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1.
J Med Chem ; 67(14): 11989-12011, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38959216

RESUMO

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.


Assuntos
Doenças Inflamatórias Intestinais , Receptores Purinérgicos P2 , Tiofenos , Animais , Tiofenos/farmacologia , Tiofenos/síntese química , Tiofenos/química , Tiofenos/uso terapêutico , Humanos , Camundongos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Receptores Purinérgicos P2/metabolismo , Relação Estrutura-Atividade , Antagonistas do Receptor Purinérgico P2/farmacologia , Antagonistas do Receptor Purinérgico P2/química , Antagonistas do Receptor Purinérgico P2/síntese química , Antagonistas do Receptor Purinérgico P2/uso terapêutico , Masculino , Descoberta de Drogas , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Amidas/uso terapêutico , Microssomos Hepáticos/metabolismo , Simulação de Dinâmica Molecular , Colite/tratamento farmacológico
2.
Nanomicro Lett ; 16(1): 251, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037551

RESUMO

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions. Microrobots have been gradually used in organisms due to their advantages of intelligent, precise and minimally invasive targeted delivery. Through the combination of control and imaging systems, microrobots with good biosafety can be delivered to the desired area for treatment. In the musculoskeletal system, microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body. Compared to traditional biomaterial and tissue engineering strategies, active motion improves the efficiency and penetration of local targeting of cells/drugs. This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system. We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

3.
Cell Rep ; 43(7): 114458, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38996070

RESUMO

Regulatory T (Treg) cells play a critical regulatory role in the immune system by suppressing excessive immune responses and maintaining immune balance. The effective migration of Treg cells is crucial for controlling the development and progression of inflammatory diseases. However, the mechanisms responsible for directing Treg cells into the inflammatory tissue remain incompletely elucidated. In this study, we identified BAF60b, a subunit of switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complexes, as a positive regulator of Treg cell migration that inhibits the progression of inflammation in experimental autoimmune encephalomyelitis (EAE) and colitis animal models. Mechanistically, transcriptome and genome-wide chromatin-landscaped analyses demonstrated that BAF60b interacts with the transcription factor RUNX1 to promote the expression of CCR9 on Treg cells, which in turn affects their ability to migrate to inflammatory tissues. Our work provides insights into the essential role of BAF60b in regulating Treg cell migration and its impact on inflammatory diseases.


Assuntos
Movimento Celular , Inflamação , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Camundongos , Inflamação/patologia , Inflamação/metabolismo , Montagem e Desmontagem da Cromatina , Proteínas Cromossômicas não Histona/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/genética , Humanos , Fatores de Transcrição/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Colite/metabolismo , Colite/patologia , Colite/imunologia , Colite/genética
4.
Orphanet J Rare Dis ; 19(1): 245, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956600

RESUMO

BACKGROUND: Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. METHODS: Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. CONCLUSIONS: Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.


Assuntos
Condrócitos , Osteocondrodisplasias , Transportadores de Sulfato , Humanos , Condrócitos/metabolismo , Condrócitos/patologia , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo , Osteocondrodisplasias/genética , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patologia , Masculino , Feminino , Homeostase/genética , Sequenciamento do Exoma
5.
Food Chem Toxicol ; 191: 114887, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39053873

RESUMO

Zearalenone (ZEN) poses a potential threat on human and animal health partly through the nuclear factor (NF)-κB signaling pathway. In silico study suggested that rutin effective against TLR4 and NF-κB. A wetting test was designed to evaluate the effect and underlying mechanism of rutin in alleviating ZEN-induced inflammation in animals. Twenty-four female mice were randomly divided into 4 groups: control (basal diet), ZEN group (basal diet + ZEN), rutin group (basic diet + rutin), Z + R group (basal diet + rutin + ZEN). Results showed that rutin effectively alleviated ZEN-induced inflammation and damage of liver and jejunum in mice. Rutin addition reduced the content of lipopolysaccharide (LPS) in serum and liver mainly by improving the intestinal barrier function resulted from the production increase of short-chain fatty acids (SCFA). In sum, this study showed that rutin alleviated ZEN-induced liver inflammation and injury by modulating the gut microbiota, increasing the production of SCFA and improving intestinal barrier function, leading to the decrease of LPS in liver and the inhibition of MyD88 independent NF-κB signaling pathway in mice. Specifically, these findings may provide useful insights into the screening of functional natural compounds and its action mechanism to alleviate ZEN induced liver inflammation.

6.
Anal Chem ; 96(29): 11923-11931, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38989922

RESUMO

The pH and humidity of the crop environment are essential indicators for monitoring crop growth status. This study reports a lead-free perovskite/polyvinylidene fluoride-hexafluoropropylene composite (LPPC) to enhance the stability and reliability of in situ plant pH and humidity monitoring. The mesh composite membrane of LPPC illustrates a hydrophobic contact angle of 101.982°, a tensile strain of 800%, and an opposing surface potential of less than -184.9 mV, which ensures fast response, high sensitivity, and stability of the sensor during long-term plant monitoring. The LPPC-coated pH electrode possesses a sensitivity of -63.90 mV/pH, which provides a fast response within 5 s and is inert to environmental temperature interference. The LPPC-coated humidity sensor obtains a sensitivity of -145.7 Ω/% RH, responds in 28 s, and works well under varying light conditions. The flexible multimodal sensor coated with an LPPC membrane completed real-time in situ monitoring of soilless strawberries for 17 consecutive days. Satisfactory consistency and accuracy performance are observed. The study provides a simple solution for developing reliable, flexible wearable multiparameter sensors for in situ monitoring of multiple parameters of crop environments.

7.
Sci Rep ; 14(1): 15486, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969732

RESUMO

The adsorption behavior of gold thiosulfate ions on the surface of kaolinite was studied using a combination of experimental research and quantum chemical calculations. Under the condition of a stirring time of 30 min, a stirring speed of 500 r·min-1, and a mass ratio of 30% kaolinite in the slurry, when the initial gold concentration of 56.50 mg·L-1,the adsorption rate of gold-thiosulfate ions from a kaolinite-containing solution was 7.44%. The results of Fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS) showed that the physical and chemical adsorption of kaolinite and gold thiosulfate occurred in solution. Quantum chemical calculations were performed using the CASTEP module in Materials Studio. The adsorption energy of gold thiosulfate on the surface of kaolinite (001) was calculated as - 438.01 kJ·mol-1.The calculated H76-O289 distance was 1.615 Å. Mulliken Charge population analysis and bond population analysis showed that gold thiosulfate ions form relatively stable bonds on the kaolinite surface (001). In the process of thiosulfate immersion, part of gold is adsorbed by kaolinite, which affects the extraction of gold. These results indicate that during the leaching process of gold thiosulfate, kaolinite has the ability to "catch" gold, which affects the leaching efficiency.

8.
Adv Mater ; : e2406922, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011798

RESUMO

Double-fibril network morphology (DFNM), in which the donor and the acceptor can self-assemble into a double-fibril structure, is beneficial for exciton dissociation and charge transport in organic solar cells. Herein, it is demonstrated that such DFNM can be constructed and optimized in all-polymer solar cells (all-PSCs) with the assistance of 2-alkoxynaphthalene volatile solid additives. It is revealed that the incorporation of 2-alkoxynaphthalene can induce a stepwise regulation in the aggregation of donor and acceptor molecules during film casting and thermal annealing processes. Through altering the alkoxy of 2-alkoxynaphthalene solid additives, both the intermolecular interactions and molecular miscibility with the host materials can be precisely tuned, which allows for the optimization of the molecular aggregation process and facilitation of molecular self-assembly, and thus leading to reinforced molecular packing and optimized DFNM. As a result, an unprecedented efficiency of 19.50% (certified as 19.1%) is obtained for 2-ethoxynaphthalene-processed PM6:PY-DT-X all-PSCs with excellent photostability (T80 = 1750 h). This work reveals that the optimization of DFNM via solid additive strategy is a promising avenue to boosting the performance of all-PSCs.

10.
Small Methods ; : e2400204, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38948952

RESUMO

The construction of reliable preclinical models is crucial for understanding the molecular mechanisms involved in gastric cancer and for advancing precision medicine. Currently, existing in vitro tumor models often do not accurately replicate the human gastric cancer environment and are unsuitable for high-throughput therapeutic drug screening. In this study, droplet microfluidic technology is employed to create novel gastric cancer assembloids by encapsulating patient-derived xenograft gastric cancer cells and patient stromal cells in Gelatin methacryloyl (GelMA)-Gelatin-Matrigel microgels. The usage of GelMA-Gelatin-Matrigel composite hydrogel effectively alleviated cell aggregation and sedimentation during the assembly process, allowing for the handling of large volumes of cell-laden hydrogel and the uniform generation of assembloids in a high-throughput manner. Notably, the patient-derived xenograft assembloids exhibited high consistency with primary tumors at both transcriptomic and histological levels, and can be efficiently scaled up for preclinical drug screening efforts. Furthermore, the drug screening results clearly demonstrated that the in vitro assembloid model closely mirrored in vivo drug responses. Thus, these findings suggest that gastric cancer assembloids, which effectively replicate the in vivo tumor microenvironment, show promise for enabling more precise high-throughput drug screening and predicting the clinical outcomes of various drugs.

11.
Adv Exp Med Biol ; 1445: 137-149, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38967756

RESUMO

Intestinal epithelium constitutes a barrier to the unrestricted movement of pathogens, and other detrimental substances from the external world (gut lumen) into the interstitial environment. Intestinal epithelial cells obstruct harmful substances passing through the epithelium as a physical and chemical barrier; Moreover, the epithelial cells can express Toll-like receptors (TLRs) and cytokines to exert innate immune function. In addition, high levels of immunoglobulin A (IgA) and other antibodies exist in the intestinal mucosa, maintaining intestinal immune homeostasis in conjunction with intestinal probiotics. Traditionally, these antibodies have been deemed to be secreted by submucosal plasma cells. Nonetheless, in recent years, it has been demonstrated that intestinal epithelial cells produce a substantial amount of Igs, especially IgA or free Ig light chains, which are involved in intestinal immune homeostasis and the survival of normal epithelial cells. Furthermore, mounting evidence affirms that many human carcinoma cells, including colorectal cancer (CRC), can overexpress Igs, particularly IgG. Cancer-derived Igs exhibit a unique V(D)J rearrangement pattern distinct from B cell-derived Ig; moreover, this cancer cell-derived IgG also has a unique sialic acid modification on the 162 site of CH1 domain (SIA-IgG). The SIA-IgG plays a crucial role in promoting cancer initiation, progression, metastasis, and tumour immune escape. Simultaneously, CRC cells can also express free Ig light chains, which promote colitis, colitis-associated colon carcinogenesis, and CRC progression. Therefore, Igs expressed by CRC cells could be a potential target for diagnosing and preventing the transformation of inflammation into cancer, as well as treating CRC.


Assuntos
Mucosa Intestinal , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Animais , Imunoglobulinas/imunologia , Imunoglobulinas/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-38954584

RESUMO

Brain functional network (BFN) analysis has become a popular method for identifying neurological diseases at their early stages and revealing sensitive biomarkers related to these diseases. Due to the fact that BFN is a graph with complex structure, graph convolutional networks (GCNs) can be naturally used in the identification of BFN, and can generally achieve an encouraging performance if given large amounts of training data. In practice, however, it is very difficult to obtain sufficient brain functional data, especially from subjects with brain disorders. As a result, GCNs usually fail to learn a reliable feature representation from limited BFNs, leading to overfitting issues. In this paper, we propose an improved GCN method to classify brain diseases by introducing a self-supervised learning (SSL) module for assisting the graph feature representation. We conduct experiments to classify subjects with mild cognitive impairment (MCI) and autism spectrum disorder (ASD) respectively from normal controls (NCs). Experimental results on two benchmark databases demonstrate that our proposed scheme tends to obtain higher classification accuracy than the baseline methods.

13.
Phytomedicine ; 132: 155833, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39008915

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and is characterised by extensive invasive and metastatic potential. Previous studies have shown that vitexicarpin extracted from the fruits of Vitex rotundifolia can impede tumour progression. However, the molecular mechanisms involved in CRC treatment are still not fully established. PURPOSE: Our study aimed to investigate the anticancer activity, targets, and molecular mechanisms of vitexicarpin in CRC hoping to provide novel therapies for patients with CRC. STUDY DESIGN/METHODS: The impact of vitexicarpin on CRC was assessed through various experiments including MTT, clone formation, EDU, cell cycle, and apoptosis assays, as well as a tumour xenograft model. CETSA, label-free quantitative proteomics, and Biacore were used to identify the vitexicarpin targets. WB, Co-IP, Ubiquitination assay, IF, molecular docking, MST, and cell transfection were used to investigate the mechanism of action of vitexicarpin in CRC cells. Furthermore, we analysed the expression patterns and correlation of target proteins in TCGA and GEPIA datasets and clinical samples. Finally, wound healing, Transwell, tail vein injection model, and tissue section staining were used to demonstrate the antimetastatic effect of vitexicarpin on CRC in vitro and in vivo. RESULTS: Our findings demonstrated that vitexicarpin exhibits anticancer activity by directly binding to inosine monophosphate dehydrogenase 2 (IMPDH2) and that it promotes c-Myc ubiquitination by disrupting the interaction between IMPDH2 and c-Myc, leading to epithelial-mesenchymal transition (EMT) inhibition. Vitexicarpin hinders the migration and invasion of CRC cells by reversing EMT both in vitro and in vivo. Additionally, these results were validated by the overexpression and knockdown of IMPDH2 in CRC cells. CONCLUSION: These results demonstrated that vitexicarpin regulates the interaction between IMPDH2 and c-Myc to inhibit CRC proliferation and metastasis both in vitro and in vivo. These discoveries introduce potential molecular targets for CRC treatment and shed light on new mechanisms for c-Myc regulation in tumours.

14.
Sensors (Basel) ; 24(14)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39066152

RESUMO

Real-world understanding serves as a medium that bridges the information world and the physical world, enabling the realization of virtual-real mapping and interaction. However, scene understanding based solely on 2D images faces problems such as a lack of geometric information and limited robustness against occlusion. The depth sensor brings new opportunities, but there are still challenges in fusing depth with geometric and semantic priors. To address these concerns, our method considers the repeatability of video stream data and the sparsity of newly generated data. We introduce a sparsely correlated network architecture (SCN) designed explicitly for online RGBD instance segmentation. Additionally, we leverage the power of object-level RGB-D SLAM systems, thereby transcending the limitations of conventional approaches that solely emphasize geometry or semantics. We establish correlation over time and leverage this correlation to develop rules and generate sparse data. We thoroughly evaluate the system's performance on the NYU Depth V2 and ScanNet V2 datasets, demonstrating that incorporating frame-to-frame correlation leads to significantly improved accuracy and consistency in instance segmentation compared to existing state-of-the-art alternatives. Moreover, using sparse data reduces data complexity while ensuring the real-time requirement of 18 fps. Furthermore, by utilizing prior knowledge of object layout understanding, we showcase a promising application of augmented reality, showcasing its potential and practicality.

15.
J Microbiol Biotechnol ; 34(8): 1-11, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-39049482

RESUMO

The quality of tobacco is directly affected by macromolecular content, fermentation is an effective method to improve biochemical properties. In this study, we utilized CBHA (cellobiohydrolase A) glycosylase, which was expressed by Pichia pastoris, as an additive for fermentation. The contents of main chemical components of tobacco leaves after fermentation were determined, and the changes of microbial community structure and abundance in tobacco leaves during fermentation were analyzed. The relationship between chemical composition and changes in microbial composition was investigated, and the function of bacteria and fungi in fermentation was predicted to identify possible metabolic pathways. After 48 h of CBHA fermentation, the contents of starch, cellulose and total nitrogen in tobacco leaf decreased by 17.60%, 28.91% and 16.05%, respectively. The microbial community structure changed significantly, with Aspergillus abundance decreasing significantly, while Filobasidum, Cladosporium, Bullera, Komagataella, etc., increased in CBHA treated group. Soluble sugar was most affected by microbial community in tobacco leaves, which was negatively correlated with starch, cellulose and total nitrogen. During the fermentation process, the relative abundance of metabolism-related functional genes increased, and the expressions of cellulase and endopeptidase also increased. The results showed that the changes of bacterial community and dominant microbial community on tobacco leaves affected the content of chemical components in tobacco leaves, and adding CBHA for fermentation had a positive effect on improving the quality of tobacco leaves.

16.
Chest ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39053646

RESUMO

BACKGROUND: For decades, the incidence and clinical characteristics of Pneumocystis jirovecii (P. jirovecii) colonization in patients with severe pneumonia was remained unclear. RESEARCH QUESTION: What are the clinical features and outcomes associated with P. jirovecii colonization in individuals diagnosed with severe pneumonia? STUDY DESIGN AND METHODS: In this multicenter, retrospective, matched study, severe pneumonia patients who underwent bronchoalveolar lavage clinical metagenomics from 2019 to 2023 in the ICUs of 17 medical centers were enrolled. Patients were diagnosed based on clinical metagenomics, pulmonary CT scans, and clinical presentations. Clinical data were collected retrospectively, and according to propensity score matching and Cox multivariate regression analysis, the prognosis of patients with P. jirovecii colonization was compared to that of P. jirovecii-negative patients. RESULTS: 40% of P. jirovecii positive patients are considered to have P. jirovecii colonization. P. jirovecii colonization group had a higher proportion of patients with immunosuppression and a lower lymphocyte count compared to P. jirovecii-negative group. More frequent detection of cytomegalovirus, Epstein-Barr virus, human herpesvirus-6B, human herpesvirus-7, and torque teno virus in the lungs was associated with P. jirovecii colonization than with P. jirovecii negativity. By constructing two cohorts through propensity score matching, we incorporated codetected microorganisms and clinical features into a Cox proportional hazards model and revealed that P. jirovecii colonization was an independent risk factor for mortality in severe pneumonia patients. According to sensitivity analyses, which included or excluded codetected microorganisms, as well as patients not receiving TMP-SMX treatment, similar conclusions were reached. INTERPRETATION: Immunosuppression and a reduced lymphocyte count were identified as risk factors for P. jirovecii colonization in non-PCP patients. More frequent detection of various viruses was observed in P. jirovecii colonization patients, and P. jirovecii colonization was associated with an increased 28-day mortality in patients with severe pneumonia.

18.
Diabetes Ther ; 15(8): 1785-1797, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38907935

RESUMO

INTRODUCTION: Insulin efsitora alfa (efsitora) is a basal insulin with a flat pharmacokinetic profile and long half-life, enabling weekly dosing. These attributes may provide stable glucose levels. This exploratory phase 1 study aimed to assess the hypoglycemic risk during experimental conditions that mimic situations encountered in daily life. METHODS: This was a single-site, open-label, two-period, fixed-sequence study in participants with type 2 diabetes (T2D) previously treated with basal insulin. The incidence, duration, and nadir glucose of hypoglycemia were assessed after treatment with efsitora versus insulin glargine (glargine) during three provocation conditions: 24-h prolonged fasting, prolonged fasting with exercise, and double dosing of study insulin. RESULTS: The 54 enrolled adults (BMI 21.8-39.7 kg/m2, HbA1c 6.5-9.4%) achieved stable fasting glucose before undergoing provocation. Most hypoglycemic events were level 1 (≥ 54 to < 70 mg/dL) and resolved spontaneously or after oral glucose. The incidences of level 1 hypoglycemia for efsitora and glargine were not significantly different: for prolonged fasting, the incidences were 44.7 vs. 42.6% and the difference in proportion was 2.1% (95% CI: - 17.2, 21.4); for prolonged fasting with exercise, the corresponding values were 65.9 vs. 50.0% and 15.9% (- 3.0, 34.8); for double dosing, the corresponding values were 68.1 vs. 61.7% and 6.4% (- 12.8, 25.6). Level 2 hypoglycemia (< 54 mg/dL) was infrequent during both treatments and all provocations. No severe hypoglycemia was observed. Mean nadir glucose (range 62.8-66.3 mg/dL) and hypoglycemia duration (range 76.6-115.2 min) were also similar for the two treatments, depending on the provocation. CONCLUSION: Overall, weekly efsitora did not increase the incidence, duration, or severity of hypoglycemia compared to daily glargine during provocation periods in patients with T2D. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04957914.

19.
Front Neurosci ; 18: 1394234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872940

RESUMO

Computer aided diagnosis methods play an important role in Attention Deficit Hyperactivity Disorder (ADHD) identification. Dynamic functional connectivity (dFC) analysis has been widely used for ADHD diagnosis based on resting-state functional magnetic resonance imaging (rs-fMRI), which can help capture abnormalities of brain activity. However, most existing dFC-based methods only focus on dependencies between two adjacent timestamps, ignoring global dynamic evolution patterns. Furthermore, the majority of these methods fail to adaptively learn dFCs. In this paper, we propose an adaptive spatial-temporal neural network (ASTNet) comprising three modules for ADHD identification based on rs-fMRI time series. Specifically, we first partition rs-fMRI time series into multiple segments using non-overlapping sliding windows. Then, adaptive functional connectivity generation (AFCG) is used to model spatial relationships among regions-of-interest (ROIs) with adaptive dFCs as input. Finally, we employ a temporal dependency mining (TDM) module which combines local and global branches to capture global temporal dependencies from the spatially-dependent pattern sequences. Experimental results on the ADHD-200 dataset demonstrate the superiority of the proposed ASTNet over competing approaches in automated ADHD classification.

20.
PLoS One ; 19(6): e0304760, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870122

RESUMO

PURPOSE: The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific distribution of HPV among females from Chengdu and Aba in Sichuan Province, which differ in geographical location, economic status, and living habits. These can serve as evidence of epidemic patterns for future design and implementation of vaccination and screening programs. METHODS: A retrospective cross-sectional study was conducted on 144 113 women who underwent cervical screening at Chengdu Women's and Children's Central Hospital from January 2015 to September 2020. Meanwhile, 1799 samples from February 2018 to December 2021 were collected from Aba Maternal and Child Health Hospital. HPV DNA genotype testing was performed using real-time PCR. The overall prevalence, annual trend, age-specific prevalence, and type distribution were analyzed. RESULTS: The overall HPV prevalence was 22.51% in Chengdu. During 2015-2020, the highest prevalence rate was observed in 2018. Age-specific HPV distribution displayed a bimodal distribution among women aged ≤25 or ≥46 years old. The top three prevalent genotypes were HPV52, -16, and -58. Although the total prevalence of HPV in Aba was 14.23%, there was an upward trend from 2018 to 2021. However, no significant differences were identified in HPV infection rate across all age groups. HPV52, -53, and -16 were the major genotypes. Furthermore, single-type HPV infections and high-risk HPV infections were identified as the most common infection types in both regions. CONCLUSION: Our findings demonstrate the overall prevalence of HPV was still high in Chengdu and Aba. The age-specific prevalence distribution demonstrated different patterns. Non-vaccine-covered HR-HPV53, -51and LR-HPV81, -CP8304 were frequently detected, which was worth significant clinical attention. In summary, regional HPV screening provides valuable clinical guidance for cervical cancer prevention and vaccine selection in Western China.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Humanos , Feminino , China/epidemiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adulto , Prevalência , Pessoa de Meia-Idade , Estudos Transversais , Estudos Retrospectivos , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Adulto Jovem , Genótipo , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , DNA Viral/genética , Colo do Útero/virologia
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