Post-procedural elevated cardiac troponin I and the association with 5-year mortality in patients undergoing elective PCI.

Background: The clinically meaningful cardiac troponin I (cTnI) threshold associated with the long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective: To assess the association between different thresholds for post-procedural cTnI and 5-year mortality. Methods: The study included 4059 consecutive patients with normal baseline cTnI values who underwent elective PCI. The post-procedural cTnI level was measured at 8-48 h after PCI. The main study endpoints were 5-year all-cause mortality and cardiovascular mortality. Results: A cTnI ≥5 times the upper reference limit (URL) as defined by the fourth universal definition of myocardial infarction (4th UDMI), ≥35 times as defined by the Academic Research Consortium-2 criteria, and ≥70 times as defined by the Society for Cardiovascular Angiography and Interventions (SCAI [2014]) was identified in 33%, 6.6%, and 3.3% of patients, respectively. During 5 years of follow-up, the all-cause mortality rate was 3.4% (n = 132) and the cardiovascular mortality rate was 2.0% (n = 77). Both all-cause mortality and cardiovascular mortality increased with higher peak cTnI, and were independently predicted by a cTnI ≥70 times the URL (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.20-5.02 and adjusted HR 3.17, 95% CI 1.31-7.67, respectively; reference, cTnI <1 × URL]. The SCAI (2014) threshold was significantly associated with 5-year cardiovascular mortality (adjusted HR 2.66, 95% CI 1.20-5.89; reference, cTnI, <70 × URL) and all-cause mortality (adjusted HR 2.23, 95% CI 1.16-4.30; reference, cTnI <70 × URL). Conclusion: In patients with normal pre-procedural cTnI who underwent elective PCI, a post-procedural cTnI ≥70 times the URL independently predicted 5-year all-cause and cardiovascular mortality. Therefore, only the SCAI (2014) post-procedural cTnI threshold was independently associated with long-term mortality.

Selenomethionine preconditioned mesenchymal stem cells derived extracellular vesicles exert enhanced therapeutic efficacy in intervertebral disc degeneration.

Extracellular vesicles (EVs) derived from Mesenchymal Stromal Cells (MSCs) have shown promising therapeutic potential for multiple diseases, including intervertebral disc degeneration (IDD). Nevertheless, the limited production and unstable quality of EVs hindered the clinical application of EVs in IDD. Selenomethionine (Se-Met), the major form of organic selenium present in the cereal diet, showed various beneficial effects, including antioxidant, immunomodulatory and anti-apoptotic effects. In the current study, Se-Met was employed to treat MSCs to investigate whether Se-Met can facilitate the secretion of EVs by MSCs and optimize their therapeutic effects on IDD. On the one hand, Se-Met promoted the production of EVs by enhancing the autophagy activity of MSCs. On the other hand, Se-Met pretreated MSC-derived EVs (Se-EVs) exhibited an enhanced protective effects on alleviating nucleus pulposus cells (NPCs) senescence and attenuating IDD compared with EVs isolated from control MSCs (C-EVs) in vitro and in vivo. Moreover, we performed a miRNA microarray sequencing analysis on EVs to explore the potential mechanism of the protective effects of EVs. The result indicated that miR-125a-5p is markedly enriched in Se-EVs compared to C-EVs. Further in vitro and in vivo experiments revealed that knockdown of miR-125a-5p in Se-EVs (miRKD-Se-EVs) impeded the protective effects of Se-EVs, while overexpression of miR-125a-5p (miROE-Se-EVs) boosted the protective effects. In conclusion, Se-Met facilitated the MSC-derived EVs production and increased miR-125a-5p delivery in Se-EVs, thereby improving the protective effects of MSC-derived EVs on alleviating NPCs senescence and attenuating IDD.

An ecological resilience model for adolescents with type 1 diabetes: a cross-sectional study.

BACKGROUND: Highly resilient adolescents with type 1 diabetes have been proved to achieve within-target glycemic outcomes and experience high quality of life. The ecological resilience model for adolescents with type 1 diabetes was developed in this study. It aims to increase our understanding of how resilience is both positively and negatively affected by internal and environmental ecological factors. METHODS: This cross-sectional study surveyed 460 adolescents with type 1 diabetes from 36 cities in 11 provinces, China. Participants completed self-report questionnaires on resilience, family functioning, peer support, peer stress, coping style, and demographics. Standard glycated hemoglobin tests were performed on the adolescents. Structural equation modeling was applied to analyze the data. RESULTS: The ecological resilience model for adolescents with type 1 diabetes was a good model with a high level of variance in resilience (62%). Family functioning was the most important predictor of resilience, followed by peer support, positive coping, and peer stress. Moreover, positive coping was the mediator of the relationship between family functioning and resilience. Positive coping and peer stress co-mediated the association between peer support and resilience. CONCLUSIONS: Family functioning, peer relationships, and positive coping are interrelated, which may jointly influence resilience. The findings provide a theoretical basis for developing resilience-promotion interventions for adolescents with type 1 diabetes, which may lead to health improvements during a vulnerable developmental period.

The role of peer social relationships in psychological distress and quality of life among adolescents with type 1 diabetes mellitus: a longitudinal study.

BACKGROUND: Adolescents with type 1 diabetes mellitus suffer from diabetes distress and poor health-related quality of life (HRQOL) since living with the condition that differentiates them from their peers. The present study investigated the effects of peer support and stress on diabetes distress and HRQOL and whether positive coping mediated the effects. METHODS: We used a prospective study design. A total of 201 adolescents with type 1 diabetes mellitus from 20 cities in 4 provinces were recruited.Participants complete two separate surveys at approximately 18-month intervals. The scales employed at both Time 1 and Time 2 included the Diabetes-Specific Peer Support Measure, Diabetes Stress Questionnaire for Youths, Simplified Coping Style Questionnaire, 5-item Problem Areas in Diabetes Scale, and the Diabetes Quality of Life for Youth scale. RESULTS: Baseline peer stress directly predicted diabetes distress and HRQOL at 18 months, even controlling for age, gender, and peer support. However, the direct effect of baseline peer support on 18-month diabetes distress and HRQOL was insignificant. Baseline peer support indirectly affected diabetes distress and HRQOL at 18 months through positive coping, indicating that positive coping plays a mediating role. CONCLUSION: The findings suggest that peer social relationships, especially peer stress, and positive coping are promising intervention targets for adolescents facing challenges in psychosocial adaptation.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Tailor-made molecular imprints for biological event intervention.

Molecular imprints, which are crosslinked architectures containing specific molecular recognition cavities for targeting compounds, have recently transitioned from in vitro diagnosis to in vivo treatment. In current application scenarios, it has become an important topic to create new biomolecular recognition pathways through molecular imprinting, thereby inhibiting the pathogenesis and regulating the development of diseases. This review starts with a pathological analysis, mainly focusing on the corresponding artificial enzymes, enzyme inhibitors and antibody mimics with enhanced functions that are created by molecular imprinting strategies. Recent advances are highlighted in the use of molecular imprints as tailor-made nanomedicines for the prevention of three major diseases: metabolic syndrome, cancer, and bacterial/viral infections.

Influence of Cation-Size Effects of Alkaline Earth (Ae) Metals on Dimensionality and Optical Anisotropy Regulation in K4AeP2S8 Thiophosphates.

Cationic substitution demonstrates significant potential for regulating structural dimensionality and physicochemical performance owing to the cation-size effect. Leveraging this characteristic, this study synthesized a new family of K4AeP2S8 (Ae = alkaline earth elements: Mg, Ca, Sr, and Ba) thiophosphates, involving the substitution of Ae2+ cations. The synthesized compounds crystallized in distinct space groups, monoclinic P2/c (Ae = Mg) versus orthorhombic Ibam (Ae = Ca, Sr, and Ba), exhibiting intriguing dimensionality transformations from zero-dimensional (0D) [Mg2P4S16]8- clusters in K4MgP2S8 to 1D ∞[AeP2S8]4- chains in other K4AeP2S8 thiophosphates owing to the varying ionic radii of Ae2+ cations, Ae-S bond lengths, and coordination numbers of AeSn (Mg: n = 6 versus other: n = 8). Experimental investigations revealed that K4AeP2S8 thiophosphates featured wide optical bandgaps (3.37-3.64 eV), and their optical absorptions were predominantly influenced by the S 3p and P 3s orbitals, with negligible contributions from the K and Ae cations. Notably, within the K4AeP2S8 series, birefringence (Δn) increased from K4MgP2S8 (Δn = 0.034) to other K4AeP2S8 (Δn = 0.050-0.079) compounds, suggesting that infinite 1D chains more significantly influence Δn origins than 0D clusters, thus offering a feasible approach for enhancing optical anisotropy and exploring potential new birefringent materials.

Central Chirality and Axial Chirality Recognition of the Enantioselective Antibodies to Herbicide Metolachlor.

Enantioselective antibodies have emerged as efficient tools in the field of chiral chemical detection and separation. However, it is complicated to obtain a highly stereoselective antibody due to the unclear recognition mechanism. In this study, the hapten of metolachlor was synthesized and enantio-separated. The absolute configuration of the four haptens obtained was identified by the computed and experimental electronic circular dichroism comparison. Five polyclonal antibodies against the Rac-metolachlor and its enantiomers were generated by immunization. The cross-activity of all the 5 antibodies with 44 structural analogues, including metolachlor enantiomers, was tested. It demonstrated that antibodies have higher specificity to recognize central chirality than axial chirality. Especially, αRR-MET-Ab exhibited excellent specificity and stereoselectivity. Accordingly, 3D-QSAR models were constructed and revealed that paired stereoisomers exhibited opposite interactions with the antibodies. It is the first time that the antibodies against four stereoisomers were prepared and analyzed, which will be conducive to the rational design of the stereoselective antibodies.

Effect of arbuscular mycorrhizal symbiosis on growth and biochemical characteristics of Chinese fir (Cunninghamia lanceolata) seedlings under low phosphorus environment.

Background: The continuous establishment of Chinese fir (Cunninghamia lanceolata) plantations across multiple generations has led to the limited impact of soil phosphorus (P) on tree growth. This challenge poses a significant obstacle in maintaining the sustainable management of Chinese fir. Methods: To investigate the effects of Arbuscular mycorrhizal fungi (AMF) on the growth and physiological characteristics of Chinese fir under different P supply treatments. We conducted an indoor pot simulation experiment in the greenhouse of the Forestry College of Fujian Agriculture and Forestry University with one-and-half-year-old seedlings of Chinese fir from March 2019 to June 2019, with the two P level treatment groups included a normal P supply treatment (1.0 mmol L-1 KH2PO4, P1) and a no P supply treatment (0 mmol L-1 KH2PO4, P0). P0 and P1 were inoculated with Funneliformis mosseae (F.m) or Rhizophagus intraradices (R.i) or not inoculated with AMF treatment. The AMF colonization rate in the root system, seedling height (SH), root collar diameter (RCD) growth, chlorophyll (Chl) photosynthetic characteristics, enzyme activities, and endogenous hormone contents of Chinese fir were estimated. Results: The results showed that the colonization rate of F.m in the roots of Chinese fir seedlings was the highest at P0, up to 85.14%, which was 1.66 times that of P1. Under P0 and P1 treatment, root inoculation with either F.m or R.i promoted SH growth, the SH of R.i treatment was 1.38 times and 1.05 times that of F.m treatment, respectively. In the P1 treatment, root inoculation with either F.m or R.i inhibited RCD growth. R.i inhibited RCD growth more aggressively than F.m. In the P0 treatment, root inoculation with F.m and R.i reduced the inhibitory effect of phosphorus deficiency on RCD. At this time, there was no significant difference in RCD between F.m, R.i and CK treatments (p < 0.05). AMF inoculation increased Fm, Fv, Fv/Fm, and Fv/Fo during the chlorophyll fluorescence response in the tested Chinese fir seedlings. Under the two phosphorus supply levels, the trend of Fv and Fm of Chinese fir seedlings in different treatment groups was F.m > R.i > CK. Under P0 treatment, The values of Fv were 235.86, 221.86 and 147.71, respectively. The values of Fm were 287.57, 275.71 and 201.57, respectively. It increased the antioxidant enzyme activity and reduced the leaf's malondialdehyde (MDA) content to a certain extent. Conclusion: It is concluded that AMF can enhance the photosynthetic capacity of the host, regulate the distribution of endogenous hormones in plants, and promote plant growth by increasing the activity of antioxidant enzymes. When the P supply is insufficient, AMF is more helpful to plants, and R.i is more effective than F.m in alleviating P starvation stress in Chinese fir.

Preoperative differentiation of gastric schwannomas and gastrointestinal stromal tumors based on computed tomography: a retrospective multicenter observational study.

Introduction: Gastric schwannoma is a rare benign tumor accounting for only 1-2% of alimentary tract mesenchymal tumors. Owing to their low incidence rate, most cases are misdiagnosed as gastrointestinal stromal tumors (GISTs), especially tumors with a diameter of less than 5 cm. Therefore, this study aimed to develop and validate a diagnostic nomogram based on computed tomography (CT) imaging features for the preoperative prediction of gastric schwannomas and GISTs (diameters = 2-5 cm). Methods: Gastric schwannomas in 47 patients and GISTs in 230 patients were confirmed by surgical pathology. Thirty-four patients with gastric schwannomas and 167 with GISTs admitted between June 2009 and August 2022 at Hospital 1 were retrospectively analyzed as the test and training sets, respectively. Seventy-six patients (13 with gastric schwannomas and 63 with GISTs) were included in the external validation set (June 2017 to September 2022 at Hospital 2). The independent factors for differentiating gastric schwannomas from GISTs were obtained by multivariate logistic regression analysis, and a corresponding nomogram model was established. The accuracy of the nomogram was evaluated using receiver operating characteristic and calibration curves. Results: Logistic regression analysis showed that the growth pattern (odds ratio [OR] 3.626; 95% confidence interval [CI] 1.105-11.900), absence of necrosis (OR 4.752; 95% CI 1.464-15.424), presence of tumor-associated lymph nodes (OR 23.978; 95% CI 6.499-88.466), the difference between CT values during the portal and arterial phases (OR 1.117; 95% CI 1.042-1.198), and the difference between CT values during the delayed and portal phases (OR 1.159; 95% CI 1.080-1.245) were independent factors in differentiating gastric schwannoma from GIST. The resulting individualized prediction nomogram showed good discrimination in the training (area under the curve [AUC], 0.937; 95% CI, 0.900-0.973) and validation (AUC, 0.921; 95% CI, 0.830-1.000) datasets. The calibration curve showed that the probability of gastric schwannomas predicted using the nomogram agreed well with the actual value. Conclusion: The proposed nomogram model based on CT imaging features can be used to differentiate gastric schwannoma from GIST before surgery.

Exploring the impact of college graduates' place attachment on entrepreneurial intention upon returning to hometowns: A study based on the theory of planned behavior.

The issue of the continuing decline of rural areas caused by urbanization has become a global concern. Encouraging college graduates to return to their hometowns to start businesses is an important initiative for countries to achieve sustainable rural development. Drawing from the Theory of Planned Behavior (TPB), this study introduces two additional variables: place attachment and entrepreneurial self-efficacy. Through a series of three model refinements, a comprehensive theoretical framework has been formulated to elucidate Chinese college graduates' hometown-based entrepreneurial intention and behavior. The samples for this study were 1151 college graduates selected from diverse universities across China. This study aims to explore the influence of college graduates' hometown-based entrepreneurial intention using Structural Equation Modelling. This analytical approach illuminates how variables such as college graduates' place attachment, entrepreneurial self-efficacy, subjective norm for hometown-based entrepreneurship, and attitude towards hometown-based entrepreneurship affected their hometown-based entrepreneurial intention. The research findings reveal the following insights: (1) The overall levels of college graduates' place attachment and hometown-based entrepreneurial intention were relatively low. (2) College graduates' place attachment, entrepreneurial self-efficacy, subjective norm for hometown-based entrepreneurship, and attitude towards hometown-based entrepreneurship, had a positive impact on their hometown-based entrepreneurial intention. (3) College graduates' place attachment and subjective norm for hometown-based entrepreneurship had a significant impact on their hometown-based entrepreneurial intention through the mediating variable of entrepreneurial self-efficacy. This study then makes policy recommendations from theoretical and managerial aspects.

Identification of HK3 as a promising immunomodulatory and prognostic target in sepsis-induced acute lung injury.

BACKGROUND: Sepsis is a life-threatening global disease with a significant impact on human health. Acute lung injury (ALI) has been identified as one of the primary causes of mortality in septic patients. This study aimed to identify candidate genes involved in sepsis-induced ALI through a comprehensive approach combining bioinformatics analysis and experimental validation. METHODS: The datasets GSE65682 and GSE32707 obtained from the Gene Expression Omnibus database were merged to screen for sepsis-induced ALI related differentially expressed genes (DEGs). Functional enrichment and immune infiltration analyses were conducted on DGEs, with the construction of protein-protein interaction (PPI) networks to identify hub genes. In vitro and in vivo models of sepsis-induced ALI were used to study the expression and function of hexokinase 3 (HK3) using various techniques including Western blot, real-time PCR, immunohistochemistry, immunofluorescence, Cell Counting Kit-8, Enzyme-linked immunosorbent assay, and flow cytometry. RESULTS: The results of bioinformatics analysis have identified HK3, MMP9, and S100A8 as hub genes with diagnostic and prognostic significance for sepsis-induced ALI. The HK3 has profound effects on sepsis-induced ALI and exhibits a correlation with immune regulation. Experimental results showed increased HK3 expression in lung tissue of septic mice, particularly in bronchial and alveolar epithelial cells. In vitro studies demonstrated upregulation of HK3 in lipopolysaccharide (LPS)-stimulated lung epithelial cells, with cytoplasmic localization around the nucleus. Interestingly, following the knockdown of HK3 expression, lung epithelial cells exhibited a significant decrease in proliferation activity and glycolytic flux, accompanied by an increase in cellular inflammatory response, oxidative stress, and cell apoptosis. CONCLUSIONS: It was observed for the first time that HK3 plays a crucial role in the progression of sepsis-induced ALI and may be a valuable target for immunomodulation and therapy.Bioinformatics analysis identified HK3, MMP9, and S100A8 as hub genes with diagnostic and prognostic relevance in sepsis-induced ALI. Experimental findings showed increased HK3 expression in the lung tissue of septic mice, particularly in bronchial and alveolar epithelial cells. In vitro experiments demonstrated increased HK3 levels in lung epithelial cells stimulated with LPS, with cytoplasmic localization near the nucleus. Knockdown of HK3 expression resulted in decreased proliferation activity and glycolytic flux, increased inflammatory response, oxidative stress, and cell apoptosis in lung epithelial cells.

Interlayer sp3 Bonds and Chirality at Bilayer Graphene Oxide/Calcium Silicate Hydrate Abnormally Enhance Its Interlayer Stress Transfer.

Graphene oxide (GO) is an ideal reinforcing material with super design capability, which can achieve the combination of strength and toughness. However, the actual effect of GO is far below the theoretical prediction. This is mainly due to the weak interface between the nanofiller and the matrix. In this paper, a controllable method for improving interlayer stress transfer of double-layer graphene oxide/C-S-H (D-GO-CSH)-layered nanostructures is proposed by using interlayer sp3 bond and chirality. The results show that, compared with the control group, the normalized shear stress and normalized pull-out energy of the OH-sp3 model are increased by 44.93 and 49.25%, respectively, while those of the OO-sp3 model are increased by 32.26 and 31.03%, respectively. The interlayer sp3 bonds lead to a great enhancement (more than 3 times) in normalized interlayer stress transfer of D-GO-CSH-layered nanostructures while exerting a little opposite effect (about 5%). The improvement effects induced by the interlayer sp3 bonds are also strongly dependent on their distributions and the chirality of GO. According to the fracture mechanic theory and molecular dynamics results, the strain energy percentage difference (bond length and bond angle) of the zigzag-cen model is 34.8% lower than that of the control group model, which proves that the interlayer sp3 bonds have a remarkably positive effect on the interlayer stress transfer of D-GO-CSH-layered nanostructures. This provides a new way to further improve the interlayer stress transfer, pull-out energy, and interlayer shear stress of D-GO-CSH-layered nanostructures.

Vitamin E biofortification: enhancement of seed tocopherol concentrations by altered chlorophyll metabolism.

Homogentisate Phytyltransferase (HPT) catalyzes condensation of homogentisate (HGA) and phytyl diphosphate (PDP) to produce tocopherols, but can also synthesize tocotrienols using geranylgeranyl diphosphate (GGDP) in plants engineered for deregulated HGA synthesis. In contrast to prior tocotrienol biofortification efforts, engineering enhanced tocopherol concentrations in green oilseeds has proven more challenging due to the integral role of chlorophyll metabolism in supplying the PDP substrate. This study show that RNAi suppression of CHLSYN coupled with HPT overexpression increases tocopherol concentrations by >two-fold in Arabidopsis seeds. We obtained additional increases in seed tocopherol concentrations by engineering increased HGA production via overexpression of bacterial TyrA that encodes chorismate mutase/prephenate dehydrogenase activities. In overexpression lines, seed tocopherol concentrations increased nearly three-fold, and resulted in modest tocotrienol accumulation. We further increased total tocochromanol concentrations by enhancing production of HGA and GGDP by overexpression of the gene for hydroxyphenylpyruvate dioxygenase (HPPD). This shifted metabolism towards increased amounts of tocotrienols relative to tocopherols, which was reflected in corresponding increases in ratios of GGDP/PDP in these seeds. Overall, our results provide a theoretical basis for genetic improvement of total tocopherol concentrations in green oilseeds (e.g., rapeseed, soybean) through strategies that include seed-suppression of CHLSYN coupled with increased HGA production.

The application of encapsulation technology in the food Industry: Classifications, recent Advances, and perspectives.

Encapsulation technology has been extensively used to enhance the stability, specificity, and bioavailability of essential food ingredients. Additionally, it plays a vital role in improving product quality and reducing production costs. This study presents a comprehensive classification of encapsulation techniques based on the state of different cores (solid, liquid, and gaseous) and offers a detailed description and analysis of these encapsulation methods. Specifically, it introduces the diverse applications of encapsulation technology in food, encompassing areas such as antioxidant, protein activity, physical stability, controlled release, delivery, antibacterial, and probiotics. The potential impact of encapsulation technology is expected to make encapsulation technology a major process and research hotspot in the food industry. Future research directions include applications of encapsulation for enzymes, microencapsulation of biosensors, and novel technologies such as self-assembly. This study provides a valuable theoretical reference for the in-depth research and wide application of encapsulation technology in the food industry.

Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

Contradictions in human-nature relationships threaten coastal resilience and sustainability in the Bohai Rim Region, China.

Under the challenge of global environmental change and rapid development, tremendous risks brought about by natural disasters and human activities have increased environmental pressures for sustainable development. How to improve coastal resilience in the process of urban development has become an important topic in academia. In this study, a variable fuzzy recognition model was used to measure the level of coastal resilience in 17 cities in the Bohai Rim region, and then the kernel density, thiel index, and random forest model were used to explore the spatiotemporal characteristics and influencing factors of coastal resilience. The results show that (1) The overall resilience level of the Bohai Rim region is increasing over time, but at a relatively slow rate. (2) Coastal resilience has significant spatial unevenness, with high-level cities dominated by Tianjin, Qingdao, Yantai, etc. and low-level cities dominated by Cangzhou, Panjin, Yingkou, Binzhou, etc. (3) The influence of economic development, infrastructure, innovation ability, technology investment, and government regulation on coastal resilience decreases in order. Based on the research findings, the study can not only make suggestions for the actual regulation strategy but also provide empirical and theoretical experience for other coastal countries.

MRI Manifestations of Breast Cancer Stroma and their Role in Predicting Molecular Subtype: A Case-control Study.

OBJECTIVE: This study explored whether breast MRI manifestations could be used to predict the stroma distribution of breast cancer (BC) and the role of tumor stroma-based MRI manifestations in molecular subtype prediction. METHODS: 57 patients with pathologically confirmed invasive BC (non-special type) who had lumpy BC on MRI within one week before surgery were retrospectively collected in the study. Stroma distributions were classified according to their characteristics in the pathological sections. The stromal distribution patterns among molecular subtypes were compared with the MRI manifestations of BC with different stroma distribution types (SDTs). RESULTS: SDTs were significantly different and depended on the BC hormone receptor (HR) (P<0.001). There were also significant differences among five SDTs on T2WI, ADC map, internal delayed enhanced features (IDEF), marginal delayed enhanced features (MDEF), and time signal intensity (TSI) curves. Spiculated margin and the absence of type-I TSI were independent predictors for BC with star grid type stroma. The appearance frequency of hypo-intensity on T2WI in HR- BCs was significantly lower (P=0.043) than in HR+ BCs. Star grid stroma and spiculated margin were key factors in predicting HR+ BCs, and the AUC was 0.927 (95% CI: 0.867-0.987). CONCLUSION: Breast MRI can be used to predict BC's stromal distribution and molecular subtypes.

Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels.

BACKGROUND & AIMS: Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B. METHODS: A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice. RESULTS: Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance. CONCLUSIONS: Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice. IMPACT AND IMPLICATIONS: Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV.

Mesopic pupil indices as potential risk factors for disability glare after intraocular Implantable Collamer Lens implantation: A prospective study.

PURPOSE: To explore the influence of preoperative factors, including varying pupil sizes and refractive attributes, on postoperative disability glare in patients undergoing Implantable Collamer Lens (ICL) implantation. SETTING: Second Affiliated Hospital, Nanchang University. DESIGN: Prospective observational study. METHODS: We analyzed the preoperative ocular characteristics and six-month postoperative glare status in eligible patients who underwent EVO-Visian ICL V4c (VICMO) implantation. The disability glare criteria encompassed a glare symptom score >6 and glare sensitivity exceeding 1:2.7. Logistic regression analysis was used to explore the relationship between the preoperative ocular parameters and post-ICL glare. RESULTS: The study included 95 patients (mean age, 26.04 ± 6.29 years), comprising 30 males (58 eyes) and 65 females (129 eyes). Multivariate analysis revealed a significant correlation between postoperative disability glare and increased spherical power in preoperative mesopic pupils (ß = -0.124, p = 0.039), as well as elevated cylinder power in preoperative mesopic (ß = -0.412, p = 0.009) and photopic pupils (ß = -0.430, p = 0.007). Moreover, a larger preoperative mesopic pupil diameter (ß = 0.561, p = 0.005) demonstrated a significant correlation with disability glare. CONCLUSIONS: Preoperative mesopic pupil dimensions and associated refractive parameters, such as sphere and cylinder were correlated with disability glare, including the cylinder aspect in photopic pupils, which can assist clinicians in optimizing preoperative selection for ICL implantation, aiding in the anticipation of potential disability glare risks.