Identification of immune infiltration and PANoptosis-related molecular clusters and predictive model in Alzheimer's disease based on transcriptome analysis.

This study aims to explore the expression profile of PANoptosis-related genes (PRGs) and immune infiltration in Alzheimer's disease (AD). Based on the Gene Expression Omnibus database, this study investigated the differentially expressed PRGs and immune cell infiltration in AD and explored related molecular clusters. Gene set variation analysis (GSVA) was used to analyze the expression of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in different clusters. Weighted gene co-expression network analysis was utilized to find co-expressed gene modules and core genes in the network. By analyzing the intersection genes in random forest, support vector machine, generalized linear model, and extreme gradient boosting (XGB), the XGB model was determined. Eventually, the first five genes (Signal Transducer and Activator of Transcription 3, Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1B, Interleukin 4 Receptor, Chloride Intracellular Channel 1, TNF Receptor Superfamily Member 10B) in XGB model were selected as predictive genes. This research explored the relationship between PANoptosis and AD and established an XGB learning model to evaluate and screen key genes. At the same time, immune infiltration analysis showed that there were different immune infiltration expression profiles in AD.

Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis.

BACKGROUND: Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. METHODS: We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. RESULTS: MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670-0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199-1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. CONCLUSION: Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.

Social support mediates social frailty with anxiety and depression.

BACKGROUND: Anxiety and depression are prevalent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, existing research has yielded conflicting findings regarding the effects of social frailty on anxiety and depression. The primary aim of this study is to validate the relationship between social frailty and social support with anxiety and depression in patients with acute exacerbations of COPD (AECOPD) and to investigate whether social support could explain the variations in prior study outcomes for patients with AECOPD. METHODS: Of the 315 patients hospitalized with AECOPD at the respiratory intensive care unit of a large tertiary care institution in Sichuan Province of China, between August 2022 and June 2023 who were surveyed, 306 were included in the analysis after excluding missing data. We conducted a logistic regression analysis to examine the associations of social frailty and social support with anxiety and depression and performed mediation analyses to examine whether social support mediates the relationship of social frailty with anxiety and depression. RESULTS: The logistic regression analysis revealed that social frailty did not associate anxiety or depression in patients with AECOPD. The mediation analysis supported this idea and indicated that while social frailty does not directly influence anxiety or depression, it can through social support. CONCLUSIONS: The findings suggest that while social frailty may not directly impact anxiety or depression in patients with AECOPD, social support plays a crucial mediating role. Enhancing social support can indirectly alleviate anxiety and depression among these patients. Enhancing social support networks should thus be prioritized by healthcare providers and family members to improve mental health outcomes in this patient population.

[Risk Prediction and Risk Factors of Thrombotic/Bleeding Events in Patients with Myeloproliferative Neoplasm].

OBJECTIVE: To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm (MPN), and explore the main influencing factors, and create a risk prediction. METHODS: The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected, and their clinical characteristics, occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively. Then, a risk prediction model for thrombotic/bleeding events in MPN patients was constructed. RESULTS: Among 126 MPN patients, 50 patients (39.7%) had experienced thrombotic/bleeding events, including 44 patients (34.9%) with thrombotic events and 6 patients (4.8%) with bleeding events. Among thrombotic diseases, cerebral thrombosis was the most common (23/44, 52.3%), followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia, occlusion and gangrene (9/44, 20.5%). Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage. Univariate analysis showed that hypertension, hyperhomocysteinemia, white blood cell (WBC) ≥10×109/L, hematocrit (HCT) ≥49%, platelet (PLT) ≥600×109/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients, while CALR gene mutation was a protective factor. Multivariate analysis showed that hypertension and PLT≥600×109/L were independent risk factors for thrombotic/bleeding events in MPN patients. The goodness of fit of the constructed risk prediction model was 0.872, and the area under the ROC curve was 0.838. The model was validated with clinical data, the sensitivity, specificity and accuracy was 78.85%, 87.83% and 84.13%, respectively . CONCLUSION: The risk of thrombotic/bleeding events in MPN patients with high WBC count, hypertension and hyperhomocysteinemia is higher. Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.

Design and characterization of a hybrid PET detector with DOI capability.

BACKGROUND: Monolithic or semi-monolithic detectors are attractive for positron emission tomography (PET) scanners with depth-of-interaction (DOI) capability. However, they often require complicated calibrations to determine the interaction positions of gamma photons. PURPOSE: We introduce a novel hybrid detector design that combines pixelated and semi-monolithic elements to achieve DOI capability while simplifying the calibrations for positioning. METHODS: A prototype detector with eight hybrid lutetium-yttrium oxyorthosilicate (LYSO) layers having dimensions of 25.8 × 12.9 × 15 mm3 was constructed. The energy-weighted and energy-squared weighted averages were used for estimating the x- (pixelated direction) and y-positions (non-pixelated direction). Pseudo-pixels were defined as discrete areas on the flood image based on the crystal look-up table (LUT). The intrinsic spatial resolutions in the pixelated and non-pixelated directions were measured. The ratio of the maximum to the sum of the multipixel photon counter (MPPC) signals was used to estimate the DOI positions. The coincidence timing resolution (CTR) was measured using the average and energy-weighted average of the earliest n time stamps. Two energy windows of 250-700 and 400-600 keV were applied for the measurements. RESULTS: The pattern of the flood images showed discrete event clusters, demonstrating that simple calibrations for determining the x- and y-positions of events could be achieved. Under 400-600 keV energy window, the average intrinsic spatial resolutions were 1.15 and 1.34 mm for the pixelated and non-pixelated directions; the average DOI resolution of the second row of pseudo-pixels was 5.1 mm in full width at half maximum (FWHM); when using the energy-weighted average of the earliest four-time stamps, the best CTR of 350 ps was achieved. Applying a broader energy window of 250-700 keV only slightly degrades the DOI resolution while maintaining the intrinsic resolution; the best CTR degrades to 410 ps. CONCLUSIONS: The proposed hybrid detector concept was verified, and a prototype detector showed high performance for 3D positioning and timing resolution. The novel detector concept shows promise for preclinical and clinical PET scanners with DOI capability.

Defective recovery of QT dispersion due to no-reflow following acute interventional therapy in patients with ST-segment elevation myocardial infarction.

Background: Previous studies have suggested that adequate myocardial reperfusion after percutaneous coronary intervention (PCI) can improve the inhomogeneity of myocardial repolarization. However, it remains unclear whether no-reflow (NR) following emergency PCI involves disadvantages related to ventricular repolarization indices. The present study aimed to determine the effect of NR on QT dispersion (QTd) in patients with ST-segment elevation myocardial infarction (STEMI) and to evaluate the prognostic value of the relative reduction of QTd on ventricular arrhythmia events (VAEs). Methods: A prospective case-control study was conducted. According to the inclusion criteria, 275 patients with STEMI who underwent primary PCI treatment at the First People's Hospital of Anqing affiliated to Anhui Medical University from January 2020 to May 2023 were enrolled. According to whether NR occurred during PCI, these patients were divided into two groups: an NR group and a non-NR group. Subsequently, the QT intervals were measured before and at 12 hours after PCI. Afterward, the QTd, corrected QTd (QTcd), and the relative reduction of QTd and QTcd 12 hours pre- and postprocedure (ΔQTd-R and ΔQTcd-R, respectively) were calculated. Finally, multivariable logistic regression analysis was performed to predict the risk of VAE occurrence. Results: In the non-NR group, there was a significant decrease from baseline in postprocedure QTd (48±17 vs. 73±22 ms; P=0.009) and QTcd (54±19 vs. 80±23 ms; P=0.01); in contrast, the NR group showed no significant difference in QTd (64±20 vs. 75±23 ms; P=0.58) or QTd (70±22 vs. 82±26 ms; P=0.45). Furthermore, the ΔQTd-R and ΔQTcd-R were both lower in the NR group than in the non-NR group (P<0.05); however, the rate of VAEs was higher in the NR group than in the non-NR group (15.2% vs. 6.2%; P=0.02). The multivariable logistic regression analysis results revealed that each increase of 12% in ΔQTcd-R was an independent predictor of VAEs (odds ratio: 0.547; 95% confidence interval: 0.228-0.976). Conclusions: The NR phenomenon following primary PCI in patients with STEMI leads to the defective recovery of QTd and QTcd. Furthermore, ΔQTcd-R can be viewed as an effective indicator for evaluating the myocardial repolarization inhomogeneity, and short-term clinical outcomes.

Risk factors of postoperative airway obstruction complications in children with oral floor mass.

The aim of the present study was to explore the risk factors of postoperative airway complications in children with oral floor mass. The first choice of auxiliary examination method for children with oral floor mass is also proposed. This retrospective study included 50 children with floor-of-mouth (FOM) masses. Medical records were reviewed, and information on age of onset, functional impacts present, age at consultation, imaging findings, history of preoperative aspiration, pathology findings, properties of biopsied fluid, treatment modality, postoperative outcomes, and operation were recorded. A total of 20 patients exhibited functional impacts such as difficulty in breathing and feeding. Ultrasound examination was performed in 28 cases; and magnetic resonance imaging, in 38 cases. The diagnosis was lymphatic malformation in 12 cases, developmental cyst in 29 cases, and solid mass in 7 cases. There were 28 cases of surgical resection, 9 cases underwent multiple puncture volume reduction followed by surgery, 11 cases treated using sclerotherapy injection, and 1 case treated using sclerotherapy injection and surgical resection. Young age, functional impact, and high grade of lymphatic duct malformation increased the risk of surgical treatment. B-scan ultrasound is the first choice for the diagnosis of FOM masses in children.

Association of triglyceride glucose index with stroke: from two large cohort studies and Mendelian randomization analysis.

INTRODUCTION: The triglyceride glucose index (TyG) is associated with cardiovascular diseases; however, its association with stroke remains unclear. This study aimed to elucidate this relationship by examining two extensive cohort studies using two-sample Mendelian randomization (MR). METHODS: Using data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) and the Medical Information Mart for Intensive Care (MIMIC)-IV, the correlation between TyG (continuous and quartile) and stroke was examined using multivariate Cox regression models and sensitivity analyses. Two-sample MR was employed to establish causality between TyG and stroke using the inverse variance weighting method. Genome-wide association study catalog queries were performed for single nucleotide polymorphism-mapped genes, and the STRING platform used to assess protein interactions. Functional annotation and enrichment analyses were also conducted. RESULTS: From the NHANES and MIMIC-IV cohorts, we included 740 and 589 participants with stroke, respectively. After adjusting for covariates, TyG was linearly associated with the risk of stroke death (NHANES: hazard ratio [HR] 0.64, 95% CI: 0.41-0.99, P =0.047; Q3 vs. Q1, HR 0.62, 95% CI: 0.40-0.96, P =0.033; MIMIC-IV: HR 0.46, 95% CI: 0.27-0.80, P =0.006; Q3 vs. Q1, HR 0.32, 95% CI: 0.12-0.86; Q4 vs. Q1, HR 0.30, 95% CI: 0.10-0.89, P =0.030, P for trend=0.017). Two-sample MR analysis showed genetic prediction supported a causal association between a higher TyG and a reduced risk of stroke (odds ratio 0.711, 95% CI: 0.641-0.788, P =7.64e -11 ). CONCLUSIONS: TyG was causally associated with a reduced risk of stroke. TyG is a critical factor for stroke risk management.

Dendrobium nobile active ingredient Dendrobin A against hepatocellular carcinoma via inhibiting nuclear factor kappa-B signaling.

OBJECTIVE: Dendrobin A, a typical active ingredient of the traditional Chinese medicine Dendrobium nobile, has potential clinical application in cancer treatment; however, its effect and mechanism in anti-hepatocellular carcinoma (HCC) remain unsolved. METHOD: The effects of Dendrobin A on the viability, migration, invasion, cycle, apoptosis, and epithelial-mesenchymal transition of HepG2 and SK-HEP-1 cells were verified by in vitro experiments. mRNA sequencing was performed to screen the differentially expressed genes (DEGs) of HCC cells before and after Dendrobin A treatment, following GO enrichment and KEGG signaling pathway analyses. Mechanistically, molecular docking was used to evaluate the binding of Dendrobin A with proteins p65 and p50, before further verifying the activation of nuclear factor kappa-B (NF-κB) signaling. Finally, the antiproliferative effect of Dendrobin A on HCC cells was explored through animal experiments. RESULTS: Dendrobin A arrested cell cycle, induced apoptosis, and inhibited proliferation, migration, invasion, and blocked epithelial-mesenchymal transition in HepG2 and SK-HEP-1 cells. mRNA sequencing identified 830 DEGs, involving various biological processes. KEGG analysis highlighted NF-κB signaling. Molecular docking revealed strong binding of Dendrobin A with p65 and p50 proteins, and western blotting confirmed reduced levels of p-p65 and p-p50 in HCC cells post Dendrobin A treatment. NF-κB agonist PMA reversed Dendrobin A-inhibited cell proliferation migration and invasion. In vivo experiments showed that Dendrobin A inhibited HCC cell growth. CONCLUSION: Our findings suggest that Dendrobin A exhibits anti-HCC properties by inhibiting the activation of the NF-κB pathway. These results provide a scientific basis for utilizing Dendrobium nobile in anti-HCC therapies.

Operation-friendly and accurate naked-eye observation assay for fast zoonotic echinococcosis and pulmonary tuberculosis monitoring in clinics.

Echinococcosis and tuberculosis are two common zoonotic diseases that can cause severe pulmonary infections. Early screening and treatment monitoring are of great significance, especially in areas with limited medical resources. Herein, we designed an operation-friendly and rapid magnetic enrichment-silver acetylene chromogenic immunoassay (Me-Sacia) to monitor the antibody. The main components included secondary antibody-modified magnetic nanoparticles (MNP-Ab2) as capture nanoparticles, specific peptide (EG95 or CFP10)-modified silver nanoparticles (AgNP-PTs) as detection nanoparticles, and alkyne-modified gold nanoflowers as chromogenic nanoparticles. Based on the magnetic separation and plasma luminescence techniques, Me-Sacia could completely replace the colorimetric assay of biological enzymes. It reduced the detection time to approximately 1 h and simplified the labor-intensive and equipment-intensive processes associated with conventional ELISA. Meanwhile, the Me-Sacia showed universality for various blood samples and intuitive observation with the naked eye. Compared to conventional ELISA, Me-Sacia lowered the detection limit by approximately 96.8 %, increased the overall speed by approximately 15 times, and improved sensitivity by approximately 7.2 %, with a 100 % specificity and a coefficient of variation (CV) of less than 15 %.

[Clinical Features and Prognosis of Patients with CD5+ Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. RESULTS: The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CONCLUSION: CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

First Case Report of Cystic Echinococcosis Caused by G7 Genotype Echinococcus intermedius Confirmed by Genetic Sequencing - Southern China, December 2023.

What is already known about this topic?: Echinococcosis exhibits a global distribution. In China, the primary endemic area is the northwest region. In December 2023, we documented a case of echinococcosis in an individual lacking any travel or residential history in endemic regions. What is added by this report?: This is the first laboratory-confirmed case of hepatic echinococcosis reported in Guangdong Province, associated with the G7 genotype of Echinococcus granulosus (E. granulosus). The most probable mode of transmission is a local infection resulting from E. granulosus introduced from endemic regions. What are the implications for public health practice?: As the circulation of agricultural products increases, it is essential to enhance the quarantine and management of livestock from epidemic areas to prevent and control the spread of echinococcosis to non-epidemic regions.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-κB pathway.

BACKGROUND: Senile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an in vitro setting. METHODS: Osteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity in vitro. For mechanistic exploration, RT-PCR and Western blotting were utilized to assess the activation of the NF-κB pathway. Additionally, protein levels of secreted cytokines and growth factors were determined using suspension array technology. RESULTS: Our findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors. CONCLUSIONS: In conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.

Mechanistic role of RND3-regulated IL33/ST2 signaling on cardiomyocyte senescence.

Hyperinflammatory responses are pivotal in the cardiomyocyte senescence pathophysiology, with IL33 serving as a crucial pro-inflammatory mediator. Our previous findings highlighted RND3's suppressive effect on IL33 expression. This study aims to explore the role of RND3 in IL33/ST2 signaling activation and in cardiomyocyte senescence. Intramyocardial injection of exogenous IL33 reduces the ejection fraction and fractional shortening of rats, inducing the appearance of senescence-associated secretory phenotype (SASP) in myocardial tissues. Recombinant IL33 treatment of AC16 cardiomyocytes significantly upregulated expression of SASP factors like IL1α, IL6, and MCP1, and increased the p-p65/p65 ratio and proportions of SA-ß-gal and γH2AX-positive cells. NF-κB inhibitor pyrrolidinedithiocarbamate ammonium (PDTC) and ST2 antibody astegolimab treatments mitigated above effects. RND3 gene knockout H9C2 cardiomyocytes using CRISPR/Cas9 technology upregulated IL33, ST2L, IL1α, IL6, and MCP1 levels, decreased sST2 levels, and increased SA-ß-gal and γH2AX-positive cells. A highly possibility of binding between RND3 and IL33 proteins was showed by molecular docking and co-immunoprecipitation, and loss of RND3 attenuated ubiquitination mediated degradation of IL33; what's more, a panel of ubiquitination regulatory genes closely related to RND3 were screened using qPCR array. In contrast, RND3 overexpression in rats by injection of AAV9-CMV-RND3 particles inhibited IL33, ST2L, IL1α, IL6, and MCP1 expression in cardiac tissues, decreased serum IL33 levels, and increased sST2 levels. These results suggest that RND3 expression in cardiomyocytes modulates cell senescence by inhibiting the IL33/ST2/NF-κB signaling pathway, underscoring its potential as a therapeutic target in cardiovascular senescence.

Dynamics and Internal Structure Evolution during the Glass Transition of the Ethylene-Cyclic Olefin Copolymers: A Molecular Dynamics Simulation.

Amorphous ethylene-cyclic olefin copolymers (COCs) which can be used in cell phone lenses and prefilled syringes have attracted increasing attention due to their excellent and tunable thermal properties. In order to better explain the influence of COC microstructure (cyclic olefin types and content) on the glass transition mechanism, we used molecular dynamics (MD) simulations to track the evolution of free volume, diffusion coefficients, atomic mobility, trans conformation probabilities, and characteristic parameters of α-relaxation kinetics during the quenching process. MD results show that for the classic COC E-co-NB (ethylene-norbornene copolymer), an increase in cyclic olefin content from 25 to 50 mol % reduces atomic mobility, limiting the molecular chain movement at higher temperatures and improving Tg. Compared to NB, the more rigid rings in tricyclopentadiene (TCPD) and exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-bridged phenylidene-1,4-bridged methylideneanthracene (HBM) have the following effects: (1) reducing the thermal expansion coefficient and overall chain mobility; (2) enhancing the diffusion energy barrier; (3) promoting the formation of local ordered structures; (4) accelerating α-relaxation dynamics at high temperatures and improving the dynamic fragility m. These lead to an upward shift in the temperature region where chain movement is limited and thus improve Tg and high-temperature dimensional stability. In this simulation, the correlation equation between Tg, m, and the microstructural parameters of COCs is established, which is of great significance for the development of COCs with high performance.

First principles calculation of interface interactions and photoelectric properties of ZnSe/SnSe heterostructure.

Heterostructure engineering is an effective technology to improve photo-electronic properties of two dimensional layered semiconductors. In this paper, based on first principles method, we studied the structure, stability, energy band, and optical properties of ZnSe/SnSe heterostructure change with film layer. Results show that all heterostructures are the type-II band arrangement, and the interlayer interaction is characterized by van der Waals. The electron concentration and charge density difference implies the electron (holes) transition from SnSe to monolayer ZnSe. By increasing the layer of SnSe films, the quantum effects are weakened leading to the band gap reduced, and eventually show metal properties. The optical properties also have obvious change, the excellent absorption ability of ZnSe/SnSe heterostructures mainly near the infrared spectroscopy. These works suggest that ZnSe/SnSe heterostructure has significant potential for future optoelectronic applications.

Landslide susceptibility assessment based on frequency ratio and semi-supervised heterogeneous ensemble learning model.

Epistemic uncertainty in data-driven landslide susceptibility assessment often tends to be increased by the limited accuracy of an individual model, as well as uncertainties associated with the selection of non-landslide samples. To address these issues, this paper centers on the landslide disaster in Ji'an City, China, and proposes a heterogeneous ensemble learning method incorporating frequency ratio (FR) and semi-supervised sample expansion. Based on the superimposed results of 12 environmental factor frequency ratios (FFR), non-landslide samples were selected and input into light gradient boosting machine (LightGBM), random forest (RF), and convolutional neural network (CNN) models for prediction along with historical landslide samples. The predicted probability values are integrated by four heterogeneous ensemble strategies to expand samples from high-confidence results. The model's performance is evaluated using the area under the receiver operating characteristic curve (AUC), partition frequency ratio (PFR), and other verification methods. The results demonstrate that the negative sample based on FFR sampling is more accurate than the random sampling method, and the FR-SSELR model based on frequency ratio sampling and semi-supervised ensemble strategy exhibits the highest performance (AUC = 0.971, ACC = 0.941). A more reasonable landslide susceptibility map was drawn based on this model, with the lowest percentage of landslides in the low and very low susceptibility zones (sum of PFR = 0.194), as well as the highest percentage of landslides in the high and very high susceptibility zones (sum of PFR = 6.800). Furthermore, the FR-SSELR model improved economic benefits by 3.82-14.2%, offering valuable guidance for decision-making regarding landslide management and the sustainability of Ji'an City.

[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

Association of Cadherin-Related Family Member 1 with Traumatic Brain Injury.

The cadherin family plays a pivotal role in orchestrating synapse formation in the central nervous system. Cadherin-related family member 1 (CDHR1) is a photoreceptor-specific calmodulin belonging to the expansive cadherin superfamily. However, its role in traumatic brain injury (TBI) remains largely unknown. CDHR1 expression across various brain tissue sites was analyzed using the GSE104687 dataset. Employing a summary-data-based Mendelian Randomization (SMR) approach, integrated analyses were performed by amalgamating genome-wide association study abstracts from TBI with public data on expressed quantitative trait loci and DNA methylation QTL from both blood and diverse brain tissues. CDHR1 expression and localization in different brain tissues were meticulously delineated using western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay. CDHR1 expression was consistently elevated in the TBI group compared to that in the sham group across multiple tissues. The inflammatory response emerged as a crucial biological mechanism, and pro-inflammatory and anti-inflammatory factors were not expressed in either group. Integrated SMR analyses encompassing both blood and brain tissues substantiated the heightened CDHR1 expression profiles, with methylation modifications emerging as potential contributing factors for increased TBI risk. This was corroborated by western blotting and immunohistochemistry, confirming augmented CDHR1 expression following TBI. This multi-omics-based genetic association study highlights the elevated TBI risk associated with CDHR1 expression coupled with putative methylation modifications. These findings provide compelling evidence for future targeted investigations and offer promising avenues for developing interventional therapies for TBI.