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Electrospun fibers prepared from water-soluble polymers (PVP, PVA, and HPMC) were loaded with pregabalin, a BCS I drug, to address its fast release and adverse effects. The drug dissolved partially (1.8–2.8 wt%) in the polymers, with excess pregabalin in crystalline form within the fibers. The solubility of the drug varied with the pH of the dissolution medium. Most of the drug encapsulated into the fibers during electrospinning, but some was lost due to technical reasons. PVP showed no impact on drug release, offering no benefit as a carrier. However, PVA-based fibers exhibited considerably slower release than the dissolution rate of the neat drug and also the release rate from fibers prepared from the other polymers. This indicates the potential of PVA for using it with pregabalin in practical drug formulations with improved release properties. The pH of the dissolution medium influenced solubility and release rate for specific polymers. Overall, the study highlights the importance of polymer selection and pH control in optimizing the release profile of pregabalin in enhanced drug delivery.

Abstract This paper develops a theoretical model of determinants influencing multimodal fake review generation using the theories of signaling, actor-network, motivation, and human–environment interaction hypothesis. Applying survey data from users of China’s three leading E-commerce platforms (Taobao, Jingdong, and Pinduoduo), we adopt structural equation modeling, machine learning technique, and Bayesian complex networks analysis to perform factor identification, path analysis, feature factor importance ranking, regime division, and network centrality analysis of full sample, male sample, and female sample to reach the following conclusions: (1) platforms’ multimodal recognition and governance capabilities exert significant negative moderating effects on merchants’ information behavior, while it shows no apparent moderating effect on users’ information behavior; users’ emotional venting, perceived value, reward mechanisms, and subjective norms positively influence multimodal fake review generation through perceptual behavior control; (2) feature factors of multimodal fake review generation can be divided into four regimes, i.e., regime 1 includes reward mechanisms and perceived social costs, indicating they are key feature factors of multimodal fake review generation; merchant perception impact is positioned in regime 2, signifying its pivotal role in multimodal fake review generation; regime 3 includes multimodal recognition and governance capabilities, supporting/disparaging merchants, and emotional venting; whereas user perception impact is positioned in regime 4, indicating its weaker influence on multimodal fake review generation; (3) both in full sample, male sample, and female sample, reward mechanisms play a crucial role in multimodal fake review generation; perceived value, hiring review control agency, multimodal recognition and governance capabilities exhibit a high degree of correlation; however, results of network centrality analysis also exhibit heterogeneity between male and female samples, i.e., male sample has different trends in closeness centrality values and betweenness centrality values than female sample. This indicates that determinants influencing multimodal fake review generation are complex and interconnected.

Background: Tripterygium glycosides (TG) is extracted from the roots of Tripterygium wilfordii Hook F (Lei gong teng, a traditional Chinese medicine). It is widely used in China to treat immunoglobulin A vasculitis nephritis (IgAVN), which is a common secondary glomerular disease. As there are no guidelines for the rational application of TG, we performed this study to evaluate the efficacy and safety of different doses of TG and to determine the optimal treatment for IgAVN. Methods: Ten databases were searched from their inception to April 2023 for randomised controlled trials (RCTs) using TG, TG combined with glucocorticoids (GC), or TG combined with traditional Chinese medicine (TCM) to treat IgAVN. A network meta-analysis was performed following the protocol (CRD42023401645). Results: Forty-four eligible RCTs involving 3402 patients were included. For effective rate, TG 1.5 mg/kg/d (TG1.5) + TCM was ranked as the best intervention, followed by TG 1.0 mg/kg/d (TG1.0) + TCM, TG1.5, TG1.0+GC, TG1.0, TCM, GC, and routine treatment (RT). TG1.0+TCM ranked best in reducing recurrence, followed by TG1.0+GC, GC, TG1.5, and RT. Compared with TG1.0, TG1.0+TCM and TG1.5+TCM effectively reduced liver injury events. Compared with TG1.5, TG1.5+TCM and TG1.0+TCM effectively reduced leukopenia events. No significant differences in the reduction of gastrointestinal events were observed between the interventions. Subgroup analyses explored the effects of the participants’ age. The intervention rankings of the outcomes generally remained consistent. Only a small difference was observed in gastrointestinal events. TCM was the best treatment for reducing gastrointestinal events in paediatric patients. Conclusions: The results showed a positive correlation between dose and efficacy, whereas no relationship was found between dose and adverse events. TCM can boost the efficacy and reduce adverse events when combined with TG. In conclusion, we consider TG1.5+TCM as the best treatment for IgAVN. However, further research is required to confirm these findings.

Background: China has experienced a COVID-19 wave caused by Omicron XBB variant starting in April 2023. Our aim is to conduct a retrospective analysis exploring the dynamics of the outbreak under counterfactual scenarios that combine the use of vaccines, antiviral drugs, and nonpharmaceutical interventions. Methods: We developed a mathematical model of XBB transmission in China, which has been calibrated using SARS-CoV-2 positive rates per week. Intrinsic age-specific infection-hospitalization risk, infection-ICU risk, and infection-fatality risk were used to estimate disease burdens, characterized as number of hospital admissions, ICU admissions, and deaths. Results: We estimated that in absence of behavioral change, the XBB outbreak in spring 2023 would have resulted in 0.86 billion infections (∼61% of the total population). Our counterfactual analysis shows that the synergetic effect of vaccination (70% vaccination coverage), antiviral treatment (20% receiving antiviral treatment), and moderate nonpharmaceutical interventions (20% isolation and L1 PHSMs) could reduce the number of deaths to levels close to seasonal influenza (1.17 vs. 0.65 per 10,000 individuals and 5.85 vs. 3.85 per 10,000 individuals aged 60+, respectively). The maximum peak prevalence of hospital and ICU admissions are estimated to be lower than the corresponding capacities (8.6 vs. 10.4 per 10,000 individuals and 1.2 vs. 2.1 per 10,000 individuals, respectively). Conclusion: Our findings suggest that the capacity of the Chinese healthcare system was adequate to face the Omicron XBB wave in spring 2023 but, at the same time, supports the importance of administering highly effective vaccine with long-lasting immune response, and the use of antiviral treatments.

Abstract. Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

Southeast Asia is suffering from extreme weather, and its carbon emissions are increasing rapidly. For efficient emission reduction, clarifying the complex sources behind is necessary. This study takes a new perspective of incorporating multiple GHGs (greenhouse gases) into the same analysis framework, employing the STIRPAT model to dissect the contributions of various socio-economic factors to the emissions of CO2, CH4, and F-gases based on panel data. The analysis reveals that the driving coefficients of total population and urbanization rate are several to 10 times higher than those of other factors and can reach up to 2.98 and 4.715 and are the most significant drivers of GHG emissions in the region. Quadratic per capita GDP shows a significant positive driving effect, indicating that most Southeast Asian countries are unlikely to reach the Kuznets point in current development trajectories. The driving coefficients of F-gases in industrialized countries are significantly higher than those of other GHGs, indicating that their growth rate of F-gases will outpace that of CO2 and CH4. In countries with a similar industrial structure, the driving coefficient of CO2 from the secondary industry is up to 0.183 and down to 0.057, shows the influence of specific sector composition in the secondary industry on emissions. These findings provide critical insights for Southeast Asian policymakers aiming to develop effective climate policies.

Modern data centers provide the foundational infrastructure of cloud computing. Workload generation, which involves simulating or constructing tasks and transactions to replicate the actual resource usage patterns of real-world systems or applications, plays essential role for efficient resource management in these centers. Data center traces, rich in information about workload execution and resource utilization, are thus ideal data for workload generation. Traditional traces provide detailed temporal resource usage data to enable fine-grained workload generation. However, modern data centers tend to favor tracing statistical metrics to reduce overhead. Therefore the accurate reconstruction of temporal resource consumption without detailed, temporized trace information become a major challenge for trace-based workload generation. To address this challenge, we propose STWGEN, a novel method that leverages statistical trace data for workload generation. STWGEN is specifically designed to generate the batch task workloads based on Alibaba trace. STWGEN contains two key components: a suite of C program-based flexible workload building blocks and a heuristic strategy to assemble building blocks for workload generation. Both components are carefully designed to reproduce synthetic batch tasks that closely replicate the observed resource usage patterns in a representative data center. Experimental results demonstrate that STWGEN outperforms state-of-the-art workload generation methods as it emulates workload-level and machine-level resource usage in much higher accuracy.

Background: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. Results: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 μGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation’s effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. Conclusions: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

Purpose: Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. Materials and methods: In this study, we irradiated C57BL/6J mice with 12.5μGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5μGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. Results and conclusions: We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3‘UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.

Increasing evidence indicates that the addictive use of social media can have a detrimental effect on marital satisfaction, due mainly to the decrease in time and focus given to one’s spouse. However, the impact of social media use among older couples remains under-investigated, and the research that does exist relies on individual-level data that do not allow the exploration of the dynamics between the dyadic partners. Therefore, the present study focused on older adults’ use of short-video platforms, as these have been shown to be particularly addictive for older adults. A sample of 264 older couples was gathered (meanage = 68.02, SD = 8.68), and both spouses completed surveys reporting addictive use of short-video platforms, negative emotions, and marital satisfaction. Using an actor–partner interdependence model, we found an asymmetrical dyadic process in that the addictive use of short-video platforms by the wives was not only related to their own negative emotions, but also those of their spouse, as well as to decreased marital satisfaction. Meanwhile, addictive use by the husbands seemed to relate only to their own increased negative emotions, as well as to decreased marital satisfaction. Together, the findings from this study reveal dyadic dynamics with delineated pathways through which the addictive use of short-video platforms can damage older couples’ interactive processes and marital satisfaction.

The carbon market is regarded as one of the important means to achieve China's dual carbon target. It has ancillary effect for reducing air pollution while regulating carbon emissions since climate change and air pollution share the same origin and homology. Research on how to design the carbon market mechanism in order to maximize the synergistic effect of reducing greenhouse gas and air pollution will have a very important practical impact for China. This study conducts a theoretical analysis of the collaborative emission reduction path of China's carbon market, and constructs an Energy-Economy-Environment (3E) model of the collaborative emission reduction effect of carbon trading system based on System Dynamics. After analyzing the feedback path of the core cycle of the model and verifying its performance, three main policy factors in the carbon market are explored, and their effects under the dual objectives of emission control and economic development are comprehensively evaluated. This study suggests that the exploration of the potential of carbon market for collaborative governance should be accelerated, and ensure the orderly expansion of coverage and precise setting of limits, so as to ensure the smooth achievement of carbon reduction targets while guaranteeing the social and economic development.

The extraction of indole from wash oil is of economic value and practical significance. In this study, deep eutectic solvents (DESs) are investigated to extract indole from wash oil. Initially, density functional theory calculations were used to explore the association of indole with aromatic compounds in wash oil, and the feasibility of indole extraction with a tetraethylammonium chloride/p-toluenesulfonic acid (TEAC/2TsOH) DES. Then, the influence of the temperature, stirring time, DESs dose, initial indole concentration, and amount of water added were investigated, followed by discussions on the comparison with other extractants and the performance of extracting of indole from real wash oil. The results show that indole associates with aromatic compounds in wash oil through π−π interactions, but that a large electrostatic interaction energy of −52.8 kJ/mol between indole and the DESs is the main driving force for the extraction process. Under optimal conditions, TEAC/2TsOH extracts more than 63.5 ± 3% of indole from wash oil, and its extraction capacity is superior to other extractants.

Since the implementation of the compulsory sorting of domestic waste policy in China, the participation rate of residents is low, which leads to the unsatisfactory result of terminal reduction of domestic waste. Therefore, the problem of domestic waste reduction still needs to rely on source reduction. Based on the panel data of 29 provincial capitals in China from 2009 to 2018, this study conducts a comprehensive threshold effect test on per capita GDP and other influencing factors of domestic waste production, conducts panel threshold regression for the factors with threshold value, and explores the nonlinear relationship between per capita GDP and domestic waste production under the influence of different threshold variables. The results show that when the urban population density is less than 272 people/km2, the increase of 1% of per capita GDP will lead to a decrease of 0.251% in the domestic waste production, otherwise, it will lead to an increase of 0.249%; when the per capita consumption expenditure is less than the threshold value of 10,260 yuan/year, the influence coefficient of per capita GDP is 0.155, which increases to 0.207 above the threshold. When the share of tertiary industry is taken as the threshold variable, the two threshold values are 61% and 71% respectively. Through the analysis of control variables, it has been found that population size and amount of courier per capita have significant positive effects on domestic waste production, while gas permeability and the number of non-governmental organizations have significant negative effects

Abstract Background The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic. Methods We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China’s current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. Results We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China’s pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. Conclusions As China’s current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

The [Fe, Al]-FER zeolites, which are prepared from the interzeolite conversion method (from MWW to FER topology) with high Al and Fe content (Si/Al of 8–18 and Si/Fe of 11–13), exhibit excellent catalytic performances and hydrothermal tolerance for NH3-SCR reaction. The interzeolite conversion process can be tuned by optimizing the zeolite synthesis conditions such as synthesis gel composition, crystallization time, crystallization temperature, and adding MWW seeds. The work can provide a new strategy to synthesize high Al and Fe content zeolite with high hydrothermal stability for NOx removal.

Abstract Heterogeneous nuclear ribonucleoproteins C (HnRNP C) is part of the hnRNP family of RNA-binding proteins. The relationship between hnRNP C and cancers has been extensively studied, and dysregulation of hnRNP C has been found in many cancers. According to existing public data, hnRNP C could promote the maturation of new heterogeneous nuclear RNAs (hnRNA s, also referred to as pre-mRNAs) into mRNAs and could stabilize mRNAs, controlling their translation. This paper reviews the regulation and dysregulation of hnRNP C in cancers. It interacts with some cancer genes and other biological molecules, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and double-stranded RNAs (dsRNAs). Even directly binds to them. The effects of hnRNP C on biological processes such as alternative cleavage and polyadenylation (APA) and N6-methyladenosine (m6A) modification differ among cancers. Its main function is regulating stability and level of translation of cancer genes, and the hnRNP C is regarded as a candidate biomarker and might be valuable for prognosis evaluation.

Summary: Background: In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods: We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmaceutical interventions. The epidemic was divided into three phases: i) sporadic infections (January 1–February 28), ii) local transmission (March 1–March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt). Findings: A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai until the end of May. The spatial distribution of the infections was highly heterogeneous, with 37% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 463 to 244 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation: Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for containing Omicron outbreaks. Funding: Key Program of the National Natural Science Foundation of China (82130093); Shanghai Rising-Star Program (22QA1402300).

Electrospun fibers containing levocetirizine, a BCS III drug, were prepared from three water-soluble polymers, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). Fiber-spinning technology was optimized for each polymer separately. The polymers contained 10 wt% of the active component. An amorphous drug was homogeneously distributed within the fibers. The solubility of the drug in the polymers used was limited, with a maximum of 2.0 wt%, but it was very large in most of the solvents used for fiber spinning and in the dissolution media. The thickness of the fibers was uniform and the presence of the drug basically did not influence it at all. The fiber diameters were in the same range, although somewhat thinner fibers could be prepared from PVA than from the other two polymers. The results showed that the drug was amorphous in the fibers. Most of the drug was located within the fibers, probably as a separate phase; the encapsulation efficiency proved to be 80–90%. The kinetics of the drug release were evaluated quantitatively by the Noyes–Whitney model. The released drug was approximately the same for all the polymers under all conditions (pH), and it changed somewhere between 80 and 100%. The release rate depended both on the type of polymer and pH and varied between 0.1 and 0.9 min−1. Consequently, the selection of the carrier polymer allowed for the adjustment of the release rate according to the requirements, thus justifying the use of electrospun fibers as carrier materials for levocetirizine.

Objective To explore the targets and signaling pathways of flavanomarein in the treatment of non-alcoholic fatty liver disease (NAFLD) by network pharmacology, and to investigate the effect and mechanisms in the treatment. Methods ① The potential active targets of flavanomarein were retrieved in the Swiss Target Prediction database, and the disease-related targets were searched in the DisGeNET database. The prediction targets of lipid metabolism of NAFLD regulated by flavanomarein was obtained through Venn analysis. The Biso Genet database was used to construct the protein-protein interaction (PPI) network diagram, the Metascape database was used to analyze GO functional enrichment and KEGG pathway enrichment, and the Cytoscape software was used to draw the "target-pathway" network diagram. ② NAFLD db/db mice was employed for in vivo verification. Thirty male db/db mice were randomly divided into db/m group, db/db model group, and db/db+flavanomarein group (50 mg/kg). After the administration of 0.5% sodium carboxymethyl cellulose solution and flavanomarein for 12 weeks, the mice were sacrificed, and the liver contents of TG, GSH and GSSG was detected. HE staining and oil red O staining were used to observe the pathological changes of the liver. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of key molecules in the lipid metabolism in the liver. ③HepG2 cells were treated with free fatty acids (FFAs, oleic acid∶palmitic acid =2∶1) and divided into normal group, FFAs treatment group (500 μmol/L), and FFAs+ low, medium and high concentrations of flavanomarein (25, 50, 100 μmol/L) for 24 h. Oil red O staining was used to detect the TG content in HepG2 cells. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of key molecules in the lipid metabolism of HepG2 cells. Results ① A total of 29 core targets of flavanomarein docking NAFLD were screened through Venn analysis, including peroxisome proliferator-activated receptor-gamma (PPARγ), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase 14 (MAPK14). The GO analysis enriched 6 molecular functions, 20 biological processes and 5 cellular components. KEGG analysis enriched 40 key signaling pathways related to the effect of flavanomarein on NAFLD, which mainly focuses on the AMPK lipid metabolism pathway, insulin resistance (IR) pathway, and apoptosis pathway. ② The results of animal experiments showed that flavanomarein treatment reduced TG level in the NAFLD mice (P < 0.05) and improved the ratio of GSH/GSSG (P < 0.05). HE and oil red O staining showed that flavanomarein could reverse hepatocyte enlargement and reduce lipid drop infiltration of hepatocytes. qRT-PCR results showed that the treatment decreased the mRNA levels of ACC1, SCD1, and FASN for lipid synthesis (P < 0.05), while increased those of ACOX-1 and CPT1α for β-oxidation (P < 0.05). Western blot assay results indicated that the expression levels of SREBP and FASN were obviously lower (P < 0.05), and those of PPARγ and PPARα were increased (P < 0.05) in the flavanomarein group than the model group. ③ In vitro cell experiments showed that flavanomarein reduced the TG content of HepG2 cells (P < 0.05) and the expression of SREBP, SCD1 and ACC1, but increased the levels of CPT1α and ACOX-1 mRNA (P < 0.05). And, the protein expression of SREBP and FASN was also significantly reduced (P < 0.05). Conclusion Flavanomarein may play a therapeutic role in NAFLD by improving oxidative stress, up-regulating fatty acid β-oxidation, reducing lipid synthesis through regulating the PPARγ/SREBP/FASN signaling pathway.

The Eastward-Moving Tibetan Plateau convective cloud clusters frequently trigger disastrous heavy rainstorm weather within the reaches of Yangtze River, which becomes one of the forecast difficulties nowadays. It is of great significance indeed to study on the eastward propagation characteristics and the evolution mechanism of the Tibetan Plateau cloud clusters, and relevant investigation is taken, thus the reviews and conclusions associated with the Eastward-Propagated Tibetan Plateau cloud clusters is systematically presented in this paper, including the observation targeted for the heavy rainstorm within the reaches of Yangtze River triggered by the Eastward-Propagated Tibetan Plateau cloud clusters, the activity characteristics and the atmospheric circulation condition of the Eastward-Propagated Tibetan Plateau cloud clusters. Then a physical conceptual model describing the evolution mechanism of the Eastward-Propagated Tibetan Plateau cloud clusters is refined based on these review summaries. Finally, a brief overview of the classic theory that describes how the topography affects the evolution of the convective precipitation is also presented in this paper.

In decisions about transportation for family vacations, the distribution of the decision-making role between fathers and other family members is subject to characteristics of the society, the travel and the household. Therefore, the purpose of this study is to present a data-mining model that identifies the relative importance of those determining characteristics in predicting the probability of the father's predominance in transportation decisions for family vacations. By investigating cases across four East Asian societies and using exhaustive chi-square automatic identification detector analysis, it was found that the primary source of the family's income was the strongest predictor of the father-determined likelihood of decisions about vacation transportation. The results also suggested that the decision tree method is appropriate for targeting the father-predominant market of transportation in cross-societal contexts.

PLA/regenerated cellulose (RC) nanocomposites containing 0.5, 1.0, 1.5, 2.0, 3.0 and 5.0 wt% cellulose were prepared by the Pickering emulsion process. The structure and the rheological properties of the composites were characterized by microscopy, the measurement of melt flow rate and oscillatory rheometry. Viscosity was modelled with the modified Carreau-Yasuda and the modified Cross models, and a new model was proposed as well. The results show that RC is a suitable reinforcement for PLA and the Pickering emulsion process produces homogeneous material. Good dispersion and the relatively large aspect ratio of the cellulose nanofiller leads to the formation of a network structure already at small cellulose content. Viscosity increases rapidly with increasing cellulose concentration and a yield stress appears already at 0.5 wt% RC content. Modeling helps the quantitative analysis of the experimental results and offers additional information about the structure and properties of the composites studied. All three models predict yield stress well, but only the new model gives reasonable values for the power law exponent. Other parameters and their composition dependence are difficult to interpret.

Background Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.Methods A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.Results Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of patients. Specific AEs of interest that occurred ≤8 weeks postinfusion included cytokine-release syndrome (CRS; 79% (grade 4: 22%)), infections (42%; grade 3/4: 19%), prolonged (not resolved by day 28) cytopenias (40%; grade 3/4: 34%), neurologic events (36%; grade 3: 10%; no grade 4 events), and tumor lysis syndrome (4%; all grade 3). Treatment for CRS included tocilizumab (40%) and corticosteroids (23%). The frequency of neurologic events increased with CRS severity (p1 year postinfusion.Conclusions This pooled analysis provides a detailed safety profile for tisagenlecleucel during the course of clinical trials, and AE management guidance, with a longer follow-up duration compared with previous reports.

This study was aimed at investigating the effectiveness of inactivated COVID-19 vaccines against the Delta variant. We performed a retrospective cohort study of close contacts of people with laboratory-confirmed SARS-CoV-2 infections in Hunan province, China, from July to August 2021. Mixed-effect logistic regression was used to estimate vaccine effectiveness (VE), and analyze the effects of the vaccination status of index cases and the exposure risk level on VE estimation. A total of 1,685 close contacts of 126 index cases were included; 835 (49.6%) had received two doses of inactivated vaccines, and the median interval between the 2nd dose and exposure was 48 days (IQR: 41 to 56 days). Full vaccination was defined as two doses at least 14 days before exposure. Adjusted VE estimates for full vaccination were 54.8% (95% CI: 7.7 to 77.9) and 68.4% (95% CI: 8.5 to 89.1) against symptomatic and moderate-to-severe COVID-19, respectively. VE for inactivated vaccines was difficult to observe if index cases had been fully vaccinated. The estimated VE with respect to infection protection was lower among household than non-household contacts. Complete primary immunization of two-dose inactivated COVID-19 vaccines protected against SARS-CoV-2 Delta variant infection. Infection risk was higher among vaccinated household contacts than vaccinated non-household contacts.

The implementation of the agricultural insurance policy and advancement of agricultural technology has great significance for the development of the agricultural economy of China, and it is an important source of national stability and modernization and development of the agriculture sector. Agricultural insurance policy uses the expansion of agricultural technology progress in the process of evaluation, investigation and claims settlement, and so on. Agricultural technology progress is effective in the reduction of some agricultural risks, it also affects farmers’ agricultural insurance behaviors, and optimizes the operating environment of agricultural insurance. The objective of this research is to explore the relationship between agricultural technology progress, agricultural insurance and farmers’ income. It also explains the mutual/cooperative relationship between agricultural technology progress and agricultural insurance. It provides the theoretical basis and data support to verify the promotion effect of agricultural insurance and agricultural technology progress on farmers’ income. This gives the improvement path for alleviating the spatial imbalance of China’s agricultural development. Keeping in view the aforementioned background and this research explores the effects of agricultural technological progress and agricultural insurance on the farmers’ income level. The panel data used for this research were from 2004 to 2019 and were grouped into two parts: high-density agricultural insurance areas and low-density agricultural insurance areas. The relationship between agricultural technology progress, agricultural insurance and farmers’ income was estimated using the Panel Vector Autoregressive (PVAR) model. The results revealed that: (i) both agricultural technology progress and agricultural insurance have a positive effect on the farmers’ income level, but this effect varies across regions; (ii) impact of the agricultural insurance on farmers’ income is greater than the impact of agricultural technology progress on farmers’ income; and (iii) the role of agricultural insurance in promoting agricultural technology progress exists only in areas with high-density agricultural insurance. Therefore, when formulating policies, the policymakers should consider regional differences and characteristics, and adopt development models keeping in view regional variations in adaptability with different agricultural insurance densities, Moreover, they should improve agricultural security policies, optimize agricultural capital allocation, promote the transformation of the agricultural economy from extensional growth to connotative growth, and further improve the agricultural productive income of rural residents.

The eastern slope of the Tibetan Plateau is a crucial corridor of water-vapor transport from the Tibetan Plateau to Eastern China. This is also a region with active cloud initiation, and the locally hatched cloud systems have a profound impact on the radiation budget and hydrological cycle over the downstream Sichuan Basin and the middle reach of the Yangtze River. It is noteworthy that there is a strong diversification in the characteristics and evolution of the ESTP cloud systems due to the complex terrain. Therefore, in this study, ground-based Ka-band millimeter-wave cloud radar measurements collected at the Ganzi (GZ), Litang (LT), Daocheng (DC), and Jiulong (JL) sites of the ESTP in 2019 were analyzed to compare the vertical structures of summer nonprecipitating clouds, including cloud occurrence frequency, radar reflectivity factor, cloud base height, cloud top height, and cloud thickness. The occurrence frequency exhibits two peaks on the ESTP with maximum values of ~20% (2–4 km) and 15% (7–9 km), respectively. The greatest (smallest) occurrence frequency occurs in the JL (GZ). The cloud occurrence frequency of all sites increases rapidly in the afternoon, and the occurrence frequency of the DC presents larger values at 2–4 km. In contrast, the occurrence frequency in the JL shows another increase from 2000 LT to midnight at 7–11 km. Stronger radar echoes occur most frequently in the LT at 5–7 km, and hydrometeor sizes and phase states vary dramatically in mixed-phase clouds. A small number of radar echoes occur at midnight in the JL. A characteristic bimodality of the cloud base height and top height for single-layer, double-layer, and triple-layer clouds was observed. Clouds show a higher base height in the GZ and higher top height in the JL. The ESTP is dominated by thin clouds with thicknesses of 200–400 m. The cloud base height, top height, and thickness exhibit an increase in the afternoon, and higher top height occurs more frequently from midnight to the next early morning in the JL because of its mountain-valley terrain.

Summary: Fibrosis, or the accumulation of extracellular matrix, is a common feature of many chronic diseases. To interrogate core molecular pathways underlying fibrosis, we cross-examine human primary cells from various tissues treated with TGF-β, as well as kidney and liver fibrosis models. Transcriptome analyses reveal that genes involved in fatty acid oxidation are significantly perturbed. Furthermore, mitochondrial dysfunction and acylcarnitine accumulation are found in fibrotic tissues. Substantial downregulation of the PGC1α gene is evident in both in vitro and in vivo fibrosis models, suggesting a common node of metabolic signature for tissue fibrosis. In order to identify suppressors of fibrosis, we carry out a compound library phenotypic screen and identify AMPK and PPAR as highly enriched targets. We further show that pharmacological treatment of MK-8722 (AMPK activator) and MK-4074 (ACC inhibitor) reduce fibrosis in vivo. Altogether, our work demonstrate that metabolic defect is integral to TGF-β signaling and fibrosis.

Abstract In this study, we compared the performance of two potential predicators, that is, El Niño–Southern Oscillation (ENSO) index (Niño‐3.4) and mega‐ENSO index, in the seasonal forecast of tropical cyclone (TC) activity and its spatial distribution over the western North Pacific (WNP) during the extended TC season, which is of public concern. Our results clearly show that, although both mega‐ENSO and Niño‐3.4 indices in the preceding May are important predictors for the seasonal predication, the relative‐sea surface temperature (SST)‐dependent mega‐ENSO exhibits a higher skill in the seasonal forecasting compared with the absolute‐SST‐dependent ENSO. Further results show that, despite of stronger destructiveness of TCs in high mega‐ENSO (El Niño) years than in low mega‐ENSO (La Niña) years, more attention should be paid to the TCs in low mega‐ENSO years, which are more likely to occur in coastal areas compared with the TCs in high mega‐ENSO years. Due to the responses of TC genesis, TC potential intensity, and large‐scale flow to the SST change in low mega‐ENSO years, the WNP TCs tend to originate in the northwestern quadrant and intensify at high latitudes and then turn northwestward over the TC prevailing region, which contributes to the northwestward migration of the WNP TC exposure in terms of track density and destructiveness density and thus imposes more risks in the coastal areas in low mega‐ENSO years. In addition, despite the significant predication skill in forecasting TC activity when using mega‐ENSO/Niño‐3.4 as a single predicator, it is still far to predict reliable WNP activity, especially its spatial distribution, without considering other predictors.

Abstract State‐of‐the‐art climate models are extremely useful tools, but they all have biases when simulating tropical cyclone (TC) genesis location. These biases contribute to discrepancies in simulating other characteristics of TC activities (e.g., track, intensity, and duration) and even the surrounding large‐scale circulation. The genesis potential index (GPI) is a useful tool to evaluate the performance of climate models in simulating TC genesis. Here, it is employed to investigate possible causes of simulation biases of TC genesis location in western North Pacific using the downscaled Community Atmosphere Model Version 5 (CAM5) climate model and observations. We find that GPI can reasonably describe the spatial pattern of TC genesis location in either observation or simulation. By having one of GPI‐related variables (i.e., low‐level absolute vorticity, middle‐level relative humidity, vertical wind shear, and potential intensity) change with the others set to stable while testing single variable, the contributions of environmental fields associated with GPI are examined and a possible cause of TC genesis biases is revealed. Due to the overestimated humidity in the east region of western North Pacific, the simulated GPI high value region is to the east of the observed one, and more TCs in the downscaled CAM5 model generate farther east than in observation. These results imply that the biases in simulated humidity and thus TC genesis location may be reduced by correcting the evaporation rate in the deep convection scheme, since the evaporation rate is closely related to environment humidity change as suggested by previous studies.

In an attempt to improve the solubility of valsartan, a BCS II drug, fibers containing the drug were prepared from three water-soluble polymers, hydroxypropyl-methyl-cellulose (HPMC), polyvinyl-pyrrolidone (PVP), and polyvinyl-alcohol (PVA). Fiber spinning technology was optimized for each polymer separately. The polymers contained 20 wt% of the active component. The drug was homogenously distributed within the fibers in the amorphous form. The presence of the drug interfered with the spinning process only slightly, the diameters of the fibers were in the same range as without the drug for the HPMC and the PVA fibers, while it doubled in PVP. The incorporation of the drug into the fibers increased its solubility in all cases compared to that of the neat drug. The solubility of the drug itself depends very much on pH and this sensitivity remained the same in the HPMC and PVP fibers; the release of the drug is dominated by the dissolution behavior of valsartan itself. On the other hand, solubility and the rate of release were practically independent of pH in the PVA fibers. The different behavior is explained by the rate of the dissolution of the respective polymer, which is larger for HPMC and PVP, and smaller for PVA than the dissolution rate of the drug. The larger extent of release compared to neat valsartan can be explained by the lack of crystallinity of the drug, its better dispersion, and the larger surface area of the fibers. Considering all facts, the preparation of electrospun devices from valsartan and water-soluble polymers is beneficial, and the use of PVA is more advantageous than that of the other two polymers.

Abstract The response of tropical cyclone (TC) destructive potential to global warming is an open issue. A number of previous studies have ignored the effect of TC size change in the context of global warming, which resulted in a significant underestimation of the TC destructive potential. The lack of reliable and consistent historical data on TC size limits the confident estimation of the linkage between the observed trend in TC size and that in sea surface temperature (SST) under the background of global climate warming. A regional atmospheric model is used in the present study to investigate the response of TC size and TC destructive potential to increases in SST. The results show that a large-scale ocean warming can lead to not only TC intensification but also TC expansion. The TC size increase in response to the ocean warming is possibly attributed to the increase in atmospheric convective instability in the TC outer region below the middle troposphere, which facilitates the local development of grid-scale ascending motion, low-level convergence and the acceleration of tangential winds. The numerical results indicate that TCs will become stronger, larger, and unexpectedly more destructive under global warming.

Objective: Hypoglycemia has been shown to promote inflammation, a common pathogenic process, in many chronic health conditions including diabetes and cardiovascular disease. The aim of this study was to investigate the association of hypoglycemia, assessed by continuous glucose monitoring (CGM) with major adverse cardiovascular event (MACE) outcomes and all-cause mortality.Methods: A retrospective cohort study was conducted with 1,520 patients with type 2 diabetes mellitus (T2DM). The severity of hypoglycemia event was assessed by CGM system.Results: Three hundred and forty-seven participants experienced hypoglycemia events (323 with mild hypoglycemia and 24 with severe hypoglycemia). A fraction of 72.62% hypoglycemia was asymptomatic. During a median follow-up of 31 months, 380 participants reached the primary outcome of MACE (61 cardiovascular death, 50 non-fatal myocardial infarction [MI], 116 non-fatal stroke, 153 unstable angina requiring hospitalization), 80 participants died before the end of the study. In multivariate Cox regression models, hypoglycemia was associated with cardiovascular death (HR 2.642[95CI% 1.398–4.994]), non-fatal stroke (HR 1.813 [95CI% 1.110–2.960]) and all-cause mortality (HR 1.960 [95 CI% 1.124- 3.418]) after the full adjustment. Hypoglycemia was not associated with non-fatal MI and unstable angina. The HR of severe hypoglycemia was higher than mild hypoglycemia for cardiovascular death. Patients with symptomatic and asymptomatic hypoglycemia had similar MACE outcomes and all-cause mortality.Conclusions: CGM is effective to detect asymptomatic and nocturnal hypoglycemia. Hypoglycemia is associated with an increased risk of non-fatal stroke, cardiovascular related death, and total mortality. The cardiovascular mortality is dose-dependent on the severity of hypoglycemia.

One of the most devastating consequences of diabetes mellitus is a chronic condition, diabetic foot ulcer. Numerous investigations are being targeted to explore newer compounds for treatment of diabetic foot ulcer wounds in diabetic patients. Hesperidin (HSP), an isoflavone glycoside has been established to exhibit antidiabetic and antioxidant potential. In the current investigation, diabetes was induced in rats by administration by streptozotocin (STZ) intraperitoneally (50 mg/kg). Wound-healing capacity was estimated in hind paw of rats by artificially initiating wound injury on the paw dorsal surface. The injured animals were administered with incremental doses of HSP suspension orally (10, 20, 40, 60, and 80 mg/kg) and insulin subcutaneously (10 IU/kg). Parameters such as wound area were estimated every 2 days, and at the end of 20 days of study, biochemical estimations in serum and histopathological observations of the wound were made. HSP (60 and 80 mg/kg) revealed statistically significant ( P

The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received