A Novel MEMS Gyroscope In-Self Calibration Approach.

This paper presents a novel approach for hand-held low-cost MEMS (micro-electro-mechanical system) gyroscope in-self calibration. This method does not need the support of external high-precision equipment compared with traditional calibration scheme and can be accomplished by user hand rotation. In this approach, Kalman filter is designed to perform the calibration procedure and estimate gyroscope bias error, scale factor error and non-orthogonal error. The system observability is analyzed and the dynamic rotating conditions under which the sensor errors become observable are derived. The design principles of optimal calibration procedure are provided as well. Both simulated and practical experiments are carried out to test the validation of the proposed calibration algorithm. The achieved results demonstrate that the introduced approach can provide promising calibration scheme for the low-cost MEMS gyroscope.

5-Hydroxyindole-Based EZH2 Inhibitors Assembled via TCCA-Catalyzed Condensation and Nenitzescu Reactions.

5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L-04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC50 = 52.6 µM). These findings revealed that compound L-04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we discovered that trichloroisocyanuric acid (TCCA) is a novel catalyst which demonstrates condensation-promoting effects. To gain insight into the reaction, in situ React IR technology was used to confirm the reactivity. Different amines were condensed in high yields with ß-diketones or ß-ketoesters in the presence of TCCA to afford the corresponding products in a short time (10~20 min), which displayed some advantages and provided an alternative condensation strategy.

l -( -) -Quebrachitol as a Ligand for Selective Copper(0)-Catalyzed N-Arylation of Nitrogen-Containing Heterocycles.

l-(-)-Quebrachitol (QCT) has been found as a ligand of copper powder for selective N-arylation of nitrogen-containing heterocycles with aryl halides. Furthermore, another potential catalytic system (copper powder/QCT/ t-BuOK) was successfully adapted to unactivated aryl chlorides.

Zinc (II)-Mediated Selective O-Benzylation of 2-Oxo-1,2-Dihydropyridines Systems.

The selective O-benzylation of 2-oxo-1,2-dihydropyridines plays a critical role in organic synthesis of natural products and biological active molecules. Herein we report a novel ternary system of ZnO, ZnCl2 and N,N-diisopropylethylamine (DIEA), that is highly effective for selective O-benzylation of 2-oxo-1,2-dihydropyridines using abundant substituted benzyl halides and related substituted 2-oxo-1,2-dihydropyridines compounds. This process allows access to a variety of O-benzyl products under mild reaction conditions, which are important synthetic intermediates in the protection of functional groups, and represents a new method toward the development for the O-benzylation of 2-oxo-1,2-dihydropyridines.

An Adaptive Low-Cost INS/GNSS Tightly-Coupled Integration Architecture Based on Redundant Measurement Noise Covariance Estimation.

The main objective of the introduced study is to design an adaptive Inertial Navigation System/Global Navigation Satellite System (INS/GNSS) tightly-coupled integration system that can provide more reliable navigation solutions by making full use of an adaptive Kalman filter (AKF) and satellite selection algorithm. To achieve this goal, we develop a novel redundant measurement noise covariance estimation (RMNCE) theorem, which adaptively estimates measurement noise properties by analyzing the difference sequences of system measurements. The proposed RMNCE approach is then applied to design both a modified weighted satellite selection algorithm and a type of adaptive unscented Kalman filter (UKF) to improve the performance of the tightly-coupled integration system. In addition, an adaptive measurement noise covariance expanding algorithm is developed to mitigate outliers when facing heavy multipath and other harsh situations. Both semi-physical simulation and field experiments were conducted to evaluate the performance of the proposed architecture and were compared with state-of-the-art algorithms. The results validate that the RMNCE provides a significant improvement in the measurement noise covariance estimation and the proposed architecture can improve the accuracy and reliability of the INS/GNSS tightly-coupled systems. The proposed architecture can effectively limit positioning errors under conditions of poor GNSS measurement quality and outperforms all the compared schemes.

Design and Implementation of Foot-Mounted Inertial Sensor Based Wearable Electronic Device for Game Play Application.

Wearable electronic devices have experienced increasing development with the advances in the semiconductor industry and have received more attention during the last decades. This paper presents the development and implementation of a novel inertial sensor-based foot-mounted wearable electronic device for a brand new application: game playing. The main objective of the introduced system is to monitor and identify the human foot stepping direction in real time, and coordinate these motions to control the player operation in games. This proposed system extends the utilized field of currently available wearable devices and introduces a convenient and portable medium to perform exercise in a more compelling way in the near future. This paper provides an overview of the previously-developed system platforms, introduces the main idea behind this novel application, and describes the implemented human foot moving direction identification algorithm. Practical experiment results demonstrate that the proposed system is capable of recognizing five foot motions, jump, step left, step right, step forward, and step backward, and has achieved an over 97% accuracy performance for different users. The functionality of the system for real-time application has also been verified through the practical experiments.

[Relationship between bedtime and BMI, waist, blood pressure in college students: a one-year follow-up study].

OBJECTIVE: To assess the relationship between bedtime and metabolic syndrome risk factors in college students. METHODS: Participants including 186 male and414 female college students from 2 junior colleges and 1 regular college in Chizhou city were selected using stratified cluster sampling. The data on bedtime and metabolic syndrome was collected in a one-year follow-up survey. The bedtime and sleep quality was evaluated using Pittsburgh sleep quality index. Indexes including body mass index, waist circumference and blood pressure were measured to evaluate metabolic syndrome risk factors. RESULTS: Compared with the students with bedtime before 12 pm, students with bedtime after 12 pm in baseline survey had significant higher risk for any two metabolic syndrome risk factors in one-year follow-up survey( adjusted OR = 2. 08, 95% CI 1. 08-4. 02). The prevalence of any two metabolic syndrome risk factors significantly increased( Ptrend= 0. 004) across students with bedtime before 12 pm in baseline in baseline survey( 5. 8%), students with bedtime after 12 pm in baseline and bedtime before 12 pm in follow-up survey( 12. 5%), and students with bedtime after 12 pm both in baseline and follow-up survey( 15. 0%). Compared with students with bedtime before 12 pm in baseline, the risk for any two metabolic syndrome risk factors among students in other two groups increased, but did not reach statistical significant( Bedtime before 12 pm: adjusted OR = 1. 92, 95% CI 0. 94- 3. 92, P = 0. 072. Bedtime after 12 pm: adjusted OR = 2. 40, 95% CI 0. 86- 6. 73, P = 0. 096). CONCLUSION: Later bedtime is significantly associated with increased risk for metabolic syndrome risk factors in college students, and the risk could not reduced through changing the bedtime during one year.

Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers.

BACKGROUND: Little is known about the relation between vitamin D status in early life and neurodevelopment outcomes. OBJECTIVE: This study was designed to examine the association of cord blood 25-hydroxyvitamin D [25(OH)D] at birth with neurocognitive development in toddlers. METHODS: As part of the China-Anhui Birth Cohort Study, 363 mother-infant pairs with complete data were selected. Concentrations of 25(OH)D in cord blood were measured by radioimmunoassay. Mental development index (MDI) and psychomotor development index (PDI) in toddlers were assessed at age 16-18 mo by using the Bayley Scales of Infant Development. The data on maternal sociodemographic characteristics and other confounding factors were also prospectively collected. RESULTS: Toddlers in the lowest quintile of cord blood 25(OH)D exhibited a deficit of 7.60 (95% CI: -12.4, -2.82; P = 0.002) and 8.04 (95% CI: -12.9, -3.11; P = 0.001) points in the MDI and PDI scores, respectively, compared with the reference category. Unexpectedly, toddlers in the highest quintile of cord blood 25(OH)D also had a significant deficit of 12.3 (95% CI: -17.9, -6.67; P < 0.001) points in PDI scores compared with the reference category. CONCLUSIONS: This prospective study suggested that there was an inverted-U-shaped relation between neonatal vitamin D status and neurocognitive development in toddlers. Additional studies on the optimal 25(OH)D concentrations in early life are needed.

An Adaptive Low-Cost GNSS/MEMS-IMU Tightly-Coupled Integration System with Aiding Measurement in a GNSS Signal-Challenged Environment.

The main aim of this paper is to develop a low-cost GNSS/MEMS-IMU tightly-coupled integration system with aiding information that can provide reliable position solutions when the GNSS signal is challenged such that less than four satellites are visible in a harsh environment. To achieve this goal, we introduce an adaptive tightly-coupled integration system with height and heading aiding (ATCA). This approach adopts a novel redundant measurement noise estimation method for an adaptive Kalman filter application and also augments external measurements in the filter to aid the position solutions, as well as uses different filters to deal with various situations. On the one hand, the adaptive Kalman filter makes use of the redundant measurement system's difference sequence to estimate and tune noise variance instead of employing a traditional innovation sequence to avoid coupling with the state vector error. On the other hand, this method uses the external height and heading angle as auxiliary references and establishes a model for the measurement equation in the filter. In the meantime, it also changes the effective filter online based on the number of tracked satellites. These measures have increasingly enhanced the position constraints and the system observability, improved the computational efficiency and have led to a good result. Both simulated and practical experiments have been carried out, and the results demonstrate that the proposed method is effective at limiting the system errors when there are less than four visible satellites, providing a satisfactory navigation solution.

[Advances of transforming growth factor-ß inhibitors].

Transforming growth factor-ß is an important cytokine with various bioactivities, including embryonic development, wound healing, chemotaxis and cell cycle regulation. Epithelial-mesenchymal transition (EMT) is the main pathway of tumor cell to obtain the ability of invasion and metastasis. The TGF-ß is the key factor known to induce EMT in cancer cells and plays an important role in the process. In recent years, some progress has been obtained. Some TGF-ß inhibitors have approved in the market or in clinical trials. TGF-ß inhibitors can play an important role on the treatment of tumors, glaucoma, liver and kidney fibrosis disease and scar repair. Novel TGF-ß inhibitors reported in recent years were reviewed in this article.

Synthesis and anti-influenza virus activity of substituted dibenzoxepine-based baloxavir derivatives.

Seasonal influenza poses a significant threat to global public health, driving the need for effective anti-influenza agents. The PA protein, which captures the pre-mRNA cap structure, is crucial for the replication of the influenza virus and serves as an important target for developing such agents. Baloxavir, a PA inhibitor, has shown excellent activity against influenza A and B viruses. In this study, its structure was optimized using bioisosteric replacement to develop novel dibenzoxepine-based derivatives for combating influenza. As the lead compounds, ATV03 (EC50 = 0.78 ± 0.10 nM, SI > 64103) and ATV07 (EC50 = 0.78 ± 0.01 nM, SI = 31603) demonstrated excellent anti-influenza A (H3N2) activity and SI, and possessed favorable anti-influenza B activity, with 2.02 ± 0.40 nM and 2.32 ± 0.29 nM of EC50 respectively. They showed improved bioavailability and metabolic stability. Mechanism studies revealed that ATV03 and ATV07 both possessed significant activity in inhibiting PA and RdRp as well as disturbing NP. Consequently, ATV03 was selected for further investigation in the fight against seasonal and pandemic influenza due to its superior bioavailability, metabolic stability, and efficacy against multiple influenza A viruses.

The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice.

Background: Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association. Methods: Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses. Results: Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota. Conclusion: This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and nucleotide analog GS-441524 conjugates with potent in vivo efficacy against coronaviruses.

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5'-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041, exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta-genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies.

Using Wool Keratin as a Structural Biomaterial and Natural Mediator to Fabricate Biocompatible and Robust Bioelectronic Platforms.

The design and fabrication of biopolymer-incorporated flexible electronics have attracted immense interest in healthcare systems, degradable implants, and electronic skin. However, the application of these soft bioelectronic devices is often hampered by their intrinsic drawbacks, such as poor stability, inferior scalability, and unsatisfactory durability. Herein, for the first time, using wool keratin (WK) as a structural biomaterial and natural mediator to fabricate soft bioelectronics is presented. Both theoretical and experimental studies reveal that the unique features of WK can endow carbon nanotubes (CNTs) with excellent water dispersibility, stability, and biocompatibility. Therefore, well-dispersed and electroconductive bio-inks can be prepared via a straightforward mixing process of WK and CNTs. The as-obtained WK/CNTs inks can be directly exploited to design versatile and high-performance bioelectronics, such as flexible circuits and electrocardiogram electrodes. More impressively, WK can also be a natural mediator to connect CNTs and polyacrylamide chains to fabricate a strain sensor with enhanced mechanical and electrical properties. With conformable and soft architectures, these WK-derived sensing units can be further assembled into an integrated glove for real-time gesture recognition and dexterous robot manipulations, suggesting the great potential of the WK/CNT composites for wearable artificial intelligence.

The relationship between triglyceride, cholesterol and lipoprotein levels, and immune responses to hepatitis B vaccine.

Cholesterol homeostasis disorder and hypertriglyceridemia, as common metabolic conditions, have rarely been reported to affect the immune responses to the hepatitis B vaccine. Our study found that higher high-density lipoprotein (HDL) level showed a significant relationship with positive anti-HBs results (cOR = 1.479, 95% CI: 1.150, 1.901, p = 0.002; aOR = 1.304, 95% CI: 1.006, 1.691, p = 0.045), especially in individuals aged 18- to 40-year-old, female, smoking more than 100 cigarettes in life, and drinking more than 12 times every year. Lower low-density lipoprotein (LDL) level was associated with a negative anti-HBs result among participants aged 18- to 40-year-old, and participants who were obese. Higher level of HDL and lower level of LDL may be protective factors of better immune effect of hepatitis B vaccine. More research should be conducted to investigate the influence of the cholesterol level on the immune responses to the hepatitis B vaccine, and more in-depth research should be performed to uncover the mechanism.

Predictive value of frailty assessment tools in patients undergoing surgery for gastrointestinal cancer: An observational cohort study.

BACKGROUND: Few studies have simultaneously compared the predictive value of various frailty assessment tools for outcome measures in patients undergoing gastrointestinal cancer surgery. Therefore, it is difficult to determine which assessment tool is most relevant to the prognosis of this population. AIM: To investigate the predictive value of three frailty assessment tools for patient prognosis in patients undergoing gastrointestinal cancer surgery. METHODS: This single-centre, observational, prospective cohort study was conducted at the Affiliated Lianyungang Hospital of Xuzhou Medical University from August 2021 to July 2022. A total of 229 patients aged ≥ 18 years who underwent surgery for gastrointestinal cancer were included in this study. We collected baseline data on the participants and administered three scales to assess frailty: The comprehensive geriatric assessment (CGA), Fried phenotype and FRAIL scale. The outcome measures were the postoperative severe complications and increased hospital costs. RESULTS: The prevalence of frailty when assessed with the CGA was 65.9%, 47.6% when assessed with the Fried phenotype, and 34.9% when assessed with the FRAIL scale. Using the CGA as a reference, kappa coefficients were 0.398 for the Fried phenotype and 0.291 for the FRAIL scale (both P < 0.001). Postoperative severe complications and increased hospital costs were observed in 29 (12.7%) and 57 (24.9%) patients, respectively. Multivariate logistic analysis confirmed that the CGA was independently associated with increased hospital costs (odds ratio = 2.298, 95% confidence interval: 1.044-5.057; P = 0.039). None of the frailty assessment tools were associated with postoperative severe complications. CONCLUSION: The CGA was an independent predictor of increased hospital costs in patients undergoing surgery for gastrointestinal cancer.

Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS-CoV-2.

S-217622 (Ensitrelvir) is a reversible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro) inhibitor which obtained emergency regulatory approval in Japan for the treatment of SARS-CoV-2 infection on Nov 22, 2022. Herein, analogs of S-271622 with deuterium-for-hydrogen replacement were synthesized for comparison of the antiviral activities and pharmacokinetic (PK) profiles. Compared to the parent compound, C11-d2-S-217622 compound YY-278 retained in vitro activity against 3CLpro and SARS-CoV-2. X-ray crystal structural studies showed similar interactions of SARS-CoV-2 3CLpro with YY-278 and S-271622. The PK profiling revealed the relatively favorable bioavailability and plasma exposure of YY-278. In addition, YY-278, as well as S-217622, displayed broadly anti-coronaviral activities against 6 other coronaviruses that infect humans and animals. These results laid the foundation for further research on the therapeutic potential of YY-278 against COVID-19 and other coronaviral diseases.

Comparison of the prevalence and associated factors of cognitive frailty between elderly and middle-young patients receiving maintenance hemodialysis.

PURPOSE: This study aimed at comparing the prevalence of cognitive frailty and explore the differences in the influencing factors between elderly and middle-young patients receiving maintenance hemodialysis (MHD). METHODS: In this cross-sectional study, the frailty phenotype, mini-mental state examination, and clinical dementia rating were used to assess the current status of cognitive frailty in 852 patients receiving MHD from four hospitals in Lianyungang City and Xuzhou City, Jiangsu Province, China; the influencing factors were then analyzed for statistical significance. RESULTS: Of the total 852 patients receiving MHD, 340 were classified into an elderly group (≥ 60 years) and 512 into a middle-young group (< 60 years). The prevalence of cognitive frailty was 35.9% and 8.8%, respectively. The results of multivariate logistic regression analysis showed that the independent factors of cognitive frailty were age (P < 0.001), education level (P = 0.010), nutritional status (P = 0.001), serum albumin level (P = 0.010), calf circumference (P = 0.024), and social support level (P < 0.001) in the elderly group and comorbidity status (P = 0.037), education level (P < 0.001), nutritional status (P = 0.008), serum creatinine level (P = 0.001), waist circumference (P < 0.001), and depression (P = 0.006) in the middle-young group. CONCLUSION: The prevalence of cognitive frailty was significantly higher in the elderly group than in the middle-young group, and the influencing factors differed between the two populations.

Characterization of the gut microbiota in hemodialysis patients with sarcopenia.

PURPOSE: Maintenance hemodialysis (MHD) patients are at high risk of sarcopenia. Gut microbiota affects host metabolic and may act in the occurrence of sarcopenia importantly. This study aimed to study the characterization of the gut microbiota in MHD patients with sarcopenia, and to further reveal the complex pathophysiology of sarcopenia in MHD patients. METHODS: Fecal samples and clinical data were collected from 30 MHD patients with sarcopenia, and 30 age-and-sex-matched MHD patients without sarcopenia in 1 general hospital of Jiangsu Province from December 2020 to March 2021. 16S rRNA sequencing technology was used to analyze the genetic sequence of the gut microbiota for evaluation of the diversity, species composition, and differential microbiota of the two groups. RESULTS: Compared to MHD patients without sarcopenia, the ACE index of patients with sarcopenia was lower (P = 0.014), and there was a structural difference in the ß-diversity between the two groups (P = 0.001). At the genus level, the relative abundance of Tyzzerella_4 in the sarcopenia group was significantly higher than in the non-sarcopenia group (P = 0.039), and the relative abundance of Megamonas (P = 0.004), Coprococcus_2 (P = 0.038), and uncultured_bacterium_f_Muribaculaceae (P = 0.040) decreased significantly. CONCLUSION: The diversity and structure of the gut microbiota of MHD patients with sarcopenia were altered. The occurrence of sarcopenia in MHD patients may be influenced by gut microbiota.

The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus driving the ongoing coronavirus disease 2019 (COVID-19) pandemic, continues to rapidly evolve. Because of the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOCs), orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously, we showed that the parent nucleoside of remdesivir, GS-441524, has potent anti-SARS-CoV-2 activity. Here, we report that esterification of the 5'-hydroxyl moieties of GS-441524 markedly improved antiviral potency. This 5'-hydroxyl-isobutyryl prodrug, ATV006, demonstrated excellent oral bioavailability in rats and cynomolgus monkeys and exhibited potent antiviral efficacy against different SARS-CoV-2 VOCs in vitro and in three mouse models. Oral administration of ATV006 reduced viral loads and alleviated lung damage when administered prophylactically and therapeutically to K18-hACE2 mice challenged with the Delta variant of SARS-CoV-2. These data indicate that ATV006 represents a promising oral antiviral drug candidate for SARS-CoV-2.