MicroRNA let-7c-5p Alleviates in Hepatocellular Carcinoma by Targeting Enhancer of Zeste Homolog 2: A Study Intersecting Bioinformatic Analysis and Validated Experiments.

Enhancer of zeste homolog 2 (EZH2)gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time [hazard ratio (HR) = 1.677, 95% confidence interval (CI) 1.316-2.137; P < 0.0001]. Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low-expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.

Tetraphenylethene-Based Molecular Cage with Coenzyme FAD: Conformationally Isomeric Complexation toward Photocatalysis-Assisted Photodynamic Therapy.

Flavin adenine dinucleotide (FAD), serving as a light-absorbing coenzyme factor, can undergo conformationally isomeric complexation within different enzymes to form various enzyme-coenzyme complexes, which exhibit photocatalytic functions that play a crucial role in physiological processes. Constructing an artificial photofunctional system using FAD or its derivatives can not only develop biocompatible photocatalytic systems with excellent activities but also further enhance our understanding of the role of FAD in biological systems. Here, we demonstrate a supramolecular approach for constructing an artificial enzyme-coenzyme-type host-guest complex with photoinduced catalytic function in water. First, we have designed and synthesized a water-soluble tetraphenylethene (TPE)-based octacationic molecular cage (1) with a large and flexible cavity, which can adaptively encapsulate with two FAD molecules with "U-shaped" conformation (uFAD) to form a 1:2 host-guest complex (1⊃uFAD2) in water. Second, based on the conformationally isomeric complexation of FAD within 1, the 1⊃uFAD2 complex facilitates electron and energy transfers to molecular oxygen upon the white-light illumination, efficiently producing reactive oxygen species (ROS) such as superoxide radical (O2•-) and singlet oxygen (1O2). To our knowledge, the 1⊃uFAD2 complex acts as a photocatalyst to achieve the highest turnover frequency (TOF) of 35.6 min-1 for the photocatalytic oxidation reaction of NADH via a photoinduced superoxide radical catalysis mechanism in an aqueous medium. At last, combining the cytotoxic effects of ROS and the disruption of the intracellular redox balance involving NADH, 1⊃uFAD2 as a supramolecular photosensitizer displays an excellent oxygen-independent photocatalysis-assisted photodynamic therapy in hypoxic tumors.

Effects of effective microorganisms on the physiological status, intestinal microbiome, and serum metabolites of Eriocheir sinensis.

The compound known as effective microorganisms (EMs) is widely used in aquaculture to improve water quality, but how they affect the health of Chinese mitten crab (Eriocheir sinensis) is unclear, especially in terms of intestinal microbiota and serum metabolites. In this study, we fed juvenile crabs with an EM-containing diet to explore the effects of EM on the physiological status, intestinal microbiome, and metabolites of E. sinensis. The activities of alanine aminotransferase and alkaline phosphatase were significantly enhanced by EM, indicating that EM supplementation effectively enhanced the antioxidant capacity of E. sinensis. Proteobacteria, Tenericutes, Firmicutes, Bacteroidetes, and Actinobacteria were the main intestinal microbes in both the control and EM groups. Linear discriminant effect size analysis showed that Fusobacteriaceae, Desulfovibrio, and Morganella were biomarkers in the control group, and Exiguobacterium and Rhodobacteraceae were biomarkers in the EM group. Metabolomics analysis revealed that EM supplementation increased cellular energy sources and decreased protein consumption, and oxidative stress. Together, these results indicate that EM can optimize the intestinal microbiome and serum metabolites, thereby benefiting the health of E. sinensis.

Elucidating the mechanisms of formononetin in modulating atherosclerotic plaque formation in ApoE-/- mice.

BACKGROUND: Atherosclerosis(AS) poses a pressing challenge in contemporary medicine. Formononetin (FMN) plays a crucial role in its prevention and treatment. However, the detailed impact of FMN on the stability of atherosclerotic plaques and its underlying mechanisms remain to be elucidated. METHODS: An intervention consisting of FMN was given along with a high-fat food regimen in the ApoE-/- mouse model. The investigation included the evaluation of the degree of atherosclerotic lesion, the main components of the plaque, lipid profiles, particular markers indicating M1/M2 macrophage phenotypes, the quantities of factors related to inflammation, the infiltration of macrophages, and the identification of markers linked to the α7nAChR/JAK2/STAT3 axis effect molecules. RESULTS: The evaluation of aortic morphology in ApoE-/-mice revealed that FMN significantly improved the plaque area, fibrous cap protrusion, lipid deposition, and structural alterations on the aortic surface, among other markers of atherosclerosis,and there is concentration dependence. Furthermore, the lipid content of mouse serum was assessed, and the results showed that the low-, medium-, and high-dosage FMN groups had significantly lower levels of LDL-C, ox-LDL, TC, and TG. The results of immunohistochemical staining indicated that the low-, medium-, and high-dose FMN therapy groups had enhanced CD206 expression and decreased expression of CD68 and iNOS. According to RT-qPCR data, FMN intervention has the potential to suppress the expression of iNOS, COX-2, miR-155-5p, IL-6, and IL-1ß mRNA, while promoting the expression of IL-10, SHIP1, and Arg-1 mRNA levels. However, the degree of inhibition varied among dosage groups. Western blot investigation of JAK/STAT signaling pathway proteins and cholinergic α7nAChR protein showed that p-JAK2 and p-STAT3 protein expression was suppressed at all dosages, whereas α7nAChR protein expression was enhanced. CONCLUSIONS: According to the aforementioned findings, FMN can reduce inflammation and atherosclerosis by influencing macrophage polarization, blocking the JAK/STAT signaling pathway, and increasing α7nAChR expression.

An Explainable Artificial Intelligence Model to Predict Malignant Cerebral Edema after Acute Anterior Circulating Large-Hemisphere Infarction.

INTRODUCTION: Malignant cerebral edema (MCE) is a serious complication and the main cause of poor prognosis in patients with large-hemisphere infarction (LHI). Therefore, the rapid and accurate identification of potential patients with MCE is essential for timely therapy. This study utilized an artificial intelligence-based machine learning approach to establish an interpretable model for predicting MCE in patients with LHI. METHODS: This study included 314 patients with LHI not undergoing recanalization therapy. The patients were divided into MCE and non-MCE groups, and the eXtreme Gradient Boosting (XGBoost) model was developed. A confusion matrix was used to measure the prediction performance of the XGBoost model. We also utilized the SHapley Additive exPlanations (SHAP) method to explain the XGBoost model. Decision curve and receiver operating characteristic curve analyses were performed to evaluate the net benefits of the model. RESULTS: MCE was observed in 121 (38.5%) of the 314 patients with LHI. The model showed excellent predictive performance, with an area under the curve of 0.916. The SHAP method revealed the top 10 predictive variables of the MCE such as ASPECTS score, NIHSS score, CS score, APACHE II score, HbA1c, AF, NLR, PLT, GCS, and age based on their importance ranking. CONCLUSION: An interpretable predictive model can increase transparency and help doctors accurately predict the occurrence of MCE in LHI patients not undergoing recanalization therapy within 48 h of onset, providing patients with better treatment strategies and enabling optimal resource allocation.

ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP.

DNA end resection is a critical step in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR). However, the mechanisms governing the extent of resection at DSB sites undergoing homology-directed repair remain unclear. Here, we show that, upon DSB induction, the key resection factor CtIP is modified by the ubiquitin-like protein SUMO at lysine 578 in a PIAS4-dependent manner. CtIP SUMOylation occurs on damaged chromatin and requires prior hyperphosphorylation by the ATM protein kinase. SUMO-modified hyperphosphorylated CtIP is targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation. Consequently, disruption of CtIP SUMOylation results in aberrant accumulation of CtIP at DSBs, which, in turn, causes uncontrolled excessive resection, defective HR, and increased cellular sensitivity to DSB-inducing agents. These findings reveal a previously unidentified regulatory mechanism that regulates CtIP activity at DSBs and thus the extent of end resection via ATM-dependent sequential posttranslational modification of CtIP.

Analysis of the phytochemical components of Prunella vulgaris using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with molecular networking and assessment of their antioxidant and anti-α-glucosidase activities.

Prunella vulgaris has long been used in traditional medicine and is consumed as a tea in China. Here, the total phenolic and flavonoid concentrations of plants from different geographical regions were measured. It was found that the total phenolic acid concentration ranged from 4.15 to 8.82 g of gallic acid equivalent per 100 g of dry weight (DW), and the total flavonoid concentration was 4.67-7.33 g of rutin equivalent per 100 g DW. Antioxidant activities were measured using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, and the results ranged from 73.47% to 94.43% and 74.54% to 93.39%, respectively, whereas α-glucosidase inhibition was between 75.31% and 95.49%. Correlation analysis showed that the total flavonoids in P. vulgaris had superior antioxidant and anti-α-glucosidase activities compared to the total phenolic compounds. The active components of P. vulgaris were analyzed using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with both classical molecular networking and feature-based molecular networking on the Global Natural Products Social platform, identifying 32 compounds, namely 14 flavonoids, 12 phenolic compounds, and 6 other chemical components. These results could provide useful information on the use of P. vulgaris as a functional tea.

Characterizing the temporal dynamics of intrinsic brain activities in depressed adolescents with prior suicide attempts.

Converging evidence has revealed disturbances in the corticostriatolimic system are associated with suicidal behaviors in adults with major depressive disorder. However, the neurobiological mechanism that confers suicidal vulnerability in depressed adolescents is largely unknown. A total of 86 depressed adolescents with and without prior suicide attempts (SA) and 47 healthy controls underwent resting-state functional imaging (R-fMRI) scans. The dynamic amplitude of low-frequency fluctuations (dALFF) was measured using sliding window approach. We identified SA-related alterations in dALFF variability primarily in the left middle temporal gyrus, inferior frontal gyrus, middle frontal gyrus (MFG), superior frontal gyrus (SFG), right SFG, supplementary motor area (SMA) and insula in depressed adolescents. Notably, dALFF variability in the left MFG and SMA was higher in depressed adolescents with recurrent suicide attempts than in those with a single suicide attempt. Moreover, dALFF variability was capable of generating better diagnostic and prediction models for suicidality than static ALFF. Our findings suggest that alterations in brain dynamics in regions involved in emotional processing, decision-making and response inhibition are associated with an increased risk of suicidal behaviors in depressed adolescents. Furthermore, dALFF variability could serve as a sensitive biomarker for revealing the neurobiological mechanisms underlying suicidal vulnerability.

Fisetin disrupts mitochondrial homeostasis via superoxide dismutase 2 acetylation in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is one of the most lethal malignant tumors with an urgent need for precision medicine strategies. The present study seeks to assess the antitumor effects of fisetin, and characterize its impact on PDAC. Multi-omic approaches include proteomic, transcriptomic, and metabolomic analyses. Further validation includes the assessment of mitochondria-derived reactive oxygen species (mtROS), mitochondrial membrane potential, as well as ATP generation. Molecular docking, immunoprecipitation, and proximity ligation assay were used to detect the interactions among fiseitn, superoxide dismutase 2 (SOD2), and sirtuin 2 (SIRT2). We showed that fisetin disrupted mitochondrial homeostasis and induced SOD2 acetylation in PDAC. Further, we produced site mutants to determine that fisetin-induced mtROS were dependent on SOD2 acetylation. Fisetin inhibited SIRT2 expression, thus blocking SOD2 deacetylation. SIRT2 overexpression could impede fisetin-induced SOD2 acetylation. Additionally, untargeted metabolomic analysis revealed an acceleration of folate metabolism with fisetin. Collectively, our findings suggest that fisetin disrupts mitochondrial homeostasis, eliciting an important cancer-suppressive role; thus, fisetin may serve as a promising therapeutic for PDAC.

[CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar â disorder].

OBJECTIVE: To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). METHODS: From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. RESULTS: Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. CONCLUSION: The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Bioinformatic Identification of Signaling Pathways and Hub Genes in Vascular Dementia.

BACKGROUND: Vascular dementia (VaD) is a prevalent neurodegenerative disease characterized by cognitive impairment due to cerebrovascular factors, affecting a significant portion of the aging population and highlighting the critical need to understand specific targets and mechanisms for effective prevention and treatment strategies. We aimed to identify pathways and crucial genes involved in the progression of VaD through bioinformatics analysis and subsequently validate these findings. METHODS: We conducted differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Protein-Protein Interaction (PPI) analysis. We utilized pheochromocytoma 12 (PC12) cells to create an in vitro oxygen-glucose deprivation (OGD) model. We investigated the impact of overexpression and interference of adrenoceptor alpha 1D (ADRA1D) on OGD PC12 cells using TdT-mediated dUTP nick-end labeling (TUNEL), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and Fluo-3-pentaacetoxymethyl ester (Fluo-3 AM) analysis. RESULTS: We found 187 differentially expressed genes (DEGs) in the red module that were strongly associated with VaD and were primarily enriched in vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathway, and cell adhesion. Among these pathways, we identified ADRA1D as a gene shared by vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction. The TUNEL assay revealed a significant decrease in PC12 cell apoptosis with ADRA1D overexpression (p < 0.01) and a significant increase in apoptosis upon silencing ADRA1D (p < 0.01). RT-qPCR and WB analysis revealed elevated ADRA1D expression (p < 0.001) and decreased phospholipase C beta (PLCß) and inositol 1,4,5-trisphosphate receptor (IP3R) expression (p < 0.05) with ADRA1D overexpression. Moreover, the Fluo-3 AM assessment indicated significantly lower intracellular Ca2+ levels with ADRA1D overexpression (p < 0.001). Conversely, interference with ADRA1D yielded opposite results. CONCLUSION: Our study provides a new perspective on the pathogenic mechanisms of VaD and potential avenues for therapeutic intervention. The results highlight the role of ADRA1D in modulating cellular responses to OGD and VaD, suggesting its potential as a target for VaD treatment.

Biomimetic Hydrogen-Bonded G ⋠C ⋠G ⋠C Quadruplex within a Tetraphenylethene-Based Octacationic Spirobicycle in Water.

In biological systems, nucleotide quadruplexes (such as G-quadruplexes) in DNA and RNA that are held together by multiple hydrogen bonds play a crucial functional role. The biomimetic formation of these hydrogen-bonded quadruplexes captured by artificial systems in water poses a significant challenge but can offer valuable insights into these complex functional structures. Herein, we report the formation of biomimetic hydrogen-bonded G ⋅ C ⋅ G ⋅ C quadruplex captured by a tetraphenylethene (TPE) based octacationic spirobicycle (1). The spirobicyclic compound possesses a three-dimensional (3D) crossing dual-cavity structure, which enables the encapsulation of four d(GpC) dinucleotide molecules, thereby realizing 1 : 4 host-guest complexation in water. The X-ray structure reveals that four d(GpC) molecules further form a two-layer G ⋅ C ⋅ G ⋅ C quadruplex with Watson-Crick hydrogen bonds, which are stabilized within the dual hydrophobic cavities of 1 through the cooperative non-covalent interactions of hydrogen bonds, CH⋅⋅⋅π interactions, and hydrophobic effect. Due to the dynamically-rotational propeller chirality of TPE units, 1 with adaptive chirality can further serve as a chiroptical sensor to exhibit opposite Cotton effects with mirror-image CD spectra for the pH-dependent hydrogen-bonded assemblies of d(GpC) including the Watson-Crick G ⋅ C ⋅ G ⋅ C (pH 9.22) and Hoogsteen G ⋅ C+ ⋅ G ⋅ C+ (pH 5.74) quartets through the host-guest chirality transfer in water.

Endogenous Adenosine Triphosphate-Assisted Three-Dimensional DNA Walker Assembled on Soft Nanoparticles for Intracellular MicroRNA Imaging.

DNA walkers, a sophisticated type of nanomachines, exhibit intelligent application in biosensing with high programmability and flexibility but usually need additional auxiliary driving force, particularly when walking on hard surfaces. Herein, we construct a three-dimensional (3D) DNA walker on the soft surface of DNA nanospheres (DSs) by using a single-stranded DNA (ssDNA), which is powered by endogenous adenosine triphosphate (ATP) of live cells, so as to sensitively image microRNA (miRNA) in the tumor microenvironment. When the DS walker enters into live cells, miR-21, a general overexpressed biomarker in cancer cells, binds with the blocking strand (B), releasing the walking strand (W) and triggering an ATP-propelled walking reaction. The walking of the DS walker then generates an increasing Cy3 fluorescence signal that indicates the content of miR-21 with about 2.73-fold increase in sensitivity and about 157-fold decrease in the detection limit. Notably, the assembly of the DS walker on soft nanoparticles needs just an easy hybridization process, which facilitates the operation. Meanwhile, this endogenous ATP-powered 3D DNA walker walking on the soft surface performs real-time in situ imaging of miR-21 in live cells, which not only avoids the complex cell treatment and signal error induced by additional auxiliary factors, but also shows high promise of designing programmable DNA nanomachines.

Temporal trends in surgery for Crohn's disease: a ten-year single-center retrospective study.

PURPOSE: Crohn's disease (CD) is a chronic inflammatory bowel disease that requires surgery in many cases. The aim of this article is to present the experience of a referral center regarding surgical interventions for CD, while also exploring the transformations that have occurred over 10 years. METHODS: The data of patients underwent abdominal surgery for CD between 2013 and 2022 were collected prospectively. Data were compared between two periods (2013-2017 and 2018-2022). Temporal trends were assessed with the Mann-Kendall trend test. RESULTS: A total of 1059 individuals underwent 1176 surgical procedures, of which 67.1% were male. The median age of patients at the time of surgery was 36.0 years, and an overall increasing trend was observed in surgical volume (z = 3.04; p = 0.002). The proportion of patients treated with biologics increased from the first period (2013-2017) to the second (2018-2022), rising from 19.2% to 33.5% (p < 0.001). In the second stage, the proportion of patients who underwent surgery for abscesses or fistulas increased (47.8% vs. 40.0%, p = 0.028), while the percentage of emergency surgeries declined (3.0% vs. 7.1%, p = 0.001). Furthermore, there was a rise in the proportion of laparoscopic surgeries (76.5% vs. 63.7%, p < 0.001), coupled with a decrease in stoma rates (15.4% vs. 30.5%, p < 0.001) and postoperative complications (23.0% vs. 30.5%, p = 0.007). CONCLUSION: The frequency of biologics use in CD surgery have increased over time, and the proportion of penetrating patients has grown. Minimally invasive surgical methods have become the norm, and surgical outcomes have markedly enhanced, evidenced by a substantial reduction in both stoma rates and complication rates.

Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice.

The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By these means, we identified synaptotagmin-7 (Syt7) as a candidate risk factor for behavioral abnormalities. We then investigated Syt7 knockout (KO) mice and observed nocturnal manic-like and diurnal depressive-like behavioral fluctuations in a majority of these animals, analogous to the mood cycling symptoms of BD. We treated the Syt7 KO mice with clinical BD drugs including olanzapine and lithium, and found that the drug treatments could efficiently regulate the behavioral abnormalities of the Syt7 KO mice. To further verify whether Syt7 deficits existed in BD patients, we investigated the plasma samples of 20 BD patients and found that the Syt7 mRNA level was significantly attenuated in the patient plasma compared to the healthy controls. We therefore concluded that Syt7 is likely a key factor for the bipolar-like behavioral abnormalities.

Correlation Analysis of Serum 3-NT, NPASDP-4, and S100ß Protein Levels with Cognitive Function in Patients Diagnosed with Cerebral Infarction.

Objective: To observe the levels of serum 3-nitrotyrosine (3-NT), neuronal PAS domain protein 4 (NPASDP-4), and S100ß protein in patients diagnosed with cerebral infarction and analyze their correlation with cognitive dysfunction in these patients. Methods: The study included a cohort of 158 patients suffering from cerebral infarction who were admitted to the Liwan District Hospital of Traditional Chinese Medicine between January 2021 and December 2022. After stabilizing vital signs, all patients underwent the Montreal Cognitive Assessment (MoCA) to assess their cognitive function. Based on the assessment results, they were divided into two groups: the cognitive dysfunction group (121 cases) and the normal cognitive function group (37 cases). The baseline characteristics and serum levels of 3-NT, neuronal PAS domain protein 4 (NPASDP-4), and S100ß protein were compared in the patient cohorts. Furthermore, the correlation between these three indicators and cognitive function in patients suffering from cerebral infarction was analyzed. A logistic regression model was constructed to analyze how serum levels of 3-NT, NPASDP-4, and S100ß protein levels affected cognitive function in patients suffering from cerebral infarction. ROC curve analysis was conducted to assess the predictive value of serum 3-NT, NPASDP-4, and S100ß protein levels for cognitive function in patients suffering from cerebral infarction. Results: Among the 158 patients with cerebral infarction, 121 (76.58%) had cognitive dysfunction, while 37 (23.42%) had normal cognitive function. The levels of 3-NT, NPASDP-4, and S100ß protein were found to be significantly higher in the cognitive dysfunction group compared to the normal cognitive function group (t = 5.788, 7.774, 6.460; P = .000, .000, .000). The point-biserial correlation analysis results showed a positive correlation between serum levels of 3-NT, NPASDP-4, and S100ß protein and the occurrence of cognitive dysfunction in patients suffering from cerebral infarction (r=0.420, 0.529, 0.424; P = .000, .000, .000). The logistic regression model demonstrated that serum levels of 3-NT(95%CI: 1.299-2.603), NPASDP-4(95%CI: 1.487-3.386), and S100ß protein(95%CI: 1.153-8.746) were risk factors for cognitive dysfunction in patients suffering from cerebral infarction (OR=1.839, 2.244, 1.429; P = .001, .000, .240). ROC curve analysis demonstrated that serum 3-NT, NPASDP-4, and S100ß protein levels exhibited a certain predictive value for cognitive function in patients with cerebral infarction (AUC = 0.789, 0.881, 0.820). Conclusion: Serum levels of 3-NT, NPASDP-4, and S100ß protein are closely related to the cognitive function of patients with cerebral infarction, and abnormal changes in these levels may exacerbate cognitive dysfunction in these patients.

Microcystin-LR-induced autophagy via miR-282-5p/PIK3R1 pathway in Eriocheir sinensis hepatopancreas.

With the intensifying climate warming, blue-green algae blooms have become more frequent and severe, releasing environmental hazards such as microcystin that pose potential threats to human and animal health. Autophagy has been shown to play a crucial role in regulating immune responses induced by environmental hazards, enabling cells to adapt to stress and protect against damage. Although microcystin-LR (MC-LR) has been identified to affect autophagy in mammalian, its impact on aquatic animals has been poorly studied. To investigate the toxicological effects of MC-LR in aquatic ecosystems, we constructed a microRNA profile of acute MC-LR stress in the hepatopancreas of the Chinese mitten crab. Interestingly, we found the MC-LR exposure activated autophagy in the hepatopancreas based on the following evidence. Specifically, mRNA expression level of ATG7, Beclin1 and Gabarap was significantly up-regulated, autophagy regulatory pathways were significantly enriched, and numerous autolysosomes and autophagosomes were observed. Additionally, we found that miR-282-5p and its target gene PIK3R1 played important regulatory roles in autophagy by in vivo and in vitro experiments. Overexpression of miR-282-5p mimicked MC-LR-induced autophagy by inhibiting PIK3R1 expression, while miR-282-5p silencing inhibited autophagy by promoting PIK3R1 expression. Altogether, our findings suggest that MC-LR increases miR-282-5p, which then targets inhibition of PIK3R1 to stimulate autophagy. This study focused on the stress response regulatory mechanisms of juvenile crabs to toxic pollutants in water, offering a potential target for alleviating the toxicity of MC-LR. These findings lay a foundation for reducing the toxicity of MC-LR and environmental hazards in organisms.

Effects of prometryn on oxidative stress, immune response and apoptosis in the hepatopancreas of Eriocheir sinensis (Crustacea: Decapoda).

Prometryn, a triazine pesticide product used to control weed growth, poses a high risk to aquatic organisms in the environment. Several toxicological evaluations have been performed on bony fish and shrimp exposed to prometryn. However, there have been no reports conducted on the toxic mechanism of prometryn with regard to Eriocheir sinensis. In this study, our research evaluated the toxic effects of prometryn via in vitro and in vivo toxicity tests on E. sinensis. Firstly, we estimated the exposure toxicity of prometryn to E. sinensis, and then we constructed a 6 h transcriptional profile and conducted an enrichment analysis. To further reveal the toxicity of prometryn, the hepatopancreas (hepatopancreatic cells) was analyzed for antioxidant, immune and lipid-metabolism-related enzymes, antioxidant- and apoptosis-related gene expression, histopathology and TUNEL. From the results, we determined that the 96 h-LD50 was 70.059 mg/kg, and using RNA-seq, we identified 933 differentially expressed genes (DEGs), which were mainly enriched in the amino and fatty acid metabolism and the cell-fate-determination-related signaling pathway. The results of the biochemical assays showed that prometryn could significantly decrease the activities/levels of CAT, SOD, GSH, AKP and ACP, reduce the levels of T-AOC, TG, TCH, C3 and C4, and increase the MDA content. In addition, the expression levels of Nrf2, GSTs and HO-1 were first upregulated and then downregulated with increasing time. Histopathology showed that prometryn damaged the structure of the hepatopancreas cells and induced apoptosis, suggesting that the PI3K-Akt signaling pathway may be involved in the damage process of hepatopancreas cells (PI3K, PDK and Akt were downregulated whereas Bax was upregulated), leading to their apoptosis. The above results indicated that prometryn could cause injury of the hepatopancreas through oxidative stress, induce cell apoptosis, disrupt the lipid metabolism and cause immune damage. This study provided useful data for understanding and evaluating the toxicity of prometryn to aquatic crustacea.

Evaluation and control of Fusarium acuminatum causing leaf spot in Saposhnikovia divaricata in Northeast China.

Saposhnikovia divaricata is an authentic Chinese herbal medicine in Northeast China named Guanfangfeng, which is made from very high quality plants for sufficient efficacy. However, leaf spot causes a very large reduction in the yield and quality of S. divaricata in Shuangyashan (126°54'E, 45°81'N), Northeast China. A total of 18 isolates were isolated from the diseased leaves of S. divaricata, following Koch's postulates, and identified as Fusarium acuminatum based on morphological, molecular biological, and phylogenetic tree analyses. To the authors' knowledge, this is the first report of F. acuminatum causing S. divaricata leaf spot in China. F. acuminatum infected perilla and mung beans, but not foxtail millet, peanuts, wheat, peas, rye, red beans, or sorghum. Susceptibility assessment of F. acuminatum to fungicides using the mycelial growth rate method showed that isolates of F. acuminatum were most sensitive to prochloraz, with EC50 values of 0.0005413-0.0009523 µg·ml-1. In the two field experiments, the average control efficacy of prochloraz at 0.450 g/l on S. divaricata leaf spot caused by F. acuminatum was 75.42%. Therefore, non-host plant rotation or intercropping with suitable chemical fungicides may be used to control S. divaricata leaf spot. This study's results provide a theoretical basis for controlling S. divaricata leaf spot and will facilitate the development of effective disease management programs.

Bioengineered Platelets Combining Chemotherapy and Immunotherapy for Postsurgical Melanoma Treatment: Internal Core-Loaded Doxorubicin and External Surface-Anchored Anti-PD-L1 Antibody Backpacks.

The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.