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Searching for superconductivity with T c near room temperature is of great interest both for fundamental science & many potential applications. Here we report the experimental discovery of superconductivity with maximum critical temperature ( T c ) above 210 K in calcium superhydrides, the new alkali earth hydrides experimentally showing superconductivity above 200 K in addition to sulfur hydride & rare-earth hydride system. The materials are synthesized at the synergetic conditions of 160~190 GPa and ~2000 K using diamond anvil cell combined with in-situ laser heating technique. The superconductivity was studied through in-situ high pressure electric conductance measurements in an applied magnetic field for the sample quenched from high temperature while maintained at high pressures. The upper critical field Hc(0) was estimated to be ~268 T while the GL coherent length is ~11 Å. The in-situ synchrotron X-ray diffraction measurements suggest that the synthesized calcium hydrides are primarily composed of CaH 6 while there may also exist other calcium hydrides with different hydrogen contents. The discovery of superconductivity in hydrides at critical temperature ( T c ) near room temperature receives intensive attentions. Here the authors report experimental synthesis and discovery of superconductivity with T c above 210 K in calcium superhydrides at 160–190 GPa.

Occludin is a key structural component of the blood-brain barrier (BBB) that has recently become an important focus of research in BBB damages. Many studies have demonstrated that occludin could regulate the integrity and permeability of the BBB. The function of BBB depends on the level of occludin protein expression in brain endothelial cells. Moreover, occludin may serve as a potential biomarker for hemorrhage transformation after acute ischemic stroke. In this review, we summarize the role of occludin in BBB integrity and the regulatory mechanisms of occludin in the permeability of BBB after ischemic stroke. Multiple factors have been found to regulate occludin protein functions in maintaining BBB permeability, such as Matrix metalloproteinas-mediated cleavage, phosphorylation, ubiquitination, and related inflammatory factors. In addition, various signaling pathways participate in regulating the occludin expression, including nuclear factor-kappa B, mitogen-activated protein kinase, protein kinase c, RhoK, and ERK1/2. Emerging therapeutic interventions for ischemic stroke targeting occludin are described, including normobaric hyperoxia, Chinese medicine, chemical drugs, genes, steroid hormones, small molecular peptides, and other therapies. Since occludin has been shown to play a critical role in regulating BBB integrity, further preclinical studies will help evaluate and validate occludin as a viable therapeutic target for ischemic stroke.

Both PNPLA3 I148M and hepatic inflammation are associated with nonalcoholic fatty liver disease (NAFLD) progression. This study aimed to elucidate whether PNPLA3 I148M is involved in NF‐kB‐related inflammation regulation in NAFLD. HepG2 cells homozygous for the PNPLA3 I148M mutation were used. The human PNPLA3 promoter sequence was screened for NF‐kB binding sites using the MATCH and PATCH tools. NF‐kB‐mediated transcriptional regulation of the PNPLA3 gene was assessed by luciferase reporter assay, EMSA and ChIP‐qPCR. Wild‐type (I148I) and mutant (M148M) PNPLA3 were overexpressed using stable lentivirus‐mediated transfection. The pCMV vector and siRNA were transiently transfected into cells to direct NF‐kB overexpression and PNPLA3 silencing, respectively. A putative NF‐kB binding site in the human PNPLA3 promoter was shown to be necessary for basal and NF‐kB‐driven transcriptional activation of PNPLA3 and protein/DNA complex formation. Supershift analysis demonstrated a protein/DNA complex specifically containing the NF‐kB p65 and p50 subunits. ChIP‐qPCR confirmed the endogenous binding of NF‐kB to the human PNPLA3 promoter in response to NF‐kB overexpression and palmitic acid (PA) challenge. The silencing of PNPLA3 blocked the overexpression of NF‐kB or PA‐induced TNF‐α up‐regulation. Moreover, mutant PNPLA3 overexpression prevented NF‐kB inhibitor–induced down‐regulation of TNF‐α expression in PA‐treated HepG2 cells. Finally, the overexpression of mutant but not wild‐type PNPLA3 increased TNF‐α expression and activated the ER stress–mediated and NF‐kB‐independent inflammatory IRE‐1α/JNK/c‐Jun pathway. Human PNPLA3 was shown to be a target of NF‐kB, and PNPLA3 I148M mediated the regulatory effect of NF‐kB on inflammation in PA‐treated HepG2 cells, most likely via the IRE‐1α/JNK/c‐Jun ER stress pathway.

BackgroundAsthma represents a significant global health challenge, exhibiting considerable variation in prevalence, incidence, mortality and disability-adjusted life years (DALYs) across regions and countries. This study evaluates global, regional and national trends in asthma burden from 1990 to 2021, analysing associations with temporal, geographical and demographical factors.MethodsUsing open data from the Global Burden of Disease (GBD) database (1990–2021), we analysed changes in asthma prevalence, incidence, mortality and DALYs by gender, age and Socio-Demographic Index (SDI) groups. Joinpoint regression analysis calculated the average annual percentage change (AAPC) and annual percentage change (APC).ResultsFrom 1990 to 2021, the age-standardised prevalence and incidence rates of asthma declined by 40.01% and 29.89%, respectively. While asthma deaths increased slightly, the age-standardised mortality rate (ASMR) declined by 46.01%. The highest prevalence was observed in South Asia, East Asia and high-income North America, while low-SDI regions exhibited elevated mortality and DALYs. The age and sex-specific patterns indicated a higher asthma burden among females. The results of the joinpoint analysis indicated a global age-standardised incidence rate increase between 2005 and 2010 for both males and females. The ASMR exhibited a statistically significant decline from 1990 to 2021.ConclusionsThe global age-standardised rate of asthma burden declined from 1990 to 2021. However, asthma remains a significant public health issue, particularly in regions with lower socioeconomic development. Understanding global and regional trends in asthma can inform future policies and interventions, aiming to promote more equitable prevention, diagnosis and treatment worldwide.

Background Multifaceted non-pharmaceutical interventions during the COVID-19 pandemic have not only reduced the transmission of SARS-CoV2, but have had an effect on the prevalence of other pathogens. This retrospective study aimed to compare and analyze the changes of respiratory pathogens in hospitalized children with community-acquired pneumonia. Methods From January 2019 to December 2020, children with community-acquired pneumonia were selected from the Department of Respiratory Medicine, Shanghai Children’s Medical Center. On the first day of hospitalization, sputum, throat swabs, venous blood samples from them were collected for detection of pathogens. Results A total of 2596 children with community-acquired pneumonia were enrolled, including 1871 patients in 2019 and 725 in 2020. The detection rate in 2020 was lower than in 2019, whether single or multiple pathogens. Compared with 2019, the detection rate of virus, especially parainfluenza virus, influenza virus and respiratory syncytial virus, all decreased in 2020. On the contrary, the prevalence of human rhinovirus was much higher than that in 2019. In addition, the positivity rate for bacteria did not change much over the two years, which seemed to be less affected by COVID-19. And Mycoplasma pneumoniae which broke out in 2019 has been in low prevalence since March 2020 even following the reopening of school. Conclusions Strict public health interventions for COVID-19 in China have effectively suppressed the spread of not only SARS-CoV2 but parainfluenza virus, influenza virus and Mycoplasma pneumonia as well. However, it had a much more limited effect on bacteria and rhinovirus. Therefore, more epidemiological surveillance of respiratory pathogens will help improve early preventive measures.

Graphitic carbon nitride (g-C3N4) fabricated from different precursors exhibits unique microstructures and photocatalytic performance under visible light. Herein, we synthesized five different microstructures of g-C3N4 by the thermal poly condensation method using guanidine hydrochloride, melamine, urea, dicyandiamide and thiourea as the precursors. The results indicated that g-C3N4 prepared from urea precursor (UCN) has a nanostructure, porous layered structure, large specific surface area, and high separation efficiency of photo generated hole-electron pairs, which showed the best photocatalytic activity among all of the as-prepared samples. As for the lowest cost among the above five precursors, urea is an ideal candidate material for preparing g-C3N4 photocatalyst for a huge potential of wide industrial applications. In addition, Pt or Ni were used as the co-catalyst and loaded onto the g-C3N4 surface for photocatalytic hydrogen production. In comparison with noble metal Pt co-catalyst, Ni co-catalyst is inexpensive and has a significant effect o enhancing the photocatalytic activity under visible light. Therefore, Ni exhibits a considerable prospect to replace noble metal co-catalysts in the photocatalytic reactions.

Lung consolidation (LC) in pediatric pneumonia could lead to complicated clinical outcomes, yet the underlying immunological mechanisms are not fully understood. This study aimed to investigate the roles of local and systemic cytokines in the development of pulmonary complications and disease progression in children with pneumonia-associated LC. Conducted at the Shanghai Children's Medical Center, this study included 169 children admitted between June 2022 and October 2023. We analyzed levels of fifteen cytokines in bronchoalveolar lavage fluid (BALF) and blood. Classification and regression tree (CART) analysis identified specific cytokines associated with pulmonary complications and hypoxemia. In children with LC, most local cytokines were found at higher levels than systemic cytokines, with no apparent correlation between the two. Notably, an elevated level of IL-8 (≥ 6615 pg/ml) in BALF was associated with an increased risk of hypoxemia. Additionally, elevated levels of IL-4 and INF-γ in BALF were closely associated with the development of multi-segmental LC. Furthermore, elevated levels of IL-2R in BALF were significantly associated with the occurrence of atelectasis, in contrast to their levels in peripheral blood. IL-4, INF-γ, IL-2R, and IL-8 levels in BALF are closely associated with pulmonary complications and disease progression in children with LC. Exploring targeted immunomodulatory therapies in these children may mitigate lung injury caused by excessive local inflammatory responses.

Objective: To estimate the clinical effectiveness of oseltamivir in children with different subtypes of influenza virus infection. Methods: A total of 998 children with acute respiratory infection were enrolled from January to March 2018, and were divided into influenza A, influenza B, influenza A + B, and non-influenza infection (IV-negative) groups. Influenza-like symptoms and duration of fever were evaluated and compared between oseltamivir-treated and non-treated groups. Results: There were no significant differences in the reduction in total febrile period and duration of fever from the onset of therapy between the oseltamivir treated and non-treated children infected with influenza A ( p = 0.6885 for total febrile period and 0.7904 for the duration of fever from the onset of treatment), influenza B ( p = 0.1462 and 0.1966), influenza A + B ( p = 0.5568 and 0.9320), and IV-negative ( p = 0.7631 and 0.4655). The duration of fever in children received oseltamivir therapy within 48 h was not significantly shorter than that beyond 48 h ( p > 0.05). Additionally, percentages and severities of influenza-like symptoms, including headache, myalgia, fatigue, bellyache, vomiting, diarrhea, sore throat, cough, and coryza were not decreased and alleviated after treatment of oseltamivir. Conclusion: Oseltamivir treatment does not significantly shorten the duration of fever, nor does it significantly relieve influenza-like symptoms in children with infection of influenza.

Hemorrhagic transformation (HT) is a severe complication following acute ischemic stroke, particularly with reperfusion interventions, leading to poor prognosis. Serum occludin level is related with blood brain barrier disruption, and the National Institute of Health stroke scale (NIHSS) score reflects stroke severity. We investigated whether the two covariates are independently associated with HT and their combination can improve the accuracy of HT prediction in ischemic stroke patients with reperfusion therapy. Seventy-six patients were screened from the established database of acute ischemic stroke in our previous study, which contains all clinical information, including serum occludin levels, baseline NIHSS score, and hemorrhagic events. Multivariate logistic regression analysis showed that serum occludin level (OR = 4.969, 95% CI: 2.069–11.935, p < 0.001) and baseline NIHSS score (OR = 1.293, 95% CI 1.079–1.550, p = 0.005) were independent risk factors of HT after adjusting for potential confounders. Compared with non-HT patients, HT patients had higher baseline NIHSS score [12 (10.5–18.0) versus 6 (4–12), p = 0.003] and serum occludin level (5.47 ± 1.25 versus 3.81 ± 1.19, p < 0.001). Moreover, receiver operating characteristic curve based on leave-one-out cross-validation showed that the combination of serum occludin level and NIHSS score significantly improved the accuracy of predicting HT (0.919, 95% CI 0.857–0.982, p < 0.001). These findings suggest that the combination of two methods may provide a better tool for HT prediction in acute ischemic stroke patients with reperfusion therapy.

Hemorrhagic transformation (HT), which occurs with or without reperfusion treatments (thrombolysis and/or thrombectomy), deteriorates the outcomes of ischemic stroke patients. It is essential to find clinically reliable biomarkers that can predict HT. In this study, we screened for potential serum biomarkers from an existing blood bank and database with 243 suspected acute ischemic stroke (AIS) patients. A total of 37 patients were enrolled, who were diagnosed as AIS without receiving reperfusion treatment. They were divided into two groups based on whether they were accompanied with HT or not (five HT and 32 non-HT). Serum samples were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and compared under NCBInr database. A total of 647 proteins in sera samples were captured, and the levels of 17 proteins (12 upregulated and five downregulated) were significantly different. These differentially expressed proteins were further categorized with Gene Ontology functional classification annotation and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis into biological processes. Further protein–protein interaction analysis using String database discovered that, among the differentially expressed proteins, 10 pairs of proteins were found to have crosstalk connections, which may have direct (physical) and indirect (functional) interactions for the development of HT. Our findings suggest that these differentially expressed proteins could serve as potential biomarkers for predicting HT after ischemic stroke.