Complement activation in wasp venom-induced acute kidney injury.

Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.

The role and mechanism of NLRP3 in wasp venom-induced acute kidney injury.

BACKGROUND: Inflammation and pyroptosis have crucial impacts on the development of acute kidney injury (AKI) and have been validated in a variety of existing AKI animal models. However, the mechanisms underlying wasp venom-induced AKI are still unclear. The involvement of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) in some mouse models of AKI has been extensively documented, and its crucial function in controlling inflammation and pyroptosis has been highlighted. The objective of our study was to investigate the role and mechanism of NLRP3 in inflammation and pyroptosis associated with wasp venom-induced AKI. METHODS: A mouse model of AKI induced by wasp venom pre-injected with an NLRP3 inhibitor was used to study the role and mechanism of NLRP3. To verify the importance of NLRP3, western blotting was performed to assess the expression of NLRP3, caspase-1 p20, and gasdermin D (GSDMD)-N. Additionally, quantitative real-time polymerase was used to determine the expression of NLRP3, caspase-1, and GSDMD. Furthermore, enzyme-linked immunosorbent assay was utilized to measure the levels of interleukin (IL)-1ß and IL-18. RESULTS: NLRP3 was found to be the downstream signal of the stimulator of interferon genes in the wasp sting venom-induced AKI model. The administration of wasp venom in mice significantly upregulated the expression of NLRP3, leading to renal dysfunction, inflammation, and pyroptosis. Treatment with an NLRP3 inhibitor reversed the renal damage induced by wasp venom and attenuated pathological injury, inflammatory response, and pyroptosis. CONCLUSION: NLRP3 activation is associated with renal failure, inflammatory response and pyroptosis in the hyper early phase of wasp venom-induced AKI. The inhibition of NLRP3 significantly weakened this phenomenon. These findings could potentially offer a viable therapeutic approach for AKI triggered by wasp venom.

Global, regional, and national burden of depressive disorders among young people aged 10-24 years, 2010-2019.

OBJECTIVE: To describe the latest disease burden, temporal trends, and risk factors of depressive disorders among young people. METHODS: Data from the Global Burden of Disease Study 2019 was utilized to analyze depressive disorders among individuals aged 10-24 years. The study focused on describing the incidence, prevalence, disability-adjusted life years (DALYs), and their attributable risk factors across 204 countries and territories from 2010 to 2019. The estimated annual percentage change (EAPC) was calculated to quantify the temporal trends. RESULTS: Globally, the incidence, prevalence, and DALYs rate of depressive disorders per 100 000 young people increased from 3003.01, 2445.69, and 448.61 in 2010 to 3035.26, 2470.67, and 452.58 in 2019, indicating a slight upward trend (EAPC = 0.11 for incidence and prevalence; EAPC = 0.09 for DALYs rate). Notably, the percentage of DALYs of depressive disorders among young people increased substantially from 3.24% in 2010 to 3.66% in 2019, an increase of 13.06% (EAPC = 1.26, 95%CI: 1.08-1.44), and the burden of depressive disorders among young people rose from fouth to second in females, and from tenth to fifth in males. Social demographic index (SDI) and other indicators were positively correlated with the percentage of DALYs of depressive disorder and negatively correlated with the EAPC of DALYs. CONCLUSION: The global burden of depressive disorders among young people is on the rise. The regional differences in depressive disorders among young people suggest the need for enhanced screening efforts in low-SDI areas, along with the adoption of more effective prevention and control measures.

The effect of TEMPOL pretreatment on postoperative cognitive function, inflammatory response, and oxidative stress in aged rats under sevoflurane anesthesia.

INTRODUCTION: The heterocyclic compound 4-hydroxy-(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. METHODS: Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. RESULTS: Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p < .05). Superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were lower, while malondialdehyde (MDA) was higher in groups S and ST rats than in groups C and T rats (p < .05). Group ST showed higher SOD, T-AOC, and GSH-Px, and lower MDA than group S (p < .05). CONCLUSIONS: TEMPOL pretreatment attenuated postoperative cognitive impairment induced by sevoflurane anesthesia in aged rats. This may be attributed to the downregulation of NR2B-CREB-BDNF pathway, reducing the inflammatory response and oxidative stress damage in hippocampal tissue.

Social visual preference mediates the effect of cortical thickness on symptom severity in children with autism spectrum disorder.

Background: Evidence suggests that there is a robust relationship between altered neuroanatomy and autistic symptoms in individuals with autism spectrum disorder (ASD). Social visual preference, which is regulated by specific brain regions, is also related to symptom severity. However, there were a few studies explored the potential relationships among brain structure, symptom severity, and social visual preference. Methods: The current study investigated relationships among brain structure, social visual preference, and symptom severity in 43 children with ASD and 26 typically developing (TD) children (aged 2-6 years). Results: Significant differences were found in social visual preference and cortical morphometry between the two groups. Decreased percentage of fixation time in digital social images (%DSI) was negatively related to not only the thickness of the left fusiform gyrus (FG) and right insula, but also the Calibrated Severity Scores for the Autism Diagnostic Observation Schedule-Social Affect (ADOS-SA-CSS). Mediation analysis showed that %DSI partially mediated the relationship between neuroanatomical alterations (specifically, thickness of the left FG and right insula) and symptom severity. Conclusion: These findings offer initial evidence that atypical neuroanatomical alterations may not only result in direct effects on symptom severity but also lead to indirect effects on symptom severity through social visual preference. This finding enhances our understanding of the multiple neural mechanisms implicated in ASD.

IMB5036 overcomes resistance to multiple chemotherapeutic drugs in human cancer cells through pyroptosis by targeting the KH-type splicing regulatory protein.

AIMS: IMB5036 is a pyridazinone compound with antiproliferative and antitumour activity against hepatoma and pancreatic cancer. In this study, we attempted to identify the target protein of IMB5036 and test its potential for overcoming multidrug resistance and inducing pyroptosis. MATERIALS AND METHODS: We examined the effects of IMB5036 on cancer cells by in vitro assays, a molecular docking model and in vivo tumour models. We performed pull-down experiments using biotinylated IMB5036 and identified the binding proteins. Gene knockdown were used to investigate the oncogenic role of KH-type splicing regulatory protein (KSRP). Western blot was used to detect for mechanism-associated molecules. KEY FINDINGS: IMB5036 could overcome resistance to multiple chemotherapeutic drugs at the cellular level and in vivo. Furthermore, IMB5036 was not a P-glycoprotein (P-gp) substrate and downregulated the expression of P-gp. We identified KSRP as a binding protein of IMB5036. The knockdown of KSRP inhibited the proliferation of MCF7 and MCF7/adriamycin (MCF7/ADR) cells. In addition, IMB5036 induced pyroptosis in both MCF7 and MCF7/ADR cells via KSRP. SIGNIFICANCE: We found IMB5036 binds to KSRP and overcomes multidrug resistance via gasdermin E (GSDME)-dependent pyroptosis.

Characterization of Premigration and Postmigration Multidomain Factors and Psychosocial Health Among Refugee Children and Adolescents After Resettlement in Australia.

Importance: A better understanding of the psychosocial health of resettled child and adolescent refugees and associated premigration and postmigration factors may help this population integrate effectively. Objective: To estimate the associations of premigration and postmigration multidomain factors with psychosocial health after resettlement among young refugees of different ages. Design, Setting, and Participants: This cross-sectional study used wave 3 data from the Building a New Life in Australia (BNLA) cohort study, as they represented the first time a BNLA study included a child module targeting children and adolescents in the migrating unit as a nested component of the broader study. The study population consisted of children aged 5 to 10 years and adolescents aged 11 to 17 years. The caregivers of the children, the adolescents themselves, and the adolescents' caregivers were invited to complete the child module. Wave 3 data were collected from October 1, 2015, to February 29, 2016. Statistical analysis was performed from May 10 to September 21, 2022. Exposures: Premigration and postmigration multidomain factors, including individual (child and caregiver), family, school, and community levels, were measured. Main Outcomes and Measures: Social and emotional adjustment and posttraumatic stress disorder (PTSD) were the dependent variables measured by the Strengths and Difficulties Questionnaire (SDQ) and an 8-item PTSD scale. Weighted multilevel linear or logistic regression models were used. Results: Of the 220 children aged 5 to 10 years (mean [SD] age, 7.4 [2.0] years), 117 (53.2%) were boys; of the 412 adolescents aged 11 to 17 years (mean [SD] age, 14.1 [2.0] years), 215 (52.2%) were boys. Among the children, compared with no exposure, exposure to premigration traumatic events (ß = 2.68 [95% CI, 0.51-4.85]) and having family conflicts after resettlement (ß = 6.30 [95% CI, 2.97-9.64]) were positively associated with SDQ total difficulties score; school achievement was negatively associated with SDQ total difficulties score (ß = -5.02 [95% CI, -9.17 to -0.87]). Among the adolescents, being treated unfairly (ß = 3.32 [95% CI, 1.41-5.22]) and parenting harshness after resettlement (ß = 0.25 [95% CI, 0.11-0.40]) were positively associated with SDQ total difficulties score; engagement in extracurricular activities (ß = -3.67 [95% CI, -6.83 to -0.50]) was negatively associated with SDQ total difficulties score. Exposure to premigration traumatic events (adjusted odds ratio [aOR], 2.49 [95% CI, 1.10-5.63]), being treated unfairly (aOR, 3.77 [95% CI, 1.60-8.91]), and facing English language barriers (aOR, 6.41 [95% CI, 1.98-20.79]) after resettlement were positively associated with the presence of PTSD. Conclusions and Relevance: In this study of refugee children and adolescents, apart from premigration traumatic experiences, several postmigration family- and school-related factors and social integration factors were associated with psychosocial health after resettlement. The findings suggest that family- and school-centered psychosocial care and social integration programs targeting related stressors merit increased attention for improving the psychosocial health of refugee children and adolescents after resettlement.

Global, regional, and national burden of ambient and household PM2.5-related neonatal disorders, 1990-2019.

Previous studies have shown a relationship between fine particulate matter (PM2.5) exposure and an increased risk of neonatal disorders. Considering the huge burden of neonatal disorders, we assessed spatiotemporal trends of neonatal disorders burden caused by ambient and household PM2.5 at the global, regional, and national levels from 1990 to 2019. The number, rate, and population attributable fraction (PAF) of ambient and household PM2.5-related neonatal disorders disability-adjusted life years (DALYs) in 204 countries and territories from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 to measure the related neonatal disorders burden by age, sex, subtype, and region. Estimated annual percentage change (EAPC) was estimated to quantify temporal trends. In 2019, approximately a fifth of the global neonatal disorders burden was attributable to PM2.5 exposure, with 7.54% for ambient PM2.5 and 13.23% for household PM2.5. Although the global neonatal disorders burden attributable to household PM2.5 has decreased substantially in the past 30 years, that attributable to ambient PM2.5 has increased, especially in lower sociodemographic index (SDI) regions. The highest rate and PAF of ambient PM2.5-related neonatal disorders DALYs in 2019 were in South Asia and East Asia, respectively, and the fastest increases were in Eastern Sub-Saharan Africa (for rate: EAPC = 2.55, 95% CI: 2.37-2.73) and South Asia (for PAF: EAPC = 3.88, 95% CI: 3.68-4.08). In addition, we found an inverted V-shaped between rates and PAFs of ambient PM2.5-related neonatal disorders DALYs in 2019, as well as corresponding EAPCs, and SDI, while rates and PAFs of household PM2.5-related neonatal disorders DALYs in 2019 were highly negatively correlated with SDI. In the past three decades, the global ambient PM2.5-related neonatal disorders burden largely increased, especially in lower SDI regions. Comparatively, the household PM2.5-related neonatal disorders burden decreased but still accounted for about two-thirds of the PM2.5-related neonatal disease burden.

Theranostic application of 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody in pancreatic cancer tumor models.

PURPOSE: Pancreatic cancer is a malignant tumor with a high degree of malignancy, strong heterogeneity, and high lethality. Trop2 is a transmembrane glycoprotein associated with the occurrence, development, and poor prognosis of pancreatic cancer. This study aims to develop 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody (hIMB1636) for positron emission tomography (PET) imaging and radioimmunotherapy (RIT) application in pancreatic cancer tumor models. METHODS: The binding kinetics of hIMB1636 to Trop2 antigen was measured by Biolayer interferometry (BLI). Western blotting was used to screen the Trop2 expression of pancreatic cancer cell lines. Flow cytometry and cell immunofluorescence were used to evaluate the binding ability of hIMB1636 and Trop2 on the cell surface. hIMB1636 were conjugated with p-SCN-Bn-NOTA (NOTA) and DOTA-NHS-ester (DOTA) for 64Cu and 177Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 in subcutaneous pancreatic cancer tumor models. RESULTS: hIMB1636 had a strong binding affinity to Trop2 according to the results of BLI. The T3M-4 cell line showed the strongest expression of Trop2 and specific binding ability of hIMB1636 according to the results of Western blotting, flow cytometry, and cell immunofluorescence. The radiochemical purity of 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of 64Cu-NOTA-hIMB1636 in T3M-4 tumor models. The maximum tumor uptake was 8.95 ± 1.07%ID/g (n = 4) at 48 h post injection (p.i.), which had significant differences with T3M-4-blocked and PaTu8988-negative groups (P < 0.001). The high-177Lu-hIMB1636 group demonstrated the strongest tumor suppression with standardized tumor volume about 94.24 ± 14.62% (n = 5) at 14 days p.i., significantly smaller than other groups (P < 0.05). Ex vivo biodistribution and histological staining verified the in vivo PET imaging and RIT results. CONCLUSIONS: This study demonstrated that 64Cu/177Lu-labeled hIMB1636 could noninvasively evaluate the expression level of Trop2 and inhibit the Trop2-overexpressed tumor growth in pancreatic cancer tumor models. Further clinical evaluation and translation of Trop2-targeted drug may be of great help in the stratification and management of pancreatic cancer patients.

RPP30 is a novel diagnostic and prognostic biomarker for gastric cancer.

Objective: This study aimed to identify the hub gene in gastric cancer (GC) tumorigenesis. A biomarker prediction model was constructed and analyzed, and protein expression in histopathological samples was verified in a validation cohort. Methods: Differentially expressed genes (DEGs) were identified from GC projects in The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis of DEGs was performed between the high- and low- Ribonuclease P protein subunit p30 (RPP30) expression groups. ROC analysis was performed to assess RPP30 expression to discriminate GC from normal tissues. Functional enrichment pathways and immune infiltration of DEGs were analyzed using GSEA and ssGSEA. Survival analysis and nomogram construction were performed to predict patient survival. Immunohistochemical staining of GC tissues was performed to validate RPP30 expression in GC and paracancerous samples. Results: Gene expression data and clinical information of 380 cases (375 GC samples and 32 para-cancerous tissues) were collected from TCGA database. The AUC for RPP30 expression was found to be 0.785. The G alpha S signaling pathway was the most significantly enriched signaling pathway. Primary therapy outcome (p < 0.001, HR = 0.243, 95% CI = 0.156-0.379), age (p = 0.012, HR = 1.748, 95% CI = 1.133-2.698), and RPP30 expression (p < 0.001, HR = 2.069, 95% CI = 1.346-3.181) were identified as independent prognostic factors. As a quantitative approach, a nomogram constructed based on RPP30 expression, age, and primary therapy outcome performed well in predicting patient survival. Nineteen of the 25 tissue samples from the validation cohort showed positive RPP30 expression in GC tissues, whereas 16 cases showed negative RPP30 staining in normal tissues. The difference between the two was statistically significant. Conclusion: High RPP30 expression was significantly correlated with disease progression and poor survival in GC, promoting tumorigenesis and angiogenesis via tRNA dysregulation. This study provides new and promising insights into the molecular pathogenesis of tRNA in GC.

The prognostic value of 18F-FDG PET/CT intra-tumoural metabolic heterogeneity in pretreatment neuroblastoma patients.

BACKGROUND: Neuroblastoma (NB) is the most common tumour in children younger than 5 years old and notable for highly heterogeneous. Our aim was to quantify the intra-tumoural metabolic heterogeneity of primary tumour lesions by using 18F-FDG PET/CT and evaluate the prognostic value of intra-tumoural metabolic heterogeneity in NB patients. METHODS: We retrospectively enrolled 38 pretreatment NB patients in our study. 18F-FDG PET/CT images were reviewed and analyzed using 3D slicer software. The semi-quantitative metabolic parameters of primary tumour were measured, including the maximum standard uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). The areas under the curve of cumulative SUV-volume histogram index (AUC-CSH index) was used to quantify intra-tumoural metabolic heterogeneity. The median follow-up was 21.3 months (range 3.6 - 33.4 months). The outcome endpoint was event-free survival (EFS), including progression-free survival and overall survival. Survival analysis was performed using Cox regression models and Kaplan Meier survival plots. RESULTS: In all 38 newly diagnosed NB patients, 2 patients died, and 17 patients experienced a relapse. The AUC-CSHtotal (r=0.630, P<0.001) showed moderate correlation with the AUC-CSH40%. In univariate analysis, chromosome 11q deletion (P=0.033), Children's Oncology Group (COG) risk grouping (P=0.009), bone marrow involvement (BMI, P=0.015), and AUC-CSHtotal (P=0.007) were associated with EFS. The AUC-CSHtotal (P=0.036) and BMI (P=0.045) remained significant in multivariate analysis. The Kaplan Meier survival analyses demonstrated that patients with higher intra-tumoural metabolic heterogeneity and BMI had worse outcomes (log-rank P=0.002). CONCLUSION: The intra-tumoural metabolic heterogeneity of primary lesions in NB was an independent prognostic factor for EFS. The combined predictive effect of intra-tumoural metabolic heterogeneity and BMI provided prognostic survival information in NB patients.

A Chess and Card Room-Induced COVID-19 Outbreak and Its Agent-Based Simulation in Yangzhou, China.

Objective: To evaluate epidemiological characteristics of the COVID-19 outbreak that resurged in Yangzhou and to simulate the impact of different control measures at different regional scales. Methods: We collected personal information from 570 laboratory-confirmed cases in Yangzhou from 28 July to 26 August 2021, and built a modified susceptible-exposed-infected-removed (SEIR) model and an agent-based model. Results: The SEIR model showed that for passengers from medium-high risk areas, pre-travel nucleic acid testing within 3 days could limit the total number of infected people in Yangzhou to 50; among elderly persons, a 60% increase in vaccination rates could reduce the estimated infections by 253. The agent-based model showed that when the population density of the chess and card room dropped by 40%, the number of infected people would decrease by 54 within 7 days. A ventilation increase in the chess and card room from 25 to 50% could reduce the total number of infections by 33 within 7 days; increasing the ventilation from 25 to 75% could reduce the total number of infections by 63 within 7 days. Conclusions: The SEIR model and agent-based model were used to simulate the impact of different control measures at different regional scales successfully. It is possible to provide references for epidemic prevention and control work.

[Programmed Necrosis Inducers for Cancer Treatment].

Programmed necrosis,a mode of cell death independent of Caspase,is mainly mediated by receptor-interacting protein kinase-1 (RIPK1),receptor-interacting protein kinase-3 (RIPK3),and mixed lineage kinase domain-like protein (MLKL).Studies have demonstrated that programmed necrosis has the dual role of promoting and inhibiting tumor growth and thus we can control the development of tumor by regulating programmed necrosis.The drugs capable of inducing programmed necrosis show potential anti-tumor activity.In addition,inducing programmed necrosis is an effective way to overcome tumor resistance to apoptosis.This paper summarized the mechanisms of programmed necrosis and its relationship with tumors.We focused on the antitumor activity of programmed necrosis inducers including natural products,chemotherapeutic drugs,death receptor ligands,kinase inhibitors,inorganic salts,metal complexes,and metal nanoparticles.These agents will provide new therapeutic candidates for the treatment of tumors,especially the tumors acquiring resistance to apoptosis.

Rational Design and Systemic Appraisal of an EGFR-Targeting Antibody-Drug Conjugate LR-DM1 for Pancreatic Cancer.

By harnessing the payload DM1 and a monoclonal antibody LR004 through a noncleavable linker succinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate, we designed and evaluated an antibody-drug conjugate LR-DM1 with an appropriate drug-antibody ratio of 3.6. LR-DM1, which was targeted toward the epidermal growth factor receptor for pancreatic cancer, exhibited potent antiproliferation activity in vitro with a half-maximal inhibitory concentration value of 7.03 nM for Capan-2 cells. Particularly, it displayed prominent tumor growth inhibition in vivo under 20 mg/kg LR-DM1 dosage in a single administration or multiple administrations without apparent abnormality of pathological observation. Moreover, LR-DM1 possessed a relatively broad therapeutic index with a half-lethal dose above 300 mg/kg, which was over 15-fold higher than the highest administration dosage of 20 mg/kg. This initial study on LR-DM1 holds promise for further development of a new antibody drug conjugate that is transformative for treatment of patients concerned.

The Analysis of Patterns of Two COVID-19 Outbreak Clusters in China.

Since the emergence of COVID-19, there have been many local outbreaks with foci at shopping malls in China. We compared and analyzed the epidemiological and spatiotemporal characteristics of local COVID-19 outbreaks in two commercial locations, a department store building (DSB) in Baodi District, Tianjin, and the Xinfadi wholesale market (XFD) in Fengtai District, Beijing. The spread of the infection at different times was analyzed by the standard deviation elliptical method. The spatial transfer mode demonstrated that outbreaks started at the center of each commercial location and spread to the periphery. The number of cases and the distance from the central outbreak showed an inverse proportional logarithmic function shape. Most cases were distributed within a 10 km radius; infected individuals who lived far from the outbreak center were mainly infected by close-contact transmission at home or in the workplace. There was no efficient and rapid detection method at the time of the DSB outbreak; the main preventative measure was the timing of COVID-19 precautions. Emergency interventions (closing shopping malls and home isolation) were initiated five days before confirmation of the first case from the shopping center. In contrast, XFD closed after the first confirmed cases appeared, but those infected during this outbreak benefitted from efficient nucleic acid testing. Quick results and isolation of infected individuals were the main methods of epidemic control in this area. The difference in the COVID-19 epidemic patterns between the two shopping malls reflects the progress of Chinese technology in the prevention and control of COVID-19.

Target-Binding Accelerated Response for Sensitive Detection of Basal H2O2 in Tumor Cells and Tissues via a Dual-Functional Fluorescence Probe.

Aberrant production of H2O2 is involved in cancer. The levels of H2O2 are significantly higher in tumor cells than in normal cells. It is important to develop fluorescent probes to image basal H2O2 selectively in tumor cells. So far, a cancer cell-targeting probe to image basal H2O2 has not been reported. Thus, we developed a fluorescent probe, BBHP, which contains benzil as a H2O2-recognition site and biotin as a target binding motif for the selective and sufficient detection of H2O2 in tumor cells. BBHP enables a selective fluorescence turn-on response to H2O2. The binding of the probe with biotin receptors can greatly accelerate the fluorescence response to H2O2. As a result, BBHP can sufficiently image basal H2O2 in biotin receptor-positive cancer cells and tumor tissues. Finally, BBHP was successfully applied to discriminate between cancerous and normal tissues.

Empathy, Theory of Mind, and Prosocial Behaviors in Autistic Children.

Background: Previous research has suggested that children with autism spectrum disorder (ASD) display fewer prosocial behaviors, and the role of empathy or Theory of Mind (ToM) in prosocial behaviors of autistic children remains unclear. Methods: Data were obtained from an ongoing longitudinal study in Guangzhou, China. A total of 96 autistic children and 167 typically developing (TD) children were enrolled. Prosocial behaviors were assessed using a subscale of the Strength and Difficulties Questionnaire and Dictator Game (DG) paradigm with stickers as incentives. Empathic traits and ToM ability were measured using the children's Empathy Quotient and the Chinese version of ToM toolkit. Generalized linear models were used to assess the differences of prosocial behaviors and empathic traits, ToM ability between the two groups and the associations between empathic traits, ToM ability and prosocial behaviors in autistic children. Results: Compared with TD children, autistic children exhibited worse ToM ability and performed less pro-socially in the DG paradigm, while there were no differences regarding empathic traits. In autistic children, empathic traits especially affective empathy, were positively associated with parent-reported prosocial behaviors [ß = 0.17, 95% confidence interval (CI): 0.07-0.27; ß = 0.47, 95%CI: 0.33-0.60]. ToM ability was associated with DG paradigm (ß = 1.03, 95%CI: 0.16-1.89). Conclusion: Autistic children showed less pro-sociality and ToM ability than TD children. In autistic children, empathic trait was associated with parent-reported prosocial behaviors while their ToM ability was associated with prosocial behaviors in experimental condition. Our findings indicated that better ToM ability and empathic trait might promote prosocial behaviors in autistic children.

Alteration of the fecal microbiota in Chinese children with autism spectrum disorder.

Autism spectrum disorder (ASD) is associated with altered gut microbiota. However, there has been little consensus on the altered bacterial species and studies have had small sample sizes. We aimed to identify the taxonomic composition and evaluate the changes in the fecal microbiota in Chinese children with ASD by using a relatively large sample size. We conducted a case-control study of 101 children with ASD and 103 healthy controls in China. Demographic information and fecal samples were collected, and the V3-V4 hypervariable regions of the bacterial 16S ribosomal RNA (rRNA) gene were sequenced. The alpha and beta diversities between the two groups were significantly different. After correcting for multiple comparisons, at the phylum level the relative abundances of Actinobacteria and Proteobacteria in the case group were significantly higher than those in the control group. The relative abundance of the Escherichia-Shigella genus in the case group was significantly higher than that of the control group, and the relative abundance of Blautia and unclassified_f__Lachnospiraceae in the control group were higher than that of the case group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that children with ASD may have disturbed functional pathways, such as amino acid metabolism, cofactor and vitamin metabolism, and the AMP-activated protein kinase signaling pathway. This study revealed the characteristics of the intestinal flora of Chinese children with ASD and provided further evidence of gut microbial dysbiosis in ASD. LAY SUMMARY: This study characterized the gut microbiota composition of 101 children with ASD and 103 healthy controls in China. The altered gut microbiota may contribute significantly to the risk of ASD, including significant increases in the relative abundances of Actinobacteria, Proteobacteria and Escherichia-Shigella and significant decrease of Blautia and unclassified_f__Lachnospiraceae. This study provided further evidence of gut microbial dysbiosis in ASD.

IMB5476, a novel microtubule inhibitor, induces mitotic catastrophe and overcomes multidrug resistance in tumors.

IMB5046 is a nitrobenzoate microtubule inhibitor we reported previously. During screening of its structural analogues, we identified a novel compound IMB5476 with increased aqueous solubility. Here, its antitumor activity and the underlying mechanism were investigated. IMB5476 disrupted microtubule networks in cells and arrested cell cycle at G2/M phase. It inhibited purified tubulin polymerization in vitro. Competition assay indicated that it bound to tubulin at the colchicine pocket. Further experiments proved that it induced cell death by mitotic catastrophe and apoptosis. Notably, it was a poor substrate of P-glycoprotein and exhibited potent cytotoxicity against drug-resistant tumor cells. In addition, IMB5476 could inhibit angiogenesis in vitro. IMB5476 also inhibited the growth of drug-resistant KBV200 xenografts in mice. Conclusively, our data reveal a novel nitrobenzoate microtubule inhibitor with improved aqueous solubility and can overcome multidrug resistance.