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BACKGROUND Direct oral anticoagulants (DOACs) combined with antiplatelet therapy for acute coronary syndrome (ACS) may reduce ischemic events, but there is no consensus on bleeding risk. Moreover, the effect of DOACs on stable coronary artery disease (CAD) needs to be elucidated. We conducted a meta-analysis to summarize the efficacy and safety of DOACs combined with antiplatelet therapy in the treatment of stable CAD and ACS. METHODS We searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials, then performed a systematic review of all 17 randomized controlled trials. RESULTS For patients with stable CAD, DOACs combined with antiplatelet therapy significantly reduced the rate of major adverse cardiovascular events (MACE) (risk ratio; 95% confidence interval: 0.88; 0.81-0.95) and ischemic stroke (0.62; 0.50-0.77), with a relatively low risk of major bleeding (1.72; 1.42-2.07). For patients with ACS, the combination of DOACs reduced the risk of MACE (0.91; 0.85-0.97), myocardial infarction (MI) (0.90; 0.83-0.98), and ischemic stroke (0.75; 0.58-0.97), accompanied by increased non-fatal bleeding events and intracranial hemorrhage (3.42; 1.76-6.65). Results were similar when restricting the analysis to phase III studies except for the rate of stroke in patients with ACS. CONCLUSIONS Combination therapy reduced the incidence of MI in ACS patients, but the risk of bleeding from intracranial hemorrhaging outweighs the benefit of MACE driven by MI. That is due to combination therapy having no positive impact on mortality; thus, the benefit-risk balance may be more favorable in patients with stable CAD.

To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8，2020，the information of 151 confirmed cases in Yueqing，Zhejiang province were obtained，including patients' infection process，population mobility between Yueqing and Wuhan，etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models，integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic，the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170，the actual monitoring number of cases in Yueqing as of April 27，2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.

Aims Computer-assisted auscultation has become available to assist clinicians with physical examinations to detect congenital heart disease (CHD). However, its accuracy and effectiveness remain to be evaluated. This study seeks to evaluate the accuracy of auscultations of abnormal heart sounds of an artificial intelligence-assisted auscultation (AI-AA) platform we create. Methods and results Initially, 1397 patients with CHD were enrolled in the study. The samples of their heart sounds were recorded and uploaded to the platform using a digital stethoscope. By the platform, both remote auscultation by a team of experienced cardiologists from Shanghai Children’s Medical Center and automatic auscultation of the heart sound samples were conducted. Samples of 35 patients were deemed unsuitable for the analysis; therefore, the remaining samples from 1362 patients (mean age—2.4 ± 3.1 years and 46% female) were analysed. Sensitivity, specificity, and accuracy were calculated for remote auscultation compared to experts’ face-to-face auscultation and for artificial intelligence automatic auscultation compared to experts’ face-to-face auscultation. Kappa coefficients were measured. Compared to face-to-face auscultation, remote auscultation detected abnormal heart sound with 98% sensitivity, 91% specificity, 97% accuracy, and kappa coefficient 0.87. AI-AA demonstrated 97% sensitivity, 89% specificity, 96% accuracy, and kappa coefficient 0.84. Conclusions The remote auscultations and automatic auscultations, using the AI-AA platform, reported high auscultation accuracy in detecting abnormal heart sound and showed excellent concordance to experts’ face-to-face auscultation. Hence, the platform may provide a feasible way to screen and detect CHD.

Metabolic homoeostasis in adipose tissue plays a major role in obesity-related insulin resistance (IR). Regulatory T (Treg) cells have been recorded to regulate metabolic homoeostasis in adipose tissue. However, their specific mechanism is not yet known. This review aims to present the role of Treg cells and other immune cells in obesity-associated IR, focusing on the balance of numbers and functions of Treg cells and other immune cells as well as the crucial role of their interactions in maintaining adipose tissue homoeostasis. Th1 cells, Th17 cells, CD8+ T cells, and pro-inflammatory macrophages mediate the occurrence of obesity and IR by antagonizing Treg cells, while anti-inflammatory dendritic cells, eosinophils and type 2 innate lymphoid cells (ILC2s) regulate the metabolic homoeostasis of adipose tissue by promoting the proliferation and differentiation of Treg cells. γ δ T cells and invariant natural killer T (iNKT) cells have complex effects on Treg cells, and their roles in obesity-associated IR are controversial. The balance of Treg cells and other immune cells can help maintain the metabolic homoeostasis of adipose tissue. Further research needs to explore more specific molecular mechanisms, thus providing more precise directions for the treatment of obesity with IR.

Despite remarkable clinical achievements, camptothecin (CPT) still suffers from poor solubility and severe toxicity. Therefore, it is necessary to redevelop CPT derivatives as supplementary antitumor agents with good water solubility and small side effects. In this work, 27 camptothecin derivatives were synthesized and screened for their cytotoxicity against A549 (lung) and HCT-116 (colon) cancer cell lines. Among them, compound B7, 7-ethyl-10-(2-oxo-2-(4-methylpiperidin-1-yl)ethoxy)camptothecin,was demonstrated in vitro to be a more potent antitumor agent than SN-38 by comparison of their inhibitory activities against cell proliferation and colony formation and interference effect on process of cell cycle and cell apoptosis. Additionally, a molecular docking model revealed that B7 can interact with the topoisomerase I-DNA complex, and that the solubility of B7 reached 5.73 μg/mL in water. Moreover, B7 significantly inhibited tumor growth in an A549 xenograft model at dosages of 0.4 and 2.0 mg/kg, and exhibited minimum lethal doses comparable to those of irinotecan. These results indicated that B7, with improved solubility, enhanced activity and acceptable acute toxicity, can be used as a lead compound for the development of novel anticancer agents.

Texture analysis is an emerging field that allows mathematical detection of changes in MRI signals that are not visible among image pixels. Alzheimer's disease, a progressive neurodegenerative disease, is the most common cause of dementia. Recently, multiple texture analysis studies in patients with Alzheimer's disease have been performed. This review summarizes the main contributors to Alzheimer's disease-associated cognitive decline, presents a brief overview of texture analysis, followed by review of various MR imaging texture analysis applications in Alzheimer's disease. We also discuss the current challenges for widespread clinical utilization. MR texture analysis could potentially be applied to develop neuroimaging biomarkers for use in Alzheimer's disease clinical trials and diagnosis.

Purpose: To seek optimal keV settings for imaging carpal tunnel in adults by dual-energy computed tomography (DECT) monoenergetic technique; to describe anatomic characteristics of carpal tunnel and to observe correlation between carpal bony and soft tissue structures. Methods: DECT images of 20 wrists (11 left and 9 right wrists; 14 men, mean age 26.93 ± 1.38 years, range 23 to 28, and 6 women, mean age 24.17 ± 0.98 years, range 23 to 26) were evaluated. Monoenergetic images were reconstructed at 42, 62, 82, 102, 122, and 142 keV. Image quality was assessed along a 5-point Likert scale, and the highest-quality images were chosen for quantitative analysis. Two musculoskeletal radiologists performed both analyses independently. Results: The optimal energy spectrum with the best contrast-to-noise ratio (CNR) for monoenergetic images were at 62 keV (19 wrists, 95%) and 61 keV (1 wrist, 5%). There was substantial interobserver agreement between the readers in the 5-point Likert scale analysis of image quality (? = 0.793). Bland-Altman plots also indicated good agreement between observers in quantitative analysis. Intra-category 1 and 2 correlation was mostly discovered at hamate hook level and middle level of pisiform (P < 0.05), while bony and soft tissue structures partly reached correlation (P < 0.05). Conclusion: The optimal energy spectrum for monoenergetic DECT imaging of carpal tunnel structures was 62 keV. DECT monoenergetic imaging could predict changes in soft tissue structures and demonstrate carpal tunnel anatomic structures. Keywords: DECT, monoenergetic, keV, carpal tunnel, Continuous...

Background Out-of-hospital cardiac arrest (OHCA) is a leading cause of sudden cardiac death worldwide. Researchers have found significant pathophysiological differences between females and males and clinically significant sex differences related to medical services. However, conflicting results exist and there is no uniform agreement regarding sex differences in survival and prognosis after OHCA. Therefore, we investigated the relationship between the prognosis of OHCA and sex factors. Methods We comprehensively searched the PubMed, Embase, and Cochrane databases and obtained a total of 1042 articles, from which 33 studies were selected for inclusion. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Results The meta-analysis included 1,268,664 patients. Compared with males, females were older (69.7 years vs. 65.4 years, p p Conclusions Our results indicate that the overall discharge survival rate of females is lower than that of males, and females face a poor prognosis of the nervous system. This is likely related to the pathophysiological characteristics of females, more conservative treatment measures compared with males, and different post-resuscitation care. However, these findings should be interpreted with caution due to the presence of several confounding factors.

Magnetic resonance imaging (MRI) as one of the most important imaging methods is widely used in clinical diagnosis and basic life science research, with advantages including noninvasiveness, high/multiple soft tissue contrast, parametric imaging and the richness of information. During recent years, there have been many advances in the instrument technology and biomedical application of MRI. Advanced techniques, such as ultra-high field, ultra-fast and ultra-sensitive imaging, are now available for routine clinical usage and research settings. Also, the MRI technology is rapidly developing via incorporating with multiple cutting-edge disciplines including big data technology, artificial intelligence and theranostics. Currently, MRI is playing an indispensable role in tumor molecular imaging, functional brain imaging and brain connectome studies. This paper introduces the history and basic principles of MRI, and summarizes the important problems in the research of MRI instrument, methodology and application, providing a perspective on the directions of future MRI research in China.

To suppress the ongoing COVID-19 pandemic, the Chinese government has implemented nonpharmaceutical interventions (NPIs). Because COVID-19 and influenza have similar means of transmission, NPIs targeting COVID-19 may also affect influenza transmission. In this study, the extent to which NPIs targeting COVID-19 have affected seasonal influenza transmission was explored. Indicators of seasonal influenza activity in the epidemiological year 2019–2020 were compared with those in 2017–2018 and 2018–2019. The incidence rate of seasonal influenza reduced by 64% in 2019–2020 (P < .001). These findings suggest that NPIs aimed at controlling COVID-19 significantly reduced seasonal influenza transmission in China.

There have been over 17 million COVID-19 infections worldwide up to July 31, 2020, but the exact transmission route remains a subject for debate. Virus load in different-sized respiratory droplets is the key to address the above question. Investigation on the droplet deposition characteristics during exhalation inside the respiratory tract will facilitate the understanding of their origin and importance in transmitting the respiratory infection. Based on a realistic respiratory model, this study utilized the computational fluid dynamic (CFD) simulation to investigate the deposition of droplets originating from infection sites like pharynx, larynx and trachea under three flow conditions, namely 30 L/min (representing the normal breathing condition), 60 L/min (speaking) and 180 L/min (coughing). The SST k - ω turbulence model integrated in ANSYS Fluent software was utilized to obtain the flow field inside the respiratory tract by solving the continuity and momentum equations, and the Lagrangian approach was used to calculate droplet motion and deposition with the discrete random walk model to account for the turbulence fluctuation effect. Evaporation of droplets was not considered inside the saturated respiratory tract. Droplet diameter, flow rate of the exhaling air, and complexity of the respiratory tract geometry are the most important factors in determining the deposition pattern of respiratory droplets. It is revealed that the largest droplet that originates from the joint of pharynx and larynx and is able to escape out of the respiratory tract is about 20 µm (30 L/min) or 10 µm (60–180 L/min) in diameter; the so-called cut-off sizes for vocal cord and trachea originated droplets are 7 µm (30 L/min), 5 µm (60 L/min) or 3 µm (180 L/min). Larynx and joint of larynx and pharynx are the most important deposition sites due to their complexity in geometry and the existence of the laryngeal jet, whose velocity is up to 102 m/s during coughing and 32 m/s during speaking; the nasal cavity is also effective in trapping relatively small droplets as the airflow has a sudden change in direction before entering the oral cavity. Under the investigated speaking scenario (60 L/min), the escape rate of 1 µm droplets is around 50%, and the maximum escape rates of 5 and 10 µm droplets are respectively 13.1% and 1.3% (originating from the joint of pharynx and larynx). Although large droplets up to several hundred micrometers can be produced inside the oral cavity due to the atomization mechanism, they seldom carry pathogen. Thus, for COVID-19 patents in the early stage of infection who show upper respiratory symptoms, the cut-off size of virus-laden droplets released into the environment is about 20 µm; with the shifting of infection to the lower respiratory tract in the later stage, the cut-off size decreases to 7 µm. Respiratory droplets evaporate immediately after escaping into the indoor environments and shrink to about one third of their initial size, so airborne route is speculated to be important in the transmission of COVID-19. Further investigations considering realistic flow conditions together with droplet sampling experiments on human volunteers are necessary to confirm these cut-off sizes.

Cardiac hypertrophy is a significant risk factor for cardiovascular disease, including heart failure, arrhythmia, and sudden death. Cardiac hypertrophy involves both embryonic gene expression and transcriptional reprogramming, which are tightly regulated by epigenetic mechanisms. An increasing number of studies have demonstrated that epigenetics plays an influential role in the occurrence and development of cardiac hypertrophy. Here, we summarize the latest research progress on epigenetics in cardiac hypertrophy involving DNA methylation, histone modification, and non-coding RNA, to help understand the mechanism of epigenetics in cardiac hypertrophy. The expression of both embryonic and functional genes can be precisely regulated by epigenetic mechanisms during cardiac hypertrophy, providing a substantial number of therapeutic targets. Thus, epigenetic treatment is expected to become a novel therapeutic strategy for cardiac hypertrophy. According to the research performed to date, epigenetic mechanisms associated with cardiac hypertrophy remain far from completely understood. Therefore, epigenetic mechanisms require further exploration to improve the prevention, diagnosis, and treatment of cardiac hypertrophy.

Recent studies have demonstrated sex-specific differences in etiology, course and brain dysfunction that are associated with cigarette smoking. However, little is known about sex-specific differences in subcortical structure and function. In this study, structural and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 cigarette smokers (25 females) and 67 nonsmokers (28 females). The structural MRI was applied to identify deficits in sex-specific subcortical volume. Using resting-state fMRI, sex-related alterations in resting-state functional connectivity (rsFC) were investigated in subcortical nuclei with volume deficits as seed regions. Compared to nonsmokers, male but not female smokers demonstrated a significantly smaller volume in the left caudate, while female but not male smokers showed a smaller volume in the right amygdala. Resting-state FC analysis revealed that male but not female smokers had increased rsFC between the left caudate and the left prefrontal cortex but decreased rsFC within the bilateral caudate and between the right amygdala and right orbitofrontal cortex (OFC). Furthermore, the right amygdala volume was negatively correlated with the impulsivity score in female but not male smokers. The rsFC of the right amygdala-OFC circuit was negatively associated with the craving score in male but not female smokers. These findings indicate that cigarette smoking may have differential effects on the caudate and amygdala volumes as well as rsFC between men and women, contributing to our knowledge of sex-specific effects of nicotine addiction. Such sex-specific differences in subcortical structure and function may provide a methodological framework for the development of sex-specific relapse prevention therapies.

Background An efficient surface cleaning strategy would first target cleaning to surfaces that make large contributions to the risk of infections. Methods In this study, we used data from the literature about methicillin-resistant Staphylococcus aureus (MRSA) and developed an ordinary differential equations based mathematical model to quantify the impact of contact heterogeneity on MRSA transmission in a hypothetical 6-bed intensive care unit (ICU). The susceptible patients are divided into two types, these who are cared by the same nurse as the MRSA infected patient (Type 1) and these who are not (Type 2). Results The results showed that the mean MRSA concentration on three kinds of susceptible patient nearby surfaces was significantly linearly associated with the hand-touch frequency (p Conclusions This study provided a framework to study the pathogen concentration dynamics on environmental surfaces and quantitatively showed the importance of cleaning patient nearby HTSs on controlling the nosocomial infection transmission via contact route.

With the development of visual human-computer interaction, non-invasive eye-tracking technology has been applied in medical diagnosis, psychological research, augmented reality and other fields. As a key step of video-based eye tracking technology, pupil detection requires strong robustness, real-time performance and high precision. Although many pupil detection algorithms have been developed, pupil detection is still a challenge when there are so many interference factors such as bright light, reflection, eyelid or eyelash occlusion, or low image resolution. Aim to address the above difficult problems of pupil detection, this paper uses cascaded Haar features and Otsu dynamic threshold segmentation to improve the performance of the existing pupil detection algorithm. The performance of the improved algorithm is verified with the public human eye image dataset from Swirski with high off-axis and severe eyelash occlusion. The results show that the accuracy of the improved algorithm is 86.3% and 89.7% in the error range of 5 pixels and 10 pixels, respectively. The detection algorithm in this paper can provide accurate pupil center coordinates for eye tracking, which lays a foundation for the high-precision calibration and measurement of the following eye tracker.

Long-term therapy with levodopa (L-DOPA) in patients with Parkinson’s disease (PD) often triggers motor complications termed as L-DOPA-induced dyskinesia (LID). However, few studies have explored the pathogenesis of LID from the perspective of neuroanatomy. This study aimed to investigate macroscopic structural changes in a rat model of LID and the underlying histological mechanisms. First, we established the hemiparkinsonism rat model through stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, followed by administration of saline (PD) or L-DOPA to induce LID. Magnetic resonance imaging (MRI) and behavioral evaluations were performed at different time points. Histological analysis was conducted to assess the correlations between MRI signal changes and cellular contributors. Voxel-based morphometry (VBM) analysis revealed progressive bilateral volume reduction in the cortical and subcortical areas in PD rats compared with the sham rats. These changes were partially reversed by chronic L-DOPA administration; moreover, there was a significant volume increase mainly in the dorsolateral striatum, substantia nigra, and piriform cortex of the lesioned side compared with that of PD rats. At the striatal cellular level, glial fibrillary acidic protein-positive (GFAP+) astrocytes were significantly increased in the lesioned dorsolateral striatum of PD rats compared with the intact side and the sham group. Prolonged L-DOPA treatment further increased GFAP levels. Neither 6-OHDA damage nor L-DOPA treatment influenced the striatal expression of vascular endothelial growth factor (VEGF). Additionally, there was a considerable increase in synapse-associated proteins (SYP, PSD95, and SAP97) in the lesioned striatum of LID rats relative to the PD rats. Golgi-Cox staining analysis of the dendritic spine morphology revealed an increased density of dendritic spines after chronic L-DOPA treatment. Taken together, our findings suggest that striatal volume changes in LID rats involve astrocyte activation, enrichment of synaptic ultrastructure and signaling proteins in the ipsilateral striatum. Meanwhile, the data highlight the enormous potential of structural MRI, especially VBM analysis, in determining the morphological phenotype of rodent models of LID.

Background School closure is a common mitigation strategy during severe influenza epidemics and pandemics. However, the effectiveness of this strategy remains controversial. In this study, we aimed to explore the effectiveness of school closure on seasonal influenza epidemics in provincial-level administrative divisions (PLADs) with varying urbanization rates in China. Methods This study analyzed influenza surveillance data between 2010 and 2019 provided by the Chinese National Influenza Center. Taking into consideration the climate, this study included a region with 3 adjacent PLADs in Northern China and another region with 4 adjacent PLADs in Southern China. The effect of school closure on influenza transmission was evaluated by the reduction of the effective reproductive number of seasonal influenza during school winter breaks compared with that before school winter breaks. An age-structured Susceptible-Infected-Recovered-Susceptible (SIRS) model was built to model influenza transmission in different levels of urbanization. Parameters were determined using the surveillance data via robust Bayesian method. Results Between 2010 and 2019, in the less urbanized provinces: Hebei, Zhejiang, Jiangsu and Anhui, during school winter breaks, the effective reproductive number of seasonal influenza epidemics reduced 14.6% [95% confidential interval (CI): 6.2–22.9%], 9.6% (95% CI: 2.5–16.6%), 7.3% (95% CI: 0.1–14.4%) and 8.2% (95% CI: 1.1–15.3%) respectively. However, in the highly urbanized cities: Beijing, Tianjin and Shanghai, it reduced only 5.2% (95% CI: -0.7–11.2%), 4.1% (95% CI: -0.9–9.1%) and 3.9% (95% CI: -1.6–9.4%) respectively. In China, urbanization is associated with decreased proportion of children and increased social contact. According to the SIRS model, both factors could reduce the impact of school closure on seasonal influenza epidemics, and the proportion of children in the population is thought to be the dominant influencing factor. Conclusions Effectiveness of school closure on the epidemics varies with the age structure in the population and social contact patterns. School closure should be recommended in the low urbanized regions in China in the influenza seasons. Graphical abstract

Patients with type 2 diabetes mellitus (T2DM) often have cognitive impairment and structural brain abnormalities. The magnetic resonance imaging (MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function, and can therefore also be used to reflect whole-brain structural changes related to T2DM. A total of 136 participants (64 men and 72 women, aged 55–86 years) were recruited for our study between January 2014 and December 2016. All participants underwent MRI and Mini-Mental State Examination assessment (including 42 healthy control, 38 T2DM without cognitive impairment, 26 with cognitive impairment but without T2DM, and 30 T2DM with cognitive impairment participants). The total and sub-category brain atrophy and lesion index scores in patients with T2DM with cognitive impairment were higher than those in healthy controls. Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2DM patients with cognitive impairment and patients with T2DM and cognitive impairment. After adjusting for age, the brain atrophy and lesion index retained its capacity to identify patients with T2DM with cognitive impairment. These findings suggest that the brain atrophy and lesion index, based on T1-weighted and T2-weighted imaging, is of clinical value for identifying patients with T2DM and cognitive impairment. Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2DM that is complicated by cognitive impairment. This study was approved by the Medical Ethics Committee of University of South China (approval No. USC20131109003) on November 9, 2013, and was retrospectively registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900024150) on June 27, 2019.

OBJECTIVE: :To evaluate the impact of socioeconomic status，population mobility，prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. METHODS: : The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19，2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects，that is, socioeconomic status，population mobility，and control measures for the pandemic. RESULTS: : According to the analysis on the 51 cities，4 development patterns of COVID-19 were obtained，including a high-incidence pattern (in Xinyu)，a late high-incidence pattern (in Ganzi)，a moderate incidence pattern (in Wenzhou and other 12 cities)，and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. CONCLUSION: : There were relatively large difference on the COVID-19 development among different cities in China，possibly affected by socioeconomic status，population mobility and prevention and control measures that were taken. Therefore，a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.

Iron-doped ZnTe (Fe2+:ZnTe) crystal can be used as promising gain media for mid-infrared laser. However, there are few studies in the optical properties of Fe2+:ZnTe crystal from mid-infrared to ultraviolet. In this work, large size Fe2+:ZnTe bulk crystal (the concentration of Fe ions is about 1019 cm−3) with a dimension of Φ30 mm × 50 mm was grown by the temperature gradient solution growth (TGSG) method. The luminescence and optical properties of Fe2+:ZnTe from terahertz wave to ultraviolet wave have been studied. The evaluated refractive index of Fe2+:ZnTe crystal is approximately 2.5–3.0 at the frequency range of 0.5–2.0 THz range. And its band gap is estimated to be about 2.24 eV. It is noted that strong absorptions at the wavelength of 2.8–4.7 μm and 705 nm were observed. Based on the experimental results, the energetic positions of Fe2+ center such as 3T1, 5T2, 5E in ZnTe crystal were proposed.

This study examined whether aggression among students in China rose or fell during 2003–2016. We applied a cross-temporal meta-analysis of 90 studies using Aggression Questionnaire (Buss & Perry, 1992) responses by 87,319 students (primary school students through senior high students). The results showed less aggression in later years. The decline in aggression was greater among junior high school students than among other students. Otherwise, the decline in aggression did not differ across gender or across regions (Eastern China, Central China, Western China).

Fluoxetine (Flx), a selective serotonin reuptake inhibitor, is extensively used to treat mood and anxiety disorders. Previous animal studies have shown that early-life exposure to Flx results in long-lasting behavioral alterations and neuroplasticity in the hippocampus and cortex, which may persist into adulthood. It remains unclear whether repeated Flx treatment in normal adult animals can induce lasting neuroplasticity and behavioral alterations persisting long beyond the treatment period. In this study, young adult rats (about 9 weeks old) were treated with Flx (10 mg/kg body weight, twice daily) for 15 consecutive days, and the effects of Flx on medial prefrontal cortex (mPFC) neuroplasticity and mPFC-related behaviors were assessed 20 days after the last injection. It was observed that the mPFC of Flx-treated rats had significant increases in the number of 5-bromodeoxyuridine-positive (BrdU+) cells, dendritic complexity/spine density in layer II/III pyramidal neurons, and brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) expression levels, as well as a significant decrease in the number of parvalbumin-positive (PV+) interneurons. The Flx-treated rats exhibited higher motivation to explore new environments, evidenced by a significantly increased number of entries into the novel arm in the Y-maze test. However, they did not show any significant changes in the anhedonia and anxiety levels measured by sucrose preference and elevated plus maze tests respectively. In conclusion, repeated Flx treatment, with the paradigm used, induces long-lasting neuroplastic changes in the mPFC of normal adult rats; such changes and related behavioral manifestations may persist up to 20 days after the last dose.

This cross-temporal meta-analysis involved 86 studies (N = 71,397) on aggression among Chinese college students conducted from 2003 to 2017. We collected articles investigating college students' aggression using the Aggression Questionnaire. The results showed that college students' aggression generally decreased steadily over 15 years. Compared to 2003, aggression in 2017 decreased by 1.030 standard deviations. The decline in physical aggression, verbal aggression, and hostility among college students were more rapid than anger. College students from the Eastern region of China demonstrated this decline more than those from the Center and Western regions. Both male and female college students showed decreasing aggression, and the decline was larger in males compared to females.

Background: Skin cutaneous melanoma (SKCM) is considered one of the most aggressive and lethal cancers of the skin. G-protein coupled receptor 143 (GPR143), which has been reported to cause congenital nystagmus, belongs to the superfamily of G protein-coupled receptors. Methods and Results: We analyzed the expression of GPR143 and survival of SKCM patients in SKCM via Gene Expression Profiling Interactive Analysis (GEPIA). Then, logistic regression and multivariate cox analysis was used to analyze the influence of GPR143 expression on clinicopathological elements and survival. We explored the immune response of 22 TIICs in SKCM via CIBERSORT and used TIMER to assess the correlation of GPR143 expression and immune infiltration level. Finally, we used gene set enrichment analysis (GSEA) to assess the TCGA dataset. The outcomes suggest that GPR143 expression in tumor samples is remarkedly higher than in normal samples and high GPR143 expression is associated with poorer prognosis. The result of multivariate analysis indicated that increased GPR143 expression is an independent prognostic factor for prognosis. We found GPR143 expression level has prominent negative correlations with infiltrating levels of B cell, CD8+ T cells, etc. GSEA indicated that pigment metabolic process, pigment biosynthetic process and other pathways were identified as differentially enriched pathways in Gene Ontology (GO). Oxidative phosphorylation, Parkinson’s disease and other pathways were showed significantly differential enrichment in GPR143 high expression phenotype in Kyoto Encyclopedia of Genes and Genomes (KEGG).Conclusions: In conclusion, GPR143 may be a novel prognostic biomarker and associated with immune infiltrates in SKCM.

BACKGROUND Atrophic gastritis is a precancerous lesion of the stomach. It has been reported that pepsinogen (PG) can reflect the morphology and function of the gastric mucosa, and it is therefore used as a marker for the early diagnosis of atrophic gastritis. AIM To evaluate the diagnostic value of serum PG for degree of gastric mucosal atrophy in asymptomatic Chinese upon physical examination. METHODS Medical data were collected from subjects who underwent transnasal gastroscopy between October 2016 and October 2018. For each study subject, serum PG levels and presence of Helicobacter pylori (H. pylori) infection were investigated. Pathology was evaluated using the Operative Link for Gastritis Assessment (OLGA) classification and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems. All statistical analyses were carried out using SPSS statistical software. RESULTS A total of 2256 subjects were enrolled and 1922 cases were finally included in the study. Based on the OLGA grading system, the levels of PGI were slightly decreased, while those of PGII were slightly increased. The PGI/PGII ratio (PGR) was reduced with increasing atrophy. The association between PG and OLGA grading was higher compared with that between PG and the OLGIM grading system. Compared with the OLGA-0 group, a statistically significant difference was observed in the mean age of OLGA-I, III, and IV groups (P < 0.05). In the H. pylori-positive subjects, the PGR levels were notably lower in the OLGA-I, II, and III groups compared with the OLGA-0 group (P < 0.05). H. pylori-positive subjects exhibited significantly higher PGI and PGII serum levels and a significantly lower PGR compared with H. pylori-negative patients in different OLGA groups (P < 0.05). CONCLUSION Serum PG levels may represent a non-invasive screening marker for gastric mucosal atrophy in asymptomatic subjects.

Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%‐72%) in the in‐flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5‐121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%‐23%), 29% (95% CI: 27%‐31%), and 50% (95% CI: 48%‐53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%‐87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2‐77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.

Converging lines of evidence indicates that smoking and internet gaming disorder (IGD) affect spontaneous brain activity, respectively. However, little is known about whether these two factors work together on the human brain. In this study, we investigated the interaction between smoking and IGD on local spontaneous brain activity using amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI (rs-fMRI). Forty-six cigarette smokers, 38 IGD individuals, 34 participants with both IGD and cigarette smoking (IGD-Smoking), and 60 healthy individuals involved in the study. Voxel-wise analysis of covariance of ALFF revealed that there were significant interactions between IGD by smoking in the right medial pre-frontal cortex (MPFC)/ventral striatum, bilateral cerebellar, and visual-related regions as well as the left temporal gyrus. In the right MPFC/ventral striatum and left temporal gyrus, ALFF in smoking group was significantly higher than healthy group while there were no significant ALFF differences between IGD-Smoking group and IGD group. While in the bilateral cerebellar and visual-related regions, ALFF in the smoking group was significantly lower than healthy group while ALFF in IGD-Smoking group did not show significant difference with IGD group. In addition, in the smoking group, ALFF of the right MPFC/ventral striatum was associated positively with anxiety and depression scores while the ALFF value in the smoking group had a trend toward negative correlation with SDS scores in the bilateral cerebellar and visual-related regions. The ALFF value in the smoking group was associated positively with anxiety score in the left temporal gyrus. These findings indicate that smoking and IGD interacted with each other in the human brain. Our results, in terms of spontaneous brain activity, may imply the fact that IGD people are more tended to get smoking. Moreover, it is possible to predict that smokers may be more easily to get internet addiction than healthy people.

Highlights • Infection risk of household contacts is 10 times higher than other contacts. • Risk of household transmission in adults is about 3-times higher than that in children. • SARS-CoV-2 is much more transmissible than SARS-CoV and Middle East Respiratory Syndrome Coronavirus in households, which challenges the home isolation of COVID-19 patients.

Background Coronavirus disease 2019 (COVID-19) continues to threaten human life worldwide. We explored how human behaviors have been influenced by the COVID-19 pandemic in Hong Kong, and how the transmission of other respiratory diseases (eg, influenza) has been influenced by human behavior. Methods We focused on the spread of COVID-19 and influenza infections based on the reported COVID-19 cases and influenza surveillance data and investigated the changes in human behavior due to COVID-19 based on mass transit railway data and the data from a telephone survey. We did the simulation based on a susceptible-exposed-infected-recovered (SEIR) model to assess the risk reduction of influenza transmission caused by the changes in human behavior. Results During the COVID-19 pandemic, the number of passengers fell by 52.0% compared with the same period in 2019. Residents spent 32.2% more time at home. Each person, on average, came into close contact with 17.6 and 7.1 people per day during the normal and pandemic periods, respectively. Students, workers, and older people reduced their daily number of close contacts by 83.0%, 48.1%, and 40.3%, respectively. The close contact rates in residences, workplaces, places of study, restaurants, shopping centers, markets, and public transport decreased by 8.3%, 30.8%, 66.0%, 38.5%, 48.6%, 41.0%, and 36.1%, respectively. Based on the simulation, these changes in human behavior reduced the effective reproduction number of influenza by 63.1%. Conclusions Human behaviors were significantly influenced by the COVID-19 pandemic in Hong Kong. Close contact control contributed more than 47% to the reduction in infection risk of COVID-19.

Background Nonpharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) are vital to reducing transmission risks. However, the relative efficiency of social distancing against COVID-19 remains controversial, since social distancing and isolation/quarantine were implemented almost at the same time in China. Methods In this study, surveillance data of COVID-19 and seasonal influenza in 2018–2020 were used to quantify the relative efficiency of NPIs against COVID-19 in China, since isolation/quarantine was not used for the influenza epidemics. Given that the relative age-dependent susceptibility to influenza and COVID-19 may vary, an age-structured susceptible/infected/recovered model was built to explore the efficiency of social distancing against COVID-19 under different population susceptibility scenarios. Results The mean effective reproductive number, Rt, of COVID-19 before NPIs was 2.12 (95% confidence interval [CI], 2.02–2.21). By 11 March 2020, the overall reduction in Rt of COVID-19 was 66.1% (95% CI, 60.1–71.2%). In the epidemiological year 2019–20, influenza transmissibility was reduced by 34.6% (95% CI, 31.3–38.2%) compared with transmissibility in epidemiological year 2018–19. Under the observed contact pattern changes in China, social distancing had similar efficiency against COVID-19 in 3 different scenarios. By assuming the same efficiency of social distancing against seasonal influenza and COVID-19 transmission, isolation/quarantine and social distancing could lead to 48.1% (95% CI, 35.4–58.1%) and 34.6% (95% CI, 31.3–38.2%) reductions of the transmissibility of COVID-19, respectively. Conclusions Though isolation/quarantine is more effective than social distancing, given that the typical basic reproductive number of COVID-19 is 2–3, isolation/quarantine alone could not contain the COVID-19 pandemic effectively in China.

By March 31, 2020, COVID-19 had spread to more than 200 countries. Over 750,000 confirmed cases were reported, leading to more than 36,000 deaths. In this study, we analysed the efficiency of various intervention strategies to prevent infection by the virus, SARS-CoV-2, using an agent-based SEIIR model, in the fully urbanised city of Shenzhen, Guangdong Province, China. Shortening the duration from symptom onset to hospital admission, quarantining recent arrivals from Hubei Province, and letting symptomatic individuals stay at home were found to be the three most important interventions to reduce the risk of infection in Shenzhen. The ideal time window for a mandatory quarantine of arrivals from Hubei Province was between 10 January and January 17, 2020, while the ideal time window for local intervention strategies was between 15 and 22 January. The risk of infection could have been reduced by 50% if all symptomatic individuals had immediately gone to hospital for isolation, and by 35% if a 14-day quarantine for arrivals from Hubei Province had been introduced one week earlier. Intervention strategies implemented in Shenzhen were effective, and the spread of infection would be controlled even if the initial basic reproduction number had doubled. Our results may be useful for other cities when choosing their intervention strategies to prevent outbreaks of COVID-19., Highlights • Shortening the delay to hospital is the most effective intervention in Shenzhen. • 10 to 17 January is the best time for a mandatory quarantine of Hubei's arrivals. • 15 to 22 January is the best time for local intervention strategy in Shenzhen. • Work/school closure and mask wearing are effective interventions in other countries. • Airport screening is not very effective.

Topoisomerases are interesting targets for drug discovery. In the present study, we attached saturated carbon atoms to the 10-position of camptothecin and synthesized 10 new camptothecin derivatives from 10-HCPT or SN-38. The activities of new compounds were evaluated both in vitro and in vivo. The most promising compound F10, 7-ethyl-10-(2-oxo-2-(piperidin-1-yl)ethoxy)camptothecin, inhibited cancer cells growth with the IC50 of 0.002, 0.003, 0.011 and 0.081 μM on Raji, HCT116, A549 and Lovo cells, respectively. Meanwhile, oral administration of F10 remarkably suppressed the HCT116-xenograft tumor growth in the nude-mice model at the dosage of 0.5, 2.0 and 8.0 mg/kg in vivo. Intraperitoneal administration of F10 can completely inhibit Raji-xenograft tumor growth in established NPG mouse model at 2.0 and 4.0 mg/kg. In addition, the minimum lethal doses of F10 and SN-38 in mice by intravenous administration were 80 and 40 mg/kg (or 0.155, 0.102 mmol/kg), respectively. The solubility of F10 reached 9.86 μg/mL in a buffer solution of pH 4.5. The oral bioavailability of F10 achieved 22.4% in mice. The molecular docking model revealed that F10 can interact with topoisomerase I-DNA complex. Our findings indicate that F10 is a new orally-oavailable antitumor agent with potent anticancer effect. Furthermore, attaching a ring hydrophobic moiety to the 10-position of camptothecin provides a favorable approach in the optimization of camptothecin.

The portable UV photodetector is used to timely remind humans of overexposure to UV radiation. However, the traditional UV photodetector cannot meet the practical demands, and the power supply problem hinders its further development. In this work, we demonstrated a flexible, transparent, and self-powered UV photodetector by coupling of triboelectric and photoelectric effects. The device integrates a flexible ZnO nanoparticle (NP) UV photodetector, a transparent- and flexible-film-based TENG (TFF-TENG), commercial chip resistors, and LEDs on the PET thin film. The TFF-TENG could harvest mechanical energy from finger tapping and sliding motion and power the ZnO NP UV photodetector to realize self-powered detection. The voltage of the constant resistors connected with the UV photodetector in series changes from 0.5 to 19 V under the UV light with power intensities increasing from 0.46 to 21.8 mW/cm2, and the voltage variation is reflected by the number of LEDs directly. The excellent flexibility and transparency of the device could extend its application scenarios; for example, such a portable device could be applied to real-time monitoring of the UV radiation to remind humans of intense UV light.

A series of tetracyclic oxindole derivatives was synthesized by asymmetric 1, 3-dipole reaction in 2–4 steps in 57–86% overall yields. These compounds were evaluated for α-glucosidase inhibitory and glucose consumption-promoting activity in vitro. Compound 4l competitively and reversibly inhibited α-glucosidase (IC50 = 3.64 μM) with activity 14-fold higher than that of acarbose. Docking analysis substantiated these findings. In addition, compound 4l exhibited significant glucose consumption promoting activity at 1 μM.

This study investigates on the molecular and mechanical markers of intestinal fibrosis in Crohn’s Disease using endoscopic photoacoustic imaging. The quantitative imaging results in vivo are validated by histology and microelastometry.

Objective: The objective was to evaluate the application of transesophageal echocardiography, left atrial appendage angiography, cardiac computed tomography angiography, and three-dimensional reconstruction model in the left atrial appendage occlusion. Methods: A total of 53 patients with persistent atrial fibrillation hospitalized from January 2015 to February 2019 were selected. Transesophageal echocardiography and cardiac computed tomography angiography were performed simultaneously before operation, and three-dimensional reconstruction of the left atrial appendage model was performed based on the cardiac computed tomography angiography findings. The morphology and size of the left atrial appendage were displayed by the left atrial appendage angiography during the operation. Results: Cardiac computed tomography angiography revealed filling defects in the left atrial appendage in four patients, whereas transesophageal echocardiography revealed thrombosis in two patients of the four patients. According to the cardiac computed tomography angiography results, the morphology of the left atrial appendage was classified into chicken wing–like, cauliflower-like, wind vane–like, and cactus-like. The diameters and depths of the left atrial appendage measured by cardiac computed tomography angiography and three-dimensional reconstruction model were found to be the greatest, and the orifice sizes and depths of the left atrial appendage measured by the left atrial appendage angiography were the smallest. Conclusion: Transesophageal echocardiography, left atrial appendage angiography, cardiac computed tomography angiography, and three-dimensional reconstruction model can evaluate the morphology and size of the left atrial appendage. The cardiac computed tomography angiography and three-dimensional reconstruction model could demonstrate the internal structure of the left atrial appendage more clearly.

This meta-analysis of 70 studies of 33,089 Chinese students examines positive and negative parenting styles’ relations with aggression, and their moderators. Children who experienced negative parenting styles showed more aggression, and those who experienced positive parenting styles showed less aggression. Both positive and negative parenting styles’ links with aggression were larger (a) with parental emotional climate rather than parental socializing behaviours, (b) with self-reported rather than other-reported parenting styles, (c) with one aggression measure (BPAQ) than with others, (d) in Eastern China than in Central or Western China, and (e) for college students, smaller for senior high school students, and smallest for junior high school and primary school students. Negative parenting style’s link with aggression was stronger (a) in Central China than in Western China and (b) for males than for females. Also, positive parenting style’s link with aggression was larger for junior high school students than primary school students.

Brain tissue survival and functional recovery after ischemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embryonic and postnatal vascular formation via binding to its receptor PlexinD1. However, whether Sema3E/PlexinD1 signaling is involved in poststroke neovascularization remains unknown. To determine the contribution of Sema3E/PlexinD1 signaling to poststroke recovery, aged rats (18 months) were subjected to a transient middle cerebral artery occlusion. We found that depletion of Sema3E/PlexinD1 signaling with lentivirus-mediated PlexinD1-specific-shRNA improves tissue survival and functional outcome. Sema3E/PlexinD1 inhibition not only increases cortical perfusion but also ameliorates blood-brain barrier damage, as determined by positron emission tomography and magnetic resonance imaging. Mechanistically, we demonstrated that Sema3E suppresses endothelial cell proliferation and angiogenic capacity. More importantly, Sema3E/PlexinD1 signaling inhibits recruitment of pericytes by decreasing production of platelet derived growth factor-BB in endothelial cells. Overall, our study revealed that inhibition of Sema3E/PlexinD1 signaling in the ischemic penumbra, which increases both endothelial angiogenic capacity and recruitment of pericytes, contributed to functional neovascularization and blood-brain barrier integrity in the aged rats. Our findings imply that Sema3E/PlexinD1 signaling is a novel therapeutic target for improving brain tissue survival and functional recovery after ischemic stroke.

An enriched environment (EE) provides multi-dimensional stimuli to the brain. EE exposure for days to months induces functional and structural neuroplasticity. In this study, manganese-enhanced magnetic resonance imaging (MEMRI) was used to map the accumulative whole-brain activities associated with a 7-day EE exposure in freely-moving adult male mice, followed by c-Fos immunochemical assessments. Relative to the mice residing in a standard environment (SE), the mice subjected to EE treatment had significantly enhanced regional MEMRI signal intensities in the prefrontal cortex, somatosensory cortices, basal ganglia, amygdala, motor thalamus, lateral hypothalamus, ventral hippocampus and midbrain dopaminergic areas at the end of the 7-day exposure, likely attributing to enhanced Mn2+ uptake/transport associated with brain activities at both the regional and macroscale network levels. Some of, but not all, the brain regions in the EE-treated mice showing enhanced MEMRI signal intensity had accompanying increases in c-Fos expression. The EE-treated mice were also found to have significantly increased overall amount of food consumption, decreased body weight gain and upregulated tyrosine hydroxylase (TH) expression in the midbrain dopaminergic areas. Taken together, these results demonstrated that the 7-day EE exposure was associated with elevated cumulative activities in the nigrostriatal, mesolimbic and corticostriatal circuits underpinning reward, motivation, cognition, motor control and appetite regulation. Such accumulative activities might have served as the substrate of EE-related neuroplasticity and the beneficial effects of EE treatment on neurological/psychiatric conditions including drug addiction, Parkinson’s disease and eating disorder.

Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in-flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%-72%) in the in-flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5-121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%-23%), 29% (95% CI: 27%-31%), and 50% (95% CI: 48%-53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%-87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2-77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.

The inflammatory process in stroke is the major contributor to blood-brain barrier (BBB) breakdown. Previous studies indicated that semaphorin 4D (Sema4D), an axon guidance molecule, initiated inflammatory microglial activation and disrupted endothelial function in the CNS. However, whether Sema4D disrupts BBB integrity after stroke remains unclear. To study the effect of Sema4D on BBB disruption in stroke, rats were subjected to transient middle cerebral artery occlusion and targeted injection of lentivirus-mediated clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene disruption of PlexinB1. We found that Sema4D synchronously increased with BBB permeability and accumulated in the perivascular area after stroke. Suppressing Sema4D/PlexinB1 signaling in the periinfarct cortex significantly decreased BBB permeability as detected by MRI and fibrin deposition, and thereby improved stroke outcome. In vitro, we confirmed that Sema4D disrupted BBB integrity and endothelial tight junctions. Moreover, we found that Sema4D induced pericytes to acquire a CD11b-positive phenotype and express proinflammatory cytokines. In addition, Sema4D inhibited AUF1-induced proinflammatory mRNA decay effect. Taken together, our data provides evidence that Sema4D disrupts BBB integrity and promotes an inflammatory response by binding to PlexinB1 in pericytes after transient middle cerebral artery occlusion. Our study indicates that Sema4D may be a novel therapeutic target for treatment in the acute phase of stroke.-Zhou, Y.-F., Li, Y.-N., Jin, H.-J., Wu, J.-H., He, Q.-W., Wang, X.-X., Lei, H., Hu, B. Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.