Research progress of anti-gout small molecules targeting the NLRP3 inflammasome / 药学学报

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

Unveiling a New Perspective on Distinguishing Omicron Breakthrough Cases and Postimmune COVID-19-Naive Individuals: Insights from Antibody Profiles.

In the situation of mass vaccination against COVID-19, few studies have reported on the early kinetics of specific antibodies (IgG/IgM/IgA) of vaccine breakthrough cases. There is still a lack of epidemiological evidence about the value of serological indicators in the auxiliary diagnosis of COVID-19 infection, especially when the nucleic acid results were undetectable. Omicron breakthrough cases post-inactivated vaccination (n = 456) and COVID-19-naive individuals with two doses of inactivated vaccination (n = 693) were enrolled. Blood samples were collected and tested for SARS-CoV-2 antibody levels based on the magnetic chemiluminescence enzyme immunoassay. Among Omicron breakthrough cases, the serum IgG antibody level was 36.34 Sample/CutOff (S/CO) (95% confidence interval [CI], 31.89 to 40.79) in the acute phase and 88.45 S/CO (95% CI, 82.79 to 94.12) in the recovery phase. Serum IgA can be detected in the first week post-symptom onset (PSO) and showed an almost linear increase within 5 weeks PSO. Compared with those of breakthrough cases, IgG and IgA titers of the postimmune group were much lower (4.70 S/CO and 0.46 S/CO, respectively). Multivariate regression showed that serum IgG and IgA levels in Omicron breakthrough cases were mainly affected by the weeks PSO (P < 0.001). Receiver operating characteristic ROC0 curve analysis showed that the area under the curve (AUC) was 0.744 and 0.806 when the cutoff values of IgA and IgG were 1 S/CO and 15 S/CO, respectively. Omicron breakthrough infection can lead to a further increase in IgG and IgA levels relative to those of the immunized population. When nucleic acid real-time PCR was negative, we would use the kinetics of IgG and IgA levels to distinguish the breakthrough cases from the immunized population. IMPORTANCE This study fills a gap in the epidemiological evidence by investigating the value of serological indicators, particularly IgG and IgA levels, in the auxiliary diagnosis of COVID-19 infections when nucleic acid results are undetectable. The findings reveal that among Omicron breakthrough cases, both IgG and IgA antibody levels exhibit significant changes. Serum IgG levels increase during the acute phase and rise further in the recovery phase. Serum IgA can be detected as early as the first week post-symptom onset (PSO), showing a consistent linear increase within 5 weeks PSO. Furthermore, receiver operating characteristic (ROC) curve analysis demonstrates the potential of IgG and IgA cutoff values as diagnostic markers. The study's conclusion underscores the importance of monitoring IgG and IgA kinetics in distinguishing Omicron breakthrough cases from vaccinated individuals. These findings contribute to the development of more accurate diagnostic approaches and help inform public health strategies during the ongoing COVID-19 pandemic.

Inhibition of USP10 induces myeloma cell apoptosis by promoting cyclin D3 degradation.

The cell cycle regulator cyclin D3 (CCND3) is highly expressed in multiple myeloma (MM) and it promotes MM cell proliferation. After a certain phase of cell cycle, CCND3 is rapidly degraded, which is essential for the strict control of MM cell cycle progress and proliferation. In the present study, we investigated the molecular mechanisms regulating CCND3 degradation in MM cells. By utilizing affinity purification-coupled tandem mass spectrometry, we identified the deubiquitinase USP10 interacting with CCND3 in human MM OPM2 and KMS11 cell lines. Furthermore, USP10 specifically prevented CCND3 from K48-linked polyubiquitination and proteasomal degradation, therefore enhancing its activity. We demonstrated that the N-terminal domain (aa. 1-205) of USP10 was dispensable for binding to and deubiquitinating CCND3. Although Thr283 was important for CCND3 activity, it was dispensable for CCND3 ubiquitination and stability modulated by USP10. By stabilizing CCND3, USP10 activated the CCND3/CDK4/6 signaling pathway, phosphorylated Rb, and upregulated CDK4, CDK6 and E2F-1 in OPM2 and KMS11 cells. Consistent with these findings, inhibition of USP10 by Spautin-1 resulted in accumulation of CCND3 with K48-linked polyubiquitination and degradation that synergized with Palbociclib, a CDK4/6 inhibitor, to induce MM cell apoptosis. In nude mice bearing myeloma xenografts with OPM2 and KMS11 cells, combined administration of Spautin-l and Palbociclib almost suppressed tumor growth within 30 days. This study thus identifies USP10 as the first deubiquitinase of CCND3 and also finds that targeting the USP10/CCND3/CDK4/6 axis may be a novel modality for the treatment of myeloma.

Overall analyses of the reactions catalyzed by acetohydroxyacid synthase/acetolactate synthase using a precolumn derivatization-HPLC method.

A precolumn derivatization-HPLC method using 2,4-dinitrophenylhydrazine and 4-nitro-o-phenylenediamine as respective labeling reagents for comprehensive analyses of the reactions catalyzed by acetohydroxyacid synthase (AHAS)/acetolactate synthase (ALS) is developed and evaluated in this research. Comparison with the classic Bauerle' UV assay which can analyze the enzymes only through measurement of acetoin production, the HPLC method shows advantages because it can analyze the enzymes not only via determination of consumption of the substrate pyruvate, but also via measurement of formation of the products including acetoin, 2,3-butanedione, and acetaldehyde in the enzymatic reactions. Thus the results deduced from the HPLC method can reflect the trait of each enzyme in a more precise manner. As far as we know, this is the first time that the reactions mediated by AHAS/ALS using pyruvate as a single substrate are globally analyzed and the features of the enzymes are properly discussed.

Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo / 中国中药杂志

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

[Research Progress in Physiological Evaluation and Treatment of Visually Induced Motion Sickness in Virtual Reality].

Visually induced motion sickness(VIMS)is the major barrier to be broken in the development of virtual reality(VR)technology,which seriously affects the progress in the VR industry.Therefore,the detection and evaluation of VIMS has become a hot research topic nowadays.We review the progress in physiological assessment of VIMS in VR based on several physiological indicators,including electroencephalogram(EEG),postural sway,eye movements,heart rate variability,and skin electrical signals,and summarize the available therapies,aiming to provide an outlook on the future research directions of VIMS.

Research Progress in Physiological Evaluation and Treatment of Visually Induced Motion Sickness in Virtual Reality / 中国医学科学院学报

Visually induced motion sickness(VIMS)is the major barrier to be broken in the development of virtual reality(VR)technology,which seriously affects the progress in the VR industry.Therefore,the detection and evaluation of VIMS has become a hot research topic nowadays.We review the progress in physiological assessment of VIMS in VR based on several physiological indicators,including electroencephalogram(EEG),postural sway,eye movements,heart rate variability,and skin electrical signals,and summarize the available therapies,aiming to provide an outlook on the future research directions of VIMS.

TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis / 中南大学学报(医学版)

OBJECTIVES@#Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.@*METHODS@#Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.@*RESULTS@#The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment.@*CONCLUSIONS@#WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

Potential Mechanisms of Biejiajian Pill in the Treatment of Diabetic Atherosclerosis Based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Background: Biejiajian pill (BJJP), a classical traditional Chinese formula, has been reported that it has an effective treatment for diabetic atherosclerosis in recent years, but its underlying mechanisms remain elusive. The study aimed to explore the potential mechanisms of BJJP on diabetic atherosclerosis by integrating network pharmacology, molecular docking, and molecular dynamics simulation. Methods: The active components of BJJP were collected by TCMSP and TCMID, and then the potential targets were obtained from the SwissTargetPrediction database. The targets related to diabetic atherosclerosis were identified from the GeneCards and OMIM databases. The intersection of the potential targets regulated by active components of BJJP and the targets of diabetic atherosclerosis were common targets, which were visualized by the Venn diagram. The common targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. The network of "Medicine-Compound-Target" was constructed with Cytoscape 3.7.1 software. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using the DAVID database and visualized through bioinformatics. The intersecting targets were input into Cytoscape 3.7.1 software, and the Network Analyzer tool was employed to screen out the key targets. Then molecular docking was used to verify the binding affinity between the active compounds and the key targets, and molecular dynamics simulation was used to investigate the stability of the binding models. Results: A total of 81 active components, 186 targets of BJJP, and 4041 targets of diabetic atherosclerosis were obtained. Furthermore, 121 overlapping targets were identified. GO functional enrichment analysis revealed that these targets were correlated with the oxidation-reduction process, negative regulation of apoptotic process, inflammatory response, and other biological processes. The results of the KEGG pathway enrichment analysis showed that the common targets mainly participated in proteoglycans in cancer, PPAR signaling pathway, adherens junction, insulin resistance, HIF-1 signaling pathway, PI3K-Akt signaling pathway, etc. The results of molecular docking confirmed that the core active components in BJJP could bind well to the key targets. Results from molecular dynamics simulation showed that the binding energies of AKT1-Luteolin, MMP9-quercetin, and MMP9-luteolin complexes were -28.93 kJ·mol-1, -37.12 kJ·mol-1, and -62.91 kJ·mol-1, respectively. Conclusion: The study revealed that BJJP is characterized as multicomponent, multitarget, and multipathway to treat diabetic atherosclerosis, which is helpful to provide ideas and a basis for pharmacological research and clinical application in the future.

Dose-response relationship between dietary inflammatory index and diabetic kidney disease in US adults.

OBJECTIVE: The impact of the dietary potential inflammatory effect on diabetic kidney disease (DKD) has not been adequately investigated. The present study aimed to explore the association between dietary inflammatory index (DII) and DKD in US adults. DESIGN: This is a cross-sectional study. SETTING: Data from the National Health and Nutrition Examination Survey (2007-2016) were used. DII was calculated from 24-h dietary recall interviews. DKD was defined as diabetes with albuminuria, impaired glomerular filtration rate or both. Logistic regression and restricted cubic spline models were adopted to evaluate the associations. PARTICIPANTS: Data from the National Health and Nutrition Examination Survey (2007-2016) were used, which can provide the information of participants. RESULTS: Four thousand two-hundred and sixty-four participants were included in this study. The adjusted OR of DKD was 1·04 (95 % CI 0·81, 1·36) for quartile 2, 1·24 (95 % CI 0·97, 1·59) for quartile 3 and 1·64 (95 % CI 1·24, 2·17) for quartile 4, respectively, compared with the quartile 1 of DII. A linear dose-response pattern was observed between DII and DKD (Pnonlinearity = 0·73). In the stratified analyses, the OR for quartile 4 of DII were significant among adults with higher educational level (OR 1·83, 95 % CI 1·26, 2·66) and overweight or obese participants (OR 1·67, 95 % CI 1·23, 2·28), but not among the corresponding another subgroup. The interaction effects between DII and stratified factors on DKD were not statistically significant (all P values for interactions were >0·05). CONCLUSIONS: Our findings suggest that a pro-inflammatory diet, shown by a higher DII score, is associated with increased odd of DKD.

Clone and Function Verification of the OPR gene in Brassica napus Related to Linoleic Acid Synthesis.

BACKGROUND: Fatty acid composition and content affect rapeseed oil quality. Fatty acid synthesis-related genes in rapeseed have been studied globally by researchers. Nevertheless, rapeseed oil is mainly composed of seven different fatty acids (FA), and each fatty acid was regulated by different genes. Furthermore, different FA affect each other, which needs continuous and in-depth research to obtain more clear results in Brassica napus. RESULTS: In this paper, broad-scale miRNA expression profiles were constructed and 21 differentially expressed miRNAs were detected. GO enrichment analysis showed that most up-regulated proteins were involved in transcription factor activity and catalytic activity. KEGG pathway enrichment analysis indicated that 20 pathways involving 36 target genes were enriched, of which the bna00592 pathway may be involved in fatty acid metabolism. The results were verified using a quantitative real-time PCR (RT-qPCR) analysis, we found that the target gene of bna-miR156b > c > g was the OPR (12-oxo-phytodienoic acid reductase). Four copies of OPR gene were found, and the over-expression vectors (pCAMBIA1300-35 s-OPR and pCAMBIA1300-RNAi-OPR) were constructed to verify their functions. In T1 and T2 generation, the content of linoleic acid (LA) increased significantly in OE but deceased in OPRi. CONCLUSIONS: This is the first study to provide four copies of the OPR gene that regulates LA metabolism, can be used for the molecular mechanism of LA and optimizing fatty acid profiles in oilseed for breeding programs.

Effect of artemisinin on improving islet function in rats fed with maternal high-fat diet.

BACKGROUND: Maternal high-fat diet (HFD) is a detrimental factor in developing glucose intolerance, obesity, and islet dysfunction. However, the effect of artemisinin on maternal HFD and whether it is related to the alterations of islet function is seldom studied since artemisinin treatments not only attenuate insulin resistance (IR) and restore islet ß cell function in Diabetes mellitus type 2. METHODS: Female rats were randomly fed a HFD (45% kcal from fat), HFD + artemisinin, or a regular chow diet (RCD) before pregnancy and during gestation. Glucose metabolism and the ß cell phenotypes were assessed. RESULTS: Maternal HFD increased islet load in female rats, proliferation of pancreatic ß cells, increased insulinogen, and decreased insulin secretion response to high glucose stimulation with delayed insulin release, increased fasting glucose, and glucose area under the curve compared with the general diet group. HFD inhibited expression of Foxo1 and PAX6 in female rats. Under the effect of both HFD and pregnancy, islet load was further increased, insulinogen was further increased, and fasting insulin level and fasting glucose were higher than RCD fed general-pregnancy group. ALDH1a3 transdifferentiation and PAX6, Foxo1, and PDX1 expression were increased in islets of high-fat pregnant rats. When adding artemisinin in HFD treated pregnant rats, islet function was significantly improved. CONCLUSIONS: Intervention with artemisinin in maternal HFD resulted in reduced islet size, decreased number of ß-cells and improved islet microcirculation, insulin processing shear process, decreased insulinogen/insulin ratio, and restored islet function through increased expression of PC1/3.

Blocking stanniocalcin 2 reduces sunitinib resistance in clear cell renal cell carcinoma.

Stanniocalcin 2 (STC2) has been identified as a prognostic marker in renal cell carcinoma. However, the role of STC2 in renal cell carcinoma is still unclear. In this study, we investigated the relationship between high expression of STC2 and sunitinib resistance in cells and the underlying mechanism. Through GEPIA platform analysis based on TCGA database, it showed that the expression of STC2 in kidney renal clear cell carcinoma (KIRC) was significantly higher than that in the normal population. Real-time quantitative PCR and western blotting detected significantly higher expression levels of STC2 in clear cell renal cell carcinoma (ccRCC) cells than that in normal renal cells. Enzyme-linked immunosorbent assay (ELISA) determined whether there is a high secretion of STC2 in ccRCC cells. The sunitinib resistance could be significantly reduced by STC2 neutralizing antibody but aggravated by the addition of recombinant human STC2 in ccRCC cells. Sunitinib suppressed STC2 expression and secretion, destroyed lysosomal acidic pH, and accumulated in the cells. However, STC2 neutralizing antibody can reduce the accumulation of sunitinib in cells to improve the inhibitory efficiency of sunitinib on cell proliferation. This study suggested STC2 could serve as a potential novel target for the treatment of ccRCC, anti-STC2 antibody might be an option of immunotherapy in the future.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

[Predictive value of comprehensive preoperative evaluation for the outcome of TURP].

Objective: To evaluate preoperative comprehensive examinations of the IPSS-voiding to storage subscore ratio (IPSS-V/S), maximum urinary flow rate (Qmax), intravesical prostatic protrusion (IPP) and postvoid residual urine volume (PVR) in predicting the outcome of transurethral resection of the prostate (TURP) for BPH. METHODS: This retrospective study included 103 cases of BPH treated by TURP in Yixing People's Hospital from December 2018 to December 2019. The patients averaged 71.92 ± 7.73 years of age, with a mean prostate volume of (58.34 ± 15.59) ml, preoperative IPSS of 23.38 ± 3.36, voiding score of 14.38 ± 2.69, storage score of 9 (8－10), V/S ratio of 1.67 (1.43－1.88), Qmax of 7 (5－8) ml/s, IPP of 4 (0－5) mm, and PVR of (117.03 ± 20.51) ml. The TURP operations were completed by the same surgeon, with mean operation time of (83.65 ± 14.31) min and intraoperative blood loss of (55.32 ± 18.92) ml. The patients were followed up for 3 months after surgery for evaluation of the outcomes based on the IPSS and quality of life (QOL) scores. RESULTS: The postoperative IPSS was significantly improved in all the patients compared with the baseline (5.36 ± 1.95 vs 23.38 ± 3.36, P < 0.05). Based on the criteria of IPSS < 7 and general satisfaction with QOL, satisfactory results were achieved in 71 (68.93%) of the patients (aged 71.04 ± 7.23 years, prostate volume: ï¼»59.68 ± 15.79ï¼½ ml, IPSS: 23.87 ± 3.42, voiding score: 14.87 ± 2.34, storage score: 9 ï¼»8－10ï¼½, V/S ratio: 1.67 ï¼»1.47－1.86ï¼½, Qmax: 6 ï¼»4－7ï¼½ ml/s, IPP: 5 ï¼»0－6ï¼½ mm, PVR: 110.53 ± 17.69 ml, operation time ï¼»85.37 ± 12.28ï¼½ min, intraoperative blood loss: ï¼»58.08 ± 14.61ï¼½ ml), and unsatisfactory results in the other 32 (31.07%) (aged 76.91 ± 8.25 years, prostate volume: ï¼»55.38 ± 14.73ï¼½ ml, IPSS: 22.53 ± 3.25, voiding score: 13.53 ± 3.21, storage score: 9 ï¼»8－12ï¼½, V/S ratio: 1.36 ï¼»1.03－1.95ï¼½, Qmax: 8 ï¼»7－9ï¼½ ml/s, IPP: 0 ï¼»0－5ï¼½ mm, PVR: ï¼»129.61 ± 20.62ï¼½ ml, operation time: ï¼»78.85 ± 10.04ï¼½ min, intraoperative blood loss: 48.76 ± 12.19 ml). CONCLUSIONS: TURP yields better results in younger BPH patients, with baseline IPSS dominantly in urinary symptoms, greater IPP, lower PVR, and lower Qmax.

Sex Differences of Acute Stroke Treatment and in Hospital Outcomes After Intravenous Thrombolysis in Patients With Ischemic Stroke.

Background: Many studies have suggested that the clinical features of male patients with ischemic stroke are different from those of female patients, but related data on Chinese patients are scarce. Therefore, this study aimed to identify the differences in treatment delays, complications related to intravenous thrombolysis, and prognosis between male and female patients with ischemic stroke in China. Methods: The data of patients with ischemic stroke who received intravenous thrombolysis were retrospectively analyzed. The data were obtained from the China Hospital Stroke Registry from January 2017 to April 2019. The general clinical characteristics, onset-to-door time, door-to-needle time, complications related to thrombolysis, National Institute of Health Stroke Scale (NIHSS) scores, and in-hospital mortality were compared between male and female patients to identify any sex differences in these factors. A multi-factorial analysis was conducted to explore whether sex is associated with in-hospital mortality and complications of intracerebral hemorrhage after thrombolysis. Results: A total of 26,475 patients with ischemic stroke who received intravenous thrombolysis were involved in the study. The data were collected from 902 hospitals in 29 provinces, autonomous regions, and municipalities in China. The door-to-needle time was longer in female than in male patients (49 [35, 67] vs. 48 [35, 65], P = 0.008). Furthermore, the frequencies of intracerebral hemorrhage (4.1 vs. 3.2%, P < 0.001) and in-hospital mortality (2.55 vs. 1.83%, P < 0.001) were higher in female vs. male patients. However, sex was not associated with intracerebral hemorrhage and in-hospital mortality according to the adjusted multi-factorial analysis. In addition, improvement in NIHSS scores was greater in female patients than in male patients [-3 (-6, -1) vs. -3 (-5, -1), P = 0.036]. Conclusions: After adjusting for other predictors sex was not associated with intracerebral hemorrhage after thrombolysis or in-hospital mortality. Further study is warranted to evaluate the long-term outcomes in the different sexes.

Growth of centimeter-scale perovskite single-crystalline thin film via surface engineering.

Modern electronic and photonic devices rely on single-crystalline thin film semiconductors for high performance and reproducibility. The emerging halide perovskites have extraordinary electronic and photonic properties and can be synthesized via low cost solution-based methods. They have been used in a variety of devices with performance approaching or over the devices based on conventional materials. However, their solution based growth method is intrinsically challenge to grow large scale single-crystalline thin film due to the random nucleation and isotropous growth of the crystal. Here, we report the growth of centimeter-scale perovskite single-crystalline thin films by controlling the nucleation density and growth rate of the crystal under a spatially confined growth condition. The hydrophobic treatment on substrates inhibits nucleation and accelerates the growth of single-crystalline thin film, providing enough space for initial nucleus growing up quickly without touching each other. Single-crystalline perovskite thin-film with an aspect ratio of 1000 (1 cm in side length, 10 µm in thickness) has been successfully grown. The low trap density and the high mobility of the as-grown thin film show a high crystallinity. The photodetector based on the perovskite thin film has achieved a gain ~ 104, benefitting from the short transit time of the carries due to the high mobility and thin thickness of the active layer. Our work opens up a new route to grow large scale perovskite single-crystalline thin films, providing a platform to develop high- performance devices.

Spin-Momentum-Locked Edge Mode for Topological Vortex Lasing.

Spin-momentum locking is a direct consequence of bulk topological order and provides a basic concept to control a carrier's spin and charge flow for new exotic phenomena in condensed matter physics. However, up to date the research on spin-momentum locking solely focuses on its in-plane transport properties. Here, we report an emerging out-of-plane radiation feature of spin-momentum locking in a non-Hermitian topological photonic system and demonstrate a high performance topological vortex laser based on it. We find that the gain saturation effect lifts the degeneracy of the paired counterpropagating spin-momentum-locked edge modes enabling lasing from a single topological edge mode. The near-field spin and orbital angular momentum of the topological edge mode lasing has a one-to-one far-field radiation correspondence. The methodology of probing the near-field topology feature by far-field lasing emission can be used to study other exotic phenomena. The device can lead to applications in superresolution imaging, optical tweezers, free-space optical sensing, and communication.

A high-performance topological bulk laser based on band-inversion-induced reflection.

Topological insulators are materials that behave as insulators in the bulk and as conductors at the edge or surface due to the particular configuration of their bulk band dispersion. However, up to date possible practical applications of this band topology on materials' bulk properties have remained abstract. Here, we propose and experimentally demonstrate a topological bulk laser. We pattern semiconductor nanodisk arrays to form a photonic crystal cavity showing topological band inversion between its interior and cladding area. In-plane light waves are reflected at topological edges forming an effective cavity feedback for lasing. This band-inversion-induced reflection mechanism induces single-mode lasing with directional vertical emission. Our topological bulk laser works at room temperature and reaches the practical requirements in terms of cavity size, threshold, linewidth, side-mode suppression ratio and directionality for most practical applications according to Institute of Electrical and Electronics Engineers and other industry standards. We believe this bulk topological effect will have applications in near-field spectroscopy, solid-state lighting, free-space optical sensing and communication.