SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye.

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

Electric field induced associations in the double layer of salt-in-ionic-liquid electrolytes.

Ionic liquids (ILs) are an extremely exciting class of electrolytes for energy storage applications. Upon dissolving alkali metal salts, such as Li or Na based salts, with the same anion as the IL, an intrinsically asymmetric electrolyte can be created for use in batteries, known as a salt-in-ionic liquid (SiIL). These SiILs have been well studied in the bulk, where negative transference numbers of the alkali metal cation have been observed from the formation of small, negatively charged clusters. The properties of these SiILs at electrified interfaces, however, have received little to no attention. Here, we develop a theory for the electrical double layer (EDL) of SiILs where we consistently account for the thermoreversible association of ions into Cayley tree aggregates. The theory predicts that the IL cations first populate the EDL at negative voltages, as they are not strongly bound to the anions. However, at large negative voltages, which are strong enough to break the alkali metal cation-anion associations, these IL cations are exchanged for the alkali metal cation because of their higher charge density. At positive voltages, we find that the SiIL actually becomes more aggregated while screening the electrode charge from the formation of large, negatively charged aggregates. Therefore, in contrast to conventional intuition of associations in the EDL, SiILs appear to become more associated in certain electric fields. We present these theoretical predictions to be verified by molecular dynamics simulations and experimental measurements.

Clinical practice of the transrectal shear-wave elastography in benign prostatic hyperplasia.

OBJECTIVE: To investigate the practical value of the transrectal two-dimensional shear-wave elastography (SWE) in benign prostatic hyperplasia (BPH). METHODS: Consecutive male participants with and without BPH constituted the BPH and control group respectively were enrolled prospectively between March and December 2022. Transrectal conventional ultrasound and SWE examinations for the prostate were performed on these participants. Data of quantitative stiffness of the transitional zone (TZ) and peripheral zone (PZ) of prostate, volume of prostate (VP) and volume of TZ (VTZ) and prostate specific androgen (PSA), etc., were collected. Linear regression analyses were used to investigate the associations between quantitative stiffness data and other clinical parameters. RESULTS: There were 200 participants evaluated, including 100 healthy participants and 100 BPH patients. For every one-year increment in age, it was correlated with 0.50 kPa increasement of TZ stiffness. VP and VTZ were correlated with TZ stiffness. Higher TZ stiffness was associated with higher free prostate specific antigen (PSA) and total PSA. CONCLUSIONS: The prostate is stiffer and larger in BPH group compared to control group. Quantitative stiffness of the TZ was related with age, VP, VTZ and PSA.

Highly Sensitive, Stable InP Quantum Dot Fluorescent Probes for Quantitative Immunoassay Through Nanostructure Tailoring and Biotin-Streptavidin Coupling.

Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.

Weight-adjusted waist index as a practical predictor for diabetes, cardiovascular disease, and non-accidental mortality risk.

BACKGROUND AND AIM: Identifying a more suitable marker among various measures of adiposity, demonstrating strong associations and predictive ability for clinical use, remains a topic of debate. Weight-adjusted waist index (WWI) has been proposed as a novel index of adiposity, yet its exploration is limited, especially in Chinese populations. This study seeks to examine the associations between body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHTR), weight-adjusted waist index (WWI), waist circumference divided by body mass to the power of 0.333 (WC/M0.333), visceral adiposity index (VAI), lipid accumulation product (LAP), and the incidence of diabetes, cardiovascular disease, and non-accidental mortality in Chinese populations. Furthermore, our goal is to compare the respective predictive values of these measures for these health outcomes. METHODS AND RESULTS: This prospective cohort study included 21,750 subjects with a 9-year follow-up period. Cox proportional hazard models were used to investigate the relationship between eight anthropometric indexes and the incidence of diabetes, cardiovascular disease, and non-accidental mortality. The predictive value of these eight indexes was compared using the area under the curve metric. Significant positive associations were found between WWI and the risk of diabetes. Using the first quartile (Q1) of WWI as the reference group, hazard ratios with 95% confidence intervals for the risk of diabetes were 1.58 (0.98-2.55) for Q2, 2.18 (1.34-3.35) for Q3, and 2.27 (1.41-3.67) for Q4. Significant associations were observed with the highest quartile of WWI for the risk of cardiovascular disease [Q2: HR 1.45 (95% CI 1.06-1.98); Q3: 1.33 (0.97-1.83); Q4: 1.55 (1.13-2.14)] and risk of non-accidental mortality [Q2: 0.94 (0.80-1.11); Q3: 1.24 (1.04-1.48); Q4: 1.44 (1.16-1.79)]. Receiver operating characteristic analysis revealed that WWI exhibited superior discrimination and accuracy in predicting cardiovascular disease and non-accidental mortality compared to other adiposity indexes (BMI, WC, WHR, WHTR, WC/M0.333, VAI, and LAP). CONCLUSION: WWI exhibited the most robust and consistent association with the incidence of cardiovascular disease and non-accidental mortality. Given its simplicity and widespread use, WWI emerges as a novel and practical predictor of diabetes, cardiovascular disease, and non-accidental mortality among the eight adiposity indexes investigated in this study.

Clinical comparative study of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones: a retrospective case-controlled study.

OBJECTIVES: To compare the clinical efficacy and safety of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones. METHODS: We enrolled 135 patients underwent reusable flexible ureteroscopy (FURS) and 78 patients underwent single-use digital FURS. Demographic, clinical variables, anatomical parameters of the lower calyx and perioperative indicators were compared in the two groups. RESULTS: Thirty-six patients in the infundibuloureter angle (IPA) < 45° subgroup had a mini-percutaneous nephrolithotomy (mini-PCNL), including 25 patients in the reusable FURS group and 11 patients in the single-use FURS group. The demographic and clinical variables in the two FURS groups were comparable. There was no statistical difference in the success rate of stone searching (P > 0.05). In terms of the success rate of lithotripsy, there was also no statistical difference in the IPA ≥ 45° subgroup (P > 0.05), whereas single-use FURS was superior in the IPA < 45° subgroup (χ2 = 6.513, P = 0.011). The length of the working fiber in the reusable FURS and single-use FURS groups was 3.20 ± 0.68 mm and 1.75 ± 0.47 mm, respectively (t = 18.297, P < 0.05). The use of a stone basket in the reusable FURS (31/135, 23.0%) was significantly higher than that in the single-use FURS (8/78, 10.3%) (χ2 = 5.336, P = 0.021). Compared with the reusable FURS group, the single-use FURS group had shorter operation times (P < 0.05) and higher stone-free rate (SFR) (χ2 = 4.230, P = 0.040). There was no statistical difference in the intraoperative transfer of mini-PCNL and postoperative complications between the two groups (P > 0.05). CONCLUSIONS: Single-use and reusable FURS are alternative methods for removal of lower pole stones (i.e., 2 cm or less). Single-use FURS has a high success rate of lithotripsy, shorter operation time, and high stone-free rate.

Cardiorespiratory fitness and metabolic risk in Chinese population: evidence from a prospective cohort study.

BACKGROUND: Studies on the association between estimated cardiorespiratory fitness (CRF) and changes in metabolic risk in the Chinese population are limited. This study aims to examine the associations between CRF and changes in metabolic risk. SUBJECTS AND METHODS: We included 4,862 and 2,700 participants recruited from 28 provinces in the China Health and Retirement Longitudinal Study (CHARLS) in the baseline (Wave 1) and follow-up (Wave 4) analyses, respectively. CRF was calculated using sex-specific longitudinal non-exercise equations. Metabolic indicators included systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose (FPG) levels. The metabolic score was calculated as the number of changes in the above metabolic indicators above the 75th percentile of the distribution of changes (equal to or below the 25th percentile for HDL-C). RESULTS: In the baseline analysis, CRF was negatively associated with SBP, DBP, TG, and FPG, and positively correlated with HDL-C after adjusting for age, smoking status, and drinking status (all P < 0.0001) in both males and females. In the follow-up analysis, higher baseline CRF was significantly related to a decrease in SBP, DBP, TG, FPG, and metabolic score (all P < 0.0005), and increased HDL-C (P < 0.0001) after further adjustment for corresponding baseline metabolic indicators. The associations remained significant after stratification by sex, except for the changes in HDL-C levels in females. Furthermore, improved CRF was associated with favorable changes in DBP, TG, HDL-C, FPG, and metabolic scores in all populations and males. Significant associations between changes in CRF and DBP, TG, and FPG levels were found in females. CONCLUSION: Higher baseline CRF and improved CRF were associated with favorable changes in metabolic indicators.

RCEAU-Net: Cascade Multi-Scale Convolution and Attention-Mechanism-Based Network for Laser Beam Target Image Segmentation with Complex Background in Coal Mine.

Accurate and reliable pose estimation of boom-type roadheaders is the key to the forming quality of the tunneling face in coal mines, which is of great importance to improve tunneling efficiency and ensure the safety of coal mine production. The multi-laser-beam target-based visual localization method is an effective way to realize accurate and reliable pose estimation of a roadheader body. However, the complex background interference in coal mines brings great challenges to the stable and accurate segmentation and extraction of laser beam features, which has become the main problem faced by the long-distance visual positioning method of underground equipment. In this paper, a semantic segmentation network for underground laser beams in coal mines, RCEAU-Net, is proposed based on U-Net. The network introduces residual connections in the convolution of the encoder and decoder parts, which effectively fuses the underlying feature information and improves the gradient circulation performance of the network. At the same time, by introducing cascade multi-scale convolution in the skipping connection section, which compensates for the lack of contextual semantic information in U-Net and improves the segmentation effect of the network model on tiny laser beams at long distance. Finally, the introduction of an efficient multi-scale attention module with cross-spatial learning in the encoder enhances the feature extraction capability of the network. Furthermore, the laser beam target dataset (LBTD) is constructed based on laser beam target images collected from several coal mines, and the proposed RCEAU-Net model is then tested and verified. The experimental results show that, compared with the original U-Net, RCEAU-Net can ensure the real-time performance of laser beam segmentation while increasing the Accuracy by 0.19%, Precision by 2.53%, Recall by 22.01%, and Intersection and Union Ratio by 8.48%, which can meet the requirements of multi-laser-beam feature segmentation and extraction under complex backgrounds in coal mines, so as to further ensure the accuracy and stability of long-distance visual positioning for boom-type roadheaders and ensure the safe production in the working face.

Self-truncated sampling produces more moderate covariation judgment and related decision than descriptive frequency information: The role of regressive frequency estimation.

Covariation judgment underlies a diversity of psychological theories and influences various everyday decisions. Information about covariation can be learned from either a summary description of frequencies (i.e., contingency tables) or trial-by-trial experience (i.e., sampling individual instances). Two studies were conducted to investigate the impact of information learning mode (i.e., description vs. self-truncated sampling) on covariation judgment and related decision. In each trial under the description condition, participants were presented with a contingency table with explicit cell frequencies, whereas in each trial under the self-truncated sampling condition, participants were allowed to determine when to stop sampling instances and thus the actual sample size. To eliminate sampling error, an other-yoked (i.e., between-subject) design was used in this research so that cell frequencies shown in a trial under the description condition were matched with those experienced in a trial under the self-truncated sampling condition. Experiment 1 showed that the self-truncated sampling condition led to more moderate covariation judgments than the description condition (i.e., a description-experience gap). Experiment 2 demonstrated further that the same gap extended to covariation-related decisions in terms of relative contingent preference (RCP). Regressive frequency estimation under self-truncated sampling appeared to underlie the consistent gaps found in the two studies, whereas the impact of regressive diagnosticity (i.e., the same sample of instances was viewed as less diagnostic under description than under self-truncated sampling) or simultaneous overestimation and underweighting of rare instances under experience was not supported by the observed data. Future research might examine alternative accounts of the observed gaps, such as the impacts of belief updating and stopping rule under self-truncated sampling.

pH responsive fabrication of PVA-stabilized selenium nano formulation encapsulated with luteolin to reduce diabetic ureteral injury by decreasing NLRP3 inflammasome via Nrf2/ARE signaling.

Diabetic ureteral injury (DUI) is a condition characterized by damage to the ureter, causing functional and morphological changes in the urinary system, which have a significant impact on a quality of life and requires appropriate medical treatment. The present study describes to novel design of luteolin (LT), a type of natural flavonoid, encapsulated selenium nanoparticles (Se NPs) to attain therapeutic potential for DUI. The physico-chemical characterizations of prepared Se NPs have benefitted zeta potential (-18 mV) and particle size (10-50 nm). In vitro assays were demonstrated the potential of LT-SeNPs by HEK 293 cells stimulated by STZ for DUI. Cytotoxicity assays on HEK 293 and NIH-3T3 showed >90% cell viability, which demonstrates the suitability of the nanoformulation for DUI treatment. The LT-SeNPs significantly inhibits the NLRP3 inflammasome through Nrf2/ARE pathway, which benefits for DUI treatment. The developed LT-SeNPs could be an effective formulation for the DUI therapy.

Effect of Multidirectional Forging and Aging Treatment on Wear Properties of ZK61 Alloy.

This study investigated the effects of multidirectional forging (MDF) and aging treatments on the wear properties of ZK61 magnesium alloy. Dry sliding wear tests were performed on homogenized, MDF, and aged samples using a friction wear machine to analyze the surface morphology by scanning electron microscopy (SEM) and white light interferometry, as well as the hardness and tensile mechanical properties. The ZK61 magnesium alloy has higher sliding wear properties after MDF due to higher strength, hardness, and work hardening. Grain refinement affects the wear resistance of the material, but aging increases the hardness and tensile strength and decreases the wear resistance.

Influence of Silane Coupling Agent and Anionic Dispersant on the Dispersion Effect of Silicon Carbide Particles.

Silicon carbide (SiC), as a widely used material, has great properties. To improve the flowability of ultrafine silicon carbide slurry, this study used sodium humate, tetramethylammonium hydroxide (TMAH), and N-(ß-monoaminoethyl)-γ-aminopropyltrimethyl(ethoxysilane) (KH792) to modify the ultrafine silicon carbide powder produced by Qingzhou Micro Powder Company. The effects of different modifiers on improving the flowability of ultrafine silicon carbide slurry were investigated by means of viscosity tests, sedimentation experiments, and SEM observations. Their modification mechanisms were investigated by means of zeta potential tests, XPS tests, and so on. In this paper, the initial modification of SiC was carried out with KH792, followed by the secondary modification with anionic and cationic modifiers (tetramethylammonium hydroxide and sodium humate), and the optimal modification conditions were investigated by means of a viscosity test, which showed that the lowest viscosity of the modified SiC reached 0.076 Pa·s and that the absolute maximum value of the zeta potential increased from 47.5 at the time of no modification to 63.7 (maximum values) at the time of modification. This means it has an improved surface charge, which improves dispersion. The adsorption results of the modifier on the silicon carbide surface were also demonstrated by the XPS test results.

Mutational and transcriptional profile predicts the prognosis of stage IV gastric cancer - Prognostic factors for metastatic gastric cancer.

BACKGROUND AND STUDY AIMS: The clinicopathological risk factors in the prognosis of stage IV gastric cancer have been comprehensively studied. However, the influencing factors of stage IV gastric cancer prognosis at genomic and transcriptional levels have not been well defined. PATIENTS AND METHODS: The mutational and transcriptional data, along with demographic, clinicopathological and prognostic information of 44 stage IV gastric cancer patients were downloaded from the TCGA database. Univariate and multivariate analyses were performed to identify the significant risk factors and a Nomogram model was established to predict the patient prognosis. RESULTS: TTN, TP53, FLG, LRP1B, SYNE1 and ARID1A were among the top mutated genes without hot-spot mutations. The mutational status of AHNAK2, ASCC3, DNAH3, DOP1A, MYLK, SIPA1L1, SORBS2, SYNE1 and ANF462 significantly stratified the patient prognosis. The transcription of several genes, such as AQP10, HOXC8/9/10, COL10A1/COL11A1, WNT7B, KRT17 and KLK6 was significantly up-regulated or down-regulated. Enrichment analysis on mutations and transcription revealed cell skeleton and membrane function, extracellular matrix function, HPV infection, and several cancer-related pathways as the main aberrancies. Univariate analyses revealed a series of significant factors stratifying patient prognosis, mainly including cancer location, several mutated genes and many up- or down-regulated genes. However, subsequent multivariate analysis revealed SYNE1 mutation, DNAH3 mutation, COMMD3 transcription level, and cancer location as the independent risk factors. A Nomogram model has been established with these significant risk factors to predict the patient prognosis. Further validation is needed to ensure the effectiveness of the model in real clinical practice. CONCLUSIONS: Cancer location, along with the mutational status of SYNE1 and DNAH3 and the transcriptional level of COMMD3 were independent risk factors of stage IV gastric cancer. A Nomogram model was established with these factors for prognosis prediction.

Case report: Prostatic malakoplakia: a rare disease that has a profile mimicking prostate cancer.

Prostatic malakoplakia (PMP) is a rare inflammatory disease, and misdiagnosis on imaging is a major reason for unnecessary punctures; however, information on imaging is even rarer. Five patients with PMP between May 2022 and February 2023 were enrolled in this study to summarize the imaging manifestations. All patients underwent ultrasound (US)-guided prostate biopsy and were confirmed by pathology, and the presence of prostate cancer was also excluded by pathology. The five patients, with a median age of 71 years (range = 58-74 years), had a median total prostate-specific antigen (T-PSA) of 10.40 ng/mL (range = 1.74-63.42 ng/mL). In two patients, chest computed tomography showed pulmonary infections. All patients underwent magnetic resonance imaging (MRI). Of these patients, four had a Prostate Imaging-Reporting and Data System (PIRADS) score of 5, while one had a score of 4. The lesions were mostly distributed in the peripheral zone of the prostate and appeared as a high signal on T1-weighted imaging (T1WI) and a low signal on T2-weighted imaging (T2WI). In the US examination, four patients had abnormal prostate morphology, with an unsmooth envelope and non-uniform parenchymal echogenicity. Four patients had increased prostate volume. US showed a hypoechoic nodule with non-uniform internal echogenicity, and an abundant internal blood flow signal was detected by color Doppler US. PSA, MRI, and US were not specific for PMP in our study, but we found that a history of co-infection may be helpful in an accurate diagnosis and to avoid unnecessary biopsy.

Soft-hard dual nanophases: a facile strategy for polymer strengthening and toughening.

Polymers often face a trade-off between stiffness and extensibility-for example, toughening rigid polymers by incorporating plasticizers or flexible polymers leads to strikingly decreased stiffness. Herein, we circumvent this long-standing tricky dilemma in materials science via constructing soft-hard dual nanophases in polymers. As-fabricated dual-nanophase PLA shows a high yield strength of 69.1 ± 4.4 MPa, a large extensibility of 279.1 ± 25.5%, and a super toughness of 115.2 ± 10.3 MJ m-3, which are 1.2, 48 and 82 times, respectively, those of neat PLA. Combined high stiffness, large ductility, and super toughness are unprecedented for PLA and enable bio-sourced PLA to replace petroleum-based resins such as PP, PET and PC. Besides, soft-hard dual nanophases in polymers are rarely reported due to significant constraints in terms of modifier dispersion/aggregation, interfacial regulation, and processing difficulties. The construction strategy described herein, combining controlled annealing and a well-designed plasticizer, can efficiently construct soft-hard dual nanophases in polymers, which will greatly advance the nanostructure design of polymers. More importantly, the proposed strategy for materials design will be widely applicable to industrial manufacturing in terms of nanophase construction and interfacial optimization due to the simplicity and availability at a large scale. We envision that this work offers an innovative and facile strategy to circumvent the trade-off between stiffness and extensibility and to advance the nanostructure design of high-performance polymers in a manner applicable to industrial manufacturing.

Healthy lifestyle decreases the risk of the first incidence of non-communicable chronic disease and its progression to multimorbidity and its mediating roles of metabolic components: a prospective cohort study in China.

OBJECTIVES: To identify the influence of healthy lifestyles on the incidence of the first NCD (FNCD), multiple chronic conditions (MCCs), and the progression from FNCD to MCCs. DESIGN: cohort study. SETTING: Zhejiang, China PARTICIPANTS: 10566 subjects (55.5 ± 13.5 years, 43.1% male) free of NCDs at baseline from the Zhejiang Metabolic Syndrome prospective cohort. MEASUREMENTS: Healthy lifestyle score (HLS) was developed by 6 common healthy lifestyle factors as smoking, alcohol drinking, physical activity, body mass index (BMI) and waist-to-hip ratio (WHR). Healthy lifestyle data and metabolic biomarkers collected via a face-to-face questionnaire-based interview, clinical health examination and routine biochemical determination. Biochemical variables were determined using biochemical auto-analyzer. Participants were stratified into four group based on the levels of HLS as ≤2, 3, 4 and ≥5. Multiple Cox proportional hazards model was applied to examine the relationship between HLS and the risk of FNCD, MCCs and the progression from FNCD to MCCs. The population-attributable fractions (PAF) were used to assess the attributable role of HLS. Mediating effect was examined by mediation package in R. RESULTS: After a median of 9.92 years of follow-up, 1572 participants (14.9%) developed FNCD, and 149 (1.4%) developed MCCs. In the fully adjusted model, the higher HLS group (≥5) was associated with lower risk of FNCD (HR = 0.68 and 95% CI: 0.56-0.82), MCCs (HR = 0.31 and 95%CI: 0.14-0.69); and the progression from FNCD to MCCs (HR = 0.39 and 95%CI: 0.18-0.85). Metabolic components (TC, TG, HDL-C, LDC-C, FPG, and UA) played the mediating roles with the proportion ranging from 5.02% to 22.2% for FNCD and 5.94% to 20.1% for MCCs. PAFs (95%CI) for poor adherence to the overall healthy lifestyle (HLS ≤ 3) were 17.5% (11.2%, 23.7%) for FNCD, 42.9% (23.4%, 61.0%) for MCCs, and 37.0% (15.5%, 56.3%) for the progression from FNCD to MCCs. CONCLUSIONS: High HLS decreases the risk of FNCD, MCCs, and the progression from FNCD to MCCs. These effects are partially mediated by metabolic components. Maintaining healthy lifestyles might reduce the disease burden of common chronic diseases.

Developing Plant Exosomes as an Advanced Delivery System for Cosmetic Peptide.

Peptides are a promising skincare ingredient, but due to their inherent instability and the barrier function of the skin's surface, they often have limited skin absorption and penetration, which can significantly hinder their skincare benefits. To address this, a novel technique called NanoGlow has been introduced for encapsulating peptide-based cosmetic raw materials into engineered nanosized plant-derived exosomes (pExo) to achieve the goal of a healthier and more radiant skin state. In this approach, pExo served as carriers for cosmetic peptides across the intact skin barrier, enhancing their biological effectiveness in skin beauty. The NanoGlow strategy combines chemical activation and physical proencapsulation, boasting a high success rate and straightforward and stable operation, making it suitable for large-scale production. Comprehensive analysis using in vitro cellular absorption and skin penetration models has demonstrated that the nanosized pExo carriers significantly improve peptide penetration into the skin compared to free peptides. Furthermore, in vivo tissue slice studies have shown that pExo carriers efficiently deliver acetyl hexapeptide-8 to the skin's dermis, surpassing the performance of free peptides. Cosmetic skincare effect analysis has also indicated that pExo-loaded cosmetic peptides deliver superior results. Therefore, the NanoGlow technique harnesses the natural size and properties of pExo to maximize the bioavailability of cosmetic peptides, holding great promise for developing advanced peptide delivery systems in both the cosmetic and medical drug industries.

The mechanism of gut-lung axis in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a terminal change of a lung disease that is marked by damage to alveolar epithelial cells, abnormal proliferative transformation of fibroblasts, excessive deposition of extracellular matrix (ECM), and concomitant inflammatory damage. Its characteristics include short median survival, high mortality rate, and limited treatment effectiveness. More in-depth studies on the mechanisms of PF are needed to provide better treatment options. The idea of the gut-lung axis has emerged as a result of comprehensive investigations into the microbiome, metabolome, and immune system. This theory is based on the material basis of microorganisms and their metabolites, while the gut-lung circulatory system and the shared mucosal immune system act as the connectors that facilitate the interplay between the gastrointestinal and respiratory systems. The emergence of a new view of the gut-lung axis is complementary and cross-cutting to the study of the mechanisms involved in PF and provides new ideas for its treatment. This article reviews the mechanisms involved in PF, the gut-lung axis theory, and the correlation between the two. Exploring the gut-lung axis mechanism and treatments related to PF from the perspectives of microorganisms, microbial metabolites, and the immune system. The study of the gut-lung axis and PF is still in its early stages. This review systematically summarizes the mechanisms of PF related to the gut-lung axis, providing ideas for subsequent research and treatment of related mechanisms.

UV-Mediated Facile Fabrication of a Robust, Fully Renewable and Controllably Biodegradable Poly(lactic acid)-Based Covalent Adaptable Network.

A robust and fully biobased covalent adaptable network (CAN) that allows recyclability, biocompatibility, and controlled biodegradability is reported. The CAN was fabricated through a simple photo-cross-linking method, wherein low-molecular-weight poly(lactic acid) (∼3 kDa) was modified with end 1,2-dithiolane rings through a one-step Steglich esterification reaction with thioctic acid (TA). These incorporated 1,2-dithiolane rings undergo photoinduced ring-opening polymerization, thus enabling the cross-linking of poly(lactic acid) with abundant dynamic disulfide bonds. The resultant CAN demonstrates excellent transparency, effective UV-blocking capabilities below 320 nm, robust tensile strength (∼39 MPa), and superior dimensional stability at 80 °C, alongside attractive biocompatibility. Moreover, owing to the dynamic exchange and redox-responsiveness of disulfide bonds, the material can be recycled by hot-pressing and a reduction-oxidation process while also being capable of controllably biodegrading at the end of its lifecycle. Furthermore, it exhibits reconfigurable shape memory properties with fast recovery. This study elucidates a straightforward approach to fabricating multifunctional and sustainable polymer materials with potential applications in diverse fields such as packaging, coating, and biomedicine.