Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study.

BACKGROUND: China has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China. METHODS: This prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305. FINDINGS: Of the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251-883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3-2·5), at 1 year was 13·7% (13·5-13·9), and at 3 years was 28·2% (27·7-28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality. INTERPRETATION: In China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved. FUNDING: National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Replacing Spartina alterniflora with northward-afforested mangroves has the potential to acquire extra blue carbon.

Climate change provides an opportunity for the northward expansion of mangroves, and thus, the afforestation of mangroves at higher latitude areas presents an achievable way for coastal restoration, especially where invasive species S. alterniflora needs to be clipped. However, it is unclear whether replacing S. alterniflora with northward-afforested mangroves would benefit carbon sequestration. In the study, we examined the key CO2 and CH4 exchange processes in a young (3 yr) northward-afforested wetland dominated by K. obovata. We also collected soil cores from various ages (3, 15, 30, and 60 years) to analyze the carbon storage characteristics of mangrove stands using a space-for-time substitution approach. Our findings revealed that the young northward mangroves exhibited obvious seasonal variations in net ecosystem CO2 exchange (NEE) and functioned as a moderate carbon sink, with an average annual NEE of -107.9 g C m-2 yr-1. Additionally, the CH4 emissions from the northward mangroves were lower in comparison to natural mangroves, with the primary source being the soil. Furthermore, when comparing the vertical distribution of soil carbon, it became evident that both S. alterniflora and mangroves contributed to organic carbon accumulation in the upper soil layers. Our study also identified a clear correlation that the biomass and carbon stocks of mangroves increased logarithmically with age (R2 = 0.69, p < 0.001). Notably, both vegetation and soil carbon stocks (especially in the deeper layers) of the 15 yr northward mangroves, were markedly higher than those of S. alterniflora. This suggests that replacing S. alterniflora with northward-afforested mangroves is an effective long-term strategy for future coasts to enhance blue carbon sequestration.

In situ surface turbidity sensor based on localized light scattering from tilted fiber Bragg gratings.

We propose a compact fiber-optic sensor for in situ and continuous turbidity monitoring, based on surface optical scattering of polarized evanescent waves from targeted particles. The sensor is composed of a tilted fiber Bragg grating (TFBG) packaged inside a microfluidic capillary. The transmission spectrum of the TFBG provides a fine comb of narrow cladding resonances that are highly sensitive to the turbidity due to the localized light scattering of polarized evanescent waves from the microparticles near the fiber surface (as opposed to traditional bulk/volumetric turbidity measurement). We also propose a transmission spectral area interrogation method and quantify the repeatable correlation between the surface turbidity and the optical spectral area response. We show that the maximum sensitive turbidity response is achieved when the wavelength of the sensing cladding resonance matches the size of surrounding solid particles.

Functioning and mechanisms of PTMs in renal diseases.

Post-translational modifications (PTMs) are crucial epigenetic mechanisms that regulate various cellular biological processes. The use of mass spectrometry (MS)-proteomics has led to the discovery of numerous novel types of protein PTMs, such as acetylation, crotonylation, 2-hydroxyisobutyrylation, ß-hydroxybutyrylation, protein propionylation and butyrylation, succinylation, malonylation, lactylation, and histone methylation. In this review, we specifically highlight the molecular mechanisms and roles of various histone and some non-histone PTMs in renal diseases, including diabetic kidney disease. PTMs exhibit diverse effects on renal diseases, which can be either protective or detrimental, depending on the specific type of protein PTMs and their respective targets. Different PTMs activate various signaling pathways in diverse renal pathological conditions, which could provide novel insights for studying epigenetic mechanisms and developing potential therapeutic strategies for renal diseases.

Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis.

Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.Communicated by Ramaswamy H. Sarma.

Implication of different frailty criteria in older people with atrial fibrillation: a prospective cohort study.

BACKGROUND: the prevalence of physical and multidimensional frailty and their prognostic impact on clinical outcomes in patients with atrial fibrillation (AF) is unclear. OBJECTIVE: to evaluated frailty in a cohort of patients with AF according to different criteria, and studied the prevalence and its prognostic impact on clinical outcomes. METHODS: in this multicenter prospective cohort, 197 inpatients ≥ 65 years old with AF were recruited from September 2018 to April 2019.We used Fried Frailty phenotype (Fried) to assess physical frailty, and comprehensive geriatric assessment-frailty index (CGA-FI) to assess multidimensional frailty. The primary outcome was a composite of all-cause mortality or rehospitalization. RESULTS: the prevalence of frailty was determined as 34.5% by Fried, 42.6% by CGA-FI. Malnutrition and ≥ 7 medications were independently associated with frailty. Kaplan-Meier survival curve showed that the presence of frailty by CGA-FI had significantly lower all-cause mortality or rehospitalization survival rate (log-rank P = 0.04) within 1 year. Multivariate Cox regression adjusted for age and sex showed that the frailty by CGA-FI was significantly associated with the risk of all-cause mortality or rehospitalization within 1 year (HR 1.79, 95% CI 1.10-2.90). However, those associations were absent with the physical frailty. After broader multivariate adjustment, those associations were no longer statistically significant for both types of frailty. CONCLUSIONS: in older people with AF, Multidimensional frailty is more significantly associated with a composite of all-cause mortality or rehospitalization within 1 year than physical frailty, but these association are attenuated after multivariate adjustment. CLINICAL TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.

Identification and Validation of a Novel Glycolysis-Related Gene Signature for Predicting the Prognosis and Therapeutic Response in Triple-Negative Breast Cancer.

INTRODUCTION: A high malignancy rate and poor prognosis are common problems with triple-negative breast cancer (TNBC). There is increasing evidence that glycolysis plays vital roles in tumorigenesis, tumor invasion, immune evasion, chemoresistance, and metastasis. However, a comprehensive analysis of the diagnostic and prognostic significance of glycolysis in TNBC is lacking. METHODS: Transcriptomic and clinical data of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, respectively. Glycolysis-related genes (GRGs) were collected from the Molecular Signatures Database (MSigDB). Differential comparative analysis was performed to obtain the differentially expressed (DE)-GRGs associated with TNBC. Based on the DE-GRGs, a glycolysis-related risk signature was established using Least Absolute Shrinkage and Selector Operation (LASSO) and multivariable Cox regression analyses. The prognostic value, tumor microenvironment, mutation status, and chemotherapy response of different risk groups were analyzed. An independent cohort from the METABRIC database was used for external validation. Furthermore, the expression patterns of five genes derived from the prognostic model were validated by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: The glycolysis-related prognostic signature included five genes (IFNG, ACSS2, IRS2, GFUS, and GAL3ST1) and predicted the prognosis of TNBC patients independent of clinical factors (p < 0.05). Patients were divided into high- and low-risk groups based on the median risk score. Compared to low-risk TNBC patients, high-risk patients had significantly decreased overall survival (HR = 2.718, p < 0.001). Receiver operating characteristic and calibration curves demonstrated that the model had high performance in terms of predicting survival and risk stratification. The results remained consistent after external verification. Additionally, the tumor immune microenvironment significantly differed between the risk groups. Low-risk TNBC patients had a better immunotherapy response than high-risk patients. High-risk TNBC patients with a poor prognosis may benefit from targeted therapy. CONCLUSIONS: This study developed a novel glycolysis and prognosis-related (GRP) signature based on GRGs to predict the prognosis of TNBC patients, and may aid clinical decision-making for these patients.

Clinical significance of the series of CYP2C9*non3 variants, an unignorable predictor of warfarin sensitivity in Chinese population.

Backgrounds: Gene polymorphisms are critical for variations in warfarin dose. To date, more than 70 CYP2C9 alleles have been identified. This study was designed to clarify the clinical significance of CYP2C9*non-3 variants to warfarin sensitivity in Chinese Han patients. Methods: The entire CYP2C9 gene region was sequenced in 1,993 individuals, and clinical data and VKORC1 genotypes were collected from 986 patients with atrial fibrillation treated with warfarin. The SKAT-O method was used to analyze the effects of CYP2C9*non-3 variants on warfarin sensitivity. Results: A total of 20 CYP2C9 variants were identified, of which four were novel. Carriers with CYP2C9*non-3 variants may have lower warfarin dose requirements, and similar to CYP2C9*3, CYP2C9*non-3 variants are clearly relevant to warfarin-sensitive and highly sensitive responders. Conclusion: Our results showed that, besides CYP2C9*3, the series of CYP2C9*non-3 variants is an unignorable predictor for warfarin sensitivity in Chinese population. From a safety consideration, people carried such variants may need a preferred choice of NOACs when they started anticoagulation therapy.

H2 S improves salt-stress recovery via organic acid turn-over in apple seedlings.

Signalling roles of hydrogen sulphide (H2 S) in stress biology are widely reported but not sufficiently established to urge its use in agronomic practice. Our lack of quantitative understanding of the metabolic rewiring in H2 S signalling makes it difficult to elucidate its functions in stress tolerance on the biochemical level. Here, Malus hupehensis Rehd. var. pingyiensis seedlings were first treated with salt stress for 2 weeks and then treated with four different concentrations of NaHS. Through vigorous investigations, including phenotypic analysis, 13 C transient labelling and targeted metabolic and transcriptomic analysis, for the first time in the seedlings of a woody fruit crop, we found out that H2 S recycles fixed carbons through glycolysis and tricarboxylic acid cycle to inhibit the futile accumulation of carbohydrates, to maintain an efficient CO2 assimilation, to keep a balanced starch metabolism, to produce sufficient H2 O2 , to maintain malate/γ-aminobutyric acid homeostasis via an H2 O2 -induced anion channel (aluminium-activated malate transporter) and eventually to improve salt-stress recovery. Our results systematically demonstrate the vital roles of central carbon metabolism in H2 S signalling and clarify the mode of action of H2 S in apple seedlings. We conclude that H2 S signalling interacts with central carbon metabolism in a bottom-up manner to recover plant growth after salt stress.

Development and Validation of an Electronic Frailty Index Using Routine Electronic Health Records: An Observational Study From a General Hospital in China.

Background: This study aimed to develop and validate an electronic frailty index (eFI) based on routine electronic health records (EHR) for older adult inpatients and to analyze the correlations between frailty and hospitalized events and costs. Methods: We created an eFI from routine EHR and validated the effectiveness by the consistency of the comprehensive geriatric assessment-frailty index (CGA-FI) with an independent prospective cohort. Then, we analyzed the correlations between frailty and hospitalized events and costs by regressions. Results: During the study period, 49,226 inpatients were included in the analysis, 42,821 (87.0%) of which had enough data to calculate an eFI. A strong correlation between the CGA-FI and eFI was shown in the validation cohort of 685 subjects (Pearson's r = 0.716, P < 0.001). The sensitivity and specificity for an eFI≥0.15, the upper tertile, to identify frailty, defined as a CGA-FI≥0.25, were 64.8 and 88.7%, respectively. After adjusting for age, sex, and operation, an eFI≥0.15 showed an independent association with long hospital stay (odds ratio [OR] = 2.889, P < 0.001) and death in hospital (OR = 19.97, P < 0.001). Moreover, eFI values (per 0.1) were positively associated with total costs (ß = 0.453, P < 0.001), examination costs (ß = 0.269, P < 0.001), treatment costs (ß = 0.414, P < 0.001), nursing costs (ß = 0.381, P < 0.001), pharmacy costs (ß = 0.524, P < 0.001), and material costs (ß = 0.578, P < 0.001) after adjusting aforementioned factors. Conclusions: We successfully developed an effective eFI from routine EHR from a general hospital in China. Frailty is an independent risk factor for long hospital stay and death in hospital. As the degree of frailty increases, the hospitalized costs increase accordingly.

Performance of Prognostic Risk Scores in Elderly Chinese Patients with Heart Failure.

PURPOSE: Elderly heart failure (HF) patients have different clinical characteristics and poorer prognosis compared with younger patients. Prognostic risk scores for HF have not been validated well in elderly patients. We aimed to validate the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in an elderly Chinese HF cohort. PATIENTS AND METHODS: This retrospective study enrolled 675 elderly HF patients (age≥70 years) discharged from our hospital between 2012 and 2017. The performance of the two risk scores was evaluated in terms of discrimination, using receiver-operating characteristic analysis, and calibration using a calibration plot and Hosmer-Lemeshow (H-L) test. Absolute risk reclassification was used to compare the two scores. RESULTS: During the mean follow-up time of 32.6 months, 193 patients (28.6%) died, and 1-year mortality was 10.5%. The predicted median 1-year mortality was 8% for the SHFM and 18% for the MAGGIC score. A Kaplan-Meier survival curve demonstrated that event rates of all-cause mortality significantly increased with increasing SHFM and MAGGIC scores. The discriminatory capacity of the SHFM was greater than that of the MAGGIC score (c-statistics were 0.72 and 0.67, respectively; P = 0.05). The calibration plot for the SHFM was better than that for MAGGIC score for 1-year mortality (SHFM: H-L χ2 =8.2, P = 0.41; MAGGIC: H-L χ2 =18.8, P =0.02). Compared with the MAGGIC score, the net reclassification index (NRI) of the SHFM was 2.96% (Z=5.88, P< 0.0001). CONCLUSION: The SHFM performs better than MAGGIC score, having good discrimination, calibration and risk classification for the prediction of 1-year mortality in elderly Chinese HF patients.

Particulate plastics-plant interaction in soil and its implications: A review.

Particulate plastics (<5 mm), including macroplastics (1 µm to 5 mm), microplastics (100 nm to 1 µm) and nanoplastics (<100 nm), have become a global environmental problem due to their widespread occurrence, distribution and ecosystem risk. Although numerous studies on particulate plastics have been conducted in aquatic systems, investigations in the soil ecosystem are lacking. Soil is the main storage place of particulate plastics, conferring significant impacts on plant growth and development. The impact of particulate plastics on plants is directly related to the safety of agricultural products. This review comprehensively examines the pollution characteristics and exposure pathways of particulate plastics in agricultural soils, highlighting plastic uptake process, and mechanisms in plants, and effects of particulate plastics, biodegradable particulate plastics and combined pollution of plastics with other environmental pollutants on plant performances. This review identifies a number of future research prospects including the development of accurate quantitative methods for plastic analysis in soil and plant samples, understanding the environmental behaviors of conventional and biodegradable particulate plastics in the presence and absence of other environmental pollutants, unravelling the fate of particulate plastics in plants, phyto-toxicity and molecular regulatory mechanisms of particultate plastics, and developing best management practices for the production of safe agricultural products in plastic-contaminated soils.

Prevalence and Incidence of Heart Failure Among Urban Patients in China: A National Population-Based Analysis.

BACKGROUND: Large-scale and population-based studies of heart failure (HF) incidence and prevalence are scarce in China. The study sought to estimate the prevalence, incidence, and cost of HF in China. METHODS: We conducted a population-based study using records of 50.0 million individuals ≥25 years old from the national urban employee basic medical insurance from 6 provinces in China in 2017. Incident cases were individuals with a diagnosis of HF (International Classification of Diseases code, and text of diagnosis) in 2017 with a 4-year disease-free period (2013-2016). We calculated standardized rates by applying age standardization to the 2010 Chinese census population. RESULTS: The age-standardized prevalence and incidence were 1.10% (1.10% among men and women) and 275 per 100 000 person-years (287 among men and 261 among women), respectively, accounting for 12.1 million patients with HF and 3.0 million patients with incident HF ≥25 years old. Both prevalence and incidence increased with increasing age (0.57%, 3.86%, and 7.55% for prevalence and 158, 892, and 1655 per 100 000 person-years for incidence among persons who were 25-64, 65-79, and ≥80 years of age, respectively). The inpatient mean cost per-capita was $4406.8 and the proportion with ≥3 hospitalizations among those hospitalized was 40.5%. The outpatient mean cost per-capita was $892.3. CONCLUSIONS: HF has placed a considerable burden on health systems in China, and strategies aimed at the prevention and treatment of HF are needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: ChiCTR2000029094.

Application of Massive Open Online Course to Grammar Teaching for English Majors Based on Deep Learning.

The study aims to explore the roles of Massive Open Online Courses (MOOCs) based on deep learning in college students' English grammar teaching. The data are collected using a survey. After the experimental data are analyzed, it is found that students have a low sense of happiness and satisfaction and are unwilling to practice oral English and learn language points in English learning. They think that college English learning only meets the needs of CET-4 and CET-6 and does not take it as the ultimate learning goal. After the necessity and problems in English grammar teaching are discussed, the advantages of flipped classrooms of MOOCs are discussed in English grammar teaching. A teaching platform is constructed to study the foreign language teaching mode under MOOCs, and classroom teaching is combined with the advantages of MOOCs following the principle of "teaching students according to their personalities" to improve the listening, speaking, reading, writing, and translation skills of foreign language majors. The results show that high-quality online teaching resources and the deep learning-based teaching environment can provide a variety of interactive tools, by which students can communicate with their peers and teachers online. Sharing open online communication, classroom discussion, and situational simulation can enhance teachers' deep learning ability, like the ability to communication and transfer thoughts. Constructivism with interaction as the core can help students grasp new knowledge easily. Extensive communication and interaction are important ways for learning and thinking. The new model provides students with profound learning experience, expands the teaching resources of MOOCs around the world, and maximizes the interaction between online and offline teachers and students, making knowledge widely rooted in the campus and realizing the combination of online resources and campus classroom teaching. Students can learn the knowledge through autonomous learning and discussion before class, which greatly broadens the learning time and space. In the classroom and after class, the internalization and sublimation of knowledge are completed through group cooperation, inquiry learning, scenario simulation, display, and evaluation, promoting students to know about new knowledge and highlighting the dominant position of students.

Flexible Fiber Probe for Efficient Neural Stimulation and Detection.

Functional probes are a leading contender for the recognition and manipulation of nervous behavior and are characterized by substantial scientific and technological potential. Despite the recent development of functional neural probes, a flexible biocompatible probe unit that allows for long-term simultaneous stimulation and signaling is still an important task. Here, a category of flexible tiny multimaterial fiber probes (<0.3 g) is described in which the metal electrodes are regularly embedded inside a biocompatible polymer fiber with a double-clad optical waveguide by thermal drawing. Significantly, this arrangement enables great improvement in mechanical properties, achieves high optical transmission (>90%), and effectively minimizes the impedance (by up to one order of magnitude) of the probe. This ability allows to realize long-term (at least 10 weeks) simultaneous optical stimulation and neural recording at the single-cell level in behaving mice with signal-to-noise ratio (SNR = 30 dB) that is more than 6 times that of the benchmark probe such as an all-polymer fiber.

Effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats.

CONTEXT: Rivaroxaban and ticagrelor are two common drugs for the treatment of atrial fibrillation and acute coronary syndrome. However, the drug-drug interaction between them is still unknown. OBJECTIVE: To investigate the effects of ticagrelor on the pharmacokinetics of rivaroxaban in rats both in vivo and in vitro. MATERIALS AND METHODS: A sensitive and reliable UPLC-MS/MS method was developed for the determination of rivaroxaban in rat plasma. Ten Sprague-Dawley rats were randomly divided into ticagrelor pre-treated group (10 mg/kg/day for 14 days) and control group. The pharmacokinetics of orally administered rivaroxaban (10 mg/kg, single dose) with or without ticagrelor pre-treatment was investigated with developed UPLC-MS/MS method. Additionally, Sprague-Dawley rat liver microsomes were also used to investigate the drug-drug interaction between these two drugs in vitro. RESULTS: The C max (221.34 ± 53.33 vs. 691.18 ± 238.31 ng/mL) and the AUC(0-t) (1060.97 ± 291.21 vs. 3483.03 ± 753.83 µg·h/L) of rivaroxaban increased significantly (p < 0.05) with ticagrelor pre-treatment. The MRT(0-∞) of rivaroxaban increased from 4.41 ± 0.79 to 5.97 ± 1.11 h, while the intrinsic clearance decreased from 9.93 ± 2.55 to 2.89 ± 0.63 L/h/kg (both p < 0.05) after pre-treated with ticagrelor. Enzyme kinetic study indicated that ticagrelor decreased rivaroxaban metabolic clearance with the IC50 value of 14.04 µmol/L. CONCLUSIONS: Our in vivo and in vitro results demonstrated that there is a drug-drug interaction between ticagrelor and rivaroxaban in rats. Further studies need to be carried out to verify whether similar interactions truly apply in humans and whether these interactions have clinical significance.

Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of frailty for elderly patients with cardiovascular disease.

The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1-2 scores; frail: 3-5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P < 0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P < 0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 µmol/mol according to the maximal Youden index. Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation, is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future.

Scalable In-Fiber Manufacture of Functional Composite Particles.

Advanced fabrication methods must be developed for magnetic-polymeric particles, which are used in medical diagnostics, drug delivery, separation, and environmental remediation. The development of scalable fabrication processes that enables simultaneously tuning of diameters and compositions of magnetic-polymeric particles remains a major challenge. Here, we proposed the production of high-quality magnetic-composite particles through a universal method based on the in-fiber Plateau-Rayleigh instability of polymeric fibers. This method can simultaneously control the particle diameter, hybrid configuration, and functional properties. The diameter of magnetic-polymeric particles can be reproducibly tuned from ∼20 nm to 1.25 mm, a wide range unachievable by conventional solution methods. The final diameter was controlled by the inner/outer fiber diameter ratio. We further showed that the prepared magnetic-polymeric composite particles can be used for the highly efficient recovery of heavy metals (98.2% for Cd2+) and for the precise separation of immune cells (CD4+ T cells). Overall, the in-fiber manufacture method can become a universal technology for the scalable preparation of different types of magnetic-polymeric composite particles with diverse functionalities.

Suppression of Laccase 2 severely impairs cuticle tanning and pathogen resistance during the pupal metamorphosis of Anopheles sinensis (Diptera: Culicidae).

BACKGROUND: Phenol oxidases (POs) catalyze the oxidation of dopa and dopamine to melanin, which is crucial for cuticle formation and innate immune maintenance in insects. Although, Laccase 2, a member of the PO family, has been reported to be a requirement for melanin-mediated cuticle tanning in the development stages of some insects, whether it participates in cuticle construction and other physiological processes during the metamorphosis of mosquito pupae is unclear. METHODS: The association between the phenotype and the expression profile of Anopheles sinensis Laccase 2 (AsLac2) was assessed from pupation to adult eclosion. Individuals showing an expression deficiency of AsLac2 that was produced by RNAi and their phenotypic defects and physiological characterizations were compared in detail with the controls. RESULTS: During the dominant expression period, knockdown of AsLac2 in pupae caused the cuticle to be unpigmented, and produced thin and very soft cuticles, which further impeded the eclosion rate of adults as well as their fitness. Moreover, melanization immune responses in the pupae were sharply decreased, leading to poor resistance to microorganism infection. Both the high conservation among Laccase 2 homologs and a very similar genomic synteny of the neighborhood in Anopheles genus implies a conservative function in the pupal stage. CONCLUSIONS: To our knowledge, this is the first study to report the serious phenotypic defects in mosquito pupae caused by the dysfunction of Laccase 2. Our findings strongly suggest that Laccase 2 is crucial for Anopheles cuticle construction and melanization immune responses to pathogen infections during pupal metamorphosis. This irreplaceability provides valuable information on the application of Lacccase 2 and/or other key genes in the melanin metabolism pathway for developing mosquito control strategies.