Key Residue in the Precursor Region of M Protein Contributes to the Neurovirulence and Neuroinvasiveness of the African Lineage of Zika Virus.

The Zika virus (ZIKV) represents an important global health threat due to its unusual association with congenital Zika syndrome. ZIKV strains are phylogenetically grouped into the African and Asian lineages. However, the viral determinants underlying the phenotypic differences between the lineages remain unknown. Here, multiple sequence alignment revealed a highly conserved residue at position 21 of the premembrane (prM) protein, which is glutamic acid and lysine in the Asian and African lineages, respectively. Using reverse genetics, we generated a recombinant virus carrying an E21K mutation based on the genomic backbone of the Asian lineage strain FSS13025 (termed E21K). The E21K mutation significantly increased viral replication in multiple neural cell lines with a higher ratio of M to prM production. Animal studies showed E21K exhibited increased neurovirulence in suckling mice, leading to more severe defects in mouse brains by causing more neural cell death and destruction of hippocampus integrity. Moreover, the E21K substitution enhanced neuroinvasiveness in interferon alpha/beta (IFN-α/ß) receptor knockout mice, as indicated by the increased mortality, and enhanced replication in mouse brains. The global transcriptional analysis showed E21K infection profoundly altered neuron development networks and induced stronger antiviral immune response than wild type (WT) in both neural cells and mouse brains. More importantly, the reverse K21E mutation based on the genomic backbone of the African strain MR766 caused less mouse neurovirulence. Overall, our findings support the 21st residue of prM functions as a determinant for neurovirulence and neuroinvasiveness of the African lineage of ZIKV. IMPORTANCE The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian. Significant differences exist between the two lineages in terms of neurovirulence and neuroinvasiveness in mice. However, the viral determinants underlying the phenotypic differences are still unknown. Here, combining reverse genetics, animal studies, and global transcriptional analysis, we provide evidence that a single E21K mutation of prM confers to the Asian lineage strain FSS130125 significantly enhanced replication in neural cell lines and more neurovirulent and neuroinvasiveness phenotypes in mice. Our findings support that the highly conserved residue at position 21 of prM functions as a determinant of neurovirulence and neuroinvasiveness of the African lineage of ZIKV in mice.

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway.

BACKGROUND: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth. METHODS: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium. RESULTS: We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells. CONCLUSIONS: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.

Identification of Anti-SNRPA as a Novel Serological Biomarker for Systemic Sclerosis Diagnosis.

Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.

Enzymatic analysis of WWP2 E3 ubiquitin ligase using protein microarrays identifies autophagy-related substrates.

WWP2 is a HECT E3 ligase that targets protein Lys residues for ubiquitination and is comprised of an N-terminal C2 domain, four central WW domains, and a C-terminal catalytic HECT domain. The peptide segment between the middle WW domains, the 2,3-linker, is known to autoinhibit the catalytic domain, and this autoinhibition can be relieved by phosphorylation at Tyr369. Several protein substrates of WWP2 have been identified, including the tumor suppressor lipid phosphatase PTEN, but the full substrate landscape and biological functions of WWP2 remain to be elucidated. Here, we used protein microarray technology and the activated enzyme phosphomimetic mutant WWP2Y369E to identify potential WWP2 substrates. We identified 31 substrate hits for WWP2Y369E using protein microarrays, of which three were known autophagy receptors (NDP52, OPTN, and SQSTM1). These three hits were validated with in vitro and cell-based transfection assays and the Lys ubiquitination sites on these proteins were mapped by mass spectrometry. Among the mapped ubiquitin sites on these autophagy receptors, many had been previously identified in the endogenous proteins. Finally, we observed that WWP2 KO SH-SH5Y neuroblastoma cells using CRISPR-Cas9 showed a defect in mitophagy, which could be rescued by WWP2Y369E transfection. These studies suggest that WWP2-mediated ubiquitination of the autophagy receptors NDP52, OPTN, and SQSTM1 may positively contribute to the regulation of autophagy.

SERTAD3 induces proteasomal degradation of ZIKV capsid protein and represents a therapeutic target.

Zika virus (ZIKV) is a mosquito-borne RNA virus that belongs to the Flaviviridae family. While flavivirus replication is known to occur in the cytoplasm, a significant portion of the viral capsid protein localizes to the nucleus during infection. However, the role of the nuclear capsid is less clear. Herein, we demonstrated SERTA domain containing 3 (SERTAD3) as an antiviral interferon stimulatory gene product had an antiviral ability to ZIKV but not JEV. Mechanistically, we found that SERTAD3 interacted with the capsid protein of ZIKV in the nucleolus and reduced capsid protein abundance through proteasomal degradation. Furthermore, an eight amino acid peptide of SERTAD3 was identified as the minimum motif that binds with ZIKV capsid protein. Remarkably, the eight amino acids synthetic peptide from SERTAD3 significantly prevented ZIKV infection in culture and pregnant mouse models. Taken together, these findings not only reveal the function of SERTAD3 in promoting proteasomal degradation of a specific viral protein but also provide a promising host-targeted therapeutic strategy against ZIKV infection.

Towards a free energy-based elastic network model and its application to the SARS-COV2 binding to ACE2.

Classical normal mode analysis (cNMA) is a standard method for studying the equilibrium vibrations of macromolecules. A major limitation of cNMA is that it requires a cumbersome step of energy minimization that also alters the input structure significantly. Variants of normal mode analysis (NMA) exist that perform NMA directly on PDB structures without energy minimization, while maintaining most of the accuracy of cNMA. Spring-based NMA (sbNMA) is such a model. sbNMA uses an all-atom force field as cNMA does, which includes bonded terms such as bond stretching, bond angle bending, torsional, improper, and non-bonded terms such as van der Waals interactions. Electrostatics was not included in sbNMA because it introduced negative spring constants. In this work, we present a way to incorporate most of the electrostatic contributions in normal mode computations, which marks another significant step toward a free-energy-based elastic network model (ENM) for NMA. The vast majority of ENMs are entropy models. One significance of having a free energy-based model for NMA is that it allows one to study the contributions of both entropy and enthalpy. As an application, we apply this model to study the binding stability between SARS-COV2 and angiotensin converting enzyme 2 (or ACE2). Our results show that the stability at the binding interface is contributed nearly equally by hydrophobic interactions and hydrogen bonds.

Non-volatile control of topological phase transition in an asymmetric ferroelectric In2Te2S monolayer.

The coupling of topological electronic states and ferroelectricity is highly desired due to their abundant physical phenomenon and potential applications in multifunctional devices. However, it is difficult to achieve such a phenomenon in a single ferroelectric (FE) monolayer because the two polarized states are topologically equivalent. Here, we demonstrate that the symmetry of polarized states can be broken by constructing a Janus structure in a FE monolayer. We illustrate such a general idea by replacing a layer of Te atoms in the In2Te3 monolayer with S atoms. Using first-principles calculations, we show that the In2Te2S monolayer has two asymmetric polarized states, which are characterized by a metal and semiconductor, respectively. Importantly, as the spin-orbit coupling is included, a band gap (50.4 meV) is created in the metallic state, resulting in a non-trivial topological phase. Thus, it proves to be a feasible method to engineer non-volatile FE control of topological order in a single-phase system. We also demonstrate the underlying physical mechanism of topological phase transition, which is unveiled to be related to the weakened intrinsic electric field resulting from charge transfer. These interesting results provide a general way to design asymmetric FE materials and shed light on their potential application in non-volatile multifunctional devices.

Differential expression profiles and functional analysis of long non-coding RNAs in calcific aortic valve disease.

AIM: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action. METHODS: The gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potential cis- or trans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hub cis- or trans-regulatory genes were verified in GSE148219 and GSE199718 respectively. RESULTS: There were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj ≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hub cis- or trans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found that MIR4435-2HG was the top hub trans-acting lncRNA which also plays a crucial role by ceRNA pattern. CONCLUSION: LncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.

Efficacy of pharmacological therapies for preventing post-dural puncture headaches in obstetric patients: a Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Post-dural puncture headache (PDPH) is a major complication of neuraxial anesthesia. PDPH usually occurs after Caesarean section in obstetric patients. The efficacy of prophylactic pharmacological therapies remains controversial. METHODS: Seven pharmacological therapies (aminophylline (AMP), dexamethasone, gabapentin/pregabalin (GBP/PGB), hydrocortisone, magnesium, ondansetron (OND), and propofol (PPF)), were studied in this Bayesian network meta-analysis. The primary outcome was the cumulative incidence of PDPH within 7 days. Secondary outcomes included the incidence of PDPH at 24 and 48 h postoperatively, the severity of headache in PDPH patients (24, 48, and 72 h postoperatively), and postoperative nausea and vomiting (PONV). RESULTS: Twenty-two randomized controlled trials with 4,921 pregnant women (2,723 parturients received prophylactic pharmacological therapies) were included. The analyses demonstrated that PPF, OND, and AMP were efficient in decreasing the cumulative incidence of PDPH during the follow-up period compared to the placebo group (OR = 0.19, 95% CI: 0.05 to 0.70; OR = 0.37, 95% CI: 0.16 to 0.87; OR = 0.40, 95% CI: 0.18 to 0.84, respectively). PPF and OND had the lower incidence of PONV compared to the placebo group (OR = 0.07, 95% CI: 0.01 to 0.30; and OR = 0.12, 95% CI: 0.02 to 0.63). No significant difference in other outcomes was found among different therapies. CONCLUSIONS: Based on available data, PPF, OND, and AMP may have better efficacy in decreasing the incidence of PDPH compared to the placebo group. No significant side effects were revealed. Better-designed studies are requested to verify these conclusions.

Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays.

To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach, a two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in phase II were further confirmed using western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635, and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB, and NOLC1 showed good specificities of 88.3%, 85.9%, and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared with that by each individual biomarker. The performances of three autoantibodies, namely anti-SPATA7, -QDPR, and -PRH2, were successfully confirmed with western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK-specific biomarker candidates, three of which could be readily adopted in a clinical setting.

Reduced CPU Workload for Human Pose Detection with the Aid of a Low-Resolution Infrared Array Sensor on Embedded Systems.

Modern embedded systems have achieved relatively high processing power. They can be used for edge computing and computer vision, where data are collected and processed locally, without the need for network communication for decision-making and data analysis purposes. Face detection, face recognition, and pose detection algorithms can be executed with acceptable performance on embedded systems and are used for home security and monitoring. However, popular machine learning frameworks, such as MediaPipe, require relatively high usage of CPU while running, even when idle with no subject in the scene. Combined with the still present false detections, this wastes CPU time, elevates the power consumption and overall system temperature, and generates unnecessary data. In this study, a low-cost low-resolution infrared thermal sensor array was used to control the execution of MediaPipe's pose detection algorithm using single-board computers, which only runs when the thermal camera detects a possible subject in its field of view. A lightweight algorithm with several filtering layers was developed, which allowed the effective detection and isolation of a person in the thermal image. The resulting hybrid computer vision proved effective in reducing the average CPU workload, especially in environments with low activity, almost eliminating MediaPipe's false detections, and reaching up to 30% power saving in the best-case scenario.

Microplastic transport during desertification in drylands: Abundance and characterization of soil microplastics in the Amu Darya-Aral Sea basin, Central Asia.

Desertification and microplastic pollution are major environmental issues that impact the function of the ecosystem and human well-being of drylands. Land desertification may influence soil microplastics' abundance, transport, and distribution, but their distribution in the dryland deserts of Central Asia's Amu Darya-Aral Sea basin is unknown. Here, we investigated the abundance and distribution of microplastics in dryland desert soils from the Amu Darya River to the Aral Sea basin in Central Asia at a spatial scale of 1000 km and soil depths ranging from 0 to 50 cm. Microplastics were found in soils from all sample locations, with abundances ranging from 182 to 17841 items kg-1 and a median of 3369. Twenty-four polymers were identified, with polyurethane (PU, 37.3%), silicone resin (SR, 17.0%), and chlorinated polyethylene (CPE, 9.8%) accounting for 64.1% of all polymer types. The abundance of microplastics was significantly higher in deep (20-50 cm) soils than in surface (0-5, 5-20 cm) soils. The main morphological characteristics of the observed microplastics were small size (20-50 µm) and irregular particles with no round edges (mean eccentricity 0.65). The abundance was significantly and positively related to soil EC and TP. According to the findings, desertification processes increase the abundance of microplastic particles in soils and promote migration to deeper soil layers. Human activities, mainly grazing, may be the region's primary cause of desertification and microplastic pollution. Our findings provide new information on the diffusion of microplastics in drylands during desertification; these findings are critical for understanding and promoting dryland plastic pollution prevention and control.

[Systemic Lupus Erythematosus Combined with Chorea: Report of One Case and Literature Review].

Systemic lupus erythematosus combined with chorea is relatively rare in China,and there are no unified diagnostic criteria or specific ancillary tests.Therefore,it is confirmed by exclusionary clinical diagnosis.To improve the understanding of this disease among rheumatologists,we report the clinical data of a patient with systemic lupus erythematosus combined with chorea admitted to the Department of Rheumatology and Immunology in the First Affiliated Hospital of Jinan University in January 2022.Furthermore,we review the relevant literature in the past 10 years and summarize the clinical features of these cases.

The association between assisted reproductive technology and cardiac remodeling in fetuses and early infants: a prospective cohort study.

BACKGROUND: Limited data exist regarding the potential impact of assisted reproductive technology (ART) on cardiac remodeling. In particular, whether different ART techniques are related to different cardiac alterations remains unclear. We aimed to evaluate cardiac changes in fetuses and infants arising from ART and fetal cardiac alterations in fetuses conceived by specific ART procedures. METHODS: This prospective and observational cohort study recruited 111 fetuses conceived by ART and 106 spontaneously conceived controls between December 2017 and April 2019. Echocardiography was performed between 28+0 and 32+6 weeks-of-gestation and at 0-2 and 6 months after birth. RESULTS: A total of 88 ART fetuses and 85 controls were included in the final analysis. Compared to controls, ART fetuses demonstrated a globular enlarged left ventricle (LV) (LV sphericity index of mid-section, 2.29 ± 0.34 vs. 2.45 ± 0.39, P = 0.006; LV area, 262.33 ± 45.96 mm2 vs. 244.25 ± 47.13 mm2, P = 0.002), a larger right ventricle (RV) (RV area, 236.10 ± 38.63 mm2 vs. 221.14 ± 42.60 mm2, P = 0.003) and reduced LV systolic deformation (LV global longitudinal strain (GLS), -19.56% ± 1.90% vs. -20.65% ± 1.88%, P = 0.013; LV GLS rate S, -3.32 ± 0.36 s-1 vs. -3.58 ± 0.39 s-1, P = 0.023). There were no significant differences between the ART and control groups at postnatal follow-ups. Furthermore, we found fetal cardiac morphometry and function were comparable between different ART procedures. Compared to controls, the fetuses derived from various ART procedures all exhibited impairments in the LV GLS and the LV GLS rate S. CONCLUSIONS: Our analysis demonstrated that subclinical cardiac remodeling and dysfunction were evident in ART fetuses, although these alterations did not persist in early infancy. In addition, various ART procedures may cause the same unfavorable changes in the fetal heart. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ) ( ChiCTR1900021672 ) on March 4, 2019, retrospectively registered.

Assessment of Endothelial Dysfunction in Patients with Kawasaki Disease: A Meta-Analysis.

Background: Kawasaki disease (KD) is a well-known systemic inflammatory vasculitis. Endothelial dysfunction is one of most easily overlooked non-coronary complications of KD. Several studies have assessed endothelial dysfunction using flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD), and biomarkers (E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1)). However, the results were inconsistent and incomplete. Methods: We searched five databases for eligible studies until March 8, 2022. The summarized weighted mean difference (WMD) with 95% confidence intervals (CIs) were estimated for FMD, NMD, and four biomarkers level between KD and healthy children. A meta-analysis with subgroup analysis was conducted. Results: 40 studies with a total of 2670 children (1665 KD patients and 1005 healthy children) were identified. During the acute phase, KD patients had lower FMD compared to the control group (WMD = -10.39, 95% CI: -13.80- -6.98). During the subacute phase, KD patients had lower FMD compared to the control group (WMD = -15.07, 95% CI: -17.61- -12.52). During the convalescence phase, KD patients had lower FMD and similar NMD compared to the control group (WMD = -4.95, 95% CI: -6.32- -3.58; WMD = -0.92, 95% CI: -2.39-0.55, respectively). During the convalescence phase, those KD patients without coronary artery lesion (CAL), with CAL, even with coronary artery aneurysm, had progressively lower FMD compared to healthy children (WMD = -3.82, 95% CI: -7.30- -0.34; WMD = -6.32, 95% CI: -7.60- -5.04; and WMD = -6.97, 95% CI: -7.99- -5.95, respectively). Compared to KD patients without CAL, those with CAL had lower FMD (WMD = -1.65, 95% CI: -2.92- -0.37). KD patients had higher levels of E-selectin, P-selectin, and ICAM-1 compared to healthy controls during different phases. KD patients had a higher level of VCAM-1 compared to healthy controls only during the acute phase (WMD = 61.62, 95% CI: 21.38-101.86). Conclusions: Endothelial dysfunction is present since the onset of KD and persists for years, confirmed by the measurement of FMD and biomarkers from different phases. An assumption is advanced that FMD impairment (the severity of endothelial dysfunction) may be positively correlated with CAL severity during the convalescence phase.

Trends in Incidence and Mortality of Esophageal Cancer in Huai'an District, a High-Risk Area in Northern Jiangsu Province, China.

PURPOSE: This study aimed to provide a clear comparable figure of the trends in incidence and mortality rates of esophageal cancer (EC) in Huai'an District, Huai'an City, Jiangsu Province, China, a high-risk area for EC. METHODS: The data for age- and sex-specific incidence rates between 1998 and 2016, the mortality rates in 1990-2016 and the number of EC patients were obtained from Huai'an District Cancer Registry. Crude rates, Age-standardized rates (ASRs) by world standard population and truncated age-standardized rates of EC incidence and mortality were calculated. The joinpoint regression analysis was used to calculate the annual percent changes (APC), average annual percent changes (AAPC), and their 95% confidence intervals (CIs). RESULTS: Overall, 20,892 new EC cases and 20,806 EC deaths were registered in Huai'an District. ASR of EC incidence from 1998 to 2016 and mortality from 1990 to 2016 were 73.32/100,000 and 60.03/100,000, respectively. The ASR illustrated that the incidence of EC had significant downward trends in total, male and female (AAPC = -4.65, -4.90, and -5.51, respectively, p <.01). The age-specific incidence and mortality rates of EC increased dramatically in people over the age of 40, and peaked in people between the ages 70-74. In the subdivisions of Huai'an District, geographical diversities in the crude incidence and mortality rates of EC were found. CONCLUSION: In summary, the incidence and mortality rates of EC showed downward trends in Huai'an District. However, the burden of EC still remained serious in this high-risk area. Cost-effective methods of intervention and health education should be enhanced for improving EC prevention.

Coexistence of intrinsic room-temperature ferromagnetism and piezoelectricity in monolayer BiCrX3 (X = S, Se, and Te).

Two-dimensional (2D) materials with intrinsic ferromagnetism and piezoelectricity have received growing attention due to their potential applications in nanoscale spintronic devices. However, their applications are highly limited by the low Curie temperatures (TC) and small piezoelectric coefficients. Here, using first-principles calculations, we have successfully predicted that BiCrX3 (X = S, Se, and Te) monolayers simultaneously possess ferromagnetism and piezoelectricity by replacing one layer of Bi atoms with Cr atoms in Bi2X3 monolayers. Our results demonstrate that BiCrX3 monolayers are not only intrinsic ferromagnetic semiconductors with indirect band gaps, adequate TC values of higher than 300 K, and significant out-of-plane magnetic anisotropic energies, but also exhibit appreciable in-plane and out-of-plane piezoelectricity. In particular, the in-plane piezoelectric coefficients of BiCrX3 monolayers with ABCAB configuration are up to 15.16 pm V-1, which is higher than those of traditional three-dimensional piezoelectric materials such as α-quartz. The coexistence of ferromagnetism and piezoelectricity in BiCrX3 monolayers gives them promising applications in spintronics and nano-sized sensors.

Intrinsic ferromagnetism and the quantum anomalous Hall effect in two-dimensional MnOCl2 monolayers.

Due to their potential application in spintronic devices, two-dimensional (2D) ferromagnetic materials are highly desired. We used first-principles calculations and Monte Carlo simulations to investigate the electronic structure and magnetic characteristics of the MnOCl2 monolayers. We discovered two stable monolayer structures, Pmna-MnOCl2 and Pmmn-MnOCl2. Our findings show that the Pmna-MnOCl2 monolayer is an intrinsic ferromagnetic semiconductor with an indirect band gap of 0.152 eV and a Curie temperature (TC) of 202 K, while the Pmmn-MnOCl2 monolayer is an intrinsic ferromagnetic Dirac semimetal with a high TC (910 K) and triaxial magnetic anisotropy. We also show that a Pmmn-MnOCl2 monolayer with a nontrivial band gap of 6.2 meV can achieve the quantum anomalous Hall effect (QAHE) with Chern number C = 1. Additionally, the existence of a gapless edge state can be flexibly regulated by choosing the terminal edges. Our studies reveal that the Pmmn-MnOCl2 monolayer can serve as a candidate material to achieve high-temperature QAHE.

Evaluation of the safety and efficacy of a novel Anatomical classification and dUal anchoRing theory to Optimize the tavR strategy for pure severe Aortic regurgitation (AURORA): a prospective cohort study.

BACKGROUND: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet. METHODS: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria. DISCUSSION: The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients. TRIAL REGISTRATION: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209 .

Safety and efficacy of the Amplatzer Amulet and Watchman 2.5 for left atrial appendage occlusion: A systematic review and meta-analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulation (OAC) to decrease the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF); however, certain complications remain a concern. Amplatzer Amulet and Watchman are the two most popular used devices for preventing stroke in patients with NVAF. We assessed the safety and efficacy of LAAO using the Amplatzer Amulet and Watchman. METHODS: A meta-analysis was conducted to compare the safety and efficacy outcomes associated with the use of the Amplatzer Amulet and Watchman 2.5. The Newcastle-Ottawa Scale has been utilized to assess the quality of study. RESULTS: The meta-analysis includes seven studies involving 2926 patients (1418 patients with an amulet and 1508 with a Watchman 2.5). Generally, adverse event rates for both systems were minimal. No significant differences between the two devices were found in safety (pericardial effusion, device embolization, and cardiac tamponade) or efficacy outcomes (death, TIA, stroke, major/minor bleeding, device leak, and thromboembolic events). CONCLUSIONS: The data suggest LAAO is a safe procedure, regardless of which device was used. LAAO devices generally have low complication rates. Outcomes were comparable between the two groups with no significant differences in their safety or efficacy.