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KNOXs, a type of homeobox genes that encode atypical homeobox proteins, play an essential role in the regulation of growth and development, hormonal response, and abiotic stress in plants. However, the KNOX gene family has not been explored in sweet potato. In this study, through sequence alignment, genomic structure analysis, and phylogenetic characterization, 17, 12 and 11 KNOXs in sweet potato (I. batatas, 2n = 6x = 90) and its two diploid relatives I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30) were identified. The protein physicochemical properties, chromosome localization, phylogenetic relationships, gene structure, protein interaction network, cis-elements of promoters, tissue-specific expression and expression patterns under hormone treatment and abiotic stresses of these 40 KNOX genes were systematically studied. IbKNOX4, -5, and - 6 were highly expressed in the leaves of the high-yield varieties Longshu9 and Xushu18. IbKNOX3 and IbKNOX8 in Class I were upregulated in initial storage roots compared to fibrous roots. IbKNOXs in Class M were specifically expressed in the stem tip and hardly expressed in other tissues. Moreover, IbKNOX2 and - 6, and their homologous genes were induced by PEG/mannitol and NaCl treatments. The results showed that KNOXs were involved in regulating growth and development, hormone crosstalk and abiotic stress responses between sweet potato and its two diploid relatives. This study provides a comparison of these KNOX genes in sweet potato and its two diploid relatives and a theoretical basis for functional studies.
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Diploidy , Gene Expression Regulation, Plant , Ipomoea batatas , Multigene Family , Phylogeny , Plant Proteins , Stress, Physiological , Ipomoea batatas/genetics , Ipomoea batatas/growth & development , Ipomoea batatas/metabolism , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Genome, Plant , Gene Expression Profiling , Promoter Regions, GeneticABSTRACT
INTRODUCTION: Stimulator of Interferon Genes (STING) is an innate immune sensor. Activation of STING triggers a downstream response that results in the expression of proinflammatory cytokines (TNF-α, IL-1ß) via nuclear factor kappa-B (NF-κB) or the expression of type I interferons (IFNs) via an interferon regulatory factor 3 (IRF3). IFNs can eventually result in promotion of the adaptive immune response including activation of tumor-specific CD8+ T cells to abolish the tumor. Consequently, activation of STING has been considered as a potential strategy for cancer treatment. AREAS COVERED: This article provides an overview on structures and pharmacological data of CDN-like and non-nucleotide STING agonists acting as anticancer agents (January 2021 to October 2023) from a medicinal chemistry perspective. The data in this review come from EPO, WIPO, RCSB PDB, CDDI. EXPERT OPINION: In recent years, several structurally diverse STING agonists have been identified. As an immune enhancer, they are used in the treatment of tumors, which has received extensive attention from scientific community and pharmaceutical companies. Despite the multiple challenges that have appeared, STING agonists may offer opportunities for immunotherapy.
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Antineoplastic Agents , Membrane Proteins , Neoplasms , Patents as Topic , Humans , Animals , Neoplasms/drug therapy , Neoplasms/pathology , Antineoplastic Agents/pharmacology , Membrane Proteins/agonists , Membrane Proteins/metabolism , Membrane Proteins/genetics , Immunity, Innate/drug effects , Immunotherapy/methodsABSTRACT
Hyperglycemia is prevalent and closely associated with pulmonary tuberculosis (PTB). This study aimed to investigate the effects of hyperglycemia on the outcomes of PTB treatment. This study comprised 791 patients with PTB in total. Patients with fasting plasma glucose levels of ≥ 6.1 mmol/L were diagnosed with hyperglycemia. Anthropometric and baseline demographic data were also collected. The treatment response was assessed based on clinical symptoms (sputum production, cough, chest pain, fever, hemoptysis, night sweats, loss of appetite, and fatigue), sputum smear, chest computed tomography (CT), and adverse gastrointestinal responses (vomiting, nausea, abdominal distension, diarrhea, and constipation). A generalized estimating equation (GEE) was used to evaluate these relationships. Hyperglycemia affected 266 (33.6%) of the 791 patients with PTB. In GEE analyses, patients with hyperglycemia exhibited a greater incidence of elevated tuberculosis (TB) scores (odds ratio (OR) 1.569; 95% CI 1.040-2.369), cough (OR 1.332; 95% CI 1.050-1.690), and night sweats (OR 1.694; 95% CI 1.288-2.335). Hyperglycemia was linked with a higher risk of positive sputum smears (OR 1.941; 95% CI 1.382-2.727). During therapy, hyperglycemia was also associated with an increased incidence of vomiting (OR 2.738; 95% CI 1.041-7.198), abdominal distension (OR 2.230; 95% CI 1.193-4.171), and constipation (OR 2.372; 95% CI 1.442-3.902). However, the CT results indicated that hyperglycemia did not affect pulmonary lesions in patients with TB. Patients with TB and hyperglycemia are at a higher risk of severe clinical manifestations, positive sputum smears, and adverse gastrointestinal effects and, therefore, the special situation of hyperglycemic patients should be considered in the prevention and treatment of TB.
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Hyperglycemia , Tuberculosis, Pulmonary , Humans , Female , Male , Hyperglycemia/complications , Middle Aged , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/complications , Treatment Outcome , Adult , Cohort Studies , Antitubercular Agents/therapeutic use , Aged , Blood Glucose/metabolism , Blood Glucose/analysis , Sputum/microbiologyABSTRACT
Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the 'floristic geo-lithology hypothesis', which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.
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Biodiversity , Magnoliopsida , Phylogeny , China , Magnoliopsida/growth & development , Altitude , Geological Phenomena , EcosystemABSTRACT
BACKGROUND: The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease. AIM: To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment. METHODS: To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD. CONCLUSION: Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
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Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.
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Apoptosis , Benzophenanthridines , Cell Proliferation , Ferroptosis , Mice, Nude , NF-E2-Related Factor 2 , Ovarian Neoplasms , Female , Benzophenanthridines/pharmacology , Humans , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , NF-E2-Related Factor 2/metabolism , Animals , Cell Line, Tumor , Ferroptosis/drug effects , Apoptosis/drug effects , Cell Proliferation/drug effects , Membrane Potential, Mitochondrial/drug effects , Mice , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolismABSTRACT
Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.
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Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.
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Male , Humans , Female , alpha-Fetoproteins , Stomach Neoplasms/genetics , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Adenocarcinoma/pathology , Biomarkers, Tumor/genetics , DNA Helicases/genetics , Nuclear Proteins , Transcription Factors/genetics , GlypicansABSTRACT
Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.
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Objective To investigate the effect of cisplatin treatment on the transcriptional level of human liver cancer cells by conducting transcriptome sequencing analysis after treating human liver cancer cell lines with differ-ent concentrations of cisplatin(CDDP).Methods Liver cancer cell lines HepG2 and Huh7 were incubated with cisplatin at different final concentrations of 0,20,50,100 and 200 μmol/L.After 12 hours,cell viability,immuno-fluorescence and RNA-sequencing(RNA-seq)were performed.Differential gene expression analysis(DEG),KEGG pathway analysis,and protein-protein interaction network analysis were conducted.Results Cisplatin de-creased cell viability and increased DNA damage in HepG2,Huh7 cells.Among the genes regulated after cisplatin treatment at different concentrations,59 genes were commonly up-regulated in both HepG2 and Huh7 cells,while 81 genes were commonly down-regulated.The commonly upregulated genes were mainly enriched in cancer initiation and progression pathways.The 81 commonly down-regulated genes were mainly enriched in Rap1 signaling pathway,Ras signaling pathway,signaling pathways regulating pluripotency of stem cells,axon guidance,and cell adhesion-related pathways.Survival analysis of key nodes in the protein-protein interaction network of commonly up-regulated and downregulated genes revealed a significant correlation between high expression of Jun proto-oncogene,AP-1 transcription factor subunit(JUN)and prolonged patient survival and a significant correlation between low ex-pression of growth arrest and DNA damage inducible alpha(GADD45A)and prolonged patient survival.Conclu-sions The study revealed common transcriptional changes in liver cancer cells under cisplatin treatment.Differential expression of JUN and GADD45A is a potential core mechanism to explain drug resistance.This conclusion provides some important prognostic indicators for clinical treatment.
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Methods:A total of 160 Wistar neonatal rats were assigned into normoxia group, HPH group, normoxia+PDGF-BB group, HPH+PDGF-BB group and HPH+PDGF-BB inhibitor (STI571) group using random number table method (32 rats in each group), each group was further assigned into 4 subgroups on d3, d7, d14 and d21 (8 rats in each subgroup). HPH model was established using nitrogen-oxygen mixture with an oxygen concentration of 10%±0.5%. PDGF-BB groups were injected with adenovirus encoding PDGF-BB in the tail vein. HPH+STI571 group was given STI571 intragastrically. On d3, d7, d14 and d21 after modeling, mean right ventricular systolic pressure (RVSP) was examined. Morphological changes of small pulmonary arteries were observed using HE staining and indicators of pulmonary vascular remodeling calculated. Immunohistochemistry was used to determine the protein levels of PDGF-BB, HIF-1α and proliferation-associated protein nuclear protein Ki67 in the pulmonary vasculature of each group. RT-qPCR was used to determine the mRNA levels of PDGF-BB, HIF-1α and Ki67 in lung tissue.Results:At all time points, RVSP was higher in the HPH group than the normoxia group ( P<0.05), higher in the HPH+PDGF-BB group than the HPH group ( P<0.05), and lower in the HPH+STI571 group than both the HPH+PDGF-BB group and the HPH group ( P<0.05). On d3 after modeling, pulmonary vascular remodeling occurred in the HPH+PDGF-BB group; on d7, pulmonary vascular remodeling occurred in the PDGF-BB group and the HPH group. Pulmonary vascular remodeling appeared later and to a lesser extent in the HPH+STI571 group than the other hypoxic groups. On d3, d7 and d21 after modeling, protein and mRNA levels of PDGF-BB, HIF-1α and Ki67 in the HPH+PDGF-BB group were higher than the other groups ( P<0.05). The protein and mRNA expression levels of PDGF-BB, HIF-1α and Ki67 in the HPH+STI571 group were lower than the HPH+PDGF-BB group and the HPH group at all timepoints ( P<0.05). Conclusions:PDGF-BB up-regulates HIF-1α expression, participates in PASMC proliferation, exacerbates pulmonary vascular remodeling and increases pulmonary artery pressure in neonatal rats with HPH.Obiective:To study the roles of platelet-derived growth factor-BB (PDGF-BB) in hypoxic pulmonary hypertension (HPH) and the mechanisms of regulating hypoxia-inducible factor-1α (HIF-1α) expression, promoting the proliferation of pulmonary arterial smooth muscle cells (PASMC) and participating in the remodeling of pulmonary vessels.
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Objective To explore the clinical characteristics and treatment scheme of periprosthetic joint infection(PJI)caused by Cutibacterium avidum(C.avidum).Methods The diagnosis and treatment process of a patient with PJI caused by C.avidum was summarized,and relevant literatures in the database were retrieved for review.Results A 65-year-old female patient with body mass index(BMI)of 31.1 kg/m2 underwent left humeral head prosthesis replacement surgery following a left proximal humerus fracture.Ten months after the surgery,the pa-tient exhibited poor wound healing and oozing,along with limited movement of the left shoulder joint,and was diag-nosed infection following shoulder arthroplasty.Patient underwent debridement of the infected lesion and removal of the prosthesis.The tissue,bone cement and prosthesis were cultured for C.avidum.Four literatures were re-trieved and screened,a total of 30 patients with PJI(28 cases hip joint infection and 2 cases shoulder joint infection)caused by C.avidum were reported through literature retrieval,and 78.6%(n=22)total hip arthroplasty(THA)surgeries were performed using direct anterior approach(DAA).The positive rate of preoperative joint fluid culture was 71.4%,29 cases underwent surgical combined with sensitive antimicrobials treatment.Except for one patient who had repeated infection and underwent three surgeries,other patients had a good prognosis.Conclusion PJI caused by C.avidum is mostly seen in THA patients who are obese and undergo DAA,with a few cases reported after shoulder arthroplasty.The high sensitivity of preoperative joint fluid culture provides an important basis for the development of surgical strategies and anti-infection protocols.
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@#Objective To explore the effect of high-intensity ultrasound focused ablation in the treatment of ⅡB cesarean scar Pregnancy.Methods A total of 365 patients in our hospital from January 2019 to December 2021 which were ⅡB Cesarean Scar Pregnancy were selected as the research objects.The research objects were divided into the experimental group pretreated by high-intensity ultrasound ablation(186 cases)and the control group without treatment(179 cases)to compare the levels of intraoperative blood loss,postoperative vaginal bleeding time,human chorionic gonadotropin(HCG)decline rate after the operation,success rate of operation and other indicators.Results The amount of intraoperative blood loss and postoperative vaginal bleeding time in the experimental group were less than those in the control group(P<0.05),and the decrease rate of blood HCG in the experimental group was higher than that in the control group(P<0.05).There was significant difference in the success rate of operation between the experimental group and the control group(P<0.05).There was no significant difference in menstrual volume between the experimental group and the control group(P>0.05),but the control group had prolonged menstruation,and the incidence of postoperative complications between the experimental group and the control group have no statistical significance.Conclusion High-intensity focused ultrasound ablation can effectively reduce intraoperative blood loss in patients of type ⅡB cesarean scar pregnancy,reduce the application of invasive methods such as laparoscopy,can be promoted as a pretreatment method for type ⅡB cesarean scar pregnancy.
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BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.
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Non-alcoholic Fatty Liver Disease , Sirtuin 1 , Animals , Mice , Sirtuin 1/metabolism , Organelle Biogenesis , Molecular Docking Simulation , Flavonoids/pharmacology , Flavonoids/therapeutic use , Glycosides/pharmacology , Non-alcoholic Fatty Liver Disease/metabolism , Liver/metabolismABSTRACT
Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.
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Artificial Intelligence , Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , High-Throughput Screening Assays , Molecular Docking SimulationABSTRACT
Objective:To investigate the accuracy of infra-acetabular screw implantation assisted by a 3D-printed personalized screw guide in vitro. Methods:The imaging data were collected of the 10 patients with acetabular fracture involving the anterior column who had been treated at Department of Orthopaedics, The Fourth Hospital of Wuhan from June 2015 to October 2021. There were 8 males and 2 females, with an average age of (42.6±2.1) years. According to the Letournel-Judet classification, there were 2 anterior column fractures, 4 anterior column + posterior semi-transverse fractures, 3 double column fractures, and 1 T-shaped fracture. The thin-slice CT scan data of the patients’ pelves were imported into the E3D software to generate digital 3D fracture models in which fracture reduction and post-reduction were simulated and personalized screw guides for infra-acetabular screw implantation were generated. After the above models were printed by a 3D printer, the fracture models were reduced in vitro and the infra-acetabular screws were implanted assisted by the personalized guide on the affected and healthy acetabulum models. After operation, the printed models were scanned by CT again, and the CT data were imported into the E3D software again to generate the postoperative digital 3D models. The position relationships were observed between the screws and the cortex around the corridor on the postoperative CT scan images. The consistency of the position parameters was compared between pre- and post-operation for each screw in the digital models. Results:Ten personalized screw guides were generalized respectively for the affected and healthy sides of the 10 patients in this group. Anatomical reduction was achieved in vitro in all the 3D printed fracture models. A total of 20 infra-acetabular screws were implanted with the assistance by the screw guide. According to the Andrew's CT grading for pedicle screw positions, 19 infra-acetabular screws were rated as grade Ⅰ and 1 was rated as grade Ⅱ. The linear distance from the midpoint of the pubic symphysis to the point of insertion, and the angles between the axis of the screw and the horizontal, sagittal and coronal planes on the health side before operation were respectively (60.65±5.55) mm, 23.96°±5.59°),2.88 °±1.25°, and 65.06°±5.48°, showing insignificant differences from the postoperative values [(60.91±5.73) mm, 24.00°±6.15°, 3.20°±1.13°, and 65.74°±5.57°] ( P>0.05); the above screw position parameters on the affected side before operation were respectively (60.76±4.41) mm, 24.77°±2.97°, 3.06° (2.66°, 3.68°), and 63.70° (62.70°, 65.60°), showing insignificant differences from the postoperative values [(60.71±4.56) mm, 24.67°±2.73°, 3.04° (2.64°, 3.51°), and 64.40°(63.20°, 65.90°)] ( P>0.05). Conclusion:In the models in vitro, implantation of infra-acetabular screws assisted by a 3D printed personalized screw guide can be highly accurate, owing to insignificant differences in all the position parameters between the simulated operations and the operations in vitro.
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Objective:To investigate the application prospect of 3D virtual reconstruction and printing technology based on thin-slice CT images in network cloud+dual-track teaching.Methods:A total of 120 medical students who were on probation in The Second Affiliated Hospital of Air Force Medical University from April 2021 to April 2022 were selected as subjects and were randomly divided into experimental group and control group, with 60 students in each group. The students in the experimental group received 3D virtual reconstruction and printing technology combined with network cloud+dual-track teaching, and those in the control group received network cloud+dual-track teaching alone. After 6 months of learning, the teaching effect was compared by closed-book examination, skill operation, speech defense, and questionnaire survey. SPSS 23.0 was used for the t-test and the chi-square test. Results:Compared with the control group in terms of department examination, the experimental group had significantly better scores of theoretical knowledge [(84.25±5.53) vs. (79.43±6.69), P<0.001] and operational skills [(87.68±5.72) vs. (82.97±5.32), P<0.001]. The experimental group had significantly higher scores than the control group in speech [(44.90±2.56) vs. (41.88±2.71), P<0.001] and defense [(45.83±2.62) vs. (43.85±2.56), P<0.001]. The questionnaire survey showed that compared with the control group, the experimental group had significantly higher scores of practical ability, active learning ability, expression ability, practice enthusiasm, and information acquisition ability ( P<0.001). Conclusion:The network cloud+dual-track teaching model assisted by 3D virtual reconstruction and printing technology can significantly improve the objective learning effect and subjective learning initiative of students and has a relatively high value of teaching application and promotion.
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ObjectiveTo improve the anti-fall capacity and safety of the smart walkers. MethodsTwo pressure sensors were placed on the handles on both sides of the walker. The confusion matrix was obtained, the corresponding operational intent labels were manually labeled, using a support vector machine (SVM) classifier for model prediction to predict the travel intent of the users. The user wore a gyroscope and the walker was equipped with a laser sensor, to measure the angular velocity, angular acceleration and the distance data, respectively, to detect the user's fall. ResultsThe classifier model established by SVM successfully predicted three operating states of the walker, namely straight ahead, left turning and right turning. The user's fall was detected by the sudden change of the following data: the combined angular velocity was greater than 100°/s, the combined angular acceleration was greater than 1.3 G, the angular acceleration of Z-axis was greater than 0.7 G or less than 0.2 G, and the distance was greater than 600 mm or less than 300 mm. ConclusionThe improvement of the walker can predict the turn intention of the user, and detect the user's fall.
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Aim To investigate the effect of quercetin (Que) on secretory otitis media (SOM) rats and its mechanism. Methods Forty-eight male SD rats were selected and randomly divided into control group (control), model group (model), Que group (100 mg • kg