Multi-Component Lithiophilic Alloy Film Modified Cu Current Collector for Long-Life Lithium Metal Batteries by a Novel FCVA Co-Deposition System.

Surface modification of Cu current collectors (CCs) is proven to be an effective method for protecting lithium metal anodes. However, few studies have focused on the quality and efficiency of modification layers. Herein, a novel home-made filtered cathode vacuum arc (FCVA) co-deposition system with high modification efficiency, good repeatability and environmental friendliness is proposed to realize the wide range regulation of film composition, structure and performance. Through this system, ZnMgTiAl quaternary alloy films, which have good affinity with Li are successfully constructed on Cu CCs, and the fully enhanced electrochemical performances are achieved. Symmetrical cells constructed with modified CCs maintained a fairly low voltage hysteresis of only 13 mV after 2100 h at a current density of 1 mA cm-2. In addition, the capacity retention rate is as high as 75.0% after 100 cycles in the full cells. The influence of alloy films on the dynamic evolution process of constructing stable artificial solid electrolyte interphase (SEI) layer is revealed by in situ infrared (IR) spectroscopy. This work provides a promising route for designing various feasible modification films for LMBs, and it displays better industrial application prospects than the traditional chemical methods owing to the remarkable controllability and scale-up capacity.

Identifying modifiable factors and their joint effect on brain health: an exposome-wide association study.

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

iLipidome: enhancing statistical power and interpretability using hidden biosynthetic interdependencies in the lipidome.

Numerous biological processes and diseases are influenced by lipid composition. Advances in lipidomics are elucidating their roles, but analyzing and interpreting lipidomics data at the systems level remain challenging. To address this, we present iLipidome, a method for analyzing lipidomics data in the context of the lipid biosynthetic network, thus accounting for the interdependence of measured lipids. iLipidome enhances statistical power, enables reliable clustering and lipid enrichment analysis, and links lipidomic changes to their genetic origins. We applied iLipidome to investigate mechanisms driving changes in cellular lipidomes following supplementation of docosahexaenoic acid (DHA) and successfully identified the genetic causes of alterations. We further demonstrated how iLipidome can disclose enzyme-substrate specificity and pinpoint prospective glioblastoma therapeutic targets. Finally, iLipidome enabled us to explore underlying mechanisms of cardiovascular disease and could guide the discovery of early lipid biomarkers. Thus, iLipidome can assist researchers studying the essence of lipidomic data and advance the field of lipid biology.

Corrigendum: Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway.

[This corrects the article DOI: 10.1177/15353702231211977.].

To elucidate the mechanism of "Scrophulariae Radix-Fritillaria" in goiter by integrated metabolomics and serum pharmaco-chemistry.

The pharmacodynamic substances in "Scrophulariae Radix-Fritillaria" and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through metabolomics and serum pharmaco-chemistry. A rat model of goiter was established using propylthiouracil (PTU), and the animals were treated using "Scrophulariae Radix-Fritillaria." The efficacy of the drug pair was evaluated in terms of thyroid gland histopathology and blood biochemical indices. Serum and urine samples of the rats were analyzed by UPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to screen potential biomarkers in urine and the corresponding metabolic pathways. The blood components of "Scrophulariae Radix-Fritillaria" were also identified, and their correlation with urine biomarkers was analyzed in order to screen for potential bioactive compounds. "Scrophulariae Radix-Fritillaria" mitigated injury to thyroid tissues and normalized the levels of the thyroid hormones FT3, FT4, and TSH. We also identified 22 urine biomarkers related to goiter, of which 19 were regulated by "Scrophulariae Radix-Fritillaria." Moreover, urine biomarkers are involved in tryptophan metabolism, steroid hormone biosynthesis, and beta-alanine metabolism, and these pathways may be targeted by the drug pair. In addition, 47 compounds of "Scrophulariae Radix-Fritillaria" were detected by serum pharmacochemistry, of which nine components, namely, syringic acid, paeonol, cedrol, and cis-ferulic acid, fetisinine, aucubigenin, linolenic acid, ussuriedine, and 5-(methylsulfanyl)pentanenitrile, were identified as potential effective substances against goiter. To summarize, we characterized the chemical components and mechanisms of "Scrophulariae Radix-Fritillaria" involved in the treatment of goiter, and our findings provide an experimental basis for its clinical application.

Whole exome sequencing analyses reveal novel genes in telomere length and their biomedical implications.

Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes.

Multiple RNA Rapid In Situ Imaging Based on Cas9 Code Key System.

Existing RNA in situ imaging strategies mostly utilize parallel repetitive nucleic acid self-assembly to achieve multiple analysis, with limitations of complicated systems and cumbersome steps. Here, a Cas9 code key system with key probe (KP) encoder and CRISPR/Cas9 signal exporter is developed. This system triggers T-protospacer adjacent motif (T-PAM structural transitions of multiple KP encoders to form coding products with uniform single-guide RNA (sgRNA) target sequences as tandem nodes. Only single sgRNA/Cas9 complex is required to cleave multiple coding products, enabling efficient "many-to-one" tandem signaling, and non-collateral cleavage activity-dependent automatic signaling output through active introduction of mismatched bases. Compared with conventional parallel multiple signaling analysis model, the proposed system greatly simplifies reaction process and enhances detection efficiency. Further, a rapid multiple RNA in situ imaging system is developed by combining the Cas9 code key system with a T-strand displacement amplification (T-SDA) signal amplifier. The constructed system is applied to tumor cells and clinicopathology slices, generating clear multi-mRNA imaging profiles in less than an hour with just one step. Therefore, this work provides reliable technical support for clinical tumor typing and molecular mechanism investigation.

Unilateral biportal endoscopy via two different approaches for upper lumbar disc herniation: a technical note.

BACKGROUND: The traditional surgical procedures for upper lumbar disc herniation (ULDH) usually lead to frequent complications. We aim to investigate the clinical efficacy of the unilateral biportal endoscopy (UBE) technique in treating upper lumbar disc herniation (ULDH). METHODS: From January 2020 to December 2021, the clinical data of 28 patients with ULDH treated with the UBE technique were collected and analyzed for surgery time under UBE, postsurgical drainage, postsurgical hospital stay, and complications. The clinical efficacy was evaluated according to the modified MacNab score, Oswestry disability index (ODI), and visual analogue scale (VAS) of low back pain and lower limb pain before the surgery; one week, one month, and three months after the surgery; and at the last follow-up. RESULTS: All patients underwent the UBE surgery successfully. The surgery time under UBE for non-fusion cases was 47.50 ± 11.84 min (monosegment) and 75.00 ± 20.66 min (two segments), while that for fusion cases was 77.50 ± 21.02 min. The postsurgical drainage for non-fusion cases was 25.00 ± 13.94 mL (monosegment) and 38.00 ± 11.83 mL (two segments), while that for fusion cases was 71.25 ± 31.72 mL. The postsurgical hospital stay was 8.28 ± 4.22 days. The follow-up time was 15.82 ± 4.54 months. The VAS score for each time period after the surgery was significantly lower (P < 0.05), while the ODI was significantly higher than that before the surgery (P < 0.05). According to the modified MacNab scoring standard, the ratio of excellent to good was 96.43% at the last follow-up. Two patients experienced transient numbness and pain in their lower limbs and no activity disorder after the surgery, and they recovered after conservative treatment. CONCLUSIONS: The clinical effect of UBE technique in treating ULDH was reliable. According to the needs of the disease, the interlaminar approach or paraspinal approach of the UBE technique was selected. This technique took into account the effect of treatment, achieved the purpose of minimal invasiveness, and did not require special instruments. Therefore, it has the potential for clinical application.

Discharge within 24 h, transvaginal natural orifice transluminal endoscopic surgery- more suitable for ambulatory surgery in gynecology procedures: a retrospective study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is an achievement in the field of minimally invasive surgery. However, the vantage point of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologicalprocedures remains unclear. The main purpose of this study was to compare vNOTES with laparo-endoscopic single-site surgery, and to determine which procedure is more suitable for ambulatory surgery in gynecologic procedures. METHODS: This retrospective observational study was conducted at the Department of Gynecology, Chengdu Women's and Children's Central Hospital. The 207 enrolled patients had accepted vNOTES and laparo-endoscopic single-site surgery in gynecology procedures from February 2021 to March 2022. Surgically relevant information regarding patients who underwent ambulatory surgery was collected, and 64 females underwent vNOTES. RESULTS: Multiple outcomes were analyzed in 207 patients. The Wilcoxon Rank-Sum test showed that there were statistically significant differences between the vNOTES and laparo-endoscopic single-site surgery groups in terms of postoperative pain score (0 vs. 1 scores, p = 0.026), duration of anesthesia (90 vs. 101 min, p = 0.025), surgery time (65 vs. 80 min, p = 0.015), estimated blood loss (20 vs. 40 mL, p < 0.001), and intestinal exhaustion time (12.20 vs. 17.14 h, p < 0.001). Treatment with vNOTES resulted in convenience, both with respect to time savings and hemorrhage volume in surgery and with respect to the quality of the prognosis. CONCLUSION: These comprehensive data reveal the capacity of vNOTES to increase surgical efficiency. vNOTES in gynecological procedures may demonstrate sufficient feasibility and provide a new medical strategy compared with laparo-endoscopic single-site surgery for ambulatory surgery in gynecological procedures.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

A role for the C. elegans Argonaute protein CSR-1 in small nuclear RNA 3' processing.

The Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3' cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. Here we developed a GFP based in vivo snRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encoding csr-1 gene resulted in widespread 3' misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss of the csr-1 gene down-regulates the germline expression of Integrator subunits 4 and 6 and is accompanied by a reduced protein translation efficiency of multiple Integrator catalytic and non-catalytic subunits. Through isoform and motif mutant analysis, we determined that CSR-1's effect on snRNA processing is dependent on its catalytic slicer activity but does not involve the CSR-1a isoform. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile between csr-1 and Integrator subunit knockdown via RNAi. Together, our findings reveal CSR-1 as a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3' processing.

Cold hypersensitivity in the hands and feet is associated with erectile dysfunction in young Taiwanese men.

Cold hypersensitivity in the hands and feet (CHHF) is a protective or predisposing factor for many diseases; however, the relationship between CHHF and erectile dysfunction (ED) remains unclear. We aimed to investigate associations between CHHF and ED among young men of Southeast Asian origin. In this cross-sectional study, sexually active Taiwanese men aged 20-40 years were enrolled via an online questionnaire comprising general demographic information, comorbidities, subjective thermal sensations of their hands and feet in the past 6 months, and their erectile function using the International Index of Erectile Function-5 (IIEF-5). Participants who reported cold sensation of hands and feet were classified to have CHHF; those with IIEF-5 score ≤ 21 were considered to have ED. Total 54.2% and 27.9% of participants had ED and CHHF, respectively. Men with CHHF were significantly younger, had lower body mass index and IIEF-5 scores (p < 0.001), and a lower prevalence of diabetes mellitus (p = 0.033) along with higher prevalence of ED, psychiatric disorders, and insomnia (p < 0.001). After adjusting for predisposing factors of ED, CHHF (odds ratio 1.410, 95% confidence interval 1.159-1.714; p = 0.001) remained an independent predictor of ED. Thus, CHHF is independently associated with ED, affecting more than a quarter of young Taiwanese men. Autonomic dysregulation and subclinical endothelial dysfunction may be common pathophysiologies of CHHF and ED.

High Urine Albumin-to-Creatinine Ratio is Associated with Increased Arterial Stiffness in Diabetes: A Chinese Cross-Sectional Study.

Purpose: Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes. Methods: From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out. Results: The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p<0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176-0.276, p<0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19-1.33, p<0.001), and 1.16 (1.08-1.25, p<0.001) respectively in diabetic patients before and after adjusting for potential confounders. Conclusion: The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.

1. The mean baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group.2. The sex-specific hierarchical analysis revealed that baPWV levels and the incidence of high baPWV were significantly elevated with increased UACR.3. Curvilinear relationships between log2-transformed UACR and the risk of high baPWV.4. Positive association between UACR and high baPWV in patients with diabetes.

MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway.

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

Genetic architecture of brain morphology and overlap with neuropsychiatric traits.

Uncovering the genetic architectures of brain morphology offers valuable insights into brain development and disease. Genetic association studies of brain morphological phenotypes have discovered thousands of loci. However, interpretation of these loci presents a significant challenge. One potential solution is exploring the genetic overlap between brain morphology and disorders, which can improve our understanding of their complex relationships, ultimately aiding in clinical applications. In this review, we examine current evidence on the genetic associations between brain morphology and neuropsychiatric traits. We discuss the impact of these associations on the diagnosis, prediction, and treatment of neuropsychiatric diseases, along with suggestions for future research directions.

Environmental DNA-based biodiversity profiling along the Houdong River in north-eastern Taiwan.

Background: This paper describes two datasets: species occurrences, which were determined by environmental DNA (eDNA) metabarcoding and their associated DNA sequences, originating from a research project which was carried out along the Houdong River (), Jiaoxi Township, Yilan, Taiwan. The Houdong River begins at an elevation of 860 m and flows for approximately 9 km before it empties into the Pacific Ocean. Meandering through mountains, hills, plains and alluvial valleys, this short river system is representative of the fluvial systems in Taiwan. The primary objective of this study was to determine eukaryotic species occurrences in the riverine ecosystem through the use of the eDNA analysis. The second goal was, based on the current dataset, to establish a metabarcoding eDNA data template that will be useful and replicable for all users, particularly the Taiwan community. The species occurrence data are accessible at the Global Biodiversity Information Facility (GBIF) portal and its associated DNA sequences have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI, respectively. A total of 12 water samples from the study yielded an average of 1.5 million reads. The subsequent species identification from the collected samples resulted in the classification of 432 Operational Taxonomic Units (OTUs) out of a total of 2,734. Furthermore, a total of 1,356 occurrences with taxon matches in GBIF were documented (excluding 4,941 incertae sedis, accessed 05-12-2023). These data will be of substantial importance for future species and habitat monitoring within the short river, such as assessment of biodiversity patterns across different elevations, zonations and time periods and its correlation to water quality, land uses and anthropogenic activities. Further, these datasets will be of importance for regional ecological studies, in particular the freshwater ecosystem and its status in the current global change scenarios. New information: The datasets are the first species diversity description of the Houdong River system using either eDNA or traditional monitoring processes.

Understanding the Mechanochemistry of Mechano-Radicals in Self-Growth Materials by Single-Molecule Force Spectroscopy.

Recent research on mechano-radicals has provided valuable insights into self-growth and adaptive responsive materials. Typically, mechanophores must remain inert in the absence of force but respond quickly to external tension before other linkages within the polymer network. Azo compounds exhibit promising combinations of mechanical stability and force-triggered reactivity, making them widely used as mechano-radicals in force-responsive materials. However, the activation conditions and behavior of azo compounds have yet to be quantitatively explored. In this study, we investigated the mechanical strength of three azo compounds using single-molecule force spectroscopy. Our results revealed that these compounds exhibit rupture forces ranging from ~500 to 1000 pN, at a loading rate of 3×104 pN s-1. Importantly, these mechanophores demonstrate distinct kinetic properties. Their unique mechanical attributes enable azo bond scission and free radical generation before causing major polymer backbone damage of entire material during polymer network deformation. This fundamental understanding of mechanophores holds significant promise for the development of self-growth materials and their related applications.

LRG1 promotes the apoptosis of pulmonary microvascular endothelial cells through KLK10 in chronic obstructive pulmonary disease.

INTRODUCTION: Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. METHODS: Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. RESULTS: LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. CONCLUSIONS: LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD.