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1.
Mol Med Rep ; 22(5): 4396-4402, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000234

RESUMO

Multiple acyl­CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder of fatty acid metabolism caused by defects in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). These defects are mainly classified into the neonatal and late­onset types, based on their clinical manifestations. ETFDH gene mutations are generally considered to be associated with the late­onset type. The present study reported an adult woman with late­onset MADD accompanied with biochemical and muscle biopsy findings indicating metabolic disorders. Gene sequencing analysis showed that the c.1514T>C homozygous mutation in the region of the 12th exon of the ETFDH gene, which led to the amino acid substitution p.I505T (isoleucine > threonine), resulting in defective ETFDH protein function. The results of family verification revealed that the homozygous mutation originated from her parents. The female patient was treated with a large dose of vitamin B2, L­carnitine and coenzyme Q10, and the symptoms were significantly relieved. The c.1514T>C mutation in the ETFDH gene, was considered as a novel pathogenic mutation that had not been previously reported. Therefore, it was hypothesized that this mutation was responsible for the clinical characteristics of the adult female patient. Overall, this novel mutation could expand the spectrum of the ETFDH gene mutation and provide the basis for the etiological and prenatal diagnosis of MADD.

2.
Histopathology ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33065755

RESUMO

AIMS: Rare data are available concerning the clinicopathologic and molecular features of early subungual melanoma (SM) in the literature, especially targeting Asian population. The aim of this study was to investigate the clinical, histologic, immunohistochemical and chromosomal features of early SM. METHODS AND RESULTS: Fifty-two in situ and 13 thin (Breslow thickness ≤ 1.0mm) SM cases were retrospectively reviewed. All the patients presented with longitudinal melanonychia involving a single digit, and the thumb was the most affected (35/65, 53.8%). Microscopically, most cases showed small to medium nuclear enlargement (58/65) and mild to moderate nuclear atypia (57/65). Hyperchromatism and irregular contours of nuclei were persistent features in all cases. The variation of melanocyte count (the number of melanocytes per mm dermal-epithelial junction) ranged from 31 to 255. Intraepithelial mitoses were identified in 34 cases (52.3%). Statistically, features of in situ lesions including higher melanocyte count (>70), presence of multinucleated melanocytes, inflammatory infiltrate and cutaneous adnexal extension, were associated with early invasion. Melan-A, HMB45, PNL2 and SOX10 antibodies (>95.0%) showed superior sensitivity than S-100 protein (83.1%). FISH results were positive in 15 of 23 successfully analyzed cases. CONCLUSIONS: This is the largest single-institution study of early SM on Asian population, and the largest cohort tested by FISH. Early SM mostly showed small to medium nuclear enlargement and mild to moderate nuclear atypia. High melanocyte count, hyperchromatism and irregular contours of nuclei, and intraepithelial mitoses are crucial diagnostic parameters. Immunohistochemistry, especially the SOX10 staining, and FISH analysis are valuable in diagnosis of SM.

3.
Mol Oncol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031638

RESUMO

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid-binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial-to-mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid ß-oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12's role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP-PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.

4.
Phytother Res ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32869425

RESUMO

Oridonin (Ori) is a natural tetracyclic diterpenoid active compound with excellent antitumor activity, but the mechanism of Ori on esophageal cancer cell, TE1, remains unclear. In this study, we examined the levels of intracellular iron, malondialdehyde, and reactive oxygen species after Ori treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1 cell proliferation is associated with ferroptosis. To understand the molecular mechanism of Ori, we performed UPLC-MS/MS metabolomics profiling on TE1 cells, which show that gamma-glutamyl amino acids (gamma-glutamylleucine, gamma-glutamylvaline), 5-oxoproline, glutamate, GSH, and GSSG are changed significantly after Ori treatment. Meanwhile, the activity of gamma-glutamyl transpeptidase 1 (GGT1) decreased. This revealed that Ori inhibited the gamma-glutamyl cycle in TE1 cells. Furthermore, we found that Ori can covalently bind to cysteine to form the conjugate oridonin-cysteine (Ori-Cys), resulting in the inhibition of glutathione synthesis, which is consistent with the decrease in the enzymatic activity of glutamate cysteine ligase catalytic subunit (GCLC). Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. In conclusion, our experiments indicated that Ori can inhibit the gamma-glutamyl cycle, thereby inducing ferroptosis to exert anti-cancer activity.

5.
Food Chem ; 339: 127885, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32866704

RESUMO

The current study develops an effective, convenient, low-cost, and environmentally friendly method for determining trans-resveratrol (TRA) in peanut oils, the unique proportion of peanut oil, by employing natural cotton fibers without any pretreatment as extraction sorbent and an in-syringe extraction device. The primary factors affecting the extraction recovery are optimized in detail. The condition of 200.0 mg of cotton fibers, six push-pull times, 2.0 mL of n-hexane as washing solvent and 2.0 mL of ethanol as desorption solvent is selected as the best. The linear range is demonstrated to be 10-1000 ng/g with a satisfactory correlation coefficient (R2 = 0.9995), while the limit of detection is calculated as 2.47 ng/g. In addition, the recoveries of TRA are obtained in the range of 93.8-104.4% with RSDs less than 5.5%. Finally, the developed method is successfully applied to determine TRA concentrations in commercial peanut oils and other edible oils.

6.
Pharm Dev Technol ; : 1-10, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-32985928

RESUMO

The use of chemotherapeutic drug paclitaxel (PTX) for the treatment of tumors has several limitations, including multidrug resistance (MDR) and serious adverse reactions. This research aims to co-encapsulate PTX and the chemosensitizer 2-methoxyestradiol (2-ME) into folate-conjugated human serum albumin nanoparticles (FA-HSANPs) to reduce multiple drug resistance and improve antitumor efficiency. The results show PTX/2-ME@FA-HSANPs had uniform particle size (180 ± 12.31 nm) and high encapsulation efficacy. It also exhibited highly potent cytotoxicity and apoptosis-inducing activities in the G2/M phase of PTX-resistant EC109/Taxol cells. Moreover, PTX/2-ME@FA-HSANPs not only displayed better inhibition of tumor growth in S-180 tumor-bearing mice than PTX alone but also reduced pathological damage to normal tissues. In summary, PTX/2-ME@FA-HSANPs could be a promising vehicle for tumor therapy and reducing drug resistance. This research will also provide references for other MDR treatment.

7.
Nat Commun ; 11(1): 4897, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994415

RESUMO

Soil microbial respiration is an important source of uncertainty in projecting future climate and carbon (C) cycle feedbacks. However, its feedbacks to climate warming and underlying microbial mechanisms are still poorly understood. Here we show that the temperature sensitivity of soil microbial respiration (Q10) in a temperate grassland ecosystem persistently decreases by 12.0 ± 3.7% across 7 years of warming. Also, the shifts of microbial communities play critical roles in regulating thermal adaptation of soil respiration. Incorporating microbial functional gene abundance data into a microbially-enabled ecosystem model significantly improves the modeling performance of soil microbial respiration by 5-19%, and reduces model parametric uncertainty by 55-71%. In addition, modeling analyses show that the microbial thermal adaptation can lead to considerably less heterotrophic respiration (11.6 ± 7.5%), and hence less soil C loss. If such microbially mediated dampening effects occur generally across different spatial and temporal scales, the potential positive feedback of soil microbial respiration in response to climate warming may be less than previously predicted.


Assuntos
Carbono/análise , Metagenoma/genética , Microbiota/fisiologia , Microbiologia do Solo , Solo/química , Aclimatação/genética , Archaea/genética , Archaea/isolamento & purificação , Archaea/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Carbono/metabolismo , Ciclo do Carbono , Celulose/metabolismo , DNA Ambiental/genética , DNA Ambiental/isolamento & purificação , Fungos/genética , Fungos/isolamento & purificação , Fungos/metabolismo , Aquecimento Global , Pradaria , Temperatura Alta/efeitos adversos , Metagenômica , Modelos Genéticos , Raízes de Plantas/química , Poaceae/química
8.
Endocrinology ; 161(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910181

RESUMO

The biologically active estrogen estradiol has important roles in adult brain physiology and sexual behavior. A single gene, Cyp19a1, encodes aromatase, the enzyme that catalyzes the conversion of testosterone to estradiol in the testis and brain of male mice. Estradiol formation was shown to regulate sexual activity in various species, but the relative contributions to sexual behavior of estrogen that arises in the brain versus from the gonads remained unclear. To determine the role of brain aromatase in regulating male sexual activity, we generated a brain-specific aromatase knockout (bArKO) mouse. A newly generated whole-body total aromatase knockout mouse of the same genetic background served as a positive control. Here we demonstrate that local aromatase expression and estrogen production in the brain is partially required for male sexual behavior and sex hormone homeostasis. Male bArKO mice exhibited decreased sexual activity in the presence of strikingly elevated circulating testosterone. In castrated adult bArKO mice, administration of testosterone only partially restored sexual behavior; full sexual behavior, however, was achieved only when both estradiol and testosterone were administered together. Thus, aromatase in the brain is, in part, necessary for testosterone-dependent male sexual activity. We also found that brain aromatase is required for negative feedback regulation of circulating testosterone of testicular origin. Our findings suggest testosterone activates male sexual behavior in part via conversion to estradiol in the brain. These studies provide foundational evidence that sexual behavior may be modified through inhibition or enhancement of brain aromatase enzyme activity and/or utilization of selective estrogen receptor modulators.

9.
J Int Med Res ; 48(9): 300060520948717, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32910705

RESUMO

OBJECTIVE: Our objective was to explore the molecular pathogenesis of the onset of gout and the mechanism underlying the effect of interleukin (IL)-37 on PDZ domain-containing 1 (PDZK1) protein through the nuclear factor-κB signaling pathway. METHODS: Real-time PCR and western blotting were used to detect expression of PDZK1 mRNA and protein, respectively, in the HK-2 cell line. The inhibitors pyrrolidine dithiocarbamate (PDTC) and wortmannin were added to HK-2 cells stimulated by IL-37, and changes in PDZK1 protein were detected by western blotting. RESULTS: Based on our previous research, we used 10 µmol/L PDTC. We detected no significant change in PDZK1 at the mRNA level among the IL-37, PDTC+IL-37, and wortmannin+IL-37 groups. With increasing IL-37 concentration, the protein level of PDZK1 increased. After adding wortmannin, the protein level of PDZK1 increased with increasing concentration of IL-37, albeit not significantly, and the level of PDZK1 remained lower than that with IL-37 alone. After adding PDTC, the protein level of PDZK1 showed a trend to decrease with increasing concentrations of IL-37 up to 40 ng/mL. The immunofluorescence results supported the western blot results. CONCLUSIONS: IL-37 can affect protein expression of PDZK1, but not at the translational level, in the pathogenesis of gout.

10.
Sci Total Environ ; 750: 141685, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32862004

RESUMO

Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine ß synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats.

11.
Med Sci Monit ; 26: e924885, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32769960

RESUMO

BACKGROUND Postextubation distress is detrimental to the prognosis of critically ill patients with successful spontaneous breathing trial. The known risk factors of failed weaning are associated with the heart, lungs, and diaphragm. The aim of this study was to explore the role of a combined model including indicators of heart, lung, and diaphragm ultrasound in predicting the weaning outcome. MATERIAL AND METHODS Patients' clinical data and ultrasonic features of heart, lungs, and diaphragm were recorded. Patients were included in either the failed weaning group (n=24) or the successful weaning group (n=81). The association of potential variables with the risk of weaning failure was determined using multivariate logistic regression analysis. The accuracy of potential indicators for predicting the weaning outcome were evaluated and a multiindicator combined model was established to improve the predictive accuracy. RESULTS Brain natriuretic peptide (odds ratio [OR]=1.120, P=0.004), left-atrial pressure (LAP) (OR=1.333, P=0.005), lung ultrasound score (LUS) (OR=1.736, P=0.001), and hemidiaphragm dysfunction (OR=3.942, P=0.014) were associated with an increased risk of weaning failure. However, all of these indicators could not accurately predict the weaning outcome independently (all areas under the curve [AUCs] <0.9). The combination of LAP, LUS, and hemidiaphragm dysfunction showed the highest AUC (AUC=0.919). CONCLUSIONS The combined model including LAP, LUS, and hemidiaphragm dysfunction were the most accurate method for the prediction.

12.
Nutr Metab Cardiovasc Dis ; 30(10): 1751-1757, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32811739

RESUMO

BACKGROUND AND AIMS: The assessment of visceral adiposity is of great significance for the prevention of hyperuricemia (HUA), especially in non-obese individuals. The metabolic score for visceral fat (METS-VF) is a newly proposed surrogate of visceral obesity. We aimed to evaluate the longitudinal associations of METS-VF with the risk of HUA in non-obese adults. METHODS AND RESULTS: A total of 16,058 non-obese adults without HUA were included for this retrospective cohort analyses. The crude incidence rate of HUA in non-obese women and men were 20.9 and 69.6 per 1000 person-years, respectively. The Cox proportional hazards model indicated that METS-VF was significantly associated with the risk of HUA in both genders. Whereas, METS-VF only had the highest HR in women, but not in men. CONCLUSIONS: METS-VF, a novel surrogate of visceral adiposity combined biochemical and anthropometric parameters, age, and gender, could be a useful tool for the hierarchical prevention and management of HUA among non-obese women.

13.
Chin Med J (Engl) ; 133(17): 2114-2115, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32804729
14.
Eur J Med Chem ; 204: 112512, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32736229

RESUMO

Targeted protein degradation using small molecules is a novel strategy for drug development. In order to solve the problem of drug resistance in the treatment of prostate cancer, proteolysis-targeting chimeras (PROTAC) was introduced into the design of anti-prostate cancer derivatives. In this work, we synthesized two series of selective androgen receptor degraders (SARDs) containing the hydrophobic degrons with different linker, and then investigated the structure-activity relationships of these hybrid compounds. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Among them, compound A9 displayed potent inhibitory activity against LNCaP prostate cancer cell line with IC50 values of 1.75 µM, as well as excellent AR degradation activity. Primary mechanism studies elucidated compound A9 arrested cell cycle at G0/G1 phase and induced a mild apoptotic response in LNCaP cells. Further study indicated that the degradation of AR was mediated through proteasome-mediated process. For all these reasons, compound A9 held promising potential as anti-proliferative agent for the development of highly efficient SARDs for drug-resistance prostate cancer therapies.

15.
Biomed Chromatogr ; : e4976, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852057

RESUMO

Multidrug resistance remains a huge challenge in the chemotherapy of cancer and numerous studies have reported that P-glycoprotein is the most common mechanism of multidrug resistance. Verapamil has been shown to be able to reverse development of multidrug resistance mediated by P-glycoprotein. However, the mechanism of action for verapamil in reversing multidrug resistance at the metabolic level has been rarely reported. In this research, we report the reversal effect of verapamil on multidrug resistance and its mechanisms of action using metabolomics. The results show that the P-glycoprotein-mediated chemotherapy drug resistance was significantly reversed by verapamil in resistant SW620/Ad300 cells. In-depth studies demonstrated that verapamil at reversal concentration had no effect on the P-glycoprotein expression level, but increased intramolecular accumulation of paclitaxel in SW620/Ad300 cells. Metabolomics revealed that the multidrug resistance of SW620/Ad300 cells was related to changes in glycerophospholipid metabolism, sphingolipid metabolism and citric acid cycle, and verapamil could antagonize the multidrug resistance by reversing the above-mentioned glycerophospholipid metabolism and sphingolipid metabolism. This research shows the multidrug resistance reversal mechanism of verapamil at the metabolic level, which helps in understanding the exact multidrug resistance mechanism of verapamil and might be potentially useful to find new multidrug resistance reversal agents. The combination of verapamil (VRP) and paclitaxel (PTX) yielded synergistic effects. VRP had no effect on the expression of P-gp, but increased intramolecular accumulation of PTX. VRP antagonized the MDR by regulating glycerophospholipid metabolism and sphingolipid metabolism.

16.
Int J Med Sci ; 17(13): 2052-2062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32788884

RESUMO

Background and aim: The outbreak of coronavirus disease 2019 (COVID-19) is quickly turning into a pandemic. We aimed to further clarify the clinical characteristics and the relationship between these features and disease severity. Methods: In this retrospective single-center study, demographic, clinical and laboratory data were collected and analyzed among moderate, severe and critically ill group patients. Results: 88 hospitalization patients confirmed COVID-19 were enrolled in this study. The average age of the patients was 57.11 years (SD, ±15.39). Of these 88 patients, the median body mass index (BMI) was 24.03 (IQR, 21.64-26.61; range 15.05-32.39), the median duration from disease onset to hospital admission were 11 days (IQR, 6.50-14.50). 46.59% patients had one or more comorbidities, with hypertension being the most common (26.14%), followed by diabetes mellitus (12.50%) and coronary atherosclerotic heart disease (CAD) (7.95%). Common symptoms at onset of disease were fever (71.59%), cough (59.09%), dyspnea (38.64%) and fatigue (29.55%). 88 patients were divided into moderate (47 [53.41%]), severe (32 [36.36%]) and critically ill (9 [10.23%]) groups. Compared with severe and moderate patients, lymphocytopenia occurred in 85.71% critically ill patients, and serum IL-2R, IL-6, IL-8, TNF-α, LDH, and cTnI were also increased in 71.42%, 83.33%, 57.14%, 71.43%, 100% and 42.86% in critically ill patients. Through our analysis, the age, comorbidities, lymphocyte count, eosinophil count, ferritin, CRP, LDH, PT and inflammatory cytokines were statistically significant along with the disease severity. Conclusion: We found some clinical characteristic and inflammatory cytokines could reveal the severity of COVID-19 during the outbreak phage. Our research could assist the clinicians recognize severe and critically ill patients timely and focus on the expectant treatment for each patient.


Assuntos
Infecções por Coronavirus/etiologia , Citocinas/sangue , Pneumonia Viral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , China , Infecções por Coronavirus/terapia , Estado Terminal , Dispneia/virologia , Feminino , Febre/virologia , Hospitalização , Humanos , Inflamação/sangue , Contagem de Leucócitos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
17.
Sci Total Environ ; 744: 140784, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32693278

RESUMO

Climate extremes have resulted in substantial vegetation changes in the marine-terrestrial transitional zone. As a climatically-sensitive region, coastal China is currently experiencing prominent environmental climate change. To identify how climatic extremes affect ecosystem function, we calculated eleven indices of climatic extremes and four mean indices for six sub-regions of coastal China. Deseasonalized thirty-year (1986-2015) net primary productivity (NPP) was used as an indicator of ecosystem productivity, and its relationships with the climate indices were investigated at multiple scales (annual and seasonal) explicitly. The results demonstrated that: (1) annual NPP indicated an overall greening trend (in 73.71% of the study area) and partial degradation (in 26.29% of the study area) over the last thirty decades years; (2) coastal areas had experienced warming overall, with higher increases in nighttime temperatures relative to daytime temperatures; (3) in southern areas, maximum/ minimum daily maximum temperature had driven increases in NPP, whereas in northern areas, this effect varied between vegetation types; (4) Diurnal temperature range (DTR) and NPP were negatively correlated in the north and positively correlated in the south; and (5) Maximum 1-day precipitation promoted vegetation production across the whole study area. Maximum 5-day precipitation promoted vegetation growth in the north but had the opposite effect in the south. Our study advances understanding of vegetation dynamics and its driving mechanisms, and provides support for scientifically informed ecological management practices in coastal China.


Assuntos
Ecossistema , Modelos Teóricos , China , Mudança Climática , Temperatura
18.
Plant Physiol ; 184(1): 283-299, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661060

RESUMO

The thylakoid membrane is a highly complex membrane system in plants and plays crucial roles in the biogenesis of the photosynthetic apparatus and plant development. However, the genetic factors involved in chloroplast development and its relationship with intracellular metabolites are largely unknown. Here, a rice (Oryza sativa) chlorotic and necrotic leaf1 (cnl1) mutant was identified and map-based cloning revealed that a single base substitution followed by a 6-bp deletion in the ATP-binding cassette transporter I family member7 (OsABCI7) resulted in chlorotic and necrotic leaves with thylakoid membrane degradation, chlorophyll breakdown, photosynthesis impairment, and cell death in cnl1 Furthermore, the expression of OsABCI7 was inducible under lower temperatures, which severely affected cnl1 chloroplast development, and etiolated cnl1 seedlings were unable to recover to a normal green state under light conditions. Functional complementation and overexpression showed that OsABCI7 could rescue the cnl1 chlorotic and necrotic phenotype. OsABCI7 interacted with HIGH CHLOROPHYLL FLUORESCENCE222 (OsHCF222) to regulate cellular reactive oxygen species (ROS) homeostasis for thylakoid membrane stability. OsABCI7 localized to thylakoid membranes, while OsHCF222 targeted to endoplasmic reticulum and chloroplasts. Exogenous application of ascorbic acid eased the yellowish leaf phenotype by increasing chlorophyll content and alleviating ROS stress in cnl1 Unlike cnl1, the CRISPR/Cas9-mediated OsHCF222 knockout lines showed chlorotic leaves but were seedling lethal. Our results provide insight into the functions of ABC transporters in rice, especially within the relationship between ROS homeostasis and stability of thylakoid membranes.

19.
Infect Dis (Lond) ; 52(12): 858-865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673126

RESUMO

BACKGROUND: Recurrent tuberculosis (TB) is a major health problem in countries with a high TB burden. It is very necessary to elucidate the situation of recurrent TB in Beijing, capital of China. OBJECTIVE: To determine the proportion of recurrent tuberculosis (TB) cases and to identify relapsed or reinfected cases, as well as risk factors associated with recurrence in Beijing. METHODS: We conducted a retrospective study that included all TB cases in Beijing that were successfully treated from 2013 to 2015. Recurrence due to relapse or reinfection was determined using the variable number of tandem repeats (VNTR) method. Risk factors associated with recurrence were analysed. RESULTS: Tuberculosis recurred in 275 of the 4043 successfully treated TB patients, giving a recurrence rate of 6.8% (275/4043). 190 of the 275 cases were culture positive in both instances, and genotyping results for both episodes were available for 58 of these patients. The cultured isolates from 40 of the 58 recurrent cases (69%) had identical genotypic patterns in both episodes, indicating a relapse. 31% (18/58) had different genotypes, indicating reinfection by a new strain and suggested recent transmission. Those people in the 30-59 age group (p < .001), and those retreated for pulmonary TB (p < .001) were more likely to have TB recurrence. CONCLUSION: Our results indicate that relapse was more common than reinfection in recurrent TB cases in Beijing from 2013 to 2015. Age and retreatment were found to be risk factors for TB recurrence.

20.
Comput Methods Programs Biomed ; 195: 105629, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32634648

RESUMO

BACKGROUND AND OBJECTIVE: Automatic artery/vein (A/V) classification in retinal images is of great importance in detecting vascular abnormalities, which may provide biomarkers for early diagnosis of many systemic diseases. It is intuitive to apply popular deep semantic segmentation network for A/V classification. However, the model is required to provide powerful representation ability since vessel is much more complex than general objects. Moreover, deep network may lead to inconsistent classification results for the same vessel due to the lack of structured optimization objective. METHODS: In this paper, we propose a novel segmentation network named AVNet, which effectively enhances the classification ability of the model by integrating category-attention weighted fusion (CWF) module, significantly improving the pixel-level A/V classification results. Then, a graph based vascular structure reconstruction (VSR) algorithm is employed to reduce the segment-wise inconsistency, verifying the effect of the graph model on noisy vessel segmentation results. RESULTS: The proposed method has been verified on three datasets, i.e. DRIVE, LES-AV and WIDE. AVNet achieves pixel-level accuracies of 90.62%, 90.34%, and 93.16%, respectively, and VSR further improves the performance by 0.19%, 1.85% and 0.64%, achieving the state-of-the-art results on these three datasets. CONCLUSION: The proposed method achieves competitive performance in A/V classification task.

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