group increased with time ( P < 0.05 or P < 0.01). The serum ET-1 and Ang II levels of rats in the OVX group increased ( P < 0.05 or P < 0.01). In the OVX group, FBG was increased ( P < 0.05 or P < 0.01), and blood lipids, especially LDL-C, were significantly increased ( P < 0.05 or P < 0.01). After the 16 th week of treatment, the myocardial tissue of OVX rats showed obvious pathological changes. EXD significantly increased serum E 2 levels ( P < 0.01), decreased ET-1 and Ang II levels ( P < 0.01), reduced the cardiac function risk factors BP, FBG, and blood lipids, and significantly improved cardiac function and structural changes in OVX rats ( P < 0.05 or P < 0.01)., Conclusions: EXD can improve abnormal cardiac structure and function in OVX rats., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yuhan Wang et al.)

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 2×104 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Image-guided percutaneous lung ablation has proven to be an alternative and effective strategy in the treatment of lung cancer and other lung malignancies. Radiofrequency ablation, microwave ablation, and cryoablation are widely used ablation modalities in clinical practice that can be performed along or combined with other treatment modalities. In this context, this article will review the application of different ablation strategies in lung malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shang, Li, Zhang, Wu, Chen, Li, Zhao and Liu.)

Introduction: Major depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment., Materials and Methods: Twenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week's treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients., Results: There were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS., Conclusion: The decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy., Competing Interests: HZ was employed by MR Scientific Marketing, Siemens Healthineers Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yi, Wang, Yang, Huang, Liu, Chen, Zhang, Zhao, Li, Fang and Liu.)

Osteoclasts (OCs) are multinucleated cells that play a major role in osteolytic diseases such as osteoporosis. Monascin (Ms) is one of the active substances in the traditional Chinese medicine red yeast rice. Studies have found that red yeast rice can maintain bone health. In this study, the anti-osteoclastogenesis effects of Ms on RANKL-induced RAW264.7 cells were assessed, and the underlying mechanism was investigated. Ms exhibited inhibitory effects on OC differentiation and formation in a dose-dependent manner and suppressed the bone-resorbing activity of mature OCs. Ms blocked OCs-typical genes (c-Fos, NFATc1, CSTK, MMP-9, TRAP, ITG-β3, OSCAR and DC-STAMP). Furthermore, Ms treatment considerably inhibited the activation of MAPKs, JNK and p38. Taken together, Ms suppresses RANKL-induced osteoclastogenesis of RAW264.7 cells by restraining MAPKs signaling pathways and is a potential therapeutic option as a novel OC inhibitor to mitigate bone erosion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cheng, Liu, Li, Ma, Song, Wang, Li, Chen and Zhang.)

The dielectric characteristics in the terahertz region contribute to a revealing insight into the material components and provide intermolecular information. The dielectric properties of adulterated honey, described as the real and imaginary parts of the complex dielectric constant (Re[ε] and Im[ε]), were obtained from 0.3 to 1.5 THz. The relationship between invert syrup proportions and complex dielectric constants at different frequencies implied the possibility of using the dielectric property as an indicator of honey authenticity. The selected effective dielectric variables of Re[ε] and Im[ε] and their combination were chosen by stability competitive adaptive reweighted sampling (SCARS) algorithm and then used to establish PLS models. The accuracy and uncertainty result revealed SCARS-PLS model based on the combination of Re[ε] and Im[ε] is the best model relatively. These findings indicated the potential utility of this rapid, non-destructive, and on-site method for authenticity verification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Adulteration of food ingredients, particularly replacement of high-value milk with low-cost milk, affects food safety. For rapid and accurate identification of the possible adulterating milk species in an unknown sample, a centrifugal microfluidic chip-based real-time fluorescent multiplex loop-mediated isothermal amplification (LAMP) assay was developed to simultaneously detect milk from cow, camel, horse, goat, and yak. Using precoated primers in different reaction wells, the centrifugal microfluidic chip markedly simplified the detection process and reduced false-positive results. The entire amplification was completed within 90 min with a genomic detection limit of 0.05 ng/µL in cow, camel, horse, and goat milk and 0.005 ng/µL in yak milk. Using simulated adulterated samples for validation, the detection limit for adulterated milk samples was 2.5%, satisfying authentication requirements, as the proportion of adulterated milk higher than 10% affects economic interests. Therefore, this simple, centrifugal, microfluidic chip-based multiplex real-time fluorescent LAMP assay can simultaneously detect common milk species in commercial products to enable accurate labeling., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Redness is the most common symptom among many facial dermatoses. With the rapid development of optical instruments, spectral imaging, and image processing technology, there appear varieties of skin color analysis methods and instruments. The aim of this study is to reveal the differences and correlations in measuring the facial redness between CSKIN ® and VISIA ® , as well as the relevance between the instrument parameters and clinical evaluation., Materials & Methods: Forty-three Chinese patients were enrolled. Images were taken and analyzed by VISIA ® from Canfield and CSKIN ® from Yanyun Technology, and the facial erythema was graded by the dermatologists., Results: Feature counts within the red areas measured by VISIA ® were found to have significantly positive correlations with red pixels and percent which were measured by CSKIN ® on both sides of the face (r = .45 ~ .566, P < .01). The parameters analyzed by CSKIN ® and VISIA ® feature counts were correlated with visual scores graded by the dermatologists, VISIA ® presented with a weak correlation (r = .213, P < .05), while CSKIN ® had a moderate correlation with the visual scores (r = .472 ~ .492, P < .001)., Conclusion: CSKIN ® may be another alternative option when encountering with measurement and follow-up of facial erythema., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The present study aimed to assess the perturbation in circular RNA (circRNA)/mRNA expression profiles and a circRNA-miRNA-mRNA coexpression network involved in the potential protective effect of diosgenin (DIO) on alveolar bone loss in rats subjected to ovariectomy (OVX)., Methods: The Wistar rats (female) manipulated with sham operation were classified as the SHAM group and the grouping of OVX rats administered with DIO, estradiol valerate or vehicle for 12 weeks was DIO group, EV group and OVX group respectively. Following treatments, the plasmatic levels of osteocalcin and tumor necrosis factor-alpha and the microstructure of alveolar bone were assayed. Based on microarray analyses, we identified differentially expressed (DE) circRNAs and mRNAs in alveolar bone of rats in both OVX and DIO group. The DE circRNAs and DE mRNAs involved in the bone metabolism pathway validated by RT-qPCR were considered key circRNAs/mRNAs. On the basis of these key circRNAs/mRNAs, we predicted the overlapping relative miRNAs of key circRNAs/mRNAs, and a circRNA-miRNA-mRNA network was built., Results: DIO showed an anti-osteopenic effect on the rat alveolar bone loss induced by OVX. In total, we found 10 DE circRNAs (6 downregulated and 4 upregulated) and 614 DE mRNAs (314 downregulated and 300 upregulated) in samples of the DIO group compared with those of the OVX group. However, only one circRNA (rno&#95;circRNA&#95;016717) and seven mRNAs (Sfrp1, Csf1, Il1rl1, Nfatc4, Tnfrsf1a, Pik3c2g, and Wnt9b) were validated by qRT-PCR and therefore considered key circRNA/mRNAs. According to these key circRNA/mRNAs and overlapping predicted miRNAs, a coexpression network was constructed. After network analysis, one circRNA-miRNA-mRNA axis (circRNA&#95;016717/miR-501-5p/Sfrp1) was identified., Conclusion: The mechanism of DIO inhibiting alveolar bone loss after OVX is possibly relevant to the simultaneous inhibition of osteogenesis and osteoclastogenesis by mediating the expression of important molecules in the Wnt, PI3K, RANK/RANKL or osteoclastogenic cytokine pathways. The circRNA&#95;016717/miR-501-5p/Sfrp1 axis may play important roles in these processes.

Many metal deposits were formed by carbonic fluids (rich in CO 2 ) as indicated by fluid inclusions in minerals, but the precise role of CO 2 in metal mineralization remains unclear. The main components in fluid inclusions, i.e. H 2 O and CO 2 , correspond to the decomposed products of organic acids, which lead us to consider that in the mineralization process the organic acids transport and then discharge metals when they are stable and unstable, respectively. Here we show that the thermal stability of copper acetate solution at 15-350 °C (0.1-830 MPa) provides insight as to the role of organic acids in metal transport. Results show that the copper acetate solution is stable at high P-T conditions under low geothermal gradient of <19 °C/km, with an isochore of P = 1.89 T + 128.58, verifying the possibility of copper transportation as acetate solution. Increasing geothermal gradient leads to thermal dissociation of copper acetate in the way of 4Cu(CH 3 COO) 2 + 2H 2 O = 4Cu + 2CO 2 + 7CH 3 COOH. The experimental results and inferences in this contribution agree well with the frequently observed fluid inclusions and wall-rock alterations of carbonate, sericite and quartz in hydrothermal deposits, and provide a new dimension in the understanding of the role of CO 2 during mineralization.

The present study aimed to assess the changes in circulating microRNA (miRNA) expression profiles associated with the potential osteoprotective effect of diosgenin (DIO) in ovariectomized (OVX) rats. Wistar rats (female) were subjected to a sham operation (SHAM group) or ovariectomy. OVX rats were treated with DIO (DIO group) or vehicle (OVX group) for 12 weeks. Following treatment, the serum estradiol, bone turnover biomarker levels, and the microarchitecture of tibias were assayed. Based on miRNA microarray and qRT-PCR analyses, differentially expressed (DE) circulating miRNAs were identified between the OVX and SHAM groups (comparison A) and between the DIO and OVX groups (comparison B). Furthermore, putative target genes of shared DE miRNAs with opposite expression trends in the two comparisons were predicted by ingenuity pathway analysis (IPA). Finally, the expression levels of the putative target genes in serum and tibia were validated by qRT-PCR. The micro-CT results demonstrated that DIO had a substantial anti-osteopenic effect on the tibias of OVX rats. In total, we found 5 DE circulating miRNAs (four upregulated and one downregulated) in comparison A and 21 DE circulating miRNAs (15 upregulated and 6 downregulated) in comparison B. However, only one DE circulating miRNA (rno-miR-20a-5p) had opposite expression trends between the two comparisons. Including rno-miR-20a-5p, 7 of the 10 selected DE circulating miRNAs between the two comparisons passed qRT-PCR validation. Specifically, based on qRT-PCR validation, DIO upregulated the expression of rno-miR-20a-5p and downregulated that of three target genes ( Tnf , Creb1 , and Tgfbr2 ) of the "osteoclast differentiation" pathway in the tibias of OVX rats. Our results suggested that DIO could change the circulating miRNA profile of OVX rats and inhibited the downregulation of miR-20a-5p in serum and tibia. DIO might exert an anti-osteoclastogenic effect on OVX rats by upregulating the expression of miR-20a-5p in circulation and bone tissue., (Copyright © 2020 Zhang, Xiang, Wang, Jiang, Cheng, Xiao, Ju and Chen.)

Background: Postoperative prolonged ventilation time (PPVT) is associated with increased mortality in acute type A aortic dissection (ATAAD). The aim of this study is to investigate risk factors for PPVT in ATAAD patients., Methods: We retrospectively collected ATAAD patient data for those who received modified aortic root procedure and extensive arch repair between June 2017 and June 2018 at our institution. Patients were included in PPVT (N = 30) and No-PPVT (N = 72) groups, according to whether postoperative ventilation time > 72 hours. Univariate and multivariate logistic regression analysis were adopted to determine the independent risk factors for PPVT., Results: More female in the PPVT Group (56.67% versus 23.61%, P < .05). Max diameter (MD) of ascending aorta was wider in the PPVT Group (4.71 ± 1.02 versus 4.30 ± 0.61, P < .05). Postoperative data showed a higher in-hospital mortality in the PPVT Group (26.67% versus 5.56%, P < .05). There were more patients in the PPVT Group who experienced postoperative acute renal failure (ARF) (36.67% versus 5.56%, P < .05). Multivariable logistic regression analysis showed female gender, MD of ascending aorta > 4.05 cm, and postoperative ARF were independent risk factors for PPVT with the OR of 3.55 (1.13 - 11.20, P < .05), 2.89 (1.02 - 8.22, P < .05), and 4.31 (1.03 - 18.02, P < .05), respectively., Conclusions: In the present study, we determined female gender, MD of ascending aorta > 4.05 cm, and postoperative ARF within 72 hours were independent risk factors for PPVT in ATAAD patients received modified root procedure and extensive arch repair.

Hydrothermal ore deposits at convergent plate boundaries represent extraordinary metal enrichment in the continental crust. They are generally associated with felsic magmatism in extensional settings at high thermal gradients. Although their formation is common during accretionary orogeny, more and more ore deposits have been discovered recently in the collisional orogens of China. Because collisional orogeny was operated in a compressional regime at low thermal gradients, it is not favorable for mobilization of ore-forming elements and thus for the production of hydrothermal ore deposits. Nevertheless, continental collision is generally preceded by oceanic subduction, which enables the preliminary enrichment of ore-forming elements in the mantle wedge due to chemical metasomatism by subducting slab-derived fluids. This gave rise to metal pre-enriched domains in the overriding lithosphere, which may be reactivated by extensional tectonism for hydrothermal mineralization either immediately during accretionary orogeny or at a later time during and after collisional orogeny. It is these tectonic processes that have resulted in the progressive enrichment of ore-forming elements through the geochemical differentiation of the subducting oceanic crust, the metasomatic mantle domains and the mafic juvenile crust, respectively, at different depths. Finally, the reactivation of metal pre-enriched domains by continental rifting in the orogenic lithosphere is the key to the metallogenesis of collisional orogens., (Copyright © 2019 Science China Press. Published by Elsevier B.V. All rights reserved.)

The present study assessed the changes in long non-coding (lnc)RNA and mRNA expression profiles when diosgenin (DIO) exerted a potential osteoprotective effect on the alveolar bone of ovariectomized (OVX) rats. Female Wistar rats underwent a sham operation (SHAM group) or ovariectomy. OVX rats were treated using vehicle (OVX group), DIO (DIO group) or estradiol valerate (EV group) for 12 weeks. After treatment, the biomarkers of bone turnover in plasma and the microstructure of alveolar bone were assessed. lncRNA microarrays were applied to assess lncRNA and mRNA expression profiles in alveolar bone in the OVX and DIO group rats. Subsequently, the differentially expressed mRNAs associated with the comprehensive bone metabolism pathway in Ingenuity Pathway Analysis (IPA) were identified and regarded as key mRNAs. Based on some of the key mRNAs and all the differentially expressed lncRNAs, a coexpression network was established and this network was further analyzed to identify the top 6 lncRNAs with the highest closeness scores (pivotal lncRNAs). Finally, 6 modules showing interactions between pivotal lncRNAs and key mRNAs were constructed. All of the pivotal lncRNAs and key mRNAs were validated with reverse transcription-quantitative polymerase chain reaction. The present findings demonstrated that DIO suppressed the loss of alveolar bone in OVX rats, and the changes to the expression of some lncRNAs or mRNAs occurred in the alveolar bone of the rats in the DIO group. Twenty-four key mRNAs were identified during pathway analysis. Furthermore, 8/24 key mRNAs ( Ctnnb1, Smad4, Tcf2, Sp7, Il1b, Il1r1, Tnf and Tnfrsf1a ) were used to establish a coexpression network, which included 1,656 nodes and 5,341 edges. During network analysis, 6 pivotal lncRNAs (XR&#95;008346, MRuc007iji, MRAK157089, MRAK076413, MRAK143591 and AB036696) were obtained, and 6 modules illustrating pivotal lncRNA-key mRNA interactions were identified. These results revealed that the anti-osteoporotic effect of DIO on alveolar bone may be associated with the promotion of a bone formation process through increasing the signaling of the Wnt and BMPs pathways and the inhibition of the bone resorption process through decreasing stimulators of osteoclastogenesis. To conclude, several pivotal lncRNAs may serve important roles in these processes via regulating some key mRNAs in the bone metabolism pathway.

A pipette-actuated capillary array comb (PAAC) system operated on a smartphone-based hand-held device has been successfully developed for the multiplex detection of bacteria in a "sample-to-answer" manner. The PAAC consists of eight open capillaries inserted into a cylindrical plastic base with a piece of chitosan-modified glass filter paper embedded in each capillary. During the sample preparation, a PAAC was mounted into a 1 mL pipette tip with an enlarged opening and was operated with a 1 mL pipette for liquid handling. The cell lysate was drawn and expelled through the capillaries three times to facilitate the DNA capture on the embedded filter discs. Following washes with water, the loop-mediated isothermal amplification (LAMP) reagents were aspirated into the capillaries, in which the primers were pre-fixed with chitosan. After that, the PAAC was loaded into the smartphone-based device for a one-hour amplification at 65 °C and end-point detection of calcein fluorescence in the capillaries. The DNA capture efficiency of a 1.1 mm-diameter filter disc was determined to be 97% of λ-DNA and the coefficient of variation among the eight capillaries in the PAAC was only 2.2%. The multiplex detection of genomic DNA extracted from Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus provided limits of detection of 200, 500, and 500 copies, respectively, without any cross-contamination and cross reactions. "Sample-to-answer" detection of E. coli samples was successfully completed in 85 minutes, demonstrating a sensitivity of 200 cfu per capillary. The multiplex "sample-to-answer" detection, the streamlined operation, and the compact device should facilitate a broad range of applications of our PAAC system in point-of-care testing.

Background: Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model., Methods: We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17β-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings., Results: The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium., Conclusion: EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level.