HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells.

Hematopoietic stem and progenitor cells (HSPCs) are cells mainly present in the bone marrow and capable of forming mature blood cells. However, the epigenetic mechanisms governing the homeostasis of HSPCs remain elusive. Here, we demonstrate an important role for histone deacetylase 6 (HDAC6) in regulating this process. Our data show that the percentage of HSPCs in Hdac6 knockout mice is lower than in wild-type mice due to decreased HSPC proliferation. HDAC6 interacts with isocitrate dehydrogenase 1 (IDH1) and deacetylates IDH1 at lysine 233. The deacetylation of IDH1 inhibits its catalytic activity and thereby decreases the 5-hydroxymethylcytosine level of ten-eleven translocation 2 (TET2) target genes, changing gene expression patterns to promote the proliferation of HSPCs. These findings uncover a role for HDAC6 and IDH1 in regulating the homeostasis of HSPCs and may have implications for the treatment of hematological diseases.

Dynamic changes of endothelial and stromal cilia are required for the maintenance of corneal homeostasis.

Primary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α-smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.

Primary cilium-mediated signaling cascade suppresses age-related biliary fibrosis.

The primary cilium is increasingly recognized as a crucial player in the physiology of biliary epithelial cells (BECs). However, the precise role of primary cilia in the development of age-related biliary fibrosis remains unclear. Herein, using cilium-deficient mice, we demonstrate that disruption of ciliary homeostasis in BECs in aged mice leads to significant bile duct proliferation, augmented biliary fibrosis, and heightened indicators of liver injury. Our RNA-sequencing data revealed a dysregulation in genes associated with various biological processes such as bile secretion, fatty acid metabolism, and inflammation. Loss of primary cilia also significantly enhanced signaling pathways driving the development of biliary fibrosis. Our findings collectively suggest that loss of primary cilia in the BECs of aged mice initiates a cascade of signaling events that contribute to biliary fibrosis, highlighting the primary cilium as a potential therapeutic target in the treatment of fibrosing cholangiopathies.

Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: For patients with advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, the suggested course of action is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Even with a high disease control rate, a majority of patients develop acquired EGFR-TKIs resistance and eventually advance. To increase the benefits of treatment, clinical trials are increasingly exploring the value of EGFR-TKIs combined with angiogenesis inhibitors as a first-line treatment in advanced NSCLC carrying EGFR mutations. METHOD: Using PubMed, EMBASE and Cochrane Library, to locate published full-text articles in print or online, a thorough literature search was done from the database's inception to February 2021. Additionally, oral presentation RCTs from ESMO and ASCO were obtained. We sifted out RCTs that used EGFR-TKIs along with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant NSCLC. ORR, AEs, OS, and PFS were the endpoints. Review Manager version 5.4.1 was used for data analysis. RESULTS: One thousand eight hundred twenty-one patients were involved in 9 RCTs. According to the results, combining EGFR-TKIs with angiogenesis inhibitors therapy prolonged PFS of advanced EGFR-mutation NSCLC patients on the whole [HR:0.65 (95%CI: 0.59~0.73, P<0.00001)]. No significant statistical difference was identified between the combination group and single drug group in OS(P=0.20) and ORR (P=0.11). There are more adverse effects when EGFR-TKIs are used in combination with angiogenesis inhibitors than when used alone. CONCLUSION: The combination of EGFR-TKIs and angiogenesis inhibitors prolonged PFS in patients with EGFR-mutant advanced NSCLC, but the OS and ORR benefit was not significant, and the risk of adverse events was higher, more pronounced with hypertension and proteinuria; PFS in subgroups suggested that the combination was associated with better PFS in the smoking, liver metastasis, and no brain metastasis groups, and the included studies suggested that the smoking group , liver metastasis group, and brain metastasis group may have a potential OS benefit.

Universal relation with regime transition for sediment transport in fine-grained rivers.

Fine-grained sediment (grain size under 2,000 µm) builds floodplains and deltas, and shapes the coastlines where much of humanity lives. However, a universal, physically based predictor of sediment flux for fine-grained rivers remains to be developed. Herein, a comprehensive sediment load database for fine-grained channels, ranging from small experimental flumes to megarivers, is used to find a predictive algorithm. Two distinct transport regimes emerge, separated by a discontinuous transition for median bed grain size within the very fine sand range (81 to 154 µm), whereby sediment flux decreases by up to 100-fold for coarser sand-bedded rivers compared to river with silt and very fine sand beds. Evidence suggests that the discontinuous change in sediment load originates from a transition of transport mode between mixed suspended bed load transport and suspension-dominated transport. Events that alter bed sediment size near the transition may significantly affect fluviocoastal morphology by drastically changing sediment flux, as shown by data from the Yellow River, China, which, over time, transitioned back and forth 3 times between states of high and low transport efficiency in response to anthropic activities.

Local resection versus radical resection for early-stage rectal cancer: a systematic review and meta-analysis.

PURPOSE: The optimal surgical approach for early-stage rectal cancer remains controversial. Radical resection is considered to be the gold standard for rectal cancer treatment. More and more studies show that local resection can replace traditional radical resection in the treatment of early rectal cancer. This research aimed to compare the efficacy of local excision and radical surgery for early-stage rectal cancer and report the evidence-based clinical advantages of both techniques. METHODS: The clinical trials comparing oncological and perioperative local and radical resection outcomes for early-stage rectal cancer were searched from 7 national and international databases. RESULTS: Finally, 3 randomized controlled trials and 14 cohort studies were included. In terms of oncology and perioperative outcomes, there were no statistically significant differences between the radical resection group and the local resection group in terms of OS (HR = 1.05, 95% CI (0.98, 1.13), DFS [HR = 1.18, 95% CI (0.93, 1.48), p = 0.168), distant metastasis rate (RR = 1.04, 95% CI (0.49, 2.20), p = 0.928), and mortality rate (RR = 1.52, 95% CI (0.80, 2.91), p = 0.200). However, there were significant differences in the outcomes of complications (RR = 2.85, 95% CI (2.07, 3.92), p < 0.001), length of hospital stays (WMD = 5.41, 95% CI (3.94, 6.87), p < 0.001), stoma rate (RR = 7.69, 95% CI (2.39, 24.77), p = 0.001), local recurrence rate (RR = 0.48, 95% CI (0.27, 0.86), p = 0.013), operative time (WMD = 74.68, 95% CI (68.00, 81.36), p < 0.001), blood loss (WMD = 156.36, 95% CI (95.48, 217.21, p < 0.001), and adverse events (RR = 1.59, 95% CI (1.05, 2.41), p = 0.027). CONCLUSION: Local excision may be a viable alternative to radical resection for early-stage rectal cancer, but higher quality clinical studies are needed to confirm this.

Effects of Yixintai Pills on Myocardial Cell Apoptosis in Rats With Adriamycin-Induced Heart Failure.

OBJECTIVE: To study the effects of Yixintai pills on myocardial cell apoptosis in rats with adriamycin (ADR)-induced heart failure (HF) and the mechanism of action. METHODS: Sixty healthy male Wistar rats randomly were divided into Control, Model, Captopril, and Yixintai pill groups. A rat model of ADR-induced HF was constructed by intraperitoneal injection of ADR (2.5 mg/kg). The control group was given an equal volume of normal saline; the Yixintai pill and Captopril groups were given corresponding mediations (5 mg/kg) by lavage. After 4 weeks of treatment, fasting blood was collected to detect the contents of plasma rennin activity (PRA), angiotensin II (AngII), and aldosterone (ALD). B ultrasound was used to detect the heart structure, and the heart weight/body weight (HW/BW) ratio was calculated. The pathology of myocardial tissues was observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL assay. The expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum were analyzed by ELISA, and the protein expression levels of protein kinase B (Akt), phosphorylated (p)-Akt, glycogen synthase kinase-3ß (GSK-3ß) and p-GSK-3ß in myocardial tissues were measured by Western blotting. RESULTS: Compared with the Control group, the PRA, AngII, ALD, left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular posterior wall thickness at end-diastole (LVPWd), interventricular septal thickness at end-systole (IVSs), interventricular septal thickness at end-diastole (IVSd), HW/BW, TNF-α and IL-6 of model group increased significantly (P < .05). PRA, AngII, ALD, LVPWs, LVPWd, IVSs, IVSd, HW/BW, TNF-α and IL-6 of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). There were no significant differences in the indices between the Yixintai pill and Captopril groups (P > .05). In the Model group, lamellar necrosis, vacuolar degeneration, increased myocardial fibers and lamellar dissolution of myocardial cells were found in myocardial tissues. However, the myocardial cells of the Control group were neatly arranged and clearly structured, and only a few ones underwent fibrosis. There were mild myocardial fibrosis and vacuolar degeneration in the Yixintai pill and Captopril groups, and the degeneration and hyperplasia of myocardial fibers were obviously relieved. Compared with the Control group, the apoptosis index (AI) of the Model group increased significantly (P < .05). The AI values of the Yixintai pill and Captopril groups were significantly lower than those of the Model group (P < .05). Compared with the Control group, the expression levels of p-Akt and p-GSK-3ß in the Model group decreased significantly (P < .05). The expression levels of p-Akt and p-GSK-3ß in the Yixintai pill and Captopril groups were significantly higher than those of the Model group (P < .05), whereas the former 2 groups had similar results (P > 0.05). CONCLUSION: Yixintai pills may inhibit myocardial cell apoptosis and ventricular remodeling in rats by up-regulating PI3K/Akt/GSK-3ß signal, thus protecting the heart function.

Changes in Prealbumin and Body Mass Index Associated with T Lymphocyte Subsets and Nutritional Status in Chronic Hepatitis B and HBV-Cirrhosis Patients.

Background: Patient immune response is one of the main factors influencing hepatitis virus (HBV) eradication or chronicity. Our study aimed to investigate the relationship between the nutritional status and immune function, and to provide the appropriate clinical diagnosis data for treatment of patients with chronic hepatitis B virus (CHB) and cirrhosis. Methods: T lymphocyte subsets were tested using flow cytometry in 100 patients (48 with CHB, 52 with cirrhosis) and 26 healthy individuals. Nutritional parameters were analyzed including body mass index (BMI), blood white blood cell count, albumin, prealbumin, and biochemistry parameters in patient and control groups. Results: Moderate and severe malnutrition (53.84%) were observed in HBV-cirrhosis patients. Serum albumin and prealbumin levels were the lowest in the cirrhosis group. There were significantly lower levels of lymphocyte subsets (CD3+, CD3+CD4+, and CD3+CD8+) in patient groups compared with the control group. There was significantly lower cholesterol, white blood cells, lymphocytes, and platelet levels in the patient group compared with the control group. Interrelation between nutritional and immune parameters showed that serum prealbumin levels were negatively correlated with CD3+, CD3+CD4+, and CD3+CD8+ count in the CHB group, and the immune parameters (CD3+, CD3+CD4+, and CD3+CD8+ count) correlated significantly with BMI in the patients with cirrhosis (r > 0.45). Conclusions: Our data demonstrate that there is a correlation between nutrition deficiency and immune dysfunction in patients with CHB and cirrhosis. It is necessary to assess the nutritional status and immune balance in these patients.

MEF2 transcription factors promotes EMT and invasiveness of hepatocellular carcinoma through TGF-ß1 autoregulation circuitry.

Invasion and metastasis is the main causes leading to the death of hepatocellular carcinoma (HCC) patients. However, the underlying mechanism is still to be explored. Transforming growth factor ß1 (TGF-ß1) is a stronger inducer of HCC cell invasion. However, the downstream effector of TGF-ß1 that promotes HCC invasion is still unknown. In this study, we found that PI3K/Akt activation takes place following the stimulation of TGF-ß1. The inhibition of PI3K/Akt activation abolished epithelial-mesenchymal transition (EMT) and invasion of HCC cells induced by TGF-ß1. Myocyte enhancer factors 2 (MEF2) family proteins were found to be overexpressed in HCC cells under the treatment of TGF-ß1 in a PI3K/Akt-dependent way. Silencing the expression of MEF2s was able to prevent the effect of TGF-ß1 on HCC EMT and invasion. Unexpectedly, MEF2 proteins were able to promote the expression of TGF-ß1 in HCC cells, suggesting the existence of regulatory circuitry consisting of TGF-ß1, PI3K/Akt, and MEF2. A natural compound, oleanolic acid, was demonstrated to suppress the invasion and EMT of HCC cells by downregulating MEF2, showing that targeting this pathway is an effective therapeutic strategy for HCC invasion. We believe that our findings can contribute to better understanding of the involved mechanism of HCC invasion and the development of preventive and therapeutic strategy.

Preparation of a novel rape pollen shell microencapsulation and its use for protein adsorption and pH-controlled release.

This study aims to synthesize hollow microspheres (HMS) from rape pollen via H3PO4 hydrothermal carbonization. The rape pollen hollow shell was used as the carrier and bovine serum albumin as a model protein. The properties of HMS were characterized by scanning electron microscope (SEM), solid-state nuclear magnetic resonance and elemental analysis. The SEM images clearly showed that the HMS had perfect spherical morphology and porous hollow surface. In the separated filtrate, a large number of sucroses were detected by high-performance liquid chromatography, suggesting that the hydrolysis of starch molecules occurred during the hydrothermal process. The formation of HMS was that the rape pollen inclusion was removed from rape pollen shell to preserve integral HMS by H3PO4 hydrothermal. The HMS possessed amphiphilic surfaces, which was suitable for protein adsorpion and pH-controlled release application.

[A literature review on Chinese medicine syndrome and syndrome elements of chronic fatigue syndrome].

OBJECTIVE: To research the distribution characteristics of Chinese medicine (CM) syndrome and syndrome elements of chronic fatigue syndrome (CFS) by analyzing literature in recent 20 years. METHODS: Relevant literature on treating CFS by syndrome differentiation of CM at home were retrieved by computer and manual ways. Database were established by using EpiData 3.1 to conduct frequency analysis of syndrome and syndrome elements. RESULTS: The most common clinical syndromes were Xin-Pi deficiency syndrome, Gan stagnation Pi deficiency syndrome, Gan-Shen yin deficiency syndrome, Gan qi stagnation syndrome, and Pi-Wei qi deficiency syndrome. Disease locations were sequenced as Pi, Gan, Shen, and Xin. The clinical pathogenesis of CFS was characterized by deficiency of vital energy, complicated with intermingled excess and deficiency. Asthenia of healthy energy was mainly manifested as qi deficiency, blood deficiency, and yin deficiency, while excess of sthenia was mainly manifested as qi stagnation, phlegm dampness, and static blood. CONCLUSIONS: Research of CM syndrome starting from syndrome elements can better unify and standardize clinical syndrome differentiation. Results of literature analysis can provide reference for further studies.

The Structure of Digestive Tract Coordinating Digestion and Respiration in an Air-Breathing Weatherloach, Misgurnus anguillicaudatus.

To clarify how the digestive tract of the weatherloach, Misgurnus anguillicaudatus, serves a dual function of digestion and respiration simultaneously, the histological structures of its digestive tract, the passage of digesta and air passing through its intestine and the rate of intestinal evacuation have been studied. The results indicate that the digestive tract is divided into five functional regions, i.e., esophagus, anterior intestine, middle intestine, posterior intestine and rectum. The diverse intestinal structures have the specialized function of coordinating digestion and respiration. An X-ray barium meal examination showed in the normal breathing state, the contents of the intestine are diffusely semifluid, and air is distributed as bubbles in the dorsal intestine 2 h after feeding. After 5 h, the contents accumulated in the mid and posterior intestine, and gas flowed above the contents as bundles. After 8 h, the intestinal food was basically evacuated. In the intestinal air-breathing restricted group, the contents of the intestine remained diffuse, and a large number of digesta entered and remained in the rectum after 5 h. After the inhibition was relieved, the contents of the rectum were rapidly discharged. Measurement of the intestinal evacuation rate in the intestine showed that the evacuation of the intestinal contents lagged behind that of the normal group in the air-breathing restricted group. Compared to the normal state and inhibited GAB (gastrointestinal air breathing), we could deduce that GAB could promote the movement of the intestine.

Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification.

Vascular calcification (VC) is considered a common pathological process in various vascular diseases. Accumulating studies have confirmed that VC is involved in the inflammatory response in heart disease, and SPP1+ macrophages play an important role in this process. In VC, studies have focused on the physiological and pathological functions of macrophages, such as pro-inflammatory or anti-inflammatory cytokines and pro-fibrotic vesicles. Additionally, macrophages and activated lymphocytes highly express SPP1 in atherosclerotic plaques, which promote the formation of fatty streaks and plaque development, and SPP1 is also involved in the calcification process of atherosclerotic plaques that results in heart failure, but the crosstalk between SPP1-mediated immune cells and VC has not been adequately addressed. In this review, we summarize the regulatory effect of SPP1 on VC in T cells, macrophages, and dendritic cells in different organs' VC, which could be a potential therapeutic target for VC.

Biochar and Manure Co-Application Increases Rice Yield in Low Productive Acid Soil by Increasing Soil pH, Organic Carbon, and Nutrient Retention and Availability.

In recent years, overuse of chemical fertilization has led to soil acidification and decreased rice yield productivity in southern China. Biochar and manure co-application remediation may have positive effects on rice yield and improve acid paddy soil fertility. This study was conducted to understand the effects of co-application of wood biochar and pig manure on rice yield and acid paddy soil quality (0-40 cm soil layers) in a 5-year field experiment. The experiment consisted of six treatments: no biochar and no fertilizer (CK); biochar only (BC); mineral fertilizer (N); mineral fertilizer combined with biochar (N + BC); manure (25% manure N replacing fertilizer N) combined with mineral fertilizer (MN); and manure combined with mineral fertilizer and biochar (MN + BC). Total nitrogen application for each treatment was the same at 270 kg nitrogen ha-1y-1, and 30 t ha-1 biochar was added to the soil only in the first year. After five years, compared with N treatments, N + BC, MN, and MN + BC treatments increased the rice yield rate to 2.8%, 4.3%, and 6.3%, respectively, by improving soil organic matter, total nitrogen, and available phosphate under a 0-40 cm soil layer. MN + BC had the strongest resistance to soil acidification among all the treatments. The interaction between fertilizers and biochar application was significant (p < 0.05) in rice yield, soil electrical conductivity (10-20 cm), and soil available phosphate (20-40 cm). Principal component analysis indicated that the effect of manure on soil property was stronger than that of biochar in the 0-40 cm soil layer. The overall rice yield and soil fertility decreased in the order of biochar + mineral fertilizer + manure > mineral fertilizer + manure > biochar + mineral fertilizer > mineral fertilizer > biochar > control. These results suggest that biochar and manure co-application is a long-term viable strategy for improving acid soil productivity due to its improvements in soil pH, organic carbon, nutrient retention, and availability.

Preparation and loading buffer study of polyvinyl alcohol-based immobilized Ti4+ affinity chromatography for phosphopeptide enrichment.

Despite recent advances in phosphoproteomics, an efficient and simple enrichment protocol is still a challenge and of high demand aiming at large-scale plant phosphoproteomics studies. Here, we developed a novel loading buffer system for synthesized immobilized metal affinity chromatography material targeting plant samples, which was prepared by a simple one-step esterification between polyvinyl alcohol and phosphoric acid and then was subjected to immobilize Ti(4+). SEM and Fourier transform IR spectroscopy were used to assure the synthesis protocol of the polyvinyl alcohol-based Ti(4+) immobilized material, and the specific surface areas and pore volumes of the polymers were measured. The selectivity for phosphopeptide enrichment from α-casein was improved by optimizing the pH and components of the loading buffer. By using potassium hydrogen phthalate/hydrochloric acid with pH at 2.50 as the loading buffer, 19 phosphopeptides with high intensity were identified. The final optimized protocol was adapted to salt-stressed maize leaves for phosphoproteome analysis. A total of 57 phosphopeptides containing 59 phosphorylated sites from 50 phosphoproteins were identified in salt-stressed maize leaf. The research was meaningful to obtain much more information about phosphoproteins leading to the comprehension of salt resistance and salt-inducible phosphorylated processes of maize leaves.

Molecular mechanism of modified Huanglian Wendan decoction in the treatment of polycystic ovary syndrome.

To investigate the mechanism of modified Huanglian Wendan decoction in the intervention of polycystic ovary syndrome (PCOS) by network pharmacology and molecular docking. The ingredients and targets of modified Huanglian Wendan decoction were retrieved from the traditional Chinese medicine Systems Pharmacology database. Related targets of PCOS were screened by Comparative Toxicogenomics Database database. Cytoscape 3.7.2 (https://cytoscape.org/) was used to draw the target network diagram of "traditional Chinese medicine - ingredient - PCOS," STRING database was used to construct the target protein interaction network. NCA tool of Cystoscape 3.7.2 was used to carried out topology analysis on PPI network, core components and key targets were obtained. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were carried out for the intersection targets by David database. AutoDockTools 1.5.6 software (https://autodock.scripps.edu/) was used to conduct molecular docking verification of key components and key targets. Ninety-one ingredients of the modified Huanglian Wendan decoction and 23,075 diseases targets were obtained, 155 Intersection targets of the drug and disease were obtained by R language, Veen plot was drawn. Gene ontology enrichment analysis obtained 432 biological processes, 67 cell components, 106 molecular functions. Fifty-four Kyoto encyclopedia of genes and genomes enrichment pathways (P < .05) including tumor necrosis factor, hypoxia-induced factors-1, calcium, and drug metabolism-cytochrome P450 signaling pathway. Molecular docking showed quercetin, luteolin, kaempferol, and baicalein were stable in docking with core targets. Network pharmacology and molecular docking were used to preliminarily study the mechanism of action of modified Huanglian Wendan decoction in the treatment of PCOS, which laid foundation for future experimental research and clinical application.

A comprehensive review of the components of nurse-coordinated care which are most effective in preventing coronary heart diseases.

Coronary artery disease occurs when there is inadequate blood flow to the heart muscle as a consequence of coronary artery blockage, resulting in heart muscle failure. During normal heart action, cardiac muscles will always need an adequate supply of blood to fulfill their oxygen requirements. Coronary heart disease is the most common kind of cardiovascular disease in adults and the leading cause of mortality in the United States. Growing understanding of the possible significance of environmental and lifestyle variables in disease development has enhanced the job of the nurse coordinator, whether at a lower or higher level of responsibility, to keep current ondiagnostic procedures, clinical symptoms, and innovative treatment choices. According to the national cardiovascular control program, secondary prevention of cardiovascular disease has increased, including measures such as cholesterol management, blood pressure monitoring, and smoking cessation. If you know more about NCC, it might be easier to figure out what roles it could play and what effects its use might have.

Repurposing fluphenazine to suppress melanoma brain, lung and bone metastasis by inducing G0/G1 cell cycle arrest and apoptosis and disrupting autophagic flux.

Brain metastasis is the main cause of treatment failure and melanoma-related death. Inadequate concentrations of therapeutic drugs in the brain due to the blood-brain barrier (BBB) pose a major challenge in the treatment of brain metastasis. Antipsychotics can cross the BBB to reach the brain. Fluphenazine (FPZ) inhibits the survival of melanoma cells in vitro. However, its efficacy in suppressing the metastasis of melanoma, especially brain metastasis, remains unknown. Therefore, we explored whether fluphenazine (FPZ) can be repurposed for treating melanoma metastasis. A subcutaneous tumor model, and experimental metastasis models that simulate the outgrowth of melanoma cells in the brain, lung, and bone were established to verify the inhibitory effect of FPZ on melanoma cells. FPZ showed potential inhibitory effects against melanoma both in vivo and in vitro. It induced G0/G1 phase arrest and-mitochondrion-mediated intrinsic apoptosis, and inhibited autophagic flux in melanoma cells in vitro. In vivo, subcutaneous tumor, brain, lung, and bone models of metastatic melanoma were established. Intraperitoneal injection of FPZ (8 mg/kg) significantly inhibited melanoma growth in the subcutaneous and experimental metastasis models. In a lung metastasis model, FPZ reduced the proportion of M2 macrophages and increased the proportion of CD8+ T cells and NK cells in vivo, thereby promoting an anticancer immune response. The findings of this study indicate that FPZ is a potential drug candidate for treating metastatic melanoma.

Global trends in polycystic ovary syndrome research: A 10-year bibliometric analysis.

Background: Polycystic ovary syndrome (PCOS) is one of the most common reproductive metabolic disorders in women, significantly affecting the biological functionalities of ovaries. This disease has garnered enormous interest from researchers. However, there is a lack of a comprehensive research concerning assessing the current status and future trends in PCOS field. This study uses bibliometric tools to comprehensively analyze the PCOS-related research progress based on the literature in the past decade. Methods: The reported PCOS literature in the past decade is downloaded from the Web of Science database. The bibliometric software is applied to analyze the co-authorship, co-citation, and co-occurrence status. Results: A total of 9936 publications imported into bibliometric tools for analysis show a sharp increase in the annual citations. The USA is dominant in terms of contribution in the field of PCOS, while China is making a significant contribution to the advancement of this field. Monash University is the most prolific institution with the highest H-index value. The contribution of University of Adelaide must be acknowledged. Legro RS and Teede HJ are the most active and influential authors in recent times, while Azziz R is the most contributed pioneer in this field. The Journal of Clinical Endocrinology & Metabolism is the most active journal with the highest number of publications and citations. The pathogenesis of PCOS had been a long-term forefront of research. In recent years, the health management in PCOS prevention and long-term complications was attracting more and more attention. The keywords like "gut microbiota", "microRNAs", "apoptosis", "Myo-inositol", "TNF-alpha", "androgen receptor", and "Vitamin D-deficient" are considered the latest research topics. Conclusion: The study comprehensively analyzes the current status and global trends in the PCOS field, providing a significant reference for researchers to explore this field effectively.

Study the Mechanism of Gualou Niubang Decoction in Treating Plasma Cell Mastitis Based on Network Pharmacology and Molecular Docking.

Objective: Explore the potential molecular mechanisms behind the therapeutic functions of Gualou Niubang decoction (GLNBD) in the treatment of plasma cell mastitis (PCM) by network pharmacology and molecular docking. Methods: GLNBD is a formula of Chinese traditional medicine consisting of 12 herbs. The potential active ingredients of GLNBD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and PCM-related target genes were obtained from GeneCards, OMIM, and NCBI databases, using R language to obtain intersection targets; then, the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb ingredient target networks. DAVID was used to perform GO and KEGG pathway enrichment analyses on the intersection target. PyMoL-2.5.0 and AutoDock Tools-1.5.6 were used to verify the molecular docking. Results: 164 ingredients and 58 intersection targets were obtained in the treatment of PCM by GLNBD. Four key active compounds and four key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that biological functions of potential target genes were associated with negative regulation of the apoptotic process, response to hypoxia, positive regulation of transcription, and DNA-templated, with related pathways involving the pathway in cancer, phosphatidylinositol 3-kinase (PI3K) Akt signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in GLNBD were further validated by molecular docking. The results showed that the docking results were stable and had good binding ability. Conclusion: This study suggested that four potential key active components, including quercetin, luteolin, fisetin, and kaempferol, were identified in GLNBD, which could interact with ALB, EGFR, IL-6, and VEGFA modulating the activation of the pathway in cancer, PI3K-Akt pathway, and AGE-RAGE signaling pathway in diabetic complications.