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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 245: 118885, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32920445

RESUMO

Ternary co-crystal, as a novel co-crystal design strategy developed on the basis of binary co-crystal, could be used to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently. However, it is difficult to obtain specific ternary co-crystals since such ternary one involves complex assembly of three different molecules. There are few reports on the micro-molecular structure respect of specific ternary co-crystal systems. In present work, 1:1:1 ternary co-crystal between acetazolamide (ACZ), nicotinamide (NAM) and 2-pyridone (2HP) has been synthesized successfully by mechanical grinding approach, and their structures are investigated by terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy combined with theoretical calculation at the molecular level. The experimental THz spectral results showed that ACZ-NAM-2HP ternary co-crystal and the starting parent materials exhibited a few distinct spectral features in frequency-domain absorption spectra. Likewise, the Raman spectral result also shows some difference between the co-crystal and starting raw materials. Through density functional theory (DFT) calculations, the theoretical THz/Raman spectra and vibrational modes of two kind of possible ternary co-crystal theoretical forms (form I and II) between ACZ, NAM and 2HP were obtained. By comparing experimental and theoretical spectral results, the most suitable structure and vibrational modes of ACZ-NAM-2HP ternary co-crystal were determined. These results provide a wealth of information and unique method for studying molecular assembly and also inter-molecular interactions in specific ternary co-crystals at the molecular level in the emerging pharmaceutical co-crystal fields.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33184920

RESUMO

A photochemical C-N coupling of aryl halides with nitroarenes is demonstrated for the first time. Catalyzed by a Ni(II) complex in the absence of any external photosensitizer, readily available nitroarenes undergo coupling with a variety of aryl halides, providing a step-economic extension to the widely used Buchwald-Hartwig C-N coupling reaction. The method tolerates coupling partners with steric-congestion and functional groups sensitive to bases and nucleophiles. Mechanistic studies suggest that the reaction proceeds via the addition of an aryl radical, generated from a Ni (I)/Ni (III) cycle, to a nitrosoarene intermediate.

3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(10): 1194-1198, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33198862

RESUMO

OBJECTIVE: To investigate the c-Jun N-terminal kinase (JNK), CCAAT/enhancer-binding protein homologous protein (CHOP) pathway apoptosis and the changes of cytokine levels in immune-related organs and tissues of sepsis mice at different time points. METHODS: Twenty-seven male BALB/c mice were divided into normal group, sepsis 6 hours group and sepsis 12 hours group by the block randomization method, with 9 mice in each group. The sepsis model was made by cecal ligation and puncture (CLP). Blood sample was collected from each group at the corresponding time point, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1ß, IL-10) were measured by enzyme linked immunosorbent assay (ELISA). The spleen, thymus and appendix tissues were taken from the mice to detect the expressions of phosphorylation-JNK (p-JNK), JNK1, CHOP and cleaved caspase-3 protein by Western Blot. RESULTS: The level of cytokines, p-JNK/JNK1 ratio, CHOP and caspase-3 in spleen tissues, and the CHOP, caspase-3 in thymus and appendix tissue in the sepsis 6 hours group were significantly higher than those in the normal group [serum TNF-α (ng/L): 24.29±3.09 vs. 2.93±2.09, serum IL-1ß (ng/L): 5.00±3.19 vs. 3.54±1.53, serum IL-10 (ng/L): 1 963.93±270.20 vs. 275.09±45.21, spleen p-JNK/JNK1 ratio: 0.257±0.126 vs. 0.154±0.068, spleen CHOP/ß-actin: 0.201±0.131 vs. 0.142±0.068, spleen caspase-3/ß-actin: 0.215±0.126 vs. 0.098±0.088, thymus CHOP/ß-actin: 0.122±0.071 vs. 0.089±0.067, thymus caspase-3/ß-actin: 0.258±0.145 vs. 0.108±0.045, appendix CHOP/ß-actin: 0.361±0.134 vs. 0.215±0.112, appendix caspase-3/ß-actin: 0.439±0.211 vs. 0.321±0.145, all P < 0.05]. However, there were no significant difference in the p-JNK/JNK1 ratio in thymus and appendix (thymus p-JNK/JNK1 ratio: 1.221±0.776 vs. 1.168±0.475, appendix p-JNK/JNK1 ratio: 2.014±1.227 vs. 1.828±0.915, both P > 0.05). Cytokine levels and the p-JNK/JNK1 ratio, CHOP, caspase-3 in spleen, thymus, and appendix in the sepsis 12 hours group were further increased when compared with those in the sepsis 6 hours group, except for a significant decrease in IL-10 level [serum IL-10 (ng/L): 1 698.98±210.52 vs. 1 963.93±270.20, serum TNF-α (ng/L): 41.66±6.57 vs. 24.29±3.09, serum IL-1ß (ng/L): 10.37±4.14 vs. 5.00±3.19, spleen p-JNK/JNK1 ratio: 0.399±0.135 vs. 0.257±0.126, spleen CHOP/ß-actin: 0.298±0.145 vs. 0.201±0.131, spleen caspase-3/ß-actin: 0.353±0.145 vs. 0.215±0.126, thymus p-JNK/JNK1 ratio: 1.667±0.891 vs. 1.221±0.776, thymus CHOP/ß-actin: 0.207±0.133 vs. 0.122±0.071, thymus caspase-3/ß-actin: 0.416±0.179 vs. 0.258±0.145, appendix p-JNK/JNK1 ratio: 2.425±1.361 vs. 2.014±1.227, appendix CHOP/ß-actin: 0.456±0.189 vs. 0.361±0.134, appendix caspase-3/ß-actin: 0.635±0.289 vs. 0.439±0.211, all P < 0.05]. CONCLUSIONS: The endoplasmic reticulum pathway JNK and CHOP pathways are involved in immune-related cell apoptosis and cytokine expression in mice with sepsis. Apoptosis is more obvious at 12 hours than at 6 hours, and the inflammatory response is stronger.


Assuntos
Sepse , Animais , Apoptose , Citocinas , MAP Quinase Quinase 4 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Fator de Necrose Tumoral alfa
4.
Obesity (Silver Spring) ; 28(12): 2424-2430, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33230966

RESUMO

OBJECTIVE: The aim of this study was to determine the relationship between telomere length (TL) in subcutaneous adipose tissue (SAT), visceral adipose tissues (VAT), and leukocytes, as well as to examine the associations of TL in these tissues with postsurgical weight loss in Asians with severe obesity. METHODS: Presurgery TL was measured in leukocytes, SAT, and VAT of 91 patients who underwent weight loss surgery. Correlation between TL in multiple tissues was assessed using Pearson correlation. The association of presurgery TL and postsurgical weight loss at 6 or 12 months, expressed as a percentage of weight loss, was determined using linear regression in 70 patients. RESULTS: Telomeres were longer in VAT compared with those in leukocytes and SAT (P < 0.001) but were highly correlated between tissues. The strongest correlation was observed between TL in VAT and leukocytes (r = 0.739, P = 6.22 × 10-17 ). Compared with individuals in the highest tertile, those in the lowest tertile of VAT TL showed greater weight loss (ß = 6.23, SE = 3.10, P = 0.044) independent of age, sex, ethnicity, types of surgery, diabetes condition, preoperative BMI, and follow-up period. CONCLUSIONS: Among patients with severe obesity, TL in leukocytes and adipose tissue was highly correlated. However, there was variability in the association of TL in these tissues with weight loss after surgery.

5.
PLoS Negl Trop Dis ; 14(10): e0008746, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33064728

RESUMO

Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.

6.
Nutr J ; 19(1): 119, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126880

RESUMO

BACKGROUND: Shorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging. Increased dietary intake of marine n-3 PUFA is associated with reduced telomere attrition. However, the effect of plasma PUFA on leukocyte telomere length (LTL) and its interaction with genetic variants are not well established. METHODS: A nested coronary artery disease (CAD) case-control study comprising 711 cases and 638 controls was conducted within the Singapore Chinese Health Study (SCHS). Samples genotyped with the Illumina ZhongHua-8 array. Plasma n-3 and n-6 PUFA were quantified using mass spectrometry (MS). LTL was measured with quantitative PCR method. Linear regression was used to test the association between PUFA and LTL. The interaction between plasma PUFAs and genetic variants was assessed by introducing an additional term (PUFA×genetic variant) in the regression model. Analysis was carried out in cases and controls separately and subsequently meta-analyzed using the inverse-variance weighted method. We further assessed the association of PUFA and LTL with CAD risk by Cox Proportional-Hazards model and whether the effect of PUFA on CAD was mediated through LTL by using structural equation modeling. RESULTS: Higher n6:n3 ratio was significantly associated with shorter LTL (p = 0.018) and increased CAD risk (p = 0.005). These associations were mainly driven by elevated plasma total n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (p < 0.05). There was a statistically significant interaction for an intergenic single nucleotide polymorphism (SNP) rs529143 with plasma total n-3 PUFA and DHA on LTL beyond the genome-wide threshold (p < 5 ×  10- 8). Mediation analysis showed that PUFA and LTL affected CAD risk independently. CONCLUSIONS: Higher plasma n6:n3 PUFA ratio, and lower EPA and DHA n-3 PUFAs were associated with shorter LTL and increased CAD risk in this Chinese population. Furthermore, genetic variants may modify the effect of PUFAs on LTL. PUFA and LTL had independent effect on CAD risk in our study population.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33087340

RESUMO

INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.

8.
Arch Toxicol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057863

RESUMO

1-Methylpyrene (1-MP) is a common environmental pollutant and animal carcinogen. After sequential activation by cytochromes P450 and sulfotransferases, it induced gene mutations and micronuclei in mammalian cells. The type of micronuclei formed, entire chromosomes or fragments, was not analysed. In this study, 1-MP and its primary metabolite, 1-hydroxymethylpyrene (1-HMP), were investigated for the induction of centromere-positive and -negative micronuclei in the human hepatoma cell line HepG2 and its derivative C3A, expressing relevant enzymes at higher levels. Under a short-exposure (9 h)/long-recovery regime (2 cell cycles in total), 1-MP and 1-HMP provided negative test results in HepG2 cells. However, they induced micronuclei in C3A cells, the effect being blocked by 1-aminobenzotriazole (inhibitor of cytochromes P450s) and reduced by pentachlorophenol (inhibitor of sulfotransferases). Immunofluorescence staining of centromere protein B in the micronuclei revealed purely clastogenic effects under this regime. Unexpectedly, 1-MP and 1-HMP at concentrations 1/5-1/4 of that required for micronuclei formation led to mitotic arrest and spindle aberrations, as detected by immunofluorescence staining of ß- and γ-tubulin. Following extended exposure (72 h, 2 cell cycles, no recovery), damage to the spindle apparatus and centrosomes was detected at even lower concentrations, with concurrent formation of micronuclei. At low concentrations (1-8 µM 1-MP, 0.25-0.5 µM 1-HMP), the micronuclei induced were unexceptionally centromere-positive. Thus, the chromosome-damaging mechanism of 1-MP was regime and concentration dependent: potently aneugenic under persistent exposure, while clastogenic at higher concentrations following a short-exposure/long-recovery regime. This is a convincing evidence for the existence of metabolic activation-dependent aneugens.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33045076

RESUMO

BACKGROUND: Telomere attrition has been proposed as a hallmark of ageing. We previously reported on the association between blood leukocyte telomere length (LTL) at mid-life and risk of chronic diseases and mortality. METHODS: In this study, we investigated the effect of mid-life LTL and genetic proxies on five markers of ageing outcomes, namely handgrip strength, timed up-and-go (TUG), Singapore-modified Mini-Mental State Examination (SM-MMSE) scores, anxiety, and depression indices, measured after a median 20-year follow-up in the Singapore Chinese Health Study (N = 9,581). RESULTS: We observed a significant association between mid-life LTL and handgrip strength later in life (P = 0.004, Padjust = 0.020), as well as a nominal significant association between mid-life LTL and TUG later in life (P = 0.036, Padjust = 0.180). The weighted Genetic Risk Score (wGRS) comprising 15 previously reported LTL reducing loci in East-Asians was not significantly associated with handgrip strength. However, results from Structural Equation Modeling (SEM) showed that the effect of this wGRS on handgrip strength was mediated through LTL (proportion of wGRS effect on handgrip strength mediated through LTL = 33.3%, P = 0.010). CONCLUSIONS: Longer mid-life LTL was associated with increased handgrip strength later in life.

10.
J Am Acad Dermatol ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031838

RESUMO

BACKGROUND: Observational studies have shown promising therapeutic effects of long-pulsed neodymium-doped yttrium aluminum garnet (LP-Nd:YAG) laser on warts. OBJECTIVE: To evaluate whether LP-Nd:YAG laser was superior to cryotherapy for cutaneous warts. METHODS: In this study, 150 adult patients with warts were randomized equally to receive laser or cryotherapy every 3-4 weeks, a maximum of 4 sessions. The primary outcomes were cure rate at 16 weeks and 6 months; secondary outcomes included time to clearance of warts and treatment-related adverse effects. RESULTS: There was no difference in the cure rate for laser versus cryotherapy at 16 weeks (54.1% vs. 46.7%) and 6 months (59.5% vs. 57.3%). However, time to clearance of warts, up to 16 weeks and 6 months, tended to be shorter for laser versus cryotherapy ( P = .04 and .08, respectively). Post-hoc analyses showed a significantly higher cure rate for laser versus cryotherapy in 3 subgroups of HPV 2/27/57-induced recalcitrant warts, but not in their counterpart subgroups. Laser had more mild adverse effects. LIMITATIONS: Single-center. CONCLUSIONS: The overall therapeutic effects of LP-Nd:YAG laser were similar to cryotherapy, but laser may be more effective to relatively recalcitrant warts and may associate with shorter time to clearance of warts.

11.
Adv Mater ; : e2003484, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030787

RESUMO

Atomically dispersed catalysts, with maximized atom utilization of expensive metal components and relatively stable ligand structures, offer high reactivity and selectivity. However, the formation of atomic-scale metals without aggregation remains a formidable challenge due to thermodynamic stabilization driving forces. Here, a top-down process is presented that starts from iron nanoparticles, using dual-metal interbonds (RhFe bonding) as a chemical facilitator to spontaneously convert Fe nanoparticles to single atoms at low temperatures. The presence of RhFe bonding between adjacent Fe and Rh single atoms contributes to the thermodynamic stability, which facilitates the stripping of a single Fe atom from the Fe nanoparticles, leading to the stabilized single atom. The dual single-atom Rh-Fe catalyst renders excellent electrocatalytic performance for the hydrogen evolution reaction in an acidic electrolyte. This discovery of dual-metal interbonding as a chemical facilitator paves a novel route for atomic dispersion of chemical metals and the design of efficient catalysts at the atomic scale.

12.
Contrast Media Mol Imaging ; 2020: 3216179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013244

RESUMO

Background: Urachal carcinoma is a rare urological malignancy. Use of 18F-FDG PET/CT in urological oncology has developed slowly because of the urinary elimination of 18F-FDG. We investigated whether delayed postdiuretic 18F-FDG PET/CT could be used for diagnosing urachal carcinoma. Methods: This retrospective study included 6 patients who underwent delayed postdiuretic 18F-FDG PET/CT for the evaluation of urachal carcinoma. The delayed postdiuretic PET/CT parameters and clinical characteristics of urachal carcinoma were investigated. Results: There was no significant difference in the SUVmax between the primary tumors and the urine in the bladder before delayed diuresis (25.4 ± 19.5 vs. 42.9 ± 31.1, P=0.18). However, the SUVmax of the primary tumors was significantly higher than the SUVmax of urine after delayed diuresis (25.4 ± 19.5 vs. 3.5 ± 1.6, P=0.002). Diuretic 18F-FDG PET/CT was positive in all patients when compared with normal liver tissues or urine after delayed diuresis. The SUVmax, TLR, and TUR of the primary tumors were 25.4 (range: 7.2-58.9), 7.0 (range: 1.8-14.7), and 6.8 (range: 3.8-11.3), respectively. Delayed postdiuretic 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis. One patient received chemotherapy after radical resection of urachal carcinoma because 18F-FDG PET/CT found lung metastases, and one patient only received chemotherapy because PET/CT found peritoneal and skeletal metastases. Conclusions: Delayed postdiuretic 18F-FDG PET/CT is a useful tool for the preoperative evaluation of urachal carcinoma. 18F-FDG PET/CT may improve clinical decision making and management of urachal carcinomas.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32912928

RESUMO

INTRODUCTION: Progressive distal symmetrical axonal neuropathy, a complication of diabetes mellitus (DM), has an unknown cause. Normal physiological metabolism and diabetic dysmetabolism are associated with the generation of γ-diketones. γ-Diketones form pyrroles with protein amines, notably with axonal proteins required for the maintenance of nerve fiber integrity, especially elongate, large-diameter peripheral nerve fibers innervating the extremities. We tested the hypothesis that neuropathy-associated γ-diketone pyrroles are elevated in DM. RESEARCH DESIGN AND METHODS: We measured the urinary concentration of γ-diketone pyrroles in age-matched and gender-matched elderly (60-84 years) persons with (n=267) or without (n=267) indicators of DM based in a community population (9411 community older adults aged ≥60 years) in Shenzhen city, Guangdong, China. We used statistical methods, including a generalized linear model, multivariate logistic regression analysis and restricted cubic splines, to assess linear and nonlinear relationships between urinary γ-diketone pyrroles and indicators of DM. RESULTS: Compared with healthy controls, those with DM had significantly higher levels of fasting blood glucose, glycated hemoglobin A1c, urinary ketone bodies and urinary γ-diketone pyrroles. The median concentration of urinary γ-diketone pyrrole adducts was significantly higher (p<0.0001) in individuals with DM (7.5 (5.4) µM) compared with healthy controls (5.9 (4.3) µM). Both linear and non-linear relations were found between urinary γ-diketone pyrroles and indicators of DM. CONCLUSIONS: Diabetic dysmetabolism includes increased generation and excretion of neuropathy-associated γ-diketone pyrroles. These findings form the foundation for studies to test whether γ-diketone pyrrole concentration correlates with quantitative sensory (vibration and temperature) and electrodiagnostic testing.

14.
Phytochemistry ; 180: 112515, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32957017

RESUMO

Conventional wisdom holds that tea (Camellia sinensis) quality can be improved by drought. To clarify the underlying mechanism, a conjoint analysis of transcriptome and metabolome profiling was carried out in tea shoots harvested under different soil water contents (SWCs). Drought had little impact on theanine, catechins and caffeine in field conditions. Besides the flavor contributions of amino acid and their derivatives, organic acids, and nucleotides and their derivatives, the obviously increased isoflavonoids and glycosylflavonoids and the sharply decreased lipids are suggested to play key roles, which is mainly due to substantial increases of type III polyketide synthase B (PKSB), flavonol synthase/flavanone 3-hydroxylase (FLS), and UDP-glycosyltransferases (UGTs), as well as the significant repression of anthocyanidin synthase (ANS) and R2R3MYBs, and downregulated lipid metabolisms. Genes of GDSL esterase/lipase (GDSL), abscisic acid (ABA) and jasmonate (JA) signaling were found to play important roles in both flavonoid accumulation and lipid reduction. These findings increased our understanding of how moderate drought improves taste and aroma of tea by interfering in the metabolism of fresh leaves, which provides new insight into balancing compounds in pre-harvest tea shoots.


Assuntos
Camellia sinensis , Secas , Metaboloma , Folhas de Planta , Melhoria de Qualidade , Chá , Transcriptoma
15.
J Am Soc Nephrol ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912934

RESUMO

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations.

16.
J Clin Endocrinol Metab ; 105(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936915

RESUMO

CONTEXT: Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations. OBJECTIVE: To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals. DESIGN AND PARTICIPANTS: We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants. RESULTS: Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P < 5 × 10-8). Of the 4 loci, 3 (ADAM15, LINC02226, JUP) were novel for HbA1c associations. At the previously reported HbA1c locus ATXN7L3-G6PC3, association analysis using the exome data fine-mapped the HbA1c associations to a 27-bp deletion (rs769664228) at SLC4A1 that reduced HbA1c by 0.38 ±â€…0.06% (P = 3.5 × 10-10). Further imputation of this variant in SiMES confirmed the association with HbA1c at SLC4A1. We also showed that these genetic variants influence HbA1c level independent of glucose level. CONCLUSION: We identified a deletion at SLC4A1 associated with HbA1c in Malay. The nonglycemic lowering of HbA1c at rs769664228 might cause individuals carrying this variant to be underdiagnosed for diabetes or prediabetes when HbA1c is used as the only diagnostic test for diabetes.

17.
Med Oncol ; 37(10): 89, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920666

RESUMO

The purpose of this study was to prospectively evaluate the distribution of PSMA-targeted, PET-avid lesions in prostate cancer (PCa) patients with biochemical recurrence in a Chinese cohort. The relationships between PSA levels, disease-free time after prostatectomy, and 68Ga-PSMA-11 PET/computed tomography (CT) findings were investigated. Inclusion criteria included histopathologically proven prostate adenocarcinoma, two consecutive PSA levels > 0.20 ng/mL, and negative CT of the abdomen and pelvis or magnetic resonance imaging of the pelvis and whole-body bone scan. Exclusion criteria were non-prostate malignancy within 3 years and persistent PSA after radical prostatectomy. Patients with findings of recurrent disease on re-staging conventional imaging were excluded, as were patients previously treated with systemic therapy and/or salvage therapy. 51 patients were enrolled in this study. 34/51 (66.7%) patients had at least one site of 68Ga-PSMA-11 uptake consistent with PCa. 23.5% of patients had recurrence in the prostate bed, 27.4% had pelvic lymph nodes, 15.7% had extrapelvic lymph node metastases, and 17.6% had bone metastases. For patients with lymph node involvement/metastasis, bone metastasis, and patients with both, their median serum PSA levels were 1.83 ng/mL, 2.54 ng/mL, and 4.03 ng/mL, respectively. They were diagnosed with recurrence with a median of 2.06 years, 2.54 years, and 1.15 years after radical prostatectomy, respectively. In this study of Chinese men with biochemical recurrence, added value for the detection of lesions compatible with sites of PCa was found with 68Ga-PSMA-11 PET/CT over conventional imaging. The observed patterns of disease spread may have implications for understanding the biology of early prostate cancer metastasis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32924504

RESUMO

Anode interface modification is crucial for the stabilization of Li-metal batteries (LMBs), which have been considered as the most promising system for the electric vehicle market owing to their high energy density (500 W h kg-1). However, the biggest challenge for LMBs lies in the preservation of anode reversibility, including plated Li morphology control and dendritic Li inhibition during cycling. Here, we propose a nanostructure modulation strategy of Li grains and plating to activate the anode kinetics of LMBs without the compromise of anode stability. This modulation is triggered by the rapid deposition of ultrathin polydopamine coating on the Cu foil (PDA@Cu), which results in an unusual interlaced growth of vertical or lie-down two-dimensional Li nanoflakes on PDA. The high binding energy (>3 eV) between Li atoms and rich imino/carbonyl groups enables a superior lithiophilicity of PDA to homogenize the Li-ion flowing and Li-mass electroplating with negligible nucleation overpotential. The high Coulombic efficiency (98%) and low voltage hysteresis (∼20 mV) are stabilized for at least 300 cycles in the Li-PDA@Cu cell architecture. This PDA@Cu electrode can even tolerate much higher current densities of 5 and 10 mA cm-2 for 170 and 100 cycles, respectively. The interlaced network of Li nanosheets reinforces the electric contact and therefore charge transfer at the anode-electrolyte interface characterized by small interfacial resistance (<3 Ω cm2) and activation energy (0.28 eV). A viewpoint of robustness loss or mechanical heterogeneity in Li plating is discussed to disclose the evolution from column-like Li grains to porous Li sponges and then to compactly stacked Li nanoflakes with porosity shrinkage.

19.
Mol Genet Genomic Med ; : e1450, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32794371

RESUMO

BACKGROUND: Haptoglobin (Hp) is a plasma protein with strong anti-inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown. METHODS: We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models. RESULTS: Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (ß = 0.073, SE = 0.030, p = 0.015) and non-hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607-0.980), p = 0.033). CONCLUSION: HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non-hypertensive individuals with the same allele had lower risk for mortality in the Chinese population.

20.
J Opt Soc Am A Opt Image Sci Vis ; 37(8): 1244-1248, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32749258

RESUMO

In this paper, a side-coupled liquid sensor and its array based on magneto-optical photonic crystal are proposed. The sensitivity and quality factor of a single magneto-optical photonic crystal sensor are 0.492 mm/RIU and 181,760, respectively. After arraying, the sensitivity of the single microcavity sensor can reach from 0.1 to 0.35 mm/RIU, and the corresponding quality factor can reach from 5×104 to 7×104. Moreover, the structure has good robustness. This work will provide reference for the design of high-performance photonic crystal microcavity sensor arrays.

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