Magterpenes A-C: Three Meroterpenoids with an Unprecedented 6/6/6/6/6 Polycyclic Skeleton Extracted from Magnolia officinalis Rehd. et Wils.

Magterpenes A-C (1-3), three unprecedented meroterpenoids featuring a unique 6/6/6/6/6 polycyclic skeleton, were isolated from the ethanol extract of Magnolia officinalis Rehd. et Wils. The compounds were obtained as racemic mixtures that were completely resolved through chiral columns. Their structures were elucidated by extensive analyses of one-dimensional (1D) and 2D nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, chemical calculations of 1H/13C NMR, and electronic circular dichroism calculations. The compounds were constructed via two Diels-Alder reactions in the proposed biosynthetic pathway. All isolates were evaluated for their nephroprotective and hepatoprotective activities. The results demonstrated that (+)-1 and (-)-1 possessed promising nephroprotective activities in a dose-dependent manner, while (-)-2 and (+)-3 exhibited moderate hepatoprotective activities.

Development and validation of a novel sleep health score in the sleep heart health study.

BACKGROUND: There is a lack of consensus in evaluating multidimensional sleep health, especially concerning its implication for mortality. A validated multidimensional sleep health score is the foundation of effective interventions. METHODS: We obtained data from 5706 participants in the Sleep Heart Health Study. First, random forest-recursive feature elimination algorithm was used to select potential predictive variables. Second, a sleep composite score was developed based on the regression coefficients from a Cox proportional hazards model evaluating the associations between selected sleep-related variables and mortality. Last, we validated the score by constructing Cox proportional hazards models to assess its association with mortality. RESULTS: The mean age of participants was 63.2 years old, and 47.6% (2715/5706) were male. Six sleep variables, including average oxygen saturation (%), spindle density (C3), sleep efficiency (%), spindle density (C4), percentage of fast spindles (%) and percentage of rapid eye movement (%) were selected to construct this multidimensional sleep health score. The average sleep composite score in participants was 6.8 of 22 (lower is better). Participants with a one-point increase in sleep composite score had an 10% higher risk of death (hazard ratio = 1.10, 95% confidence interval: 1.08-1.12). CONCLUSIONS: This study constructed and validated a novel multidimensional sleep health score to better predict death based on sleep, with significant associations between sleep composite score and all-cause mortality. Integrating questionnaire information and sleep microstructures, our sleep composite score is more appropriately applied for mortality risk stratification.

Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation.

Viral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of spike protein in the endoplasmic reticulum likely due to decreased N-glycan transfer, and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy.

Investigation of the feasibility of NRAV as a biomarker for hepatocellular carcinoma.

The long non-coding RNA, Negative Regulator of Antiviral Response (NRAV) has been identified as a participant in both respiratory virus replication and immune checkpoints, however, its involvement in pan-cancer immune regulation and prognosis, particularly those of hepatocellular carcinoma (HCC), remains unclear. To address this knowledge gap, we analyzed expression profiles obtained from The Cancer Genome Atlas (TCGA) database, comparing normal and malignant tumor tissues. We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues. Kaplan-Meier (K-M) analysis revealed the prognostic power of NRAV, wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients. Furthermore, noteworthy associations were observed between NRAV, immune checkpoints, immune cell infiltration, genes related to autophagy, epithelial-mesenchymal transition (EMT), pyroptosis, tumor mutational burden (TMB), and microsatellite instability (MSI) across different cancer types, including HCC. Moreover, NRAV upregulation expression was associated with multiple pathological stages by clinical observations. Furthermore, our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells. The inhibition of NRAV resulted in the inhibition of cell proliferation, migration, and invasion in HCC cells, while also influencing the expression of CD274 (PD-L1) and CD44, along with various biomarkers associated with EMT, autophagy, and pyroptosis. The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

Cryoprotective effects and mechanisms of soybean oligosaccharides on the grass carp (Ctenopharyngodon idellus) surimi during frozen storage.

BACKGROUND: Conventional cryoprotectant mixtures (sucrose and sorbitol) impart excessive sweetness and calories to surimi. Therefore, there is a need to explore alternative cryoprotectants with low sweetness and low-calorie content. The cryoprotective effects and possible mechanisms of soybean oligosaccharides (SBOS) on the frozen stability of grass carp (Ctenopharyngodon idellus) surimi were investigated during 120 days of frozen storage in a comparison with commercial cryoprotectants (4% sucrose and 4% sorbitol, w/w). RESULTS: SBOS at 6-8% (w/w) and commercial cryoprotectants could restrain water mobility and reduce thawing loss of frozen surimi by increasing non-freezable water content. SBOS could maintain the structural stability of proteins by preventing sulfhydryl groups from being rapidly oxidized to disulfide bonds, retarding the reduction of the solubility, Ca2+-ATPase activity and α-helix content of myofibrillar proteins (MP), as well as hindering the increasing surface hydrophobicity of MP of surimi during 120 days of frozen storage. The introduction of SBOS increased the gel strength and water-holding capacity of frozen-stored surimi. Compared with commercial cryoprotectants, 8% SBOS was more effective in stabilizing protein structure, whereas it was slightly less effective with respect to ice-forming inhibition. CONCLUSION: The results obtained in the present study suggest that 8% SBOS could be potentially developed as a new cryoprotectant for surimi as a result of its ice-forming inhibition abilities and protein structure stability. © 2024 Society of Chemical Industry.

Blood urea nitrogen to serum albumin ratio: a novel mortality indicator in intensive care unit patients with coronary heart disease.

The blood urea nitrogen to albumin ratio (BAR) has been demonstrated as a prognostic factor in sepsis and respiratory diseases, yet its role in severe coronary heart disease (CHD) remains unexplored. This retrospective study, utilizing data from the Medical Information Mart for Intensive Care-IV database, included 4254 CHD patients, predominantly male (63.54%), with a median age of 74 years (IQR 64-83). Primary outcomes included in-hospital, 28-day and 1-year all-cause mortality after ICU admission. The Kaplan-Meier curves, Cox regression analysis, multivariable restricted cubic spline regression were employed to assess association between BAR index and mortality. In-hospital, within 28-day and 1-year mortality rates were 16.93%, 20.76% and 38.11%, respectively. Multivariable Cox proportional hazards analysis revealed associations between the increased BAR index and higher in-hospital mortality (HR 1.11, 95% CI 1.02-1.21), 28-day mortality (HR 1.17, 95% CI 1.08-1.27) and 1-year mortality (HR 1.23, 95% CI 1.16-1.31). Non-linear relationships were observed for 28-day and 1-year mortality with increasing BAR index (both P for non-linearity < 0.05). Elevated BAR index was a predictor for mortality in ICU patients with CHD, offering potential value for early high-risk patient identification and proactive management by clinicians.

Multi-strategy orthogonal enhancement and analysis of aldo-keto reductase thermal stability.

Given their outstanding efficiency and selectivity, enzymes are integral in various domains such as drug synthesis, the food industry, and environmental management. However, the inherent instability of natural enzymes limits their widespread industrial application. In this study, we underscore the efficacy of enhancing protein thermal stability through comprehensive protein design strategies, encompassing elements such as the free energy of protein folding, internal forces within proteins, and the overall structural design. We also demonstrate the efficiency and precision of combinatorial screening in the thermal stability design of aldo-keto reductase (AKR7-2-1). In our research, three single-point mutations and five combinatorial mutations were strategically introduced into AKR7-2-1, using multiple computational techniques. Notably, the E12I/S235I mutant showed a significant increase of 25.4 °C in its melting temperature (Tm). Furthermore, the optimal mutant, E12V/S235I, maintained 80 % of its activity while realizing a 16.8 °C elevation in Tm. Remarkably, its half-life at 50 °C was increased to twenty times that of the wild type. Structural analysis indicates that this enhanced thermal stability primarily arises from reduced oscillation in the loop region and increased internal hydrogen bonding. The promising results achieved with AKR7-2-1 demonstrate that our strategy could serve as a valuable reference for enhancing the thermal stability of other industrial enzymes.

Borate-Functionalized Disiloxane as Effective Electrolyte Additive for 4.5 V LiNi0.8Co0.1Mn0.1O2/Graphite Batteries.

Ni-rich LiNi0.8Co0.1Mn0.1O2 (NCM811) is considered the most prominent cathode material to establish a practical high energy density of lithium-ion batteries (LIBs) for future electric vehicles. The energy density of LIBs is greatly determined by the capacity of electrode materials and the operating voltage of the cells. To further improve the cycle lifespan of NCM811 batteries to meet the requirement of driving range for the electric vehicle market, it is vital to design a novel electrolyte additive that can enhance the stability of the cathode/electrolyte interface at a wide range of voltage. Herein, a novel borate functionalized disiloxane compound, 1,1,1,3,3-pentamethyl-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl) disiloxane (PMBPDS), is synthesized as cathode electrolyte interphase (CEI) film-forming additive to improve the cycling performance of NCM811 batteries. Systematic studies reveal that PMBPDS can construct a stable CEI film on the NCM811 surface and efficiently scavenge hydrofluoric acid (HF). The PMBPDS-derived CEI prevents the dissolution of transmission metals in the NCM811 cathode and enhances the capacity retention of NCM811/graphite cells from 68.3 to 70.6% after 200 cycles at 1 C in the voltage window of 3-4.5 V. This work provides more understanding on designing the molecular structure of additive compounds for improving the electrochemical performance of LIBs.

Metformin adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2004 to 2022.

BACKGROUND: Metformin has the potential for treating numerous diseases, but there are still many unrecognized and unreported adverse events (AEs). METHODS: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2022 for disproportionality analysis to assess the association between metformin and related adverse events. RESULTS: In this study 10,500,295 case reports were collected from the FAERS database, of which 56,674 adverse events related to metformin were reported. A total of 643 preferred terms (PTs) and 27 system organ classes (SOCs) that were significant disproportionality conforming to the four algorithms simultaneously were included. The SOCs included metabolic and nutritional disorders (p = 0.00E + 00), gastrointestinal disorders (p = 0.00E + 00) and others. PT levels were screened for adverse drug reaction (ADR) signals such as acute pancreatitis (p = 0.00E + 00), melas syndrome, pemphigoid (p = 0.00E + 00), skin eruption (p = 0.00E + 00) and drug exposure during pregnancy (p = 0.00E + 00). CONCLUSION: Most of our results were consistent with the specification, but some new signals of adverse reactions such as acute pancreatitis were not included. Therefore, further studies are needed to validate unlabeled adverse reactions and provide important support for clinical monitoring and risk identification of metformin.

Development and validation of a stacking ensemble model for death prediction in the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

OBJECTIVE: This study aimed to develop and validate a mortality risk prediction model for older people based on the Chinese Longitudinal Healthy Longevity Survey using the stacking ensemble strategy. MATERIAL AND METHODS: A total of 12,769 participants aged 65 or more at baseline were included. Ensemble machine learning models were applied to develop a mortality prediction model. We selected three base learners, including logistic regression, eXtreme Gradient Boosting, and Categorical + Boosting, and used logistic regression as the meta-learner. The primary outcome was five-year survival. Variable importance was evaluated by the SHapley Additive exPlanations method. RESULTS: The mean age at baseline was 88, and 57.8 % of participants were women. The CatBoost model performed the best among the three base learners, the area under the receiver operating characteristics curve (AUC) reached 0.8469 (95%CI: 0.8345-0.8593), and the stacking ensemble model further improved the discrimination ability (AUC = 0.8486, 95%CI: 0.8367-0.8612, P = 0.046). Conventional logistic regression had comparable performance (AUC = 0.8470, 95 % CI: 0.8346-0.8595). Older age, higher scores for self-care activities of daily living, being male, higher objective physical performance capacity scores, not undertaking housework, and lower scores on the Mini-Mental State Examination contributed to higher risk. CONCLUSIONS: We successfully constructed and validated a few death risk prediction models for a Chinese population of older adults. While the stacking ensemble approach had the best prediction performance, the improvement over conventional logistic regression was insubstantial.

Metabolic coupling of arsenic, carbon, nitrogen, and sulfur in high arsenic geothermal groundwater: Evidence from molecular mechanisms to community ecology.

Groundwater arsenic (As) poses a global environmental problem and is regulated by complex biogeochemical processes. However, the As biogeochemistry and its metabolic coupling with carbon (C), nitrogen (N), and sulfur (S) in high As geothermal groundwater remain unclear. Here, we reported significant shifts in the geothermal groundwater microbiome and its functional ecological clusters along the flow path with increased As levels and dynamic As-C-N-S biogeochemical cycle from the Guide Basin, China. Strong associations among As(III), NH4+, HCO3-, and corresponding functional microbial taxa suggest that microbe-mediated As transformation, ammonification, and organic carbon biodegradation potentially contributed to the As mobilization in the discharge area. And As oxidizers (coupling with denitrification or carbon fixation) and S oxidizers were closely linked to the transformation of As(III) to immobile As(V) in the recharge area. Our study provides a comprehensive insight into the complex microbial As-C-N-S coupling network and its potential role in groundwater As mobilization under hydrological disturbances.

Altered fatty acid composition confers improved drought acclimation in maize.

Drought induces alteration in membrane lipid composition in plants; however, still little is known about whether membrane lipid remodeling plays a role in plant drought acclimation, including both drought tolerance and recovery, especially in crops. Here, we imposed natural progressive drought and re-watering in 18 maize genotypes at the seedling stage, and analyzed the physiological responses, drought tolerance and drought acclimation capabilities, contents of lipids, and fatty acid compositions. The results showed that drought caused significant reductions in shoot dry weight, relative water content, Fv/Fm, total lipid content, and double bond index (DBI) in most genotypes, while re-watering partially recovered these reductions. Meanwhile, the total lipid content, fatty acid composition, and DBI were also changed obviously in response to drought and re-watering. In order to explore the relationship between membrane lipid change and plant drought response, we did a principal component analysis. The results showed that C18:3 fatty acid contributed greatly to drought tolerance, and C16:2 and C16:3 fatty acids were more responsible for drought recovery. Meanwhile, DBI showed significant positive correlations with shoot dry weight and relative water content, but a negative association with lipid peroxidation, and more importantly, DBI was important for both drought tolerance and recovery. These alterations in membrane lipid composition may facilitate increasing membrane fluidity and decreasing membrane damage, thus maintaining the high photosynthetic capability under drought. Our results suggest that lipid remodeling is important for drought tolerance and recovery in crops, and different fatty acid species have different roles in crop drought acclimation.

Conditional Knockout of IL-1R1 in Endothelial Cells Attenuates Seizures and Neurodegeneration via Inhibiting Neuroinflammation Mediated by Nrf2/HO-1/NLRP3 Signaling in Status Epilepticus Model.

Studies on the bench and at bedside have demonstrated that the process of epileptogenesis is involved in neuroinflammatory responses. As the receptor of proinflammatory cytokine IL-1ß, IL-1ß type 1 receptor (IL-1R1) is reported to express abundantly in the endothelial cells in epileptic brains, which is deemed to be implicated in the epileptogenic process. However, whether and how endothelial IL-1R1 modulates neuroinflammatory responses in the pathological process of epileptic seizures and/or status epilepticus (SE) remains obscure. Here, we indicated endothelial IL-1R1 is involved in neuroinflammation, facilitating epilepsy progress via Nrf2/HO-1/NLRP3. In vitro, we observed upregulation of inflammatory cytokines in co-culture model under IL-1ß challenge, as well as in BV2 cells after stimulation with conditional medium (CM) from IL-1ß-stimulated bEnd.3 cells. In vivo, mice with conditional knockout of endothelial IL-1R1 (IL-1R1-CKO) were generated by hybrid IL-1R1flox/flox mice with Tek-Cre mice. IL-1R1-CKO reduced seizure susceptibility in kainic acid (KA)-induced SE model. In addition, IL-1R1-CKO KA mice exhibited lessened hippocampal neuroinflammation, mitigated neuronal damage, and decreased abnormal neurogenesis. In cognitive behavioral tests, IL-1R1-CKO KA mice presented improvement in learning and memory. Furthermore, we also indicated blockage of endothelial IL-1R1 downregulated the expressions of Nrf2/HO-1/NLRP3 pathway-related proteins. Nrf2-siRNA reversed the downregulation of HO-1, NLRP3, caspase-1, and IL-1ß. These results demonstrated CKO of endothelial IL-1R1 reduces seizure susceptibility and attenuates SE-related neurobehavioral damage by suppressing hippocampal neuroinflammation via Nrf2/HO-1/NLRP3.

Effect of melting combined with ice recrystallization on porous starch preparation: Pore-forming properties, granular morphology, functionality, and multi-scale structures.

In this work, critical melting (CM) combined with freeze-thawing treatment (FT, freezing at -20 â„ƒ and -80 â„ƒ, respectively) was used to prepare porous starch. The results showed that CM combined with the slow freezing rate (-20 â„ƒ) can prepare porous starch with characteristics of grooves and cavities, while combined with the rapid freezing rate (-80 â„ƒ) can prepare with holes and channels, especially after repeating FT cycles. Compared with the native counterpart, the specific surface area, pore volume, and average diameter of CMFT-prepared porous starch were significantly increased to 4.07 m2/g, 7.29 cm3/g × 10-3, and 3.57 nm, respectively. CMFT significantly increased the thermal stability of starch, in which the To, Tp, and Tc significantly increased from 63.32, 69.62, and 72.90 (native) to ∼69, 72, and 76 °C, respectively. CMFT significantly increased water and oil absorption of porous starch from 91.20 % and 72.00 % (native) up to ∼163 % and 94 %, respectively. Moreover, CMFT-prepared porous starch had a more ordered double-helical structure, which showed in the significantly increased relative crystallinity, semi-crystalline lamellae structure, and the proportion of the double helix structure of starch. The synergistic effect of melting combined with ice recrystallization can be used as an effective way to prepare structure-stabilized porous starch.

Optimal Control for Constrained Discrete-Time Nonlinear Systems Based on Safe Reinforcement Learning.

The state and input constraints of nonlinear systems could greatly impede the realization of their optimal control when using reinforcement learning (RL)-based approaches since the commonly used quadratic utility functions cannot meet the requirements of solving constrained optimization problems. This article develops a novel optimal control approach for constrained discrete-time (DT) nonlinear systems based on safe RL. Specifically, a barrier function (BF) is introduced and incorporated with the value function to help transform a constrained optimization problem into an unconstrained one. Meanwhile, the minimum of such an optimization problem can be guaranteed to occur at the origin. Then a constrained policy iteration (PI) algorithm is developed to realize the optimal control of the nonlinear system and to enable the state and input constraints to be satisfied. The constrained optimal control policy and its corresponding value function are derived through the implementation of two neural networks (NNs). Performance analysis shows that the proposed control approach still retains the convergence and optimality properties of the traditional PI algorithm. Simulation results of three examples reveal its effectiveness.

[A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes].

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Specific coenzyme preference switching for an aldo-keto reductase that synthesizes the chiral intermediate of duloxetine.

The synthesis of chiral intermediates for the traditional antidepressant duloxetine has gained significant attention as the number of depressed patients continues to grow. S-N, N-Dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamide (S-DHTP) is a critical intermediate in the synthesis of duloxetine, and the chemical synthesis process is complex and environmentally unfriendly. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a major cost driver in the biocatalytic production of S-DHTP from N, N-Dimethyl-3-keto-3-(2-thienyl)-1-propanamide (DKTP). Here, we successfully modified the coenzyme preference of an aldo-keto reductase (AKR7-2-1) to use the cheaper reduced nicotinamide adenine dinucleotide (NADH) through a coenzyme preference modification approach. We utilized protein engineering to create a superior mutant, Y53F, which increased the coenzyme specificity of AKR7-2-1 by 875-fold and improved its thermal stability, enhancing its potential for industrial applications. Molecular dynamics simulations were performed to demonstrate the effect of mutations at key sites on the protein, revealing the altered coenzyme preference and increased thermal stability from structural and energetic changes. This study validates the viability of the coenzyme preference modification strategy for aldo-keto reductase, offering valuable insights for fellow researchers and guiding future investigations.

Performance Evaluation of CentiSpace Navigation Augmentation Experiment Satellites.

This paper presents the performance analysis of CentiSpace low earth orbit (LEO) experiment satellites. Distinguishing them from other LEO navigation augmentation systems, the co-time and co-frequency (CCST) self-interference suppression technique is employed in CentiSpace to mitigate significant self-interference caused by augmentation signals. Consequently, CentiSpace exhibits the capability of receiving navigation signals from the Global Navigation Satellite System (GNSS) while simultaneously broadcasting augmentation signals within the same frequency bands, thus ensuring excellent compatibility for GNSS receivers. CentiSpace is a pioneering LEO navigation system to successfully complete in-orbit verification of this technique. Leveraging the on-board experiment data, this study analyzes the performance of space-borne GNSS receivers equipped with self-interference suppression and evaluates the quality of navigation augmentation signals. The results show that CentiSpace space-borne GNSS receivers are capable of covering more than 90% visible GNSS satellites and the precision of self-orbit determination is at the centimeter level. Furthermore, the quality of augmentation signals meets the requirements outlined in the BDS interface control documents. These findings underscore the potential of the CentiSpace LEO augmentation system for the establishment of global integrity monitoring and GNSS signal augmentation. Moreover, these results contribute to subsequent research on LEO augmentation techniques.

Predicting functional dependency using machine learning among a middle-aged and older Chinese population.

OBJECTIVE: To develop prediction models for assessing functional dependency in a middle-aged and older Chinese population. METHOD: Adults ≥45 years old from the China Health and Retirement Longitudinal Study (CHARLS) and without functional dependency at baseline were included. Functional dependency was defined as needing any help in any basic activities of daily living (ADL) or instrumental activities of daily living (IADL). The outcomes were overall functional dependency, ADL and IADL dependency. Stacked ensemble models were constructed based on five selected machine learning models. Models were trained and tested in the 2011-2015 cohort, and were externally validated in the 2015-2018 cohort. SHapley Additive exPlanations (SHAP) was utilized to quantify the significance of predictors. RESULT: In the training cohort, a total of 6,297 participants were included at baseline, 1,893 developed functional dependency during the follow-up period. The stacked ensemble model achieved the best performance in terms of discrimination ability for predicting overall functional dependency, ADL and IADL dependency, with AUCs of 0.750, 0.690 and 0.748, respectively; in external validation cohort, the corresponding AUCs were 0.725, 0.719 and 0.727, respectively. A compact model was further developed and maintained similar predictive performance. CONCLUSION: The stacked ensemble approach can serve as a useful tool for identifying the risk of functional dependency in a large Chinese population. For ADL dependency, arthritis, age, self-report health, and waist circumference were identified as highly significant predictors. Conversely, cognitive function, age, living in rural areas, and performance in chair stand test emerged as highly ranked predictors for IADL dependency.