Treg Immunomodulation Contributes to the Anti-atherosclerotic Effects of Huxin Formula in ApoE-/- Mice.

OBJECTIVE: To explore the effects of Huxin formula (HXF) in curtailing atherosclerosis and its underlying mechanism. METHODS: According to random number table method, 24 specific pathogen free male ApoE-/- mice were randomly divided into model group, HXF low-dose (HXF-L) group (8.4 g/kg daily), HXF high-dose (HXF-H) group (16.8 g/kg daily), and pravastatin (8 mg/kg daily) group in Experiment I (n=6 per group). C57BL/6J mice served as the control group (n=6). ApoE-/- mice in HXF-L, HXF-H, pravastatin groups were fed a Western diet and administered continuously by gavage for 12 weeks, while C57BL/6J mice in the control group were fed conventional lab mouse chow for 12 weeks. Further, Tregs were depleted by weekly intraperitoneal injection of purified anti-mouse CD25 antibody (PC61, 250 µg per mouse) for 4 weeks in Experiment II (n=6 per group). Oil Red O and Masson staining were used to evaluate the plaque area and aortic root fibrosis. The CD4+CD25+Foxp3+Treg counts in the lymph nodes and spleen cells were detected using flow cytometric analysis. The transforming growth factor-ß1 (TGF-ß1), interleukin (IL)-10, and IL-6 serum levels were examined by MILLIPLEX® MAP technology. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were utilized to assess the expression of TGF-ß mRNA and protein in the aorta. The expression of CD4+T lymphocytes, macrophages and smooth muscle cells in the aortic root were detected by immunofluorescence staining. RESULTS: HXF reduced plaque area in ApoE-/- mice (P<0.01). HXF increased the Treg counts in the lymph nodes and spleen cells (P<0.05 or P<0.01). Moreover, HXF alleviated inflammatory response via elevating IL-10 and TGF-ß 1 serum levels (P<0.05), while decreasing the IL-6 serum levels in ApoE-/- mice (P>0.05). Also, HXF upregulated the expression of TGF-ß mRNA and protein in the aorta (P<0.05). Additionally, HXF attenuated CD4+T lymphocytes, macrophages and smooth muscle cells in aortic root plaque (P<0.01). Furthermore, the depletion of Tregs with CD25 antibody (PC61) curtailed the reduction in plaque area and aortic root fibrosis by HXF (P<0.01). CONCLUSION: HXF relieved atherosclerosis, probably by restraining inflammatory response, reducing inflammatory cell infiltration and attenuating aortic root fibrosis by increasing Treg counts.

Development and validation of a scale for the assessment of the knowledge-attitude-practice of parents towards children snoring.

BACKGROUND: Children Snoring is a common childhood disorder that affects the growth and development of children and is detrimental to their health. Increasing awareness of Children Snoring among parents is important. AIM: To develop the Knowledge-Attitude-Practice of Parents towards Children Snoring Scale and test the reliability and validity of the scale. METHODS: The development of the tool was divided into two phases involving 1257 parents from China. In the first phase, an initial project bank was created through a literature review. This was followed by a Delphi expert consultation, group discussion and pre-survey. The second stage screened the items and conducted an exploratory factor analysis, then conducted a confirmatory factor analysis and tested for reliability and validity. RESULTS: Support was found for the 25-item Knowledge-Attitude-Practice toward Children Snoring scale. Exploratory and confirmatory factor analyses provide support for four subscales: (parental basic cognition toward Children Snoring; parents' perception of complications of Children Snoring; parents' attitude towards Children Snoring; parents' concern and prevention of Children Snoring). Internal consistency for the total scale was high (Cronbach's α = 0.93). The intraclass correlation coefficient of test-retest reliability was 0.92 (95%CI: 0.85 to 0.95), which provided support for the stability of the scale. CONCLUSION: The Knowledge-Attitude-Practice of Parents towards Children Snoring scale shows promise as a measure that may be used by medical workers and community children's health managers.

Establishment of a hydrodynamic delivery system in ducks.

Chronic hepatitis B virus (HBV) poses a significant global health challenge as it can lead to acute or chronic liver disease and hepatocellular carcinoma (HCC). To establish a safety experimental model, a homolog of HBV-duck HBV (DHBV) is often used for HBV research. Hydrodynamic-based gene delivery (HGD) is an efficient method to introduce exogenous genes into the liver, making it suitable for basic research. In this study, a duck HGD system was first constructed by injecting the reporter plasmid pLIVE-SEAP via the ankle vein. The highest expression of SEAP occurred when ducks were injected with 5 µg/mL plasmid pLIVE-SEAP in 10% bodyweight volume of physiological saline for 6 s. To verify the distribution and expression of exogenous genes in multiple tissues, the relative level of foreign gene DNA and ß-galactosidase staining of LacZ were evaluated, which showed the plasmids and their products were located mainly in the liver. Additionally, ß-galactosidase staining and fluorescence imaging indicated the delivered exogenous genes could be expressed in a short time. Further, the application of the duck HGD model on DHBV treatment was investigated by transferring representative anti-HBV genes IFNα and IFNγ into DHBV-infected ducks. Delivery of plasmids expressing IFNα and IFNγ inhibited DHBV infection and we established a novel efficient HGD method in ducks, which could be useful for drug screening of new genes, mRNAs and proteins for anti-HBV treatment.

[Effects of Combined Stress of High Density Polyethylene Microplastics and Chlorimuron-ethyl on Soybean Growth and Rhizosphere Bacterial Community].

With the vigorous development of agriculture in China， plastic mulch film and pesticides are widely used in agricultural production. However， the accumulation of microplastics （formed by the degradation of plastic mulch film） and pesticides in soil has also caused many environmental problems. At present， the environmental biological effects of microplastics or pesticides have been reported， but there are few studies on the combined effects on crop growth and the rhizosphere soil bacterial community. Therefore， in this study， the high density polyethylene microplastics （HDPE， 500 mesh） were designed to be co-treated with sulfonylurea herbicide chlorimuron-ethyl to study their effects on soybean growth. In addition， the effects of the combined stress of HDPE and chlorimuron-ethyl on soybean rhizosphere soil bacterial community diversity， structure composition， microbial community network， and soil function were investigated using high-throughput sequencing technology， interaction network， and PICRUSt2 function analysis to clarify the combined toxicity of HDPE and chlorimuron-ethyl to soybean. The results showed that the half-life of chlorimuron-ethyl in soil was prolonged by the 1% HDPE treatment （from 11.5 d to 14.3 d）， and the combined stress of HDPE and chlorimuron-ethyl had more obvious inhibition effects on soybean growth than that of the single pollutant or control. The HiSeq 2 500 sequencing showed that the rhizosphere bacterial community of soybean was composed of 20 phyla and 312 genera under combined stress， the number of phyla and genera was significantly less than that of the control and single pollutant treatment， and the relative abundances of bacteria with potential biological control and plant growth-promoting characteristics （such as Nocardioides and Sphingomonas） were reduced. Alpha diversity analysis showed that the combined stress significantly reduced the richness and diversity of the soybean rhizosphere bacterial community， and Beta diversity analysis showed that the combined stress significantly changed the structure of the bacterial community. The dominant flora of the rhizosphere bacterial community were regulated， and the abundances of secondary functional layers such as amino acid metabolism， energy metabolism， and lipid metabolism were reduced under combined stress by the analysis of LEfSe and PICRUSt2. It was inferred from the network analysis that the combined stress of HDPE and chlorimuron-ethyl reduced the total number of connections and network density of soil bacteria， simplified the network structure， and changed the important flora species to maintain the stability of the network. The results above indicated that the combined stress of HDPE and chlorimuron-ethyl significantly affected the growth of soybean and changed the rhizosphere bacterial community structure， soil function， and network structure. Compared with that of the single pollutant treatment， the potential risk of combined stress was greater. The results of this study can provide guidance for evaluating the ecological risks of polyethylene microplastics and chlorimuron-ethyl and for the remediation of contaminated soil.

Environmental surveillance in Jinan city of East China (2014-2022) reveals improved air quality but remained health risks attributable to PM2.5-bound metal contaminants.

PM2.5-bound metal contaminants are associated with multiple chronic diseases in human. At global level, the contamination status has not been well controlled yet. Here we report findings from a long-term air pollution surveillance in Jinan city of Shandong, China. During 2014-2022, the dynamics and trends of PM2.5-bound heavy metal contaminants were monitored in an industrial area and a downtown area. The surveillance targets included: antimony (Sb), aluminum (Al), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), manganese (Mn), nickel (Ni), selenium (Se). The human exposure and health risks were calculated and we found that the health risks of most contaminants showed peak values in autumn and winter. But Al, Mn, Hg and Be were found to result in highest health risk in spring or summer in the downtown area. In the industrial area we identified 100% alarming health index >1 (ranged from 1.12 to 3.35) in autumn and winter. In winter the total non-carcinogenic HI was all above 1 (peak value 2.21). Mn and As together posed >85% non-carcinogenic risk. As and Cd were ranked as major drivers of carcinogenic risks (5.84 × 10-6 and 2.78 × 10-6). Pd and Cd both showed non-negligible environmental levels but risk assessment model for their air-exposure associated non-carcinogenic risks are not yet available. This study updates air pollution data and status for air pollution status in China. This study provides valuable 9 year long-term reference to experimental and field studies in the related fields.

Acute effects of athletic taping on arch deformity and plantar pressure in young female adults with flexible flatfoot.

OBJECTIVE: This work aimed to explore the acute effects of athletic taping techniques on foot arch deformity and plantar pressure in young female adults with flexible flatfoot (FFT). METHODS: Twenty young female adults with FFT were recruited in the current study. Each participant was randomly divided into two taping groups, namely, augmented low-dye (ALD) and modified low-dye (MLD). The foot arch deformity and plantar pressure were measured at baseline, after taping and after 20 min of walking. The foot arch deformity was determined based on navicular drop distance (NDD) and resting calcaneal stance position (RCSP). RESULTS: Compared with baseline, the NDD values were significantly lower after taping. After 20 min of walking, ALD taping resulted in a lower NDD value than MLD (p < 0.001). ALD maintained a higher RCSP than baseline after 20 min of walking (p = 0.004). Furthermore, compared with baseline, medial midfoot force-time integration (p = 0.013) and contact area (p = 0.022) increased after taping with MLD, and peak pressure in the medial midfoot increased after walking for 20 min with MLD (p = 0.026). Peak pressure in the second to fifth toes significantly decreased after 20 min of walking with ALD compared with that after taping immediately (p = 0.002). CONCLUSIONS: ALD and MLD taping could improve FFT arch deformity and plantar pressure distribution, prospectively changing peak pressure of the second to fifth toe area and medial midfoot after 20 min of walking, integrated contact area and force-time integration medial midfoot during walking in young female adults. Furthermore, ALD taping could improve FFT deformity more than using MLD after 20 min of walking. Thus, when treating FFT in young female adults, ALD taping should be considered adaptively to guide arch support production and correct midfoot pronation.

Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study.

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19. Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes. Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2-46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84-1.40 or 1.09, 0.92-1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01-1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26-1.64; 0.95, 0.36-2.54; and 1.01, 0.53-1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82-1.66; 1.18, 0.78-1.77; and 1.22, 0.92-1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31-2.81; 0.97, 0.25-3.74 and 1.05, 0.44-2.49, respectively) compared to those not using medication. Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling.

Fluid shear stress (FSS) from blood flow is sensed by vascular endothelial cells (ECs) to determine vessel stability, remodeling and susceptibility to atherosclerosis and other inflammatory diseases but the regulatory networks that govern these behaviors are only partially understood. We used cSTAR, a powerful new computational method, to define EC transcriptomic states under low shear stress (LSS) that triggers vessel inward remodeling, physiological shear stress (PSS) that stabilizes vessels, high shear stress (HSS) that triggers outward remodeling, and oscillatory shear stress (OSS) that confers disease susceptibility, all in comparison to cells under static conditions (STAT). We combined these results with the LINCS database where EC transcriptomic responses to drug treatments to define a preliminary regulatory network in which the cyclin-dependent kinases CDK1/2 play a central role in promoting vessel stability. Experimental analysis showed that PSS induced a strong late G1 cell cycle arrest in which CDK2 was activated. EC deletion of CDK2 in mice resulted in inward artery remodeling and both pulmonary and systemic hypertension. These results validate use of cSTAR to determine EC state and in vivo vessel behavior, reveal unexpected features of EC phenotype under different FSS conditions, and identify CDK2 as a key element within the EC regulatory network that governs artery remodeling.

A Method for Identification of Biotype-Specific Salivary Effector Candidates of Aphid.

Polyphagous aphids often consist of host-specialized biotypes that perform poorly in non-native hosts. The underlying mechanisms remain unknown. Host-specialized biotypes may express biotype-specific salivary effectors or elicitors that determine aphid hosts. Here, we tried three strategies to identify possible effectors in Malvaceae- (MA) and Cucurbitaceae-specialized (CU) biotypes of the cotton-melon aphid Aphis gossypii Glover. The whole-aphid RNA-seq identified 765 differentially expressed genes (DEGs), and 139 of them were possible effectors; aphid-head RNA-seq identified 523 DEGs were identified, and 98 of them were possible effectors. The homologous genes of published aphid effectors were not differentially expressed between CU and MA. Next, quantitative proteomic analyses of saliva identified 177 possible proteins, and 44 of them were different proteins. However, none of the genes of the 44 proteins were differentially expressed, reflecting the discrepancy between transcriptome and proteome data. Finally, we searched for DEGs of the 177 salivary proteins in the aphid-head transcriptomes, and the salivary proteins with expression differences were regarded as effector candidates. Through this strategy, 11 effector candidates were identified, and their expression differences were all confirmed by RT-qPCR. The combinatorial analysis has great potential to identify biotype-specific effector candidates in aphids and other sap-sucking insects.

The cognitive effects of adjunctive repetitive transcranial magnetic stimulation for late-onset depression: a randomized controlled trial with 4 week follow-up.

Objectives: Cognitive impairment is common and linked to poor outcomes in patients with late-onset depression (LOD). The cognitive effects of repetitive transcranial magnetic stimulation (rTMS) for LOD are not well understood. This study aimed to investigate the effects of rTMS on cognitive function in elderly patients with LOD. Methods: In total, 58 elderly patients (aged 60 to 75 years) with depression were enrolled and randomly assigned to an active rTMS group or a sham group. The participants received active or sham rTMS over the left dorsolateral prefrontal cortex for 4 weeks, 5 days a week, at a frequency of 10 Hz rTMS and 120% of the motor threshold (MT). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline, the end of the 4 week treatment period, and at the 4 week follow-up. Results: The active rTMS group showed significant improvements in immediate memory and attention scores on the RBANS compared to the sham group. However, no significant differences were observed between the two groups in other cognitive domains assessed by the RBANS. No serious adverse events related to rTMS treatment were observed. Conclusion: Treatment with 120% MT rTMS was associated with improvement in cognitive defects related to the active phase of LOD. These findings suggest that rTMS could provide early improvements in cognitive function in clinical settings for elderly patients with LOD.Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=40698, identifier ChiCTR1900024445.

Effects of plantar-sensory treatments on postural control in chronic ankle instability: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to examine the effects of plantar-sensory treatments on postural control in individuals with chronic ankle instability (CAI). METHODS: This study was registered in PROSPERO (registration number CRD42022329985) on May 14, 2022. An extensive search was performed in Pubmed, Embase, Cochrane, Web of Science, and Scopus to identify the potential studies on plantar-sensory treatments affecting postural control before May 2022. The methodological quality of involved studies was assessed using the scale of Physiotherapy Evidence Database (PEDro). The Cochrane Tool and the Risk of Bias in Non-randomized Studies of Interventions assessment tool were used to evaluate the risk of bias in randomised controlled trials (RCTs) and non-RCTs respectively. RevMan 5.4 was utilised to calculate the standardised mean difference (SMD), with 95% confidence interval (CI). RESULTS: Eight RCTs with a mean PEDro rating of 6 and four non-RCTs with a mean PEDro rating of 4.75 were included in the quantitative analysis. The types of plantar-sensory treatments included plantar massage, whole-body vibration and textured surface-stimulation treatment. A significant effect of static balance with eyes open (SMD = -0.54; 95% CI: -0.81 to -0.27; p < 0.001) was found and subgroup analysis showed that plantar massage (SMD = -0.49; 95% CI: -0.84 to -0.14; p = 0.006) and whole-body vibration (SMD = -0.66; 95% CI: -1.12 to -0.19; p = 0.005) had positive effects. In the subgroup analysis of anterior dynamic balance, whole-body vibration revealed a significant increase (SMD = 0.60; 95% CI: 0.06-1.14; p = 0.03). The pooled results or subgroup analysis including eyes-closed static balance and other directions of dynamic balance indicated no significant difference (p > 0.05). CONCLUSIONS: This meta-analysis indicated that plantar-sensory treatments could improve postural control in CAI, especially the treatments of plantar massage and long-term whole-body vibration.

Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine.

Objective: We admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlations among genotype, phenotype, and clinical drug response. Methods: We described the clinical characteristics of an infant with refractory epilepsy. Whole exome sequencing (WES) was used to screen for the pathogenic variant. Whole-cell patch-clamp was performed to determine functional outcomes of the variant. Results: WES identified a novel de novo SCN2A variant (c.468 G > C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that SCN2A-K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na+ channel, all of which suggested a loss-of-function (LOF) of Nav1.2 channel. Conclusion: We showed the importance of functional analysis for a SCN2A variant with unknown significance to determine pathogenicity, drug reactions, and genotype-phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some SCN2A-related epilepsies requires vigilance to assess the possibility of epilepsy worsening.

Effects of high-heeled shoes on lower extremity biomechanics and balance in females: a systematic review and meta-analysis.

BACKGROUND: High-heeled shoes (HHS) are widely worn by women in daily life. Limited quantitative studies have been conducted to investigate the biomechanical performance between wearing HHS and wearing flat shoes or barefoot. This study aimed to compare spatiotemporal parameters, kinematics, kinetics and muscle function during walking and balance between wearing HHS and flat shoes or barefoot. METHODS: According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, PubMed Medline, Cochrane, EMBASE, CINAHL Complete and Web of Science databases were searched from the earliest record to December 2021. A modified quality index was applied to evaluate the risk of bias, and effect sizes with 95% confidence intervals were calculated as the standardized mean differences (SMD). Potential publication bias was evaluated graphically using funnel plot and the robustness of the overall results was assessed using sensitivity analyses. RESULTS: Eighty-one studies (n = 1501 participants) were included in this study. The reduced area of support requires the body to establish a safer and more stable gait pattern by changing gait characteristics when walking in HHS compared with walking in flats shoes or barefoot. Walking in HHS has a slight effect on hip kinematics, with biomechanical changes and adaptations concentrated in the knee and foot-ankle complex. Females wearing HHS performed greater ground reaction forces earlier, accompanied by an anterior shift in plantar pressure compared with those wearing flat shoes/barefoot. Furthermore, large effect sizes indicate that wearing HHS resulted in poor static and dynamic balance. CONCLUSION: Spatiotemporal, kinematic, kinetic and balance variables are affected by wearing HHS. The effect of specific heel heights on women's biomechanics would benefit from further research.

Age-Related Changes in Plantar Sensation and Ankle Proprioception in Adolescents to Older Adults.

BACKGROUND: Plantar sensation and ankle proprioception occur in a stage-like variance across the life span. However, changes in adolescents, young adults, middle-aged adults, and older adults remain unclear. The aim of this study was to investigate the differences of plantar sensation and ankle proprioception in adolescents to older adults. METHODS: A total of 212 participants were recruited in the study and were divided into four groups, including adolescents (n = 46), young adults (n = 55), middle-aged adults (n = 47), and older adults (n = 54). Plantar tactile sensitivity/tactile acuity/vibration threshold and ankle movement threshold/joint position sense/force sense were assessed in all groups. The Kruskal-Wallis H test was used to analyze the differences in Semmes-Weinstein monofilaments between different age groups in different plantar positions. One-way analysis of variance was used to determine differences in foot vibration threshold, two-point discrimination, and ankle proprioception between different age groups. RESULTS: Significant differences were found in the Semmes-Weinstein monofilament test (p < .001), the two-point discrimination test (p < .05), and the vibration threshold test (p < .05) in the six tested plantar positions among adolescents, young adults, middle-aged adults, and older adults. For ankle proprioception, significant differences were found in movement thresholds in ankle plantar flexion (p = .01), ankle dorsiflexion (p < .001), ankle inversion (p < .001), and ankle eversion (p < .001), as well as relative absolute errors in the ankle force senses of ankle plantar flexion (p = .02) and ankle dorsiflexion (p = .02) across the four age groups. CONCLUSION: Plantar sensation and ankle proprioception were sensitive in adolescents and young adults than in middle-aged adults and older adults.

Catalytic Antibodies: Design, Expression, and Their Applications in Medicine.

Catalytic antibodies made it feasible to develop new catalysts, which had previously been the subject of research. Scientists have discovered natural antibodies that can hydrolyze substrates such as nucleic acids, proteins, and polysaccharides during decades of research, as well as several ways of producing antibodies with specialized characteristics and catalytic functions. These antibodies are widely used in chemistry, biology, and medicine. Catalytic antibodies can continue to play a role and even fully prevent the emergence of autoimmune disorders, especially in the field of infection and immunity, where the process of its occurrence and development often takes a long time. In this work, the development, design and evolution methodologies, and the expression systems and applications of catalytic antibodies, are discussed. Trial registration: not applicable.

Can haze warning policy reduce traffic accidents: evidence from China.

Haze pollution may decrease drivers' driving performance by worsening their physical and psychological states. This paper explores the effects of haze warning policy on traffic accidents for the first time. We use the daily-city traffic accident data from 2016 to 2019 in China and construct Regression Discontinuity (RD) strategies based on the warning signal thresholds of PM2.5 concentration for estimations. The results show that one yellow warning and one orange warning can reduce traffic accidents by 8.8% and 13.1% on that day respectively, while the red warning does not work significantly possibly due to the self-perceived channel rather than the warning-signal channel. We also find that the effects may vary among different groups of drivers, vehicles, and roads. Our results prove that the haze warning policy is a non-negligible tool to reduce traffic accidents, which is useful to policy-making both related to haze pollution regulation and transportation safety.

BMPR1A promotes ID2-ZEB1 interaction to suppress excessive endothelial to mesenchymal transition.

AIMS: Components of bone morphogenetic protein (BMP) signalling have been implicated in both pathogenesis of pulmonary arterial hypertension (PAH) and endothelial-mesenchymal transition (EndoMT). In particular, the importance of BMP type 2 receptor in these processes has been extensively analysed. However, the contribution of BMP type 1 receptors (BMPR1s) to the onset of PAH and EndoMT remains poorly understood. BMPR1A, one of BMPR1s, was recently implicated in the pathogenesis of PAH, and was found to be down-regulated in the lungs of PAH patients, neither the downstream mechanism nor its contribution to EndoMT has been described. Therefore, we aim to delineate the role of endothelial BMPR1A in modulating EndoMT and pathogenesis of PAH. METHODS AND RESULTS: We find that BMPR1A knockdown in endothelial cells (ECs) induces hallmarks of EndoMT, and deletion of endothelial Bmpr1a in adult mice (Bmpr1aiECKO) leads to development of PAH-like symptoms due to excessive EndoMT. By lineage tracing, we show that endothelial-derived smooth muscle cells are increased in endothelial Bmpr1a-deleted mice. Mechanistically, we identify ZEB1 as a primary target for BMPR1A in this setting; upon BMPR1A activation, ID2 physically interacts and sequesters ZEB1 to attenuate transcription of Tgfbr2, which in turn lowers the responses of ECs towards transforming growth factor beta (TGFß) stimulation and prevents excessive EndoMT. In Bmpr1aiECKO mice, administering endothelial targeting lipid nanoparticles containing siRNA against Tgfbr2 effectively ameliorate PAH, reiterating the importance of BMPR1A-ID2/ZEB1-TGFBR2 axis in modulating progression of EndoMT and pathogenesis of PAH. CONCLUSIONS: We demonstrate that BMPR1A is key to maintain endothelial identity and to prevent excessive EndoMT. We identify BMPR1A-induced interaction between ID2 and ZEB1 is the key regulatory step for onset of EndoMT and pathogenesis of PAH. Our findings indicate that BMPR1A-ID2/ZEB1-TGFBR2 signalling axis could serve as a potential novel therapeutic target for PAH and other EndoMT-related vascular disorders.

Mapping the early life gut microbiome in neonates with critical congenital heart disease: multiomics insights and implications for host metabolic and immunological health.

BACKGROUND: The early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD. METHODS: Deep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis. RESULTS: Gut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD. CONCLUSIONS: We demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD. Video Abstract.

Antibiotic Toxicity Isolated and as Binary Mixture to Freshwater Algae Raphidocelis subcapitata: Growth Inhibition, Prediction Model, and Environmental Risk Assessment.

Antibiotics in aqueous environments can have extremely adverse effects on non-targeted organisms. However, many research projects have only focused on the toxicological evaluation of individual antibiotics in various environments. In the present work, individual and binary mixture toxicity experiments have been conducted with the model organism Raphidocelis subcapitata (R. subcapitata), and a mixture concentration-response curve was established and contrasted with the estimated effects on the basis of both the concentration addition (CA) and the independent action (IA) models. In addition, different risk assessment methods were used and compared to evaluate the environmental risk of binary mixtures. The toxic ranking of the selected antibiotics to R. subcapitata was erythromycin (ERY) > sulfamethoxazole (SMX) > sulfamethazine (SMZ). In general, the conclusion of this study is that the adverse effects of binary mixtures are higher than the individual antibiotics. The CA model and RQSTU are more suitable for toxicity prediction and risk assessment of binary mixtures. This study reveals the potential ecological risks that antibiotics and their mixtures may pose to water ecosystems, thus providing scientific information for environmental quality regulation.