Selenium binding protein 1 protects renal tubular epithelial cells from ferroptosis by upregulating glutathione peroxidase 4.

Ferroptosis is a form of programmed cell death involved in various types of acute kidney injury (AKI). It is characterized by inactivation of the selenoprotein, glutathione peroxidase 4 (GPX4), and upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Since urinary selenium binding protein 1 (SBP1/SELENBP1) is a potential biomarker for AKI, this study investigated whether SBP1 plays a role in AKI. First, we showed that SBP1 is expressed in proximal tubular cells in normal human kidney, but is significant downregulated in cases of AKI in association with reduced GPX4 expression and increased ACSL4 expression. In mouse renal ischemia-reperfusion injury (I/R), the rapid downregulation of SBP1 protein levels preceded downregulation of GPX4 and the onset of necrosis. In vitro, hypoxia/reoxygenation (H/R) stimulation in human proximal tubular epithelial (HK-2) cells induced ferroptotic cell death in associated with an acute reduction in SBP1 and GPX4 expression, and increased oxidative stress. Knockdown of SBP1 reduced GPX4 expression and increased the susceptibility of HK-2 cells to H/R-induced cell death, whereas overexpression of SBP1 reduced oxidative stress, maintained GPX4 expression, reduced mitochondrial damage, and reduced H/R-induced cell death. Finally, selenium deficiency reduced GPX4 expression and promoted H/R-induced cell death, whereas addition of selenium was protective against H/R-induced oxidative stress. In conclusion, SBP1 plays a functional role in hypoxia-induced tubular cell death. Enhancing SBP1 expression is a potential therapeutic approach for the treatment of AKI.

Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

[Traditional Chinese medicine used as anti-aging agent by targeting nuclear factor erythroid 2-related factor 2 signaling pathway].

The imbalance of redox homeostasis is a major characteristic of aging and contributes to the pathogenesis of various aging-related diseases. As a regulatory hub of redox homeostasis, nuclear factor erythroid 2-related factor 2 (NRF2) can attenuate oxidative stress by activating the transcription of many antioxidant enzymes. China is the birthplace of traditional Chinese medicine (TCM) which has been wildly used as medicine for thousands of years. Recently, TCM as anti-aging medicine has attracted enormous attention. Focusing on the NRF2 signaling pathway, this paper summarizes the correlation between various anti-aging TCM and the NRF2 signaling, and discusses the common key mechanisms by which TCM slows the aging process by targeting the NRF2 signaling network.

Comparison of the Metabolomics of Different Dendrobium Species by UPLC-QTOF-MS.

Dendrobium Sw. (family Orchidaceae) is a renowned edible and medicinal plant in China. Although widely cultivated and used, less research has been conducted on differential Dendrobium species. In this study, stems from seven distinct Dendrobium species were subjected to UPLC-QTOF-MS/MS analysis. A total of 242 metabolites were annotated, and multivariate statistical analysis was employed to explore the variance in the extracted metabolites across the various groups. The analysis demonstrated that D. nobile displays conspicuous differences from other species of Dendrobium. Specifically, D. nobile stands out from the remaining six taxa of Dendrobium based on 170 distinct metabolites, mainly terpene and flavonoid components, associated with cysteine and methionine metabolism, flavonoid biosynthesis, and galactose metabolism. It is believed that the variations between D. nobile and other Dendrobium species are mainly attributed to three metabolite synthesis pathways. By comparing the chemical composition of seven species of Dendrobium, this study identified the qualitative components of each species. D. nobile was found to differ significantly from other species, with higher levels of terpenoids, flavonoids, and other compounds that are for the cardiovascular field. By comparing the chemical composition of seven species of Dendrobium, these qualitative components have relevance for establishing quality standards for Dendrobium.

Tinosporae radix: A Review of Traditional Use, Botany, Phytochemistry, Bioactivity, and Quality Marker.

BACKGROUND: Tinosporae radix is the root tuber of Tinospora capillipes Gagnep of the Menispermaceae family. It has the effects of clearing away heat and toxins, benefiting the throat, relieving pain, and treating sore throat, carbuncle and boils, and other diseases in clinical practice. METHODS: The related references about T. radix in this review were collected by online databases, including PubMed, Elsevier, Web of Science, Willy, SciFinder, SpringLink, Google Scholar, Baidu Scholar, ACS publications, Scopus, and CNKI. The other information about T. radix was acquired from ancient books and classical works. RESULTS: T. radix is an important medicinal plant with a variety of traditional uses according to the theory of Chinese medicine. Previous studies revealed that T. radix contained a variety of chemical components, including diterpenoids, alkaloids, steroids, cinnamic acid derivatives, and other compounds. Many pharmacological researches have exhibited that T. radix possesses various biological activities, including anti-cancer, hypoglycemic, anti-inflammatory, anti-bacterial, anti-ulcer, and anti-oxidant activities. Furthermore, the quality markers of T. radix were summarized and analyzed in this paper. CONCLUSION: The traditional use, botany, phytochemistry, bioactivity, and quality markers of T. radix were reviewed in this paper. It will not only provide an important clue for further studying T. radix, but also supply an important theoretical basis and a valuable reference for in-depth research and exploitations of this plant in the future.

Microbial modifications with Lycium barbarum L. oligosaccharides decrease hepatic fibrosis and mitochondrial abnormalities in mice.

BACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied. PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis. STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices). RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and ß-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis. CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.

Comprehensive genomic analysis of puerarin in inhibiting bladder urothelial carcinoma cell proliferation and migration.

BACKGROUND: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms. METHODS: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation. RESULTS: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218µmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients. CONCLUSION: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

Myricetin improves pathological changes in 3×Tg-AD mice by regulating the mitochondria-NLRP3 inflammasome-microglia channel by targeting P38 MAPK signaling pathway.

BACKGROUND: Alzheimer's disease (AD) represents the common neurodegenerative disease featured by the manifestations of cognitive impairment and memory loss. AD could be alleviated with medication and improving quality of life. Clinical treatment of AD is mainly aimed at improving the cognitive function of patients. Donepezil, memantine and galantamine are commonly used drug. But they could only relieve AD, not cure it. Therefore, new treatment strategies focusing on AD pathogenesis are of great significance and value. Myricetin (Myr) is a natural flavonoid extracted from Myrica rubra. And it shows different bioactivities, such as anti-inflammation, antioxidation as well as central nervous system (CNS) activities. Nonetheless, its associated mechanism in treating AD remains unknown. PURPOSE: Here we focused on investigating Myr's effect on treating AD and exploring if its protection on the nervous system activity was associated with specifically inhibiting P38 MAPK signaling pathway while regulating mitochondria-NLRP3 inflammasome-microglia. STUDY DESIGN AND METHODS: This work utilized triple transgenic mice (3 × Tg-AD) as AD models and Aß25-35 was used to induce BV2 cells to build an in vitro AD model. Behavioristics, pathology and related inflammatory factors were examined. Molecular mechanisms are investigated by western-blot, immunofluorescence staining, CETSA, molecular docking, network pharmacology. RESULTS: According to our findings, Myr could remarkably improve memory loss, spatial learning ability, Aß plaque deposition, neuronal and synaptic damage in 3 × Tg-AD mice through specifically inhibiting P38 MAPK pathway activation while restraining microglial hyperactivation. Furthermore, Myr promoted the transformation of microglial phenotype, restored the mitochondrial fission-fusion balance, facilitated mitochondrial biogenesis, and restrained NLRP3 inflammasome activation and neuroinflammation. For the in-vitro experiments, P38 agonist dehydrocorydaline (DHC) was utilized to confirm the key regulatory role of P38 MAPK signaling pathway on the mitochondria-NLRP3 inflammasome-microglia channel. CONCLUSIONS: Our results revealed the therapeutic efficacy of Myr in experimental AD, and implied that the associated mechanism is possibly associated with inhibiting tmitochondrial dysfunction, activating NLRP3 inflammasome, and neuroinflammation which was mediated by P38 MAPK pathway. Myr is the drug candidate in AD therapy via targeting P38 MAPK pathway.

[Biological mechanisms of Oxalis corniculata regulating human prostate cancer PC-3 cells: An investigation based on the NF-κB pathway].

OBJECTIVE: To investigate the biological mechanisms underlying the effect of the Chinese herbal medicine Oxalis corniculata on human prostate cancer PC-3 cells. METHODS: Through in vitro experiment, we treated human prostate cancer PC-3 cells with different concentrations of Oxalis corniculata, assessed the viability of the cells by MTT assay, examined their apoptosis by flow cytometry, evaluated their migration and invasiveness by Transwell assay, and determined the expressions of the proteins p65, p-p65, IκBα and p-IκBα in the NF-κB pathway using protein imprinting technology. RESULTS: Compared with the blank control, Oxalis corniculata significantly inhibited the proliferation and induced the apoptosis of the PC-3 cells (P< 0.05), suppressed their migration and invasiveness in a dose-dependent manner (P< 0.05), and upregulated the expression of IκBα and downregulated those of p-p65 and p-IκBα in the NF-κB pathway (P< 0.05). CONCLUSION: Oxalis corniculata can inhibit the proliferation, migration and invasiveness and induce the apoptosis of human prostate cancer PC cells, which may be attributed to its abilities of inhibiting the expressions of p-p65 and p-IκBα and regulating the activity of the NF-κB pathway.

[Action mechanisms of Xiaoluowan (II) in the treatment of epididymitis: A network pharmacology-based study].

OBJECTIVE: To explore the potential action mechanisms of Xiaoluowan (II) (XLW-II) in the treatment of epididymitis through a network pharmacology approach. METHODS: We searched various databases for relevant targets associated with epididymitis and XLW-II and obtained the common targets of epididymitis and XLW-II on the Venny platform. We acquired the protein-protein interactions (PPI) using the STRING data and had them visualized with the Cytoscape software. After topological analysis, we retrieved the key targets, followed by gene ontology (GO) and KEGG pathway enrichment analyses using the DAVID database. RESULTS: A total of 2 38 drug targets, 2 150 disease targets and 85 common targets were identified. The core targets for the treatment of epididymitis with XLW-II identified by PPI network analysis included TNF, IL6, IL1B, MMP9, AKT1, PTGS2 and TP53. GO function analysis revealed the involvement of the common targets in such biological processes as response to hypoxia, regulation of apoptotic processes, inflammatory response, and positive regulation of the MAPK cascade. KEGG pathway analysis suggested that the signaling pathways such as the cancer pathway, PI3K-Akt pathway, protein glycosylation pathway in cancer, Ras pathway and chemokine pathway might be related to the action mechanisms of XLW-II in the treatment of epididymitis. CONCLUSION: The potential targets and signaling pathways of Xiaoluowan (II) in the treatment of epididymitis were identified on the basis of network pharmacology, which has provided a novel insight into its action mechanisms and offered a new direction for further relevant studies.

Jerusalem artichoke inulin supplementation ameliorates hepatic lipid metabolism in type 2 diabetes mellitus mice by modulating the gut microbiota and fecal metabolome.

The main focus of this study was on the protection mechanism of Jerusalem artichoke inulin (DI) against type 2 diabetes mellitus (T2DM) associated with abnormal hepatic lipid metabolism and gut microbiota dysfunction in high-fat diet and streptozotocin-induced diabetic mice. It was determined that the consumption of DI significantly improved the biochemical parameters and physiological indices linked to T2DM, including the reduction in blood glucose, HbA1c, triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels as well as the contents of serum pro-inflammatory cytokines. Supplementation with DI also ameliorated abnormal hepatic lipid metabolism by altering the expression of genes involved in the production and breakdown of lipids and cholesterol. Microbiological analysis showed that DI supplementation resulted in an enrichment of Prevotellaceae UCG-001, Parasutterella, Prevotellaceae UCG-003, and Dubosiella. Metabolomics revealed 89 differential metabolites closely related to DI intervention, and showed that DI supplementation regulated amino acid metabolism (e.g., indole), lipid metabolism (e.g., phosphocholine), cofactor and vitamin metabolism (e.g., cholecalciferol), nucleotide metabolism (e.g., thymine) and the digestive system (e.g., 7-ketolithocholic acid). Overall, Jerusalem artichoke inulin has a remarkable capacity to ameliorate abnormal hepatic lipid metabolism and gut microbiota dysfunction linked to T2DM.

De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement.

Proteins containing the FERM (four-point-one, ezrin, radixin, and moesin) domain link the plasma membrane with cytoskeletal structures at specific cellular locations and have been implicated in the localization of cell-membrane-associated proteins and/or phosphoinositides. FERM domain-containing protein 5 (FRMD5) localizes at cell adherens junctions and stabilizes cell-cell contacts. To date, variants in FRMD5 have not been associated with a Mendelian disease in OMIM. Here, we describe eight probands with rare heterozygous missense variants in FRMD5 who present with developmental delay, intellectual disability, ataxia, seizures, and abnormalities of eye movement. The variants are de novo in all for whom parental testing was available (six out of eight probands), and human genetic datasets suggest that FRMD5 is intolerant to loss of function (LoF). We found that the fly ortholog of FRMD5, CG5022 (dFrmd), is expressed in the larval and adult central nervous systems where it is present in neurons but not in glia. dFrmd LoF mutant flies are viable but are extremely sensitive to heat shock, which induces severe seizures. The mutants also exhibit defective responses to light. The human FRMD5 reference (Ref) cDNA rescues the fly dFrmd LoF phenotypes. In contrast, all the FRMD5 variants tested in this study (c.340T>C, c.1051A>G, c.1053C>G, c.1054T>C, c.1045A>C, and c.1637A>G) behave as partial LoF variants. In addition, our results indicate that two variants that were tested have dominant-negative effects. In summary, the evidence supports that the observed variants in FRMD5 cause neurological symptoms in humans.

Combined metabolomics and proteomics to reveal beneficial mechanisms of Dendrobium fimbriatum against gastric mucosal injury.

As a dietary and medicinal plant, Dendrobium fimbriatum (DF) is widely utilized in China for improving stomach disease for centuries. However, the underlying mechanisms against gastric mucosal injury have not been fully disclosed. Here, metabolomics and proteomics were integrated to clarify the in-depth molecular mechanisms using cyclophosphamide-induced gastric mucosal injury model in mice. As a result, three metabolic pathways, such as creatine metabolism, arginine and proline metabolism, and pyrimidine metabolism were hit contributing to DF protective benefits. Additionally, γ-L-glutamyl-putrescine, cytosine, and thymine might be the eligible biomarkers to reflect gastric mucosal injury tatus, and DF anti-gastric mucosal injury effects were mediated by the so-called target proteins such as Ckm, Arg1, Ctps2, Pycr3, and Cmpk2. This finding provided meaningful information for the molecular mechanisms of DF and also offered a promising strategy to clarify the therapeutic mechanisms of functional foods.

Research into the mechanism of intervention of SanQi in endometriosis based on network pharmacology and molecular docking technology.

BACKGROUND: By using network pharmacology and molecular docking technology, we have explored the mechanism of action of Sanqi in the treatment of endometriosis (EMS), in order to provide reference for clinical studies of Chinese medicine treatment of Ems and Chinese medicine pharmacology. METHODS: There are 123 intersecting targets between the active ingredients of Sanqi and disease targets. In the Protein-Protein Interaction network, Jun proto-oncogene, AP-1 transcription factor subunit, tumor necrosis factor, interleukin 6, etc., are the core proteins. The top 20 genes ranked by degree have been analyzed according to the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analysis, and 20 pathways have been identified. RESULTS: On the Kyoto Encyclopedia of Genes and Genomes pathway, the most important part is the phosphatidylinositol 3'-kinase-Akt signaling pathway, and on the Gene Ontology pathway, it is the Heme binding. The top 3 targets docked to quercetin have a certain affinity when it is docked to their degree value. Among the chemical components of Sanqi, quercetin has the most targets, suggesting that it may play a major role in the treatment of EMS. CONCLUSION: The results of molecular docking provide further evidence of the potential role of Sanqi for EMS. Overall, our study provides a new direction for the treatment of EMS and provides the basis for Sanqi as a drug for the treatment of EMS.

Network pharmacological analysis and molecular docking of Huangqin-Baizhu herb pair in the treatment of threatened abortion.

BACKGROUND: The incidence of threatened abortion (TA) is increasing due to poor diet and living habits, which brings great pressure to pregnant women and their families. Huangqin-Baizhu herb pair recorded in ancient books of traditional Chinese medicine has been widely used in the treatment of TA with remarkable effect. In this study, we will use the network pharmacology method to predict the target and mechanism of Huangqin-Baizhu herb pair. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to screen the active components of Huangqin-Baizhu herb pair. Pubchem and Swiss Target Prediction databases were used to predict the action targets. Genecards, OMIM, and Drugbank databases were used to predict the related targets of TA. The intersection of drug target and disease target was selected and the intersection genes were uploaded to STRING database to construct protein-protein interaction network and conduct module analysis. Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which was imported into Cytoscape software to construct component-pathway-gene network and finally verified by molecular docking. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy. RESULTS: The main active components of the herb pair are baicalein, flavanone, and norwogonin, etc. The main targets are AKT1, VEGFA, STAT3, MAPK1, SRC, etc. Cluster module analysis shows that the targets are related to cell metabolism, immune regulation and hormone level regulation. There were 2073, 3169, and 161 KEGG pathways involved in the biological processes, cell components, and molecular functions of Gene Ontology analysis, respectively. The main KEGG pathways involved in the intervention were HIF1 signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway. Molecular docking showed that the main active components of the herb pair were well combined with the key targets. CONCLUSIONS: In this study, 42 active components, 152 potential targets and 11 key targets of Huangqin-Baizhu herb pair for the treatment of TA were revealed, participating in multiple signaling pathways such as PI3K-Akt, providing a theoretical basis for further experimental research.

Radon attenuation characteristics of compacted soil layer for uranium mill tailings pond subjected to drying-wetting cycles.

Compacted soil layer (CSL) is generally designed for uranium mill tailings (UMTs) pond to form the radon seals, whereas it is usually affected by drying-wetting environmental conditions. To summarize the radon attenuation degradation performance of CSL subjected to drying-wetting cycles, an experiment with the application of meteorological data was developed. This paper focuses on the evolution of the soil apparent porosity, soil integrity and radon attenuation characteristics of CSL during continuous drying-wetting cycles. Image processing and a nonmetal acoustic wave detector were applied to analyze variations in the soil surface and internal defects, and the radon concentration was measured to reveal the radon attenuation performance of the CSL. The results reveal that with successive drying-wetting cycles, the soil apparent porosity increased, and the soil pores were enlarged. The soil integrity underwent dynamic recombination or reorganization and eventually reached a steady state. Moreover, it was observed that the saturated state of the uppermost soil led to a sharp increase in radon concentration (capping effect), and the decrease in accumulated radon concentration during the initial period resulted from the coupling effect of soil moisture, temperature and ambient pressure. The observations confirm that the drying-wetting environmental conditions markedly affect the radon migration channels and environment in the CSL, which provides a theoretical foundation for UMTs pond governance and radiation safety management.

Exploring the relationship between osteoporosis and polycystic ovary syndrome based on bioinformatics.

BACKGROUND: In recent years, clinical studies have found that there is a close relationship between osteoporosis and polycystic ovary syndrome. However, there are few literature on the pathogenesis of osteoporosis and polycystic ovary syndrome. In order to clarify their common pathogenic mechanism and provide potential targets for drugs to regulate them at the same time, bioinformatics methods are used to explore, so as to provide a new direction for the study of the relationship between diseases in the future. METHODS: To screen the targets of osteoporosis and polycystic ovary syndrome by Genecards, Online Mendelian Inheritance in Man databases and Therapeutic Target Database to take the intersection of the two mappings and upload the intersection targets to the STRING database to construct protein-protein interaction network; to screen the core targets by degree value and import them to Metascape database for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis; and finally, to construct the visualization network of core targets and pathways by Cytoscape software. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy. RESULTS: The core targets of polycystic ovary syndrome and osteoporosis were insulin gene, insulin-like growth factor 1, CTNNB1, serine/threonine kinase 1, signal transducer and activator of transcription 3, LEP, etc. The biological processes involved include the regulation of protein phosphorylation, cell proliferation and differentiation, hormone endocrine, reproductive system and skeletal system. The related pathways were concentrated in Foxo signaling pathway, HTLV-I infection, PI3K-AKT signaling pathway, MAPK signaling pathway and AGE-RAGE signaling pathway in diabetic complications. CONCLUSIONS: There is a close relationship between osteoporosis and polycystic ovary syndrome in terms of target and molecular mechanism. This study used bioinformatics to clarify their targets and mechanisms, providing potential targets for drugs to regulate both diseases simultaneously and providing new directions to explore the relationship between the diseases.

Acupuncture Ameliorates Depressive Behaviors by Modulating the Expression of Hippocampal Iba-1 and HMGB1 in Rats Exposed to Chronic Restraint Stress.

The antidepressant mechanism of acupuncture has not been fully elucidated recently. Thus, the objective of the present study is to investigate the antidepressant mechanism of acupuncture of modulating the neuroinflammation induced by high mobility group box-1 (HMGB1) in rats subjected to chronic restraint stress (CRS). Forty-four male Sprague Dawley rats were randomly divided into control, model, escitalopram, and acupuncture group. Except for rats in the control group, all rats were exposed to CRS for 21 days continuously. Rats in the escitalopram group were subjected to a suspension of escitalopram and saline. One hour before CRS procedures, acupuncture was performed at Baihui (GV20) and Yintang (GV29) for rats in the acupuncture group, 20 min per day for 21 days. All rats in each group were conducted to detect the body weight, sucrose preference test at 0, 7, 14, 21 days to evaluate the depression-like behaviors. The expression of microglial activation and HMGB1 in the hippocampus was detected by immunofluorescence. The expression of hippocampal interleukin-10 (IL-10) was detected by western blot. And the content of serum tumor necrosis factor-α (TNF-α) was detected by the enzyme-linked immunosorbent assay method. CRS-exposed rats showed obviously decreased body weight and sucrose preference when compared with the control group, which was reversed by acupuncture. The results have also shown that acupuncture ameliorated the CRS-induced activation of microglia and HMGB1 in the hippocampus CA1 region. Furthermore, acupuncture reduced the stress-induced upregulation of TNF-α in serum. Collectively, the current study highlights the role of acupuncture in alleviating depressive behavior associated with stress-induced neuroinflammation mediated by HMGB1 in the CRS model of depression.

Superconductivity in Mo-P compounds under pressure and in double-Weyl semimetal Hex-MoP2.

Based on first-principles calculations, we predict five global stable molybdenum phosphorus compounds in the pressure range of 0-300 GPa. All of them display superconductivity with different transition temperatures. Meanwhile, we find that a metastable crystal hex-MoP2, crystallized in a noncentrosymmetric structure, is a double-Weyl semimetal and the Weyl point is in the H-K path. The long Fermi arcs and the topological surface states, which can be observed by angle-resolved photoemission spectroscopy, emerge at the (100) surface below the Fermi level. Furthermore, we find that the superconductivity in hex-MoP2 can be enhanced by carrier doping. Due to the breaking of inversion symmetry, the unconventional spin-triplet pairing coexists with spin-singlet pairing in channel . Based on our theoretical model, there are the superconducting band gaps in both pairings. Our work provides a new platform of hex-MoP2 for studying both topological double-Weyl semimetal and superconductivity.

The clinical application value of the extracellular-water-to-total-body-water ratio obtained by bioelectrical impedance analysis in people with advanced cancer.

OBJECTIVES: Body-composition analysis using bioelectrical impedance analysis is gradually becoming more widely used in clinical practice. The ratio of extracellular water (ECW) to total body water (TBW) is thought to be related to the prognosis of a variety of diseases. However, its performance in people with advanced cancer deserves further discussion. METHODS: A retrospective analysis was performed on 784 people with advanced cancer. Anthropometric indicators, serologic indicators, nutritional status, health-related quality of life, and body composition were analyzed. Participants were grouped into two groups according to ECW/TBW ratio. We used t tests and χ2 tests to analyze differences between the groups. Univariate and multivariate Cox regressions were conducted to analyze the factors influencing overall survival. Logistic regression was used to analyze the related factors of malnutrition, and linear regression for factors of health-related quality of life. RESULTS: Age, body mass index, Patient-Generated Subjective Global Assessment score, Karnofsky Performance Status questionnaire score, skeletal muscle mass index, and fat-free mass index were statistically different between the non-overhydrated and overhydrated groups. Univariate and multivariate Cox regression models showed that an ECW/TBW ≥ 0.40 is a risk factor for poor prognosis in people with advanced cancer (hazard ratio = 1.511; 95% confidence interval, 1.103-2.070; P = 0.010). Subgroup analyses were next conducted according to tumor type, with ECW/TBW ≥ 0.40 emerging as a risk factor for poor prognosis for people with advanced breast cancer and advanced gastric cancer. Logistic regression showed that ECW/TBW ≥ 0.40 is a risk factor for malnutrition in people with advanced cancer (odds ratio = 1.988; 95% confidence interval, 1.049-3.767; P = 0.035). The univariate and multivariate linear regression models showed that the ECW/TBW ratio is an influencing factor for health-related quality of life in the domains of physical functioning, role functioning, and constipation. CONCLUSION: We found that in people with cancer, an ECW/TBW ≥ 0.40 was a risk factor for malnutrition and lower health-related quality of life, and in people with advanced cancer, it was a risk factor for poor prognosis.