KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

Biochanin A inhibits endothelial dysfunction induced by IL­6­stimulated endothelial microparticles in Perthes disease via the NFκB pathway.

Endothelial dysfunction caused by the stimulation of endothelial microparticles (EMPs) by the inflammatory factor IL-6 is one of the pathogenic pathways associated with Perthes disease. The natural active product biochanin A (BCA) has an anti-inflammatory effect; however, whether it can alleviate endothelial dysfunction in Perthes disease is not known. The present in vitro experiments on human umbilical vein endothelial cells showed that 0-100 pg/ml IL-6-EMPs could induce endothelial dysfunction in a concentration-dependent manner, and the results of the Cell Counting Kit 8 assay revealed that, at concentrations of <20 µM, BCA had no cytotoxic effect. Reverse transcription-quantitative PCR demonstrated that BCA reduced the expression levels of the endothelial dysfunction indexes E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) in a concentration-dependent manner. Immunofluorescence and western blotting illustrated that BCA increased the expression levels of zonula occludens-1 and decreased those of ICAM-1. Mechanistic studies showed that BCA inhibited activation of the NFκB pathway. In vivo experiments demonstrated that IL-6 was significantly increased in the rat model of ischemic necrosis of the femoral head, whereas BCA inhibited IL-6 production. Therefore, in Perthes disease, BCA may inhibit the NFκB pathway to suppress IL-6-EMP-induced endothelial dysfunction, and could thus be regarded as a potential treatment for Perthes disease.

Ultra-thin and Mechanically Stable LiCoO2 -Electrolyte Interphase Enabled by Mg2+ Involved Electrolyte.

LiCoO2 (LCO) cathode materials have attracted significant attention for its potential to provide higher energy density in current Lithium-ion batteries (LIBs). However, the structure and performance degradation are exacerbated by increasing voltage due to the catastrophic reaction between the applied electrolyte and delithiated LCO. The present study focuses on the construction of physically and chemically robust Mg-integrated cathode-electrolyte interface (MCEI) to address this issue, by incorporating Magnesium bis(trifluoromethanesulfonyl)imide (Mg[TFSI]2 ) as an electrolyte additive. During formation cycles, the strong MCEI is formed and maintained its 2 nm thickness throughout long-term cycling. Notably, Mg is detected not only in the robust MCEI, but also imbedded in the surface of the LCO lattice. As a result, the parasitic interfacial side reactions, surface phase reconstruction, particle cracking, Co dissolution and shuttling are considerably suppressed, resulting in long-term cycling stability of LCO up to 4.5 V. Therefore, benefit from the double protection of the strong MCEI, the Li||LCO coin cell and the Ah-level Graphite||LCO pouch cell exhibit high capacity retention by using Mg-electrolyte, which are 88.13% after 200 cycles and 90.4% after 300 cycles, respectively. This work provides a novel approach for the rational design of traditional electrolyte additives.

Assessing the learning curve for transumbilical single-site laparoscopy for endometrial cancer.

Introduction: Applying transumbilical laparoendoscopic single-site surgery to endometrial cancers is worldwide, and the depiction of the learning curve is rarely described, which leads to the vagueness of young clinical practitioners. We accumulated the data to identify the completion of the learning curve by analyzing the operative and postoperative outcomes of the patients with endometrial cancer for transumbilical laparoendoscopic single-site surgery (TU-LESS). Methods: This was a retrospective, consecutive single-center study of patients with endometrial cancer undergoing standard endometrial cancer comprehensive staging surgery (extrafascial hysterectomy, bilateral salpingectomy, and pelvic lymphadenectomy) through TU-LESS by an experienced surgeon from December, 2017 to June, 2021 in the Department of Gynecologic Oncology, West China Second Hospital, Sichuan University, China. Results: After applying the inclusion and exclusion criteria, 42 patients were included in the study. The learning curve for this study was evaluated using both cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) methods. Applying CUSUM and RA-CUSUM has grouped 42 cases into three phases. The prior five cases represented the learning period. The following six cases were needed to lay a technical foundation (cases 6-11). The third phase was regarded as achieving proficiency (cases 12-42). The operative time decreased drastically with the learning curve. There were no significant differences in terms of postoperative complications and lymph node retrieval among the three phases. More difficult patients were confronted in the third phase. Discussion: In our study, the learning curve was composed of three phases. According to the results of our study, 11 cases were required for experienced surgeons to achieve a technical foundation.

Single-cell RNA sequencing reveals the immune microenvironment landscape of osteosarcoma before and after chemotherapy.

Chemotherapy, a primary treatment for osteosarcoma (OS), has limited knowledge regarding its impact on tumor immune microenvironment (TIME). Here, tissues from 6 chemotherapy-naive OS patients underwent single-cell RNA sequencing (scRNA-seq) and were analyzed alongside public dataset (GSE152048) containing 7 post-chemotherapy OS tissues. CD45+ (PTPRC+) cells were used for cell clustering and annotation. Changes in immune cell composition pre- and post-chemotherapy were characterized. Totally, 28,636 high-quality CD45+ (PTPRC+) cells were extracted. Following chemotherapy, the proportions of regulatory T cells (Tregs) and activated CD8 T cells decreased, while CD8 effector T cells increased. GO analysis indicated that differentially expressed genes (DEGs) in T cells were associated with cell activation, adaptive immune response, and immune response to tumor cells. Furthermore, the proportions of plasma cells increased, while naive B cells decreased. B cell surface receptors expression was upregulated, and GO analysis revealed DEGs of B cells were mainly enriched in B cell-mediated immunity and B cell activation. Moreover, M2 polarization of macrophages was suppressed post-chemotherapy. Overall, this study elucidates chemotherapy remodels the OS TIME landscape, triggering immune heterogeneity and enhancing anti-tumor properties.

Reversing the Natural Drug Resistance of Gram-Negative Bacteria to Fusidic Acid via Forming Drug-Phospholipid Complex.

Drug resistance substantially compromises antibiotic therapy and poses a serious threat to public health. Fusidic acid (FA) is commonly used to treat staphylococcal infections, such as pneumonia, osteomyelitis and skin infections. However, Gram-negative bacteria have natural resistance to FA, which is almost restrained in cell membranes due to the strong interactions between FA and phospholipids. Herein, we aim to utilize the strong FA-phospholipid interaction to pre-form a complex of FA with the exogenous phospholipid. The FA, in the form of an FA-phospholipid complex (FA-PC), no longer interacts with the endogenous membrane phospholipids and thus can be delivered into bacteria cells successfully. We found that the water solubility of FA (5 µg/mL) was improved to 133 µg/mL by forming the FA-PC (molar ratio 1:1). Furthermore, upon incubation for 6 h, the FA-PC (20 µg/mL) caused a 99.9% viability loss of E. coli and 99.1% loss of P. aeruginosa, while free FA did not work. The morphology of the elongated bacteria cells after treatment with the FA-PC was demonstrated by SEM. The successful intracellular delivery was shown by confocal laser scanning microscopy in the form of coumarin 6-PC (C6-PC), where C6 served as a fluorescent probe. Interestingly, the antibacterial effect of the FA-PC was significantly compromised by adding extra phospholipid in the medium, indicating that there may be a phospholipid-based transmembrane transport mechanism underlying the intracellular delivery of the FA-PC. This is the first report regarding FA-PC formation and its successful reversing of Gram-negative bacteria resistance to FA, and it provides a platform to reverse transmembrane delivery-related drug resistance. The ready availability of phospholipid and the simple preparation allow it to have great potential for clinical use.

Comparing the efficacy and safety of three surgical approaches for total hysterectomy (TSATH): protocol for a multicentre, single-blind, parallel-group, randomised controlled trial.

INTRODUCTION: Hysterectomy is the most common surgical procedure in the field of gynaecology. The traditional multiport laparoscopy, transumbilical laparoendoscopic single-site surgery (TU-LESS) and transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy approaches have been implemented to varying degrees in clinical practice. At present, although their feasibility has been proven, there are no large randomised controlled studies on postoperative rehabilitation. This study aims to evaluate postoperative recovery and assess the safety and effectiveness of these three surgical approaches for total laparoscopic hysterectomy. METHOD AND ANALYSIS: This is a multicentre, randomised, single-blind, three-arm, parallel-group, interventional clinical trial. Recruitment will be carried out in five tertiary hospitals in China. Patients diagnosed with benign uterine disease or precancerous lesions will be assigned to the vNOTES group, TU-LESS group and conventional laparoscopy group at a 1:1:1 ratio. The achievement rate of comprehensive indices of enhanced recovery after surgery (ERAS) within 24 hours postoperatively will be considered the primary outcome (the comprehensive indicators of ERAS include fluid intake, passing flatus, urination after catheter removal, ambulation and a Visual Analogue Scale score ≤3.) This study will use a non-inferiority test, with a power (1-ß) of 80% and a margin of -0.15, at a one-sided α of 0.0125. The sample size will be 480 patients (including an assumed 15% dropout rate), calculated according to the primary outcome. ETHICS AND DISSEMINATION: This study was approved on 25 April 2022 by the Medical Ethics Committee of West China Second University Hospital (2022(057)), Sichuan University, Chengdu, China. All participants will be required to provide informed consent before their participation in the study. The results of the trial will be submitted for publication in a peer-reviewed journal and presented at international conferences. PROTOCOL VERSION: V.3.0, 31 August 2023. TRIAL REGISTRATION NUMBER: ChiCTR2200057405.

Prediction of the active compounds and mechanism of Biochanin A in the treatment of Legg-Calvé-Perthes disease based on network pharmacology and molecular docking.

BACKGROUND: Legg-Calvé-Perthes disease is a special self-limited disease in pediatric orthopedics with a high disability rate and a long-term course, and there is still no clear and effective therapeutic drug in clinic. This study aimed to investigate the potential efficacy of biochanin A, a kind of oxygen-methylated isoflavone compound, in treating Perthes disease based on network pharmacology, molecular docking and in vitro experiments. METHODS: IL-6 was used to stimulate human umbilical vein endothelial cells to construct endothelial cell dysfunction model. We demonstrated whether biochanin A could alleviate endothelial dysfunction through CCK8 assay, immunofluorescence. Targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. Targets of endothelial dysfunction were obtained from Genecards and OMIM databases. Protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomics analyses were used to analyze the potential target and the key pathway of the anti-endothelial dysfunction activity of biochanin A. To validate the potential target-drug interactions, molecular docking and molecular dynamics simulations were performed and the result was proved by western blot. RESULTS: It was found that biochanin A can promote the expression of ZO-1, reduce the expression of ICAM-1, which means improving endothelial dysfunction. A total of 585 targets of biochanin A from pharmMappeer, SWISS, and TargetNet databases were screened. A total of 10,832 targets of endothelial dysfunction were obtained from Genecards and OMIM databases. A total of 527 overlapping targets of endothelial dysfunction and biochanin A were obtained. AKT1, TNF-α, VCAM1, ICAM1, and NOS3 might be the key targets of the anti-endothelial dysfunction activity of biochanin A, and the key pathways might be PI3K-Akt and TNF signaling pathways. Molecular docking results indicated that the AKT1 and TNF-α had the highest affinity binding with biochanin A. CONCLUSION: This study indicates that biochanin A can target AKT1 and TNF-α to alleviate endothelial dysfunction induced by IL-6 in Perthes disease, which provides a theoretical basis for the treatment of Perthes disease by using biochanin A.

Drug-free and multifunctional sodium bicarbonate/hyaluronic acid hybrid dressing for synergistic healing of infected wounds.

Skin wounds are susceptible to microbial infections which commonly lead to the delayed wound healing. Rapid clearance of pathogens from the wound is of great significance and importance for efficient healing of the infected wounds. Herein, we report a multifunctional hybrid dressing, which simply combines sodium bicarbonate (NaHCO3) and hyaluronic acid (HA) for the synergistic wound healing. Addition of NaHCO3 allows the hybrid dressing to have the great antibacterial and antioxidant activity, while maintaining the intrinsic skin repair function of HA. As a result, NaHCO3/HA hybrid dressing showed the great antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) pathogens, the ability to improve the fibroblasts proliferation and migration, the cell-protection capacity under H2O2-induced oxidative stress, and most importantly, the great healing efficacy for the mice wound infected by S. aureus. We further found that the epidermal regeneration, the collagen deposition and the angiogenesis were enhanced by NaHCO3/HA hybrid dressing. All these effects were NaHCO3 concentration-dependent. Since the NaHCO3/HA hybrid dressing is drug-free, easily fabricated, biocompatible, and efficient for wound healing, it may have great potentials for clinical management of infected wounds.

Operando X-Ray Diffraction Boosting Understanding of Graphite Phase Evolution in Lithium-Ion Batteries.

The fast charging/discharging performance of lithium-ion batteries is closely related to the properties of electrode materials, especially the phase evolution and Li+ diffusion kinetics. The phase evolution and intrinsic properties of an electrode material under different C-rates can be investigated by applying operando X-ray diffraction (XRD). In this study, a transmission X-ray diffractometer is used in operando monitoring the behaviors of NCM811/Graphite pouch cells during charging/discharging at low rate (0.1C) and high rate (2.5C), especially the structure changes, phase evolution, and relaxation of graphite anode. The variations in XRD patterns, as well as and the inconsistency between the state of charge (SOC) of full cells and the SOC of electrodes, are explained based on genetic algorithm and shrinking annuli model. Furthermore, from the perspectives of monitoring and identification of electrode state, structural design of materials and electrodes, and optimization of charging/discharging protocols, practical suggestions for understanding the state and improving the performance of electrodes are proposed.

Solvent-pair surfactants enabled assembly of clusters and copolymers towards programmed mesoporous metal oxides.

Organic-inorganic molecular assembly has led to numerous nano/mesostructured materials with fantastic properties, but it is dependent on and limited to the direct interaction between host organic structure-directing molecules and guest inorganic species. Here, we report a "solvent-pair surfactants" enabled assembly (SPEA) method to achieve a general synthesis of mesostructured materials requiring no direct host-guest interaction. Taking the synthesis of mesoporous metal oxides as an example, the dimethylformamide/water solvent pairs behave as surfactants and induce the formation of mesostructured polyoxometalates/copolymers nanocomposites, which can be converted into metal oxides. This SPEA method enables the synthesis of functional ordered mesoporous metal oxides with different pore sizes, structures, compositions and tailored pore-wall microenvironments that are difficult to access via conventional direct organic-inorganic assembly. Typically, nitrogen-doped mesoporous ε-WO3 with high specific surface area, uniform mesopores and stable framework is obtained and exhibits great application potentials such as gas sensing.

Challenges and approaches of single-crystal Ni-rich layered cathodes in lithium batteries.

High energy density and high safety are incompatible with each other in a lithium battery, which challenges today's energy storage and power applications. Ni-rich layered transition metal oxides (NMCs) have been identified as the primary cathode candidate for powering next-generation electric vehicles and have been extensively studied in the last two decades, leading to the fast growth of their market share, including both polycrystalline and single-crystal NMC cathodes. Single-crystal NMCs appear to be superior to polycrystalline NMCs, especially at low Ni content (≤60%). However, Ni-rich single-crystal NMC cathodes experience even faster capacity decay than polycrystalline NMC cathodes, rendering them unsuitable for practical application. Accordingly, this work will systematically review the attenuation mechanism of single-crystal NMCs and generate fresh insights into valuable research pathways. This perspective will provide a direction for the development of Ni-rich single-crystal NMC cathodes.

Circ_0102231 inactivates the PI3K/AKT signaling pathway by regulating the miR-635/NOVA2 pathway to promote the progression of non-small cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs) are involved in the malignant development of tumors. However, the mechanism of circ_0102231 in non-small cell lung cancer (NSCLC) has rarely been discussed and reported. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of circ_0102231, miR-635 and NOVA alternative splicing regulator 2 (NOVA2) in NSCLC tissues and cells. Western blot was applied to detect the protein expression. Cell proliferation was monitored by cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) experiments. The angiogenesis ability of cells was tested by angiogenesis assay. Flow cytometry was used to analyze cell apoptosis. The relationship between circ_0102231 and NOVA2 or miR-635 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. An in vivo transplanted tumor model was established to confirm the effect of circ_0102231 on tumor formation. RESULTS: Circ_0102231 was abnormally upregulated in NSCLC tissues and correlated with clinical stage. Silencing of circ_0102231 inhibited cell proliferation and angiogenesis but significantly promoted the apoptosis of NSCLC cells. There were target binding sites between circ_0102231 and miR-635, miR-635 and NOVA2. Importantly, circ_0102231 acted as a sponge for miR-635, increased the expression of NOVA2, and activated the PI3K/AKT signaling pathway. Finally, silencing of circ_0102231 also had obvious antitumor effects in vivo. CONCLUSION: Circ_0102231 increased the expression of NOVA2 by interacting with miR-635 to promote the malignant progression of NSCLC.

Quinary RuRhPdPtAu high-entropy alloy as an efficient electrocatalyst for the hydrogen evolution reaction.

Quinary RuRhPdPtAu high-entropy alloy nanoparticles (HEA-NPs) were prepared for the first time from a deep eutectic solvent by an electrochemical method. Owing to the benefits of high entropy and abundant surface active sites, the RuRhPdPtAu HEA-NPs exhibit outstanding electrocatalytic performance for the hydrogen evolution reaction.

Chinese Women's Acceptance of Intimate Partner Violence Against Women.

Few studies have empirically examined factors influencing attitudes toward acceptance of intimate partner violence (IPV), and no study has yet studied the topic in China. We empirically test the effects of attitudes toward gender roles and exposure to violence during childhood on the acceptance of IPV and the moderating effects of education and income on these relationships. Using survey data collected from 600 Chinese women from southern China, we found that education and income moderate the relationship between belief in gender equality and acceptance of IPV. The effect of exposure to parental physical violence on the acceptance of IPV is moderated by education.

Association of Non-Invasive Markers with Significant Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

Purpose: The identification of significant fibrosis is critical for predicting the prognosis of non-alcoholic fatty liver disease (NAFLD). This study aimed to compare the predictive value of chitinase-3-like protein 1 (CHl3L1) and other non-invasive biomarkers, as well as to establish a novel non-invasive diagnostic model for assessing the risk of significant fibrosis in NAFLD. Patients and Methods: A total of 71 patients with confirmed NAFLD based on liver biopsy were included in this study. Serum CHI3L1 levels and other non-invasive fibrosis assessment measures were determined. The aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (FIB-4) were calculated to assess the diagnostic superiority of serum CHI3L1 compared to other non-invasive fibrosis assessment measures. Multivariate logistic regression analysis was conducted to identify relevant variables for constructing a diagnostic model. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of each index, including the area under ROC curve (AUC), sensitivity, and specificity. A nomogram was established based on the logistic regression model. Results: Serum CHI3LI levels were found to be higher in NAFLD patients with significant fibrosis compared to those without significant fibrosis. Multivariate logistic regression analysis revealed that aspartate aminotransferase (AST), type IV collagen (IV-C), CHI3L1, and liver stiffness measurement (LSM) were identified as potential independent risk factors associated with significant fibrosis in patients. The AUC of CHI3L1 for diagnosing significant liver fibrosis was 0.716 (0.596,0.836), with the optimal cut-off point of 125.315. The nomogram incorporating CHI3LI, AST, IV-C, and LSM further improved the potential predictive value, with an AUC for diagnosing significant fibrosis of 0.864 (0.766,0.962). This was superior to IV-C, CHI3L1, LSM, and APRI (all p < 0.05). Conclusion: The diagnostic model constructed by CHI3L1 combined with the existing non-invasive markers AST, IV-C, and LSM can help assess the risk of significant liver fibrosis in NAFLD.

[Regulation of non-coding RNA in type H vessels angiogenesis of bone].

Objective: To summarize the regulatory effect of non-coding RNA (ncRNA) on type H vessels angiogenesis of bone. Methods: Recent domestic and foreign related literature about the regulation of ncRNA in type H vessels angiogenesis was widely reviewed and summarized. Results: Type H vessels is a special subtype of bone vessels with the ability to couple bone formation. At present, the research on ncRNA regulating type H vessels angiogenesis in bone diseases mainly focuses on microRNA, long ncRNA, and small interfering RNA, which can affect the expressions of hypoxia inducible factor 1α, platelet derived growth factor BB, slit guidance ligand 3, and other factors through their own unique ways of action, thus regulating type H vessels angiogenesis and participating in the occurrence and development of bone diseases. Conclusion: At present, the mechanism of ncRNA regulating bone type H vessels angiogenesis has been preliminarily explored. With the deepening of research, ncRNA is expected to be a new target for the diagnosis and treatment of vascular related bone diseases.

Trends in the prevalence of elevated cardiovascular risk and the control of its risk factors Among US adults, 2001-2020.

Background: An accurate assessment of current trends in cardiovascular risks could inform public health policy. This study aims to determine 20-year trends in the prevalence of elevated cardiovascular risk and its risk factors' control among US adults. Methods: In this serial cross-sectional analysis of 23,594 adults, aged 40-79 years, without clinical atherosclerotic cardiovascular disease (ASCVD) in the National Health and Nutrition Examination Survey from 2001 to 2020, we calculated the prevalence of elevated cardiovascular risk (10-year ASCVD risk ≥ 7.5%) for all participants and subgroups with their risk factors controlled for diabetes, hypertension, or dyslipidemia. Results: The age- and sex-adjusted prevalence of elevated cardiovascular risk slightly decreased from 41.5% (95% CI, 39.7-43.3%) in 2001-2004 to 38.6% (95% CI, 36.1-41.1%) in 2017-2020 (P for trend = 0.169) while the respective sex-adjusted prevalence significantly increased from 34.4% (95% CI, 32.8-36.0%) to 39.5% (95% CI, 37.0-42.0%; P for trend <0.001). Sex and race continued to show disparities in cardiovascular risk. Furthermore, a worsening disparity in age- and sex-adjusted prevalence of elevated cardiovascular risk between young and old and a narrowing gap among different education and poverty index levels (all P trend for interaction <0.05). Differential decomposition analysis found that demographic changes (primarily population aging) led to an 8.8% increase in the prevalence of elevated cardiovascular risk from 2001 to 2004 to 2017-2020, while risk factor control led to a 3.8% decrease. The rate of individuals receiving treatment for diabetes, hypertension, or dyslipidemia increased significantly between 2001 and 2020 (all P for trend <0.05). The rate of participants with hypertension who achieved blood pressure under 130/80 mmHg and those with dyslipidemia who achieved a non-high-density lipoprotein cholesterol level under 130 mg/dl increased significantly (all P for trend <0.001). Conclusions: There is a slight reduction in the prevalence of age- and sex-adjusted elevated cardiovascular risk among US adults without clinical ASCVD between 2001 and 2020, while the sex-adjusted prevalence significantly increased. The decrease in elevated cardiovascular risk prevalence was mainly attributed to risk factor control, while demographic changes contributed to an increase.

Nondestructive monitoring of annealing and chemical-mechanical planarization behavior using ellipsometry and deep learning.

The Cu-filling process in through-silicon via (TSV-Cu) is a key technology for chip stacking and three-dimensional vertical packaging. During this process, defects resulting from chemical-mechanical planarization (CMP) and annealing severely affect the reliability of the chips. Traditional methods of defect characterization are destructive and cumbersome. In this study, a new defect inspection method was developed using Mueller matrix spectroscopic ellipsometry. TSV-Cu with a 3-µm-diameter and 8-µm-deep Cu filling showed three typical types of characteristics: overdishing (defect-OD), protrusion (defect-P), and defect-free. The process dimension for each defect was 13 nm. First, the three typical defects caused by CMP and annealing were investigated. With single-channel deep learning and a Mueller matrix element (MME), the TSV-Cu defect types could be distinguished with an accuracy rate of 99.94%. Next, seven effective MMEs were used as independent channels in the artificial neural network to quantify the height variation in the Cu filling in the z-direction. The accuracy rate was 98.92% after training, and the recognition accuracy reached 1 nm. The proposed approach rapidly and nondestructively evaluates the annealing bonding performance of CMP processes, which can improve the reliability of high-density integration.

Carbohydrate polymer-based bioadhesive formulations and their potentials for the treatment of ocular diseases: A review.

Eyes are directly exposed to the outer environment and susceptible to infections, leading to various ocular disorders. Local medication is preferred to treat eye diseases due to its convenience and compliance. However, the rapid clearance of the local formulations highly limits the therapeutic efficacy. In the past decades, several carbohydrate bioadhesive polymers (CBPs), such as chitosan and hyaluronic acid, have been used in ophthalmology for sustained ocular drug delivery. These CBP-based delivery systems have improved the treatment of ocular diseases to a large extent but also caused some undesired effects. Herein, we aim to summarize the applications of some typical CBPs (including chitosan, hyaluronic acid, cellulose, cyclodextrin, alginate and pectin) in treating ocular diseases from the general view of ocular physiology, pathophysiology and drug delivery, and to provide a comprehensive understanding of the design of the CBP-based formulations for ocular use. The patents and clinical trials of CBPs for ocular management are also discussed. In addition, a discussion on the concerns of CBPs in clinical use and the possible solutions is presented.