The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective:To explore the clinical characteristics, outcomes and influencing factors of influenza A virus-induced pneumonia in renal allograft recipients.Methods:During the 2015-2019 influenza season, 21 patients with influenza A virus-induced pneumonia after renal transplantation(RT)were prospectively recruited with 42 matched non-immunocompromised inpatients with influenza A virus-induced pneumonia.Clinical data, outcomes and follow-up observations after discharge were collected for analyzing the clinical characteristics of influenza A virus-induced pneumonia after RT.Continuous variables were compared by t-test or Mann-Whitney U test.And categorical variables were compared by Chi-Square test.Results:The median time after RT was 5(0.88, 10.50)years for RT recipients.In RT group, none received seasonal influenza vaccination with a vaccination rate of zero.The influenza vaccination rate of non-immunocompromised patients in current season was 42.86%(18/42)and inter-group difference was statistically significant( P<0.001). The levels of hemoglobin, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase in RT recipients were(108.47±22.39)g/L, 21.00(16.00, 46.50)U/L, 15.00(12.00, 21.00)U/L and 314.00(207.25, 374.00)U/L.And the values were lower than those of non-immunocompromised patients[(130.24±21.74)g/L, 48.50(36.00, 79.50)U/L, 32.00(20.00, 52.25)U/L and 466.00(227.00, 781.75)U/L]. The differences were statistically significant( P=0.001, P<0.001, P<0.001, P=0.005). The levels of blood urea nitrogen and serum creatinine were 8.27(6.69, 12.48)mmol/L and 130.30(94.15, 204.70)mmol/L versus 5.42(3.37, 7.65)mmol/L and 65.90(48.98, 82.13)mmol/L in non-immunocompromised patients.The differences were statistically significant(all P< 0.001). No significant differences existed in the levels of C-reactive protein and procalcitonin between RT recipients and non-immunocompromised patients( P=0.774 and 0.821). The level of ESR and oxygenation index at admission were 39.00(13.00, 53.00)mm/h and(306.95±90.97)in renal recipients and 18.00(11.50, 23.00)mm/h and(200.17±116.35)in non-immunocompromised patients.The differences were statistically significant( P=0.045 and 0.001). Imaging studies indicated that multiple lobar involvement was a major imaging feature in both renal recipients and non-immunocompromised patients.The probability of pulmonary consolidation was 33.33%(7/21)in renal recipients and it was lower than that in non-immunocompromised patients.And the probability of pleural effusion was 42.86%(9/21)and it was higher than control.The inter-group differences were statistically significant( P=0.020 & 0.024). Rate of mechanical ventilation, CRRT and mortality were 42.86%(9/21), 23.81%(5/21)and 28.57%(6/21). All of them were higher than non-immunocompromised patients[21.43%(9/42), 9.52%(4/42)and 9.52%(4/42)]. However, there was no significant inter-group difference( P=0.076, 0.252 & 0.113). The median score of CURB-65 was 1(0.5, 1). Conclusions:Renal damage is prominent in hospitalized patients with influenza A virus-induced pneumonia after RT.There are a high rate of mechanical ventilation and CRRT during hospitalization and a high mortality.The prognosis remains poor for hospitalized patients with influenza A virus-induced pneumonia after RT.No matter how serious their conditions are at admission, they need to be closely monitored and aggressively treated.

Referring to Building Block Innovation concepts, the article addresses the development and current practices of the doctoral education in the intersection of medicine and engineering from modules such as scientific research, tutor guidance, curriculum study, integration of study and industry, and evaluation mechanism. The article proposes inspiration and recommendation to further improve the quality of the doctoral education from dimensions including the management system, the organization system, and the education system.

Since the enrollment in 2002, the cultivation model of "4+4" program of clinical medicine in Shanghai Jiao Tong University School of Medicine has been continuously explored and practiced. With the goal of cultivating high-level compound outstanding medical innovative talents with multi-disciplinary cross-capacity, through strengthening the heuristic teaching, establishing the medical-engineering cross-course, emphasizing the training of scientific research ability, and taking teaching reform in the basic clinical single-circulation organ system integration course, we have established a talent training system with the characteristics of Shanghai Jiao Tong University School of Medicine, which is characterized by "thick foundation, strong practice, re-transformation, shaping norms, and international integration", and intend to make further exploration in the field of post-graduation education convergence.