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- Chen, DS, et al.
(författare)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Tidskriftsartikel (refereegranskat)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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- Chen, NS, et al.
(författare)
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Diagnosis, differential diagnosis, and treatment for sudden sensorineural hearing loss: Current otolaryngology practices in China
- 2023
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 14, s. 1121324-
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Tidskriftsartikel (refereegranskat)abstract
- Although sudden sensorineural hearing loss (SSNHL) has been attempted to be understood for 70 years, diagnosis and treatment strategies still have strong heterogeneity worldwide, which are reflected in the guidelines issued by countries and the clinical practice of otolaryngologists.MethodsQuestionnaires were sent to registered otolaryngologists nationwide via an online questionnaire system. We investigated the current views and clinical practices of otolaryngologists in mainland China about the diagnosis, examination, and treatment strategies of SSNHL.ResultsMost otolaryngologists supported diagnostic classification via audiograms. Regional economic situation and hospital grade affected application strategies for differential diagnosis. Regarding corticosteroid therapy, 54.9% of respondents opted to discontinue the drug 5 days after systemic administration. Both intratympanic therapy and post-auricular injections were selected by more than half of the respondents as initial and salvage treatments.DiscussionChinese otolaryngologists exhibit heterogeneity in clinical practices for SSNHL, including distinct approaches to combination therapy and local application of steroids. This study pointed out Chinese doctors' similarities, differences, and unique strategies in diagnosing and treating SSNHL and analyzed the possible reasons to help the world understand the current otolaryngology practices in China.
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- Guo, JP, et al.
(författare)
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Sequencing of the MHC region defines HLA-DQA1 as the major genetic risk for seropositive rheumatoid arthritis in Han Chinese population
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:6, s. 773-780
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Tidskriftsartikel (refereegranskat)abstract
- The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC.MethodsWe first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case–control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants.ResultsHLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10−36, OR=2.29). DRβ1:37N had an independent protective effect (p=5.81×10−16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRβ1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.ConclusionsWe provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.
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- Li, WM, et al.
(författare)
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Plasma metabolomics and lipidomics signatures of motoric cognitive risk syndrome in community-dwelling older adults
- 2022
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Ingår i: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14, s. 977191-
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Tidskriftsartikel (refereegranskat)abstract
- Motoric cognitive risk syndrome (MCR) is characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Metabolomics and lipidomics may potentiate disclosure of the underlying mechanisms of MCR.MethodsThis was a cross-sectional study from the West China Health and Aging Trend cohort study (WCHAT). The operational definition of MCR is the presence of SCCs and SG without dementia or mobility disability. The test and analysis were based on untargeted metabolomics and lipidomics, consensus clustering, lasso regression and 10-fold cross-validation.ResultsThis study enrolled 6,031 individuals for clinical analysis and 577 plasma samples for omics analysis. The overall prevalence of MCR was 9.7%, and the prevalence of MCR-only, assessed cognitive impairment-only (CI-only) and MCR-CI were 7.5, 13.3, and 2.1%, respectively. By consensus clustering analysis, MCR-only was clustered into three metabolic subtypes, MCR-I, MCR-II and MCR-III. Clinically, body fat mass (OR = 0.89, CI = 0.82–0.96) was negatively correlated with MCR-I, and comorbidity (OR = 2.19, CI = 1.10–4.38) was positively correlated with MCR-III. Diabetes mellitus had the highest ORs above 1 in MCR-II and MCR-III (OR = 3.18, CI = 1.02–9.91; OR = 2.83, CI = 1.33–6.04, respectively). The risk metabolites of MCR-III showed relatively high similarity with those of cognitive impairment. Notably, L-proline, L-cystine, ADMA, and N1-acetylspermidine were significantly changed in MCR-only, and PC(40:3), SM(32:1), TG(51:3), eicosanoic acid(20:1), methyl-D-galactoside and TG(50:3) contributed most to the prediction model for MCR-III.InterpretationPre-dementia syndrome of MCR has distinct metabolic subtypes, and SCCs and SG may cause different metabolic changes to develop MCR.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Shen, LY, et al.
(författare)
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The Effectiveness of an Educational Intervention on Knowledge, Attitudes and Reported Practices on Antibiotic Use in Humans and Pigs: A Quasi-Experimental Study in Twelve Villages in Shandong Province, China
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to evaluate the effectiveness of an intervention for residents in rural China on knowledge, attitudes and reported practices (KAP) on antibiotic use in humans and pigs. A quasi-experimental study was conducted in 12 villages in rural Shandong province, divided into intervention and control groups, covering a two-year period from July 2015 to June 2017. A package of health education-based interventions including training sessions, speakerphone messages, posters and handbooks for residents was developed and implemented over a one-year period to improve the use of antibiotics in humans and pigs. The intervention net effects were evaluated by Difference-in-Difference (DID) analysis based on responses to a questionnaire concerning KAP towards antibiotic use in humans and pigs. A total of 629 participants completed both baseline and post-trial questionnaires, including 127 participants with backyard pig farms. Significant improvements were found in KAP towards antibiotic use in humans, but changes related to antibiotic use for pigs were not significant. Participants who were in the intervention group (p < 0.001) were more likely to have improved their knowledge on antibiotic use in humans. Participants who had higher attitude scores were less likely to report self-medicating with stored antibiotics in the previous year (p < 0.001). Our results suggest that our health education-based intervention was effective in improving KAP on human antibiotic use, but it had little effect regarding antibiotic use for pigs.
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- Hosaka, K, et al.
(författare)
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Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3704-
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Tidskriftsartikel (refereegranskat)abstract
- FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2+ tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2+ pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2+ tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2+ breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
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- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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- Sun, XT, et al.
(författare)
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Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism
- 2022
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 71:1, s. 129-147
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy.DesignTwo unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33–ST2–CXCL3–CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models.ResultsIL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33–ST2–MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3–CXCR2 signalling. Type III collagen was identified as the CXCL3–CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis.ConclusionsOur work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.
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