课程文献中心 更多>>

关键词： Multicomponent vaccine   influenza   SARS-CoV-2   messenger RNA   phase 1/2   randomized clinical trial  

摘要： A multicomponent vaccine against seasonal influenza and COVID-19 could reduce disease burden in adults by providing simultaneous protection in a single-dose regimen. The first-generation, mRNA-based, multicomponent mRNA-1073 vaccine, combining antigens encoded by mRNA-1010 (influenza) and mRNA-1273 (COVID-19) vaccines, was investigated in a phase 1/2 clinical trial. This stratified, observer-blinded study randomly assigned healthy adults (18-75 years) to receive mRNA-1073 (25-mu g, 50-mu g, or 100-mu g) + placebo, mRNA-1273 (50-mu g) + placebo, mRNA-1010 (50-mu g) + placebo, or co-administered mRNA-1010 (50-mu g) + mRNA-1273 (50-mu g) on day 1. Primary study objectives were safety and reactogenicity. Secondary study objectives assessed humoral immunogenicity against vaccine-matched influenza and SARS-CoV-2 strains at day 29 and all evaluable time points through day 181. An exploratory objective was to further characterize immune responses across the study vaccines. Overall, 550 participants were randomly assigned to receive study vaccination. mRNA-1073 exhibited dose-dependent reactogenicity. Most solicited adverse reactions were grade 1 or 2 in severity;no grade 4 events, serious adverse events related to study vaccination, or deaths were reported. A single dose of mRNA-1073 elicited durable immune responses through 6 months against all vaccine-matched influenza and SARS-CoV-2 strains. Systems serology analysis indicated that mRNA-1073 induced robust, balanced antibody responses with comparable immune profiles to mRNA-1010 + mRNA-1273. mRNA-1073 had an acceptable safety profile and elicited durable immune responses against all vaccine-matched influenza and SARS-CoV-2 strains, supporting ongoing evaluations of mRNA-based multicomponent vaccines that simultaneously protect against seasonal influenza and COVID-19 in a single dose.Registration: *** identifier: NCT05375838 (https://***/study/NCT05375838).

关键词： Acute kidney injury   cisplatin   ischemia reperfusion injury   salvianolic acid C   gluconeogenesis   fructose-1, 6-bisphosphatase 1  

摘要： This research was targeted to investigate the pharmacological effects and mechanisms of Salvianolic acid C (SAC a natural compound extracted from the Chinese traditional herbal Danshen (Salviae Miltiorrhizae Radix et Rhizoma in acute kidney injury (AKI). Male C57BL/6J mice were used to create animal models and SAC (10 mg/kg, i.p.) or saline was administered 24 h before modeling. In both ischemia reperfusion injury (IRI) induced AKI and cisplatin (Cis) induced AKI models, SAC significantly alleviated the decline of renal function and destruction of renal pathological structure, which were correlated with reduced expression of renal injury markers and inhibited renal cell apoptosis. Non-targeted metabolomics sequencing revealed that the gluconeogenesis pathway was downstream of the renal protective effect of SAC in AKI. Further experiments revealed that the expression of key gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) was significantly decreased in AKI kidneys. AKI induced the reduction in glucose levels from serum and increase in lactate levels from serum and renal tissue. All of these metabolic changes were improved after the SAC treatment. The protective effects of SAC were reversed by an FBP1 inhibitor. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) and forkhead box O1 (FOXO1 identified as gluconeogenesis promoting factor, were decreased after injection of cisplatin, which were reversed by SAC. Finally, molecular docking and SPR experiments revealed the direction interaction between FBP1 and SAC. Collectively, SAC possibly exerts its effect through a dual regulatory mechanism: by modulating the FOXO1/PGC1 alpha/FBP1 signaling axis and via direct interaction with FBP1.

关键词： Land subsidence   machine learning   SHAP   features optimization  

摘要： Land subsidence constitutes a major geological hazard, especially in swiftly urbanizing areas. This study examines the principal cities of southwestern China (Chengdu and Chongqing where comprehending the processes contributing to subsidence and forecasting future dangers is crucial. Nevertheless, contemporary research seldom highlights a systematic feature screening procedure. This study utilized SHAP values in place of the conventional random forest method to measure land subsidence characteristics and employed a neural network to forecast regions at risk of future susceptibility. The findings indicate that the BP neural network model (RMSE = 0.468, MAE = 0.219) surpassed the RF model (RMSE = 0.557, MAE = 0.310). Following feature improvement, the model's performance was enhanced, resulting in a more precise prediction, with the obtained factors aligning with prior research. This feature optimization technique can aid in the selection of input variables and offer a robust theoretical framework for addressing and alleviating urban land subsidence.

关键词： Sentinel-1 data   rapeseed mapping   phenological stages   radar scattering   polarization decomposition  

摘要： Accurate and timely rapeseed mapping is critical for assuring national food security and supporting agricultural regulation. Time series synthetic aperture radar (SAR) data is widely used to monitor the growth of rapeseeds and identify rapeseed distribution in cloudy and rainy regions. However, the spatial and temporal variations in plantation conditions keep presenting a challenge for SAR-based rapeseed mapping over large areas. Additionally, the temporal dynamic patterns and mechanism of SAR scattering could be investigated to enhance the mapping of rapeseed. Therefore, using time-series Sentinel-1 SAR data, this study proposed a general multi-phenology rapeseed index (MPRI) for automatic rapeseed mapping. Central to this method is establishing the linkage between time-series SAR backscattering (including intensity and polarimetric) patterns with rapeseed phenology. First, the rapid growth, flowering, and maturity stages of rapeseed were identified using a pseudo scattering-type parameter that was derived from polarimetric decomposition on Sentinel-1 SAR data. Second, the multi-phenology rapeseed index (MPRI) was developed by incorporating three stage-specific indices. Third, an optimal threshold was applied on the MPRI probability maps to generate binary masks of rapeseed distribution. The proposed MPRI approach is further evaluated by mapping rapeseed across three sites with varying planting conditions in China's Yangtze River Basin. Comparative experiments were conducted against with three available standard methods, including the RSG-OC, CARM, and SARM methods. Results show that the MPRI approach achieved the best performance for rapeseed mapping, with an overall accuracy and an F1 score above 0.90 at all three sites, which exceed these comparative methods by 0.02 similar to 0.10 in overall accuracy and 0.03 similar to 0.12 in the F1 score. Further discussion also reveals that by explicitly incorporating the temporal dynamics of microwave scattering throughout

关键词： Yishen Qingzhuo oral liquid   chronic renal failure   ferroptosis   Nrf2/HO-1 signaling pathway   oxidative stress  

摘要： This study investigated the therapeutic effect and underlying mechanism of Yishen Qingzhuo oral liquid (YSQZ) in a rat model of chronic renal failure (CRF). The CRF model was established by 5/6 nephrectomy. Rats were randomly divided into the sham, CRF, and CRF + low/high-dose YSQZ groups (CRF+YSQZ-L/H). Based on the therapeutic effect, the optimal drug dosage was selected. Subsequently, a ferroptosis inducer (erastin) and Nrf2 inhibitor (ML385) were administered, and rats were further divided into the CRF, CRF+YSQZ, CRF+YSQZ+erastin, and CRF+YSQZ+ML385 groups. The CRF group exhibited impaired renal function, along with elevated urinary protein and ferrous ion levels, relative to those in the sham group. Oxidative stress markers were also dysregulated. Histopathological damage was severe in the CRF group, including increased iron deposition, reduced mitochondrial counts, decreased or even complete loss of mitochondrial cristae, and extensive rupture of the mitochondrial outer membrane, indicators of ferroptosis. The expression of Nrf2/HO-1 pathway-related proteins was decreased, whereas fibrosis-related proteins were upregulated. Whereas the CRF group exhibited marked renal impairment, the CRF+YSQZ-L and CRF+YSQZ-H groups displayed significant improvement in renal function. These treatment groups also exhibited reductions in renal pathological damage, iron deposition, and ferroptosis. The expression of proteins related to the Nrf2/HO-1 ferroptosis pathway was increased, whereas fibrosis-associated proteins were downregulated, with more pronounced effects observed in the high-dose group. However, these protective effects of YSQZ were reversed by co-treatment with erastin or ML385. YSQZ exerts therapeutic effects in rats with CRF, likely by inhibiting ferroptosis through activation of the Nrf2/HO-1 signaling pathway.

关键词： HTLV   STLV   Africa   molecular epidemiology   accessory proteins  

摘要： Central Africa is the largest region of human T-cell Leukaemia virus (HTLV-1) endemicity with several million people estimated to be infected. Based on the study of the LTR region, it is also the region with the highest HTLV-1 diversity, with the presence of genotypes a-b and d-g. However, complete genomic sequences are still lacking for Central African genotypes. Here, we report the first large collection of complete HTLV-1 sequences for genotypes b, d and f from Central Africa and neighbouring countries. We identified substantial diversity within the HTLV-1b genotype, including a newly defined clade that we designated HTLV-1b-del. It mainly comprises strains from the Democratic Republic of the Congo (COD) and neighbouring countries and is characterized by a distinctive 12-bp-long deletion. We also generated the complete sequence of the STLV-1 strain from Allenopithecus nigroviridis from the COD. This strain belongs to the PTLV-1b genotype and carries a 12-bp duplication in the pX region. Lastly, we found that, except for HTLV-1a strains, HTLV-1 genomes generally lack open reading frames encoding the canonical accessory protein P12;instead, they encode either shorter versions of the protein or an ORF lacking a start ATG codon. This work substantially expands the genomic landscape of HTLV-1 in Central Africa and provides a critical resource for understanding viral diversity.

关键词： Sentinel-1   Sentinel-2   post-earthquake recovery monitoring   backscatter coefficients   Noto Peninsula earthquake   time-series analysis  

摘要： Sentinel-1 and Sentinel-2 have been widely used for earthquake damage detection;however, their use in monitoring long-term recovery activities remains largely unexplored. This study evaluates the effectiveness of Sentinel-1 and Sentinel-2 satellite observations for monitoring post-earthquake recovery processes. Focusing on the 2024 Noto Peninsula earthquake, indices were used to assess the detectability of surface changes associated with two key recovery activities: debris removal and temporary housing construction. A detailed analysis of the long-term Sentinel-1 backscatter time-series monitoring was conducted. Public demolition sites exhibited characteristic temporal changes in the vertical transmit-horizontal receive polarization: an initial increase associated with debris generation, followed by a gradual decrease, and then a sharp decline corresponding to the commencement of demolition. At the temporary housing construction sites, the vertical transmit-vertical receive polarization values increased rapidly during construction and remained elevated. The findings revealed that different recovery activities produce distinct backscatter signatures, suggesting that synthetic aperture radar time-series analysis can serve as an effective tool for characterizing post-disaster recovery. Applying these temporal patterns across wider areas enables the identification of collapsed structures and newly constructed temporary housing. This study demonstrated the potential of freely available satellite data to systematically monitor reconstruction processes.

关键词： Treatment-experienced   patients with HIV   INSTI-based triple-drug regimen   switch   simplification   DTG/3tc   efficacy   safety  

摘要： Background: Real-world data on switching from INSTI-based triple therapy to DTG/3TC in the Chinese population are lacking. Methods: This retrospective study included 214 treatment-experienced patients with HIV from Chongqing Public Health Medical Center (2021-2022) on an INSTI-based triple-drug regimen for >= 6 months who switched to DTG/3TC for >12 months. Patients with pre-existing metabolic diseases were excluded. Participants were categorized: INSTI+TAF-free (n = 100, prior TDF/AZT/ABC INSTI+TAF (n = 56, prior BIC/FTC/TAF and INSTI+TAF+COBI (n = 58, prior EVG/c/FTC/TAF). Virological, immunological, and metabolic parameters were assessed at weeks 24 and 48. Results: The INSTI+TAF+COBI group was significantly older (p=0.000). Virological suppression rates (<50 copies/mL) were high at switch (93%, 85.7%, 91.4%). The INSTI+TAF+COBI group had lower eGFR and higher TG, TC, HDL, and LDL at baseline (p < 0.05). After switching, virological suppression remained high (>= 90%) at weeks 24 and 48. CD4+ T-cell increases showed no significant intergroup differences. Metabolic changes differed: TC changes were 0.57 mmol/L (IQR: -0.19-0.91) in INSTI+TAF-free, -0.09 mmol/L (-0.47-0.71) in INSTI+TAF, and -0.25 mmol/L (-0.99-0.33) in INSTI+TAF+COBI. LDL changes were 0.23 mmol/L (-0.23-0.67 -0.15 mmol/L (-0.39-0.01 and -0.18 mmol/L (-0.71-0.10 respectively. TC and LDL changes differed significantly among groups (p < 0.05). Conclusion: Switching to DTG/3TC maintained virological suppression and stable immunological outcomes. Patients previously on TAF-containing regimens demonstrated greater metabolic benefits than those on TAF-free regimens, possibly related to baseline TDF effects, requiring further confirmation.

关键词： Osteoporosis   immunometabolism   ferroptosis   HIF-1 alpha   glycolysis   macrophage polarization  

摘要： BackgroundPostmenopausal osteoporosis (PMOP) is characterized by exacerbated bone resorption and inadequate bone formation, with macrophage-driven inflammation playing a key role. However, how immunometabolic reprogramming of macrophages modulates osteoblast fate remains unknown.MethodsUsing integrated single-cell and bulk transcriptomics, we identified a hypermetabolic macrophage subpopulation in PMOP marrow reliant on HIF-1 alpha-glycolysis. We pharmacologically disrupted this axis with the HDAC inhibitor valproic acid (VPA) and validated its function using the HIF-1 alpha stabilizer DMOG. The paracrine effects on osteoblasts were assessed via conditioned medium, focusing on ferroptosis and differentiation. Therapeutic efficacy was tested in ovariectomized rats.ResultsVPA upregulated HIF1AN, enhancing its binding to HIF-1 alpha and promoting its degradation. This suppressed glycolytic flux and M1 polarization, reducing IL-6 secretion. The altered secretome protected osteoblasts from ferroptosis by inhibiting the IL-6/p-STAT3/HIF-1 alpha/TFRC axis and rebalancing GPX4/ACSL4. Osteogenic differentiation was restored. In OVX rats, VPA improved bone mass and microstructure, effects abolished by DMOG.ConclusionWe unveil a macrophage-centric immunometabolic checkpoint that is linked to osteoblast ferroptosis via IL-6/STAT3 signaling. Targeting this HIF-1 alpha-glycolysis axis, exemplified by VPA, represents a novel therapeutic strategy for PMOP.

关键词： Atopic dermatitis   eczema   patient-reported outcomes   itch   quality-of-life   upadacitinib  

摘要： Objectives: Atopic dermatitis (AD a chronic, immune-mediated inflammatory disease, is characterized by intense itch, eczematous rash, and skin pain, which can have negative impacts to quality-of-life (QoL sleep, and mental health (especially anxiety and depression). Evaluation of the impacts of AD on the patient's lived experience are most accurately assessed by the patient, making measures of patient-reported outcomes (PROs) indispensable. The objective of the current study was to assess the long-term impact of upadacitinib, a once-daily oral selective Janus kinase inhibitor approved for the treatment of moderate-to-severe AD, on patient-reported outcomes, providing a comprehensive in-depth evaluation of results of patient experience across multiple domains. Methods: Using integrated data from the Measure Up 1 & 2 trials, the current study characterizes the efficacy of upadacitinib on several measures that assess the impact of AD on patients' lives, including patient-reported disease and symptom severity, sleep, emotional well-being, daily activities, QoL, and treatment satisfaction. Results: Results demonstrated that rapid improvements in PRO measures of itch, sleep, daily activities, QoL, and emotional well-being reported at week 16 and week 52 were sustained or further improved at week 140 for patients with moderate-to-severe AD continuing upadacitinib 15 mg or 30 mg therapy, with no new safety signals observed. Conclusions: These findings support upadacitinib as a long-term treatment option to improve patient-reported burdensome symptoms of AD across 140 weeks of exposure.