Mussel byssus-inspired dual-functionalization of zirconia dental implants for improved bone integration.

Zirconia faces challenges in dental implant applications due to its inherent biological inertness, which compromises osseointegration, a critical factor for the long-term success of implants that rely heavily on specific cell adhesion and enhanced osteogenic activity. Here, we fabricated a dual-functional coating that incorporates strontium ions, aimed at enhancing osteogenic activity, along with an integrin-targeting sequence to improve cell adhesion by mussel byssus-inspired surface chemistry. The results indicated that although the integrin-targeting sequence at the interface solely enhances osteoblast adhesion without directly increasing osteogenic activity, its synergistic interaction with the continuously released strontium ions from the coating, as compared to the release of strontium ions alone, significantly enhances the overall osteogenic effect. More importantly, compared to traditional polydopamine surface chemistry, the coating surface is enriched with amino groups capable of undergoing various chemical reactions and exhibits enhanced stability and aesthetic appeal. Therefore, the synergistic interplay between strontium and the functionally customizable surface offers considerable potential to improve the success of zirconia implantation.

Exploration of poly (ADP-ribose) polymerase inhibitor resistance in the treatment of BRCA1/2-mutated cancer.

Breast cancer susceptibility 1/2 (BRCA1/2) genes play a crucial role in DNA damage repair, yet mutations in these genes increase the susceptibility to tumorigenesis. Exploiting the synthetic lethality mechanism between BRCA1/2 mutations and poly(ADP-ribose) polymerase (PARP) inhibition has led to the development and clinical approval of PARP inhibitor (PARPi), representing a milestone in targeted therapy for BRCA1/2 mutant tumors. This approach has paved the way for leveraging synthetic lethality in tumor treatment strategies. Despite the initial success of PARPis, resistance to these agents diminishes their efficacy in BRCA1/2-mutant tumors. Investigations into PARPi resistance have identified replication fork stability and homologous recombination repair as key factors sensitive to PARPis. Additionally, studies suggest that replication gaps may also confer sensitivity to PARPis. Moreover, emerging evidence indicates a correlation between PARPi resistance and cisplatin resistance, suggesting a potential overlap in the mechanisms underlying resistance to both agents. Given these findings, it is imperative to explore the interplay between replication gaps and PARPi resistance, particularly in the context of platinum resistance. Understanding the impact of replication gaps on PARPi resistance may offer insights into novel therapeutic strategies to overcome resistance mechanisms and enhance the efficacy of targeted therapies in BRCA1/2-mutant tumors.

Blood Coagulation-Inspired Fibrin Hydrogel for Portable Detection of Thrombin Based on Personal Glucometer.

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0-0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs.

Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation combined with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Currently published studies have not observed consistent results on the efficacy and safety of direct oral anticoagulants (DOACs) use in patients with chronic kidney disease (CKD) combined with atrial fibrillation (AF). Therefore, this study conducted a meta-analysis of the efficacy and safety of DOACs for patients with AF complicated with CKD. METHODS: Database literature was searched up to May 30, 2023, to include randomized controlled trials (RCT) involving patients with AF complicated with CKD DOACs and vitamin K antagonists (VKAs). Stroke, systemic embolism (SE), and all-cause mortality were used as effectiveness indicators, and major bleeding, intracranial hemorrhage (ICH), fatal bleeding, gastrointestinal bleeding (GIB), and clinically relevant non-major bleeding (CRNMB) were used as safety outcomes. RESULTS: Nine RCT studies were included for analysis according to the inclusion criteria. Results of the efficacy analysis showed that compared with VKAs, DOACs reduced the incidence of stroke/SE (OR = 0.75, 95% CI 0.67-0.84) and all-cause deaths (OR = 0.84, 95% CI 0.75-0.93) in patients with AF who had comorbid CKD. Safety analyses showed that compared with VKAs, DOACs improved safety by reducing the risk of major bleeding (OR = 0.76, 95%CI 0.65-0.90), ICH (OR = 0.46, 95%CI 0.38-0.56), and fatal bleeding (OR = 0.75, 95%CI 0.65-0.87), but did not reduce the incidence of GIB and CRNMB. CONCLUSION: Compared with VKAs, DOACs may increase efficacy and improve safety in AF patients with CKD (90 ml/min> Crcl≥15 ml/min), and shows at least similar efficacy and safety in AF patients with Kidney failure (Crcl<15 ml/min).

Dynamic repulsive interaction enables an asymmetric electron-phonon coupling for improving Raman scattering.

Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.

Multifunctional Sensors Made with Conductive Microframework and Biomass Hydrogel for Detecting Packaging Pressure and Food Freshness.

Food packaging detection devices have attracted attention to optimize storage situations and reduce food spoilage. However, low-cost and highly sensitive multifunctional sensors for detecting both food freshness and packaging pressure are still lacking. In this study, a multifunctional sensor was developed consisting of a MXene coated alcohol-soluble polyurethane fiber network (MXene/APU) and composite biohydrogel films made of konjac glucomannan, chitosan, and blueberry anthocyanin (KCB). Based on the pressure sensitivity of MXene/APU and the color changes of KCB in response to pH values, the sensor can detect internal package bulging, external squeezing, and food deterioration. The pressure sensor shows a sensitivity of 1.16 kPa-1, a response time of 200 ms, a wide strain range of 1092%, and stability over multiple loops. The pressure sensor could detect human motion and identify surface morphologies. The excellent sensor performance was attributed to the porous structure and large specific surface area of microfiber networks, conductivity of MXene nanosheets, and protective effect of KCB films coated on the conductive membrane. Besides, the microfluidic blow-spinning method used to prepare microfiber networks showed the advantages of low energy consumption and high production efficiency. Based on the color changes of blueberry anthocyanin loaded in KCB films in response to pH, the sensor realized sensitive spoilage detection of food containing protein. This study provides a new multifunctional food packaging sensing device and a greater understanding of the optimization and application of related devices.

Addition of konjac glucomannan improves spraying efficiency on fruits and vegetables: Effect of surface hydrophilicity and molecular weight.

Biomacromolecules have attracted interest as spraying additives due to their degradability, renewability, and non-toxicity. However, microscopic mechanism of the biomacromolecules regulating the droplet behavior on fruits and vegetables is still unclear. In this study, konjac glucomannan (KGM) was used to improve the spraying efficiency and the fresh-keeping performance of tea polyphenols solution. KGM increased effective spreading ratio on hydrophilic surfaces and retention ratio of the main droplet on hydrophobic surfaces, thus improving spraying efficiency. Computational fluid dynamics and Brown dynamics simulations were implemented to investigate KGM behaviors during droplets colliding on hydrophilic and hydrophobic surfaces. Most KGM molecules extended and then collapsed in gradually weakened shear flow. Meanwhile, on the hydrophobic surface, most KGM molecules were continuously stretched by the unstable flow field. As the KGM extended, the kinetic energy of droplets converted into elastic energy stored in the KGM, promoting the stability of droplets on target surfaces and improving the spraying efficiency. The KGM molecular weight of 3.8 × 105 Da was optimal from the point of energy storage density. This study provides more understanding of the mechanism of biomacromolecules on spraying efficiency and guidance to develop biomass spraying additives for fruit and vegetable preservation.

Flexiplex: a versatile demultiplexer and search tool for omics data.

MOTIVATION: The process of analyzing high throughput sequencing data often requires the identification and extraction of specific target sequences. This could include tasks, such as identifying cellular barcodes and UMIs in single-cell data, and specific genetic variants for genotyping. However, existing tools, which perform these functions are often task-specific, such as only demultiplexing barcodes for a dedicated type of experiment, or are not tolerant to noise in the sequencing data. RESULTS: To overcome these limitations, we developed Flexiplex, a versatile and fast sequence searching and demultiplexing tool for omics data, which is based on the Levenshtein distance and thus allows imperfect matches. We demonstrate Flexiplex's application on three use cases, identifying cell-line-specific sequences in Illumina short-read single-cell data, and discovering and demultiplexing cellular barcodes from noisy long-read single-cell RNA-seq data. We show that Flexiplex achieves an excellent balance of accuracy and computational efficiency compared to leading task-specific tools. AVAILABILITY AND IMPLEMENTATION: Flexiplex is available at https://davidsongroup.github.io/flexiplex/.

All-in-one porous membrane enables full protection in guided bone regeneration.

The sophisticated hierarchical structure that precisely combines contradictory mechanical and biological characteristics is ideal for biomaterials, but it is challenging to achieve. Herein, we engineer a spatiotemporally hierarchical guided bone regeneration (GBR) membrane by rational bilayer integration of densely porous N-halamine functionalized bacterial cellulose nanonetwork facing the gingiva and loosely porous chitosan-hydroxyapatite composite micronetwork facing the alveolar bone. Our GBR membrane asymmetrically combine stiffness and flexibility, ingrowth barrier and ingrowth guiding, as well as anti-bacteria and cell-activation. The dense layer has a mechanically matched space maintenance capacity toward gingiva, continuously blocks fibroblasts, and prevents bacterial invasion with multiple mechanisms including release-killing, contact-killing, anti-adhesion, and nanopore-blocking; the loose layer is ultra-soft to conformally cover bone surfaces and defect cavity edges, enables ingrowth of osteogenesis-associated cells, and creates a favorable osteogenic microenvironment. As a result, our all-in-one porous membrane possesses full protective abilities in GBR.

Palladium-catalysed fragmentary esterification-induced allylic alkylation of allyl carbonates and cyclic vinylogous anhydrides.

An unprecedented palladium-catalysed fragmentary esterification-induced allylic alkylation (FEAA) of cyclic vinylogous anhydrides (CVAs) and allyl carbonates has been disclosed. The protocol features broad sp3-rich scaffold tolerance, rendering highly functionalized 1,6 and 1,7-dicarbonyls in up to high yields and diastereoselectivities. Three-component FEAA is also well tolerant to generate 1,6-dicarbonyls through the addition of extra O/N-nucleophiles. Furthermore, cyclic allyl carbonate-involved FEAA provides an efficient approach for the synthesis of structurally complex medium-sized rings.

Large-area, size-controlled and transferable graphene oxide-metal films for humidity sensor.

The lack of low-cost methods to synthesize large-area graphene-based materials is still an important factor that limits the practical application of graphene devices. Herein, we present a facile method for producing large-area graphene oxide-metal (GO-M) films, which are size controllable and transferable. The sensor constructed using the GO-M film exhibited humidity sensitivity while being unaffected by pressure. The relationship between the sensor's resistance and relative humidity followed an exponential trend. The GO-Mg sensor was the most sensitive among all the tested sensors. The facile synthesis of GO-M films will accelerate the widespread utilization of graphene-based materials.

Risk factors for anticoagulant-associated gastrointestinal hemorrhage: a systematic review and meta-analysis.

BACKGROUND/AIMS: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. METHODS: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. RESULTS: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. CONCLUSION: The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

Comparison of the Correlation Between Coagulation Indices and Rivaroxaban Concentrations.

BACKGROUND: Rivaroxaban has predictable pharmacokinetics and pharmacodynamics. However, monitoring rivaroxaban concentrations should be provided for special patients with hepatic insufficiency, high bleeding risk, and high thrombotic risk. OBJECTIVE: This study aimed to correlate chromogenic anti-Xa assay, prothrombin time (PT), activated partial thromboplastin time (APTT), thromboelastogram reaction time (TEG R-time), and rivaroxaban concentration measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) (MS-Riva). METHODS: Peripheral venous blood was collected from recruited patients 30 minutes before and 2 to 4 hours after drug administration. High-performance liquid chromatography-tandem mass spectrometry and chromogenic anti-Xa assay measured rivaroxaban concentration. Different assays were compared by Pearson correlation coefficient and Bland-Altman analysis. RESULTS: A total of 104 patients with 191 plasma were included in the study. Overall analysis shows that chromogenic anti-Xa assay, PT, APTT, and TEG R-time strongly correlated with MS-Riva (r = 0.986; r = 0.884; r = 0.741; r = 0.739; P < 0.001). Rivaroxaban peak concentration detected by HPLC-MS/MS (MS-peak) showed a very strong correlation with the chromogenic anti-Xa assay (r = 0.977, P < 0.001) and moderate correlation with PT, APTT, and TEG R-time (r = 0.670; r = 0.571; r = 0.481, P < 0.001). Rivaroxaban trough concentration detected by HPLC-MS/MS (MS-trough) correlated strongly with the chromogenic anti-Xa assay (r = 0.884, P < 0.001), weakly with APTT (r = 0.313; P = 0.043), and not significantly with PT and TEG R-time (P = 0.140; P = 0.341). CONCLUSION AND RELEVANCE: High-performance liquid chromatography-tandem mass spectrometry/MS is the preferred choice for monitoring peak and tough concentrations, followed by anti-Xa, while PT is only suitable for peak concentrations. This study can help the clinicians to better adjust the medication regimen and reduce the risk of recurrence of thrombosis as well as the risk of bleeding.

Comparison of the Efficacy and Safety of Rivaroxaban and Low Molecular Heparin in Preventing Venous Thromboembolism in Inpatient Cancer Patients.

BACKGROUND: There are few studies on using rivaroxaban and low molecular heparin (LMWH) to prevent venous thromboembolism (VTE) in hospitalized cancer patients. OBJECTIVE: We conducted a retrospective study to evaluate the efficacy and safety of rivaroxaban versus LMWH for the primary prevention of VTE in inpatient cancer patients. METHODS: Information on patients was collected through 6-month follow-up and medical record inquiries. Clinical outcomes included VTE, total bleeding, thrombosis, major bleeding, minor bleeding, all-cause death, and a composite endpoint of bleeding, thrombosis, and death. RESULTS: A total of 602 hospitalized cancer patients were included in this study. During 6 months of follow-up, there were 26 VTE events (8.6%), 42 total bleeding events (7.0%), 62 all-cause deaths (10.3%), and 140 composite endpoints (23.3%). After adjusting for various confounding factors, there were no significant differences between the rivaroxaban and LMWH for VTE events (OR = 0.851, 95% CI [0.387-1.872], P=0.688), total bleeding (OR = 1.690, 95% CI [0.768-3.719], P = 0.192], thrombosis events (OR = 0.919, 95% CI [0.520-1.624], P = 0.772], major bleeding (OR = 0.276, 95% CI [0.037-2.059], P = 0.209), all-cause death (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), and composite endpoints (OR = 0.994, 95% CI [0.492-2.009], P = 0.987), while minor bleeding (OR = 3.661 95% CI [1.000-7.083], P = 0.050) was significantly higher in the rivaroxaban than in the LMWH. CONCLUSIONS AND RELEVANCE: In thromboprophylaxis in inpatient cancer patients, rivaroxaban has a similar rate of VTE and bleeding events as LMWH. Our results may provide a reference for the clinical use of rivaroxaban to prevent VTE in hospitalized cancer patients.

Masking effects on iso-valeric acid recognition by sub-threshold odor mixture.

Masking unpleasant odors with pleasant-smelling odorants has a long history and is utilized in various industries, including perfumery and consumer products. However, the effectiveness of odor masking is idiosyncratic and temporary. In this study, we employed Sniff olfactometry (SO) to investigate the psychophysics of masking using brief 70 ms stimulations with mixtures of the mal-odorant iso-valeric acid (IVA) and different masking agents. IVA is a component of human sweat that can overpower its smell and is often associated with unpleasant descriptors such as "gym locker," "smelly feet," "dirty clothes," and so on. Traditionally, high concentrations of pleasant-smelling odorants are used to mitigate the unpleasantness of IVA in situations involving clothing or environments contaminated with IVA. To examine the masking effects of sub-threshold levels of various masking agents (neohivernal, geraniol, florhydral, decanal, iso-longifolanone, methyl iso-eugenol, and s-limonene) on IVA, we conducted experiments using SO to measure the probability of recognizing IVA after 70 ms stimulations with headspaces containing mixtures of super-threshold concentrations of IVA and sub-threshold concentrations of IVA suppressors. The study involved nine subjects, and on average, a single masking agent was found to decrease IVA recognition probability by 14-72%. Moreover, a sub-threshold odor mixture consisting of 6 masking agents demonstrated a substantial decrease in IVA recognition, with a reduction of 96%.

Oxfendazole Induces Apoptosis in Ovarian Cancer Cells by Activating JNK/MAPK Pathway and Inducing Reactive Oxygen Species Generation.

Ovarian cancer (OC) is one of the most common and high mortality type of cancer among women worldwide. The majority of patients with OC respond to chemotherapy initially; however, most of them become resistant to chemotherapy and results in a high level of treatment failure in OC. Therefore, novel agents for the treatment of OC are urgently required. Benzimidazole anthelmintics might have the promising efficacy for cancer therapy as their selectively binding activity to ß-tubulin. Recent study has shown that one of the benzimidazole anthelmintics oxfendazole inhibited cell growth of non-small cell lung cancer cells, revealing its anti-cancer activity; however, the pharmacological action and detailed mechanism underlying the effects of oxfendazole on OC cells remain unclear. Therefore, the present study investigated the cytotoxic effects of oxfendazole on OC cells. Our results demonstrated that oxfendazole significantly decreased the viability of OC cells. Oxfendazole inhibited the proliferation, induced G2/M phase arrest and apoptotic cell death in A2780 cells. The c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway was activated and reactive oxygen species (ROS) generation was increased in OC cells treated with oxfendazole; oxfendazole-induced apoptosis was notably abrogated when co-treated with JNK inhibitor SP600125 and ROS scavenger N-acetyl-L-cysteine (NAC), indicating that JNK/MAPK pathway activation and ROS accumulation was associated with the oxfendazole-induced apoptosis of OC cells. Moreover, oxfendazole could also induce the proliferation inhibition and apoptosis of cisplatin resistant cells. Collectively, these results revealed that oxfendazole may serve as a potential therapeutic agent for the treatment of OC.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study.

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis. RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12-2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19-2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14-4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66-5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46-6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23-13.54, P = 0.577). CONCLUSIONS: Higher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Machine Learning-Enhanced Biomass Pressure Sensor with Embedded Wrinkle Structures Created by Surface Buckling.

Flexible piezoresistive sensors are core components of many wearable devices to detect deformation and motion. However, it is still a challenge to conveniently prepare high-precision sensors using natural materials and identify similar short vibration signals. In this study, inspired by microstructures of human skins, biomass flexible piezoresistive sensors were prepared by assembling two wrinkled surfaces of konjac glucomannan and k-carrageenan composite hydrogel. The wrinkle structures were conveniently created by hardness gradient-induced surface buckling and coated with MXene sheets to capture weak pressure signals. The sensor was applied to detect various slight body movements, and a machine learning method was used to enhance the identification of similar and short throat vibration signals. The results showed that the sensor exhibited a high sensitivity of 5.1 kPa-1 under low pressure (50 Pa), a fast response time (104 ms), and high stability over 100 cycles. The XGBoost machine learning model accurately distinguished short voice vibrations similar to those of individual English letters. Moreover, experiments and numerical simulations were carried out to reveal the mechanism of the wrinkle structure preparation and the excellent sensing performance. This biomass sensor preparation and the machine learning method will promote the optimization and application of wearable devices.

Global, regional, and national burden of ischaemic heart disease and its trends, 1990-2019.

OBJECTIVES: Ischemic heart disease (IHD) has high morbidity, disability, and mortality rates and is a major contributor to the global disease burden. This study aimed to obtain a more detailed description of the burden of IHD through secondary analysis of data from the Global Burden of Disease (GBD) 2019. STUDY DESIGN: This is an epidemiological study. METHODS: Data for this study were obtained from the GBD 2019 database. Annual average percentage change (AAPC) was calculated to assess trends in IHD prevalence, morbidity, mortality, and disability-adjusted life years (DALYs). Regional and national burden of IHD was assessed by stratifying by sex, age, and socio-demographic index (SDI). RESULTS: From 1990 to 2019, the global prevalence of IHD, morbidity cases, deaths, and DALYs increased, but the age-standardized rates of IHD burden decreased. Morbidity, mortality, and DALY rates for IHD in both sexes increased with age. The prevalence, incidence, mortality, and DALY rates were higher in men than women in all age groups. In particular, the male-to-female ratios for mortality and DALY rates peaked among 35-39 year olds, while the male-to-female ratios for prevalence and morbidity peaked among 55-59 year olds. Age-standardized prevalence, incidence, and DALY rates were higher in low- and middle-income regions than in other SDI regions. CONCLUSION: Although age-standardized prevalence, morbidity, mortality, and age-standardized DALY rates due to IHD decreased globally from 1990 to 2019, age-standardized prevalence and morbidity of IHD increased in Low SDI, Low-middle SDI, and Middle SDI regions.

The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation.

BACKGROUND: The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients. PATIENTS AND METHODS: This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications. RESULTS: A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. CONCLUSION: This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.