Giant Reduction of Stabilized Pressure for the Superconducting Re0.8V0.2Se2 Phase.

Access to new superconducting phases in transition-metal dichalcogenides (TMDs) via pressure treatment has been the primary target in this field. As equally essential as the fabrication of new superconducting materials at high pressure, maneuvering new superconducting phases at moderate pressures is also one of the core goals in the synthesis community. Here, we successfully reduced the synthesized pressure of the superconducting phase in ReSe2 by combining V-doping and high-pressure techniques, with a reduction in pressure of 50% in contrast to ReSe2. Our electrical transport measurements displayed that metallization appeared at 10 GPa and subsequently superconductivity appeared at about 52.4 GPa with Tc ∼ 1.9 K. There was a giant reduction in the stable pressure of the superconducting phase derived from the d-electrons and interlayer interaction changes, as evidenced by the Hall effect and X-ray diffraction measurements. These findings serve as ideal starting points and guidance for designing superconducting TMDs at moderate pressures.

Evaluation of Fetal Cardiac Function in Maternal Gestational Diabetes Mellitus by Speckle-Tracking Echocardiography.

OBJECTIVES: Gestational diabetes mellitus (GDM) is the most common metabolic disease that occurs during pregnancy and may result in fetal cardiac dysfunction. Our study aimed to assess the cardiac function in fetuses of mothers with GDM by a quantitative analysis software based on speckle-tracking echocardiography. METHODS: Forty-nine fetuses exposed to GDM and 50 normal fetuses were enrolled, and fetal echocardiography were performed and analyzed in this prospective cross-sectional study. We compared cardiac systolic function between the two groups using fetal cardiac quantitative analysis software. RESULTS: In the GDM group, left ventricular (24 ± 4 versus 28 ± 4, P < .001) and right ventricular global longitudinal strain (23 ± 4 versus 26 ± 4, P = .002) and right ventricular free wall strain (26 ± 6 versus 29 ± 5, P = .006) were significantly lower compared with the control group, whereas there was no significant difference in global spherical index (1.2 ± 0.1 versus 1.2 ± 0.1, P = .425). Additionally, 24-segment transverse fraction shortening of the right ventricle was more impaired than the left, and the segments with reduced fraction shortening were mainly located in the mid and apical sections of the right ventricle, and midsection of the left ventricle. CONCLUSION: Fetuses exposed to GDM may have cardiac dysfunction before the onset of cardiac morphologic abnormalities, and the right ventricle is more vulnerable than the left during fetal development.

Integrated Gradient-Based Continuous Wavelet Transform for Bearing Fault Diagnosis.

Bearing fault diagnosis is important to ensure safe operation and reduce loss for most rotating machinery. In recent years, deep learning (DL) has been widely used for bearing fault diagnosis and has achieved excellent results. Continuous wavelet transform (CWT), which can convert original sensor data to time-frequency images, is often used to preprocess vibration data for the DL model. However, in time-frequency images, some frequency components may be important, and some may be unimportant for DL models for fault diagnosis. So, how to choose a frequency range of important frequency components is needed for CWT. In this paper, an Integrated Gradient-based continuous wavelet transform (IG-CWT) method is proposed to address this issue. Through IG-CWT, the important frequency components and the component frequency range can be detected and used for data preprocessing. To verify our method, experiments are conducted on four famous bearing datasets using 3 DL models, separately, and compared with CWT, and the results are compared with the original CWT. The comparisons show that the proposed IG-CWT can achieve higher fault diagnosis accuracy.

Semi-Supervised Defect Detection Method with Data-Expanding Strategy for PCB Quality Inspection.

Printed circuit board (PCB) defect detection plays a crucial role in PCB production, and the popular methods are based on deep learning and require large-scale datasets with high-level ground-truth labels, in which it is time-consuming and costly to label these datasets. Semi-supervised learning (SSL) methods, which reduce the need for labeled samples by leveraging unlabeled samples, can address this problem well. However, for PCB defects, the detection accuracy on small numbers of labeled samples still needs to be improved because the number of labeled samples is small, and the training process will be disturbed by the unlabeled samples. To overcome this problem, this paper proposed a semi-supervised defect detection method with a data-expanding strategy (DE-SSD). The proposed DE-SSD uses both the labeled and unlabeled samples, which can reduce the cost of data labeling, and a batch-adding strategy (BA-SSL) is introduced to leverage the unlabeled data with less disturbance. Moreover, a data-expanding (DE) strategy is proposed to use the labeled samples from other datasets to expand the target dataset, which can also prevent the disturbance by the unlabeled samples. Based on the improvements, the proposed DE-SSD can achieve competitive results for PCB defects with fewer labeled samples. The experimental results on DeepPCB indicate that the proposed DE-SSD achieves state-of-the-art performance, which is improved by 4.7 mAP at least compared with the previous methods.

Hypervalent Iodine(III)-Mediated Tosyloxylation of 4-Hydroxycoumarins.

An efficient approach was developed for synthesis of 3-tosyloxy-4-hydroxycoumarins under mild conditions by using Koser's reagents. The reaction tolerated various functional groups, and the products served as useful aromatic building blocks. Additionally, a plausible mechanism via iodonium ylide was proposed, and the oral anticoagulant Warfarin was synthesized in good yield.

[A simple error-prone PCR method through dATP reduction].

UNLABELLED: The error-prone PCR is one of the main methods for in vitro gene mutagenesis, usually through adding Mn2+ increasing Mg2+ and dCTP/dTTP concentration. OBJECTIVE AND METHODS: In this study, both the antifungal protein gene Ace-AMP1 from Allium cepa and the Bt toxin gene cry1A(c) from Bacillus thuringiensis were subjected to PCR mutagenesis through reducing the dATP concentration, but without adding Mn2+ or adjusting other PCR components. RESULTS: The result showed that the rates of base mutation and sequence variation were increased along with the decrease of dATP concentrations. When dTTP/dCTP/dGTP: dATP equaled 20:1-40:1, the rate of base mutation was between 1.4% and 1.8%, and the rate of sequence variation was between 77.8% and 100%. DISCUSSION AND CONCLUSION: This method is simple and practical, and enables the process optimization of several mutagenic factors in conventional error-prone PCR. Moreover, as the resulting base mutations were mainly A x T-->G x C transition, the present method provides a new way to improve the GC content of gene by in vitro mutagenesis. The mutagenesis method of simply reducing single dNTP concentration could improve AT or GC content of the target gene, it is an expansion of error-prone PCR.

Epigallocatechin gallate (EGCG) alleviates inflammation and endothelial dysfunction and improves pregnancy outcomes in preeclampsia (PE)-like rats via eNOS/Nrf2/HO-1 pathway.

BACKGROUND AND PURPOSE: Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats. METHODS AND MATERIALS: PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50 mg/kg (High, H) from gestational day (GD) 6-17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured. RESULTS: EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG. CONCLUSION: EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.

Pressure-driven dome-shaped superconductivity in topological insulator GeBi2Te4.

The discovery of new superconductors based on topological insulators always captures special attention due to their unique structural and electronic properties. High pressure is an effective way to regulate the lattice as well as electronic states in the topological insulators, thus altering their electronic properties. Herein, we report the structural and electrical transport properties of the topological insulator GeBi2Te4by using high-pressure techniques. The synchrotron x-ray diffraction revealed that GeBi2Te4underwent two structural phase transitions fromR-3m(phase I) toC2/m(phase II) and then intoIm-3m(phase III). Superconductivity was observed at 6.6 GPa to be associated with the first structural phase transition. The superconducting transition temperatureTcreached a maximum value of 8.4 K, accompanied by theRHsign changing from negative to positive at 14.6 GPa, then gradually decreased with increasing pressure in phase III, showing a dome-shaped phase diagram. The present results provide a platform for understanding the interplay between the crystal structure and superconductivity by the regulation of pressure in the topological insulator materials.

Improvements of myocardial strain and work in diabetes patients with normal ejection fraction after empagliflozin treatment.

AIMS/INTRODUCTION: To assess the effect of empagliflozin treatment on left ventricular (LV), right ventricular (RV) and left atrial (LA) functions in diabetes patients with normal ejection fraction. MATERIALS AND METHODS: The study included a total of 128 diabetes patients with multiple cardiovascular risk factors who were subjected to a 6-month follow up from the initiation of empagliflozin treatment. Before and after treatment with empagliflozin, LV, RV and LA strain, and noninvasive myocardial work parameters were evaluated by speckle tracking echocardiography. RESULTS: In 128 diabetes patients (mean age 56 ± 8 years, 85 men) with multiple cardiovascular risk factors, myocardial strain and work parameters were impaired, despite the absence of significant clinical symptoms of heart failure. After 6-month treatment with empagliflozin, the absolute value of LV strain in all directions increased, represented by LV global longitudinal strain (-18.0 ± 1.7% to -19.2 ± 1.7% [mean ± SD]). The same trend in LV global work efficiency (93 [91-94] % to 94 [93-95] % [median (IQR)]), RV free-wall longitudinal strain (-24.0 ± 2.7% to -25.0 ± 2.8%), LA reservoir (31 ± 5% to 34 ± 5%) and conduit strain (-14 ± 4% to -16 ± 4%) was also observed. LV mass index (106.9 ± 16.8-103.6 ± 16.4 g/m2) and LV global wasted work (143 [111-185] mmHg% to 108 [88-141] mmHg%) decreased after treatment (P < 0.05 for all). LV volume and LA volume index remained unchanged after treatment. In the multivariable analysis, the change in LA reservoir strain (ß = 0.050, P = 0.035) and baseline global longitudinal strain (ß = -0.488, P < 0.001) were independent predictors of improvement in LV global longitudinal strain. CONCLUSIONS: This study suggests that 6-month treatment with empagliflozin improved LV, RV and LA functions in diabetes patients with normal ejection fraction.

Relative apical sparing obtained with speckle tracking echocardiography is not a sensitive parameter for diagnosing light-chain cardiac amyloidosis.

Background: Distinguishing light-chain cardiac amyloidosis (AL CA) from left ventricular wall thickening (LVWT) resulted from other etiologies has proven to be challenging. This study aimed to determine the sensitivity and specificity of relative apical sparing in diagnosing AL CA and investigate the differences in clinical and echocardiographic characteristics between AL CA patients with apical sparing and those with non-apical sparing. Methods: A total of 63 consecutive patients with AL CA, 102 consecutive patients with LVWT (including 51 hypertrophic cardiomyopathy (HCM) and 51 hypertension) and 33 healthy individuals were recruited retrospectively at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Conventional and speckle tracking echocardiography were performed on all subjects. Results: Although wall thickening was observed in all patients, almost all functional parameters were worse in AL CA, except for relative apical longitudinal strain (LS) (P=0.906). Of 63 patients with AL CA, only 17.5% (n=11) showed an apical sparing pattern. Patients with apical sparing had poorer cardiac performance than those with non-apical sparing. Relative apical sparing showed the lowest diagnostic accuracy with an area under the curve (AUC) of 0.58 [95% confidence interval (CI): 0.49-0.67, sensitivity: 17.5%, specificity: 98.0%, P=0.095] to detect AL CA, but right ventricular strain (RVS) (AUC: 0.86, P<0.001) showed the highest among all echocardiographic parameters. When diagnosing AL CA patients with non-apical sparing, RVS continued to maintain excellent diagnostic accuracy (AUC: 0.84, P<0.001), followed by left atrial reservoir strain (LASr) (AUC: 0.77, P<0.001). Conclusions: The diagnostic value of relative apical sparing for AL CA was limited with low sensitivity. In clinical practice, the diagnosis of early AL CA patients should not solely rely on relative apical sparing.

A Radiomics-Based Nomogram Using Ultrasound Carotid Plaque Evaluation For Predicting Cerebro-Cardiovascular Events In Asymptomatic Patients.

RATIONALE AND OBJECTIVES: This study aims to assess whether a radiomics-based nomogram correlates with a higher risk of future cerebro-cardiovascular events in patients with asymptomatic carotid plaques. Additionally, it investigates the nomogram's contribution to the revised Framingham Stroke Risk Profile (rFSRP) for predicting cerebro-cardiovascular risk. MATERIALS AND METHODS: Predictive models aimed at identifying an increased risk of future cerebro-cardiovascular events were developed and internally validated at one center, then externally validated at two other centers. Survival curves, constructed using the Kaplan-Meier method, were compared through the log-rank test. RESULTS: This study included a total of 2009 patients (3946 images). The final nomogram was generated using multivariate Cox regression variables, including dyslipidemia, lumen diameter, plaque echogenicity, and ultrasonography (US)-based radiomics risk. The Harrell's concordance index (C-index) for predicting events-free survival (EFS) was 0.708 in the training cohort, 0.574 in the external validation cohort 1, 0.632 in the internal validation cohort, and 0.639 in the external validation cohort 2. The final nomogram showed a significant increase in C-index compared to the clinical, conventional US, and US-based radiomics models (all P < 0.05). Furthermore, the final nomogram-assisted method significantly improved the sensitivity and accuracy of radiologists' visual qualitative score of plaque (both P < 0.001). Among 1058 patients with corresponding 1588 plaque US images classified as low-risk by the rFSRP, 75 (7.1%) patients with corresponding 93 (5.9%) carotid plaque images were appropriately reclassified to the high-risk category by the final nomogram. CONCLUSION: The radiomics-based nomogram demonstrated accurate prediction of cerebro-cardiovascular events in patients with asymptomatic carotid plaques. It also improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque and enhanced the risk stratification ability of rFSRP. SUMMARY: The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. KEY RESULTS: The radiomics-based nomogram allowed accurate prediction of cerebro-cardiovascular events, especially ipsilateral ischemic stroke in patients with asymptomatic carotid atherosclerotic plaques. The radiomics-based nomogram improved the sensitivity and accuracy of radiologists' visual qualitative score of carotid plaque. The radiomics-based nomogram improved the discrimination of high-risk populations from low-risk populations in asymptomatic patients with carotid atherosclerotic plaques and the risk stratification capability of the rFSRP.

Research Status and Application Prospects of the Medicinal Mushroom Armillaria mellea.

Armillaria is one of the most common diseases underlying chronic root rot in woody plants. Although there is no particularly effective way to prevent it, soil disinfection is a common effective protective measure. However, Armillaria itself has important medicinal value and is a symbiotic fungus in the cultivation of Gastrodia elata and Polyporus umbellatus. Therefore, researching Armillaria is of great practical significance. In this review, the biological characteristics, cultivation methods, chemical components, food and medicinal value and efficacy of Armillaria were all reviewed, and its development and utilization direction were analyzed and discussed.

Effects of Human Capital on Energy Consumption: The Role of Income Inequality.

High-quality human capital (HC) development has a strong influence on achieving a win-win target of economic growth and energy consumption mitigation based on the background of the contemporary "carbon neutrality" constraints in China. We here aim to empirically assess the effect of HC on energy consumption (EC) in 30 provinces of China from 2000 to 2019. Moreover, we broaden the literature by discussing the effect of HC in terms of impact mechanism and nonlinear relationship. Based on methods of the augmented mean group (AMG), the estimation of long-term impacts indicates that the improvement of HC significantly discourages the increase in EC. The intrinsic mechanism shows that the accumulation of HC significantly promotes the decline of EC through economic structure adjustment and technological innovation. Moreover, the threshold model indicates that income equality lifts the inhibitory impact of HC on EC. Accordingly, the development of HC should be involved in the policy preference of China's provincial and national development strategies considering its effectiveness in stimulating the reduction of energy consumption.

lncRNA XIST is associated with preeclampsia and mediates trophoblast cell invasion via miR-340-5p/KCNJ16 signaling pathway.

BACKGROUND: Preeclampsia (PE) is a syndrome commonly occurring among the pregnant. Shallow trophoblast invasion is considered to be closely related to PE. Therefore, in trophoblast cells, we explored the potential mechanisms of lncRNA XIST in the modulation of trophoblast invasion and proliferation. METHODS: GEO online analyzer was used to screen the abnormally expressed RNAs in placenta tissues from patients with severe PE and healthy controls. The prediction of target bindings was performed on TargetScan and starBase. Transfection was conducted to regulate the RNA expression levels in trophoblast cells, HTR-8/SVneo. RT-qPCR measured expression of lncRNA XIST, miR-340-5p and KCNJ16. The CCK-8 assay examined cell viability. Flow cytometer analyzed apoptosis and luciferase assay determined the luciferase activity. Transwell assays detected the invasion and western blot verified the changes in protein expression of MMP2, MMP9 and KCNJ16 in trophoblast cells. RESULTS: lncRNA XIST expression was enhanced in PE patients. Upregulation of lncRNA XIST in HTR-8/SVneo cells inhibited the cell proliferation and invasion, and induced apoptosis. XIST upregulation inhibited MMP2 and MMP9 protein expression. lncRNA XIST/ KCNJ16 interplayed as ceRNAs of miR-340-5p. Specifically,miR-340-5p overexpression reversed the effect of XIST upregulation on the cell apoptosis, proliferation and invasive ability and the knockdown of KCNJ16 could add to the effect of miR-340-5p overexpression in HTR-8/SVneo. CONCLUSION: lncRNA XIST was upregulated in PE. Upregulation of lncRNA XIST exerted the inhibitory effects on the proliferation and invasion of trophoblast cells through the interactions with miR-340-5p/KCNJ16, which suggests that the lncRNA XIST/miR-340-5p/KCNJ16 axis might play a role in PE.

Pathogenicity of Beauveria bassiana PfBb and Immune Responses of a Non-Target Host, Spodoptera frugiperda (Lepidoptera: Noctuidae).

Exploring the pathogenicity of a new fungus strain to non-target host pests can provide essential information on a large scale for potential application in pest control. In this study, we tested the pathogenicity of Beauveria bassiana PfBb on the important agricultural pest Spodoptera frugiperda (Lepidoptera: Noctuidae) by determining the relative activities of protective enzymes and detoxifying enzymes in different larval instars. Our results show that the B. bassiana PfBb strain could infect all six larval instars of S. frugiperda, and its virulence to S. frugiperda larvae gradually increased with an increase in spore concentration. Seven days after inoculation, the LC50 of B. bassiana PfBb was 7.7 × 105, 5.5 × 106, 2.2 × 107, 3.1 × 108, 9.6 × 108, and 2.5 × 1011 spores/mL for first to sixth instars of S. frugiperda, respectively, and the LC50 and LC90 of B. bassiana PfBb for each S. frugiperda instar decreased with infection time, indicating a significant dose effect. Furthermore, the virulence of B. bassiana PfBb to S. frugiperda larvae gradually decreased with an increase in larval instar. The activities of protective enzymes (i.e., catalase, peroxidase, and superoxide dismutase) and detoxifying enzymes (i.e., glutathione S-transferases, carboxylesterase, and cytochrome P450) in S. frugiperda larvae of the first three instars infected with B. bassiana PfBb changed significantly with infection time, but such variations were not obvious in the fifth and sixth instars. Additionally, after being infected with B. bassiana PfBb, the activities of protective enzymes and detoxification enzymes in S. frugiperda larvae usually lasted from 12 to 48 h, which was significantly longer than the control. These results indicate that the pathogenicity of B. bassiana PfBb on the non-target host S. frugiperda was significant but depended on the instar stage. Therefore, the findings of this study suggest that B. bassiana PfBb can be used as a bio-insecticide to control young larvae of S. frugiperda in an integrated pest management program.

The Global, Regional, and National Burden and Trends of Infective Endocarditis From 1990 to 2019: Results From the Global Burden of Disease Study 2019.

Introduction: Infective endocarditis (IE) presents with increasing incidence and mortality in some regions and countries, as well as serious socioeconomic burden. The current study aims to compare and interpret the IE burden and temporal trends globally and in different regions from 1990 to 2019. Methods: Data on the incidence, deaths and disability-adjusted life years (DALYs) caused by IE were extracted and analyzed from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPC) were adopted to quantify the change trends of age-standardized rates (ASRs). Besides, potential contributors of serious IE burden were also evaluated including age, gender, social-demographic index (SDI), and age-standardized incident rate (ASIR) in 1990. Results: Globally, the number of IE cases and deaths has increased sharply during the past 30 years from 478,000 in 1990 to 1,090,530 in 2019 and from 28,750 in 1990 to 66,320 in 2019, and both presented an upward temporal trend annually (EAPC:1.2 for incidence and 0.71 for death). However, the EAPC of age-standardized DALYs demonstrated a negative temporal trend despite increasing DALYs from 1,118,120 in 1990 to 1,723,590 in 2019. Moreover, older patients and men were more severely affected. Meanwhile, different SDI regions had different disease burdens, and correlation analyses indicated that SDI presented a positive association with ASIR (R = 0.58, P < 0.0001), no association with age-standardized death rate (R = -0.06, P = 0.10), and a negative association with age-standardized DALYs (R = -0.40, P < 0.0001). In addition, the incidence of IE increased in most countries during the past 30 years (190 out of 204 countries). However, the change trends of deaths and DALYs were heterogeneous across regions and countries. Finally, we discovered positive associations of the EAPC of ASRs with the SDI in 2019 among 204 countries and territories but few associations with the ASIR in 1990. Conclusion: Generally, the global burden of IE is increasing, and there is substantial heterogeneity in different genders, ages and regions, which may help policy-makers and medical staff respond to IE and formulate cost-effective interventional measures.

Predicting prognosis and immune responses in hepatocellular carcinoma based on N7-methylguanosine-related long noncoding RNAs.

Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan-Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients.

Persistent Endothelial Dysfunction in Coronavirus Disease-2019 Survivors Late After Recovery.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can result in an endothelial dysfunction in acute phase. However, information on the late vascular consequences of COVID-19 is limited. METHODS: Brachial artery flow-mediated dilation (FMD) examination were performed, and inflammatory biomarkers were assessed in 86 survivors of COVID-19 for 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. RESULTS: Brachial artery FMD was significantly lower in the survivors of COVID-19 than in the healthy controls and risk factor-matched controls [median (IQR) 7.7 (5.1-10.7)% for healthy controls, 6.9 (5.5-9.4)% for risk factor-matched controls, and 3.5(2.2-4.6)% for COVID-19, respectively, p < 0.001]. The FMD was lower in 25 patients with elevated tumor necrosis factor (TNF)-α [2.7(1.2-3.9)] than in 61 patients without elevated TNF-α [3.8(2.6-5.3), p = 0.012]. Furthermore, FMD was inversely correlated with serum concentration of TNF-α (r = -0.237, p = 0.007). CONCLUSION: Survivors of COVID-19 have a reduced brachial artery FMD, which is inversely correlated with increased serum concentration of TNF-α. Prospective studies on the association of endothelial dysfunction with long-term cardiovascular outcomes, especially the early onset of atherosclerosis, are warranted in survivors of COVID-19.

Lipid-polymer composite microspheres for colon-specific drug delivery prepared using an ultrasonic spray freeze-drying technique.

Lipid-polymer composite microspheres (LP-MS) for colon-specific drug delivery were prepared using an ultrasonic spray freeze-drying technique. These microspheres, which consist of the pH-sensitive polymer Eudragit S100 and the non-polar lipid Compritol 888 ATO, were characterized by morphological and physicochemical properties. It was found that the LP-MS have a spherical lipid porous matrix with a smooth pH-sensitive polymer film on both internal and external surfaces, and the insoluble drug 10-hydroxycamptothecin was dispersed in an amorphous state in the carrier. Morphological changes of microparticles under different pH conditions were observed by confocal laser scanning microscopy, which showed that the lipid matrix in LP-MS restricted the swelling property of the polymer at pH 6.8. In drug release studies, less than 15% of the drug was released below pH 6.8, whereas more than 30% was released with a sustained-release model at pH 7.4. The LP-MS could provide a promising vehicle for colon drug delivery.

Combined pharmacophore modeling, docking, and 3D-QSAR studies of PLK1 inhibitors.

Polo-like kinase 1, an important enzyme with diverse biological actions in cell mitosis, is a promising target for developing novel anticancer drugs. A combined molecular docking, structure-based pharmacophore modeling and three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a set of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. The common substructure, molecular docking and pharmacophore-based alignment were used to develop different 3D-QSAR models. The comparative molecular field analysis (CoMFA) and comparative molecule similarity indices analysis (CoMSIA) models gave statistically significant results. These models showed good q(2) and r(2) (pred) values and revealed a good response to test set validation. All of the structural insights obtained from the 3D-QSAR contour maps are consistent with the available crystal structure of PLK1. The contour maps obtained from the 3D-QSAR models in combination with the structure based pharmacophore model help to better interpret the structure-activity relationship. These satisfactory results may aid the design of novel PLK1 inhibitors. This is the first report on 3D-QSAR study of PLK1 inhibitors.