Impacts of ultrasound-assisted Fenton degradation and alkaline de-esterification on structural properties and biological effects of pectic polysaccharides from Tartary buckwheat leaves.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) leaf has abundant rhamnogalacturonan-I enriched pectic polysaccharides, which exert various health-promoting effects. Nevertheless, the potential relationship between the chemical structure and the biological function of pectic polysaccharides from Tartary buckwheat leaves (TBP) remains unclear. Therefore, to bridge the gap between the chemical structure and the biological function of TBP, the impacts of ultrasound-assisted Fenton degradation (UFD) and mild alkaline de-esterification (MAD) on structural properties and biological effects of TBP were systematically studied. Compared with the native TBP (molecular mass, 9.537 × 104 Da), the molecular masses of degraded TBPs (TBP-MMW, 4.811 × 104 Da; TBP-LMW, 2.101 × 104 Da) were significantly reduced by the UFD modification, while their primary chemical structures were overall stable. Besides, compared with the native TBP (esterification degree, 22.73 %), the esterification degrees of de-esterified TBPs (TBP-MDE, 14.27 %; TBP-LDE, 6.59 %) were notably reduced by the MAD modification, while their primary chemical structures were also overall stable. Furthermore, the results revealed that both UFD and MAD modifications could significantly improve the antioxidant, antiglycation, and immunostimulatory effects of TBP. Indeed, TBP's biological effects were negatively correlated to its molecular mass and esterification degree, while positively linked to its free uronic acids. The findings demonstrate that both UFD and MAD modifications are promising techniques for the structural modification of TBP, which can remarkedly promote its biological effects. Besides, the present results are conducive to better understanding TBP's structure-bioactivity relationship.

Lipid metabolism disorder in diabetic kidney disease.

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.

Prenatal and postnatal early life exposure to greenness and particulate matter of different size fractions in relation to childhood rhinitis - A multi-center study in China.

The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM1, PM2.5, and PM10) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0-1 year old) and the second (1-2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0-40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis.

The cellular expression patterns of gdnfa and gdnfb in the gonads of Nile tilapia and their differential response to retinoic acid.

In mammals, glial cell derived neurotrophic factor (GDNF) plays a critical role in the self-renewal and maintenance of spermatogonial stem cells (SSCs) in testis and oogenesis in ovary, whilst retinoic acid (RA), the key factor of meiosis initiation, can downregulate its expression. Unlike mammals, two Gdnf replication genes are widely present in teleost fishes, however, our understanding of them is still poor. In the present study, two paralogous gdnf from Nile tilapia (Oreochromis niloticus), namely as Ongdnfa and Ongdnfb, were characterized, and then their cellular expression profiles in testis and ovary and responsiveness to RA treatment at the tissue and cellular levels were investigated. In phylogenetic tree, the Gdnfa and Gdnfb from teleost fishes were clustered into two different subclasses, respectively, and then clustered with the homologs from cartilaginous fish and tetrapods, suggesting that OnGdnfa and OnGdnfb are orthologous to GDNF and paralogous to each other. Ongdnfa is expressed in Sertoli cells and Leydig cells in testis and oocytes in ovary. The expression pattern of Ongdnfb is similar to Ongdnfa. In the ex vivo testicular organ culture, RA down-regulated the expression of Ongdnfa, whereas up-regulated the expression of Ongdnfb (P < 0.05), suggesting that they have differential responsiveness to RA signaling. RA treatment of the cultured cells derived from adult Nile tilapia testis which have the expression of RA receptors (RAR), Ongdnfa and Ongdnfb further confirmed the above result. Collectively, our study suggests that Ongdnfa and Ongdnfb have non-germline expression patterns in testis and germline expression patterns in ovary; furthermore, they have differential responsiveness to RA signaling, implying that they might have differential biological functions. This study broadens and enriches our understanding of fish GDNF homologs and lays foundation for the study of their biological functions in the future.

The role of zyxin in signal transduction and its relationship with diseases.

This review highlighted the pivotal role of zyxin, an essential cell focal adhesions protein, in cellular biology and various diseases. Zyxin can orchestrate the restructuring and dynamic alterations of the cellular cytoskeleton, which is involved in cell proliferation, adhesion, motility, and gene transcription. Aberrant zyxin expression is closely correlated with tumor cell activity and cardiac function in both tumorigenesis and cardiovascular diseases. Moreover, in fibrotic and inflammatory conditions, zyxin can modulate cellular functions and inflammatory responses. Therefore, a comprehensive understanding of zyxin is crucial for deciphering signal transduction networks and disease pathogenesis. Investigating its role in diseases holds promise for novel avenues in early diagnosis and therapeutic strategies. Nevertheless, targeting zyxin as a therapeutic focal point presents challenges in terms of specificity, safety, drug delivery, and resistance. Nonetheless, in-depth studies on zyxin and the application of precision medicine could offer new possibilities for personalized treatment modalities.

Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years. The embryo is regarded as a semi-allogeneic graft to the mother. A successful pregnancy requires transition to an immune environment conducive to embryo survival at the maternal-fetal interface. As an important member of regulatory immunity, regulatory T (Treg) cells play a key role in regulating immune tolerance at the maternal-fetal interface. This review will focus on the phenotypic plasticity and lineage stability of Treg cells to illustrate its relationship with URSA.

Network medicine-based analysis of the hepatoprotective effects of Amomum villosum Lour. on alcoholic liver disease in rats.

Alcoholic liver disease (ALD) is characterized by high morbidity and mortality, and mainly results from prolonged and excessive alcohol use. Amomum villosum Lour. (A. villosum), a well-known traditional Chinese medicine (TCM), has hepatoprotective properties. However, its ability to combat alcohol-induced liver injury has not been fully explored. The objective of this study was to investigate the hepatoprotective effects of A. villosum in a rat model of alcohol-induced liver disease, thereby establishing a scientific foundation for the potential preventive use of A. villosum in ALD. We established a Chinese liquor (Baijiu)-induced liver injury model in rats. Hematoxylin and eosin (HE) staining, in combination with biochemical tests, was used to evaluate the protective effects of A. villosum on the liver. The integration of network medicine analysis with experimental validation was used to explore the hepatoprotective effects and potential mechanisms of A. villosum in rats. Our findings showed that A. villosum ameliorated alcohol-induced changes in body weight, liver index, hepatic steatosis, inflammation, blood lipid metabolism, and liver function in rats. Network proximity analysis was employed to identify 18 potentially active ingredients of A. villosum for ALD treatment. These potentially active ingredients in the blood were further identified using mass spectrometry (MS). Our results showed that A. villosum plays a hepatoprotective role by modulating the protein levels of estrogen receptor 1 (ESR1), anti-nuclear receptor subfamily 3 group C member 1 (NR3C1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). In conclusion, the results of the current study suggested that A. villosum potentially exerts hepatoprotective effects on ALD in rats, possibly through regulating the protein levels of ESR1, NR3C1, IL-6, and TNF-α.

Glycolic acid-induced disruption of epidermal homeostasis in a skin equivalent model: Insights into temporal dynamics and mechanisms.

Glycolic acid (GA) is extensively used in cosmetic formulations and skin peeling treatments but its adverse effects, notably severe disruption of epidermal structure, limit its clinical utility. However, the detailed impact of GA on epidermal homeostasis, including changes in structure and protein expression over time, is not fully understood. This study employed a reconstructed human epidermis (RHE) model to assess the effects of varying GA concentrations on epidermal proliferation, differentiation, and desquamation at different time points. Through histology, immunofluorescence, and immunohistochemistry, we observed that 35% GA concentration adversely caused abnormal epidermal homeostasis by affecting epidermal proliferation, differentiation and desquamation. Our findings reveal time-specific responses of key proteins to GA: Filaggrin, Involucrin, Loricrin, and Ki67 showed very early responses; KLK10 an early response; and AQP3 and K10 late responses. This research provides a detailed characterization of GA's effects in an RHE model, mimicking clinical superficial peeling and identifying optimal times for detecting GA-induced changes. Our results offer insights for designing interventions to mitigate GA's adverse effects on skin, enhancing the safety and efficacy of GA peeling treatments.

Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function.

BACKGROUND: Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. METHODS: Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni-NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. RESULTS: In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αß T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. CONCLUSION: Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

Evaluation of the Effectiveness of In-Hospital Exercise Rehabilitation in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus Combined with Sarcopenia Effect of Lifestyle Management on Disease Status in Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of this study was to explore the effects of in-hospital exercise rehabilitation on glucose and lipid metabolism and healthy physical fitness in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM) combined with sarcopenia, and to provide a reference for the effective implementation of exercise rehabilitation for middle-aged and elderly patients with T2DM combined with sarcopenia in healthcare institutions. METHODS: This study retrospectively included 122 patients with T2DM combined with sarcopenia treated at the General Hospital of Ningxia Medical University from August 2017 to August 2020 and randomly divided into a control group and an experimental group. The control group was given conventional treatment and the experimental group was given exercise rehabilitation in the hospital for 12 weeks to compare the indexes related to glucose and lipid metabolism and healthy fitness in the two groups. RESULTS: After the intervention, the experimental group showed significant decreases in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C) and body fat percentage (p < 0.05), while high-density cholesterol (HDL-C), grip strength, lower limb extension, lower limb flexion, peak oxygen uptake were significantly higher (p < 0.05) and were more significant at 12 weeks compared to the 6-week intervention (p < 0.05). However, there were no significant changes in any of the glucose metabolism indicators in the control group before and after the intervention. A two-way repeated measures ANOVA showed that at control baseline levels, HbA1c decreased significantly in the experimental group after both 6 and 12 weeks of intervention compared to the control group (p < 0.05). After 6 weeks of intervention, the experimental group showed a significant decrease in body fat percentage and a significant increase in grip strength. After 12 weeks of intervention, the experimental group showed an increase in glycemic control from 33.3% to 73.3%, a significant decrease in body fat percentage and a significant increase in grip strength, lower limb extension and lower limb flexion strength and peak oxygen uptake. CONCLUSION: In-hospital exercise rehabilitation can effectively improve the glycemic and lipid profiles of patients with T2DM combined with sarcopenia and enhance their health fitness, with good clinical rehabilitation effects.

Associations of Long-Term Exposure to Fine Particulate Constituents With Cardiovascular Diseases and Underlying Metabolic Mediations: A Prospective Population-Based Cohort in Southwest China.

BACKGROUND: The health effects of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) might differ depending on compositional variations. Little is known about the joint effect of PM2.5 constituents on metabolic syndrome and cardiovascular disease (CVD). This study aims to evaluate the combined associations of PM2.5 components with CVD, identify the most detrimental constituent, and further quantify the mediation effect of metabolic syndrome. METHODS AND RESULTS: A total of 14 427 adults were included in a cohort study in Sichuan, China, and were followed to obtain the diagnosis of CVD until 2021. Metabolic syndrome was defined by the simultaneous occurrence of multiple metabolic disorders measured at baseline. The concentrations of PM2.5 chemical constituents within a 1-km2 grid were derived based on satellite- and ground-based detection methods. Cox proportional hazard models showed that black carbon, organic matter (OM), nitrate, ammonium, chloride, and sulfate were positively associated with CVD risks, with hazard ratios (HRs) ranging from 1.24 to 2.11 (all P<0.05). Quantile g-computation showed positive associations with 4 types of CVD risks (HRs ranging from 1.48 to 2.25, all P<0.05). OM and chloride had maximum weights for CVD risks. Causal mediation analysis showed that the positive association of OM with total CVD was mediated by metabolic syndrome, with a mediation proportion of 1.3% (all P<0.05). CONCLUSIONS: Long-term exposure to PM2.5 chemical constituents is positively associated with CVD risks. OM and chloride appear to play the most responsible role in the positive associations between PM2.5 and CVD. OM is probably associated with CVD through metabolic-related pathways.

A biocompatible electrode/exoelectrogens interface augments bidirectional electron transfer and bioelectrochemical reactions.

Bidirectional electron transfer is about that exoelectrogens produce bioelectricity via extracellular electron transfer at anode and drive cytoplasmic biochemical reactions via extracellular electron uptake at cathode. The key factor to determine above bioelectrochemical performances is the electron transfer efficiency under biocompatible abiotic/biotic interface. Here, a graphene/polyaniline (GO/PANI) nanocomposite electrode specially interfacing exoelectrogens (Shewanella loihica) and augmenting bidirectional electron transfer was conducted by in-situ electrochemical modification on carbon paper (CP). Impressively, the GO/PANI@CP electrode tremendously improved the performance of exoelectrogens at anode for wastewater treatment and bioelectricity generation (about 54 folds increase of power density compared to blank CP electrode). The bacteria on electrode surface not only showed fast electron release but also exhibited high electricity density of extracellular electron uptake through the proposed direct electron transfer pathway. Thus, the cathode applications of microbial electrosynthesis and bio-denitrification were developed via GO/PANI@CP electrode, which assisted the close contact between microbial outer-membrane cytochromes and nanocomposite electrode for efficient nitrate removal (0.333 mM/h). Overall, nanocomposite modified electrode with biocompatible interfaces has great potential to enhance bioelectrochemical reactions with exoelectrogens.

Ganoderic acid A ameliorates depressive-like behaviors in CSDS mice: Insights from proteomic profiling and molecular mechanisms.

OBJECTIVE: Ganoderic Acid A (GAA), a primary bioactive component in Ganoderma, has demonstrated ameliorative effects on depressive-like behaviors in a Chronic Social Defeat Stress (CSDS) mouse model. This study aims to elucidate the underlying molecular mechanisms through proteomic analysis. METHODS: C57BL/6 J mice were allocated into control (CON), chronic social defeat stress (CSDS), GAA, and imipramine (IMI) groups. Post-depression induction via CSDS, the GAA and IMI groups received respective treatments of GAA (2.5 mg/kg) and imipramine (10 mg/kg) for five days. Behavioral assessments utilized standardized tests. Proteins from the prefrontal cortex were analyzed using LC-MS, with further examination via bioinformatics and PRM for differential expression. Western blot analysis confirmed protein expression levels. RESULTS: Chronic social defeat stress (CSDS) induced depressive-like behaviors in mice, which were significantly alleviated by GAA treatment, comparably to imipramine (IMI). Proteomic analysis identified distinct proteins in control (305), GAA-treated (949), and IMI-treated (289) groups. Enrichment in mitochondrial and synaptic proteins was evident from GO and PPI analyses. PRM analysis revealed significant expression changes in proteins crucial for mitochondrial and synaptic functions (namely, Naa30, Bnip1, Tubgcp4, Atxn3, Carmil1, Nup37, Apoh, Mrpl42, Tprkb, Acbd5, Dcx, Erbb4, Ppp1r2, Fam3c, Rnf112, and Cep41). Western blot validation in the prefrontal cortex showed increased levels of Mrpl42, Dcx, Fam3c, Ppp1r2, Rnf112, and Naa30 following GAA treatment. CONCLUSION: GAA exhibits potential antidepressant properties, with its action potentially tied to the modulation of synaptic functions and mitochondrial activities.

Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction.

Introduction: While astrocytes participate in the CNS innate immunity against herpes simplex virus type 1 (HSV-1) infection, they are the major target for the virus. Therefore, it is of importance to understand the interplay between the astrocyte-mediated immunity and HSV-1 infection. Methods: Both primary human astrocytes and the astrocyte line (U373) were used in this study. RT-qPCR and Western blot assay were used to measure IFNs, the antiviral IFN-stimulated genes (ISGs), IFN regulatory factors (IRFs) and HSV-1 DNA. IRF1 knockout or knockdown was performed with CRISPR/Cas9 and siRNA transfection techniques. Results: Poly(dA:dT) could inhibit HSV-1 replication and induce IFN-ß/IFN-λs production in human astrocytes. Poly(dA:dT) treatment of astrocytes also induced the expression of the antiviral ISGs (Viperin, ISG56 and MxA). Among IRFs members examined, poly(dA:dT) selectively unregulated IRF1 and IRF9, particularly IRF1 in human astrocytes. The inductive effects of poly(dA:dT) on IFNs and ISGs were diminished in the IRF1 knockout cells. In addition, IRF1 knockout attenuated poly(dA:dT)-mediated HSV-1 inhibition in the cells. Conclusion: The DNA sensors activation induces astrocyte intracellular innate immunity against HSV-1. Therefore, targeting the DNA sensors has potential for immune activation-based HSV-1 therapy.

Explosion of research on psychopathology and social media use after COVID-19: A scientometric study.

BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

[Rules of prescriptions for heart failure of dilated cardiomyopathy based on latent structure model and association rules].

The latent structure model and association rules analysis were employed to explore the compatibility rules of prescriptions for heart failure of dilated cardiomyopathy, with a view to providing theoretical support for the clinical treatment of this disease based on syndrome differentiation and the formulation of guidelines. The articles about the treatment of heart failure of dilated cardiomyopathy were retrieved from CNKI, Wanfang, VIP, and SinoMed. The database was established in Microsoft Excel 2019. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of Chinese medicine with the frequency greater than 4.00%. Furthermore, the frequency structure model was used to mine the rules of prescriptions for heart failure of dilated cardiomyopathy. The study included 175 traditional Chinese medicine(TCM) prescriptions, involving 128 Chinese medicines, with the cumulative frequency of 1 847. High-frequency medicines included Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, with the main effects of tonifying, activating blood, resolving stasis, and releasing exterior. A total of 17 hidden variables, 34 hidden categories, and 6 comprehensive cluster models, along with 15 core prescriptions, were obtained. According to the prescriptions, the patients mainly had the syndromes of heart-Yang and Qi deficiency, Qi deficiency and blood stasis, heart-kidney Yang deficiency or Qi-Yin deficiency. Fifty-four strong association rules were obtained through association rule analysis. The highest degree of support was observed for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix, while the highest degree of confidence was found for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Cinnamomi Ramulus-Ophiopogonis Radix-Astragali Radix. The heart failure of dilated cardiomyopathy, characterized by internal deficiency and excess manifestations, is attributed to deficiency, stasis, and water. These factors are closely associated with the heart, lung, and spleen. The treatment should follow the principle of invigorating Qi and warming Yang, and meanwhile the method of activating blood and resolve stasis or moving Qi and promoting urination can be adopted according to the specific syndrome of patients.

Residential greenness and chronic obstructive pulmonary disease in a large cohort in southern China: Potential causal links, risk trajectories, and mediation pathways.

INTRODUCTION: Residential greenness may influence COPD mortality, but the causal links, risk trajectories, and mediation pathways between them remain poorly understood. OBJECTIVES: We aim to comprehensively identify the potential causal links, characterize the dynamic progression of hospitalization or posthospital risk, and quantify mediation effects between greenness and COPD. METHODS: This study was conducted using a community-based cohort enrolling individuals aged ≥ 18 years in southern China from January 1, 2009 to December 31, 2015. Greenness was characterized by normalized difference vegetation index (NDVI) around participants' residential addresses. We applied doubly robust Cox proportional hazards model, multi-state model, and multiple mediation method, to investigate the potential causal links, risk trajectories among baseline, COPD hospitalization, first readmission due to COPD or COPD-related complications, and all-cause death, as well as the multiple mediation pathways (particulate matter [PM], temperature, body mass index [BMI] and physical activity) connecting greenness exposure to COPD mortality. RESULTS: Our final analysis included 581,785 participants (52.52% female; average age: 48.36 [Standard Deviation (SD): 17.56]). Each interquartile range (IQR: 0.06) increase in NDVI was associated with a reduced COPD mortality risk, yielding a hazard ratio (HR) of 0.88 (95 % CI: 0.81, 0.96). Furthermore, we observed per IQR (0.04) increase in NDVI was inversely associated with the risk of multiple transitions (baseline - COPD hospitalization, baseline - death, and readmission - death risks), especially a declined risk of all-cause death after readmission (HR = 0.66 [95 %CI: 0.44, 0.99]). Within the observed association between greenness and COPD mortality, three mediators were identified, namely PM, temperature, and BMI (HR for the total indirect effect: 0.773 [95 % CI: 0.703, 0.851]), with PM showing the highest mediating effect. CONCLUSIONS: Our findings revealed greenness may be a beneficial factor for COPD morbidity, prognosis, and mortality. This protective effect is primarily attributed to the reduction in PM concentration.

Numerical simulation of the influence of nasal cycle on nasal airflow.

To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to construct a three-dimensional model of the nasal cavity to be used as simulation domain. A sinusoidal airflow velocity is set at the nasal cavity entrance to reproduce the breathing pattern of a healthy human. There was a significant difference in the cross-sectional area between the two sides of the nasal cavity. Particularly, the decongested side is characterized by a larger cross-section area, and consequently, by a larger volume with respect to the congested side. The airflow velocity, pressure, and nasal resistance were higher on the congested narrow side. The temperature regulation ability on the congested narrow side was stronger than that on the decongested wider side. During the nasal cycle, there are differences in the nasal cavity function between the congested and decongested sides. Therefore, when evaluating the impact of various factors on nasal cavity function, the nasal cycle should be considered.