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1.
Bioessays ; 45(10): e2300012, 2023 10.
Article in English | MEDLINE | ID: mdl-37246247

ABSTRACT

Precise spatiotemporal control of gene expression during normal development and cell differentiation is achieved by the combined action of proximal (promoters) and distal (enhancers) cis-regulatory elements. Recent studies have reported that a subset of promoters, termed Epromoters, works also as enhancers to regulate distal genes. This new paradigm opened novel questions regarding the complexity of our genome and raises the possibility that genetic variation within Epromoters has pleiotropic effects on various physiological and pathological traits by differentially impacting multiple proximal and distal genes. Here, we discuss the different observations pointing to an important role of Epromoters in the regulatory landscape and summarize the evidence supporting a pleiotropic impact of these elements in disease. We further hypothesize that Epromoter might represent a major contributor to phenotypic variation and disease.


Subject(s)
Enhancer Elements, Genetic , Enhancer Elements, Genetic/genetics , Promoter Regions, Genetic , Cell Differentiation
2.
Plant J ; 116(1): 234-250, 2023 10.
Article in English | MEDLINE | ID: mdl-37387536

ABSTRACT

Enhancers are critical cis-regulatory elements controlling gene expression during cell development and differentiation. However, genome-wide enhancer characterization has been challenging due to the lack of a well-defined relationship between enhancers and genes. Function-based methods are the gold standard for determining the biological function of cis-regulatory elements; however, these methods have not been widely applied to plants. Here, we applied a massively parallel reporter assay on Arabidopsis to measure enhancer activities across the genome. We identified 4327 enhancers with various combinations of epigenetic modifications distinctively different from animal enhancers. Furthermore, we showed that enhancers differ from promoters in their preference for transcription factors. Although some enhancers are not conserved and overlap with transposable elements forming clusters, enhancers are generally conserved across thousand Arabidopsis accessions, suggesting they are selected under evolution pressure and could play critical roles in the regulation of important genes. Moreover, comparison analysis reveals that enhancers identified by different strategies do not overlap, suggesting these methods are complementary in nature. In sum, we systematically investigated the features of enhancers identified by functional assay in A. thaliana, which lays the foundation for further investigation into enhancers' functional mechanisms in plants.


Subject(s)
Arabidopsis , Animals , Arabidopsis/genetics , Enhancer Elements, Genetic/genetics , Promoter Regions, Genetic/genetics , Transcription Factors/genetics , Epigenesis, Genetic
3.
J Am Chem Soc ; 146(32): 22485-22497, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39078367

ABSTRACT

Stereochemically defined organofluorine compounds are central to drug discovery and development. Here, we present a catalytic cross-metathesis method for the synthesis of Z-trisubstituted olefins that contain a Cl- and a CF3-bound carbon terminus. Notably, the process is stereoselective, which is in contrast to the existing stereoretentive strategies that also involve a trisubstituted olefin as starting material. Reactions are catalyzed by a Mo monoaryloxide pyrrolide alkylidene, involve a trisubstituted alkene and gem-Cl,CF3-substituted alkene, and are fully Z-selective. Catalytic cross-coupling can be used to convert the C-Cl bond of the trisubstituted olefin to C-B, C-D, and different C-C bonds. We elucidate the role of Cl,CF3-disubstituted Mo alkylidenes. Experimental and computational (DFT) data show that in some instances a disubstituted alkylidene is formed and then transformed to a more active complex. In other cases, the Cl,CF3-disubstituted alkylidene is a direct participant in a catalytic cycle. The studies described shed new light on the chemistry of high oxidation-state disubstituted alkylidenes-scarcely investigated entities likely to be pivotal to approaches for stereocontrolled synthesis of tetrasubstituted alkenes through olefin metathesis.

4.
BMC Cardiovasc Disord ; 24(1): 458, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198732

ABSTRACT

BACKGROUND: Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). METHODS: This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2-3) and poor CCC formation group (Rentrop grade 0-1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. RESULTS: A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose-response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95% CI: 0.584-0.651, P < 0.001). Furthermore, the net reclassification index (NRI) and integrated discrimination index (IDI) for PIV, concerning the prediction of poor CCC formation, were found to be 0.272 (95% CI: 0.142-0.352, P < 0.001) and 0.051 (95% CI: 0.037-0.065, P < 0.001), respectively. It's noteworthy that both the NRI and IDI values were higher for PIV compared to other inflammatory biomarkers, suggesting its superiority in predictive capacity. CONCLUSIONS: PIV was associated with the formation of CCC. Notably, PIV exhibited potential as a predictor for poor CCC formation and showcased superior predictive performance compared to other complete blood count-based inflammatory biomarkers.


Subject(s)
Collateral Circulation , Coronary Angiography , Coronary Circulation , Coronary Occlusion , Inflammation Mediators , Inflammation , Predictive Value of Tests , Humans , Male , Middle Aged , Coronary Occlusion/physiopathology , Coronary Occlusion/diagnostic imaging , Female , Retrospective Studies , Chronic Disease , Aged , Inflammation/diagnosis , Inflammation/blood , Inflammation/immunology , Inflammation/physiopathology , Inflammation Mediators/blood , Risk Assessment , China , Biomarkers/blood , Risk Factors , Prognosis
5.
BMC Geriatr ; 24(1): 216, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38431549

ABSTRACT

BACKGROUND: The early detection of dementia depends on efficient methods for the assessment of cognitive capacity. Existing cognitive screening tools are ill-suited to the differentiation of cognitive status, particularly when dealing with early-stage impairment. METHODS: The study included 8,979 individuals (> 50 years) with unimpaired cognitive functions, mild cognitive impairment (MCI), or dementia. This study sought to determine optimal cutoffs values for the Cognitive Abilities Screening Instrument (CASI) aimed at differentiating between individuals with or without dementia as well as between individuals with or without mild cognitive impairment. Cox proportional hazards models were used to evaluate the value of CASI tasks in predicting conversion from MCI to all-cause dementia, dementia of Alzheimer's type (DAT), or to vascular dementia (VaD). RESULTS: Our optimized cutoff scores achieved high accuracy in differentiating between individuals with or without dementia (AUC = 0.87-0.93) and moderate accuracy in differentiating between CU and MCI individuals (AUC = 0.67 - 0.74). Among individuals without cognitive impairment, scores that were at least 1.5 × the standard deviation below the mean scores on CASI memory tasks were predictive of conversion to dementia within roughly 2 years after the first assessment (all-cause dementia: hazard ratio [HR] = 2.81 - 3.53; DAT: 1.28 - 1.49; VaD: 1.58). Note that the cutoff scores derived in this study were lower than those reported in previous studies. CONCLUSION: Our results in this study underline the importance of establishing optimal cutoff scores for individuals with specific demographic characteristics and establishing profiles by which to guide CASI analysis.


Subject(s)
Alzheimer Disease , Cognition Disorders , Cognitive Dysfunction , Dementia, Vascular , Humans , Alzheimer Disease/diagnosis , Taiwan/epidemiology , Cognitive Dysfunction/diagnosis , Cognition Disorders/diagnosis , Dementia, Vascular/diagnosis , Cognition , Neuropsychological Tests
6.
Molecules ; 29(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38999159

ABSTRACT

Poly(p-phenylene ethynylene) (PPE) molecular wires are one-dimensional materials with distinctive properties and can be applied in electronic devices. Here, the approach called first-principles quantum transport is utilized to investigate the PPE molecular wire field-effect transistor (FET) efficiency limit through the geometry of the gate-all-around (GAA) instrument. It is observed that the n-type GAA PPE molecular wire FETs with a suitable gate length (Lg = 5 nm) and underlap (UL = 1, 2, 3 nm) can gratify the on-state current (Ion), power dissipation (PDP), and delay period (τ) concerning the conditions in 2028 to achieve the higher performance (HP) request of the International Roadmap for Device and Systems (IRDS, 2022 version). In contrast, the p-type GAA PPE molecular wire FETs with Lg = 5, 3 nm, and UL of 1, 2, 3 nm could gratify the Ion, PDP, and τ concerning the 2028 needs to achieve the HP request of the IRDS in 2022, while Lg = 5 and UL = 3 nm could meet the Ion and τ concerning the 2028 needs to achieve the LP request of the IRDS in 2022. More importantly, this is the first one-dimensional carbon-based ambipolar FET. Therefore, the GAA PPE molecular wire FETs could be a latent choice to downscale Moore's law to 3 nm.

7.
Angew Chem Int Ed Engl ; : e202409435, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38945832

ABSTRACT

In situ analysis of Li plating/stripping processes and evolution of solid electrolyte interphase (SEI) are critical for optimizing all-solid-state Li metal batteries (ASSLMB). However, the buried solid-solid interfaces present a challenge for detection which preclude the employment of multiple analysis techniques. Herein, by employing complementary in situ characterizations, morphological/chemical evolution, Li plating/stripping dynamics and SEI dynamics were directly detected. As a mixed ionic-electronic conducting interface, Li|Li10GeP2S12 (LGPS) performed distinct interfacial morphological/chemical evolution and dynamics from ionic-conducting/electronic-isolating interface like Li|Li3PS4 (LPS), which were revealed by combination of in situ atomic force microscopy and in situ X-ray photoelectron spectroscopy. Though Li plating speed in LGPS was higher than LPS, speed of SSE decomposition was similar and ~85 % interfacial SSE turned into SEI during plating and remained unchanged in stripping. To leverage strengths of different SSEs, an LPS-LGPS-LPS sandwich electrolyte was developed, demonstrating enhanced ionic conductivity and improved interfacial stability with less SSE decomposition (25 %). Using in situ Kelvin probe force microscopy, Li-ion behavior at interface between different SSEs was effectively visualized, uncovering distribution of Li ions at LGPS|LPS interface under different potentials.

8.
Angew Chem Int Ed Engl ; 63(13): e202316837, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38315104

ABSTRACT

The interfacial processes, mainly the lithium (Li) plating/stripping and the evolution of the solid electrolyte interphase (SEI), are directly related to the performance of all-solid-state Li-metal batteries (ASSLBs). However, the complex processes at solid-solid interfaces are embedded under the solid-state electrolyte, making it challenging to analyze the dynamic processes in real time. Here, using in situ electrochemical atomic force microscopy and optical microscopy, we directly visualized the Li plating/stripping/replating behavior, and measured the morphological and mechanical properties of the on-site formed SEI at nanoscale. Li spheres plating/stripping/replating at the argyrodite solid electrolyte (Li6 PS5 Cl)/Li electrode interface is coupled with the formation/wrinkling/inflating of the SEI on its surface. Combined with in situ X-ray photoelectron spectroscopy, details of the stepwise formation and physicochemical properties of SEI on the Li spheres are obtained. It is shown that higher operation rates can decrease the uniformity of the Li+ -conducting networks in the SEI and worsen Li plating/stripping reversibility. By regulating the applied current rates, uniform nucleation and reversible plating/stripping processes can be achieved, leading to the extension of the cycling life. The in situ analysis of the on-site formed SEI at solid-solid interfaces provides the correlation between the interfacial evolution and the electrochemical performance in ASSLBs.

9.
J Am Chem Soc ; 145(14): 8001-8006, 2023 Apr 12.
Article in English | MEDLINE | ID: mdl-36988463

ABSTRACT

The solid electrolyte interphase (SEI) is regarded as the most important yet least understood component in Li-ion batteries. Considerable effort has been devoted to unravelling its chemistry, structure, and ion-transport mechanism; however, the nucleation and growth mode of SEI, which underlies all these properties, remains the missing piece. We quantify the growth mode of two representative SEIs on carbonaceous anodes based on classical nucleation theories and in situ atomic force microscopy imaging. The formation of inorganic SEI obeys the mixed 2D/3D growth model and is highly dependent on overpotential, whereby large overpotential favors 2D growth. Organic SEI strictly follows the 2D instantaneous nucleation and growth model regardless of overpotential and enables perfect epitaxial passivation of electrodes. We further demonstrate the use of large current pulses during battery formation to promote 2D inorganic SEI growth and improve capacity retention. These insights offer the potential to tailor desired interphases at the nanoscale for future electrochemical devices.

10.
Small ; 19(38): e2302015, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37222119

ABSTRACT

Heterojunctions are a promising class of materials for high-efficiency bifunctional oxygen electrocatalysts in both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, the conventional theories fail to explain why many catalysts behave differently in ORR and OER, despite a reversible path (* O2 ⇋* OOH⇋* O⇋* OH). This study proposes the electron-/hole-rich catalytic center theory (e/h-CCT) to supplement the existing theories, it suggests that the Fermi level of catalysts determines the direction of electron transfer, which affects the direction of the oxidation/reduction reaction, and the density of states (DOS) near the Fermi level determines the accessibility for injecting electrons and holes. Additionally, heterojunctions with different Fermi levels form electron-/hole-rich catalytic centers near the Fermi levels to promote ORR/OER, respectively. To verify the universality of the e/h-CCT theory, this study reveals the randomly synthesized heterostructural Fe3 N-FeN0.0324 (Fex N@PC with DFT calculations and electrochemical tests. The results show that the heterostructural F3 N-FeN0.0324 facilitates the catalytic activities for ORR and OER simultaneously by forming an internal electron-/hole-rich interface. The rechargeable ZABs with Fex N@PC cathode display a high open circuit potential of 1.504 V, high power density of 223.67 mW cm-2 , high specific capacity of 766.20 mAh g-1 at 5 mA cm-2 , and excellent stability for over 300 h.

11.
Rev Cardiovasc Med ; 24(10): 305, 2023 Oct.
Article in English | MEDLINE | ID: mdl-39077586

ABSTRACT

Background: The atherogenic index of plasma (AIP), determined by the logarithmic transformation of the ratio of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), was found to be a marker of cardiovascular disease. We sought to investigate the correlation between the atherogenic AIP and coronary collateral circulation (CCC) formation in chronic total occlusive (CTOs) patients. Methods: This retrospective cohort study included 665 non-CTOs and 345 CTOs patients. CTOs were divided into 206 CCC poor formation patients and 139 CCC good formation patients according to the Cohen-Rentrop grade. Spearman correlation analysis was carried out to obtain the relationship between AIP and the Rentrop grade. We used multivariate logistic regression analysis to assess CTOs and CCC poor formation risk factors. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold for AIP to predict CTOs and CCC poor formation. The predicted increment of AIP on CTOs and CCC poor formation was evaluated by calculating the Net Reclassification Index (NRI) and the Integrated Discriminant Index (IDI). Results: AIP in CTOs was significantly elevated compared to non-CTOs patients [(1.55 (1.02, 2.59)) vs (1.26 (0.82, 1.90)), p < 0.001] AIP in the CCC poor formation group was significantly higher than that in the CCC good formation group [(1.73 (1.12, 2.90)) vs (1.37 (0.84, 2.13)), p = 0.002]. There was a negative correlation between AIP and the Rentrop grade (r = -0.145, p = 0.007). The results of multivariate logistic regression revealed that AIP was an independent predictor of CTOs (OR = 4.371, 95% CI: 2.436-7.844, p < 0.001) and CCC poor formation (OR = 3.749, 95% CI: 1.628-8.635, p = 0.002). In the ROC analysis, the area under the curve of AIP for identifying CTOs and CCC poor formation was 0.596 (OR = 3.680, 95% CI: 1.490-9.090, p = 0.005) and 0.597 (95% CI: 0.535-0.658, p = 0.002), respectively. Conclusions: Contrary to previous research, we found that AIP is a moderate but not powerful indicator for detecting both CTO patients and poor CCC formation.

12.
BMC Cancer ; 23(1): 104, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36717819

ABSTRACT

PURPOSE: To explore the potential pathogenesis and clinical features of second primary glioblastoma (spGBM) following first primary renal cell carcinoma (fpRCC). METHODS: Patients with spGBM after fpRCC were enrolled from our institution and the SEER dataset. Sanger sequencing, whole genome sequencing, and immunehistochemistry were used to detect molecular biomarkers. RESULTS: Four and 122 cases from our institution and the SEER dataset, respectively, were collected with an overall median age of 69 years at spGBM diagnosis following fpRCC. The median interval time between fpRCC and spGBM was 50.7 months and 4 years, for the four and 122 cases respectively. The median overall survival time was 11.2 and 6.0 months for the two datasets. In addition, spGBM patients of younger age (< 75 years) or shorter interval time (< 1 year) had favorable prognosis (p = 0.081 and 0.05, respectively). Moreover, the spGBM cases were molecularly classified as TERT only paired with TP53 mutation, PIK3CA mutation, EGFR alteration, low tumor mutation burden, and stable microsatellite status. CONCLUSIONS: This is the first study to investigate the pathogenesis and clinical features of spGBM following spRCC. We found that spGBMs are old-age related, highly malignant, and have short survival time. Moreover, they might be misdiagnosed and treated as brain metastases from RCC. Thus, the incidence of spGBMs after fpRCC is underestimated. Further studies are needed to investigate the underlying molecular mechanisms and clinical biomarkers for the development of spGBM following fpRCC.


Subject(s)
Carcinoma, Renal Cell , Glioblastoma , Kidney Neoplasms , Humans , Aged , Carcinoma, Renal Cell/pathology , Glioblastoma/pathology , Mutation , Genomics , Biomarkers, Tumor/genetics , Prognosis , Kidney Neoplasms/pathology
13.
Acta Oncol ; 62(12): 1757-1766, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37738252

ABSTRACT

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Receptor, EphA7 , STAT3 Transcription Factor , Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , Signal Transduction , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Receptor, EphA7/metabolism
14.
BMC Cardiovasc Disord ; 23(1): 369, 2023 07 22.
Article in English | MEDLINE | ID: mdl-37481526

ABSTRACT

OBJECTIVE: To determine the association between different antihypertensive regimens and cardiovascular disease (CVD) outcomes in hypertensive patients. METHOD: This single center retrospective cohort study analyzed 602 hypertensive patients with complete medical records at Zhongnan Hospital of Wuhan University, China, from January 2016 to November 2022. Baseline data and follow-up data of the included patients were collected, including demographic and clinical characteristics and laboratory results. RESULTS: During the 5-year follow-up period, CVD outcomes occurred in 244 hypertensive patients (40.53%). Compared with patients receiving regular antihypertensive treatment, the incidence of adverse cardiovascular events in patients receiving irregular antihypertensive treatment was significantly higher (62 [55.86%] vs 182 [37.07%], HR 1.642, 95% CI 1.227-2.197, p < 0.001). In subgroup analysis, the results showed that the incidence of CVD was not identical (χ2 = 9.170, p = 0.010). The incidence of adverse cardiovascular events was highest in the single-drug antihypertensive treatment group (43.60%), followed by the multi-drug combination group (41.51%), and lowest in the two-drug combination group (29.58%). Kaplan-Meier curve showed that hypertensive patients treated with two-drug combination antihypertensive had longer overall survival time. We further compared the incidence of CVD between standard blood pressure and intensive blood pressure control, and found no significant difference in the incidence of adverse cardiovascular events between treatment to a systolic blood pressure (SBP) target of less than 140 mmHg compared with a SBP target of less than 120 mmHg (105 [43.93%] vs 35 [29.66%], HR 1.334, 95% CI 0.908-1.961, p = 0.142). CONCLUSION: The incidence of adverse cardiovascular events was significantly different among different antihypertension treatments. Kaplan-Meier survival curve showed that hypertensive patients receiving two-drug combination antihypertensive treatment had longer overall survival time.


Subject(s)
Cardiovascular Diseases , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Antihypertensive Agents/adverse effects , Retrospective Studies , Prognosis , Blood Pressure
15.
BMC Cardiovasc Disord ; 23(1): 534, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37915029

ABSTRACT

OBJECTIVE: The present study aimed to investigate the association of triglyceride-glucose (TyG) index and neutrophil-to-lymphocyte ratio (NLR) with coronary artery disease (CAD), and evaluate the cumulative value of TyG index and NLR in identifying CAD, as well as the severity of CAD. METHODS: This retrospective study enrolled 2867 patients who underwent coronary angiography (CAG) for the first time between January 2013 and June 2022 in Zhongnan Hospital of Wuhan University. There were 2109 patients with CAD and 758 patients without CAD. The CAD patients were divided into two groups based on the median of Gensini score (mild stenosis CAD group: Gensini score < 26 points; severe stenosis CAD group: Gensini score ≥ 26 points). To further evaluate the cumulative value of TyG index and NLR in identifying CAD and CAD severity, all patients were classified into four groups based on median of TyG index and NLR: (1) the control group: patients with low-TyG and low-NLR; (2) isolated high-NLR group: patients with low-TyG and high- NLR; (3) isolated high- TyG group: patients with high-TyG and low- NLR; (4) high-TyG combined with high-NLR group: patients with high-TyG and high- NLR. RESULTS: Multivariate logistic regression analysis showed that both the TyG index and NLR were independent risk factors for CAD, and they were also independent risk factors for severe stenosis in CAD (P < 0.05). Compared with the low-TyG and low- NLR group, patients in high-TyG and high- NLR group had a 1.418 times higher odds ratio (OR) of having CAD and a 1.692 times higher OR of having severe stenosis in CAD in the multivariable logistic regression model. It is worth noting that the OR values of the high-TyG and high- NLR group were higher than those of the isolated high-NLR group and the isolated high- TyG group. The ROC analysis showed that the combination of the TyG index and NLR was superior to TyG index or NLR in predicting CAD and CAD severity. CONCLUSION: Compared to TyG index or NLR, the combination of the TyG index and NLR is beneficial to improve the diagnostic accuracy of CAD and CAD severity.


Subject(s)
Coronary Artery Disease , Humans , Coronary Artery Disease/diagnostic imaging , Glucose , Neutrophils , Retrospective Studies , Constriction, Pathologic , Triglycerides , Lymphocytes , Risk Factors , Biomarkers , Blood Glucose
16.
IEEE Trans Electron Devices ; 70(3): 1236-1242, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36972181

ABSTRACT

In this work, a novel sensing structure based on Au nanoparticles/HfO2/fully depleted silicon-on-insulator (AuNPs/HfO2/FDSOI) MOSFET is fabricated. Using such a planar double gate MOSFET, the electrostatic enrichment (ESE) process is proposed for the ultrasensitive and rapid detection of the coronavirus disease 2019 (COVID-19) ORF1ab gene. The back-gate (BG) bias can induce the required electric field that enables the ESE process in the testing liquid analyte with indirect contact with the top-Si layer. It is revealed that the ESE process can rapidly and effectively accumulate ORF1ab genes close to the HfO2 surface, which can significantly change the MOSFET threshold voltage ([Formula: see text]). The proposed MOSFET successfully demonstrates the detection of zeptomole (zM) COVID-19 ORF1ab gene with an ultralow detection limit down to 67 zM (~0.04 copy/[Formula: see text]) for a test time of less than 15 min even in a high ionic-strength solution. Besides, the quantitative dependence of [Formula: see text] variation on COVID-19 ORF1ab gene concentration from 200 zM to 100 femtomole is also revealed, which is further confirmed by TCAD simulation.

17.
Clin Exp Hypertens ; 45(1): 2185252, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-36863333

ABSTRACT

BACKGROUND: Major adverse cardiovascular events (MACE) are common in patients with hypertension and are associated with higher mortality. METHODS: This study aimed to observe the incidence of MACE in hypertensive patients and the correlation between the electrocardiogram (ECG) T-wave abnormalities and echocardiographic changes. This retrospective cohort study analyzed the incidence of adverse cardiovascular events and changes in echocardiographic features in 430 hypertensive patients admitted to Zhongnan Hospital of Wuhan University from January 2016 to January 2022. Patients were grouped according to a diagnosis of electrocardiographic T-wave abnormalities. RESULTS: Compared with the normal T-wave group, the incidence of adverse cardiovascular events was significantly higher in hypertensive patients with abnormal T-wave (141 [54.9%] vs 120 [69.4%], x^2 = 9.113, P = .003). However, Kaplan-Meier survival curve showed that no survival advantage was observed in the normal T-wave group at all in the hypertensive patients (P = .83). Echocardiographic values associated with cardiac structural markers, including ascending aorta diameter (AAO), left atrial diameter (LA), and interventricular septal thickness (IVS), were significantly higher in the group with abnormal T-wave than those in the group with normal T-wave at baseline and follow-up (P <.05 for all). In addition, in an exploratory Cox regression analysis model stratified by clinical characteristics of hypertensive patients, the forest plot indicated that the variables, including the age (>65 years), hypertension history (>5 years), premature atrial beats, and severe valvular regurgitation were significantly associated with adverse cardiovascular events (P <.05). CONCLUSION: Hypertensive patients with abnormal T-wave show a higher incidence of adverse cardiovascular events. The values of cardiac structural markers were significantly higher in the group with abnormal T-wave.


Subject(s)
Echocardiography , Hypertension , Humans , Aged , Retrospective Studies , Hypertension/complications , Electrocardiography , Aorta
18.
Ann Gen Psychiatry ; 22(1): 40, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37833704

ABSTRACT

OBJECTIVE: Schizophrenia is a serious mental disorder with complex clinical manifestations, while its pathophysiological mechanism is not fully understood. Accumulated evidence suggested the alteration in epigenetic pathway was associated with clinical features and brain dysfunctions in schizophrenia. DNA methyltransferases (DNMTs), a key enzyme for DNA methylation, are related to the development of schizophrenia, whereas the current research evidence is not sufficient. The aim of study was to explore the effects of gene polymorphisms of DNMTs on the susceptibility and symptoms of schizophrenia. METHODS: The study was case-control study that designed and employed the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the diagnostic standard. 134 hospitalized patients with schizophrenia in the Third People's Hospital of Zhongshan City from January 2018 to April 2020 (Case group) as well as 64 healthy controls (Control group) from the same region were involved. Single nucleotide polymorphisms (SNPs) of DNMT1 genes (r s2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) were determined with massARRAY. Linkage disequilibrium analysis and haplotype analysis were performed, and genotype and allele frequencies were compared. The Hardy-Weinberg equilibrium was tested by the Chi-square test in SPSS software (version 20.0, SPSS Inc., USA). The severity of clinical symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS). The correlation between DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs2424932, rs1569686, rs6119954 and rs2424908) and clinical features was analyzed. RESULTS: There were no significant differences in genotype, allele frequency and haplotype of DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) between the case and healthy control group. There were significant differences in the PANSS total positive symptom scores, P3 (hallucinatory behavior), P6 (suspicious/persecution), G7 (motor retardation), and G15 (preoccupation) in patients with different DNMT1 gene rs 2114724 and rs 2228611 genotypes. The linkage disequilibrium analysis of gene polymorphic loci revealed that rs 2114724-rs 2228611 was complete linkage disequilibrium, and rs 1569686-rs 2424908, rs 2424932-rs 1569696 and rs 2424932-rs 2424908 were strongly linkage disequilibrium. CONCLUSION: The polymorphisms alteration in genetic pathway may be associated with development of specific clinical features in schizophrenia.

19.
J Environ Manage ; 344: 118615, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37454450

ABSTRACT

Rapid urbanisation has caused a significant impact on the ecological environment of urban lakes in the world. To maintain the harmonious development of urban progress and water quality, it is essential to evaluate water quality variation and explore the driving factors quantitatively. A comprehensive evaluation method with cluster analysis and Kriging interpolation was used to explore the spatiotemporal variation in a typical urban lake in China, Chaohu Lake, from 2011 to 2020. The correlation between water quality and socioeconomic factors was evaluated by Pearson correlation analysis. Results indicated that: total phosphorus (TP) and total nitrogen (TN) were the key pollution parameters of Chaohu Lake. The pollution situation was gradually improving, however, and the improvement in chemical oxygen demand (COD) is more evident due to anthropogenic control. The spatial heterogeneity of water quality in Chaohu Lake is remarkable, and the water quality is poor in the west but better in the east. Natural attributes of lakes and external load were the main reasons for the spatial heterogeneity. The western residential areas of Chaohu Lake Basin (CLB) are concentrated, and a large amount of industrial and domestic sewage exacerbates water pollution in the west of tributaries. In contrast, the implementation of water environmental governance policies in recent years has alleviated water pollution. From 2011 to 2020, water quality has improved by 23%-35% in the west and 7%-14% in the east. This study provided a framework for quantitatively assessing water quality variation and its driving forces in urban lakes.


Subject(s)
Water Pollutants, Chemical , Water Quality , Lakes , Environmental Monitoring/methods , Conservation of Natural Resources , Environmental Policy , China , Nitrogen/analysis , Phosphorus/analysis , Water Pollutants, Chemical/analysis
20.
Acta Cardiol Sin ; 39(3): 469-479, 2023 May.
Article in English | MEDLINE | ID: mdl-37229327

ABSTRACT

Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue disease (CTD). CTD-associated PAH (CTD-PAH) is the most common subgroup of PAH in East Asia. We prospectively collected 41 patients with CTD-PAH and followed them for a mean period of 43 ± 36 months. The long-term survival rates of the CTD-PAH patients at 1, 2, 3 and 5 years were 90%, 80%, 77%, and 60%, respectively. The non-survivors had more dilated main pulmonary arteries, higher pulmonary artery pressure and pulmonary vascular resistance (PVR). PAH-specific therapy resulted in improvements in functional class, 6-minute walk distance, serum uric acid, right ventricular function and PVR. Increased C-reactive protein during follow-up, indicating inflammatory processes, was also crucial for the management of CTD-PAH. Therefore targeting both PAH and inflammation is important in this specific subgroup of PAH. The results of this study may help develop treatment strategies for CTD-PAH patients.

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