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1.
Front Genet ; 12: 738746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630528

RESUMO

Eimeria species are intracellular parasites residing inside the intestinal epithelial cell, which cause poultry coccidiosis and result in significant financial losses in the poultry industry. Genome editing of Eimeria is of immense importance for the development of vaccines and drugs. CRISPR/Cas9 has been utilized for manipulating the genome of Eimeria tenella (E. tenella). Ectopic expression of Cas9, i.e., via plasmids, would introduce transgene, which substantially limits its application, especially for vaccine development. In this study, we initially optimized the condition of the transfection protocol. We demonstrated that with the optimized condition, the transfection of FnCas12a (also known as "FnCpf1") protein and crRNA targeting EtHistone H4 triggered DNA double-strand breaks in vivo. We then used this strategy to knock-in a coding cassette for an enhanced yellow fluorescent protein (EYFP) and dihydrofolate reductase-thymidylate synthase gene (DHFR) as a selection marker to tag endogenous EtActin. The engineered E. tenella parasite possesses EYFP expression in its entire life cycle. Our results demonstrated that FnCas12a could trigger genome editing in E. tenella, which augments the applicability of the dissection of gene function and the development of anticoccidial drugs and vaccines for Eimeria species.

2.
Front Pediatr ; 9: 722471, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631622

RESUMO

Objective: Birth weight, an important indicator of fetal nutrition and degree of development, may affect the risk of subsequent leukemia. At present, little is known about the effect of birth weight on acute myeloid leukemia (AML) and whether there is a dose-dependent relationship of birth weight with acute lymphoid leukemia (ALL) and AML. To address these questions, the present work aimed to systematically investigate the relationship between birth weight and the risk of subsequent leukemia based on the current epidemiological studies Methods: Relevant studies were systematically retrieved from electronic databases PubMed, Embase, and Cochrane Library, from inception to May 15th, 2021. Finally, 28 studies (including 21 case-control studies and 7 cohort studies) were included for the final meta-analysis. Results in cohort studies were performed by risk ratios (RRs), while those in case-control studies by odds ratios (ORs), and all results were assessed by adopting the random-effect model. Besides, a dose-dependent analysis was conducted based on the cohort studies. Results: Compared with the population with normal birth weight (NBW), the population with high birth weight (HBW) might have an increased risk of leukemia (OR 1.33, 95%CI 1.20-1.49; I 2 0%). Meanwhile, low birth weight (LBW) was associated with a decreased risk of ALL, as evidenced from the pooled analysis of case-control studies (OR 0.83, 95% CI 0.75-0.92; I 2 23.3%). However, relative to NBW population, the HBW population might have an increased risk of ALL (OR 1.28, 95% CI 1.20-1.35; I 2 7%). There was no obvious evidence supporting the relationship between LBW and the risk of AML from the pooled analysis of case-control studies (OR, 1.11 95% CI 0.87-1.42; I 2 31.7%). Conclusions: Overall, in children and young adults, HBW population may be associated with the risks of subsequent leukemia and AML relative to NBW population, but the supporting dose-dependent evidence is lacking. In addition, compared with NBW population, there is stronger evidence supporting a significantly increased risk of subsequent ALL in HBW population, and a decreased risk in LBW population in a dose-dependent manner. More prospective studies with large samples are warranted in the future to validate and complement these findings.

3.
Bioengineered ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635009

RESUMO

In recent researches, circular RNAs (circRNAs) have been shown to exert critical functions in osteosarcoma biology. Nevertheless, the contribution of circRNAs to osteosarcoma remains largely unclear. Results indicated that expression of circATRNL1 was higher in osteosarcoma tissues and cells. The high-expression of circATRNL1 was significantly correlated with aggressive features and acted as an independent risk factor for osteosarcoma patients' overall survival. Functionally, our findings demonstrate that circATRNL1 promotes the osteosarcoma aerobic glycolysis in vitro. Mechanistically, circATRNL1 up-regulated the expression level of LDHA, which was also targeted by miR-409-3p. Therefore, circATRNL1 exerted the accelerative roles of osteosarcoma aerobic glycolysis through miR-409-3p/LDHA axis. In conclusion, circATRNL1 promoted osteosarcoma progression by enhancing glycolysis via circATRNL1/miR-409-3p/LDHA axis, which may inspire a novel therapeutic target for osteosarcoma.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34628559

RESUMO

A novel Gram-staining positive, aerobic, rod-shaped, non-motile and yellow-pigmented actinobacterium, designated strain WY83T, was isolated from a marine sediment of Indian Ocean. Strain WY83T grew optimally at 30-35 °C, pH 7-8 and with 0-3% (w/v) NaCl. The predominant menaquinones were MK-10, MK-11 and MK-12, and the major fatty acids were C19:1 ω9c/C19:1 ω11c, anteiso-C15:0, C17:0 3OH, and iso-C16:0. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The cell-wall peptidoglycan contained lysine as a diamino acid. The DNA G + C content was 72.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences and ninety-two bacterial core genes indicated that strain WY83T formed an evolutionary lineage with Chryseoglobus frigidaquae JCM 14730T, Chryseoglobus indicus CTD02-10-2T, Yonghaparkia alkaliphila JCM 15138T, Microcella alkaliphila DSM 18851T and Microcella putealis DSM 19627T within the radiation enclosing members of the family Microbacteriaceae. All pairwise percentage of conserved proteins between strain WY83T and the closely related phylogenetic neighbors were greater than 65%. The average nucleotide identity and in silico DNA-DNA hybridization values were both below the thresholds used for the delineation of a new species. On the basis of the evidence presented, strains WY83T, Y. alkaliphila JCM 15138T, C. frigidaquae JCM 14730T, M. alkaliphila DSM 18851T and M. putealis DSM 19627T should belong to different species of the same genus. Strain WY83T represents a novel species of the genus Microcella, for which the name Microcella flavibacter sp. nov. is proposed. The type strain is WY83T (= KCTC 39637T = MCCC 1A07099T). Furthermore, Chryseoglobus frigidaquae, Chryseoglobus indicus, and Yonghaparkia alkaliphila were reclassified as Microcella frigidaquae comb. nov., Microcella indica nom. nov., and Microcella alkalica nom. nov., respectively.

5.
Adv Mater ; : e2105228, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599775

RESUMO

Encapsulation of lithium in the confined spaces within individual nanocapsules is intriguing and highly desirable for developing high-performance Li metal anodes. This work aims for a mechanistic understanding of Li encapsulation and its confined growth kinetics inside 1D enclosed spaces. To achieve this, amorphous carbon nanotubes are employed as a model host using in situ transmission electron microscopy. The carbon shells have dual roles, providing geometric/mechanical constraints and electron/ion transport channels, which profoundly alter the Li growth patterns. Li growth/dissolution takes place via atom addition/removal at the free surfaces through Li+ diffusion along the shells in the electric field direction, resulting in the formation of unusual Li structures, such as poly-crystalline nanowires and free-standing 2D ultrathin (1-2 nm) Li membranes. Such confined front-growth processes are dominated by Li {110} or {200} growing faces, distinct from the root growth of single-crystal Li dendrites outside the nanotubes. Controlled experiments show that high lithiophilicity/permeability, enabled by sufficient nitrogen/oxygen doping or pre-lithiation, is critical for the stable encapsulation of lithium inside carbonaceous nanocapsules. First-principles-based calculations reveal that N/O doping can reduce the diffusion barrier for Li+ penetration, and facilitate Li filling driven by energy minimization associated with the formation of low-energy Li/C interfaces.

6.
J Cancer ; 12(21): 6310-6319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659521

RESUMO

Mitochondria are involved in various biological processes including intracellular homeostasis, proliferation, senescence, and death, and mitochondrial mitophagy is closely related to the development and regression of malignant tumors. Recent studies confirmed that the hypoglycemic drug metformin (Met) exerted various antitumor effects, protected neural cells, and improved immunity, while arsenic trioxide (ATO) is an effective chemotherapeutic agent for the clinical treatment of leukemia and various solid tumors. However, the possible combined antitumor effects of Met and ATO and their cellular molecular mechanisms are unclear. We investigated the role of Parkin-mediated mitochondrial mitophagy in the anti-tumor mechanism of Met and ATO by studying the effects of Met and/or ATO on the proliferation and apoptosis of cervical cancer HeLa cells. Both Met and ATO effectively inhibited the proliferative activity of HeLa cells and induced apoptosis by activating Bax and inhibiting Bcl-2. Met and ATO treatment alone or in combination stimulated mitophagosome accumulation in HeLa cells, increased the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and decreased levels of the mitophagic lysosomal substrate protein P62. The mitochondrial membrane potential of HeLa cells also decreased, accompanied by activation of the mitochondrial translocase TOM system and the Pink1/Parkin signaling pathway. These results suggested that Met and/or ATO could induce mitophagy in HeLa cells via the Pink1/Parkin signaling pathway, leading to mitophagic apoptosis and inhibition of tumor cell proliferation. The combination of Met and ATO thus has enhanced antitumor effects, suggesting that this combination has potential clinical applications for the treatment of cervical cancer and other tumors.

7.
Natl Sci Rev ; 8(3): nwaa180, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34691592

RESUMO

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we constructed a single-cell transcriptional atlas of blood cells (ABC) on the basis of both protein-coding genes and long noncoding RNAs (lncRNAs), and showed a high consistence between them. Notably, putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified. While common transcription factor regulatory networks were activated in neutrophils and monocytes, lymphoid cells dramatically changed their regulatory networks during differentiation. Furthermore, we showed a subset of nucleated erythrocytes actively expressing immune signals, suggesting the existence of erythroid precursors with immune functions. Finally, a web portal offering transcriptome browsing and blood cell type prediction has been established. Thus, our work provides a transcriptional map of human blood cells at single-cell resolution, thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

8.
Mol Cancer Res ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654722

RESUMO

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common EBV-associated head and neck malignancy. However, the effect of EBV on NPC LN metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF-1a hyperactivity and subsequent VEGF-C transcriptional activation. Additionally, administration of anti-VEGF-C antibody or HIF-1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF-1a and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis.

10.
Front Cardiovasc Med ; 8: 745810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660743

RESUMO

Sepsis, a pathology resulting from excessive inflammatory response that leads to multiple organ failure, is a major cause of mortality in intensive care units. Macrophages play an important role in the pathophysiology of sepsis. Accumulating evidence has suggested an upregulated rate of aerobic glycolysis as a key common feature of activated proinflammatory macrophages. Here, we identified a crucial role of myeloid 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3), a glycolytic activator in lipopolysaccharide (LPS)-induced endotoxemia in mice. Pfkfb3 expression is substantially increased in bone marrow derived macrophages (BMDMs) treated with LPS in vitro and in lung macrophages of mice challenged with LPS in vivo. Myeloid-specific knockout of Pfkfb3 in mice protects against LPS-induced lung edema, cardiac dysfunction and hypotension, which were associated with decreased expression of interleukin 1 beta (Il1b), interleukin 6 (Il6) and nitric oxide synthase 2 (Nos2), as well as reduced infiltration of neutrophils and macrophages in lung tissue. Pfkfb3 ablation in cultured macrophages attenuated LPS-induced glycolytic flux, resulting in a decrease in proinflammatory gene expression. Mechanistically, Pfkfb3 ablation or inhibition with a Pfkfb3 inhibitor AZ26 suppresses LPS-induced proinflammatory gene expression via the NF-κB signaling pathway. In summary, our study reveals the critical role of Pfkfb3 in LPS-induced sepsis via reprogramming macrophage metabolism and regulating proinflammatory gene expression. Therefore, PFKFB3 is a potential target for the prevention and treatment of inflammatory diseases such as sepsis.

11.
Radiat Oncol ; 16(1): 187, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563216

RESUMO

Pelvic radiotherapy is the key treatment for pelvic malignancies, usually including pelvic primary tumour lesions and lymphatic drainage areas in the pelvic region. Therefore, the intestinal tract in the radiation field is inevitably damaged, a phenomenon clinically referred to as radiation enteritis, and diarrhoea is the most common clinical symptom of radiation enteritis. Therefore, it is necessary to study the mechanism of radiation-induced diarrhoea. It has been found that the gut microbiome plays an important role in the development of diarrhoea in response to pelvic radiotherapy, and the species and distribution of intestinal microbiota are significantly altered in patients after pelvic radiotherapy. In this study, we searched for articles indexed in the Cochrane Library, Web of Science, EMBASE and PubMed databases in English and CNKI, Wanfang data and SINOMED in Chinese from their inception dates through 13 March 2020 to collect studies on the gut microbiome in pelvic radiotherapy patients. Eventually, we included eight studies: one study report on prostatic carcinoma, five studies on gynaecological carcinoma and two papers on pelvic carcinomas. All studies were designed as self-controlled studies, except for one that compared toxicity to nontoxicity. The results from all the studies showed that the diversity of intestinal flora decreased during and after pelvic radiotherapy, and the diversity of intestinal flora decreased significantly in patients with diarrhoea after radiotherapy. Five studies observed that the community composition of the gut microbiota changed at the phylum, order or genus level before, during, and after pelvic radiotherapy at different time points. In addition, the composition of the gut microbiota before radiotherapy was different between patients with postradiotherapy diarrhoea and those without diarrhoea in five studies. However, relevant studies have not reached consistent results regarding the changes in microbiota composition. Changes in the intestinal flora induced by pelvic radiotherapy and their relationship between changes in intestinal flora and the occurrence of radiation-induced diarrhoea (RID) are discussed in this study, providing a theoretical basis for the causes of RID after pelvic radiotherapy.

12.
Cell Death Discov ; 7(1): 230, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482379

RESUMO

Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer's disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in ß-amyloid protein (Aß)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aß aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD.

13.
Innovation (N Y) ; 2(1): 100091, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34557745

RESUMO

Infertility is one of the most common non-communicable diseases, affecting both men and women equally. Ovarian reserve, the number of primordial follicles in the ovaries is believed to be the most important determinants for female fertility. Anti-Müllerian hormone (AMH) secreted from granulosa cells of growing follicles is recognized as the most important biomarker for ovarian reserve. Ovarian reserve models have been developed using AMH and other hormonal indicators, thus childbearing plans and reproductive choices could be arranged by women. In assisted reproductive technology cycles, measurement of AMH helps to predict ovarian response and guide recombinant follicle-stimulating hormone dosing in women. Serum AMH level is increasingly being recognized as a potential surrogate marker for polycystic ovarian morphology, one of the criteria for diagnosis of polycystic ovarian syndrome. AMH is also secreted by Sertoli cells of testes in men, and AMH measurements in the prediction of surgical sperm recovery rate in men have also been investigated. AMH levels are significantly higher in boys than in girls before puberty. Therefore, serum levels of AMH in combination with testosterone is used for the differential diagnosis of disorders of sex development, anorchia, non-obstructive azoospermia, and persistent Müllerian duct syndrome. Recently, serum AMH measurements have also been used in fertility preservation programs in oncofertility, screening for granulosa cell tumors, and prediction of menopause applications. In this review, we will focus on clinical application of AMH in fertility assessments for healthy men and women, as well as for cancer patients.

14.
J Colloid Interface Sci ; 607(Pt 1): 470-478, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34509729

RESUMO

Effective electronic interactions between molecular catalysts and supports are critical for heterogeneous enzyme mimics, yet they are frequently neglected in most catalyst designs. Taking the enzyme mimics of hemin immobilized on graphdiyne (Hemin-GDY) as an example, we explicate for the first time the underlying role of GDY as a co-catalyst. Based on the robust conjugation between GDY and hemin, the delocalized π-electrons in GDY act as a ligand for Fe ions so that the orbital interactions including electron transport from GDY â†’ Fe can induce the formation of an electron-rich Fe center and an electron-deficient π-electron conjugated system. This mechanism was validated by electron paramagnetic resonance (EPR), Raman spectroscopy, and DFT calculations. Moreover, both EPR spetra and Lineweaver-Burk plots revealed that Hemin-GDY could efficiently catalyze the decomposition of hydrogen peroxide (H2O2) to produce hydroxyl radical (•OH) and superoxide anion (O2•-) by a ping-pong type catalytic mechanism, and particularly, the catalytic activity was increased by 2.3-fold comparing to that of hemin immobilized on graphene (Hemin-GR). In addition, Hemin-GDY with the exceptional activity and stability was demonstrated for efficient catalytic degradation of organic pollutants under acidic conditions. Collectively, this work provides a theoretical basis for the design of GDY supported catalysts and renders great promises of the GDY based enzyme mimics.

15.
Theriogenology ; 176: 54-62, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34571398

RESUMO

The efficiency of animal artificial breeding in vitro is still low. Oxidative damage is an important obstacle for in vitro artificial breeding of animals. Melatonin can reduce the degree of oxidative damage to both gametes and embryos caused by the external environment. However, there is still some controversy concerning the effect of melatonin on frozen semen, especially in the processes of freezing semen, IVM, IVF and IVC. Here, the effects of melatonin on the whole processes of sperm cryopreservation, oocyte maturation, and embryonic development were studied. The results demonstrated that melatonin at 10-3 M concentration significantly improved progressive sperm viability, plasma membrane integrity, mitochondrial membrane integrity, and acrosome integrity; however, there were also individual differences between bulls, depending on the age of different individuals. The 10-3 M melatonin treatment reduced the reactive oxygen species (ROS) level by nearly 50% in sperm during IVF. Meanwhile, during IVM, the addition of 10-7 M melatonin significantly increased the maturation rate of oocytes and reduced the ROS levels by 58.8%. In addition, 10-7 M melatonin improved the total cell numbers of the IVF blastocysts. Notably, treatment of IVF embryos with melatonin significantly reduced the levels of ROS and influenced the expression levels of key regulatory genes associated with embryo genome activation. This study is of significance for understanding the function of melatonin in animal artificial breeding.

16.
Pediatr Investig ; : e12282, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34540320

RESUMO

Importance: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians. Objective: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China. Methods: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. Interpretation: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

17.
BJOG ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559941

RESUMO

OBJECTIVE: To assess the current status of cesarean delivery (CD) in China, propose reference CD rates for China overall and by regions, investigate the main indications for CDs, and identify possible areas for safe reduction. DESIGN: A multi-center cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterize CDs in subgroups and by regions, and the WHO C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015 and 2016, the overall CD rate in China was 38.9% (95% CI: 38.6% to 39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95%CI: 28.3% to 28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% of relative reduction) may be considered. The CD rate varied substantially by regions. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labor dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). 12.7% women had prelabor CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by cesarean in China but a quarter of reduction may be considered. Repeat CD contributed more than one-third of total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD.

18.
Inflammation ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480251

RESUMO

Asthma is a common chronic respiratory disease that affects millions of people worldwide. The incidence of asthma has continued to increase every year. Bronchial asthma involves a variety of cells, including airway inflammatory cells, structural cells, and neutrophils, which have gained more attention because they secrete substances that play an important role in the occurrence and development of asthma. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and non-histone molecules that can be secreted from neutrophils. NETs can enrich anti-bacterial substances and limit pathogen migration, thus having a protective effect in case of inflammation. However, despite of their anti-inflammatory properties, NETs have been shown to trigger allergic asthma and worsen asthma progression. Here, we provide a systematic review of the roles of NETs in asthma.

19.
Front Immunol ; 12: 713276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526989

RESUMO

Autoreactive CD8+ T cells play an indispensable key role in the destruction of pancreatic islet ß-cells and the initiation of type 1 diabetes (T1D). Insulin is an essential ß-cell autoantigen in T1D. An HLA-A*0201-restricted epitope of insulin A chain (mInsA2-10) is an immunodominant ligand for autoreactive CD8+ T cells in NOD.ß2mnull .HHD mice. Altered peptide ligands (APLs) carrying amino acid substitutions at T cell receptor (TCR) contact positions within an epitope are potential to modulate autoimmune responses via triggering altered TCR signaling. Here, we used a molecular simulation strategy to guide the generation of APL candidates by substitution of L-amino acids with D-amino acids at potential TCR contact residues (positions 4 and 6) of mInsA2-10, named mInsA2-10DQ4 and mInsA2-10DC6, respectively. We found that administration of mInsA2-10DQ4, but not DC6, significantly suppressed the development of T1D in NOD.ß2mnull .HHD mice. Mechanistically, treatment with mInsA2-10DQ4 not only notably eliminated mInsA2-10 autoreactive CD8+ T cell responses but also prevented the infiltration of CD4+ T and CD8+ T cells, as well as the inflammatory responses in the pancreas of NOD.ß2mnull.HHD mice. This study provides a new strategy for the development of APL vaccines for T1D prevention.

20.
Lancet Reg Health West Pac ; 15: 100252, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34528018

RESUMO

Background In Western developed countries, food-based dietary patterns have been associated with the risk of cardiometabolic diseases, but little is known about such associations in less developed ethnic minority regions (LEMRs), where the cardiometabolic disease burden is growing rapidly and food patterns differ substantially. Methods Between May 2018 and September 2019, we recruited 99556 participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC) Study. We measured habitual dietary intake with validated food frequency questionnaire (FFQ) and then calculated dietary pattern scores for two of the most studied a priori dietary patterns, i.e., Dietary Approaches to Stop Hypertension (DASH) and alternative Mediterranean (aMED) style diets, and three a posteriori dietary patterns. Four cardiometabolic risks, including hypertension, diabetes, dyslipidaemia and metabolic syndrome (MetS), were newly diagnosed by medical examination and blood tests. We estimated adjusted odds ratios (OR) relating various dietary pattern scores to cardiometabolic risks using marginal structural models under the guidance of directed acyclic graphs. For the above associations, we further calculated the proportion mediated by overweight (PM) using regression-based mediation analysis for better public health implications. Findings The final study sample consisted of 68834 participants. Among them, we newly diagnosed 12803 hypertension, 3527 diabetes, 16342 hyperlipidaemia, and 8198 MetS cases. Overall, all 5 dietary patterns showed considerable associations with risks of hypertension and MetS. Comparing the highest with the lowest quintiles, the DASH score showed the strongest inverse associations with risks of hypertension (OR=0.74, 95% CI:0.70-0.79; PM=10%) and MetS (OR=0.79, 95% CI:0.74-0.85; PM=35%); conversely, scores of the localized a posteriori Yunnan-Guizhou plateau dietary pattern in LEMRs showed the strongest positive associations with risks of hypertension (OR=1.44, 95% CI:1.35-1.52; PM=10%) and MetS (OR=1.35, 95% CI:1.26-1.46; PM=33%), with all P values for trend <0.001. These associations were consistent in various subgroups defined by sex, age, smoking and physical activity, but with magnitudes that differed substantially across different ethnic regions and urbanicity. By investigating the single-component effects of dietary patterns, the dairy intake component contributed a major proportion to the beneficial effects of DASH (41.9% for hypertension and 100.5% for MetS). Interpretation Substantial socioeconomic status and ethnic disparities in diet quality and related cardiometabolic risks were seen in LEMRs, with hypertension being the top diet-related cardiometabolic risk. Our findings support that DASH provides superior dietary guidance compared to aMED for reducing cardiometabolic risks in LEMRs. In particular, the dairy intake encouraged by DASH may produce considerable beneficial effects. Funding This study was funded by the National Key R&D Program of China; full funding sources listed in the acknowledgements.

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