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1.
Transgend Health ; 9(3): 222-231, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39109260

RÉSUMÉ

Purpose: Although transgender women (TGW) bear the highest HIV burden worldwide, routine surveillance of this group is rare. We aimed to evaluate the trends in health characteristics of Chinese TGW. Methods: Three cross-sectional studies using snowball sampling were conducted in 2014, 2017, and 2019, primarily in Shenyang, China. A questionnaire and voluntary HIV testing were used to obtain information on background characteristics, sexual behaviors, pre-exposure prophylaxis (PrEP) willingness, and HIV status. Results: There were 220 respondents in 2014, 198 in 2017, and 247 in 2019 (average age 31.1±7.6 to 33.5±9.6 years). HIV prevalence significantly decreased from 29.5% (95% confidence interval [CI]: 25.3-38.4%) in 2014 to 19.4% (95% CI: 14.7-24.9%) in 2019 (p<0.05). The proportion of participants reporting condomless anal intercourse (CAI) with any partner fluctuated from 30.8% (95% CI: 25.1-36.1%) to 53.0% (95% CI: 45.8-60.1%). The proportion of participants willing to use PrEP decreased from 86.4% (95% CI: 81.1-90.6%) in 2014 to 62.8% (95% CI: 56.4-68.8%) in 2019. Factors significantly associated with HIV infection were CAI with any partner (multivariate odds ratio [ORm]: 3.58, 95% CI: 1.55-8.29 in 2017; ORm: 3.18, 95% CI: 1.56-6.46 in 2019) and PrEP willingness (ORm: 0.26, 95% CI: 0.12-0.58 in 2017). Conclusion: HIV prevalence and associated risk factors remain substantial among Chinese TGW. There is an urgent need to strengthen HIV surveillance in this population, and develop trans-friendly and effective interventions to minimize HIV prevalence and transmission.

2.
Nat Sci Sleep ; 16: 1141-1152, 2024.
Article de Anglais | MEDLINE | ID: mdl-39109266

RÉSUMÉ

Purpose: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term. Patients and Methods: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT. Results: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05). Conclusion: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients. Clinical Trial Registration: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.

3.
Hepatol Int ; 2024 Aug 13.
Article de Anglais | MEDLINE | ID: mdl-39138757

RÉSUMÉ

BACKGROUND & AIMS: Despite increasing knowledge regarding the cellular and molecular mechanisms of liver fibrogenesis, there is currently no approved drug for the treatment of liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells representing an attractive therapeutic tool for tissue damage and inflammation. This study was designed to determine the protective effect and underlying mechanism of human umbilical cord-derived MSCs (UC-MSCs) on thioacetamide-induced liver fibrosis. METHODS: Liver fibrosis was induced in mice by intraperitoneal injection of thioacetamide (TAA). Some mice were then given injection of UC-MSCs or UC-MSCs-derived exosomes (UC-MSCs-Exo) via the tail vein. Liver tissues were collected for histologic analysis. RESULTS: We found that administration of UC-MSCs significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, and attenuated hepatic inflammation and fibrosis. Moreover, the therapeutic effect of UC-MSCs-derived exosomes was similar to that of UC-MSCs. Intriguingly, UC-MSCs-Exo treatment downregulated the expression of smoothened (SMO), a fundamental component of Hedgehog signaling which plays a critical role in fibrogenesis, and subsequently inhibited the activation of hepatic stellate cells, a central driver of fibrosis in experimental and human liver injury. Furthermore, the anti-inflammatory and anti-fibrotic effects of UCMSCs- Exo was reversed by the SMO agonist SAG treatment in mice. CONCLUSION: Our findings suggest that UC-MSCs-Exo exert therapeutic effects on liver fibrosis, at least in part, through inhibiting the Hedgehog/SMO signaling pathway.

4.
Phys Rev Lett ; 133(3): 030601, 2024 Jul 19.
Article de Anglais | MEDLINE | ID: mdl-39094134

RÉSUMÉ

An interesting problem in the field of quantum error correction involves finding a physical system that hosts a "passively protected quantum memory," defined as an encoded qubit coupled to an environment that naturally wants to correct errors. To date, a quantum memory stable against finite-temperature effects is known only in four spatial dimensions or higher. Here, we take a different approach to realize a stable quantum memory by relying on a driven-dissipative environment. We propose a new model, the photonic-Ising model, which appears to passively correct against both bit-flip and phase-flip errors in two dimensions: a square lattice composed of photonic "cat qubits" coupled via dissipative terms which tend to fix errors locally. Inspired by the presence of two distinct Z_{2}-symmetry-broken phases, our scheme relies on Ising-like dissipators to protect against bit flips and on a driven-dissipative photonic environment to protect against phase flips. We also discuss possible ways to realize the photonic-Ising model.

5.
Ecol Evol ; 14(8): e70051, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39114161

RÉSUMÉ

Sand rice (Agriophyllum squarrosum), widely distributed in Central Arid Asia and prevalent in the sand dunes of northern China, presents a promising potential as a climate-resilient crop. The plasticity of hypocotyl growth is the key trait for sand rice to cope with wind erosion and sand burial, ensure seedling emergence, and determine plant architecture. In this study, we assessed the overall hypocotyl phenotype of six sand rice elite lines, which were collected from different regions of northern China, and selected by our group over past decade through common garden trials. Significant phenotypic variations were observed in thousand-seed weight (TSW), seedling emergence percentage, hypocotyl length and diameter, and seedling fresh weight among the lines. The elite line Aerxiang (AEX) exhibited excellent agronomic performance with superior and synchronous emergence, and high survival percentage, distinguishing itself as a prime candidate for further large-scale cultivation. Contrastingly, the lines from the arid regions showed markedly lower performance. Partial Least Squares Path Modeling (PLSPM) was used to assess the impact of seed provenance climate factors, including annual mean temperature (AMT) and annual mean precipitation (AMP), on trait variability among lines. The findings indicate a significant correlation between climate factors and hypocotyl length, highlighting the intricate adaptation of sand rice to local climate. The comprehensive understanding of the mechanisms behind phenotypic variations offers valuable insights for sand rice de novo domestication and innovative germplasm resources, and lays the foundation for ecological restoration in sandy areas.

6.
Front Endocrinol (Lausanne) ; 15: 1380187, 2024.
Article de Anglais | MEDLINE | ID: mdl-39045277

RÉSUMÉ

Objective: This study aims to evaluate the effectiveness of the Vaginal Microecology Evaluation System (VMES) in assessing the dynamics of the vaginal microbiome (VM) throughout the process of in vitro fertilization and embryo transfer (IVF-ET). Furthermore, it seeks to explore the potential correlation between distinct types of VM ecology and the success rate of IVF-ET. Methods: This study employed VMES to ascertain the composition of the VM. Data were collected from infertile women who underwent their initial IVF-ET treatment for tubal factor between January 2018 and December 2021. A retrospective analysis of pregnancy outcomes resulting from their fresh embryo transfer was conducted to determine the predictive significance of the vaginal microenvironment. Results: We demonstrate that VMES is able to predict IVF-ET outcomes in patients diagnosed with Bacterial Vaginosis (BV). Notably, a discernible shift in the VM was observed in a decent subset of patients following Controlled Ovarian Stimulation (COS), though this phenomenon was not universal across all participants. Specifically, there was a noteworthy increase in the proportion of patients exhibiting BV and uncharacterized dysbiosis subsequent to COS. Furthermore, our investigation revealed a significant correlation between VM and both the live birth rate and early miscarriage rate. Employing a multivariable logistic regression model, we identified that VM status pre-COS, VM status post-COS, patient age, and the number of embryos transferred emerged as independent predictors of the live birth rate. Conclusion: Our study suggests that, during IVF-ET treatment, the VMES can effectively detect changes in the VM, which are strongly correlated with the pregnancy outcome of IVF-ET procedures.


Sujet(s)
Transfert d'embryon , Fécondation in vitro , Microbiote , Issue de la grossesse , Vagin , Humains , Femelle , Fécondation in vitro/méthodes , Études rétrospectives , Grossesse , Vagin/microbiologie , Adulte , Transfert d'embryon/méthodes , Infertilité féminine/microbiologie , Infertilité féminine/thérapie , Taux de grossesse , Vaginose bactérienne/microbiologie , Vaginose bactérienne/diagnostic
7.
BMC Public Health ; 24(1): 1865, 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-38997689

RÉSUMÉ

BACKGROUND: The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. METHODS: This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. RESULTS: In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (ßCMEC = 0.068, ßUK-Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (ßCMEC = 0.027, ßUK-Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. CONCLUSIONS: Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.


Sujet(s)
Glycémie , Diabète de type 2 , Jeûne , Stéatose hépatique non alcoolique , Humains , Chine/épidémiologie , Diabète de type 2/épidémiologie , Royaume-Uni/épidémiologie , Stéatose hépatique non alcoolique/épidémiologie , Stéatose hépatique non alcoolique/sang , Femelle , Mâle , Adulte d'âge moyen , Glycémie/analyse , Études longitudinales , Jeûne/sang , Adulte , Sujet âgé , Facteurs temps , Facteurs de risque , Modèles des risques proportionnels
8.
Am J Otolaryngol ; 45(5): 104430, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39059172

RÉSUMÉ

OBJECTIVES: To analyze anatomic variations of the temporal bone in congenital aural atresia (CAA) and their correlation with the Jahrsdoerfer score, in order to guide clinical selection of surgical treatment methods. MATERIAL AND METHODS: We retrospectively studied 53 patients (72 ears) with unilateral or bilateral CAA, including 34 ears with normal hearing as controls. Audiological and imaging data were collected and analyzed. We evaluated the Jahrsdoerfer score and anatomical variations, including tegmen mastoideum position, anterior sigmoid sinus displacement, and elevated jugular bulb. RESULTS: The average air conduction hearing threshold (PTA4) ranged from 0.5 to 4 kHz was 65.48 ± 8.19 dBHL, with an average Jahrsdoerfer score of 4.93 ± 2.78. In CAA group, there was a higher prevalence and severity of anterior sigmoid sinus and low position of the tegmen mastoideum (P < 0.01). However, there was no significant difference in incidence rates among groups with high jugular bulb (P > 0.05). Anterior sigmoid sinus and high jugular bulb showed no correlation with the Jahrsdoerfer score, while the low position of the tegmen mastoideum had a weak correlation. The Jahrsdoerfer score did not adequately predict temporal bone anatomical abnormalities in CAA patients. CONCLUSION: CAA exhibit a higher incidence and greater severity of temporal bone anatomical abnormalities compared to the control group, and the Jahrsdoerfer score inadequately assesses these abnormalities. Anomalies like low position of the tegmen mastoideum, anterior sigmoid sinus, and high jugular bulb should also be considered as independent factors influencing surgical decisions for atresiaplasty.

9.
Int J Biol Macromol ; 277(Pt 2): 134208, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39069059

RÉSUMÉ

Antibacterial hydrogels as burn wound dressings are capable of efficaciously defending against bacterial infection and accelerating burn wound healing. Thus far, a large plethora of antibacterial hydrogels have adopted numerous components and intricate preparation processes, yet restricting their practical industrialization applications. Simple and effective preparation methods of antibacterial hydrogels are hence urgently needed. Herein, an easy but efficacious strategy with the employment of two natural products pullulan and ε-poly-l-lysine (ε-PL) was designed to fabricate composite antibacterial hydrogels for burn wound healing for the first time. The hydrogel crosslinking networks were formed through amidation reactions between carboxylated pullulan derivative (CP) and ε-poly-l-lysine hydrochloride (ε-PL·HCl). The resulting hydrogels possessed high transparency, porous structures, tunable gelation time and gel content, relatively low swelling ratios, appropriate self-degradability, proper mechanical properties, strong in vitro bacteriostatic activities, non-cytotoxicity, capacities of facilitating cell migration and excellent hemocompatibility. In the infected burn model of mice, the hydrogels were observed to display prominent in vivo antibacterial activities and enable the acceleration of burn wound healing. We opine the simply and effectively prepared antibacterial hydrogels as promising dressings for burn wound recovery have broad industrialization prospects.

10.
BioDrugs ; 38(4): 571-588, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38890199

RÉSUMÉ

BACKGROUND AND OBJECTIVE: Tocilizumab is an immunoglobulin G1 monoclonal antibody targeting the interleukin-6 receptor (IL-6R). BAT1806/BIIB800 (tocilizumab-bavi) has been developed as a biosimilar to the reference product tocilizumab (TCZ). The objective of this study was to demonstrate physicochemical and functional similarity between BAT1806/BIIB800 and TCZ in a comprehensive comparability exercise. METHODS: A comprehensive panel of over 20 methods was used to generate datasets comparing critical and non-critical product quality attributes for 10 BAT1806/BIIB800 lots and 44 TCZ lots (16 sourced from China, 16 from the EU, and 12 from the US). Primary structure, higher-order structure, and physicochemical properties were assessed using liquid chromatography, mass spectrometry, various spectroscopy techniques/methods, capillary electrophoresis, and thermoanalytical techniques. Fragment antigen-binding (Fab)- and fragment crystallizable (Fc)-mediated biological properties were assessed using cell-based assays, immunoassays, flow cytometry, and kinetic binding assays. RESULTS: BAT1806/BIIB800 and TCZ (irrespective of source) were shown to be similar in terms of structural and functional properties. No differences were observed in terms of the most critical quality attributes, that is, soluble-IL-6R binding and inhibition of IL-6-mediated cell proliferation. BAT1806/BIIB800 and TCZ demonstrated similarity in terms of Fab- and Fc-mediated binding and biological activity. Minor differences were observed in glycosylation (afucosylation and sialylation), glycation, aggregation, and charge variants, which were demonstrated to be not clinically relevant. CONCLUSION: BAT1806/BIIB800 and TCZ were highly similar for all critical quality attributes. Where differences were observed in less critical quality attributes, additional analytical assessments and clinical study results determined these to be not clinically meaningful.


Sujet(s)
Anticorps monoclonaux humanisés , Produits pharmaceutiques biosimilaires , Récepteurs à l'interleukine-6 , Produits pharmaceutiques biosimilaires/composition chimique , Produits pharmaceutiques biosimilaires/pharmacologie , Humains , Anticorps monoclonaux humanisés/composition chimique , Anticorps monoclonaux humanisés/pharmacologie , Chine
11.
Nanoscale ; 16(27): 12957-12966, 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38898817

RÉSUMÉ

The doping of semiconductor materials through some facile and appropriate methods holds significant promise in enhancing the catalytic performance of catalysts. Herein, NiCo2O4/g-C3N4 composite catalysts were synthesized via a high-energy ball milling method. The microstructure and physicochemical characterization of the as-prepared composites confirmed the successful loading of NiCo2O4 nanoparticles onto the g-C3N4 nanosheets. The NiCo2O4/g-C3N4 composites showed excellent catalytic effect under visible light/ultrasonic irradiation, and the efficiency of tetracycline hydrochloride (TCH) degradation reached 90% within 15 min. The optical properties of g-C3N4 nanosheets were improved by doping, and the diffusion of active materials and carrier migration rate were improved by ultrasonic assistance. Possible catalytic mechanisms and potential pathways of the NiCo2O4/g-C3N4 composites for the degradation of TCH triggered by visible light/ultrasonic irradiation were proposed. This study provides a new strategy for energy-assisted photocatalytic degradation of organic pollutants.

12.
Anal Methods ; 16(27): 4582-4589, 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38919038

RÉSUMÉ

As of now, the global COVID-19 pandemic caused by SARS-CoV-2, which began in 2019, has been effectively controlled. However, the symptoms of influenza A virus infection were similar to those of SARS-CoV-2 infection, but they required different treatment approaches. To make the detection more accurate and the treatment more targeted. We developed a system that integrates RPA and CRISPR assays, allowing for the rapid, highly specific, and sensitive detection and differentiation of SARS-CoV-2, H1N1, and H3N2. Under isothermal amplification conditions, the RPA-CRISPR Cas12a detection system achieved a detection limit as low as 5 copies per µL, demonstrating excellent specificity. The measurement time was approximately 30 minutes. The RPA-CRISPR Cas12a detection system combined with the microfluidic chip we designed to simultaneously detect three viruses, providing a potential solution for efficient and reliable diagnosis.


Sujet(s)
COVID-19 , Grippe humaine , SARS-CoV-2 , SARS-CoV-2/génétique , SARS-CoV-2/isolement et purification , Humains , Grippe humaine/diagnostic , COVID-19/diagnostic , Sous-type H1N1 du virus de la grippe A/isolement et purification , Sous-type H1N1 du virus de la grippe A/génétique , Techniques d'amplification d'acides nucléiques/méthodes , Sous-type H3N2 du virus de la grippe A/isolement et purification , Sous-type H3N2 du virus de la grippe A/génétique , Systèmes CRISPR-Cas/génétique , Laboratoires sur puces , Techniques d'analyse microfluidique/méthodes , Techniques d'analyse microfluidique/instrumentation , Limite de détection , Techniques de diagnostic moléculaire/méthodes , Virus de la grippe A/isolement et purification , Virus de la grippe A/génétique , Sensibilité et spécificité
13.
Sci Total Environ ; 944: 173798, 2024 Sep 20.
Article de Anglais | MEDLINE | ID: mdl-38844236

RÉSUMÉ

Trehalase gene is mainly expressed in the digestive circulatory system for regulating energy metabolism and chitin synthesis in insects, but it is significantly expressed in gill for immunomodulation in shrimp. However, its function in regulating immunity, particularly metal resistance in crustaceans has yet to be elucidated. In this study, one Tre2 gene (NdTre2) was isolated from Neocaridina denticulata sinensis. It could bind to Cd2+ and inhibit its toxicity. Spatiotemporal expression analysis showed that the expression of NdTre2 was highest in the gill and significantly reduced at 12 h after Cd2+ stimulation. The transcriptomic analysis of the gill after NdTre2 knockdown showed that the expression of genes synthetizing 20E was up-regulated and the increased 20E could further induce apoptosis by activating the intrinsic mitochondrial pathway, exogenous death receptor-ligand pathway, and MAPK pathway. In vitro, overexpressing NdTre2 enhanced the tolerance of E. coli in Cd2+ environment. In summary, these results indicate that NdTre2 plays an essential role in regulating immunity and chitin metabolism in N. denticulata sinensis.


Sujet(s)
Apoptose , Cadmium , alpha, alpha-Trehalase , Cadmium/toxicité , Animaux , Apoptose/effets des médicaments et des substances chimiques , alpha, alpha-Trehalase/métabolisme , alpha, alpha-Trehalase/génétique , Polluants chimiques de l'eau/toxicité , Decapoda (crustacea)/physiologie , Decapoda (crustacea)/génétique
14.
Int Immunopharmacol ; 137: 112424, 2024 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-38878486

RÉSUMÉ

Colorectal cancer is a major global health burden, with limited efficacy of traditional treatment modalities in improving survival rates. However, recently advances in immunotherapy has improved treatment outcomes for patients with this cancer. To address the continuing need for improved treatment efficacy, this study introduced a novel tri-specific antibody, IMT030122, that targets EpCAM, 4-1BB, and CD3. We evaluated the pharmacological efficacy and mechanism of action of IMT030122 in vitro and in vivo. In in vitro studies, IMT030122 exhibited differential binding to antigens and cells expressing EpCAM, 4-1BB, and CD3. Moreover, IMT030122 relied on EpCAM-targeted activation of intracellular CD3 and 4-1BB signaling and mediated T cell cytotoxicity specific to HCT116 colorectal cancer cells. In vivo, IMT030122 demonstrated potent anti-tumor activity, significantly inhibiting the growth of colon cancer HCT116 and MC38-hEpCAM subcutaneous grafts. Further pharmacological analysis revealed that IMT030122 recruited lymphocytes from peripheral blood into colorectal cancer tissue and exerted durable anti-tumor activity, predominantly by promoting the activation, proliferation, and differentiation of CD8T cells. Notably, IMT030122 still exhibited anti-tumor efficacy even in the presence of significantly depleted lymphocytes in colorectal cancer tissue. The potent pharmacological activity and anti-tumor effects of IMT030122 suggest it may enhance treatment efficacy and substantially extend the survival of patients with colorectal cancer in the future.


Sujet(s)
Antigènes CD3 , Tumeurs colorectales , Molécule d'adhérence des cellules épithéliales , Animaux , Humains , Tumeurs colorectales/traitement médicamenteux , Tumeurs colorectales/immunologie , Tumeurs colorectales/thérapie , Molécule d'adhérence des cellules épithéliales/métabolisme , Antigènes CD3/immunologie , Souris , Antigènes CD137/métabolisme , Cellules HCT116 , Tests d'activité antitumorale sur modèle de xénogreffe , Antinéoplasiques immunologiques/pharmacologie , Antinéoplasiques immunologiques/usage thérapeutique , Femelle , Lignée cellulaire tumorale , Anticorps monoclonaux/pharmacologie , Anticorps monoclonaux/usage thérapeutique , Souris de lignée BALB C , Lymphocytes T/immunologie , Lymphocytes T/effets des médicaments et des substances chimiques , Anticorps bispécifiques/pharmacologie , Anticorps bispécifiques/usage thérapeutique , Immunothérapie/méthodes
15.
Am J Hum Genet ; 111(7): 1420-1430, 2024 07 11.
Article de Anglais | MEDLINE | ID: mdl-38838674

RÉSUMÉ

Numerous variants, including both single-nucleotide variants (SNVs) in DNA and A>G RNA edits in mRNA as essential drivers of cellular proliferation and tumorigenesis, are commonly associated with cancer progression and growth. Thus, mining and summarizing single-cell variants will provide a refined and higher-resolution view of cancer and further contribute to precision medicine. Here, we established a database, CanCellVar, which aims to provide and visualize the comprehensive atlas of single-cell variants in tumor microenvironment. The current CanCellVar identified ∼3 million variants (∼1.4 million SNVs and ∼1.4 million A>G RNA edits) involved in 2,754,531 cells of 5 major cell types across 37 cancer types. CanCellVar provides the basic annotation information as well as cellular and molecular function properties of variants. In addition, the clinical relevance of variants can be obtained including tumor grade, treatment, metastasis, and others. Several flexible tools were also developed to aid retrieval and to analyze cell-cell interactions, gene expression, cell-development trajectories, regulation, and molecular structure affected by variants. Collectively, CanCellVar will serve as a valuable resource for investigating the functions and characteristics of single-cell variations and their roles in human tumor evolution and treatment.


Sujet(s)
Bases de données génétiques , Tumeurs , Polymorphisme de nucléotide simple , Analyse sur cellule unique , Humains , Tumeurs/génétique , Tumeurs/anatomopathologie , Microenvironnement tumoral/génétique
16.
J Natl Cancer Inst ; 2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38833681

RÉSUMÉ

BACKGROUND: Despite the wide use of a three-month gonadotropin-releasing hormone agonist (3M GnRHa) for ovarian function suppression (OFS) in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a one-month GnRHa regimen (1M GnRHa) when combined with selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs), especially in younger patients. METHODS: This retrospective cohort study included 1109 premenopausal hormone receptor-positive (HR+) breast cancer patients treated with GnRHa plus SERM or AI. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1M or 3M GnRHa in cohorts and different subgroups was analyzed. RESULTS: Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1M and 3M groups achieved >90% E2 inhibition within 24 months (94.53% vs 92.84%, 95% CI (-4.78%, 1.41%)), confirming the non-inferiority of 3M GnRHa. Both 1M and 3M GnRHa rapidly and consistently reduced E2 levels. 60 (6.3%) patients experienced incomplete ovarian function suppression (iOFS), with similar rates in the 1M and 3M groups (5.5% vs 7.2%). iOFS mainly occurred within the first 12 months, with age <40 years and no prior chemotherapy being the risk factors. Similar disease-free survival (DFS) and overall survival (OS) were found in the 1M and 3M groups, and in patients with complete and incomplete OFS (p > .05). CONCLUSIONS: The OFS with 3M GnRHa was not inferior to that with 1M GnRHa, regardless of age or combination with a SERM or an AI.

17.
Article de Anglais | MEDLINE | ID: mdl-38829052

RÉSUMÉ

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

18.
Digit Health ; 10: 20552076241259047, 2024.
Article de Anglais | MEDLINE | ID: mdl-38840661

RÉSUMÉ

Background: Falls pose a serious health risk for the elderly, particular for those who are living alone. The utilization of WiFi-based fall detection, employing Channel State Information (CSI), emerges as a promising solution due to its non-intrusive nature and privacy preservation. Despite these advantages, the challenge lies in optimizing cross-individual performance for CSI-based methods. Objective: This study aimed to develop a resilient real-time fall detection system across individuals utilizing CSI, named TCS-Fall. This method was designed to offer continuous monitoring of activities over an extended timeframe, ensuring accurate and prompt detection of falls. Methods: Extensive CSI data on 1800 falls and 2400 daily activities was collected from 20 volunteers. The grouped coefficient of variation of CSI amplitudes were utilized as input features. These features capture signal fluctuations and are input to a convolutional neural network classifier. Cross-individual performance was extensively evaluated using various train/test participant splits. Additionally, a user-friendly CSI data collection and detection tool was developed using PyQT. To achieve real-time performance, data parsing and pre-processing computations were optimized using Numba's just-in-time compilation. Results: The proposed TCS-Fall method achieved excellent performance in cross-individual fall detection. On the test set, AUC reached 0.999, no error warning ratio score reached 0. 955 and correct warning ratio score reached of 0.975 when trained with data from only two volunteers. Performance can be further improved to 1.00 when 10 volunteers were included in training data. The optimized data parsing/pre-processing achieved over 20× speedup compared to previous method. The PyQT tool parsed and detected the fall within 100 ms. Conclusions: TCS-Fall method enables excellent real-time cross-individual fall detection utilizing WiFi CSI, promising swift alerts and timely assistance to elderly. Additionally, the optimized data processing led to a significant speedup. These results highlight the potential of our approach in enhancing real-time fall detection systems.

19.
Harmful Algae ; 136: 102652, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38876530

RÉSUMÉ

Microplastics are well known as contaminants in marine environments. With the development of biofilms, most microplastics will eventually sink and deposit in benthic environment. However, little research has been done on benthic toxic dinoflagellates, and the effects of microplastics on benthic dinoflagellates are unknown. Prorocentrum lima is a cosmopolitan toxic benthic dinoflagellate, which can produce a range of polyether metabolites, such as diarrhetic shellfish poisoning (DSP) toxins. In order to explore the impact of microplastics on marine benthic dinoflagellates, in this paper, we studied the effects of polystyrene (PS) on the growth and toxin production of P. lima. The molecular response of P. lima to microplastic stress was analyzed by transcriptomics. We selected 100 nm, 10 µm and 100 µm PS, and set three concentrations of 1 mg L-1, 10 mg L-1 and 100 mg L-1. The results showed that PS exposure had limited effects on cell growth, but increased the OA and extracellular polysaccharide content at high concentrations. After exposure to PS MPs, genes associated with DSP toxins synthesis, carbohydrate synthesis and energy metabolism, such as glycolysis, TCA cycle and pyruvate metabolism, were significantly up-regulated. We speculated that after exposure to microplastics, P. lima may increase the synthesis of DSP toxins and extracellular polysaccharides, improve the level of energy metabolism and gene expression of ABC transporter, thereby protecting algal cells from damage. Our findings provide new insights into the effects of microplastics on toxic benthic dinoflagellates.


Sujet(s)
Dinoflagellida , Microplastiques , Polystyrènes , Dinoflagellida/effets des médicaments et des substances chimiques , Dinoflagellida/génétique , Dinoflagellida/physiologie , Microplastiques/toxicité , Toxines de la flore et de la faune marines , Polluants chimiques de l'eau/toxicité , Transcriptome/effets des médicaments et des substances chimiques
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