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1.
Nature ; 604(7907): 763-770, 2022 04.
Article in English | MEDLINE | ID: mdl-35418678

ABSTRACT

Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes1-6. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence7-12. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with Gs: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-ß-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W6.53 and the constitution of a hydrogen-bond network formed by Q7.49/Y7.49 and the P6.47/V6.47φφG6.50 motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and Gs coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common Gs-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with Gs. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their Gs coupling.


Subject(s)
Peptides , Receptors, G-Protein-Coupled , Binding Sites , Cryoelectron Microscopy , Protein Domains , Protein Structure, Secondary , Receptors, G-Protein-Coupled/metabolism , Structure-Activity Relationship
2.
Nucleic Acids Res ; 52(11): 6114-6128, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38709881

ABSTRACT

Inferring the developmental potential of single cells from scRNA-Seq data and reconstructing the pseudo-temporal path of cell development are fundamental but challenging tasks in single-cell analysis. Although single-cell transcriptional diversity (SCTD) measured by the number of expressed genes per cell has been widely used as a hallmark of developmental potential, it may lead to incorrect estimation of differentiation states in some cases where gene expression does not decrease monotonously during the development process. In this study, we propose a novel metric called single-cell transcriptional complexity (SCTC), which draws on insights from the economic complexity theory and takes into account the sophisticated structure information of scRNA-Seq count matrix. We show that SCTC characterizes developmental potential more accurately than SCTD, especially in the early stages of development where cells typically have lower diversity but higher complexity than those in the later stages. Based on the SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interplay between cells and genes determines the developmental potential, providing new insights into the understanding of biological development from the perspective of complexity theory.


Subject(s)
Single-Cell Analysis , Single-Cell Analysis/methods , Animals , Cell Differentiation/genetics , Mice , Transcription, Genetic , Gene Expression Regulation, Developmental , Gene Expression Profiling/methods , Algorithms , Humans , Sequence Analysis, RNA/methods
3.
Brief Bioinform ; 24(1)2023 01 19.
Article in English | MEDLINE | ID: mdl-36642414

ABSTRACT

The proliferation of single-cell multimodal sequencing technologies has enabled us to understand cellular heterogeneity with multiple views, providing novel and actionable biological insights into the disease-driving mechanisms. Here, we propose a comprehensive end-to-end single-cell multimodal analysis framework named Deep Parametric Inference (DPI). DPI transforms single-cell multimodal data into a multimodal parameter space by inferring individual modal parameters. Analysis of cord blood mononuclear cells (CBMC) reveals that the multimodal parameter space can characterize the heterogeneity of cells more comprehensively than individual modalities. Furthermore, comparisons with the state-of-the-art methods on multiple datasets show that DPI has superior performance. Additionally, DPI can reference and query cell types without batch effects. As a result, DPI can successfully analyze the progression of COVID-19 disease in peripheral blood mononuclear cells (PBMC). Notably, we further propose a cell state vector field and analyze the transformation pattern of bone marrow cells (BMC) states. In conclusion, DPI is a powerful single-cell multimodal analysis framework that can provide new biological insights into biomedical researchers. The python packages, datasets and user-friendly manuals of DPI are freely available at https://github.com/studentiz/dpi.


Subject(s)
COVID-19 , Leukocytes, Mononuclear , Humans , Single-Cell Analysis/methods , Computational Biology/methods
4.
Article in English | MEDLINE | ID: mdl-38761998

ABSTRACT

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

5.
BMC Plant Biol ; 24(1): 587, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38902638

ABSTRACT

BACKGROUND: Monoacylglycerol lipase (MAGL) genes belong to the alpha/beta hydrolase superfamily, catalyze the terminal step of triglyceride (TAG) hydrolysis, converting monoacylglycerol (MAG) into free fatty acids and glycerol. RESULTS: In this study, 30 MAGL genes in upland cotton have been identified, which have been classified into eight subgroups. The duplication of GhMAGL genes in upland cotton was predominantly influenced by segmental duplication events, as revealed through synteny analysis. Furthermore, all GhMAGL genes were found to contain light-responsive elements. Through comprehensive association and haplotype analyses using resequencing data from 355 cotton accessions, GhMAGL3 and GhMAGL6 were detected as key genes related to lipid hydrolysis processes, suggesting a negative regulatory effect. CONCLUSIONS: In summary, MAGL has never been studied in upland cotton previously. This study provides the genetic mechanism foundation for the discover of new genes involved in lipid metabolism to improve cottonseed oil content, which will provide a strategic avenue for marker-assisted breeding aimed at incorporating desirable traits into cultivated cotton varieties.


Subject(s)
Gossypium , Monoacylglycerol Lipases , Gossypium/genetics , Gossypium/enzymology , Monoacylglycerol Lipases/genetics , Monoacylglycerol Lipases/metabolism , Alleles , Multigene Family , Genome-Wide Association Study , Genome, Plant , Genetic Variation , Phylogeny , Genes, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Haplotypes
6.
BMC Cancer ; 24(1): 368, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519974

ABSTRACT

OBJECTIVE: This study aimed to develop and validate an artificial intelligence radiopathological model using preoperative CT scans and postoperative hematoxylin and eosin (HE) stained slides to predict the pathological staging of gastric cancer (stage I-II and stage III). METHODS: This study included a total of 202 gastric cancer patients with confirmed pathological staging (training cohort: n = 141; validation cohort: n = 61). Pathological histological features were extracted from HE slides, and pathological models were constructed using logistic regression (LR), support vector machine (SVM), and NaiveBayes. The optimal pathological model was selected through receiver operating characteristic (ROC) curve analysis. Machine learnin algorithms were employed to construct radiomic models and radiopathological models using the optimal pathological model. Model performance was evaluated using ROC curve analysis, and clinical utility was estimated using decision curve analysis (DCA). RESULTS: A total of 311 pathological histological features were extracted from the HE images, including 101 Term Frequency-Inverse Document Frequency (TF-IDF) features and 210 deep learning features. A pathological model was constructed using 19 selected pathological features through dimension reduction, with the SVM model demonstrating superior predictive performance (AUC, training cohort: 0.949; validation cohort: 0.777). Radiomic features were constructed using 6 selected features from 1834 radiomic features extracted from CT scans via SVM machine algorithm. Simultaneously, a radiopathomics model was built using 17 non-zero coefficient features obtained through dimension reduction from a total of 2145 features (combining both radiomics and pathomics features). The best discriminative ability was observed in the SVM_radiopathomics model (AUC, training cohort: 0.953; validation cohort: 0.851), and clinical decision curve analysis (DCA) demonstrated excellent clinical utility. CONCLUSION: The radiopathomics model, combining pathological and radiomic features, exhibited superior performance in distinguishing between stage I-II and stage III gastric cancer. This study is based on the prediction of pathological staging using pathological tissue slides from surgical specimens after gastric cancer curative surgery and preoperative CT images, highlighting the feasibility of conducting research on pathological staging using pathological slides and CT images.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnostic imaging , Artificial Intelligence , Algorithms , Eosine Yellowish-(YS) , Tomography, X-Ray Computed
7.
J Appl Microbiol ; 135(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38299790

ABSTRACT

AIMS: During fermentation, the accumulation of acidic products can induce media acidification, which restrains the growth of Bifidobacterium animalis subsp. lactis Bb12 (Bb12). This study investigated the nutrient consumption patterns of Bb12 under acid stress and effects of specific nutrients on the acid resistance of Bb12. METHODS AND RESULTS: Bb12 was cultured in chemically defined medium (CDM) at different initial pH values. Nutrient consumption patterns were analyzed in CDM at pH 5.3, 5.7, and 6.7. The patterns varied with pH: Asp + Asn had the highest consumption rate at pH 5.3 and 5.7, while Ala was predominant at pH 6.7. Regardless of the pH levels (5.3, 5.7, or 6.7), ascorbic acid, adenine, and Fe2+ were vitamins, nucleobases, and metal ions with the highest consumption rates, respectively. Nutrients whose consumption rates exceeded 50% were added individually in CDM at pH 5.3, 5.7, and 6.7. It was demonstrated that only some of them could promote the growth of Bb12. Mixed nutrients that could promote the growth of Bb12 were added to three different CDM. In CDM at pH 5.3, 5.7, and 6.7, it was found that the viable cell count of Bb12 was the highest after adding mixed nutrients, which were 8.87, 9.02, and 9.10 log CFU ml-1, respectively. CONCLUSIONS: The findings suggest that the initial pH of the culture medium affects the nutrient consumption patterns of Bb12. Specific nutrients can enhance the growth of Bb12 under acidic conditions and increase its acid resistance.


Subject(s)
Bifidobacterium animalis , Probiotics , Acids , Purines , Nutrients , Pyrimidines , Hydrogen-Ion Concentration
8.
Acta Pharmacol Sin ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811774

ABSTRACT

Exercise training effectively relieves anxiety disorders via modulating specific brain networks. The role of post-translational modification of proteins in this process, however, has been underappreciated. Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise, in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex (mPFC). In particular, exercise was proposed to modulate the phosphorylation of Nogo-A protein, which drives the ras homolog family member A (RhoA)/ Rho-associated coiled-coil-containing protein kinases 1(ROCK1) signaling cascade. Further mechanistic studies found that liver-derived kynurenic acid (KYNA) can affect the kynurenine metabolism within the mPFC, to modulate this RhoA/ROCK1 pathway for conferring stress resilience. In sum, we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC, and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.

9.
BMC Psychiatry ; 24(1): 262, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594695

ABSTRACT

BACKGROUND: Schizophrenia (SCZ) is a profound mental disorder with a multifactorial etiology, including genetics, environmental factors, and demographic influences such as ethnicity and geography. Among these, the studies of SCZ also shows racial and regional differences. METHODS: We first established a database of biological samples for SCZ in China's ethnic minorities, followed by a serum metabolomic analysis of SCZ patients from various ethnic groups within the same region using the LC-HRMS platform. RESULTS: Analysis identified 47 metabolites associated with SCZ, with 46 showing significant differences between Miao and Han SCZ patients. These metabolites, primarily fatty acids, amino acids, benzene, and derivatives, are involved in fatty acid metabolism pathways. Notably, L-Carnitine, L-Cystine, Aspartylphenylalanine, and Methionine sulfoxide demonstrated greater diagnostic efficacy in Miao SCZ patients compared to Han SCZ patients. CONCLUSION: Preliminary findings suggest that there are differences in metabolic levels among SCZ patients of different ethnicities in the same region, offering insights for developing objective diagnostic or therapeutic monitoring strategies that incorporate ethnic considerations of SCZ.


Subject(s)
Schizophrenia , Humans , Asian People/ethnology , China , Ethnic and Racial Minorities , Ethnicity , Genetic Predisposition to Disease , Schizophrenia/diagnosis , Schizophrenia/ethnology , Schizophrenia/metabolism
10.
Appl Opt ; 63(5): 1306-1312, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38437310

ABSTRACT

A broadband and narrowband switchable terahertz (THz) absorber based on a bulk Dirac semimetal (BDS) and strontium titanate (STO) is proposed. Narrowband and broadband absorption can be switched by adjusting the Fermi level of the BDS. When the Fermi level of the BDS is 100 meV, the device is an absorber with three narrowband absorption peaks. The frequencies are 0.44, 0.86, and 1.96 THz, respectively, when the temperature of STO is 250 K. By adjusting the temperature of STO from 250 to 500 K, the blue shifts of the frequencies are approximately 0.14, 0.32, and 0.60 THz, respectively. The sensitivities of the three absorption peaks are 0.56, 1.27, and 2.38 GHz/K, respectively. When the Fermi level of the BDS is adjusted from 100 to 30 meV, the device can be switched to a broadband absorber with a bandwidth of 0.70 THz. By adjusting the temperature of STO from 250 to 500 K, the central frequency shifts from 1.40 to 1.79 THz, and the bandwidth broadens from 0.70 to 0.96 THz. The sensitivity of the central frequency is 1.57 GHz/K. The absorber also has a wide range of potential applications in multifunctional tunable devices, such as temperature sensors, stealth equipment, and filters.

11.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: mdl-33947811

ABSTRACT

Invadopodia are integrin-mediated adhesions with abundant PI(3,4)P2 However, the functional role of PI(3,4)P2 in adhesion signaling remains unclear. Here, we find that the PI(3,4)P2 biogenesis regulates the integrin endocytosis at invadopodia. PI(3,4)P2 is locally produced by PIK3CA and SHIP2 and is concentrated at the trailing edge of the invadopodium arc. The PI(3,4)P2-rich compartment locally forms small puncta (membrane buds) in a SNX9-dependent manner, recruits dynein activator Hook1 through AKTIP, and rearranges into micrometer-long tubular invaginations (membrane tubes). The uncurving membrane tube extends rapidly, follows the retrograde movement of dynein along microtubule tracks, and disconnects from the plasma membrane. Activated integrin-beta3 is locally internalized through the pathway of PI(3,4)P2-mediated membrane invagination and is then actively recycled. Blockages of PI3K, SHIP2, and SNX9 suppress integrin-beta3 endocytosis, delay adhesion turnover, and impede transwell invasion of MEF-Src and MDA-MB-231 cells. Thus, the production of PI(3,4)P2 promotes invasive cell migration by stimulating the trafficking of integrin receptor at the invadopodium.


Subject(s)
Cell Movement/drug effects , Integrins/metabolism , Phosphatidylinositols/metabolism , Phosphatidylinositols/pharmacology , Cell Adhesion/drug effects , Cell Line , Cell Membrane/metabolism , Class I Phosphatidylinositol 3-Kinases/metabolism , Endocytosis/drug effects , Humans , Integrin beta3/metabolism , Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/metabolism , Podosomes , Signal Transduction/physiology
12.
J Sci Food Agric ; 104(10): 5982-5990, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38427028

ABSTRACT

BACKGROUND: One of the greatest challenges in using Lactobacillus acidophilus as a probiotic is acid stress. The current research aimed to identify substances that help L. acidophilus resist acid stress; this was achieved through assessing its nutrient consumption patterns under various pH conditions. RESULTS: The consumption rates of alanine, uracil, adenine, guanine, niacin, and manganese were consistently higher than 60% for L. acidophilus LA-5 cultured at pH 5.8, 4.9, and 4.4. The consumption rates of glutamic acid + glutamine and thiamine increased with decreasing pH and were higher than 60% at pH 4.9 and 4.4. The viable counts of L. acidophilus LA-5 were significantly increased under the corresponding acidic stress conditions (pH 4.9 and 4.4) through the appropriate addition of either alanine (3.37 and 2.81 mmol L-1), glutamic acid + glutamine (4.77 mmol L-1), guanine (0.13 and 0.17 mmol L-1), niacin (0.02 mmol L-1), thiamine (0.009 mmol L-1), or manganese (0.73 and 0.64 mmol L-1) (P < 0.05). The viable counts of L. acidophilus LA-5 cultured in a medium supplemented with combined nutritional factors was 1.02-1.03-fold of the counts observed in control medium under all acid conditions (P < 0.05). CONCLUSION: Alanine, glutamic acid + glutamine, guanine, niacin, thiamine, and manganese can improve the growth of L. acidophilus LA-5 in an acidic environment in the present study. The results will contribute to optimizing strategies to enhance the acid resistance of L. acidophilus and expand its application in the fermentation industry. © 2024 Society of Chemical Industry.


Subject(s)
Lactobacillus acidophilus , Probiotics , Lactobacillus acidophilus/metabolism , Lactobacillus acidophilus/growth & development , Hydrogen-Ion Concentration , Nutrients/metabolism , Fermentation
13.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2532-2543, 2024 May.
Article in Zh | MEDLINE | ID: mdl-38812149

ABSTRACT

This study employed knowledge graph technology to analyze the research status and hot spots of Realgar and provide guidance for clinical application and further research of this drug. The research articles both in English and Chinese involving Realgar were retrieved from five databases including CNKI, Wanfang, VIP, SinoMed, and Web of Science. And NoteExpress, a literature management software was used to screen literature. CiteSpace was utilized for visualized analysis and presentations of the authors, institutions, and keywords. 2 879 articles in Chinese and 194 articles in English were included. China Journal of Chinese Materia Medica and Journal of Ethnopharmacology were the top Chinese and English journals in terms of publication volume. Realgar is widely used in the treatment of skin diseases, blood diseases, and cancer. JIANG Hong was the author who have published more articles in Chinese and English working with teams. School of Public Health of China Medical University and China Academy of Chinese Medical Sciences published the most articles in Chinese and English. The research on Realgar mainly focuses on clinical application, mechanism of action, reduction of toxicity, and enhancement of efficacy. The authors and institutions of Realgar research are mainly concentrated in China. The study on the mechanism of treating hematological diseases and cancer with Realgar, as well as the research on its effects of reducing toxicity and enhancing efficacy, are the current research hotspots. The mechanism of "same treatment for different diseases" in Realgar needs to be further explored. It is urgent to carry out interdisciplinary research on Realgar. This study can provide a refe-rence for the clinical application of Realgar and provide ideas for further research on Realgar.


Subject(s)
Arsenicals , Sulfides , Humans , Arsenicals/chemistry , China , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Biomedical Research
14.
J Clin Microbiol ; 61(6): e0183222, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37249422

ABSTRACT

The Xpert MTB/XDR assay met the critical need for etiologic diagnosis of tuberculosis and rifampin resistance in previous studies. However, its benefits in tailoring the treatment regimen and improving the outcome for patients with rifampin-resistant tuberculosis (RR-TB) require further investigation. In this study, the Xpert MTB/XDR assay was used to determine the resistance profile of second-line drugs for RR-TB patients in two registered multicenter clinical trials, TB-TRUST (NCT03867136) and TB-TRUST-plus (NCT04717908), with the aim of testing the efficacy of all-oral shorter regimens in RR-TB patients in China. Patients would receive the fluoroquinolone-based all-oral shorter regimen, the injectable-containing regimen, or the bedaquiline-based regimen depending on fluoroquinolone susceptibility by using Xpert MTB/XDR. Among the 497 patients performed with Xpert MTB/XDR, 128 (25.8%) had infections resistant to fluoroquinolones and/or second-line injectable drugs (SLIDs). A total of 371 participants were recruited for the trials, and whole-genome sequencing (WGS) was performed on all corresponding culture-positive baseline strains. Taking the WGS results as the standard, the accuracy of the Xpert MTB/XDR assay in terms of resistance detection was 95.2% to 99.0% for all drugs. A total of 33 cases had inconsistent results, 9 of which were due to resistance heterogeneity. Most of the patients (241/281, 85.8%) had sputum culture conversion at 2 months. In conclusion, the Xpert MTB/XDR assay has the potential to serve as a quick reflex test in patients with RR-TB, as detected via Xpert MTB/RIF, to provide a reliable drug susceptibility profile of the infecting Mycobacterium tuberculosis strain and to initiate optimized treatment promptly.


Subject(s)
Antibiotics, Antitubercular , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Humans , Rifampin/pharmacology , Rifampin/therapeutic use , Antibiotics, Antitubercular/pharmacology , Sensitivity and Specificity , Tuberculosis/diagnosis , Mycobacterium tuberculosis/genetics , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Drug Resistance, Bacterial , Sputum/microbiology
15.
BMC Infect Dis ; 23(1): 300, 2023 May 08.
Article in English | MEDLINE | ID: mdl-37158831

ABSTRACT

BACKGROUND: Standard treatment for drug-susceptible tuberculosis (DS-TB) includes a multidrug regimen requiring at least 6 months of treatment, and this lengthy treatment easily leads to poor adherence. There is an urgent need to simplify and shorten treatment regimens to reduce interruption and adverse event rates, improve compliance, and reduce costs. METHODS: ORIENT is a multicenter, randomized controlled, open-label, phase II/III, non-inferiority trial involving DS-TB patients to evaluate the safety and efficacy of short-term regimens compared with the standardized six-month treatment regimen. In stage 1, corresponding to a phase II trial, a total of 400 patients are randomly divided into four arms, stratified by site and the presence of lung cavitation. Investigational arms include 3 short-term regimens with rifapentine 10 mg/kg, 15 mg/kg, and 20 mg/kg, while the control arm uses the standardized six-month treatment regimen. A combination of rifapentine, isoniazid, pyrazinamide, and moxifloxacin is administered for 17 or 26 weeks in rifapentine arms, while a 26-week regimen containing rifampicin, isoniazid, pyrazinamide, and ethambutol is applied in the control arm. After the safety and preliminary effectiveness analysis of patients in stage 1, the control arm and the investigational arm meeting the conditions will enter into stage 2, which is equivalent to a phase III trial and will be expanded to recruit DS-TB patients. If all investigational arms do not meet the safety conditions, stage 2 will be canceled. In stage 1, the primary safety endpoint is permanent regimen discontinuation at 8 weeks after the first dose. The primary efficacy endpoint is the proportion of favorable outcomes at 78 weeks after the first dose for both two stages. DISCUSSION: This trial will contribute to the optimal dose of rifapentine in the Chinese population and suggest the feasibility of the short-course treatment regimen containing high-dose rifapentine and moxifloxacin for DS-TB. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov on 28 May 2022 with the identifier NCT05401071.


Subject(s)
Rifampin , Tuberculosis , Humans , Rifampin/adverse effects , Isoniazid/adverse effects , Pyrazinamide , Moxifloxacin/therapeutic use , Tuberculosis/drug therapy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic
16.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 126-131, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38279463

ABSTRACT

Colorectal cancer (CRC) is one of the most common and lethal malignancies. According to our analysis in the GEPIA database, SPTBN2 was found to be significantly elevated in COAD patients.Western blot also verified this result, and SPTBN2 was highly expressed in two types of colorectal cancer cells, Caco2 and HCT-8. Therefore, we knocked down SPTBN2 to investigate its function in colorectal cancer, and the results of CCK-8 and Transwell assays showed that SPTBN2 deletion inhibited the proliferation, migration and invasion of CRC cells. In addition, we found that SPTBN2 may be a target of miR-214-3p through the staebase database. miR-214-3p inhibitors promote CRC cell proliferation, migration and invasion. And inhibition of SPTBN2 partially reversed the effect of miR-214-3p in CRC. Taken together, we demonstrated that SPTBN2 acts as an important target of miR-214-3p in CRC. Our study lays the foundation for the mechanism of CRC.


Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , Caco-2 Cells , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , MicroRNAs/genetics , Spectrin/metabolism
17.
BMC Psychiatry ; 23(1): 490, 2023 07 10.
Article in English | MEDLINE | ID: mdl-37430235

ABSTRACT

BACKGROUND: Individuals with diabetes have increased risk of depression, but there are limited nationally representative studies on this topic. We aimed to investigate the prevalence and predictors of depression, as well as its impact on all-cause and cardiovascular mortality in adults with type 2 diabetes (T2DM) using a prospective cohort study and a representative sample of the U.S. METHODS: We analyzed National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018 and linked it with the most recent publicly available National Death Index (NDI) data. Individuals aged 20 years or old who had depression measurements were included. Depression was defined as a Patient Health Questionnaire (PHQ-9) score ≥ 10, and categorized into moderate (10-14 points) and moderately severe to severe (≥ 15 points). Cox proportional hazard models were used to estimate the association between depression and mortality. RESULTS: Among 5695 participants with T2DM, 11.6% had depression. Depression was associated with female gender, younger age, overweight, lower education, being unmarried, smoking, and a history of coronary heart disease and stroke. During a mean follow-up period of 78.2 months, 1161 all-cause deaths occurred. Total depression and moderately severe to severe depression significantly increased all-cause mortality (adjusted hazard ratio [aHR] 1.36, 95% CI [1.09-1.70]; 1.67 [1.19-2.34]) and non-cardiovascular mortality (aHR 1.36, 95% CI [1.04-1.78]; 1.78, 95% CI [1.20-2.64]), but not cardiovascular mortality. Subgroup analysis showed a significant association between total depression and all-cause mortality in males (aHR 1.46, 95% CI [1.08-1.98]) and those aged 60 years or older (aHR 1.35, 95% CI [1.02-1.78]). Any severity of depression was not significantly associated with cardiovascular mortality in age- or gender- stratified subgroups. CONCLUSIONS: In a nationally representative sample of U.S. adults with T2DM, approximately 10% experienced depression. Depression did not significantly associate with cardiovascular mortality. However, comorbid depression in T2DM patients increased the risk of all-cause and non-cardiovascular mortality. The impact of depression on mortality varied across subgroups. Therefore, healthcare providers should consider incorporating depression screening and management into routine care, especially for subgroups with specific risk factors, due to the increased risk of all-cause mortality in T2DM patients with depression.


Subject(s)
Diabetes Mellitus, Type 2 , Adult , Male , Humans , Female , Nutrition Surveys , Diabetes Mellitus, Type 2/complications , Cohort Studies , Prevalence , Prospective Studies
18.
Appl Opt ; 62(21): 5822-5829, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37707202

ABSTRACT

In this study, a perfect metamaterial absorber based on strontium titanate and bulk Dirac semimetals is proposed. When the temperature of strontium titanate was 300K, the dual-band absorptions were 99.74% and 99.99% at 1.227 and 1.552 THz, respectively. The sensitivities based on a transverse magnetic (TM) wave were 0.95 and 1.22 GHz/K; the sensitivity based on a transverse electric (TE) wave was 0.76 GHz/K. The TE and TM waves were modulated by inserting a bulk Dirac semimetal between the concave and convex devices. The modulation depth of the TE wave was 97.9% at 1.1 THz; the extinction ratio was 16.9 dB. The modulation depth of the TE wave at 1.435 THz was 95.9%; the extinction ratio was 13.89 dB. The TM wave modulation depth at 1.552 THz was 95.9%; the extinction ratio was 13.98 dB. Irrespective of a TE or TM wave, the terahertz absorber has good switching and temperature-sensing performance based on strontium titanate and bulk Dirac semimetals as well as broad application prospects in temperature sensing and switching devices.

19.
Langenbecks Arch Surg ; 408(1): 131, 2023 Mar 29.
Article in English | MEDLINE | ID: mdl-36991272

ABSTRACT

PURPOSE: The study's objectives were to compare the short-term outcomes of robotic radical distal gastrectomy (RDG) with laparoscopic radical distal gastrectomy (LDG) for patients with gastric cancer and investigate the learning curve of RDG. METHODS: The cumulative sum (CUSUM) method was used to retrospectively analyze consecutive gastric cancer patients undergoing RDG between January 2019 and October 2021. The duration of surgery, clinical-pathological characteristics, and short-term outcomes were evaluated according to the two phases of the learning curve (learning period versus mastery period). We also compared the clinical-pathological characteristics and short-term outcomes between cases in the mastery period and LDG. RESULTS: Data from 290 patients were included in this analysis, 135 RDG and 155 LDG cases. The learning period was 20 cases. There were no significant differences in clinical-pathological characteristics between the learning period and mastery period. Compared with the learning period, the mastery period had a significant reduction in total operation time, docking time, pure operation time, and estimated blood loss, and a significant increase in hospital costs (P=0.000, 0.000, 0.000, 0.003, and 0.026, respectively). Compared with LDG, robotic cases in mastery period had a longer operative time, shorter first postoperative flatus time, and more hospital costs (P=0.000, 0.005, and 0.000, respectively). CONCLUSIONS: RGD may fasten to recover gastrointestinal function faster after the operation, can be mastered easily after a reasonable number of cases, and was associated with safe and satisfactory short-term outcomes before and after the learning curve.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Stomach Neoplasms , Humans , Robotic Surgical Procedures/methods , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Retrospective Studies , Treatment Outcome , Gastrectomy/methods , Laparoscopy/methods
20.
World J Surg Oncol ; 21(1): 317, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37817203

ABSTRACT

PURPOSE: The study aimed to analyze the clinical efficacy and safety of hand-sewn anastomosis for the digestive tract with Da Vinci robot in rectal cancer surgery. METHODS: A retrospective study was conducted to collect the clinical data from 27 patients who underwent Da Vinci robotic rectal cancer radical surgery in the department of gastrointestinal surgery at the Second Affiliated Hospital of Dalian Medical University from August 2019 to February 2022. All patients received a manual suture for digestive tract reconstruction. After the posterior wall was sutured, the anterior wall was sutured continuously. Finally, a prilling thread was used to sew the junction of the front and rear walls. Perioperative indexes and complications were recorded. RESULTS: All 27 patients successfully underwent the operation. Neither conversion to laparotomy nor perioperative death occurred. The operation time and intraoperative blood loss were 183.6 ± 44.8 min and 54.8 ± 34.4 ml, respectively. A total of 15.3 ± 7.8 lymph nodes were harvested. The pain score 24 h after operation was 1.3 ± 1.3. The time out of bed, the time to exhaust, and the time to eat were 15.6 ± 2.9 h, 2.2 ± 0.8 days, and 2.1 ± 0.6 days, respectively. A total of 4 patients (14.8%) developed complications after the operation. Grade B anastomotic leakage gradually resolved after drainage and antibiotic therapy in 1 case. A patient with grade C anastomotic leakage received a second operation for ileostomy. One patient with postoperative pneumonia recovered after anti-infective treatment. Another patient with intraperitoneal hemorrhage improved after symptomatic treatment with blood transfusion and hemostasis. The postoperative hospitalization time and total hospitalization costs were 8.9 ± 4.4 days and 89,236.1 ± 13,527.9 yuan, respectively. CONCLUSIONS: Manual suture with Da Vinci robotic surgery system is safe and feasible for reconstructing the digestive tract in rectal cancer surgery.


Subject(s)
Rectal Neoplasms , Robotics , Humans , Anastomotic Leak/etiology , Retrospective Studies , Rectum/surgery , Rectal Neoplasms/surgery , Treatment Outcome , Anastomosis, Surgical
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