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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.

Siglec-7 (sialic acid–binding immunoglobulin-like lectin 7) is an immune checkpoint-like glycan recognition protein on natural killer (NK) cells. Cancer cells often upregulate Siglec ligands to subvert immunosurveillance, but the molecular basis of Siglec ligands has been elusive. In this study, we investigated Siglec-7 ligands on chronic lymphocytic leukemia (CLL) B cells. CLL B cells express higher levels of Siglec-7 ligands compared with healthy donor B cells, and enzymatic removal of sialic acids or sialomucins makes them more sensitive to NK cell cytotoxicity. Gene knockout experiments have revealed that the sialyltransferase ST6GalNAc-IV is responsible for the biosynthesis of disialyl-T (Neu5Acα2–3Galβ1–3[Neu5Acα2–6]GalNAcα1–), which is the glycotope recognized by Siglec-7, and that CD162 and CD45 are the major carriers of this glycotope on CLL B cells. Analysis of public transcriptomic datasets indicated that the low expression of GCNT1 (encoding core 2 GlcNAc transferase, an enzyme that competes against ST6GalNAc-IV) and high expression of ST6GALNAC4 (encoding ST6GalNAc-IV) in CLL B cells, together enhancing the expression of the disialyl-T glycotope, are associated with poor patient prognosis. Taken together, our results determined the molecular basis of Siglec-7 ligand overexpression that protects CLL B cells from NK cell cytotoxicity and identified disialyl-T as a potential prognostic marker of CLL.

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.

Motor impairment is one of the most common defects after stroke, which could seriously affect the life quality of stroke patients. Exercise intervention gradually becomes a popular alternative rehabilitation therapy because of its safety and applicability. To systematically assess the effect of Qigong exercise on motor function in stroke patients. Randomized controlled trials that evaluated the effect of Qigong on motor function of stroke patients were obtained from PubMed and Chinese National Knowledge Infrastructure through May 2022. Mean values and standard deviations of the post-intervention score in both experimental group and control group were collected to calculate the mean difference (MD) and corresponkding 95% confidence interval (95% CI) of each study, which were quantificationally summarized using the Review Manager 5.3 software. Nineteen randomized controlled trials enrolling 1487 stroke patients were included. Pooled results indicated that Qigong exercise had beneficial effect on balance function (Berg Balance Scale [MD: 7.56, 95% CI: 4.09–11.02]), limb motor function (Fugl-Meyer Assessment [total score: MD: 7.54, 95% CI: 6.38–8.69; upper limb: MD: 3.57, 95% CI: 0.71–6.43; lower limb: MD: 2.44, 95% CI: 0.59–4.29]) and walking function (6-min walking test [MD: 62.21, 95% CI: 11.70–112.73]) of stroke patients. It was also found to be associated with an improvement in trunk function as indicated by the Trunk Impairment Scale. Available evidence supported potential benefits of Qigong exercise for improving motor functions of stroke patients. As a safe and widely applicable exercise, Qigong is worthy of further promotion in the rehabilitation of stroke patients. [ABSTRACT FROM AUTHOR]

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein–Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein–Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross‐reactivity between gp350 antibodies and SADs‐associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen. [ABSTRACT FROM AUTHOR]

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.

Siglecs, a family of receptor-like lectins, recognize glycoproteins and/or glycolipids containing sialic acid in the extracellular space and transduce intracellular signaling. Recently, researchers uncovered significant contributions of Siglecs in cancer immunity, renewing interest in this family of proteins. Previous extensive studies have defined how Siglecs recognize glycan epitopes (glycotopes). Nevertheless, the biological role of these glycotopes has not been fully evaluated. Recent studies using live cells have begun unraveling the constituents of Siglec ligands. These studies demonstrated that glycoprotein scaffolds (counter-receptors) displaying glycotopes are sometimes just as important as the glycotope itself. These new insights may guide future efforts to develop therapeutic agents to target the Siglec – ligand axis.

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.

Researchers have indicated that many children from Asian countries have the experience of learning English prior to school at home or at private institutes. The Taiwanese government promotes informal and play-based teaching of English in the home if the parents would like their young children to learn English prior to formal instruction. This study is designed to investigate how Taiwanese mothers attempt to facilitate their children's English development by exploring how they engage their children in English learning at home. We also investigate whether there is a relationship between maternal educational attainment and maternal teaching practices and the use of resources. The sample consists of 647 mothers of preschoolers who responded to a questionnaire which surveyed their practices and resources utilized at home. The results showed that mothers differed in the extent to which they engaged in shared reading and provided toys and computer media for English instruction, and that maternal education is related to the types of strategies and resources provided. The findings provide significant information about what the mothers utilized to assist their young children to learn English language. (Contains 3 tables.)

The pathological characteristics of Parkinson's disease (PD) include dopaminergic neuron damage, specifically disorders caused by dopamine synthesis, in vivo. Plastrum testudinis extract (PTE) and its bioactive ingredient ethyl stearate (PubChem CID: 8122) were reported to be correlated with tyrosine hydroxylase (TH), which is a biomarker of dopaminergic neurons. This suggests that PTE and its small-molecule active ingredient ethyl stearate have potential for development as a therapeutic drug for PD. In this study, we treated 6-hydroxydopamine (6-OHDA)-induced model rats and PC12 cells with PTE. The mechanism of action of PTE and ethyl stearate was investigated by western blotting, bisulfite sequencing PCR (BSP), real-time PCR, immunofluorescence and siRNA transfection. PTE effectively upregulated the TH expression and downregulated the alpha-synuclein expression in both the substantia nigra and the striatum of the midbrain in a PD model rat. The PC12 cell model showed that both PTE and its active monomer ethyl stearate significantly promoted TH expression and blocked alpha-synuclein, agreeing with the in vivo results. BSP showed that PTE and ethyl stearate increased the methylation level of the Snca intron 1 region. These findings suggest that some of the protective effects of PTE on dopaminergic neurons are mediated by ethyl stearate. The mechanism of ethyl stearate may involve disrupting the abnormal aggregation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) with alpha-synuclein by releasing DNMT1, upregulating Snca intron 1 CpG island methylation, and ultimately, reducing the expression of alpha-synuclein.

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.

The call by policymakers, education stakeholders, and families for children to enter school 'ready' has led to numerous empirical studies that seek to identify how children and their families are or are not prepared for school. In the United States, this empirical work tends to identify particular children and their families 'at-risk' for school success and often seeks out ways to intervene so that such risks are addressed. Absent from this work is an understanding of how families conceptualise school readiness, and how those understandings influence their conceptions of whether or not their own children are ready for school. Such work could assist educators and other school personnel in supporting families and their children as they enter their programmes. This article examines this issue by presenting findings from a qualitative metasynthesis of studies that investigated how families conceptualised school readiness. Analysing, synthesising, and interpreting their conceptions of school readiness offers the chance to consider how early childhood stakeholders can be ready for families as they enter their programmes as well as support their efforts in readying their children for school.

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.

High-tech protected cropping holds great potential to improve global food security, but high cooling energy costs in warm climates pose difficulties in propagating the industry. Emerging technologies, such as diffuse glasses fitted with photoselective thin films, have interactions with crops and other cooling technologies which are not well-characterized for warm-climate glasshouses. A light-blocking film (LBF) was chosen as a high-tech, climate-controlled greenhouse cover permitting transmission of 85% of photosynthetically-active light and blocking heat-generating radiation. Two consecutive 7-month trials of two capsicum crops were grown under warm climate conditions partially impacted by bushfire smoke, with 2 cultivars (Gina and Û06614) in the first trial, and 2 cultivars (Gina and Kathia) in the second trial. Capsicum fruit yield decreased by 3% in Gina and increased by 3% in O06614 for the first trial, and decreased by 13% in Gina, 26% in Kathia for the second trial. Cooling energy use increased by 11% and 12% for both capsicum crops in AE and SE respectively, with small but insignificant decreases in fertigation demand (2%-5%). Cooling potential was significantly different from material specifications, with indications that convection from LBF interfaces was responsible for higher heat loads. LBF and similar absorptive glasses may still be beneficial for reducing nutrient, water, and energy use in warm climate glasshouses. However, yield is cultivar-dependent and may decrease with below-optimal crop lighting, whereas energy savings are more dependent on LBF orientation and building geometry than outside climate. [ABSTRACT FROM AUTHOR]

Owing to the urgency of the climate change crisis and the emerging greenwashing issue that companies face, greenwashing in companies' carbon reduction is exceptionally important in the progress of global carbon reduction and the achievement of the Paris Agreement goals. Therefore, this study focused on multinational corporations (MNCs) listed on the 2021 Fortune Global 500 list (2001–2020) and used institutional theory to theoretically discuss and empirically test the relationship between MNCs' environmental scores and carbon emissions/intensity, as well as the moderating effect of national culture. Our results demonstrate that the environmental scores of MNCs positively affect their carbon emissions and intensity, meaning that managers tend to use high scores to hide their poor carbon reduction, showing a typical "talk" more and "act" less (i.e., greenwashing) behavior. Meanwhile, the moderating effects of individualism, masculinity, and uncertainty avoidance were negative. These revealed that the balance of MNCs' "talk" and "act" can be influenced by the domestic national cultural characteristics. Further analysis showed that the Paris Agreement did not prevent MNCs' greenwashing in carbon reduction. Such greenwashing behavior has become even worse in societies with power distance characteristics after the Paris Agreement. To the best of our knowledge, this is the first study to investigate companies' greenwashing in terms of carbon reduction. The goal is to enhance our understanding of why and how greenwashing occurs based on the institutional theory perspective, extend the application of institutional theory, enrich the literature on companies' greenwashing and national culture, and offer insight into interdisciplinary research between national culture and green transition management. Finally, suggestions for policymakers on how to prevent MNCs' greenwashing in carbon reduction, considering national cultural influence, were provided. [ABSTRACT FROM AUTHOR]