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Objective To analyze the effect of asymptomatic carotid atherosclerosis on the progression of cerebral small vessel disease (CSVD) in Shunyi cohort community population. Methods A total of 658 residents aged ≥ 35 years old from Shunyi cohort population (from June 2013 to April 2016) were selected as study subjects. Carotid ultrasound was used to assess the presence of baseline carotid plaque, and CSVD progression was assessed by baseline and follow ⁃ up MRI, which included lacunes, cerebral microbleeds (CMBs) and white matter hyperintensity (WMH). Univariate and multivariate Logistic regression was used to analyze the effect of carotid plaque on incident lacunes or CMBs, and linear regression was used to analyze the linear correlation between baseline carotid plaque and WMH progression. Results Among 658 people 250 people (37.99%) had carotid plaque at baseline. After (5.57 ± 0.49) years of follow⁃up, 70 people (10.64%) developed incident lacunes and 56 people (8.51%) had incident CMBs. The annual WMH progression was 0.28 (0.14, 0.55) cm3/year. Logistic regression analysis showed the presence of baseline carotid plaque significantly predicted incident CMBs (OR = 2.411, 95%CI: 1.240- 4.687; P = 0.009). Conclusions Prensence of carotid plaque increased CMBs progression during five⁃year follow⁃up, but the influence on lacunes and WMH progression requires a longer cumulative effect.

Protein modifications such as post-translational modifications (PTMs) and sequence variants (SVs) occur frequently during protein biosynthesis and have received great attention by biopharma industry and regulatory agencies. In this study, an aberrant peak near light chain (LC) was observed in the non-reduced capillary electrophoresis sodium dodecyl sulfate (nrCE-SDS) electrophoretogram during cell line development of one bispecific antibody (BsAb) product, and the detected mass was about 944 Da higher than LC. The corresponding peak was then enriched by denaturing size-exclusion chromatography (SEC-HPLC) and further characterized by nrCE-SDS and peptide mapping analyses. De novo mass spectra/mass spectra (MS/MS) analysis revealed that the aberrant peak was LC related sequence variant, with the truncated C-terminal sequence “SFNR” (“GEC”deleted) linked with downstream SV40 promotor sequence “EAEAASASELFQ”. The unusual sequence was further confirmed by comparing with the direct synthetic peptide “SFNREAEAASASELFQ”. It was demonstrated by mRNA sequencing of the cell pool that the sequence variant was caused by aberrant splicing at the transcription step. The prepared product containing this extension variant maintained well-folded structure and good functional properties though the LC/Heavy chain (HC) inter-chain disulfide was not formed. Several control strategies to mitigate the risk of this LC related sequence variant were also proposed.

Some immune-mediated diseases may originate in early childhood. The authors mapped eQTLs and response eQTLs to various stimuli in neonatal myeloid cells and T cells, and revealed their potential role in immune-mediated diseases using colocalisation and Mendelian randomisation.

Introduction The thyroid cancer incidence has been increasing all over the world. However, the aetiology of thyroid cancer remains unclear. A growing body of evidence suggested exposure to persistent organic pollutants (POPs) may play a role in the initiation of thyroid cancer, but the results are generally inconsistent across studies. This review aims to synthesise the evidence for the health effects of POPs on the risk of thyroid cancer.Methods and analysis This protocol was reported in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) statements. A comprehensive search, including electronic database search (eg, PubMed, Embase, ProQuest and CNKI), website search and manual search, will be performed to identify all eligible studies. The Population, Exposure, Comparator and Outcome framework was used to clarify the inclusion and exclusion criteria. The Newcastle-Ottawa Scale will be used to assess the quality of included studies. Maximally adjusted effect estimates from individual studies will be summarised with random-effect models in a conservative manner. I2 statistics and Q-tests will be used to test the heterogeneity across studies. We will perform extensive sensitivity analyses, such as confounding risk ratio (confounding), E-value, fixed-effect models, excluding the most relatively weighted study, including only the high-quality studies and many predesigned subgroup analyses, etc. The findings will be reported in accordance to the PRISMA guidelines.Ethics and dissemination Ethical approval is not required in this systematic review of published literatures. The results will be published in a peer-reviewed journal and presented at relevant conferences.PROSPERO registration number CRD42020181343.

Aluminum composites reinforced by graphene nanoplates(GNP) with a mass fraction of 0.5% (0.5 wt.% GNP/Al) were fabricated using cold pressing and hot pressing. An orthogonal test was used to optimize the fabrication parameters. Ball milling time, ball milling speed, and ultrasonic time have the largest influence on the uniformity of the graphene in the composites. Afterwards, the microstructure, interfacial properties, and fracture morphology of the composites obtained with different parameters were further analyzed. The results show that ball milling time and ball milling speed have obvious influences on the mechanical properties of the composite. In this paper, when the ball milling speed is 300 r/min and the ball milling time is 6 h, the dispersion uniformity of graphene in the 0.5 wt.% GNP/Al composite is the best, the agglomeration is the lowest, and the mechanical properties of the composites are the best, among which the tensile strength is 156.8 MPa, 56.6% higher than that of pure aluminum fabricated by the same process (100.1 MPa), and the elongation is 19.9%, 39.8% lower than that of pure aluminum (33.1%).

Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk ‘atopic’ cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma.

Background: The aim of this study was to compare 6 weeks short-term moderate intensity aerobic exercise and dieting on serum metabolomics and cardio-metabolic risk factors in pre-menopausal women. Methods: Ninety previously inactive overweight and obese (BMI 25–35 kg/m2) women (age 41.5 ± 7.6 years) were randomized to either a 6-week Nordic walking exercise program (EX, n = 45) or dietary counseling group (DI, n = 45). Body composition, serum glucose, insulin and lipids were measured. Serum low-molecular-weight metabolites and lipid constituents were analyzed by nuclear magnetic resonance spectroscopy. Measurements were done at baseline and 7 days after the last training session. Results: Six weeks aerobic exercise program yielded reductions in serum free fatty acids (−34.7%, 95% confidence interval (CI), −50 to −18, p

Anti-aging effect of Radix polygoni multiflori preparata in aging mice model was examined by bioassay method and explore new model of quality control of Traditional Chinese Medicine. Model of aging mice induced by D-galactose were used. The activity of senescence associated molecular markers such as superoxide dismutase, malondialdehyde and glutathione peroxidase in serum or homogenate were determined to evaluate the anti-aging activity. The results showed that the polysaccharide content in the 0.4, 0.8 g/mL decoction were 80.1, 160.2 mg/mL respectively. The HPLC results showed that stibene glucoside content in the 0.4 and 0.8 g/mL decoction were 404 and 808 mg/mL respectively. Experimental results showed that 10 week-old mice were the most sensitive to SOD activity in homogenate. In conclusion, Radix polygoni multiflori preparata has anti-aging effect probably by removing ROS.

BackgroundThe gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults.ObjectiveWe sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD).MethodsShallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status.ResultsA total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities.ConclusionsThe gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.

Asthma is a genetically complex, chronic lung disease defined clinically as episodic airflow limitation and breathlessness that is at least partially reversible, either spontaneously or in response to therapy. Whereas asthma was rare in the late 1800s and early 1900s, the marked increase its incidence and prevalence since the 1960’s points to substantial gene x environment interactions occurring over a period of years, but these interactions are very poorly understood1-6. It is widely believed that the majority of asthma begins during childhood and manifests first as intermittent wheeze. However, wheeze is also very common in infancy and only a subset of wheezy children progress to persistent asthma for reasons that are largely obscure. Here, we review the current literature regarding causal pathways leading to early asthma development and chronicity. Given the complex interactions of many risk factors over time eventually leading to apparently multiple asthma phenotypes, we suggest that deeply phenotyped cohort studies combined with sophisticated network models will be required to derive the next generation of biological and clinical insights in asthma pathogenesis.

In this reflective essay, I share lessons learned when COVID-19 necessitated immediate changes to service-learning during the spring 2020 semester. The pandemic created an environment that heightened awareness about meeting underrepresented students' needs and the benefits of solidarity and reciprocity when collaborating with community partners. As the pandemic unfolded, my focus shifted from honoring commitments to community partners and course learning objectives to recognizing that the complex realities of students' lives made being responsive to their needs paramount. One nontraditional student serves as a case study; her story underscores the deep ways the pandemic affected a student's personal and professional life. I close the article with four generalizable lessons learned that faculty can employ in support of students' success in service-learning: exercising solidarity, reciprocity, and flexibility; providing guidance in project selection; serving as model learner; and embedding support for parenting and caregiving students.

PURPOSE: To examine the prevalence of refractive errors and prevalence and causes of vision loss among preschool and school children in East China. METHODS: Using a random cluster sampling in a cross-sectional school-based study design, children with an age of 4-18 years were selected from kindergartens, primary schools, and junior and senior high schools in the rural Guanxian County and the city of Weihai. All children underwent a complete ocular examination including measurement of uncorrected (UCVA) and best corrected visual acuity (BCVA) and auto-refractometry under cycloplegia. Myopia was defined as refractive error of ≤-0.5 diopters (D), high myopia as ≤ -6.0D, and amblyopia as BCVA ≤ 20/32 without any obvious reason for vision reduction and with strabismus or refractive errors as potential reasons. RESULTS: Out of 6364 eligible children, 6026 (94.7%) children participated. Prevalence of myopia (overall: 36.9 ± 0.6%;95% confidence interval (CI):36.0,38.0) increased (P

Vitamin D is well known for its regulatory role in calcium and phosphate homeostasis, but its role in muscle mass and strength during growth remains inconclusive. We explored the association of serum 25-hydroxyvitamin D (25(OH)D) with muscle development in girls from 11 to 18-years old. Whole body lean tissue mass (LMWB), appendicular lean mass (aLM), muscle cross-sectional area at the lower leg (mCSA), maximal voluntary contraction of elbow flexors (MVC elbow) and knee extensors (MVC knee) were assessed in 217 girls aged 10-13 years (at baseline), 215 in 2-year and 226 in 7.5-year follow-up. Serum concentration of 25(OH)D and intact parathyroid hormone (PTH) were analyzed retrospectively and girls were categorized according to their 25(OH)D levels (consistently insufficient 25(OH)D GLL 50 nmol/l from baseline to 7-year follow-up). We found that 25(OH)D level declined until menarche (p

Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco-dynamics could greatly contribute to understanding various aspects of functional diversity.