Causal Association between Tea Intake and Acute Cerebrovascular Events: A Multivariate Mendelian Randomized Study in European Populations.

BACKGROUND: Numerous research works have investigated the association between tea consumption and the risk of acute cerebrovascular events; however, the results are inconsistent. OBJECTIVES: We used Mendelian randomization (MR) to evaluate the causal association between tea intake and several acute cerebrovascular events, including any ischemic stroke, large atherosclerotic stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), intracranial hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We obtained summary genome-wide association study (GWAS) data on tea intake and acute cerebrovascular events in populations of European ancestry. The GWAS on tea intake is derived from the UK Biobank, where we have chosen single-nucleotide polymorphisms (SNPs) closely associated with it as instrumental variables. We also obtained summary data on ischemic stroke from a GWAS meta-analysis, as well as summary data on ICH and SAH from the FinnGen study. We first explored the causal association between tea intake and several acute cerebrovascular events using univariate Mendelian randomization (UVMR), and then further assessed the causal association between tea intake and SVS using multivariate Mendelian randomization (MVMR) corrected for multiple confounders. RESULTS: In UVMR, genetically predicted increases in tea intake were linked to a lower risk of SVS (OR: 0.58; 95% CI: 0.39, 0.86). There was no causal association between tea intake and the risk of other acute cerebrovascular events. In the MVMR, our results show that there was still a significant causal association between drinking tea and SVS, after adjusting body mass index, total cholesterol, low-density lipoprotein cholesterol, diabetes, hypertension, smoking, and alcohol consumption. CONCLUSION: This MR study provides new genetic evidence that increased tea intake reduces the risk of SVS in the European population. However, possibly because of limited statistical power, the study did not find that tea consumption reduced the risk of several other acute cerebrovascular events.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

Causal association between plant foods intake and Alzheimer's disease: a Mendelian randomization study.

BACKGROUND: Alzheimer's disease (AD) is a degenerative disease of the nervous system. Observational studies have found an association between plant food intake and AD. However, it is unclear whether this association is influenced by confounding factors. We aimed to explore the causal relationship between plant-based diet and the risk of AD using two-sample Mendelian randomization. MATERIALS AND METHODS: We obtained datasets of exposure from the IEU Open GWAS project, including dried fruit intake, fresh fruit intake, raw vegetable intake, cooked vegetable intake, and cereal intake. The summary data for AD were obtained from a large GWAS meta-analysis containing 71,880 cases and 383,378 controls. RESULTS: Increased intake of dried fruits was associated with a reduced risk of AD (IVW: OR = 0.88, 95CI = 0.82-0.95). No causal association was found between the intake of other foods and AD. CONCLUSION: This MR study suggests that genetically predicted increased intake of dried fruits is a causal protective factor for AD.

Hypothyroidism's effect on stroke limited to specific subtypes: A Mendelian randomization study.

BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes. RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant. CONCLUSION: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.

Serum Hs-CRP level and clinical significance of patients with stress ulcer caused by massive blood loss after trauma.

Stress ulcer refers to a specific type of irritation of the inner wall of the gastrointestinal tract that occurs rapidly due to acute physiological stress such as severe disease, infection, or trauma. This study investigated the serum Hs-CRP level and clinical significance of patients with stress ulcers caused by massive blood loss after trauma. For this purpose, we studied 113 patients with enormous blood loss after trauma. During the study, 26 patients developed stress ulcers. Therefore, patients with massive blood loss after trauma were divided into two groups with and without stress ulcers. In addition to clinical and demographical evaluations, serum Hs-CRP levels were measured by ELISA test method in all patients at baseline, 6, and 12 days after starting the study. Results showed that 24 patients were excluded from the study due to termination of cooperation or death. Finally, 89 patients participated in the final analysis. Of these 89 patients, 26 developed stress ulcers. There was a significant difference between the two groups with stress and non-stress ulcers in terms of mean age (P=0.001) and gender (P=0.041). Also, there was a significant difference between the two groups regarding re-bleeding (P=0.012), the number of hospitalization days (P=0.001), and a decrease in hemoglobin (P=0.035). But there was no difference between the two groups regarding the need for re-surgery (P=0.276). The results of this study showed that increased serum hs-CRP levels are directly related to stress ulcers. Patients with higher serum Hs-CRP levels were more likely to develop stress ulcers than patients without stress ulcers during six days (P=0.04) and twelve days after starting the study (P=0.001). Current research results also show that the prevalence of stress ulcers occurs in men more than women. The risk of stress ulcers increases among older patients. People with stress ulcers also lose more hemoglobin, and finally, patients with more trauma and more extended hospital stays have a higher chance of developing stress ulcers.

The relationship between menopausal syndrome and gut microbes.

BACKGROUND: Gut microbes were closely related to women's health. Previous studies reported that the gut microbes of premenopausal women were different from those of postmenopausal women. However, little was known about the relationship between gut microbiota dysbiosis and menopausal syndrome (MPS). The aim of this study was to explore the relationship between MPS and gut microbes. METHODS: Patients with MPS (P group, n = 77) and healthy women (H group, n = 24) at menopause were recruited in this study. The stool specimen and clinical parameters (demographic data, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), et al) of participants' were collected. We evaluated the differences in gut microbes by 16S ribosomal RNA gene sequencing. We used LEfSe to identify gut microbes with varying abundances in different groups. The Spearman correlation coefficients of clinical parameters and gut microbes were calculated. PICRUSt was used to predict the potential KEGG Ortholog functional profiles of microbial communities. RESULTS: The abundance of 14 species differed substantially between the MPS and menopausal healthy women (LDA significance threshold > 2.0) according to LEfSe analysis. Using Spearman's correlation analysis, it was discovered that E2 had a positive correlation with Aggregatibacter segnis, Bifidobacterium animalis, Acinetobacter guillouiae (p < 0.05, these three species were enriched in menopausal healthy women), while FSH and LH had a negative correlation with them (p < 0.05). KEGG level3 metabolic pathways relevant to cardiovascular disease and carbohydrate metabolism were enriched in the MPS (p < 0.05), according to functional prediction by PICRUST and analyzed by Dunn test. CONCLUSION: There was gut microbiota dysbiosis in MPS, which is reflected in the deficiency of the abundance of Aggregatibacter segnis, Bifidobacterium animalis and Acinetobacter guillouiae related to the level of sex hormones. In MPS individuals, species with altered abundances and unique functional pathways were found.

The Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of Chronic Kidney Diseases.

BACKGROUND AND OBJECTIVES: This study was to characterize the association of cumulative exposure to increased high-sensitivity C-reactive protein (hs-CRP) with chronic kidney diseases (CKD). METHODS: We included 35,194 participants with hs-CRP measured at three examinations in 2006, 2008, 2010. Participants were classified into nonexposed group (hs-CRP <3.0 mg/L in all 3 examinations), 1-exposed group (hs-CRP ≥3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs-CRP ≥3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP ≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs-CRP with incident CKD. CKD includes an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urinary protein positive. RESULTS: The study showed the risk of CKD as the number of years of exposure to hs-CRP increases. Participants in 3-exposed group had significantly increased CKD risk with hazard ratio (HR) (95% confidence interval, CI) of 1.70 (1.49-1.93), in comparison with 1.47 (1.34-1.62) for participants in the 2-exposed group, and 1.08 (1.00-1.16) for those in the 1-exposed group (p < 0.01); meanwhile, the similar and significant associations were also observed for eGFR <60 mL/min/1.73 m2, proteinuria positive, in participants of the 3-exposed group in comparison with the nonexposed group, with respective HRs (95% CI) of 1.27 (1.01-1.58) and 2.27 (1.87-2.76). CONCLUSIONS: Cumulative exposure to hs-CRP was associated with a subsequent increased risk of CKD and was of great value to risk prediction.

Superconducting nanowire single photon detection system for space applications.

Superconducting nanowire single photon detectors (SNSPDs) have advanced various frontier scientific and technological fields such as quantum key distribution and deep space communications. However, limited by available cooling technology, all past experimental demonstrations have had ground-based applications. In this work, we demonstrate a SNSPD system using a hybrid cryocooler that could ultimately be compatible with space applications. With a minimum operational temperature of 2.8 K, this SNSPD system presents a maximum system detection efficiency of over 50% and a timing jitter of 48 ps, which paves the way for various space applications.

Characterization of the Stroke-Induced Changes in the Variability and Complexity of Handgrip Force.

Introduction: The variability and complexity of handgrip forces in various modulations were investigated to identify post-stroke changes in force modulation, and extend our understanding of stroke-induced deficits. Methods: Eleven post-stroke subjects and ten age-matched controls performed voluntary grip force control tasks (power-grip tasks) at three contraction levels, and stationary dynamometer holding tasks (stationary holding tasks). Variability and complexity were described with root mean square jerk (RMS-jerk) and fuzzy approximate entropy (fApEn), respectively. Force magnitude, Fugl-Meyer upper extremity assessment and Wolf motor function test were also evaluated. Results: Comparing the affected side with the controls, fApEn was significantly decreased and RMS-jerk increased across the three levels in power-grip tasks, and fApEn was significantly decreased in stationary holding tasks. There were significant strong correlations between RMS-jerk and clinical scales in power-grip tasks. Discussion: Abnormal neuromuscular control, altered mechanical properties, and atrophic motoneurons could be the main causes of the differences in complexity and variability in post-stroke subjects.

Clinical efficacy and safety of traditional Chinese medicine combined with Western Medicine in patients with diabetic acute ischemic stroke.

OBJECTIVE: To observe the clinical efficacy and safety of Traditional Chinese Medicine (TCM) combined with Western Medicine (WM) in patients with diabetic acute ischemic stroke. METHODS: Ninety patients with diabetic acute ischemic stroke were randomly divided into a treatment group and a control group. The 45 patients in the treatment group were given standardized treatment with TCM combined with WM. They received corresponding oral Chinese decoctions three times daily, according to their TCM syndromes, along with basic western medical treatment. The 45 patients in the control group were given non-standardized treatment with TCM combined with WM. They received an oral Chinese decoction for promotion of blood circulation to inhibit hemostasis, regardless of their TCM syndromes, along with basic western medical treatment. The treatments lasted for 4 weeks. Scores were evaluated on the National Institutes of Health Stroke Scale (NIHSS) score, activity of daily life (ADL) scores, and TCM symptoms before treatment and 2 and 4 weeks after treatment. RESULTS: Analysis of variance for repeated measurements showed that there were significant differences in NIHSS and ADL score before and after treatment in both groups (P < 0.05). There were also significant differences between the scores at 2 and 4 weeks after treatment. There were significant differences in TCM syndrome scores before and after treatment in both groups (P < 0.05). There were also significant differences between the scores at 2 and 4 weeks after treatment. The X2 test showed no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). CONCLUSION: Standardized treatment was superior to non-standardized treatment for clinical efficacy of TCM combined with WM in patients with diabetic acute ischemic stroke, and the superiority was more obvious in improving neural dysfunction, ADL score, and TCM symptoms. The adverse reactions were similar in the two treatment groups.

Dahuang zhechong pill ameliorates hepatic fibrosis by regulating gut microbiota and metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: DHZCP is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber" that has been often used in the treatment of hepatic disorders, gynecopathy and atherosclerosis. However, its underlying mechanisms in preventing hepatic fibrosis remain incompletely understood. AIM OF THE STUDY: This study aims to explore the therapeutic efficacy and potential mechanism of DHZCP in a CCL4-induced experimental hepatic fibrosis rat model. MATERIALS AND METHODS: DHZCP was orally administered at doses of 0.168, 0.084 and 0.042 g⋅kg-1⋅d-1 in a CCL4-induced hepatic fibrosis model using SD rats. Histopathology, immunohistochemistry and biochemical analysis, ELISA, Flow cytometry, WB, RT-PCR, 16 S rRNA, and untargeted metabolomic analysis were used to determine the therapeutic effects and mechanisms of DHZCP in the treatment of CCL4-induced hepatic fibrosis. RESULTS: Pharmacodynamically, DHZCP inhibited ALT and AST, improved liver function, decreased NF-κB, TNF-α and IL-6 in liver tissue, indicating its role in inhibiting CCL4-induced liver inflammation. Most importantly, it reduces the level of fibrosis in serum and liver tissue. Histological analysis also showed that DHZCP could effectively inhibit inflammatory cytokine infiltration and excessive collagen deposition. Mechanistically, DHZCP regulates gut microbiota, improves the proportion of firmicutes and bacteroidota at the phylum level, and increases the abundance of beneficial bacteria at the genus level, such as muribagulaceae unclassified, prevotella, alloprevotella, closteriales unclassified, lachnospiraceae unclassified and phascolarctobacterium. Instead, it reduced the abundance of two harmful bacteria, desulfovibrio and colidextribacter. Four types of metabolites such as hydrocarbons, organic nitrogen compounds, organic oxygen compounds, and organosulfur compounds were added. Furthermore, DHZCP was found to reduce the damage of intestinal barrier caused by changes in gut microbiota and metabolites. CONCLUSION: DHZCP is an effective inhibitor of hepatic fibrosis by regulating gut microbiota and metabolites, improving the integrity of the intestinal barrier.

Dahuang Zhechong Pill Alleviates Liver Fibrosis Progression by Regulating p38 MAPK/NF-κ B/TGF-ß1 Pathway.

OBJECTIVE: To explore the effect and mechanism of Dahuang Zhechong Pill (DHZCP) on liver fibrosis. METHODS: Liver fibrosis cell model was induced by transforming growth factor-ß (TGF-ß) in hepatic stellate cells (HSC-T6). DHZCP medicated serum (DMS) was prepared in rats. HSC-T6 cells were divided into the control (15% normal blank serum culture), TGF-ß (15% normal blank serum + 5 ng/mL TGF-ß), DHZCP (15% DMS + 5 ng/mL TGF-ß), DHZCP+PDTC [15% DMS + 4 mmol/L ammonium pyrrolidine dithiocarbamate (PDTC)+ 5 ng/mL TGF-ß], and PDTC groups (4 mmol/L PDTC + 5 ng/mL TGF-ß). Cell activity was detected by cell counting kit 8 and levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cell supernatant were determined by enzyme-linked immunosorbnent assay. Western blot was used to measure the expressions of p38 mitogen-activated protein kinase/nuclear factor kappa B/transforming growth factor-ß1 (p38 MAPK/NF-κ B/TGF-ß1) pathway related proteins, and the localization and expressions of these proteins were observed by immunofluorescence staining. RESULTS: DHZCP improves the viability of cells damaged by TGF-ß and reduces inflammatory cytokines and ALT and AST levels in the supernatant of HSC-T6 cells induced with TGF-ß (P<0.05 or P<0.01). Compared with the TGF-ß group, NF-κ B p65 levels in the DHZCP group were decreased (P<0.05). p38 MAPK and NF-κ B p65 levels in the DHZCP+PDTC were also reduced (P<0.01). Compared with the TGF-ß group, the protein expression of Smad2 showed a downward trend in the DHZCP, DHZCP+PDTC, and PDTC groups (all P<0.01), and the decreasing trend of Samd3 was statistically significant only in DHZCP+PDTC group (P<0.01), whereas Smad7 was increased (P<0.05 or P<0.01). CONCLUSION: DHZCP can inhibit the process of HSC-T6 cell fibrosis by down-regulating the expression of p38 MAPK/NF-κ B/TGF-ß1 pathway.

Active landslide detection using integrated remote sensing technologies for a wide region and multiple stages: A case study in southwestern China.

While significant progress has been achieved in utilizing remote sensing technologies for landslide investigation in China, there remains a notable gap in consolidating information on applicable conditions, application stages, and workflows across various remote sensing methodologies. This paper proposes a comprehensive framework for active landslide detection, incorporating multiple stages and data sources, successfully implemented in a vast region of southwestern China. Furthermore, detailed discussions are provided on the effects of the geometric distortion, land cover type, and various InSAR methods on the accuracy of active landslide identification results. Additionally, the paper delves into the advantages of integrated remote sensing technology in active landslide investigation, encompassing the assessment of current landslide activity status, precise delineation of boundaries, identification of different deformation stages, and determination of damage patterns. Through comprehensive analysis of multisource data, it enhances understanding of the active landslide process, ultimately contributing to the mitigation of casualties and property damage.

Modifiable factors for migraine prophylaxis: A mendelian randomization analysis.

Objective: To examine the causal effect of potentially modifiable risk factors contributing to migraine pathogenesis. Methods: We performed Mendelian randomization analyses and acquired data from United Kingdom Biobank, FinnGen Biobank, and the MRC IEU OpenGWAS data infrastructure. An inverse-variance weighted (IVW) model was used to examine the relationship between 51 potentially modifiable risk factors and migraine in 3215 participants with migraine without aura (MwoA), 3541 participants with migraine with aura (MwA), and 176,107 controls. We adopted a Bonferroni-corrected threshold of p = 9.8 × 10-4 (.05 divided by 51 exposures) as a sign of significant effect, and a p < .05 was considered as the sign of a suggestive association. Results: More years of schooling significantly correlated with lower odds of MwoA pathogenesis (OR .57 [95%CI .44 to .75], p < .0001). More vitamin B12 intake (OR .49 [95%CI .24 to .99], p = .046) and lower level of stress [OR 8.17 (95%CI 1.5 to 44.36), p = .015] or anxiety disorder (OR 1.92 × 109 [95%CI 8.76 to 4.23*1017], p = .029) were suggestive to be correlated lower odds of MwoA pathogenesis. More coffee intake (OR .39 [95%CI .22 to .7], p = .001), lower level of eicosapentaenoic acid status (OR 2.54 [95%CI 1.03 to 6.26], p = .043), and more light physical activity (OR .09 [95%CI .01 to .94], p = .046) were suggestive to be associated with lower odds of MwA. Conclusion: The years of schooling, light physical activity, vitamin B12 intake, and coffee intake were the protective factors for migraine; stress, anxiety, and eicosapentaenoic acid status were harmful factors. Interventions could be developed based on modifying these factors for migraine prophylaxis.

Matching adjusted indirect comparison of acupuncture versus fremanezumab in the preventive treatment of episodic migraine.

OBJECTIVE: Acupuncture and fremanezumab are second-line treatments for migraine prophylaxis. We aimed to compare acupuncture with fremanezumab in the preventive treatment of episodic migraine by using a matching-adjusted indirect comparison analysis (MAIC). METHODS: We acquired participant-level data from an acupuncture trial recruiting 302 participants and summary-level data from a fremanezumab trial recruiting 875 participants (290 participants received monthly fremanezumab [MF] and 291 received single-dose fremanezumab [SF]). The primary outcome was the mean reduction in monthly headache days. The secondary outcomes were the mean reduction in monthly moderate-to-severe headache days, days with acute medication, and the adverse events rate. RESULTS: Before matching, the acupuncture arm had significantly lower BMI, fewer headache days with at least moderate severity, and fewer days with acute medication. After matching, the baseline variables were comparable between groups. The three arms had no difference in the change of monthly migraine days (MF vs. acupuncture: mean difference 0.3, 95%CI -0.5 to 1.1, p-value = 0.473; SF vs. acupuncture: mean difference 0.5, 95%CI -0.3 to 1.3, p-value = 0.214). The results were similar in the analyses of secondary outcomes sensitivity analyses. Thirty-six (25%) participants in the acupuncture arm reported adverse events, versus 192(66%) participants in the MF arm and 193 (66%) in the SF arm. CONCLUSION: The preventive treatment effect of acupuncture is equivalent to fremanezumab, and it presented with a lower adverse event rate, which indicates that acupuncture can be an alternative to fremanezumab.

Corydalis yanhusuo Polysaccharides Ameliorate Chronic Stress-Induced Depression in Mice through Gut Microbiota-Derived Short-Chain Fatty Acid Activation of 5-Hydroxytryptamine Signaling.

Depression, a prevalent psychiatric disorder, presents a serious health risk to humans. Increasing evidence suggested that the gut microbiota and the 5-hydroxytryptamine (5-HT) pathway both contribute significantly to depression. This research aimed to investigate how Corydalis yanhusuo polysaccharides (CYP) could potentially alleviate depression induced by chronic unpredictable mild stress in mice, as well as its underlying mechanism. The sucrose preference test, tail suspension test, and forced swimming test were employed to evaluate the behavior of mice. Enzyme-linked immunosorbent assay and PCR techniques were utilized to measure depression-related factors (dopamine [DA], 5-HT, norepinephrine [NE], brain-derived neurotrophic factor [BDNF], tryptophan hydroxylase 2 [TPH-2], 5-hydroxytryptophan [5-HTP], and tryptophan hydroxylase [TPH-1] levels). Hematoxylin and eosin staining and Nissl staining were conducted to observe histopathological changes in the hippocampus, the differences in the diversity of gut flora between groups were analyzed using 16S rRNA sequencing, and gas chromatography-mass spectrometry metabolomics was utilized to evaluate short-chain fatty acid (SCFA) concentrations. The findings indicated that CYP treatment increased the sucrose preference index, decreased the immobility time, and improved neuropathological injury. In depressed mice, CYP improved the dysregulation of the gut microbiota, and increased the SCFA levels. In addition, CYP enhanced the DA, 5-HT, NE, BDNF, and TPH-2 levels in the brain and the expression of 5-HTP and TPH-1 in the colon, while SCFAs were positively correlated with these levels. In summary, our study suggested that CYP may mitigate depression by ameliorating gut microbiota dysregulation, promoting the generation of SCFAs, and activation of 5-HT signaling expression.

The Role of MiR-29 in the Mechanism of Fibrosis.

Fibrosis is a pathological process characterized by tissue scarring that can occur in various human body organs. The fibrosis of the organ is manifested as an increase in fibrous connective tissue and a decrease in parenchymal cells in the organ tissue, leading to structural damage and functional decline of the organ. At present, the incidence and medical burden of fibrosis are increasing worldwide, which has presented severe negative impacts on human health. Although many of the cellular and molecular processes for underlying fibrosis have been discerned, there are still gaps for effective therapies and target fibrogenesis specifically. Recent studies have shown that the microRNA- 29 family (miR-29a, b, c) plays an essential role in the process of multiorgan fibrosis. It is a class of highly conserved single-stranded noncoding RNAs composed of 20-26 nucleotides. Through its 5' untranslated region (UTR) pairing with the 3'UTR of the target mRNA, the mRNA of the target gene is degraded to complete the physiological process of inhibiting the transcription and translation of the target gene. Here, we summarize the interaction of miR-29 with multiple cytokines, describe the mechanism by which miR-29 regulates major fibrotic pathways such as TGF- ß1/Smad, PI3K/Akt/mTOR, DNA methylation, and found that miR-29 is closely linked to epithelial- mesenchymal transition (EMT). These findings point to a common or similar regulatory mechanism by miR-29 in fibrogenesis. Finally, we review the antifibrotic activity of miR-29 mimicked in current studies and highlight miR-29 as a promising therapeutic reagent or target for the treatment of pulmonary fibrosis. Besides, there is an urgent need to screen and identify small compounds to modulate miR-29 expression in vivo.

Phylogeny and molecular evolution of the first local monkeypox virus cluster in Guangdong Province, China.

The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.

Network pharmacology analysis of molecular targets and related mechanisms of Guizhi decoction in treating of menopausal syndrome.

Compared with hormone therapy, TCM had the advantages of overall adjustment and less side effects in the treatment of menopausal syndrome. But due to the complex pharmacodynamic composition of Guizhi decoction (GZD), the mechanism of TCM treating diseases was not clear. Network pharmacology could analyze drug action pathways through multi-pathway and multi-target, which provide a new direction for TCM mechanism research. The common targets of GZD and menopausal syndrome (MPS) were obtained by TCMSP and DisGeNET databases. And for the common targets, protein-protein interaction networks were established using the STRING database and analyzed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. (Our research does not require ethical approval). One hundred forty-six active ingredients with 283 targets were obtained from GZD by network pharmacological analysis. Besides, 230 target genes were found to have interactions with MPS, 52 of which were common targets between MPS and GZD and were predicted to be potential targets for MPS treatment of GZD. GO enrichment analysis revealed that GZD could affect 51 biological processes, 15 cellular components, and 13 molecular functions. Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded a total of 223. The pathways that are closely related to the pathogenesis of MPS are MAPK, PI3K-Akt. In this study, the relevant targets and mechanisms of GZD in the treatment of MPS were discussed from the perspective of network pharmacological analysis, reflecting the characteristics of multi-component, multi-target and multiple pathways, and it provides a good theoretical basis for the clinical application of GZD.

Leukoencephalopathy hypomyelination with brainstem and spinal cord involvement and leg spasticity caused by DARS1 mutations.

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), caused by aspartyl-tRNA synthetase (DARS1) gene mutations, is extremely rare, with only a few cases reported worldwide; thus, reports on HBSL treatment are few. In this review, we summarized the clinical manifestations, imaging features, treatment methods, and gene mutations responsible for HBSL based on relevant studies and cases.