Background This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-β1 stimulated hepatic stellate cells (HSC-MVs, TGF-β1HSC-MVs) on H 2 O 2 -induced human umbilical vein ...endothelial cells (HUVECs) injury and CCl 4 -induced rat hepatic vascular injury. Methods HUVECs were exposed to hydrogen peroxide (H 2 O 2 ) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-β1HSC-MVs were co-cultured with H 2 O 2 -treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl 4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-β1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. Results In H 2 O 2 -treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-β1 HSC-MVs exhibited opposite effects. CCl 4 - induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-β1HSC-MVs demonstrated opposite effects. Conclusion HSC-MVs demonstrated a protective effect on H 2 O 2 -treated HUVECs and CCl 4 -induced rat hepatic injury, while TGF-β1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.
To estimate the prevalence of pain among people aged 45 years and older in China, to analyze the effect factors of pain and pain related economic burden.
Nationally representative sample was derived ...from China Health and Retirement Longitudinal Study (CHARLS). Pain data, medical cost data were obtained, as well as information of demographic characteristics, social structure, social-economic status, other health needs and health behaviors. The prevalence of pain in 2011, 2013, and 2015 was calculated. Univariate analysis and multivariate analysis were used to find the effect factors of pain. An optimization two-part model was used to calculate the range of the direct medical costs caused by pain.
The prevalence of pain among people 45 years or older in China was 31.73% in 2011, 37.27% in 2013 and 28.62% in 2015. When evaluating factors lead a higher prevalence of pain, the results of the multi-variable after one-way analysis were older age, female, lower education, rural residents, without insurance status, abstained from alcohol and lower body mass index (BMI). Through the optimization of two-part model, the direct medical costs caused by pain was 898.9-1563.0 yuan in 2011, 2035.8-2568.7 yuan in 2013 and 2628.8-3945.7 yuan in 2015 (129.9US$ - 225.9US$ in 2011, 294.2 US$ - 371.2US$ in 2013 and 379.9US$ - 570.2US$ in 2015, converted to 2010 RMB).
The prevalence of pain among middle-aged and elderly Chinese is high. Residents with older age, female, lower education, rural residents, without insurance status, abstained from alcohol and lower BMI seem to have a higher pain prevalence. Pain can cause extra direct medical costs and will cause more economic loss with the progress of time. Future research should pay more attention to effective treatment, management and prevention of pain to decrease its burden.
The shuttling effect of polysulfides species seriously deteriorates the performance of Li–S batteries, representing the major obstacle for their practical use. However, the exploration of ideal ...cathodes that can suppress the shuttling of all polysulfides species is challenging. Herein, we propose an ingenious and effective strategy for constructing hybrid-crystal-phase TiO2/covalent organic framework (HCPT@COF) composites where hybrid anatase/rutile TiO2 nanodots (10 nm) are uniformly embedded in the interlayers of porous COFs. The synthesis was realized via a multiple-step reaction relay accompanying by a pseudo-topotactic transformation of three-dimensional layered structures from 1,4-dicyanobenzene monomer-embedded Ti-intermediate networks to HCPT nanodots-embedded COF frameworks. The HCPT@COF/S cathodes show superior comprehensive performance such as high specific capacity, long cycling stability, and remarkable rate capability for Li–S batteries, owing to the complementary anchoring effect of hybrid anatase/rutile TiO2 in the HCPT@COF composite, which is evidenced by substantial characterizations including X-ray photoelectron spectroscopy and density functional theory calculations.
Energy-consuming rights trading (ECRT) policy represents a critical policy instrument for China striving to achieve its “dual carbon” objectives, captivating significant attention for its potential ...to reduce pollution and carbon emissions. This study utilizes panel data from 290 Chinese cities spanning 2010 to 2021, leveraging the ECRT policy as a quasi-natural experiment. Employing Difference-in-Differences (DID) and Propensity Score Matching-Difference-in-Differences (PSM-DID) methodologies, we assess the effect of the ECRT policy on urban pollution and carbon reduction levels. The findings indicate: 1) Relative to non-demonstration cities, the ECRT policy significantly enhances pollution and carbon reduction levels in demonstration cities; this conclusion remains robust after rigorous testing. 2) Heterogeneity analysis indicates that the policy’s effect on pollution and carbon reduction is more significant in the central and western regions, and particularly evident in key and resource-based cities. 3) Mechanism tests demonstrate that the policy facilitates urban pollution and carbon reduction by cultivating green technological innovation and industrial structure upgrading. Therefore, to further advance the ECRT policy, it is necessary to expand the breadth, depth, and flexibility of policy implementation, while also optimizing environmental regulations to fully leverage the system’s potential in enhancing urban pollution and carbon emissions.
Background Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains dismal, with a very ...poor 5-year survival rate. Consequently, identifying more effective and less toxic chemotherapeutic alternatives is critical for enhancing clinical outcomes for BC patients. Isorhapontigenin (ISO), a novel stilbene isolated from a Gnetum found in certain provinces of China, has shown potential as an anticancer agent due to its diverse anticancer activities. Despite its promising profile, the specific anticancer effects of ISO on BC and the underlying mechanisms are still largely unexplored. Methods The anchorage-independent growth, migration and invasion of BC cells were assessed by soft agar and transwell invasion assays, respectively. The RNA levels of SOX2, miR-129 and SNHG1 were quantified by qRT-PCR, while the protein expression levels were validated through Western blotting. Furthermore, methylation-specific PCR was employed to assess the methylation status of the miR-129 promoter. Functional assays utilized siRNA knockdown, plasmid-mediated overexpression, and chemical inhibition approaches. Results Our study demonstrated that ISO treatment significantly reduced SNHG1 expression in a dose- and time-dependent manner in BC cells, leading to the inhibition of anchorage-independent growth and invasion in human basal MIBC cells. This effect was accompanied by the downregulation of MMP-2 and MMP-9 and the upregulation of the tumor suppressor PTEN. Further mechanistic investigations revealed that SOX2, a key upstream regulator of SNHG1, played a crucial role in mediating the ISO-induced transcriptional suppression of SNHG1. Additionally, we found that ISO treatment led to a decrease in DNMT3b protein levels, which in turn mediated the hypomethylation of the miR-129 promoter and the subsequent suppression of SOX2 mRNA 3'-UTR activity, highlighting a novel pathway through which ISO exerts its anticancer effects. Conclusions Collectively, our study highlights the critical role of SNHG1 downregulation as well as its upstream DNMT3b/miR-129/SOX2 axis in mediating ISO anticancer activity. These findings not only elucidate the mechanism of action of ISO but also suggest novel targets for BC therapy. Keywords: ISO, SNHG1, DNMT3b, miR-129, Basal bladder cancer
The abundant genetic resources of wild rice in China represent a key gene pool for modern rice breeding, contributing to food production and agricultural development in China and worldwide. Between ...the 1970s and the 2010s, two national wild rice surveys were carried out in China. More than 20 000 accessions of three species Oryza rufipogon, O. officinalis and O. meyeriana have been conserved ex situ. An in situ conservation system has also been set up to protect notable and endangered populations. This review summarized the geographical distribution of wild rice in China, the current status of conservation, the discovery of elite genes, and the application of research into the origin and domestication of rice.
Anaerobic digestion (AD) is an established method for sustainable energy production. Anaerobic digestion model No.1 (ADM1) was used to simulate methane production (MP) and volatile fatty acid (VFA) ...concentrations at different ammonium concentrations. In accordance with the incomplete description of several biochemical reactions and the omission of several reaction processes, ADM1 was modified with the consideration of acetic acid inhibition and valeric acid existence. ADM1_ac (ADM1 added acetic acid inhibition) could obtain better simulation accuracy of MP (goodness‐of‐fit value = 0.945), and VFA concentrations (goodness‐of‐fit values > 0.39) were all higher than ADM1_original, but cannot explain the valeric acid production. ADM1_va (ADM1 added valeric acid existence) could achieve better simulation of valeric acid (achieving a breakthrough of zero), nevertheless the accuracy of propionic and butyric acids was poorer than ADM1_ac with differences between experimental and simulation values were 5%–10% lower. With both factors coordinated, MP and VFA concentrations could be simulated accurately by ADM1_ac_va (ADM1 added acetic acid inhibition and valeric acid existence), with the highest goodness‐of‐fit values (>0.85). The results of a verification experiment with ADM1_ac_va simulation further indicated that acetic acid inhibition and valeric acid as new component were both important in ADM1.
Practitioner points
ADM1_ac could simulate MP and acetate, propionate and butyrate concentrations better.
ADM1_va could explain the valerate production during AD of glucose.
ADM1_ac_va could simulate AD process quite accurately, with the highest goodness‐of‐fit values (>0.85).
Acetate inhibition and valerate existence were both important and should be considered in ADM1.
Modified anaerobic digestion model No.1 (ADM1) for modeling anaerobic digestion process at different ammonium concentrations.
The aim of this study is to summarize currently available evidence on vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
A systematic review was conducted ...following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis Statement.
A total of 22 studies comprising 83 neonates born to mothers diagnosed with coronavirus disease 2019 were included in the present systematic review. Among these neonates, three were confirmed with SARS-CoV-2 infection at 16, 36, and 72 hours after birth, respectively, by nasopharyngeal swab real-time polymerase chain reaction (RT-PCR) tests; another six had elevated virus-specific antibody levels in serum samples collected after birth, but negative RT-PCR test results. However, without positive RT-PCR tests of amniotic fluid, placenta, or cord blood, there is a lack of virologic evidence for intrauterine vertical transmission.
There is currently no direct evidence to support intrauterine vertical transmission of SARS-CoV-2. Additional RT-PCR tests on amniotic fluid, placenta, and cord blood are needed to ascertain the possibility of intrauterine vertical transmission. For pregnant women infected during their first and second trimesters, further studies focusing on long-term outcomes are needed.
· We review neonates of mothers diagnosed with coronavirus disease 2019 detected by RT-PCR.. · No direct virologic evidence of vertical transmission has been reported.. · No evidence that cesarean delivery is safer than vaginal delivery.. · More RT-PCR tests on amniotic fluid, placenta, and cord blood are recommended..
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•The SARS-CoV-2 virus binds to human ACE2 much weaker at 40 °C than 37 °C.•The infection efficiency of SARS-CoV-2 is much weaker at high febrile temperature.•The temperature ...dependence of viral infection co-evolves with inflammatory response.
The SARS-CoV-2 virus and its homolog SARS-CoV penetrate human cells by binding of viral spike protein and human angiotensin converting enzyme II (ACE2). SARS-CoV causes high fever in almost all patients, while SARS-CoV-2 does not. Moreover, analysis of the clinical data revealed that the higher body temperature is a protective factor in COVID-19 patients, making us to hypothesize a temperature-dependent binding affinity of SARS-CoV-2 to human ACE2 receptor. In this study, our molecular dynamics simulation and protein surface plasmon resonance cohesively proved the SARS-CoV-2-ACE2 binding was less affinitive and stable under 40 °C (~18 nM) than the optimum temperature 37 °C (6.2 nM), while SARS-CoV-ACE2 binding was not (6.4 nM vs. 8.5 nM), which evidenced the temperature-dependent affinity and explained that higher temperature is related to better clinical outcome. The decreased infection at higher temperature was also validated by pseudovirus entry assay using Vero and Caco-2 cells. We also demonstrated the structural basis of the distinct temperature-dependence of the two coronaviruses. Furthermore, the meta-analysis revealed a milder inflammatory response happened in the early stage of COVID-19, which explained the low fever tendency of COVID-19 and indicated the co-evolution of the viral protein structure and the inflammatory response. The temperature dependence of the binding affinity also indicated that higher body temperature at early stages might be beneficial to the COVID-19 patients.
Background:
99mTechnetium labeled methylene diphosphonate bone scans (BSs) are commonly used to monitor disease progression in bone for patients with metastatic breast cancer (MBC). However, new BS ...lesions may represent osteoblastic bone healing, which we now define as bone pseudoprogression. In this study, we aimed to assess the clinical significance and determination methods of bone pseudoprogression.
Methods:
This retrospective analysis was conducted among 48 patients with hormone receptor-positive MBC treated with first-line endocrine therapy. Four months after initiating therapy, all the participants did not show extraosseous disease progression. Participants were divided into two groups according to the presence of new BS lesions. All the patients continued on treatment until explicit disease progression (extraosseous disease progression or progressive lysis on bone lesions). Explicit progression-free survival (PFS) and extraosseous objective response rate were analyzed between the two groups.
Results:
New BS lesions were observed in 11 of 48 (22.9%) patients. All the new BS lesions appeared as osteoblastic bone lesions on computed tomography. For patients with new BS lesions, the median PFS was 26.57 months 95% confidence interval (CI) 15.46–37.68, which was similar to that (29.57 months; 95% CI 19.24–39.90) in patients without new BS lesions hazard ratio: 1.098 (95% CI 0.482–2.503), p = 0.818. Notably, 82.9% of patients without new BS lesions showed an extraosseous objective response, whereas 85.7% of patients with new BS lesions demonstrated an extraosseous objective response odds ratio: 0.806 (95% CI 0.061–5.682), p = 0.999. The median interval between bone pseudoprogression and true disease progression was 21.26 months (95% CI 10.11–32.42).
Conclusions:
Osteoblastic new BS lesions detected on follow-up BSs may represent bone pseudoprogression. Clinicians should raise awareness of bone pseudoprogression, thereby avoiding premature discontinuation of therapy and maximizing the opportunity to benefit from endocrine therapy. Due to the small sample size and retrospective nature of the study, large prospective clinical trials are needed to confirm our findings.
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