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 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 hepatocellular carcinoma in vivo, we conducted multiplex immunohistochemistry (mIHC) experiments on human HCC specimens. To explore the role of OXCT1 in mouse hepatocellular carcinoma 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 H3K4 trimethylation (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 decreasing CD8+ T-cell exhaustion and deceleration of tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in HCC patients. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping HCC progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for HCC. Here, we found that ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. And the strategic pharmacological intervention or genetic downregulation of OXCT1 in TAMs enhances the antitumor immunity and decelerated tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

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.

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.

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.

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.

Association of Frailty with Patient-Report Outcomes and Major Clinical Determinants in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: This study aimed to explore the correlation of frailty status with disease characteristics and patient-reported outcomes (PROs) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and determine the sensitivity and specificity of modified COPD PRO scale (mCOPD-PRO) for detecting frailty. Patients and Methods: This cross-sectional study surveyed 315 inpatients with AECOPD from a tertiary hospital in China from August 2022 to June 2023. Patient frailty and PROs were assessed using the validated FRAIL scale and mCOPD-PRO, respectively. Spearman's ρ was used to assess the relevance of lung disease indicators commonly used in clinical practice, and ordinal logistic regression analyses were used to identify the variables associated with frailty status. The validity of mCOPD-PRO in discriminating frail or non-frail individuals was determined using the receiver operating characteristic curve. Results: The participants (N=302, mean age 72.4±9.1 years) were predominantly males (73.2%). Among them, 43 (14.3%) patients were not frail, whereas 123 (40.7%) and 136 (45.0%) patients were pre-frail and frail, respectively. The FRAIL scale was moderately correlated with the mCOPD-PRO scores (Spearman's rank correlation coefficient [Rs]=0.52, P<0.01) for all dimensions (Rs=0.43-0.49, P<0.01). Patients residing in rural areas (odds ratio [OR], 1.67; 95% confidence interval [95% CI], 1.01-2.76) and with higher mCOPD-PRO scores (OR, 4.78; 95% CI, 2.75-8.32) were more likely to be frail. Physically active patients (OR, 0.42; 95% CI, 0.21-0.84) were less likely to be frail. In addition, mCOPD-PRO had good discriminate validity for detecting frailty (area under the curve=0.78), with a sensitivity and specificity of 84.6% and 60.8%, respectively. The optimal probability threshold for mCOPD-PRO was ≥1.52 points. Conclusion: In patients with AECOPD, frailty is closely related to PROs and disease characteristics. Additionally, the mCOPD-PRO score can distinguish well between frail and non-frail patients. Our findings provide support for interventions targeting frail populations with AECOPD.

Patients with chronic obstructive pulmonary disease often have concomitant frailty that may lead to disease deterioration such as acute exacerbations, hospital readmissions, disability, and premature death. Patient-reported outcomes are often used in clinical practice to measure patients' disease characteristics and overall status. Whether patients' frailty state is associated with patient-reported outcomes and if so, which factors are associated with frailty remain unclear. This study, conducted in China, examined their relationship as well as identified factors associated with frailty states. 302 hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease completed a questionnaire answering questions about disease severity, frailty state, anxiety, and depression. The findings suggest that people who live in rural areas, self-reported more severe overall conditions, and are physically inactive are more likely to be frail. Patient-reported outcomes can distinguish between frail and non-frail patients. Therefore, patient-reported outcomes can be used to assess the extent of frailty; early screening of AECOPD combined frailty population and implementation of interventions can help mitigate the adverse effects of frailty.

[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.

HIF-1α-mediated LAMC1 overexpression is an unfavorable predictor of prognosis for glioma patients: evidence from pan-cancer analysis and validation experiments.

BACKGROUND: Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited. METHODS: We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored. RESULTS: LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion. CONCLUSIONS: High expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.

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.

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.

Utilizing a novel model of PANoptosis-related genes for enhanced prognosis and immune status prediction in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common histopathologic type of renal cell carcinoma. PANoptosis, a cell death pathway that involves an interplay between pyroptosis, apoptosis and necroptosis, is associated with cancer immunity and development. However, the prognostic significance of PANoptosis in KIRC remains unclear. RNA-sequencing expression and mutational profiles from 532 KIRC samples and 72 normal samples with sufficient clinical data were retrieved from the Cancer Genome Atlas (TCGA) database. A prognostic model was constructed using differentially expressed genes (DEGs) related to PANoptosis in the TCGA cohort and was validated in a Gene Expression Omnibus (GEO) cohorts. Incorporating various clinical features, the risk model remained an independent prognostic factor in multivariate analysis, and it demonstrated superior performance compared to unsupervised clustering of the 21 PANoptosis-related genes alone. Further mutational analysis showed fewer VHL and more BAP1 alterations in the high-risk group, with alterations in both genes also associated with patient prognosis. The high-risk group was characterized by an unfavorable immune microenvironment, marked by reduced levels of CD4 + T cells and natural killer cells, but increased M2 macrophages and regulatory T cells. Finally, the risk model was predictive of response to immune checkpoint blockade, as well as sensitivity to sunitinib and paclitaxel. The PANoptosis-related risk model developed in this study enables accurate prognostic prediction in KIRC patients. Its associations with the tumor immune microenvironment and drug efficacy may offer potential therapeutic targets and inform clinical decisions.

Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis.

Objective: The aims of this study are to screen novel differentially expressed genes (DEGs) for intracerebral hemorrhage (ICH) and reveal the role of Lipocalin-2 (LCN2) in ICH. Methods: We constructed the ICH model by injection of autologous whole blood into the right basal ganglia in rats. RNA-sequencing and bioinformatics analyses were performed to identify the DEGs between ICH and sham rats, and some important ones were confirmed using quantitative real-time PCR (qRT-PCR). LCN shRNA was used to knockdown of LCN2 in ICH rats. Pathological examination was carried out using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Hematoxylin-eosin (HE) staining. Immunohistochemistry detected Caspase-3, and co-staining of Terminal dUTP nick end labeling (TUNEL) and NEUN staining were performed for neuron apoptosis assessment. Western blot analysis was performed to quantify pyroptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory cytokine levels. Results: ICH rats exhibited significant hematomas, higher brain water content, obvious interstitial edema, and inflammatory infiltration, as well as more apoptotic cells in brain tissues. RNA-seq analysis identified 103 upregulated and 81 downregulated DEGs. The expression of LCN2, HSPB1, CXCL10, and MEF2B were upregulated in ICH rats. ICH triggered the release of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and IL-18, and promoted the expression of pyroptosis-related proteins Caspase-1, GSDMD, NLRP3, and ASC. LCN2 knockdown attenuated the pathological characteristics of ICH, and also reduced pyroptosis in brain tissues. Conclusion: Inhibition of LCN2 attenuates brain injury after ICH via suppressing pyroptosis, which provide guidance for ICH management.

Highly branched bolapolyphilic liquid crystals with a cubic A15 network at the triangle-square transition.

Rod-like bolapolyphiles with highly branched carbosilane-based side-chains self-assemble into several honeycomb structures if the oligo(p-phenylene ethynylene) core is polyfluorinated, whereas for the non-fluorinated series an A15 type cubic network of rod-bundles was observed instead, suggesting a brand new pathway for the transition between triangular and square honeycomb phases.

A multi-resolution TOF-DOI detector for human brain dedicated PET scanner.

Objective. We propose a single-ended readout, multi-resolution detector design that can achieve high spatial, depth-of-interaction (DOI), and time-of-flight (TOF) resolutions, as well as high sensitivity for human brain-dedicated positron emission tomography (PET) scanners.Approach. The detector comprised two layers of LYSO crystal arrays and a lightguide in between. The top (gamma ray entrance) layer consisted of a 16 × 16 array of 1.53 × 1.53 × 6 mm3LYSO crystals for providing high spatial resolution. The bottom layer consisted of an 8 × 8 array of 3.0 × 3.0 × 15 mm3LYSO crystals that were one-to-one coupled to an 8 × 8 multipixel photon counter (MPPC) array for providing high TOF resolution. The 2 mm thick lightguide introduces inter-crystal light sharing that causes variations of the light distribution patterns for high DOI resolution. The detector was read out by a PETsys TOFPET2 application-specific integrated circuit.Main result. The top and bottom layers were distinguished by a convolutional neural network with 97% accuracy. All crystals in the top and bottom layers were resolved. The inter-crystal scatter (ICS) events in the bottom layer were identified, and the measured average DOI resolution of the bottom layer was 4.1 mm. The coincidence time resolution (CTR) for the top-top, top-bottom, and bottom-bottom coincidences was 476 ps, 405 ps, and 298 ps, respectively. When ICS events were excluded from the bottom layer, the CTR of the bottom-bottom coincidence was 277 ps.Significance. The top layer of the proposed two-layer detector achieved a high spatial resolution and the bottom layer achieved a high TOF resolution. Together with its high DOI resolution and detection efficiency, the proposed detector is well suited for next-generation high-performance brain-dedicated PET scanners.

Association between triglyceride glucose index and all-cause mortality in patients with cerebrovascular disease: a retrospective study.

BACKGROUND: Triglyceride glucose (TyG) is associated with stroke, atherosclerosis, and adverse clinical outcomes. However, its correlation with cerebrovascular disease (CVD) mortality remains unclear. This study aimed to investigate the relationship between TyG index and mortality in patients with CVD. METHODS: Patient data sourced from the Medical Information Mart for Intensive Care -IV database were categorized based on TyG quartiles. Kaplan-Meier survival analysis was used to estimate survival disparities among the TyG subgroups. Cox proportional risk modeling was used to examine the association between the TyG index and mortality. Generalized summation models were applied to fit the smoothed curves. log-likelihood ratio test were used to analyze the non-linear relationship. RESULTS: The study comprised 1,965 patients (50.18% were male). The 28-day and 90-day mortality rates were 20.10% and 24.48%, respectively. The TyG index exhibited a linear relationship with the 28-day mortality (Hazards ratio (HR), 1.16; 95% confidence interval (CI), 0.99-1.36) and the 90-day mortality (HR, 1.18; 95% CI, 1.02-1.37). In the TyG Q4 group, each 1 mg/dl increase was linked to a 35% rise in the risk of 28-day mortality and a 38% increase in the risk of 90-day mortality. Subgroup analyses highlighted a more substantial association between TyG index and 90-day mortality in the diabetic group. CONCLUSION: Our findings underscore the positive association between TyG and the 28- and 90-day mortality rates in patients with CVD. This insight may prove pivotal for identifying at-risk populations and enhancing risk prediction in the clinical management of CVD.

The natural polycyclic tetramate macrolactam HSAF inhibit Fusarium graminearum through altering cell membrane integrity by targeting FgORP1.

Fusarium graminearum is a dominant phytopathogenic fungus causing Fusarium head blight (FHB) in cereal crops. Heat-stable antifungal factor (HSAF) is a polycyclic tetramate macrolactam (PoTeM) isolated from Lysobacter enzymogenes that exhibits strong antifungal activity against F. graminearum. HSAF significantly reduces the DON production and virulence of F. graminearum. Importantly, HSAF exhibited no cross-resistance to carbendazim, phenamacril, tebuconazole and pydiflumetofen. However, the target protein of HSAF in F. graminearum is unclear. In this study, the oxysterol-binding protein FgORP1 was identified as the potential target of HSAF using surface plasmon resonance (SPR) combined with RNA-sequence (RNA-seq). The RNA-seq results showed cell membrane and ergosterol biosynthesis were significantly impacted by HSAF in F. graminearum. Molecular docking showed that HSAF binds with arginine 1205 and glutamic acid 1212, which are located in the oxysterol-binding domain of FgORP1. The two amino acids in FgORP1 are responsible for HSAF resistance in F. graminearum though site-directed mutagenesis. Furthermore, deletion of FgORP1 led to significantly decreased sensitivity to HSAF. Additionally, FgORP1 regulates the mycelial growth, conidiation, DON production, ergosterol biosynthesis and virulence in F. graminearum. Overall, our findings revealed the mode of action of HSAF against F. graminearum, indicating that HSAF is a promising fungicide for controlling FHB.

Cone-Traced Supersampling with Subpixel Edge Reconstruction.

While signed distance fields (SDFs) in theory offer infinite level of detail, they are typically rendered using the sphere tracing algorithm at finite resolutions, which causes the common rasterized image synthesis problem of aliasing. Most existing optimized antialiasing solutions rely on polygon mesh representations; SDF-based geometry can only be directly antialiased with the computationally expensive supersampling or with post-processing filters that may produce undesirable blurriness and ghosting. In this work, we present cone-traced supersampling (CTSS), an efficient and robust spatial antialiasing solution that naturally complements the sphere tracing algorithm, does not require casting additional rays per pixel or offline prefiltering, and can be easily implemented in existing real-time SDF renderers. CTSS performs supersampling along the traced ray near surfaces with partial visibility - object contours - identified by evaluating cone intersections within a pixel's view frustum. We further introduce subpixel edge reconstruction (SER), a technique that extends CTSS to locate and resolve complex pixels with geometric edges in relatively flat regions, which are otherwise undetected by cone intersections. Our combined solution relies on a specialized sampling strategy to minimize the number of shading computations and correlates sample visibility to aggregate the samples. With comparable antialiasing quality at significantly lower computational cost, CTSS is a reliable practical alternative to conventional supersampling.

[Effects of Tomato Planting Years on Soil Physical and Chemical Properties and Microbial Communities].

Long-term continuous cropping of facility soils could influence soil properties; however, the differences in soil properties among different continuous cropping years are still not well understood. The objective of this study was to explore the effects of continuous cropping years of tomato on the physical and chemical properties and biological characteristics of facility soil. Conventional analysis, high-throughput sequencing, and other methods were used to examine the soil physicochemical properties, soil microbial community diversity, and enzyme activities in facility soil after continuous tomato cropping for 1-3 years, 5-7 years, and more than 10 years. As the continuous tomato cropping years increased, soil bulk density and pH decreased; soil maximal water holding capacity increased; and organic matter, total nitrogen, and total phosphorus accumulated. As continuous cropping years increased, the total salt and EC value decreased with continuous cropping for 5-7 years and increased from 5-7 years to more than 10 years continuous cropping and showed a trend of secondary soil salinization. There was a significant increase in alkaline phosphatase for 1-3 years to 5-7 years continuous tomato cropping. There were significant differences in fungal community abundance among different cropping years. The Simpson index and Shannon index of fungi showed a trend of increasing first and then decreasing with the extension of continuous cropping years and reached the maximum value at 5 years of continuous cropping. The Chao1 index decreased continuously following the cropping years. As continuous cropping years increased, Streptomyces became the dominant bacteria, and Aspergillus and Pseudaleuria became the dominant fungi. The key factors affected by continuous cropping years were available potassium and available nitrogen based on the redundancy analysis. The results of this study lay the foundation for future research on the influence of continuous cropping years on the health of facility soil.

[Microbial Diversity and Population Structure of Different Salinized Soil Types in Hebei Province].

The objective of this study was to explore the microbial diversity and community composition under saline soil and to screen the salt-tolerant microbial flora from salinization habitats. The soil from three different habitats(primary salinization, secondary salinization, and healthy soil) in Hebei Province were sampled. The convention method and high-throughput sequencing technology were used to examine the physicochemical properties and microorganism diversity. The soil chemical properties of the three habitats were significantly different. Compared with those of field soil, the soil OM, AP, AK, TS, and EC values of greenhouse soil and TS and EC values of coastal saline soil were significantly higher. However, other chemical indexes of coastal saline soil were significantly lower. The diversity index and abundance of soil bacteria in greenhouse soil were the highest, followed by those in field soil and coastal saline soil as the lowest. The diversity index and abundance of fungi in two saline habitats were significantly lower than that in field soil. The community structure of saline soil was analyzed at the phylum and genus levels. Chloroflexi and its genera and Ascomycota and its genera, such as Trichocladium and Fusarium, were the dominant microbial groups in saline soil. EC and TS were the main factors affecting microbial diversity and community composition. EC and TS were positively correlated with unclassified_A4b, unclassified_Chloroflexi, unclassified_α-Proteobacteria, Trichocladium, unclassified_Chaetomiaceae, Crassicarpon, Cephaliophora, and Sodiomyces. The results of this study lay the foundation for future research on screening microbial resources needed for saline soil remediation.

Electrocatalytic Degradation of Rhodamine B on the Sb-Doped SnO2/Ti Electrode in Alkaline Medium.

To realize efficient electrocatalytic degradation of organic compounds in alkaline wastewater, an Sb-doped SnO2/Ti electrode was fabricated and employed for the removal of Rhodamine B (RhB), and the electrocatalytic oxidation performance of this electrode was assessed in an alkaline medium. In an alkaline solution (pH 11), the complete fading of 50 mg·L-1 RhB could be achieved after 150 min of degradation, the removal efficiency of the chemical oxygen demand reached 56.1% at 300 min, and the degradation process of RhB followed the pseudo-first-order kinetic model very well. Under the attack of hydroxyl radicals, partial RhB was degraded to low-molecular-weight organic acids through N-demethylation and the destruction of the conjugated chromophore. Various techniques including scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and cycle voltammetry were used to examine the changes in the morphology and structure, as well as the activity of the Sb-doped SnO2/Ti electrode before and after use. The Sb-doped SnO2/Ti electrode could be reproduced in batches, and each electrode was reused up to eight times without a significant decrease in degradation ability; the leaching amount of antimony was significantly lower than the national emission standard. The electrocatalytic oxidation of the dye wastewater sample was also performed with the desired results, indicating that electrochemical oxidation is a very promising technology for the treatment of alkaline dye wastewater using a Sb-doped SnO2/Ti electrode.