Epromoters are new players in the regulatory landscape with potential pleiotropic roles.

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.

Genome-wide enhancer identification by massively parallel reporter assay in Arabidopsis.

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.

Synthesis of Z-gem-Cl,CF3-Substituted Alkenes by Stereoselective Cross-Metathesis and the Role of Disubstituted Mo Alkylidenes.

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.

Amorphous AlOCl Compounds Enabling Nanocrystalline LiCl with Abnormally High Ionic Conductivity.

LiCl is a promising solid electrolyte, providing it possesses high ionic conductivity. Numerous efforts have been made to enhance its ionic conductivity through aliovalent doping. However, aliovalent substitution changes the intrinsic structure of LiCl, compromising its cost-effectiveness and electrochemical stability. Here, we report nanocrystalline LiCl embedded in amorphous AlOCl compounds with a heterogeneous structure to enhance its ionic conductivity. Nanocrystallization enlarges the LiCl unit cell, while amorphization facilitates interfacial ion transport. As a result, the amorphous AlOCl-modified LiCl nanocrystal (AlOCl-nanoLiCl) demonstrates a high ionic conductivity of 1.02 mS cm-1, which is 5 orders of magnitude higher than that of LiCl. Additionally, it exhibits high oxidative stability, low cost ($19.87 US kg-1), and low Young's modulus (2-3 GPa). When AlOCl-nanoLiCl is coupled with Li-rich cathodes (Li1.17Mn0.55Ni0.24Co0.05O2, 4.8 V vs Li+/Li), all-solid-state batteries exhibit remarkable long-term cycling stability (>1000 cycles). This work presents a novel strategy to enhance the ionic conductivity of alkaline chlorides without compromising their intrinsic advantages.

Realizing Stable Luminescence in Antimony Doped Hybrid Tin(IV) Chloride toward Full Spectrum WLED and Anticounterfeiting Applications.

The outstanding optical properties empower Sb3+-doped zero-dimensional hybrid metal halides as cutting-edge luminescent materials. In this research, we present an efficient hybrid tin chloride, TEA2SnCl6:Sb3+ (TEA = tetraethylammonium), with broad dual emission bands peaking in the blue and orange regions that arise from the singlet and triplet state emissions of [SbCl5]2-, respectively. TEA2SnCl6:Sb3+ demonstrates a high photoluminescence quantum yield (PLQY) of 83.5% under 328 nm excitation, while 358 nm light induces an orange emission with a PLQY of 92.5% and a low thermal quenching behavior (73.9% at 423 K). Benefiting from the appealing luminescence properties of TEA2SnCl6:Sb3+, a full spectrum white light-emitting diode (WLED) device and an anticounterfeiting model were constructed, affirming the potential use of Sb3+-doped TEA2SnCl6 hybrid metal halide in versatile application fields.

Association between the pan-immune-inflammation value and coronary collateral circulation in chronic total coronary occlusive patients.

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.

Determining optimal cutoff scores of Cognitive Abilities Screening Instrument to identify dementia and mild cognitive impairment in Taiwan.

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.

High-Performance One-Dimensional Sub-5 nm Transistors Based on Poly(p-phenylene ethynylene) Molecular Wires.

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.

Nanoscale Visualization of Lithium Plating/Stripping Tuned by On-site Formed Solid Electrolyte Interphase in All-Solid-State Lithium-Metal Batteries.

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.

In Situ Analysis of Interfacial Morphological and Chemical Evolution in All-Solid-State Lithium-Metal Batteries.

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.

Nucleation and Growth Mode of Solid Electrolyte Interphase in Li-Ion Batteries.

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.

Spontaneous Internal Electric Field in Heterojunction Boosts Bifunctional Oxygen Electrocatalysts for Zinc-Air Batteries: Theory, Experiment, and Application.

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.

The Atherogenic Index of Plasma is a Predictor for Chronic Total Occlusion and Coronary Collateral Circulation Formation in CTOs Patients.

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.

Clinical and genomic features in patients with second primary glioblastoma following first primary renal cell carcinoma.

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.

STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma.

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.

The correlation between different antihypertensive treatments and prognosis of cardiovascular disease in hypertensive patients.

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.

Association of triglyceride-glucose index and neutrophil-to-lymphocyte ratio with coronary artery disease.

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.

Au Nanoparticles/HfO2/Fully Depleted Silicon-on-Insulator MOSFET Enabled Rapid Detection of Zeptomole COVID-19 Gene With Electrostatic Enrichment Process.

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.

The correlation between T-wave abnormalities and adverse cardiovascular events and echocardiographic changes in hypertensive patients.

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.

DNMT1 SNPs (rs2114724 and rs2228611) associated with positive symptoms in Chinese patients with schizophrenia.

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.