Decreased GATA3 levels cause changed mouse cutaneous innate lymphoid cell fate, facilitating hair follicle recycling.

In mice, skin-resident type 2 innate lymphoid cells (ILC2s) exhibit some ILC3-like characteristics. However, the underlying mechanism remains elusive. Here, we observed lower expression of the ILC2 master regulator GATA3 specifically in cutaneous ILC2s (cILC2s) compared with canonical ILC2s, in line with its functionally divergent role in transcriptional control in cILC2s. Decreased levels of GATA3 enabled the expansion of RORγt fate-mapped (RORγtfm+) cILC2s after postnatal days, displaying certain similarities to ILC3s. Single-cell trajectory analysis showed a sequential promotion of the RORγtfm+ cILC2 divergency by RORγt and GATA3. Notably, during hair follicle recycling, these RORγtfm+ cILC2s accumulated around the hair follicle dermal papilla (DP) region to facilitate the process. Mechanistically, we found that GATA3-mediated integrin α3ß1 upregulation on RORγtfm+ cILC2s was required for their positioning around the DP. Overall, our study demonstrates a distinct regulatory role of GATA3 in cILC2s, particularly in promoting the divergence of RORγtfm+ cILC2s to facilitate hair follicle recycling.

Environmental triggers of autoimmunity: The association between bisphenol analogues and systemic lupus erythematosus.

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.

The Ang-(1-7)/MasR axis ameliorates neuroinflammation in hypothermic traumatic brain injury in mice by modulating phenotypic transformation of microglia.

The Ang-(1-7)/MasR axis is critically involved in treating several diseases; For example, Ang-(1-7) improves inflammatory response and neurological function after traumatic brain injury and inhibits post-inflammatory hypothermia. However, its function in traumatic brain injury (TBI) combined with seawater immersion hypothermia remains unclear. Here, we used a mice model of hypothermic TBI and a BV2 cell model of hypothermic inflammation to investigate whether the Ang-(1-7)/MasR axis is involved in ameliorating hypothermic TBI. Quantitative reverse transcription PCR, western blotting assay, and immunofluorescence assay were performed to confirm microglia polarization and cytokine regulation. Hematoxylin-eosin staining, Nissl staining, and immunohistochemical assay were conducted to assess the extent of hypothermic TBI-induced damage and the ameliorative effect of Ang-(1-7) in mice. An open field experiment and neurological function scoring with two approaches were used to assess the degree of recovery and prognosis in mice. After hypothermic TBI establishment in BV2 cells, the Ang-(1-7)/MasR axis induced phenotypic transformation of microglia from M1 to M2, inhibited IL-6 and IL-1ß release, and upregulated IL-4 and IL-10 levels. After hypothermic TBI development in mice, intraperitoneally administered Ang-(1-7) attenuated histological damage and promoted neurological recovery. These findings suggest that hypothermia exacerbates TBI-induced damage and that the Ang-(1-7)/MasR axis can ameliorate hypothermic TBI and directly affect prognosis.

Asymmetric synthesis of atropisomeric arylpyrazoles via direct arylation of 5-aminopyrazoles with naphthoquinones.

Construction of axially chiral arylpyrazoles represents an attractive challenge due to the relatively low rotational barrier of biaryl structures containing five-membered heterocycles. This work describes the catalytic asymmetric construction of axially chiral arylpyrazoles using 5-aminopyrazoles and naphthoquinone derivatives. The chiral axis could be formed through a central-to-axial chirality relay step of the chiral phosphoric acid-catalyzed arylation reaction, which features excellent yields and enantioselectivities with a broad substrate scope under mild reaction conditions.

Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma.

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.

Vaginal micro-environment disorder promotes malignant prognosis of low-grade cervical intraepithelial neoplasia: a prospective community cohort study in Shanxi Province, China.

PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

Assessing the influence of simulated environmental gradients on the spatial heterogeneity of landscape patterns in the Tibetan Plateau.

Landscape patterns are pivotal in the realms of land use planning and ecological development, yet there remains a dearth of comprehensive research pertaining to the prediction of changes in landscape pattern characteristics. Within this study, we adopt the PLUS-CA-Markov and Fragstats models to forecast landscape patterns on the Tibetan Plateau spanning the period from 2030 to 2050. Through qualitative and quantitative analyses, we explore the spatiotemporal characteristics of landscape pattern changes between 2000 and 2050, concurrently identifying correlations among landscape pattern indices. Moreover, acknowledging the distinctive environmental gradients encompassing the plateau, notably elevation, slope, temperature, and precipitation, we investigate their implications on landscape pattern changes. Our findings indicate that: (1) Grassland degradation exhibited the utmost severity between 2000 and 2020, primarily attributed to overgrazing and climate-induced glacial melt. In contrast, cropland, forest, and water showcased divergent trends from 2020 to 2050 when compared to the preceding two decades, indicative of the efficacy of climate change control measures. (2) The distribution of landscape patterns on the Tibetan Plateau exhibited a considerable level of instability, marked by a decline in aggregation, reduced diversity and complexity, and amplified ecological connectivity between 2000 and 2020, signifying a partial amelioration in ecological quality. Between 2020 and 2050, landscape aggregation decreased alongside landscape fragmentation and the number of connectivity paths, signifying a discernible degradation of the plateau's ecosystem. (3) The most significant trade-off relationship was observed between landscape division index and largest patch index, while the synergistic relationship between landscape shape index and mean shape index was more pronounced. (4) Landscape aggregation, division, and largest patch index demonstrated non-linear quadratic trends in relation to elevation and temperature. Landscape shape index and patch density exhibited irregular non-linear effects. Largest patch index was predominantly influenced by slope, whereas division index was most affected by precipitation.

Designing a Magnesium/Sodium Hybrid Battery Using Hierarchical Iron Selenide Architecture as Cathode Material and Modified Dual-Ion Salts in Ether as Electrolyte.

We developed a magnesium/sodium (Mg/Na) hybrid battery using a hierarchical disk-whisker FeSe2 architecture (HD-FeSe2) as the cathode material and a modified dual-ion electrolyte. The polarizable Se2- anion reduced the Mg2+ migration barrier, and the 3D configuration possessed a large surface area, which facilitated both Mg2+/Na+ cation diffusion and electron transport. The dual-ion salts with NaTFSI in ether reduced the Mg plating/stripping overvoltage in a symmetric cell. The hybrid battery exhibited an energy density of 260.9 Wh kg-1 and a power density of 600.8 W kg-1 at 0.2 A g-1. It showed a capacity retention of 154 mAh g-1 and a Coulombic efficiency of over 99.5% under 1.0 A g-1 after 800 long cycles. The battery also displayed outstanding temperature tolerance. The findings of 3D architecture as cathode material and hybrid electrolyte provide a pathway to design a highly reliable Mg/Na hybrid battery.

Design and rationale of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study: A cluster randomized controlled trial for hypertension management in primary care.

BACKGROUND: Hypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multifaceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings. MATERIALS AND METHODS: The CHESS evaluation study is a parallel-group, cluster-randomized controlled trial conducted in primary care settings in China. Forty-one primary care sites from 3 counties of China are randomly assigned to either the usual care or the intervention group with the implementation of the CHESS system, more than 1,600 patients aged 35 to 80 years with uncontrolled hypertension and access to a smartphone by themselves or relatives are recruited into the study and followed up for 12 months. In the intervention group, participants receive patient-tailored reminders and alerts via messages or intelligent voice calls triggered by uploaded home blood pressure monitoring data and participants' characteristics, while physicians receive guideline-based prescription instructions according to updated individual data from each visit, and administrators receive auto-renewed feedback of hypertension management performance from the data analysis platform. The multiple components of the CHESS system can work synergistically and have undergone rigorous development and pilot evaluation using a theory-informed approach. The primary outcome is the mean change in 24-hour ambulatory systolic BP from baseline to 12 months. DISCUSSION: The CHESS trial will provide evidence and novel insight into the effectiveness and feasibility of an implementation strategy using a comprehensive digital BP management system for reducing hypertension burden in primary care settings. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, NCT05605418.

Development of a machine learning-based model for predicting individual responses to antihypertensive treatments.

BACKGROUND AND AIMS: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications. METHODS AND RESULTS: We used data from a pragmatic, cluster-randomized trial on hypertension management in China. Each patient's multiple visit records were included, and two consecutive visits were paired as the index and subsequent visits. The least absolute shrinkage and selection operator method was used to select index visit variables for predicting subsequent BP. The dataset was randomly divided into training and test sets in a 7:3 ratio. Model performance was evaluated using mean absolute error (MAE) and R-square in the test set. A total of 19,013 hypertension management visit records (6282 patients) were included. The mean age of the study population was 63.9 years, and 2657 (42.3%) were females. A total of 12 phenotypical features (age, sex, smoking within seven days, body mass index, waist circumference, index visit systolic BP, diastolic BP, heart rate, comorbidities of diabetes, dyslipidemia, coronary heart disease, and stroke), together with currently taking any prescribed antihypertensive medication regimens and visits time interval were selected to build the model. The Extreme Gradient Boost model performed best among all candidate algorithms, with an MAE of 8.57 mmHg and an R2 = 0.28 in the test set. CONCLUSION: The ML techniques exhibit significant potential for predicting individual responses to antihypertensive treatments, thereby aiding clinicians in achieving optimal BP control safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03636334. Registered July 3, 2018, https://clinicaltrials.gov/study/NCT03636334.

Identification of key differentially methylated genes in regulating muscle development and intramuscular fat deposition in chickens.

Muscle development and intramuscular fat (IMF) deposition are intricate physiological processes characterized by multiple gene expressions and interactions. In this research, the phenotypic variations in the breast muscle of Jingyuan chickens were examined at three different time points: 42, 126, and 180 days old. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify differentially methylated genes (DMGs) responsible for regulating muscle development and IMF deposition. The findings indicate a significant increase in breast muscle weight (BMW), myofiber diameter, and cross-sectional area, as well as IMF content, in correlation with the progressive number of growing days in Jingyuan chickens. The findings also revealed that 380 hypo-methylated and 253 hyper-methylated DMGs were identified between the three groups of breast muscle. Module gene and DMG association analysis identified m6A methylation-mediated multiple DMGs associated with muscle development and fat metabolism. In vitro cell modeling analysis reveals stage-specific differences in the expression of CUBN, MEGF10, BOP1, and BMPR2 during the differentiation of myoblasts and intramuscular preadipocytes. Cycloleucine treatment significantly inhibited the expression levels of CUBN, BOP1, and BMPR2, and promoted the expression of MEGF10. These results suggest that m6A methylation-mediated CUBN, MEGF10, BOP1, and BMPR2 can serve as potential candidate genes for regulating muscle development and IMF deposition, and provide an important theoretical basis for further investigation of the functional mechanism of m6A modification involved in adipogenesis.

Linearized EUV mask optimization based on the adjoint method.

Mask optimization, a compensation method for the thick mask effect and the optical proximity effect in projection lithography, is essential for advanced EUV-enabled production nodes. However, owing to high computation costs and the absence of gradient calculations, it is challenging to optimize EUV masks under rigorous consideration of the thick mask effect. In this work, a linearized EUV mask optimization method based on the adjoint method is proposed to provide fast and effective optimizations. The adjoint method is introduced to calculate the gradient of the EUV mask model. Additionally, a linearized gradient is proposed to quickly compensate for wafer pattern distortion caused by the prominent thick mask effect. Two examples of the EUV mask optimization implemented with a two-step strategy were provided, from which it was observed that the linearized gradient can improve the efficiency by about 40% in the coarse optimization step. The proposed method is promising for accurate full-chip EUV mask optimization.

Perceived Economic Burden, Mortality, and Health Status in Patients With Heart Failure.

Importance: In the face of an emerging heart failure (HF) epidemic, describing the association between perceived economic burden (PEB) and health care outcomes is an important step toward more equitable and achievable care. Objectives: To examine the association between PEB and risk of 1-year clinical outcomes and HF-specific health status in patients with acute decompensated HF. Design, Setting, and Participants: This prospective, multicenter, hospital-based cohort study prospectively enrolled adult patients hospitalized for acute decompensated HF at 52 hospitals in China from August 2016 to May 2018, with 1-year follow-up. Data were analyzed on June 17, 2022. Exposure: Perceived economic burden, categorized as severe (cannot undertake expenses), moderate (can almost undertake expenses), or little (can easily undertake expenses). Main Outcomes and Measures: The clinical outcomes of the study were 1-year all-cause death and rehospitalization for HF. Heart failure-specific health status was assessed by the 12-Item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Results: Among 3386 patients, median age was 67 years (IQR, 58-75 years) and 2116 (62.5%) were men. Of these patients, 404 (11.9%) had severe PEB; 2021 (59.7%), moderate PEB; and 961 (28.4%), little PEB. Compared with patients with little PEB, those with severe PEB had increased risk of 1-year mortality (hazard ratio [HR], 1.61; 95% CI, 1.21-2.13; P < .001) but not 1-year HF rehospitalization (HR, 1.21; 95% CI, 0.98-1.49; P = .07). The mean (SD) adjusted KCCQ-12 score was lowest in patients with severe PEB and highest in patients with little PEB at baseline (40.0 [1.7] and 50.2 [1.0] points, respectively; P < .001) and at each visit (eg, 12 months: 61.5 [1.6] and 75.5 [0.9] points respectively; P < .001). Patients reporting severe PEB had a clinically significant lower 1-year KCCQ-12 score compared with those reporting little PEB (mean difference, -11.3 points; 95% CI, -14.9 to -7.6 points; P < .001). Conclusions and Relevance: In this cohort study of patients with acute decompensated HF, greater PEB was associated with higher risk of mortality and poorer health status but not with risk of HF rehospitalization. The findings suggest that PEB may serve as a convenient tool for risk estimation and as a potential target for quality-improvement interventions for patients with HF.

Home Blood Pressure Monitoring and Its Association With Blood Pressure Control Among Hypertensive Patients With High Cardiovascular Risk in China.

Objective: Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence. Methods: This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment. Results: A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of anti-hypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11-1.72, P = 0.004). Conclusions: HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients' misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Wearable 12-Lead ECG Acquisition Using a Novel Deep Learning Approach from Frank or EASI Leads with Clinical Validation.

The 12-lead electrocardiogram (ECG) is crucial in assessing patient decisions. However, portable ECG devices capable of acquiring a complete 12-lead ECG are scarce. For the first time, a deep learning-based method is proposed to reconstruct the 12-lead ECG from Frank leads (VX, VY, and VZ) or EASI leads (VES, VAS, and VAI). The innovative ECG reconstruction network called M2Eformer is composed of a 2D-ECGblock and a ProbDecoder module. The 2D-ECGblock module adaptively segments EASI leads into multi-periods based on frequency energy, transforming the 1D time series into a 2D tensor representing within-cycle and between-cycle variations. The ProbDecoder module aims to extract Probsparse self-attention and achieve one-step output for the target leads. Experimental results from comparing recorded and reconstructed 12-lead ECG using Frank leads indicate that M2Eformer outperforms traditional ECG reconstruction methods on a public database. In this study, a self-constructed database (10 healthy individuals + 15 patients) was utilized for the clinical diagnostic validation of ECG reconstructed from EASI leads. Subsequently, both the ECG reconstructed using EASI and the recorded 12-lead ECG were subjected to a double-blind diagnostic experiment conducted by three cardiologists. The overall diagnostic consensus among three cardiology experts, reaching a rate of 96%, indicates the significant utility of EASI-reconstructed 12-lead ECG in facilitating the diagnosis of cardiac conditions.

Engineering strong man-made cellulosic fibers: a review of the wet spinning process based on cellulose nanofibrils.

With the goal of sustainable development, manufacturing continuous high-performance fibers based on sustainable resources is an emerging research direction. However, compared to traditional synthetic fibers, plant fibers have limited length/diameter and uncontrollable natural defects, while regenerated cellulose fibers such as viscose and Lyocell suffer from inferior mechanical properties. Wet-spun fibers based on nanocelluloses especially cellulose nanofibrils (CNFs) offer superior mechanical performance since CNFs are the fundamental high-performance building blocks of plant cell walls. This review aims to summarize the progress of making CNF wet-spun fibers, emphasizing on the whole wet spinning process including spinning suspension preparation, spinning, coagulation, washing, drying and post-stretching steps. By establishing the relationships between the nano-scale assembling structure and the macroscopic changes in the CNF dope from gels to dried fibers, effective methods and strategies to improve the mechanical properties of the final fibers are analyzed and proposed. Based on this, the opportunities and challenges for potential industrial-scale production are discussed.

Transgenic Tg(Kcnj10-ZsGreen) fluorescent reporter mice allow visualization of intermediate cells in the stria vascularis.

The stria vascularis (SV) is a stratified epithelium in the lateral wall of the mammalian cochlea, responsible for both endolymphatic ion homeostasis and generation of the endocochlear potential (EP) critical for normal hearing. The SV has three layers consisting predominantly of basal, intermediate, and marginal cells. Intermediate and marginal cells form an intricate interdigitated network of cell projections making discrimination of the cells challenging. To enable intermediate cell visualization, we engineered by BAC transgenesis, reporter mouse lines expressing ZsGreen fluorescent protein under the control of Kcnj10 promoter and regulatory sequences. Kcnj10 encodes KCNJ10 protein (also known as Kir4.1 or Kir1.2), an ATP-sensitive inwardly-rectifying potassium channel critical to EP generation, highly expressed in SV intermediate cells. In these transgenic mice, ZsGreen fluorescence mimics Kcnj10 endogenous expression in the cochlea and was detected in the intermediate cells of the SV, in the inner phalangeal cells, Hensen's, Deiters' and pillar cells, in a subset of spiral ganglion neurons, and in glial cells. We show that expression of the transgene in hemizygous mice does not alter auditory function, nor EP. These transgenic Tg(Kcnj10-ZsGreen) mice allow live and fixed tissue visualization of ZsGreen-expressing intermediate cells and will facilitate future studies of stria vascularis cell function.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

A higher non-HDL-C/HDL-C ratio was associated with an increased risk of progression of nonculprit coronary lesion in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The ratio of nonhigh-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) has been shown associated with various metabolic diseases and atherosclerosis in primary prevention. However, there is limited evidence on the relationship between the non-HDL-C/HDL-C ratio and progression of nonculprit coronary lesion (NCCL) after percutaneous coronary intervention (PCI). HYPOTHESIS: Our study aimed to investigate the potential association between the non-HDL-C/HDL-C ratio and NCCL progression in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: We conducted a retrospective analysis of ACS patients who underwent coronary angiography twice at a single center from 2016 to 2022. Lipid measurements, demographic, clinical, and other laboratory data were collected from electronic medical records. NCCLs were evaluated using quantitative coronary angiography. The primary outcome was the progression of NCCL. Patients were categorized based on NCCL progression and tertiles of the non-HDL-C/HDL-C ratio. Associations were analyzed using univariate and multivariate logistic regression analysis. RESULTS: The study included 329 ACS patients who underwent PCI, with a median follow-up angiography of 1.09 years. We found NCCL progression in 95 (28.9%) patients with acceptable low-density lipoprotein cholesterol control (median: 1.81 mmol/L). Patients in the top tertile of the non-HDL-C/HDL-C ratio had a higher risk of NCCL progression. After adjusting for potential confounding factors, the non-HDL-C/HDL-C ratio remained a significant predictor for NCCL progression (adjusted odds ratio: 1.45; 95% confidence interval: 1.14-1.86; p < 0.05). CONCLUSIONS: The non-HDL-C/HDL-C ratio predicts NCCL progression in ACS patients following PCI, providing a valuable tool for risk assessment and enhancing secondary prevention of atherosclerotic cardiovascular disease.