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1.
Article in English | MEDLINE | ID: mdl-39175277

ABSTRACT

OBJECTIVE: The aim of the present study was to investigate the incidence of intrahepatic cholestasis of pregnancy (ICP) as well as neonatal outcomes between conception via in vitro fertilization (IVF) compared with spontaneous conception (SC) and screen the risk factors of ICP in IVF. METHODS: This retrospective cohort study included 4467 puerperae who conceived via IVF, and 28 336 puerperae who conceived spontaneously and linked the information from neonates. The general linear model (GLM), multivariate logistic regression analysis, a forest plot, and nomogram were used to assess impact factors and risk prediction. RESULTS: Logistic analysis adjusted for confounders revealed significant differences in the ICP rate of singleton delivery (4.24% vs 3.41%, adjusted OR [aOR] = 1.26; 95% confidence interval [CI] 1.03-1.53, P = 0.025) and in groups with total bile acids (TBA) ≥40 and <100 µmol/L (14.77% vs 10.39%, aOR = 1.31; 95% CI: 1.06-1.63, P = 0.023) between IVF and SC. When we divided newborns into singleton and twins delivery, the GLM revealed a higher rate with Apgar score <7 (13.44% vs 3.87%, aOR = 3.85; 95% CI: 2.07-7.17, P < 0.001) and fetal distress for IVF in comparison with SC (19.32% vs 5.55%, OR = 3.48; 95% CI: 2.39-6.95, P < 0.001) in the singleton group. In multivariate logistic regression analysis, body mass index (BMI) (aOR = 1.29; P = 0.031), number of embryo transfers (ET) (single ET vs double ET, aOR = 2.82; P < 0.001), E2 level on the ET day (aOR = 2.79; P = 0.011), fresh ET which compared with frozen ET (FET) (aOR = 1.45; P = 0.014), embryo stage (cleavage embryo vs blastocyst, aOR = 1.75; P = 0.009) and severe ovarian hyperstimulation syndrome (OHSS) which compared with non-OHSS (aOR = 3.73; P = 0.006) were independent predictors of ICP. These predictive factors in the logistic regression model were integrated into the nomogram (C-index = 0.735; 95% CI: 0.702-0.764); for each patient, higher total points indicated a higher risk of ICP. CONCLUSION: We observed that the ICP rate of singleton delivery was higher in IVF than in SC. In ICP patients, there were higher rates of neonatal Apgar score <7 and fetal distress in IVF than SC and found the predictors of ICP in IVF.

2.
Article in English | MEDLINE | ID: mdl-39177139

ABSTRACT

AIM: To discover new therapeutic targets for Type 2 diabetes (T2D) and develop a new diagnostic model. BACKGROUND: T2D is a chronic disease that can be controlled by oral hypoglycemic drugs, however, it cannot be fully cured. The continued increase in the prevalence of T2D and the limitations of existing treatments urgently call for the development of new drugs to be able to effectively control the progression of the disease. OBJECTIVE: We aimed to discover new therapeutic targets for T2D and to develop a new diagnostic model. METHOD: Single-cell transcriptome, web-based systematic pharmacology, and transcriptology were applied to identify T2D diagnostic targets and drug candidates and to analyze the underlying molecular mechanisms. RESULTS: By single-cell clustering analysis, we identified seven subsets between the normal islet ß-cell samples and T2D islet ß-cell samples. A total of 27 key genes in the intersection of insulin- related genes and diabetes-related genes were selected by protein-protein interaction (PPI) analysis and MolecularComplexDetection (MCODE) analysis. Notably, ESR1, MME, and CCR5 had the area under curves (AUC) values as high as 67.95%, 66.67%, and 66.03% for the diagnosis of T2D, respectively. Since the expression of MME in T2D samples was significantly higher than in normal samples, we screened 155 drug candidates against MME in T2D. Finally, the molecular docking revealed a strong binding strength between MME and DB05490, which was one of the most effective candidate drugs for treating T2D. CONCLUSION: Our study screens for diagnostic signatures and potential therapeutic agents for T2D, which provides valuable insights into the development of T2D biomarkers and their drug discovery.

3.
J Assist Reprod Genet ; 41(9): 2385-2396, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39001951

ABSTRACT

BACKGROUND: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes. METHODS: This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses. SETTING: Single reproductive medical center. SUBJECTS: All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included. EXPOSURE: Next-generation sequencing platforms for chromosomal analysis. MAIN OUTCOME MEASURES: Blastocyst formation and euploid blastocyst rates. RESULTS: In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy. CONCLUSION: In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.


Subject(s)
Aneuploidy , Blastocyst , Fertilization in Vitro , Gonadotropins , Oocytes , Ovulation Induction , Preimplantation Diagnosis , Humans , Female , Blastocyst/metabolism , Blastocyst/drug effects , Preimplantation Diagnosis/methods , Adult , Oocytes/growth & development , Oocytes/drug effects , Pregnancy , Ovulation Induction/methods , Gonadotropins/administration & dosage , Fertilization in Vitro/methods , Retrospective Studies , Embryo Transfer/methods , Oocyte Retrieval/methods , Pregnancy Rate , Genetic Testing/methods , Anti-Mullerian Hormone/blood
4.
Plants (Basel) ; 13(7)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38611539

ABSTRACT

Fatty acyl-CoA reductase (FAR) is an important NADPH-dependent enzyme that can produce primary alcohol from fatty acyl-CoA or fatty acyl-carrier proteins as substrates. It plays a pivotal role in plant growth, development, and stress resistance. Herein, we performed genome-wide identification and expression analysis of FAR members in rice using bioinformatics methods. A total of eight OsFAR genes were identified, and the OsFARs were comprehensively analyzed in terms of phylogenetic relationships, duplication events, protein motifs, etc. The cis-elements of the OsFARs were predicted to respond to growth and development, light, hormones, and abiotic stresses. Gene ontology annotation analysis revealed that OsFAR proteins participate in biological processes as fatty acyl-CoA reductase during lipid metabolism. Numerous microRNA target sites were present in OsFARs mRNAs. The expression analysis showed that OsFARs were expressed at different levels during different developmental periods and in various tissues. Furthermore, the expression levels of OsFARs were altered under abiotic stresses, suggesting that FARs may be involved in abiotic stress tolerance in rice. The findings presented here serve as a solid basis for further exploring the functions of OsFARs.

5.
Nat Commun ; 15(1): 416, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38195701

ABSTRACT

The performances of single-atom catalysts are governed by their local coordination environments. Here, a thermal replacement strategy is developed for the synthesis of single-atom catalysts with precisely controlled and adjustable local coordination environments. A series of Co-SxN4-x (x = 0, 1, 2, 3) single-atom catalysts are successfully synthesized by thermally replacing coordinated N with S at elevated temperature, and a volcano relationship between coordinations and catalytic performances toward electrochemical CO2 reduction is observed. The Co-S1N3 catalyst has the balanced COOH*and CO* bindings, and thus locates at the apex of the volcano with the highest performance toward electrochemical CO2 reduction to CO, with the maximum CO Faradaic efficiency of 98 ± 1.8% and high turnover frequency of 4564 h-1 at an overpotential of 410 mV tested in H-cell with CO2-saturated 0.5 M KHCO3, surpassing most of the reported single-atom catalysts. This work provides a rational approach to control the local coordination environment of the single-atom catalysts, which is important for further fine-tuning the catalytic performance.

6.
PeerJ ; 11: e15755, 2023.
Article in English | MEDLINE | ID: mdl-37483988

ABSTRACT

Background: Globally, metabolic syndrome (MS) and Helicobacter pylori (HP) infection, which have gained an epidemic status, are major challenges to human health, society, and medical professionals. Recent studies have demonstrated that MS is closely related to HP infection. Additionally, HP is an important risk factor for gastric cancer. However, systematic reviews on HP are lacking. This review aimed to summarize and analyze the potential correlation of HP infection with MS and its components, as well as the underlying mechanism, to provide reference and strategies for clinical prevention and treatment. Methodology: Previous studies examining the correlation between HP and MS since 1990 were retrieved from the PubMed, Web of Science, and Embase databases. The potential correlation between HP infection and MS and its components was comprehensively analyzed. The keywords "Helicobacter pylori," "HP," "metabolic syndrome," "hypertension," "obesity," "diabetes," or "dyslipidemia" were used in all fields. No language restrictions were imposed. Results: MS was strongly correlated to HP infection. The inflammatory response and inflammatory factors produced during HP infection are important etiological factors for insulin resistance and MS. The co-occurrence of long-term chronic inflammation and immune dysfunction with MS may be the predisposing factor for HP infection. MS components, such as diabetes, hypertension, dyslipidemia, and obesity were also correlated with HP infection in one or both directions. Conclusions: HP infection and MS may promote the pathogenesis of each other. The contribution of HP infection and MS to gastric cancer cannot be ruled out based on co-occurrence. The MS components diabetes and obesity may be bidirectionally correlated with HP infection.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Hypertension , Metabolic Syndrome , Stomach Neoplasms , Humans , Helicobacter Infections/epidemiology , Obesity
7.
Int J Mol Sci ; 25(1)2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38203283

ABSTRACT

Stearoyl-acyl carrier protein (ACP) Δ9 desaturase (SAD) is a critical fatty acid dehydrogenase in plants, playing a prominent role in regulating the synthesis of unsaturated fatty acids (UFAs) and having a significant impact on plant growth and development. In this study, we conducted a comprehensive genomic analysis of the SAD family in barley (Hordeum vulgare L.), identifying 14 HvSADs with the FA_desaturase_2 domain, which were divided into four subgroups based on sequence composition and phylogenetic analysis, with members of the same subgroup possessing similar genes and motif structures. Gene replication analysis suggested that tandem and segmental duplication may be the major reasons for the expansion of the SAD family in barley. The promoters of HvSADs contained various cis-regulatory elements (CREs) related to light, abscisic acid (ABA), and methyl jasmonate (MeJA). In addition, expression analysis indicated that HvSADs exhibit multiple tissue expression patterns in barley as well as different response characteristics under three abiotic stresses: salt, drought, and cold. Briefly, this evolutionary and expression analysis of HvSADs provides insight into the biological functions of barley, supporting a comprehensive analysis of the regulatory mechanisms of oil biosynthesis and metabolism in plants under abiotic stress.


Subject(s)
Hordeum , Hordeum/genetics , Acyl Carrier Protein , Phylogeny , Genomics , Fatty Acid Desaturases
8.
Front Microbiol ; 13: 1002482, 2022.
Article in English | MEDLINE | ID: mdl-36267191

ABSTRACT

Biofilm plays important roles in the life cycle of Bacillus species, such as promoting host and object surface colonization and resisting heavy metal stress. This study utilized transcriptomics to evaluate the impacts of cadmium on the components, morphology, and function of biofilms of Bacillus subtilis strain 1JN2. Under cadmium ion stress, the morphology of the B. subtilis 1JN2 biofilm was flattened, and its mobility increased. Moreover, differential gene expression analysis showed that the main regulator of biofilm formation, Spo0A, decreased in expression under cadmium ion stress, thereby inhibiting extracellular polysaccharide synthesis through the SinI/SinR two-component regulatory system and the AbrB pathway. Cadmium ion treatment also increased the SigD content significantly, thereby increasing the expression of the flagella encoding and assembly genes in the strain. This promoted poly-γ-glutamic acid production via the DegS/DegU two-component regulatory system and the conversion of biofilm extracellular polysaccharide to poly-γ-glutamic acid. This conferred cadmium stress tolerance in the strain. Additionally, the cadmium ion-mediated changes in the biofilm composition affected the colonization of the strain on the host plant root surface. Cadmium ions also induced surfactin synthesis. These findings illustrate the potential of Bacillus species as biocontrol strains that can mitigate plant pathogenic infections and heavy metal stress. The results also provide a basis for the screening of multifunctional biocontrol strains.

9.
Transl Pediatr ; 11(8): 1301-1310, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36072544

ABSTRACT

Background: Thyroid dysfunction is linked with adverse pregnancy outcomes, an upper limit of a normal thyroid-stimulating hormone (TSH) threshold of 4.12-4.5 mIU/L should be considered for subclinical hypothyroidism in the infertile female population. Whereas, it's controversial whether or not the infertility thresholds for upper limit of TSH threshold of 2.5 mIU/L. In our study examines the correlation of optimal TSH levels and clinical pregnancy outcomes after fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) embryo transfer cycles. Methods: Patients who underwent fresh IVF/ICSI embryo transfer cycles for the first time who presented between January 1, 2015 and December 31, 2017 at the Chongqing Institute of Reproductive and Genetic, Chongqing Health Center for Women and Children were enrolled. We excluded patients with ≥40 years, body mass index (BMI) ≤18 or ≥28 kg/m2, the man with severe oligoasthenospermia, women with poor ovarian reserve, and presence of endocrine disorders, uterine anomaly, sactosalpinx, abnormal thyroid function, preimplantation genetic diagnosis, and chromosomal abnormality or polymorphism. Baseline characteristics and clinical pregnancy outcomes were observed in our study. We detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by Receiver operating characteristic (ROC) curves and logical regression. Results: A total of 6,088 patients who undergo IVF/ICSI were included. We first detected that the live birth rate had a statistically significant difference when the TSH level was 3 mIU/L. With the TSH ≤3 mIU/L group having a higher live birth rate than the TSH >3 mIU/L group (51.79% vs. 47.89%, P=0.024), meanwhile no significant difference were revealed between the early miscarriage rate (12.54% vs. 14.97%, P=0.091) and early clinical pregnancy rate (59.21% vs. 56.32%, P=0.114). There were no differences in pregnancy outcomes when the TSH threshold was at 3.5 or 4 mIU/L and no association was detected between TSH levels and clinical pregnancy outcomes in patients undergoing IVF/ICSI by ROC curves and logical regression. Conclusions: Patients undergoing IVF/ICSI with a serum TSH level ≤3 mIU/L may have a higher live birth rate rather than ≤2.5 or ≤4 mIU/L.

10.
Front Genet ; 13: 967288, 2022.
Article in English | MEDLINE | ID: mdl-36072676

ABSTRACT

Background: This study aims to describe clinical and diagnostic phenotype and identify pathogenic variants of a female with unknown causes of infertility. Methods: Clinical assessment was performed for the phenotype diagnosis. Whole-exome sequencing (WES) and the followed cDNA-PCR sequencing were applied to identify the pathogenic variant and investigate the potentially aberrant mRNA splicing event. The pathogenicity of the variant was analysed using multiple in silico prediction tools, including the 3D protein remodelling. Quantitative RT-PCR (qRT-PCR) was performed to measure PATL2 mRNA expression in the peripheral blood leukocytes of the proband and controls. Results: The proband was diagnosed with the female infertility due to oocyte germinal vesicle (GV) arrest. A novel homozygous splice site variant of PATL2 (NM_001145112.2, c.871-1G>A), inherited from her asymptomatic heterozygous parents, was detected by WES. Sequencing of cDNA amplification products demonstrated that this variant resulted in the exon 10 skipping and in-frame loss of 54 nucleotides in the PATL2 transcript. Quantitative RT-PCR suggested that the mutant transcript escape the mRNA degradation. Conclusion: We identified a novel pathogenic homozygous splice site of PATL2 (c.871-1G>A) underlying the oocyte GV arrest phenotype and elucidated its molecular mechanism. This study expands the variant spectrum of PATL2 and benefits our understanding of its genotype-phenotype correlations.

11.
Front Genet ; 13: 843931, 2022.
Article in English | MEDLINE | ID: mdl-35360848

ABSTRACT

Meckel syndrome (MKS), also known as the Meckel-Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of the primary cilia during early embryogenesis. The diagnostic criteria are based on clinical variability and genetic heterogeneity. Mutations in the MKS1 gene constitute approximately 7% of all MKS cases. Herein, we present a non-consanguineous couple with three abnormal pregnancies as the fetuses showed MKS-related phenotypes of the central nervous system malformation and postaxial polydactyly. Whole-exome sequencing identified two novel heterozygous mutations of MKS1: c.350C>A and c.1408-14A>G. The nonsense mutation c.350C>A produced a premature stop codon and induced the truncation of the MKS1 protein (p.S117*). Reverse-transcription polymerase chain reaction (RT-PCR) showed that c.1408-14A>G skipped exon 16 and encoded the mutant MKS1 p.E471Lfs*92. Functional studies showed that these two mutations disrupted the B9-C2 domain of the MKS1 protein and attenuated the interactions with B9D2, the essential component of the ciliary transition zone. The couple finally got a healthy baby through preimplantation genetic testing for monogenic disorder (PGT-M) with haplotype linkage analysis. Thus, this study expanded the mutation spectrum of MKS1 and elucidated the genetic heterogeneity of MKS1 in clinical cases.

12.
Nat Commun ; 13(1): 1322, 2022 Mar 11.
Article in English | MEDLINE | ID: mdl-35277523

ABSTRACT

Copper-based materials can reliably convert carbon dioxide into multi-carbon products but they suffer from poor activity and product selectivity. The atomic structure-activity relationship of electrocatalysts for the selectivity is controversial due to the lacking of systemic multiple dimensions for operando condition study. Herein, we synthesized high-performance CO2RR catalyst comprising of CuO clusters supported on N-doped carbon nanosheets, which exhibited high C2+ products Faradaic efficiency of 73% including decent ethanol selectivity of 51% with a partial current density of 14.4 mA/cm-2 at -1.1 V vs. RHE. We evidenced catalyst restructuring and tracked the variation of the active states under reaction conditions, presenting the atomic structure-activity relationship of this catalyst. Operando XAS, XANES simulations and Quasi-in-situ XPS analyses identified a reversible potential-dependent transformation from dispersed CuO clusters to Cu2-CuN3 clusters which are the optimal sites. This cluster can't exist without the applied potential. The N-doping dispersed the reduced Cun clusters uniformly and maintained excellent stability and high activity with adjusting the charge distribution between the Cu atoms and N-doped carbon interface. By combining Operando FTIR and DFT calculations, it was recognized that the Cu2-CuN3 clusters displayed charge-asymmetric sites which were intensified by CH3* adsorbing, beneficial to the formation of the high-efficiency asymmetric ethanol.

13.
Chem Commun (Camb) ; 57(87): 11561-11564, 2021 Nov 02.
Article in English | MEDLINE | ID: mdl-34668004

ABSTRACT

A Pd-doped Pt3Sn-based single atom alloy catalyst (Pd-Pt3Sn) was synthesized via a hydrothermal method. The overpotential of Pd-Pt3Sn is lower than that of commercial Pd/C and IrO2 catalysts at 10 mA cm-2. This is due to the synergistic effect between Pt, Sn and Pd and the influence of electronic effects on their catalytic performance.

14.
Stem Cell Reports ; 16(9): 2305-2319, 2021 09 14.
Article in English | MEDLINE | ID: mdl-34388364

ABSTRACT

Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with high morbidity and mortality. Existing evidence suggests that the central pathogenesis to aHUS might be endothelial cell damage. Nevertheless, the role of endothelial cell alterations in aHUS has not been well characterized and the underlying mechanisms remain unclear. Utilizing an induced pluripotent stem cell-derived endothelial cell (iPSC-EC) model, we showed that anti-complement factor H autoantibody-associated aHUS patient-specific iPSC-ECs exhibited an intrinsic defect in endothelial functions. Stimulation using aHUS serums exacerbated endothelial dysfunctions, leading to cell apoptosis in iPSC-ECs. Importantly, we identified p38 as a novel signaling pathway contributing to endothelial dysfunctions in aHUS. These results illustrate that iPSC-ECs can be a reliable model to recapitulate EC pathological features, thus providing a unique platform for gaining mechanistic insights into EC injury in aHUS. Our findings highlight that the p38 MAPK signaling pathway can be a therapeutic target for treatment of aHUS.


Subject(s)
Atypical Hemolytic Uremic Syndrome/etiology , Atypical Hemolytic Uremic Syndrome/metabolism , Endothelial Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , MAP Kinase Signaling System , p38 Mitogen-Activated Protein Kinases/metabolism , Apoptosis , Atypical Hemolytic Uremic Syndrome/diagnosis , Autoantibodies/immunology , Autoimmunity , Biomarkers , Complement Factor H/immunology , Disease Susceptibility , Endothelial Cells/cytology , Endothelium/metabolism , Endothelium/physiopathology , Humans , Phenotype
15.
Medicine (Baltimore) ; 100(12): e25145, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33761681

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor therapy for non-small cell lung cancer is widely used in clinical practice. However, there has not been a systematic statistical proof of the efficacy of PD-1 inhibitors in patients with advanced cancer. This meta-analysis aims to evaluate its efficacy and related influencing factors, so as to provide a basis for clinical diagnosis and treatment. OBJECTIVE: To assess the effectiveness and safety of programmed death-1 (PD-1)/PD ligand 1 (PD-L1) inhibitors versus chemotherapy as second-line or late-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) via a systematic review of published randomized controlled trials (RCTs). METHODS: Studies were identified through PubMed, EMBASE, and Cochrane Library electronic databases. RevMan 5.3.5 was used to analyze the data extracted from all eligible studies. RESULTS: All 4122 eligible patients from 8 RCTs were included in this study. The meta-analysis showed that PD-1/PD-L1 inhibitors could significantly improve overall survival (hazards ratio [HR] 0.71, 95% confidence interval [CI] 0.66-0.77, P < .001), progression-free survival (HR 0.88, 95%CI 0.81-0.94, P = .01), and objective response rate (HR 2.03, 95%CI 1.66-2.49, P < .001) compared with chemotherapy drugs. The incidence of side effects of any grade (HR 0.34, 95%CI 0.29-0.39, P < .001) or grades 3 to 5 (HR 0.15, 95%CI 0.10-0.23, P < .001) consistently showed that PD-1/PD-L1 inhibitors were safer than chemotherapy. Furthermore, subgroup analysis based on tumor proportion score or pathology classification revealed that PD-1/PD-L1 inhibitors significantly improved overall survival compared with chemotherapy. CONCLUSION: As a second-line or late-line treatment, PD-1/PD-L1 inhibitors are safer and more effective than chemotherapy in patients with advanced NSCLC.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Adolescent , Adult , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Progression-Free Survival , Proportional Hazards Models , Randomized Controlled Trials as Topic , Treatment Outcome , Young Adult
16.
Stem Cell Res ; 48: 101965, 2020 10.
Article in English | MEDLINE | ID: mdl-32916635

ABSTRACT

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease in which the right ventricular myocardium is replaced by progressive fibrous adipose tissue. ARVC is clinically characterized by right ventricular enlargement, ventricular arrhythmia, and sudden cardiac death. It eventually leads to heart failure, and thus has a significant impact on the patient's health. In this study, human dermal fibroblasts were obtained from a patient with ARVC, which were subsequently reprogrammed with a non-integrated Sendai virus to generate a patient-specific induced pluripotent stem cell (iPSC) line. The iPSC line exhibited normal karyotype and morphology, expressed pluripotency markers, and was capable of differentiating into three germ layers.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia , Induced Pluripotent Stem Cells , Arrhythmogenic Right Ventricular Dysplasia/genetics , Cell Line , Fibroblasts , Humans , Mutation , Plakophilins/genetics
17.
Angew Chem Int Ed Engl ; 59(50): 22465-22469, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-32876989

ABSTRACT

Main-group element indium (In) is a promising electrocatalyst which triggers CO2 reduction to formate, while the high overpotential and low Faradaic efficiency (FE) hinder its practical application. Herein, we rationally design a new In single-atom catalyst containing exclusive isolated Inδ+ -N4 atomic interface sites for CO2 electroreduction to formate with high efficiency. This catalyst exhibits an extremely large turnover frequency (TOF) up to 12500 h-1 at -0.95 V versus the reversible hydrogen electrode (RHE), with a FE for formate of 96 % and current density of 8.87 mA cm-2 at low potential of -0.65 V versus RHE. Our findings present a feasible strategy for the accurate regulation of main-group indium catalysts for CO2 reduction at atomic scale.

18.
Nano Lett ; 20(7): 5443-5450, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32515966

ABSTRACT

Oxygen-involved electrochemical reactions are crucial for plenty of energy conversion techniques. Herein, we rationally designed a carbon-based Mn-N2C2 bifunctional electrocatalyst. It exhibits a half-wave potential of 0.915 V versus reversible hydrogen electrode for oxygen reduction reaction (ORR), and the overpotential is 350 mV at 10 mA cm-2 during oxygen evolution reaction (OER) in alkaline condition. Furthermore, by means of operando X-ray absorption fine structure measurements, we reveal that the bond-length-extended Mn2+-N2C2 atomic interface sites act as active centers during the ORR process, while the bond-length-shortened high-valence Mn4+-N2C2 moieties serve as the catalytic sites for OER, which is consistent with the density functional theory results. The atomic and electronic synergistic effects for the isolated Mn sites and the carbon support play a critical role to promote the oxygen-involved catalytic performance, by regulating the reaction free energy of intermediate adsorption. Our results give an atomic interface strategy for nonprecious bifunctional single-atom electrocatalysts.

19.
Medicine (Baltimore) ; 99(26): e21007, 2020 Jun 26.
Article in English | MEDLINE | ID: mdl-32590817

ABSTRACT

The aim of this study was to investigate the changes of retinal vessel density (VD) and choriocapillary blood flow area (CBFA) in macula after an acute intraocular pressure (IOP) elevation observed using optical coherence tomography angiography.This was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and 1 hour after the LPI. The retinal VDs and CBFAs of the macula were measured using optical coherence tomography angiography at the baseline and 1 hour after the LPI.A total of 88 eyes of 88 individuals were enrolled in our study, and 70 eyes of 70 individuals finally completed the study with a mean IOP rise of 10.2 ±â€Š7.5 mm Hg after the LPI. The VDs and areas of foveal avascular zone of all of the subjects did not differ significantly between the measurements obtained at the baseline and 1 hour after the LPI (P > .05). However, there were statistically significant differences in the CBFAs at the baseline and 1 hour after the LPI (P < .05). Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤ 10 mm Hg, group B = 10 mm Hg < IOP rise ≤20 mm Hg, and group C = IOP rise > 20 mmHg. The VDs of the macula measured at the baseline were significantly different from the measurements obtained 1 hour after the LPI in group C in either the superficial retinal layer or deep retinal layer (P < .05). Compared with baseline, the CBFAs measured at 1 hour after the LPI were decreased in group B and group C (P < .05).In these subjects with narrow antenior chamber, the blood flow in macula began to be affected with the acute IOP rise greater than 10 mm Hg. It was confirmed that the retina and choroid showed some different ability to regulate its blood flow in response to changes in IOP.


Subject(s)
Choroid/blood supply , Macula Lutea/blood supply , Ocular Hypertension/physiopathology , Retina/physiopathology , Aged , Capillaries , Choroid/physiopathology , Female , Humans , Intraocular Pressure , Macula Lutea/physiopathology , Male , Middle Aged , Prospective Studies , Tomography, Optical Coherence/methods
20.
Nat Commun ; 11(1): 3049, 2020 Jun 16.
Article in English | MEDLINE | ID: mdl-32546781

ABSTRACT

Atomic interface regulation is thought to be an efficient method to adjust the performance of single atom catalysts. Herein, a practical strategy was reported to rationally design single copper atoms coordinated with both sulfur and nitrogen atoms in metal-organic framework derived hierarchically porous carbon (S-Cu-ISA/SNC). The atomic interface configuration of the copper site in S-Cu-ISA/SNC is detected to be an unsymmetrically arranged Cu-S1N3 moiety. The catalyst exhibits excellent oxygen reduction reaction activity with a half-wave potential of 0.918 V vs. RHE. Additionally, through in situ X-ray absorption fine structure tests, we discover that the low-valent Cuprous-S1N3 moiety acts as an active center during the oxygen reduction process. Our discovery provides a universal scheme for the controllable synthesis and performance regulation of single metal atom catalysts toward energy applications.

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