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1.
Hum Genomics ; 17(1): 77, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592328

RESUMO

BACKGROUND: Thalassemia is an extremely prevalent monogenic inherited blood disorder in southern China. It is important to comprehensively understand the molecular spectrum of thalassemia in an area with such a high prevalence of thalassemia before taking appropriate actions for the prevention and treatment of this disorder. Herein, we explored the clinical feasibility of using next-generation sequencing (NGS) for large-scale population screening to illustrate the prevalence and spectrum of thalassemia in Southern Jiangxi. METHODS: Blood samples collected from 136,312 residents of reproductive age in Southern Jiangxi were characterized for thalassemia by NGS. A retrospective analysis was then conducted on blood samples determined to be positive for thalassemia. RESULTS: In total, 19,827 (14.545%) subjects were diagnosed as thalassemia carriers, and the thalassemia prevalence rate significantly varied by geographical region (p < 0.001). A total of 40 α-thalassemia genotypes including 21 rare genotypes were identified, with -@-SEA/αα being the most prevalent genotype. 42 ß-thalassemia genotypes including 27 rare genotypes were identified, with the most common mutation IVS II-654 C > T accounting for 35.257% of these ß-thalassemia genotypes. Furthermore, 74 genotypes were identified among 608 individuals with combined α- and ß-thalassemia. Notably, most individuals with rare thalassemia mutations had mildly abnormal hematologic parameters including microcytic hypochromia. CONCLUSIONS: Our findings demonstrate the great heterogeneity and diverse spectrum of thalassemia in Southern Jiangxi, emphasizing the importance and necessity of persistent prevention and control of thalassemia in this region. Additionally, our findings further suggest that NGS can effectively identify rare mutations and reduce the misdiagnosis rate of thalassemia.


Assuntos
Talassemia alfa , Talassemia beta , Humanos , Talassemia beta/epidemiologia , Talassemia beta/genética , Estudos Retrospectivos , Talassemia alfa/epidemiologia , Talassemia alfa/genética , Sequenciamento de Nucleotídeos em Larga Escala , China/epidemiologia
2.
Cell Biol Int ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894536

RESUMO

Lung adenocarcinoma (LUAD) is the most common subtype of NSCLC, characterized by poor prognosis and frequently diagnosed at advanced. While previous studies have demonstrated pleckstrin-2 (PLEK2) as aberrantly expressed and implicated in tumorigenesis across various tumor types, including LUAD, the molecular mechanisms underlying PLEK2-mediated LUAD progression remain incompletely understood. In this study, we obtained data from The Cancer Genome Atlas (TCGA) database to assess PLEK2 expression in LUAD, a finding further confirmed through analysis of human tissue specimens. PLEK2-silenced LUAD cellular models were subsequently constructed to examine the functional role of PLEK2 both in vitro and in vivo. Our results showed elevated PLEK2 expression in LUAD, correlating with poor patients' prognosis. PLEK2 knockdown led to a significant suppression of LUAD cell proliferation and migration, accompanied by enhanced apoptosis. Moreover, tumor growth in mice injected with PLEK2-silencing LUAD cells was impaired. Gene expression profiling and Co-IP assays suggested direct interaction between PLEK2 and SPC25, with downregulation of SPC25 similarly impairing cell proliferation and migration. Additionally, we revealed phosphoinositide 3-kinase (PI3K)/AKT signaling activation as requisite for PLEK2-induced malignant phenotypes in LUAD. Collectively, our findings underscore PLEK2's oncogenic potential in LUAD, suggesting its utility as a prognostic indicator and therapeutic target for LUAD management.

3.
Molecules ; 29(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38611798

RESUMO

Efforts to develop high-performance electrocatalysts for the hydrogen evolution reaction (HER) are of utmost importance in ensuring sustainable hydrogen production. The controllable fabrication of inexpensive, durable, and high-efficient HER catalysts still remains a great challenge. Herein, we introduce a universal strategy aiming to achieve rapid synthesis of highly active hydrogen evolution catalysts using a controllable hydrogen insertion method and solvothermal process. Hydrogen vanadium bronze HxV2O5 was obtained through controlling the ethanol reaction rate in the oxidization process of hydrogen peroxide. Subsequently, the intermetallic PtCoVO supported on two-dimensional graphitic carbon nitride (g-C3N4) nanosheets was prepared by a solvothermal method at the oil/water interface. In terms of HER performance, PtCoVO/g-C3N4 demonstrates superior characteristics compared to PtCo/g-C3N4 and PtCoV/g-C3N4. This superiority can be attributed to the notable influence of oxygen vacancies in HxV2O5 on the electrical properties of the catalyst. By adjusting the relative proportions of metal atoms in the PtCoVO/g-C3N4 nanomaterials, the PtCoVO/g-C3N4 nanocomposites show significant HER overpotential of η10 = 92 mV, a Tafel slope of 65.21 mV dec-1, and outstanding stability (a continuous test lasting 48 h). The nanoarchitecture of a g-C3N4-supported PtCoVO nanoalloy catalyst exhibits exceptional resistance to nanoparticle migration and corrosion, owing to the strong interaction between the metal nanoparticles and the g-C3N4 support. Pt, Co, and V simultaneous doping has been shown by Density Functional Theory (DFT) calculations to enhance the density of states (DOS) at the Fermi level. This augmentation leads to a higher charge density and a reduction in the adsorption energy of intermediates.

4.
Langmuir ; 39(38): 13688-13694, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37683112

RESUMO

In this work, a "fish cage" material for trapping Pb(II) ions has been successfully obtained, which is a novel clathrate functionalized metal-oganic framework (Cage-MOF) by introducing free adsorption sites (SO42-). The three-dimensional (3D) cage structure of Cage-MOF gives it a larger contact area and can capture "swimming fish" (Pb(II)) like a "fishing cage" in a water solution. This is the first high-efficiency adsorption material obtained by introducing free coordination groups. Cage-MOF not only has excellent water stability but also improves the selectivity and affinity for Pb(II) ions in water because of the presence of sulfate adsorption sites, and its adsorption capacity is as high as 806 mg/g. This work shows a novel and effective idea for the synthesis of water restoration materials.

5.
Phys Chem Chem Phys ; 25(32): 21661-21672, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37551545

RESUMO

Since electrocatalytic oxygen evolution (OER) is a four-electron transfer reaction with very slow kinetics, there is great competition to develop cheap, durable and efficient catalysts for oxygen evolution. A molecular model is designed for density functional theory (DFT) simulation calculations to guide the experiment, and this hypothesis is fully supported by the experimental data. Herein, regulating the composition and morphology of the bimetallic VCo and MoCo sulfide and monometallic sulfide nanoparticles (NPs) at the oil-water interface was achieved via a one-step hydrothermal method for efficient and durable OER electrocatalysts. Compared to CoS and MoCoS, the VCoS NPs show superior OER performance. By adjusting the atomic composition ratio of the VCoS nanoparticles, the VCoS NPs (1 : 2 : 1.5 mole ratio) showed a significant OER overpotential η = 255 mV (10 mA cm-2), and their outstanding stability was demonstrated after 48 h of continuous testing. The CoS and MoCoS NPs were also tested for comparison. Density functional theory (DFT) calculations showed that appropriate V doping (VCoS) can heighten the density of states (DOS) of the Fermi level, which generates more charge density and reduces the intermediate adsorption energy. This study not only provides efficient and powerful integrated catalysts, but also details a DFT calculation model guided by experiments to regulate the oxygen insertion technology, thus leading to the design of ideal materials and enabling more far-reaching applications in electrocatalysis.

6.
Environ Res ; 236(Pt 1): 116658, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37454799

RESUMO

Seagrass meadows play vital ecological roles in the marine ecosystem. Global climate change poses considerable threats to seagrass survival. However, it is unclear how seagrass and its associated bacteria will respond under future complex climate change scenarios. This study explored the effects of ocean warming (+2 °C) and ocean acidification (-0.4 units) on seagrass physiological indexes and bacterial communities (sediment and rhizosphere bacteria) of the seagrass Thalassia hemprichii during an experimental exposure of 30 days. Results demonstrated that the synergistic effect of ocean warming and ocean acidification differed from that of one single factor on seagrass and the associated bacterial community. The seagrass showed a weak resistance to ocean warming and ocean acidification, which manifested through the increase in the activity of typical oxidoreductase enzymes. Moreover, the synergistic effect of ocean warming and ocean acidification caused a significant decrease in seagrass's chlorophyll content. Although the bacterial community diversity exhibited higher resistance to ocean warming and ocean acidification, further bacterial functional analysis revealed the synergistic effect of ocean warming and ocean acidification led to significant increases in SOX-related genes abundance which potentially supported the seagrass in resisting climate stress by producing sulfates and oxidizing hydrogen sulfide. More stable bacterial communities were detected in the seagrass rhizosphere under combined ocean warming and ocean acidification. While for one single environmental stress, simpler networks were detected in the rhizosphere. In addition, the observed significant correlations between several modules of the bacterial community and the physiological indexes of the seagrass indicate the possible intimate interaction between seagrass and bacteria under ocean warming and ocean acidification. This study extends our understanding regarding the role of seagrass associated bacterial communities and sheds light on both the prediction and preservation of the seagrass meadow ecosystems in response to global climate change.


Assuntos
Hydrocharitaceae , Água do Mar , Ecossistema , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Mudança Climática , Bactérias/genética , Oceanos e Mares , Aquecimento Global
7.
Cell Mol Life Sci ; 79(5): 272, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503385

RESUMO

Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and the major contributor to cardiovascular disease (CVD) mortality. Adipose tissue serves a primary role as a lipid-storage organ, secreting cytokines known as adipokines that affect whole-body metabolism, inflammation, and endocrine functions. Emerging evidence suggests that adipokines can play important roles in atherosclerosis development, progression, as well as regression. Here, we review the versatile functions of various adipokines in atherosclerosis and divide these respective functions into three major groups: protective, deteriorative, and undefined. The protective adipokines represented here are adiponectin, fibroblast growth factor 21 (FGF-21), C1q tumor necrosis factor-related protein 9 (CTRP9), and progranulin, while the deteriorative adipokines listed include leptin, chemerin, resistin, Interleukin- 6 (IL-6), and more, with additional adipokines that have unclear roles denoted as undefined adipokines. Comprehensively categorizing adipokines in the context of atherosclerosis can help elucidate the various pathways involved and potentially pave novel therapeutic approaches to treat CVDs.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Adipocinas/metabolismo , Adiponectina/metabolismo , Adiposidade , Aterosclerose/metabolismo , Humanos , Interleucina-6/metabolismo , Leptina/metabolismo , Obesidade/metabolismo
8.
Hemoglobin ; 47(4): 172-179, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37818638

RESUMO

We reported the identification of two rare α-thalassemia silent carriers with novel HBA1 mutations of CD 39 -C [Thr > Pro] (HBA1: c.114del; p.Thr39Profs*11) and CD 109 ACC > CCC [Thr > Pro] (HBA1: c.325A > C; p. Thr109Pro), respectively. The two probands were pregnant women diagnosed with mild hypochromic anemia or microcytic hypochromic anemia by routine blood tests. They started iron therapy before taking differential diagnosis from iron deficiency anemia. After wait and watch approach, they both accepted thalassemia genetic screening, which identified CD 39 -C [Thr > Pro] and CD 109 ACC > CCC [Thr > Pro], respectively. Due to inappropriate iron therapy, worse anemia and iron overload were noticed in the first proband, but no obvious side effect was found in both probands. Functional analysis showed that, relative to the wild type, CD 39 -C [Thr > Pro] considerably reduced the expression of the HBA1 protein while CD 109 ACC > CCC [Thr > Pro] only had a minor impact. Our study highlighted the importance of gestational thalassemia screening based on next-generation sequencing for identifying novel rare thalassemia variants and increased our understanding about the relationship between genotype and phenotype of α-thalassemia.


Assuntos
Anemia Hipocrômica , Anemia , Talassemia alfa , Feminino , Humanos , Gravidez , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Anemia Hipocrômica/diagnóstico , População do Leste Asiático , Hemoglobinas Glicadas , Ferro , Mutação , Heterozigoto
9.
Int J Mol Sci ; 24(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37047668

RESUMO

The cryopreservation of red blood cells (RBCs) holds great potential for ensuring timely blood transfusions and maintaining an adequate RBC inventory. The conventional cryoprotectants (CPAs) have a lot of limitations, and there is an obvious need for novel, efficient, and biocompatible CPAs. Here, it is shown for the first time that the addition of dimethylglycine (DMG) improved the thawed RBC recovery from 11.55 ± 1.40% to 72.15 ± 1.22%. We found that DMG could reduce the mechanical damage by inhibiting ice formation and recrystallization during cryopreservation. DMG can also scavenge reactive oxygen species (ROS) and maintain endogenous antioxidant enzyme activities to decrease oxidative damage during cryopreservation. Furthermore, the properties of thawed RBCs were found to be similar to the fresh RBCs in the control. Finally, the technique for order performance by similarity to ideal solution (TOPSIS) was used to compare the performance of glycerol (Gly), hydroxyethyl starch (HES), and DMG in cryopreservation, and DMG exhibited the best efficiency. This work confirms the use of DMG as a novel CPA for cryopreservation of RBCs and may promote clinical transfusion therapy.


Assuntos
Criopreservação , Gelo , Criopreservação/métodos , Crioprotetores/farmacologia , Crioprotetores/química , Eritrócitos , Estresse Oxidativo
10.
Molecules ; 28(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37298935

RESUMO

α-Synuclein aggregation under pathological conditions is one of the causes of related neurodegenerative diseases. PROTACs (proteolysis targeting chimeras) are bifunctional small molecules that induce a post-translational erasure of proteins via the ubiquitination of target proteins by E3 ubiquitin ligase and subsequent proteasomal degradation. However, few research studies have been conducted for targeted protein degradation of α-synuclein aggregates. In this article, we have designed and synthesized a series of small-molecule degraders 1-9 based on a known α-synuclein aggregation inhibitor sery384. In silico docking studies of sery384 with α-synuclein aggregates were accomplished to ensure that the compounds bound to α-synuclein aggregates specifically. The protein level of α-synuclein aggregates was determined to evaluate the degradation efficiency of PROTAC molecules on α-synuclein aggregates in vitro. The results show that compound 5 had the most significant degradation effect, with DC50 of 5.049 µM, and could induce the degradation of α-synuclein aggregates in a time- and dose-dependent manner in vitro. Furthermore, compound 5 could inhibit the elevation of the ROS level caused by overexpression and aggregation of α-synuclein and protect H293T cells from α-synuclein toxicity. Conclusively, our results provide a new class of small-molecule degraders and an experimental basis for the treatment of α-synuclein related neurodegenerative diseases.


Assuntos
Ubiquitina-Proteína Ligases , alfa-Sinucleína , Proteólise , alfa-Sinucleína/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
11.
Ergonomics ; 66(12): 2025-2038, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36762820

RESUMO

This study examined how large touchscreen buttons affect user task completion time, error rate, and subjective satisfaction (ease of pointing and clicking on targets). In this experiment, 31 participants completed button click tasks of square targets placed at 30 (5 × 6) different locations, with seven button sizes (10 mm, 30 mm, 50 mm, 70 mm, 90 mm, 110 mm, and 130 mm). Repeated measures ANOVAs showed that on a 65'' large touch screen (W 1428 × H 803 mm), 70 mm buttons achieved essentially the best performance in completion time, 50 mm in error rates, and 90 mm in subjective satisfaction, respectively. We also compare the differences in efficiency among different button areas and button sizes. The surrounding area and lower area require a bigger button size to achieve the best performance in terms of error rates and subjective satisfaction. The right area requires a bigger optimal button size than the left area considering error rates, while it is the opposite for subjective satisfaction.Practitioner summary: This study investigates how the size and location of buttons on the increasingly popular large touch screen affect user experience. The study reveals that 70, 50, 90 mm size buttons are recommended when speed, accuracy and satisfaction are priorities respectively. The interaction between button size and button area is significantly different. The surrounding area and lower area require a bigger button size to achieve the best performance in terms of error rate and subjective satisfaction. Considering error rates, the right area requires a bigger optimal button size than the left area, while it is opposite for subjective satisfaction. These findings could facilitate the optimal design of usable large touch screens.


Assuntos
Interface Usuário-Computador , Humanos , Desenho de Equipamento
12.
J Environ Sci (China) ; 124: 557-569, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182163

RESUMO

Atmospheric oxidizing capacity (AOC) is the fundamental driving factors of chemistry process (e.g., the formation of ozone (O3) and secondary organic aerosols (SOA)) in the troposphere. However, accurate quantification of AOC still remains uncertainty. In this study, a comprehensive field campaign was conducted during autumn 2019 in downtown of Beijing, where O3 and PM2.5 episodes had been experienced successively. The observation-based model (OBM) is used to quantify the AOC at O3 and PM2.5 episodes. The strong intensity of AOC is found at O3 and PM2.5 episodes, and hydroxyl radical (OH) is the dominating daytime oxidant for both episodes. The photolysis of O3 is main source of OH at O3 episode; the photolysis of nitrous acid (HONO) and formaldehyde (HCHO) plays important role in OH formation at PM2.5 episode. The radicals loss routines vary according to precursor pollutants, resulting in different types of air pollution. O3 budgets and sensitivity analysis indicates that O3 production is transition regime (both VOC and NOx-limited) at O3 episode. The heterogeneous reaction of hydroperoxy radicals (HO2) on aerosol surfaces has significant influence on OH and O3 production rates. The HO2 uptake coefficient (γHO2) is the determining factor and required accurate measurement in real atmospheric environment. Our findings could provide the important bases for coordinated control of PM2.5 and O3 pollution.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , Pequim , China , Monitoramento Ambiental , Formaldeído , Radical Hidroxila/análise , Ácido Nitroso , Oxidantes , Oxirredução , Ozônio/análise , Material Particulado/análise , Compostos Orgânicos Voláteis/análise
13.
Clin Immunol ; 241: 109057, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35667550

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects various organs or systems. We performed metabolomic and lipidomic profiles analyses of 133 SLE patients and 30 HCs. Differential metabolites and lipids were integrated, and then the biomarker panel was identified using binary logistic regression. We found that a combination of four metabolites or lipids could distinguish SLE from HC with an AUC of 0.998. Three lipids were combined to differentiate inactive SLE and active SLE. The AUC was 0.767. In addition, we also identified the biomarkers for different organ phenotypes of SLE. The AUCs for diagnosing SLE patients with only kidney involvement, skin involvement, blood system involvement, and multisystem involvement were 0.766, 0.718, 0.951, and 0.909, respectively. Our study succeeded in identifying biomarkers associated with different clinical phenotypes in SLE patients, which could facilitate a more precise diagnosis and assessment of disease progression in SLE.


Assuntos
Lipidômica , Lúpus Eritematoso Sistêmico , Biomarcadores , Humanos , Lipídeos , Lúpus Eritematoso Sistêmico/genética , Metabolômica
14.
Biochem Biophys Res Commun ; 618: 86-92, 2022 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-35716600

RESUMO

The transcription factor Bach2 serves as a crucial regulator of the germinal center (GC) reaction, which is required for production of high-affinity antibodies and establishment of long-lived B cell memory. However, the stage at which Bach2 controls the GC programs and the precise mechanism underlying these processes remain poorly understood. In this study, we show that genetic ablation of Bach2 in GC B cells of mice impairs their survival and maintenance, and memory B cell formation. These defects can be rescued by enforced expression of anti-apoptotic gene Bcl2. As expected, Bach2-deficient GC B cells are defective in antibody affinity maturation, but have normal somatic hyper mutation and class switch recombination of immunoglobulin genes. Mechanistically, Bach2 controls the GC programs by directly repressing pro-apoptotic gene Bim and a set of genes involved in cell stress response and metabolic processes. Thus, our work reveals the precise roles of Bach2 in the GC biology, and demonstrates that Bach2 acts as a crucial survival regulator of GC B cells, providing a key mechanism underlying GC B maintenance and B cell memory formation.


Assuntos
Linfócitos B , Fatores de Transcrição de Zíper de Leucina Básica , Centro Germinativo , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Sobrevivência Celular/fisiologia , Centro Germinativo/citologia , Centro Germinativo/imunologia , Memória Imunológica , Camundongos , Fatores de Transcrição/metabolismo
15.
Biochem Biophys Res Commun ; 627: 200-206, 2022 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-36049358

RESUMO

Breast cancer is a prevalent female malignancy and tamoxifen remains the first-line treatment for breast cancer, but tamoxifen resistance is a frequent clinical problem. Circular RNAs (circRNAs) are a bunch of noncoding RNAs with circular structures and play crucial roles in cancer development. Here, we aimed to explore the unreported function of circMET in the modulation of tamoxifen resistance of breast cancer cells. The expression of circMET was upregulated in tamoxifen-resistant breast cancer cells. The depletion of circMET significantly reduced the cell viability and proliferation in tamoxifen-resistant breast cancer cells and the co-treatment of tamoxifen promoted the effect. Mechanically, the luciferase activity of circMET and was repressed by miR-204-5p and AHR 3'UTR in the cells. The expression of miR-204-5p was elevated by circMET knockdown. The expression of AHR was downregulated by miR-204-5p or circMET depletion, while the miR-204-5p inhibitor reversed the effect of circMET depletion in cells. The overexpression of circMET enhanced the cell viability and proliferation of MCF7-Re and T47D-Re cells but miR-204-5p or AHR depletion blocked the phenotype. Clinically, the expression of circMET and AHR has enhanced in tamoxifen-resistant samples compared with tamoxifen sensitive samples, but miR-204-5p presented a revered expression in the samples. Consequently, we concluded that circular RNA circMET contributed to tamoxifen resistance of breast cancer cells by targeting miR-204-5p/AHR signaling.


Assuntos
MicroRNAs , Neoplasias , Animais , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , RNA Circular/genética , Tamoxifeno/farmacologia
16.
Microb Cell Fact ; 21(1): 111, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659293

RESUMO

BACKGROUND: Yak (Bos grunniens) mainly inhabiting Tibet Plateau, displayed a high incidence of diarrhea due to harsh living environment and nutritional deficit. Gut microbial community has been reported to be closely related to many diseases including diabetes, obesity and inflammatory bowel disease, but information regarding diarrheic influence on gut microbiota in yaks remains scarce. Here, this study was performed to investigate the gut bacterial and fungal alternations of diarrheic yaks. RESULTS: Results revealed that the gut bacterial and fungal communities of diarrheic yaks showed a distinct decline in alpha diversity, accompanied by significant shifts in taxonomic compositions. Specifically, diarrhea caused a distinct increase in the relative abundance of 1 phylum and 8 genera as well as a distinct decrease in 3 phyla and 30 genera. Fungal taxonomic analysis indicated that the relative richness of 1 phylum and 2 genera dramatically increased, whereas the relative richness of 2 phylum and 43 genera significantly decreased during diarrhea. Surprisingly, 2 bacterial genera and 5 fungal genera even cannot be detected in the gut microbiota of diarrheic yaks. CONCLUSIONS: In summary, this study indicated that the gut bacterial and fungal compositions and diversities of yaks altered significantly during diarrhea. Moreover, these findings also contribute to understanding the gut microbial composition and diversity of yaks and developing strategies to alleviate and prevent diarrhea from gut microbial perspective.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Bactérias , Bovinos , Diarreia/epidemiologia , Diarreia/veterinária
17.
Environ Sci Technol ; 56(8): 4828-4837, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35297613

RESUMO

Atmospheric nitrous acid (HONO) is a dominant precursor of hydroxyl (OH) radicals, and its formation mechanisms are still controversial. Few studies have simultaneously explored effects of different combustion processes on HONO sources. Hereby, synchronous HONO measurement in urban (BJ), suburban (XH) and rural (DBT) areas with different combustion processes is performed in the North China Plain in winter. A box model is utilized to analyze HONO formation mechanisms. HONO concentration is the highest at the DBT site (2.51 ± 1.90 ppb), followed by the XH (2.18 ± 1.95 ppb) and BJ (1.17 ± 1.20 ppb) sites. Vehicle exhaust and coal combustion significantly contribute to nocturnal HONO at urban and rural sites, respectively. During a stagnant pollution period, the NO+OH reaction and combustion emissions are more crucial to HONO in urban and rural areas; meanwhile, the heterogeneous reaction of NO2 is more significant in suburban areas. Moreover, the production rate of OH from HONO photolysis is about 2 orders of magnitude higher than that from ozone photolysis. Consequently, vehicle exhaust and coal combustion can effectively emit HONO, further causing environmental pollution and health risks. It is necessary to expand the implementation of the clean energy transition policy in China, especially in areas with substantial coal combustion.


Assuntos
Ácido Nitroso , Emissões de Veículos , China , Carvão Mineral , Radical Hidroxila
18.
Proc Natl Acad Sci U S A ; 116(37): 18550-18560, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451659

RESUMO

Excessive self-reactive and inadequate affinity-matured antigen-specific antibody responses have been reported to coexist in lupus, with elusive cellular and molecular mechanisms. Here, we report that the antigen-specific germinal center (GC) response-a process critical for antibody affinity maturation-is compromised in murine lupus models. Importantly, this defect can be triggered by excessive autoimmunity-relevant CD11c+Tbet+ age-associated B cells (ABCs). In B cell-intrinsic Ship-deficient (ShipΔB) lupus mice, excessive CD11c+Tbet+ ABCs induce deregulated follicular T-helper (TFH) cell differentiation through their potent antigen-presenting function and consequently compromise affinity-based GC selection. Excessive CD11c+Tbet+ ABCs and deregulated TFH cell are also present in other lupus models and patients. Further, over-activated Toll-like receptor signaling in Ship-deficient B cells is critical for CD11c+Tbet+ ABC differentiation, and blocking CD11c+Tbet+ ABC differentiation in ShipΔB mice by ablating MyD88 normalizes TFH cell differentiation and rescues antigen-specific GC responses, as well as prevents autoantibody production. Our study suggests that excessive CD11c+Tbet+ ABCs not only contribute significantly to autoantibody production but also compromise antigen-specific GC B-cell responses and antibody-affinity maturation, providing a cellular link between the coexisting autoantibodies and inadequate affinity-matured antigen-specific antibodies in lupus models and a potential target for treating lupus.


Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Centro Germinativo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Animais , Autoimunidade/imunologia , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Antígenos CD11/metabolismo , Estudos de Casos e Controles , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Lúpus Eritematoso Sistêmico/genética , Linfonodos/citologia , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Transdução de Sinais/imunologia , Proteínas com Domínio T/metabolismo
19.
J Card Surg ; 37(12): 5034-5040, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36403278

RESUMO

OBJECTIVES: Acute type A aortic dissection involving the aortic sinus is often combined with varying degrees of aortic regurgitation, while the structure of the aortic valve is often undamaged. The aim of this study was to evaluate the clinical effects of reconstruction of the aortic sinus using patches in patients with acute type A aortic dissection. METHODS: From January 2016 to December 2019, 52 patients with acute type A aortic dissection involving the aortic sinus were treated with aortic sinus reconstruction using pericardial or artificial vascular patches. The clinical and follow-up data were summarized. RESULTS: Bovine pericardial patches were used in 31 cases and artificial vascular patches were used in 21 cases for aortic sinus reconstruction. Cardiopulmonary bypass time was (250.4 ± 65.7) min, aortic cross clamp time was (143.7 ± 42.3) min, and hypothermic circulatory arrest time was (9.6 ± 8.1) min. Three patients died in hospital, with a mortality rate of 5.8%. Fifteen patients (28.8%) had mild postoperative aortic regurgitation. The follow-up duration was 40 ± 12 (range, 21-66) months. Five patients (10.2%) developed moderate to severe aortic regurgitation and 3 (6.1%) died during the follow-up period. CONCLUSIONS: The application of patches for aortic sinus reconstruction is a relatively easy method in aortic valve-sparing root reconstruction for acute type A aortic dissection involving the aortic sinus. The clinical and follow-up results are favorable.


Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Insuficiência da Valva Aórtica , Seio Aórtico , Humanos , Animais , Bovinos , Aneurisma Aórtico/cirurgia , Seio Aórtico/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Dissecção Aórtica/cirurgia , Aorta/cirurgia , Valva Aórtica/cirurgia , Resultado do Tratamento
20.
Int J Mol Sci ; 23(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35955596

RESUMO

The cryopreservation of red blood cells (RBCs) plays a key role in blood transfusion therapy. Traditional cryoprotectants (CPAs) are mostly organic solvents and may cause side effects to RBCs, such as hemolysis and membrane damage. Therefore, it is necessary to find CPAs with a better performance and lower toxicity. Herein, we report for the first time that N-[Tri(hydroxymethyl)methyl]glycine (tricine) showed a great potential in the cryopreservation of sheep RBCs. The addition of tricine significantly increased the thawed RBCs' recovery from 19.5 ± 1.8% to 81.2 ± 8.5%. The properties of thawed RBCs were also maintained normally. Through mathematical modeling analysis, tricine showed a great efficiency in cryopreservation. We found that tricine had a good osmotic regulation capacity, which could mitigate the dehydration of RBCs during cryopreservation. In addition, tricine inhibited ice recrystallization, thereby decreasing the mechanical damage from ice. Tricine could also reduce oxidative damage during freezing and thawing by scavenging reactive oxygen species (ROS) and maintaining the activities of endogenous antioxidant enzymes. This work is expected to open up a new path for the study of novel CPAs and promote the development of cryopreservation of RBCs.


Assuntos
Antioxidantes , Gelo , Animais , Antioxidantes/farmacologia , Criopreservação , Crioprotetores/química , Crioprotetores/farmacologia , Eritrócitos , Glicina/análogos & derivados , Glicina/farmacologia , Ovinos
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