Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Association Between Clonal Hematopoiesis and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy.

Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.

Development and validation of the job stressor scale for specialty nurses.

Objectives: Specialty nurses play a crucial role in specialized nursing practice, teaching, management, and research. These nurses often face significant work pressure; therefore, scientifically and effectively assessing their job stress and its sources is vital for enhancing the quality of their work. However, there is currently a dearth of verified assessment tools for measuring job stressors among specialty nurses. Therefore, this study aimed to develop and test an instrument to assess the job stressors applicable to specialty nurses. Methods: We conducted a multiphase mixed-methods study. The initial scale items were developed from a literature review and structured interviews. The scale was then refined through two rounds of expert consultation (N = 14) and a primary test (N = 20). A main survey (N = 552) was then conducted to evaluate the scale's construct validity and reliability using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Results: The final scale comprises four dimensions with 27 items. The factors included "specialized nursing and work," "workload and time allocation," "patient care," and "work resources and environment." The EFA explained 69.10% of the variance, while the CFA confirmed a good model fit. The content validity index was 0.980 at the scale level and 0.790-1.000 at the item level. The scale's reliability was supported by its high Cronbach's α (0.958), test-retest reliability (0.946), and split-half reliability (0.868). Conclusion: Our findings indicate that the job stressor scale developed in this study is valid and reliable, and is recommended for use among specialty nurses to assess their stressors.

Short-term temperature changes affected the predation ability of Orius similis on Bemisia tabaci nymphs.

Bemisia tabaci (Gennadius), a major pest that can adversely affect economies and agriculture globally, is particularly sensitive to climate change-induced temperature fluctuations, which can intensify its outbreaks. Orius similis Zheng, a primary natural predator of B. tabaci, also experiences temperature-related effects that influence its biocontrol efficacy. Thus, understanding the response of O. similis to temperature changes is pivotal for optimizing its biocontrol potential. Herein, our investigations showed that the functional response of O. similis to both high- and low-instar nymphs of B. tabaci adheres to the type II model at temperatures of 19, 22, 25, 28, and 31 °C. At 28 °C, O. similis exhibits the highest instantaneous attack rate (high-instar: 1.1580, low-instar: 1.2112), and the shortest handling time per prey (high-instar: 0.0218, low-instar: 0.0191). The efficacy of O. similis in controlling B. tabaci nymphs follows the sequence: 28 °C > 25 °C > 31 °C > 22 °C > 19 °C. Additionally, search efficiency inversely correlates with prey density. Simulations using the Hessell-Varley interference model indicate that increased density of O. similis under any temperature condition leads to reduced predation rates. Moreover, O. similis shows a predation preference for low-instar nymphs of B. tabaci, with higher predation level observed at the same temperature. In conclusion, for effective control of B. tabaci in field releases, O. similis should be optimally released at temperatures between 25 and 28 °C to preferably target the egg or early nymph stages of B. tabaci and determining the appropriate number of O. similis is important to minimize interference among individuals and enhance biocontrol efficacy.

Genome of Halimeda opuntia reveals differentiation of subgenomes and molecular bases of multinucleation and calcification in algae.

Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.

Strategic engineering of cationic systems for spatial & temporal anti-counterfeiting applications in zero-dimensional Mn(II) halides.

While spatial and time-resolved anti-counterfeiting technologies have gained increasing attention owing to their excellent tunable photoluminescence, achieving high-security-level anti-counterfeiting remains a challenge. Herein, we developed a spatial-time-dual-resolved anti-counterfeiting system using zero-dimensional (0D) organic-inorganic Mn(II) metal halides: (EMMZ)2MnBr4 (named M-1, EMMZ=1-Ethyl-3-Methylimidazolium Bromide) and (EDMMZ)2MnBr4 (named M-2, EDMMZ=1-Ethyl-2,3-Dimethylimidazolium Bromide). M-1 shows a bright green emission with a quantum yield of 78 %. It undergoes a phase transformation from the crystalline to molten state with phosphorescence quenching at 350 K. Reversible phase and luminescent conversion was observed after cooling down for 15 s. Notably, M-2 exhibits green light emission similar to M-1 but undergoes phase conversion and phosphorescence quenching at 390 K, with reversible conversion observed after cooling down for 5 s. The photoluminescence switching mode of on(green)-off-on(green) can be achieved by temperature control, demonstrating excellent performance with short response times and ultra-high cyclic reversibility. By leveraging the different quenching temperatures and reversible PL conversion times of M-1 and M-2, we propose a spatial-time-dual-resolved photoluminescence (PL) switching system that combines M-1 and M-2. This system enables multi-fold tuning of the PL switch for encryption and decryption through cationic engineering strategies by modulating temperature and cooling time. This work presents a novel and feasible design strategy for advanced-level anti-counterfeiting technology based on a spatial-time-dual-resolved system.

Association between admission blood pressure and spontaneous reperfusion and long-term prognosis in STEMI patients: an observational and multicenter study.

BACKGROUND: This study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients. METHODS: Data from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2-3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics. RESULTS: Admission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95% CI: 0.706-0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958-1.084, p = 0.552). In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality compared with those SBP ≤ 120mmHg (adjusted HR: 0.653; 95% CI: 0.495-0.862; p = 0.003). In addition, subgroups analysis with Killip class I-II showed SBP ≤ 120mmHg was still associated with increased risk of mortality. CONCLUSION: The present study revealed admission SBP above 120 mmHg was associated with higher SR,30-d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04996901), 07/27/2021.

Low-carbon treatment and remediation of oil sludge in mid-to-high latitude regions: A coupled approach of freeze-thaw and supercritical CO2 extraction.

The oil sludge produced while extracting large oil and gas fields in the middle and high latitude regions has caused serious pollution to the surrounding soil. The key to solving this problem in the future is to unify the remediation of soil and the treatment of oil sludge. This study uses supercritical carbon dioxide(scCO2) technology to construct a low-carbon method, providing a new approach to achieve this goal. The study determines the optimal extraction conditions for black calcareous soil with 15% oil content to be 55 °C, 25 MPa, and 90 min through single factor and response surface experiments. Experiments on the scCO2 extraction coupled with freeze-thaw cycles show that oil sludge with a water content of 10% can improve the extraction efficiency of scCO2 by about 2.69% after less than five freeze-thaw cycles. The study also compares the extraction efficiency of the four soils, with a difference of 6.03% observed under the same conditions. Additionally, we analyze the impact of the extraction process on changes in the properties of the oil and soil in the oil sludge. Comprehensive tests, including scanning electron microscope (SEM), nutrient detection, X-ray powder diffractometer (XRD), fourier transform infrared spectroscopy (FTIR), and Gas Chromatography (GC), have been conducted. Results show that standalone scCO2 extraction can remove up to 98.2% of petroleum hydrocarbons from the oil sludge, while simultaneously causing small changes to the soil microstructure and the crystal structure of the oil sludge. Furthermore, this process does not lead to a significant depletion of key nutrients or the generation of new pollutants.

Discussion on the relationship between the distribution characteristics of TCM syndrome types and related objective indicators in hepatolenticular degeneration.

Hepatolenticular degeneration is a rare treatable autosomal recessive inherited copper metabolism disorder with a diverse clinical phenotype and an exceptionally complex pathogenesis. Early definitive phenotypic diagnosis and targeted treatment are major challenges worldwide. In this study, we strictly followed the "National Standards of the People's Republic of China - Terminology of Traditional Chinese Medicine Clinical Diagnosis and Treatment (Syndrome Part)," "Chinese Medicine Nomenclature," and the clinical investigation-determined traditional Chinese medicine syndrome differentiation standards at Anhui University of Chinese Medicine to select 6 of the most common traditional Chinese medicine syndrome differentiations. This study retrospectively analyzed 107 patients admitted between 2019 and 2023 with Wilson's disease based on real-world data. After testing for normal distribution and homogeneity of variance, corresponding analysis of variance was selected, followed by post hoc multiple comparisons. Of the selected 25 objective influencing factors, 22 exhibited normal distribution, while red blood cells, hemoglobin, and type IV collagen did not pass the homogeneity of variance test. After analysis of variance, the factors ceruloplasmin (CP) and copper oxidase (SCO) showed significant differences among patients with different traditional Chinese medicine syndromes (P < .05), with partial η2 for CP being 0.13 > 0.06 and for SCO being 0.143 > 0.14. Post hoc multiple comparison results indicated significant differences in CP and SCO among patients with certain traditional Chinese medicine syndromes (P < .05). There were significant differences in the factors CP and SCO among patients with different traditional Chinese medicine syndromes. Significant differences were observed in the copper blue protein factor between damp-heat syndrome and liver and kidney deficiency syndrome, liver and kidney deficiency syndrome and liver and kidney yin deficiency syndrome, liver and kidney deficiency syndrome and phlegm heat and wind syndrome, as well as liver and kidney deficiency syndrome and syndrome of phlegm and blood stasis (P < .05). Significant differences were also found in the SCO factor between damp-heat syndrome and liver and kidney deficiency syndrome, liver and kidney deficiency syndrome and liver and kidney yin deficiency syndrome, liver and kidney deficiency syndrome and phlegm heat and wind syndrome, and liver and kidney deficiency syndrome and syndrome of phlegm and blood stasis (P < .05).

The recent advances of MnFe2O4-based nanoparticles in environmental application: A review.

The manganese ferrite (MnFe2O4)-based nanoparticles showed a substantial potential to remediate the various pollutants in environmental application due to low cost, simple magnetic separation and high removal capacity. Herein, the functionalization of various MnFe2O4-based nanoparticles was briefly summarized; Then the recent advances concerning the removal of pollutants (i.e., organics, heavy metals and antibacterial activity) on different MnFe2O4-based nanoparticles were reviewed in details. The reactivity of MnFe2O4-based nanoparticles was significantly influenced by environmental factors. It is demonstrated that interaction mechanism of various pollutants on magnetic MnFe2O4-based nanoparticles included degradation, adsorption, coordination, redox and precipitation. Finally, the current problems and future perspective of MnFe2O4-based nanoparticles were proposed. The highlight of this review is to compare the removal performance of MnFe2O4-based nanoparticles with the different hybrids. This review is crucial for the application of MnFe2O4-based nanoparticles in the environmental remediation.

Gastrodin alleviates diabetic peripheral neuropathy by regulating energy homeostasis via activating AMPK and inhibiting MMP9.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes that lacks effective treatment. Gastrodin, the primary bioactive compound derived from Rhizoma Gastrodiae, has a long history in treating epilepsy and various central nervous system disorders. However, its effect on DPN remains uncertain. PURPOSE: This study aims to explore the therapeutic potential and underlying mechanisms of gastrodin in the treatment of DPN. METHOD: DPN model rats were induced with streptozotocin (STZ) injection and divided into four groups receiving either gastrodin at two doses (30 and 60 mg kg-1 per day), α-lipoic acid (positive drug, 60 mg kg-1 per day), or placebo. Healthy rats were administrated with placebo. The administrations began eight weeks post-STZ injection and continued for six weeks. Following a comprehensive evaluation of the neuroprotective effects, a systematic pharmacology-based approach was subsequently employed to investigate the underlying mechanism of gastrodin in vivo and in vitro. RESULTS: Gastrodin was demonstrated to effectively enhance peripheral nerve function and reduce pathological damages in DPN rats. Furthermore, gastrodin facilitated the expression of remyelination-related proteins and mitigated oxidative stress in DPN rats. Transcriptomic analysis indicated that the modulation of energy metabolism was pivotal in the neuroprotective effect of gastrodin, corroborated by targeted metabolomic analysis using high-performance ion chromatography coupled with mass spectrometry. Using network pharmacology analysis, 12 potential targets of gastrodin were identified. Among these, matrix metallopeptidase 9 (MMP9) was further validated as the primary target through molecular docking and cellular thermal shift assays. Functional Analysis of the potential targets underscored the pivotal role of AMPK signaling, and gastrodin demonstrated the capability to activate AMPK and inhibit MMP9 in vivo. In vitro studies further found that gastrodin enhanced antioxidant capacity and mitochondrial function of high glucose-cultured rat Schwann cells RSC96 in an AMPK-dependent manner. Inhibition of AMPK hindered the decrease of MMP9 induced by gastrodin in vitro. CONCLUSION: This study revealed the new role of gastrodin in alleviating DPN by restoring the homeostasis of energy metabolism through activating AMPK and inhibiting MMP9. These findings highlight gastrodin's potential as a novel therapeutic candidate against DPN, and underscores an appealing strategy of regulating energy metabolism for DPN therapy.

Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial.

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial.

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.

Autism and Intellectual Disability-Associated MYT1L Mutation Alters Human Cortical Interneuron Differentiation, Maturation, and Physiology.

MYT1L is a neuronal transcription factor highly expressed in the developing and adult brain. While pathogenic MYT1L mutation causes neurodevelopmental disorders, these have not been characterized in human models of neurodevelopment. Here, we defined the consequences of pathogenic MYT1L mutation in human pluripotent stem cell-derived cortical interneurons. During differentiation, mutation reduced MYT1L expression and increased progenitor cell cycle exit and neuronal differentiation and synapse-related gene expression, morphological complexity, and synaptic puncta formation. Conversely, interneuron maturation was compromised, while variant neurons exhibited altered sodium and potassium channel activity and reduced function in electrophysiological analyses. CRISPRi-based knockdown similarly impaired interneuron differentiation and maturation, supporting loss of function-based effects. We further defined MYT1L genome-wide occupancy in interneurons and related this to the transcriptomic dysregulation resulting from MYT1L mutation, to identify direct targets that could mediate these phenotypic consequences. Together, this work delineates contributors to the etiology of neurodevelopmental disorders resulting from MYT1L mutation.

G3BP2 promotes tumor progression and gemcitabine resistance in PDAC via regulating PDIA3-DKC1-hENT in a stress granules-dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is distinguished by its aggressive malignancy, limited treatment avenues and a tendency towards chemotherapy resistance, underscoring the critical need for advanced research to uncover new therapeutic approaches. Stress granules (SGs) that is implicated in cellular self-protection mechanism, along with its associated family molecules have shown pro-cancer effects and are closely related to tumor chemotherapy resistance. In this study we investigated the relationship between Ras GTPase-activating protein-binding proteins 2 (G3BP2), a core component of SGs, and the malignancy of PDAC as well as its resistance to the chemotherapy drug gemcitabine. Analyzing TCGA dataset revealed that the expression of G3BP1 and G3BP2 was significantly upregulated in PDAC compared with adjacent normal pancreatic tissues, and the high expression of G3BP2 rather than G3BP1 was significantly associated with poorer overall survival (OS) in PDAC patients. We demonstrated that knockdown of G3BP2 inhibited the proliferation and invasion of PANC-1 and CFPAC-1 cells in vitro and in vivo. By analyzing the differentially expressed genes in G3BP2 knockdown and overexpressed PANC-1 cells, we identified DKC1 that was associated with RNA stability and regulation as the target of G3BP2. We demonstrated that G3BP2 bound to PDIA3 mRNA and recruited them into SGs, increasing the stability of PDIA3 mRNA and attenuating its translation efficiency, thereby promoting DKC1 expression. Furthermore, DKC1 could bind to hENT mRNA and inhibited its expression, which enhanced gemcitabine resistance of PDAC. Therefore, we propose a novel mechanism wherein G3BP2 facilitates PDAC's resistance to chemotherapy by modulating PDIA3-DKC1-hENT in a SGs-dependent way, suggesting G3BP2 SGs a protentional therapeutic target for the treatment in PDAC.

A hierarchical residual correction-based hyperspectral inversion method for soil heavy metals considering spatial heterogeneity.

Promising hyperspectral remote sensing exhibits substantial potential in monitoring soil heavy metal (SHM) contamination. Nevertheless, the local spatial perturbation effects induced by environmental factors introduce considerable variability in SHM distribution. This engenders non-stationary relationship between SHM concentrations and spectral reflectance, posing challenges for accurate inversion of SHM globally. Addressing this gap, a novel Hierarchical Residual Correction-based Hyperspectral Inversion Method (HRCHIM) is proposed for SHM, considering their spatial heterogeneity. Initially, a global model is constructed using ground hyperspectral data to predict SHM concentration, capturing overarching contamination trends. Subsequently, four hierarchical levels, segmented by residual standard deviation (SD) intervals, identify critical environmental factors via Geodetector. These factors inform local residual correction models, refining global model predictions. HRCHIM aims to synergize global trends and local stochasticity to enhance prediction accuracy and interpretation of SHM spatial heterogeneity. Validated through a case study of a Cadmium(Cd)-contaminated mine area, six critical environmental factors were identified, exhibiting significant differences across hierarchical levels. By incorporating hierarchical correction models, HRCHIM demonstrated superior inversion performance compared to other conventional methods, achieving optimal prediction accuracies (Rv2 = 0.94, RMSEv = 0.21, and RPDv = 4.11). This innovative method can facilitate more precise and targeted strategies for preventing and controlling SHM contamination.

Krüppel-like transcription factor 14 alleviates alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress in pulmonaryfibrosis.

Pulmonary fibrosis (PF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults with poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. However, the molecular mechanisms regulating AEC senescence in PF are incompletely understood. Herein, we provided evidence to support the function of Krüppel-like factor 14 (KLF14), a novel Krüppel-like transcription factor, in the regulation of AEC senescence during PF. We confirmed that the expression of KLF14 was up-regulated in PF patients and mice treated with bleomycin (BLM). KLF14 knockdown resulted in more pronounced structural disruption of the lung tissue and swelling of the alveolar septum, which led to significantly increased mortality in BLM-induced PF mice. Mechanistically, RNA-seq analysis indicated that KLF14 decreased the senescence of AECs by inhibiting endoplasmic reticulum (ER) stress. Furthermore, the pharmacological activation of KLF14 conferred protection against PF in mice. In conclusion, our findings reveal a protective role for KLF14 in preventing AECs from senescence and shed light on the development of KLF14-targeted therapeutics for PF.

Hypertension and its correlation with autonomic nervous system dysfunction, heart rate variability and chronic inflammation.

OBJECTIVE: This study investigates the relationship between hypertension, dysregulation of the autonomic nervous system, heart rate variability (HRV), and chronic inflammation. METHODS: We analysed a cohort of 50 hypertensive patients treated at the affiliated Hospital of Jianghan University. The average systolic and diastolic blood pressures (BPs) in this group were 155.26 and 95.32 mmHg, respectively. A control group of 50 healthy volunteers, undergoing routine physical examinations at the same hospital, was also analysed. RESULTS: The average systolic BP of the control group was 115.64 ± 10.27 mmHg, and the average diastolic BP was 75.33 ± 8.25 mmHg. In contrast, the experimental group exhibited an average systolic BP of 155.26 ± 20.13 mmHg and an average diastolic BP of 95.32 ± 12.16 mmHg. Both systolic and diastolic BPs were significantly higher in the hypertensive group (p < 0.05). The experimental group also demonstrated reduced HRV and skin conductance response, alongside increased BP variability (BPV), urinary epinephrine levels and prolonged pupillary light reaction time compared to controls (p < 0.05). Notably, Standard Deviation of Normal to Normal Intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD) values were significantly lower in the experimental group (p < 0.05). Furthermore, levels of inflammatory markers such as CRP, TNF-α, IL-6 and IL-1ß were markedly elevated in hypertensive patients (p < 0.05). Negative correlations were observed between systolic and diastolic BP with HRV metrics, while positive correlations were found between BP and BPV as well as urinary adrenaline levels. CONCLUSIONS: The findings indicate that hypertension is closely associated with autonomic nervous system dysfunction, reduced HRV and increased chronic inflammation. A comprehensive approach to hypertension management should integrate these interrelated physiological and pathological mechanisms, with potential therapeutic interventions targeting autonomic function and inflammatory states.

Hypertension represents a global health challenge. Autonomic nervous system dysfunction and chronic inflammation assumes a pivotal role in hypertension pathogenesis. Reduced heart rate variability (HRV) is a surrogate marker of autonomic dysfunction. This study endeavours to elucidate the intricate relationship between hypertension and autonomic dysfunction, HRV and chronic inflammation, thereby advancing our comprehension of hypertension pathophysiology.

The prognosis and metabolite changes of NSCLC patients receiving first-line immunotherapy combined chemotherapy in different M1c categories according to 9th edition of TNM classification.

BACKGROUND: The 9th edition of the TNM Classification for lung cancer delineates M1c into two subcategories: M1c1 (Multiple extrathoracic lesions within a single organ system) and M1c2 (Multiple extrathoracic lesions involving multiple organ systems). Existing research indicates that patients with lung cancer in stage M1c1 exhibit superior overall survival compared to those in stage M1c2. The primary frontline therapy for patients with advanced non-small cell lung cancer (NSCLC), lacking driver gene mutations, involves the use of immune checkpoint inhibitors (ICIs) combined with chemotherapy. Nevertheless, a dearth of evidence exists regarding potential survival disparities between NSCLC patients with M1c1 and M1c2 undergoing first-line immune-chemotherapy, and reliable biomarkers for predicting treatment outcomes are elusive. Serum metabolic profiles may elucidate distinct prognostic mechanisms, necessitating the identification of divergent metabolites in M1c1 and M1c2 undergoing combination therapy. This study seeks to scrutinize survival discrepancies between various metastatic patterns (M1c1 and M1c2) and pinpoint metabolites associated with treatment outcomes in NSCLC patients undergoing first-line ICIs combined with chemotherapy. METHOD: In this study, 33 NSCLC patients lacking driver gene mutations diagnosed with M1c1, and 22 similarly diagnosed with M1c2 according to the 9th edition of TNM Classification, were enrolled. These patients received first-line PD-1 inhibitor plus chemotherapy. The relationship between metastatic patterns and progression-free survival (PFS) in patients undergoing combination therapy was analyzed using univariate and multivariate Cox regression models. Serum samples were obtained from all patients before treatment initiation for untargeted metabolomics analysis, aiming to identify differential metabolites. RESULTS: In the univariate analysis of PFS, NSCLC patients in M1c1 receiving first-line PD-1 inhibitor plus chemotherapy exhibited an extended PFS (HR = 0.49, 95% CI, 0.27-0.88, p = 0.017). In multivariate PFS analyses, these M1c1 patients receiving first-line PD-1 inhibitor plus chemotherapy also demonstrated prolonged PFS (HR = 0.45, 95% CI, 0.22-0.92, p = 0.028). The serum metabolic profiles of M1c1 and M1c2 undergoing first-line PD-1 inhibitors plus chemotherapy displayed notable distinctions. In comparison to M1c1 patients, M1c2 patients exhibited alterations in various pathways pretreatment, including platelet activation, linoleic acid metabolism, and the VEGF signaling pathway. Diminished levels of lipid-associated metabolites (diacylglycerol, sphingomyelin) were correlated with adverse outcomes. CONCLUSION: NSCLC patients in M1c1, devoid of driver gene mutations, receiving first-line PD-1 inhibitors combined with chemotherapy, experienced superior outcomes compared to M1c2 patients. Moreover, metabolomic profiles strongly correlated with the prognosis of these patients, and M1c2 patients with unfavorable outcomes manifested distinct changes in metabolic pathways before treatment. These changes predominantly involved alterations in lipid metabolism, such as decreased diacylglycerol and sphingomyelin, which may impact tumor migration and invasion.

Exploring the relationship between metal ion valency and electron transfer in copigmentation processes of cyanidin-3-O-glucoside in simulated fruit wine solutions.

In this experiment, five metal ions (K+, Mg2+, Al3+, Ga3+, and Sn4+) were utilized as copigments to investigate their copigmentation processes with cyanidin-3-O-glucoside (C3OG) in simulated fruit wine solutions. The color characteristics were analyzed using Glories and CIELAB methods, and the copigmentation effects were determined spectrophotometrically. Thermodynamic parameters, including the equilibrium constant (K) and standard Gibbs free energy (ΔG°), were calculated to comprehend the binding affinity between metal ions and C3OG. Ultra-fast femtosecond spectroscopy was employed to monitor the photoinduced electron transfer process between C3OG and cations. Theoretical calculations were also conducted to support experimental findings. The results revealed that the presence of metal ions significantly enhanced the color intensity of C3OG in simulated fruit wine solutions. Higher valency cations, particularly Sn4+, Ga3+, and Al3+, exhibited superior copigmentation effects, resulting in significant bathochromic and hyperchromic changes. Thermodynamic analysis confirmed that the interaction between C3OG and metal ions was spontaneous and exothermic. Ultra-fast femtosecond spectroscopy demonstrated that electron transfer from C3OG to metal ions occurred, with the efficiency of transfer being dependent on valency. Theoretical calculations corroborated the experimental results by highlighting the role of metal ions in stabilizing C3OG/metal complexes through electron transfer. The findings presented in this study contribute to a more comprehensive understanding of pigment/metal complexes and the underlying chemistry behind fruit wine color. Furthermore, it advances the theoretical foundation of copigmentation and broadens its applications in the beverage industry.