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1.
J Environ Sci (China) ; 125: 630-640, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375945

RESUMO

Biogenic hydrogen sulfide is an odorous, toxic and corrosive gas released from sewage in sewers. To control sulfide generation and emission, nitrate is extensively applied in sewer systems for decades. However, the unexpected sulfide rebound after nitrate addition is being questioned in recent studies. Possible reasons for the sulfide rebounds have been studied, but the mechanism is still unclear, so the countermeasure is not yet proposed. In this study, a lab-scale sewer system was developed for investigating the unexpected sulfide rebounds via the traditional strategy of nitrate addition during 195-days of operation. It was observed that the sulfide pollution was even severe in a sewer receiving nitrate addition. The mechanism for the sulfide rebound can be differentiated into short-term and long-term effects based on the dominant contribution. The accumulation of intermediate elemental sulfur in biofilm resulted in a rapid sulfide rebound via the high-rate sulfur reduction after the depletion of nitrate in a short period. The presence of nitrate in sewer promoted the microorganism proliferation in biofilm, increased the biofilm thickness, re-shaped the microbial community and enhanced biological denitrification and sulfur production, which further weakened the effect of nitrate on sulfide control during the long-term operation. An optimized biofilm-initiated sewer process model demonstrated that neither the intermittent nitrate addition nor the continuous nitrate addition was a sustainable strategy for the sulfide control. To minimize the negative impact from sulfide rebounds, a (bi)monthly routine maintenance (e.g., hydraulic flushing with nitrate spike) to remove the proliferative microorganism in biofilm is necessary.


Assuntos
Sulfeto de Hidrogênio , Nitratos , Esgotos , Sulfetos , Enxofre , Óxidos de Nitrogênio
2.
Chem Sci ; 13(39): 11648-11655, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36320381

RESUMO

Disclosed here is a catalytic asymmetric azidation reaction for the efficient synthesis of α-azido ketones bearing a labile tertiary stereocenter. With a superb chiral squaramide catalyst, a mild asymmetric formal H-N3 insertion of α-carbonyl sulfoxonium ylides proceeded with excellent efficiency and enantioselectivity. This organocatalytic process not only complements the previous α-azidation approaches for the formation of quaternary stereocenters and mostly for 1,3-dicarbonyl compounds, but also has advantages over the well-known metal-catalyzed asymmetric carbene insertion chemistry using α-diazocarbonyl compounds. Detailed mechanistic studies via control reactions and NMR studies provided important insights into the reaction pathway, which features reversible protonation and dynamic kinetic resolution. The curiosity in mechanism also led to the development of a simplified alternative protocol with a cheaper HN3 source.

3.
Molecules ; 27(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36364157

RESUMO

Cancer is a leading cause of death worldwide, with an increasing mortality rate over the past years. The early detection of cancer contributes to early diagnosis and subsequent treatment. How to detect early cancer has become one of the hot research directions of cancer. Tumor biomarkers, biochemical parameters for reflecting cancer occurrence and progression have caused much attention in cancer early detection. Due to high sensitivity, convenience and low cost, biosensors have been largely developed to detect tumor biomarkers. This review describes the application of various biosensors in detecting tumor markers. Firstly, several typical tumor makers, such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), squamous cell carcinoma antigen (SCCA), carbohydrate, antigen19-9 (CA19-9) and tumor suppressor p53 (TP53), which may be helpful for early cancer detection in the clinic, are briefly described. Then, various biosensors, mainly focusing on electrochemical biosensors, optical biosensors, photoelectrochemical biosensors, piezoelectric biosensors and aptamer sensors, are discussed. Specifically, the operation principles of biosensors, nanomaterials used in biosensors and the application of biosensors in tumor marker detection have been comprehensively reviewed and provided. Lastly, the challenges and prospects for developing effective biosensors for early cancer diagnosis are discussed.


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Neoplasias , Masculino , Humanos , Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias/diagnóstico , Biomarcadores
4.
Diabetol Metab Syndr ; 14(1): 167, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369095

RESUMO

BACKGROUND: It is still debatable whether glycated albumin/glycated hemoglobin A1C (GA/HbA1C) ratio is associated with metabolic dysfunction-associated fatty liver disease (MAFLD), and few studies have been conducted in type 2 diabetes mellitus (T2DM). Therefore, we aimed to investigate the association between GA/HbA1C ratio and MAFLD and to evaluate whether GA/HbA1C ratio can be used an indicator of MAFLD in Chinese patients with T2DM. METHODS: This cross-sectional study consisted of 7117 T2DM patients including 3296 men and 3821 women from real-world settings. Abdominal ultrasonography was performed to diagnose MAFLD. In addition to comparing the clinical characteristics among the GA/HbA1C ratio quartile groups, we also investigated the associations of GA/HbA1C ratio and quartiles with MAFLD in T2DM subjects. RESULTS: There was a significantly decreased trend in the MAFLD prevalence across the GA/HbA1C ratio quartiles (56.3%, 47.4%, 37.8%, and 35.6% for the first, second, third, and fourth quartile, respectively, P < 0.001 for trend) after adjusting for gender, age, and diabetes duration. Fully adjusted Binary logistic regression indicated that both GA/HbA1C ratio (OR: 0.575, 95% CI: 0.471 to 0.702, P < 0.001) and quartiles (P < 0.001 for trend) were inversely associated with the presence of MAFLD among T2DM patients. Additionally, HOMA2-IR values were clearly increased in the T2DM subjects with MAFLD compared with those without MAFLD (P < 0.001), and markedly increased from the highest to the lowest GA/HbA1C ratio quartile (P < 0.001 for trend). CONCLUSIONS: GA/HbA1C ratio is closely and negatively associated with MAFLD in T2DM subjects, which may attribute to that GA/HbA1C ratio reflects the degree of insulin resistance. GA/HbA1C ratio may act as a simple and practical indicator to evaluate the risk of MAFLD in T2DM.

5.
Langmuir ; 38(45): 13955-13962, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377412

RESUMO

Three self-assembled nanoaggregates (CPUL1-LA NAs, CPUL1-DA NAs, and CPUL1-AA NAs) were constructed through lipoic acid (LA), dithiodipropionic acid (DA), and adipic acid (AA) decorated TrxR inhibitor (CPUL1), respectively. Measurements of DLS, TEM, UV-vis, fluorescence, 1H NMR, ITC, and MTT assays verified disulfide-containing CPUL1-LA NAs and CPUL1-DA NAs spontaneously assembled carrier-free nanoparticles in aqueous solution, which possessed high drug contents, excellent stability, improved cytotoxicity against HUH7 hepatoma cells, and potential biosafety because of low cytotoxicity against L02 normal cells. In contrast, disulfide-free CPUL1-AA NAs happened to aggregate and precipitate after 48 h, which showed distinct instability in aqueous solution. Thus, disulfide units seemed to be crucial for constructing controllable and stable nanoaggregates. While measuring the reduction of nanoaggregates by TrxR/NADPH and GSH/GR/NADPH, cyclic disulfide of LA and linear disulfide of DA were verified to endow the nanoaggregates with targeting ability to respond specifically to TrxR over GSH. Furthermore, by tests of flow cytometry, fluorescence images, and CLSM, both CPUL1-LA NAs and CPUL1-DA NAs displayed a faster cellular uptake characteristic to be internalized by cancer cells and could generate more abundant ROS to induce cell apoptosis than that of free CPUL1, resulting in significantly improved antitumor efficacy against HUH7 cells in vitro.


Assuntos
Dissulfetos , Nanopartículas , Dissulfetos/farmacologia , Dissulfetos/química , NADP , Nanopartículas/química , Transporte Biológico
6.
Plant Biotechnol (Tokyo) ; 39(3): 251-257, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36349228

RESUMO

Codonopsis pilosula, a traditional Chinese medicinal and edible plant, contains several bioactive components. However, the biosynthetic mechanism is unclear because of the difficulties associated with functional gene analysis. Therefore, it is important to establish an efficient genetic transformation system for gene function analysis. In this study, we established a highly efficient Agrobacterium-mediated callus genetic transformation system for C. pilosula using stems as explants. After being pre-cultured for 3 days, the explants were infected with Agrobacterium tumefaciens strain GV3101 harboring pCAMBIA1381-35S::GUS at an OD600 value of 0.3 for 15 min, followed by co-cultivation on MS induction medium for 1 day and delayed cultivation on medium supplemented with 250 mg l-1 cefotaxime sodium for 12 days. The transformed calli were selected on screening medium supplemented with 250 mg l-1 cefotaxime sodium and 2.0 mg l-1 hygromycin and further confirmed by PCR amplification of the GUS gene and histochemical GUS assay. Based on the optimal protocol, the induction and transformation efficiency of calli reached a maximum of 91.07%. The establishment of a genetic transformation system for C. pilosula calli lays the foundation for the functional analysis of genes related to bioactive components through genetic engineering technology.

7.
Ecol Evol ; 12(11): e9464, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36349253

RESUMO

Sanjiangyuan National Park (SNP), the first national park in China, is one of the most important biodiversity conservation areas in the Sanjiangyuan National Nature Reserve (SNNR) and even the world. The threatened ungulates play an irreplaceable role in maintaining the ecosystem diversity and stability in SNNR. Here, based on 1434 occurrence records of six ungulates, the maximum entropy model, with two different strategies, was utilized to determine the priority reserves. The results indicated that the priority reserves in SNNR was mainly located in and around SNP, which were mainly distributed in the middle east, middle west, and southwest of SNNR. Six ungulates shared preference for altitude ranging 4000-5000 m, the average annual temperature below -3.0°C, and average annual precipitation ranging 200-400 mm on meadow, steppe, and unused land. The proportion of high and medium suitable areas for ungulates in SNP was higher than that in SNNR. As the SNP is not contiguously spaced in space, and some core wildlife habitats are not included, it is suggested to optimize the functional areas and adjust the boundary range on the basis of the pilot scope of SNP, so as to enhance the integrity and connectivity of each functional area.

8.
Neuropsychiatr Dis Treat ; 18: 2529-2541, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349344

RESUMO

Objective: Scavenger receptor A (SRA), a pattern recognition molecule, is implicated in immune response after acute brain injury. We strived to identify serum soluble SRA (sSRA) as a potential biomarker of prognosis after aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective observational study, we quantified serum sSRA levels of 131 aSAH patients and 131 healthy controls. A poor outcome was defined as extended Glasgow outcome scale (GOSE) scores of 1-4 at 90 days after injury. Relations of serum sSRA levels to severity, delayed cerebral ischemia (DCI) and poor outcome were assessed using multivariate analysis. Predictive efficiency was determined via area under receiver operating characteristic curve (AUC). Results: Serum sSRA levels were markedly higher in aSAH patients than in controls (median, 2.9 ng/mL versus 1.0 ng/mL; P < 0.001). Serum sSRA levels were independently correlated with Hunt-Hess scores (beta, 0.569; 95% confidence interval (CI), 0.244-0.894; P = 0.001), modified Fisher scores (beta, 0.664; 95% CI, 0.254-1.074; P = 0.002) and 90-day GOSE scores (beta, -0.275; 95% CI, -0.440-0.110; P = 0.005). Serum sSRA levels independently predicted DCI (odds ratio, 1.305; 95% CI, 1.012-1.687; P = 0.040) and a poor outcome (odds ratio, 2.444; 95% CI, 1.264-4.726; P = 0.008), as well as showed significant accuracy for the discrimination of DCI (AUC, 0.753; 95% CI, 0.649-0.857; P < 0.001) and a poor outcome (AUC, 0.800; 95% CI, 0.721-0.880; P < 0.001). Its combination with Hunt-Hess scores and modified Fisher scores displayed significantly improved AUCs for predicting DCI and poor outcome, as compared to any of them (all P < 0.05). Conclusion: There is a significant elevation of serum sSRA levels after aSAH, which in close correlation with illness severity, are independently associated with DCI and poor clinical outcome after aSAH. Hypothetically, SRA may regulate immune response in acute brain injury after aSAH and serum sSRA is presumed to be a potential prognostic biomarker of aSAH.

9.
J Gastrointest Oncol ; 13(5): 2553-2564, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388690

RESUMO

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36360959

RESUMO

BACKGROUND: Our study sought to characterize the knowledge and willingness levels regarding vaccinations against pertussis and seasonal influenza (influenza) among pregnant women in Guizhou province, China, which have previously been unclear. METHODS: In total, 11 hospitals that carried out obstetrics and antenatal examination services were randomly included in the target organizations, and 564 questionnaires completed by the pregnant women were collected and analyzed in Guizhou province. The questionnaires contained questions addressing awareness and knowledge of pertussis and influenza, willingness to be vaccinated at different life stages, and the basic statuses of subjects. A two-paired McNemar test was used to compare the knowledge levels on pertussis and influenza. A Friedman test was used to compare the willingness to be vaccinated at different life stages. To explore the factors influencing knowledge levels, a chi-square test and binary logistic regression were used with stepwise backward regression. RESULTS: In total, 11.9 percent of the pregnant women had received influenza vaccines in the year prior to their pregnancy in Guizhou province. The pregnant women had poorer knowledge of pertussis than of influenza. Given a vaccine was available, the willingness of pregnant women to partake in the following vaccination-related actions could be ranked, from highest to lowest: free vaccination of babies, recommend vaccination to family members, postpartum vaccination, vaccination of babies at mothers' expense, and vaccination during pregnancy. Knowledge levels played different roles in the women's willingness to receive vaccinations at different life stages. Common knowledge of pertussis and influenza played a limited role in the willingness to receive maternal vaccinations. Among the pregnant women, the factors influencing the low levels of pertussis knowledge were occupation as nonmedical-institution staff, lower educational level, pregnancy stage past the first trimester, and not bearing children; for influenza, the factors were occupation as nonmedical-institution staff, lower educational level, denial of pregnancy-induced disease, and lower monthly household income per capita. CONCLUSIONS: Pregnant women have poorer levels of knowledge on pertussis than influenza, whereas there was no significant difference in their willingness to be vaccinated against these conditions. Health education on pertussis should be strengthened and we called for vaccines given at birth.


Assuntos
Vacinas contra Influenza , Influenza Humana , Complicações Infecciosas na Gravidez , Coqueluche , Recém-Nascido , Criança , Feminino , Gravidez , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Gestantes , Coqueluche/prevenção & controle , Vacina contra Coqueluche/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Vacinação , Conhecimentos, Atitudes e Prática em Saúde , Complicações Infecciosas na Gravidez/prevenção & controle , Parto
11.
Pharmacol Res ; 186: 106529, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36328301

RESUMO

Poly ADP-ribose polymerase (PARP) plays a critical role in many cellular processes such as DNA damage repair, gene transcription and cell apoptosis. Therefore, targeting PARP represents a promising strategy for cancer therapy. To date, numerous small molecule PARP1 inhibitors have been identified, but many of them suffer from limited clinical efficacy and serious toxicity. Hence, PARP1 inhibitor-based combination therapies, and other PARP1 modulators (e.g. PROTAC degraders, dual acting agents) have attracted great attention with significant advancements achieved in the past few years. In this review, we overviewed the recent progress on PARP1-based drug discovery with a focus on PARP1 inhibitor-based drug combination therapy and other PARP1-targeting strategies (e.g. selective PARP1 inhibitors, PARP1-based dual-target inhibitors, PROTAC PARP1 degraders, and prodrugs of PARP1 inhibitors). In addition, we also summarized the reported co-crystal structures of PARP1 inhibitors in complex with their target proteins as well as the binding interactions. Finally, the challenges and future directions for PARP-based drug discovery in cancer therapy are also discussed in detail.

12.
Nat Commun ; 13(1): 6669, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335134

RESUMO

Biological ion channels rely on ions as charge carriers and unidirectional ion flow to produce and transmit signals. To realize artificial biological inspired circuitry and seamless human-machine communication, ion-transport-based rectification devices should be developed. In this research, poly(methyl methacrylate) (PMMA) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) gel polymer electrolytes (GPEs) are assembled to construct a novel ionic diode, enabling ion rectification through ion-diffusion/migration that emulates biological systems. This ion rectification results from the different diffusion/migration behaviors of mobile ions transporting in the GPE heterojunction. The electrical tests of the GPE heterojunction reveal outstanding rectifying ratio of 23.11. The GPE ionic diode operates in wide temperature window, from -20 °C (anti-freezing) to 125 °C (thermal tolerance). The absence of redox reactions is verified in the cyclic voltammogram. The GPE ionic diodes are used to construct ionic logic gates for signal communication. Furthermore, rectification of a triboelectric nanogenerator and potential for synaptic devices are demonstrated.


Assuntos
Eletrólitos , Polímeros , Humanos , Íons , Polimetil Metacrilato , Transporte de Íons
13.
RSC Adv ; 12(49): 32056-32060, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36415556

RESUMO

Catalytic asymmetric α-regioselective Michael additions of vinylogous α-ketoester enolate are described herein. With 0.1-1.0 mol% loadings of a chiral bifunctional organocatalyst, the addition of a deconjugated α-keto ester to a series of nitroolefins, including the challenging ß-alkylnitroalkenes, efficiently proceed, providing the Rauhut-Currier type products after isomerization of the terminal double bond in good yields (60-88%) with excellent regio- and enantioselectivities (94-99% ee, TON up to 160 with 0.5 mol% of the catalyst).

14.
Toxicol Lett ; 373: 22-32, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375637

RESUMO

Dasatinib, a second-generation BCR-ABL inhibitor, is currently used as first-line treatment for patients with chronic myeloid leukemia. However, dasatinib treatment increases the risk of severe cutaneous toxicity, which limits its long-term safe use in clinic. The underlying mechanism for dasatinib-induced cutaneous toxicity has not been clarified. In this study, we tested the toxicity of dasatinib on human immortal keratinocyte line (HaCaT) and normal human epidermal keratinocytes (NHEK). We found that dasatinib directly caused cytotoxicity on keratinocytes, which could be the explanation of the clinical characteristic of pathology. Mechanistically, dasatinib impaired mitophagy by downregulating HMGB1 protein level in keratinocytes, which led to the accumulation of dysfunctional mitochondria. Mitochondria-derived ROS caused DNA damage and cell apoptosis. More importantly, we confirmed that overexpression of HMGB1 could reverse dasatinib-induced keratinocyte apoptosis, and preliminarily explored the intervention effect of saikosaponin A, which could increase HMGB1 expression, on cutaneous toxicity caused by dasatinib. Collectively, our study revealed that dasatinib induced keratinocyte apoptosis via inhibiting HMGB1-mediated mitophagy and saikosaponin A could be a viable strategy for prevention of dasatinib-induced cutaneous toxicity.

15.
Front Immunol ; 13: 1009621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389707

RESUMO

Background: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. Methods: A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. Results: Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. Conclusion: Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Humanos , Neoplasias Pulmonares/patologia , Imunoterapia/métodos , Fatores Imunológicos/uso terapêutico , Biomarcadores
16.
Front Endocrinol (Lausanne) ; 13: 948338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407305

RESUMO

Aims: We aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (<6.2, 6.2-7.9, 8.0-8.9, 9.0-10.9, and >10.9 µmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression. Results: The prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747-0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647-0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles. Conclusions: Serum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Humanos , Masculino , Feminino , Espessura Intima-Media Carotídea , Estudos Transversais , Constrição Patológica/complicações , Aterosclerose/complicações , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/epidemiologia , Placa Aterosclerótica/complicações , Bilirrubina
17.
Commun Biol ; 5(1): 1134, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289367

RESUMO

As global warming intensifies, heat stress has become a major environmental constraint threatening crop production and quality worldwide. Here, we characterize Heat-induced long intergenic noncoding RNA 1 (HILinc1), a cytoplasm-enriched lincRNA that plays a key role in thermotolerance regulation of pear (Pyrus spp.). HILinc1 Target 1 (PbHILT1) which is the target transcript of HILinc1, was stabilized via complementary base pairing to upregulate its expression. PbHILT1 could bind to Heat shock transcription factor A1b (PbHSFA1b) to enhance its transcriptional activity, leading to the upregulation of a major downstream transcriptional regulator, Multiprotein bridging factor 1c (PbMBF1c), during heat response. Transient overexpressing of either HILinc1 or PbHILT1 increases thermotolerance in pear, while transient silencing of HILinc1 or PbHILT1 makes pear plants more heat sensitive. These findings provide evidences for a new regulatory mechanism by which HILinc1 facilitates PbHSFA1b activity and enhances pear thermotolerance through stabilizing PbHILT1 transcripts.


Assuntos
Pyrus , RNA Longo não Codificante , Termotolerância , Pyrus/genética , Pyrus/metabolismo , Termotolerância/genética , Fatores de Transcrição de Choque Térmico/metabolismo , RNA Longo não Codificante/genética , Pareamento de Bases , Proteínas de Choque Térmico/metabolismo
18.
Small ; 18(46): e2204707, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36193958

RESUMO

Boosting reversible solid-liquid phase transformation from lithium polysulfides to Li2 S and suppressing the shuttling of lithium polysulfides from the cathode to the lithium anode are critical challenges in lithium-sulfur batteries. Here, sulfiphilic single atomic cobalt implanted in lithiophilic heteroatoms-dopped carbon (SACo@HC) matrix with a CoN3 S structure for high-performance lithium-sulfur batteries is reported. Density functional theory calculation and in situ experiments demonstrate that the optimal CoN3 S structure in SACo@HC can effectively improve the adsorption and redox conversion efficiency of lithium polysulfides. Consequently, the S-SACo@HC composite with sulfur loading of 80 wt% delivers a high capacity of 1425.1 mAh g-1 at 0.05 C and outstanding rate performance with 745.9 mAh g-1 at 4 C. Furthermore, a capacity of 680.8 mAh g-1 at 0.5 C with a low electrolyte/sulfur ratio (6 µL mg-1 ) can be achieved even after 300 cycles. With the harsh conditions of lean electrolyte (E/S = 4 µL mg-1 ) and high sulfur loading (5.4 mg cm-2 ), a superior area capacity of 5.8 mAh cm-2 can be obtained. This work contributes to building a profound understanding of the adsorption and interface engineering of lithium polysulfides and provides ideas to tackle the long-standing polysulfide shuttle problem of lithium-sulfur batteries.

19.
Angew Chem Int Ed Engl ; : e202214545, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36278974

RESUMO

Serious safety risks caused by the high reactivity of lithium metal against electrolytes severely hamper the practicability of lithium metal batteries. By introducing unique polymerization site and more fluoride substitution, we built an in situ formed polymer-rich solid electrolyte interphase upon lithium anode to improve battery safety. The fluorine-rich and hydrogen-free polymer exhibits high thermal stability, which effectively reduces the continuous exothermic reaction between electrolyte and anode/cathode. As a result, the critical temperature for thermal safety of 1.0 Ah lithium-LiNi0.5 Co0.2 Mn0.3 O2 pouch cell can be increased from 143.2 °C to 174.2 °C. The more dangerous "ignition" point of lithium metal batteries, the starting temperature of battery thermal runaway, has been dramatically raised from 240.0 °C to 338.0 °C. This work affords novel strategies upon electrolyte design, aiming to pave the way for high-energy-density and thermally safe lithium metal batteries.

20.
Cell Death Dis ; 13(10): 873, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243874

RESUMO

Lung squamous cell carcinoma (LUSC) is a histological subtype of non-small cell lung cancer with the worse progression. SRY-Box Transcription Factor 2 (SOX2) copy number amplification (CNA) is the oncogenic driver in ~60% of patients diagnosed with LUSC. Thus, SOX2 represents an effective therapeutic target in SOX2-amplified LUSC. However, SOX2 protein was considered undruggable. Here, we report the expression of a circular RNA, cicSOX2 in SOX2-amplified LUSC. Patients with SOX2-CAN LUSC expressing circSOX2 manifested increased survival outcomes. CircSOX2 suppressed the proliferation, metastasis, and sphere formation in SOX2-amplified LUSC in vitro and in vivo. CircSOX2 originates in the reverse strand of the SOX2 gene and its sequence was reverse complement to partial 3'UTR of SOX2-coding transcript (mSOX2). CircSOX2 bound to AUF1 and occupied in the 3'UTR of mSOX2, inducing the degradation of mSOX2. In general, circSOX2 is an endogenous self-restricted circRNA in SOX2-amplified LUSC. CircSOX2 might be an effective and stable nucleic acid drug candidate in SOX2-amplified LUSC with low immunogenicity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Regiões 3' não Traduzidas , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , RNA Circular/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Fatores de Transcrição/metabolismo
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