Resveratrol ameliorates cyprodinil-induced zebrafish cardiac developmental defects as an aryl hydrocarbon receptor antagonist.

Cyprodinil, a globally utilized broad-spectrum pyrimidine amine fungicide, has been observed to elicit cardiac abnormality. Resveratrol (RSV), a naturally occurring polyphenolic compound, showcases remarkable defensive properties in nurturing cardiac development. To investigate whether RSV could protect against cyprodinil-induced cardiac defects, we exposed zebrafish embryos to cyprodinil (500 µg/L) in the presence or absence of RSV (1 µM). Our results showed that RSV significantly mitigated the decrease of survival rate and embryo movement and the hatching delay induced by cyprodinil. In addition, RSV also improved cyprodinil-induced zebrafish cardiac developmental toxicity, including pericardial edema and cardiac function impairment. In mechanism, RSV attenuated the cyprodinil-induced changes in mRNA expression involved in cardiac development, such as myh6, myl7, tbx5, and gata4, and calcium ion channels, such as ncx1h, slc8a4a, and atp2a2b. We further showed that RSV might inhibit the activity of aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. In summary, our findings establish that the protective effects of RSV against the cardiac developmental toxicity are induced by cyprodinil due to its remarkable ability to inhibit AhR activity. Our findings not only shed light on a new avenue for regulating and ensuring the safe utilization of cyprodinil but also presents a novel concept to promote its responsible use.

AcMYB266, a key regulator of the red coloration in pineapple peel: a case of subfunctionalization in tandem duplicated genes.

Red fruit peel is an attractive target for pineapple breeding. Various pineapple accessions with distinct red coloration patterns exist; however, the precise molecular mechanism accounting for these differences remains unknown, which hinders the pineapple breeding process from combining high fruit quality with red peel. In this study, we characterized a transcription factor, AcMYB266, which is preferentially expressed in pineapple peel and positively regulates anthocyanin accumulation. Transgenic pineapple, Arabidopsis, and tobacco plants overexpressing AcMYB266 exhibited significant anthocyanin accumulation. Conversely, transient silencing of this gene led to decreased anthocyanin accumulation in pineapple red bracts. In-depth analysis indicated that variations of AcMYB266 sequences in the promoter instead of the protein-coding region seem to contribute to different red coloration patterns in peels of three representative pineapple varieties. In addition, we found that AcMYB266 was located in a cluster of four MYB genes exclusive to and conserved in Ananas species. Of this cluster, each was proved to regulate anthocyanin synthesis in different pineapple tissues, illustrating an interesting case of gene subfunctionalization after tandem duplication. In summary, we have characterized AcMYB266 as a key regulator of pineapple red fruit peel and identified an MYB cluster whose members were subfunctionalized to specifically regulate the red coloration of different pineapple tissues. The present study will assist in establishing a theoretical mechanism for pineapple breeding for red fruit peel and provide an interesting case for the investigation of gene subfunctionalization in plants.

Genome-Wide Identification and Characterization of Gibberellic Acid-Stimulated Arabidopsis Gene Family in Pineapple (Ananas comosus).

The gibberellic acid-stimulated Arabidopsis (GASA) gene family plays a crucial role in growth, development, and stress response, and it is specific to plants. This gene family has been extensively studied in various plant species, and its functional role in pineapple has yet to be characterized. In this study, 15 AcGASA genes were identified in pineapple through a genome-wide scan and categorized into three major branches based on a phylogenetic tree. All AcGASA proteins share a common structural domain with 12 cysteine residues, but they exhibit slight variations in their physicochemical properties and motif composition. Predictions regarding subcellular localization suggest that AcGASA proteins are present in the cell membrane, Golgi apparatus, nucleus, and cell wall. An analysis of gene synteny indicated that both tandem and segmental repeats have a significant impact on the expansion of the AcGASA gene family. Our findings demonstrate the differing regulatory effects of these hormones (GA, NAA, IAA, MeJA, and ABA) on the AcGASA genes. We analyzed the expression profiles of GASA genes in different pineapple tissue parts, and the results indicated that AcGASA genes exhibit diverse expression patterns during the development of different plant tissues, particularly in the regulation of floral organ development. This study provides a comprehensive understanding of GASA family genes in pineapple. It serves as a valuable reference for future studies on the functional characterization of GASA genes in other perennial herbaceous plants.

Islet amyloid polypeptide triggers α-synuclein pathology in Parkinson's disease.

Pathologic aggregation and prion-like propagation of α-synuclein (α-syn) are the hallmarks of Parkinson's disease (PD). Emerging evidence shows that type 2 diabetes mellitus (T2DM) is a risk factor for PD. Interestingly, T2DM is characterized by the amyloid deposition of islet amyloid polypeptide (IAPP) in the pancreas. Although T2DM and PD share pathological similarities, the underlying molecular mechanisms bridging these two diseases remain unknown. Here, we report that IAPP co-deposits with α-syn in the brains of PD patients. IAPP interacts with α-syn and accelerates its aggregation. In addition, the IAPP-seeded α-syn fibrils show enhanced seeding activity and neurotoxicity compared with pure α-syn fibrils in vitro and in vivo. Strikingly, intravenous injection of IAPP fibrils into α-syn A53T transgenic mice or human SNCA transgenic mice accelerated the aggregation of α-syn and PD-like motor deficits. Taken together, these findings support that IAPP acts as a trigger of α-syn pathology in PD, and provide a mechanistic explanation for the increased risk and faster progression of PD in patients with T2DM.

Comparison of Performances among Four Bleeding-Prediction Scores in Elderly Cancer Patients with Venous Thromboembolism.

The performances of RIETE, VTE-BLEED, SWITCO65 + , and Hokusai-VTE scores for predicting major bleeding events in hospitalized elderly cancer patients with venous thromboembolism (VTE) have not been evaluated. This study validated the performances of these scoring systems in a cohort of elderly cancer patients with VTE. Between June 2015 and March 2021, a total of 408 cancer patients (aged ≥ 65 years) with acute VTE were consecutively enrolled. The overall rates of in-hospital major bleeding and clinically relevant bleeding (CRB) were 8.3% (34/408) and 11.8% (48/408), respectively. RIETE score could categorize patients with increasing rate of major bleeding and CRB into low-/intermediate- and high-risk categories (7.1 vs. 14.1%, p = 0.05 and 10.1 vs. 19.7%, p = 0.02, respectively). The discriminative power of the four scores for predicting major bleeding was poor to moderate, indicated by areas under the receiver operating characteristic curves (0.45 [95% confidence interval, CI: 0.35-0.55] for Hokusai-VTE, 0.54 [95% CI: 0.43-0.64] for SWITCO65 + , 0.58 [95% CI: 0.49-0.68] for VTE-BLEED, and 0.61 [95% CI: 0.51-0.71] for RIETE). RIETE score might be used to predict major bleeding in hospitalized elderly cancer patients with acute VTE.

Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells.

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer.

Mutually communicated model based on multi-parametric MRI for automated segmentation and classification of prostate cancer.

BACKGROUND: Multiparametric magnetic resonance imaging (mp-MRI) is introduced and established as a noninvasive alternative for prostate cancer (PCa) detection and characterization. PURPOSE: To develop and evaluate a mutually communicated deep learning segmentation and classification network (MC-DSCN) based on mp-MRI for prostate segmentation and PCa diagnosis. METHODS: The proposed MC-DSCN can transfer mutual information between segmentation and classification components and facilitate each other in a bootstrapping way. For classification task, the MC-DSCN can transfer the masks produced by the coarse segmentation component to the classification component to exclude irrelevant regions and facilitate classification. For segmentation task, this model can transfer the high-quality localization information learned by the classification component to the fine segmentation component to mitigate the impact of inaccurate localization on segmentation results. Consecutive MRI exams of patients were retrospectively collected from two medical centers (referred to as center A and B). Two experienced radiologists segmented the prostate regions, and the ground truth of the classification refers to the prostate biopsy results. MC-DSCN was designed, trained, and validated using different combinations of distinct MRI sequences as input (e.g., T2-weighted and apparent diffusion coefficient) and the effect of different architectures on the network's performance was tested and discussed. Data from center A were used for training, validation, and internal testing, while another center's data were used for external testing. The statistical analysis is performed to evaluate the performance of the MC-DSCN. The DeLong test and paired t-test were used to assess the performance of classification and segmentation, respectively. RESULTS: In total, 134 patients were included. The proposed MC-DSCN outperforms the networks that were designed solely for segmentation or classification. Regarding the segmentation task, the classification localization information helped to improve the IOU in center A: from 84.5% to 87.8% (p < 0.01) and in center B: from 83.8% to 87.1% (p < 0.01), while the area under curve (AUC) of PCa classification was improved in center A: from 0.946 to 0.991 (p < 0.02) and in center B: from 0.926 to 0.955 (p < 0.01) as a result of the additional information provided by the prostate segmentation. CONCLUSION: The proposed architecture could effectively transfer mutual information between segmentation and classification components and facilitate each other in a bootstrapping way, thus outperforming the networks designed to perform only one task.

Surgical and medical co-management optimizes surgical outcomes in older patients with chronic diseases undergoing robot-assisted laparoscopic radical prostatectomy.

INTRODUCTION: While robotic-assisted laparoscopic radical prostatectomy (RRP) is a standard mode for localized prostate cancer (PC), the risk of complications in older patients with chronic diseases and complex medical conditions can be a deterrent to surgery. Surgical and medical co-management (SMC) is a new strategy to improve patients' healthcare outcomes in surgical settings. METHODS: We reviewed the clinical data of older patients with chronic diseases who were cared for with SMC undergoing RRP in our hospital in the past 3 years and compared them with the clinical data from the general urology ward. Preoperative conditions and related indicators of recovery, and incidence of postoperative complications with the Clavien Grade System were compared between these two groups. RESULTS: The indicators of recovery were significantly better, and the incidence rates of complications were significantly reduced in the SMC group at grades I-IV (p < 0.05), as compared to the general urology ward group. CONCLUSIONS: The provision of care by SMC for older patients focused on early identification, comorbidity management, preoperative optimization, and collaborative management would significantly improve surgical outcomes. The SMC strategy is worthy of further clinical promotion in RRP treatment in older men with chronic diseases and complex medical conditions.

Exposure to dithiocarbamate fungicide maneb in vitro and in vivo: Neuronal apoptosis and underlying mechanisms.

Maneb, a widely-used dithiocarbamate fungicide, remains in the environment and exerts adverse health effects. Epidemiological evidence shows that maneb exposure is associated with a higher risk of Parkinson's disease (PD), one of the most common neurodegenerative diseases. However, the molecular mechanisms underlying maneb-induced neurotoxicity remain unclear. Here we investigated the toxic effects and the underlying mechanisms of maneb on the degeneration of dopaminergic cells and α-synuclein in A53T transgenic mice. In SH-SY5Y cells, exposure to maneb reduces cell viability, triggers neuronal apoptosis, induces mitochondrial dysfunction, and generates reactive oxidative species (ROS) in a dose-dependent manner. Furthermore, Western blot analysis found that the mitochondrial apoptosis pathway (Bcl-2, Bax, cytochrome c, activated caspase-3) and the PKA/CREB signaling pathway (PKA, PDE10A, CREB, p-CREB) were changed by maneb both in vitro and in vivo. In addition, the activation of the mitochondrial apoptosis pathway induced by maneb was attenuated by activating PKA. Therefore, these results suggest that the PKA/CREB signaling pathway is involved in maneb-induced apoptosis. This study provides novel insights into maneb-induced neurotoxicity and the underlying mechanisms, which may serve as a guide for further toxicological assessment and standard application of maneb.

Differentiation of malignant from benign pleural effusions based on artificial intelligence.

INTRODUCTION: This study aimed to construct artificial intelligence models based on thoracic CT images to perform segmentation and classification of benign pleural effusion (BPE) and malignant pleural effusion (MPE). METHODS: A total of 918 patients with pleural effusion were initially included, with 607 randomly selected cases used as the training cohort and the other 311 as the internal testing cohort; another independent external testing cohort with 362 cases was used. We developed a pleural effusion segmentation model (M1) by combining 3D spatially weighted U-Net with 2D classical U-Net. Then, a classification model (M2) was built to identify BPE and MPE using a CT volume and its 3D pleural effusion mask as inputs. RESULTS: The average Dice similarity coefficient, Jaccard coefficient, precision, sensitivity, Hausdorff distance 95% (HD95) and average surface distance indicators in M1 were 87.6±5.0%, 82.2±6.2%, 99.0±1.0%, 83.0±6.6%, 6.9±3.8 and 1.6±1.1, respectively, which were better than those of the 3D U-Net and 3D spatially weighted U-Net. Regarding M2, the area under the receiver operating characteristic curve, sensitivity and specificity obtained with volume concat masks as input were 0.842 (95% CI 0.801 to 0.878), 89.4% (95% CI 84.4% to 93.2%) and 65.1% (95% CI 57.3% to 72.3%) in the external testing cohort. These performance metrics were significantly improved compared with those for the other input patterns. CONCLUSIONS: We applied a deep learning model to the segmentation of pleural effusions, and the model showed encouraging performance in the differential diagnosis of BPE and MPE.

Effects of Soil Properties on Pb, Cd, and Cu Contents in Tobacco Leaves of Longyan, China, and Their Prediction Models.

Longyan City in Fujian Province is one of China's top-quality tobacco-producing areas and plays an essential role in local economic development. To determine the correlation between heavy metal content in tobacco leaves and soil factors, soil physical and chemical properties and heavy metal contents of lead, cadmium, and copper in tobacco leaves were measured and analyzed by the correlation regression method. The content of lead, cadmium, and copper in soil was determined using hydrochloric acid extraction-AAS and graphite furnace atomic absorption spectrometry. Inductively coupled plasma-mass spectrometry was used to determine heavy metal in tobacco leaf. The findings revealed that the average concentrations of lead, cadmium, and copper in the soil were 12.1, 0.092, and 3.88 mg/kg, respectively. In contrast, the average levels of lead, cadmium, and copper in tobacco leaves were 2.33, 4.89, and 4.35 mg/kg, respectively. The cadmium enrichment coefficient of 54.3 was higher than lead and copper, indicating a greater health risk. Soil pH value was negatively correlated with lead content in tobacco leaf, while potassium and phosphorus nutrient levels were negatively correlated with copper content. In contrast, a positive correlation was established between the presence of organic matter with cadmium content in tobacco leaves. The prediction models of lead, cadmium, and copper in tobacco leaves can be expressed by the regression equation corresponding to each heavy metal as follows: YPb=2.33 - 0.005∗ XK+0.007∗XN - 0.271∗XpH+0.065∗XPb (R2 = 0.787), YCd=1.55+0.012∗XOM - 0.014∗XCu+34.6∗XCd (R2 = 0.891), and YCu=4.64 - 0.029∗XP - 0.007∗XK+0.245∗XCu (R2 = 0.724), respectively. The prediction models above provide an effective predictive tool for assessing heavy metal risk in tobacco leaves using soil properties in the study area.

IDH1 Promotes Foam Cell Formation by Aggravating Macrophage Ferroptosis.

A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced ferroptosis in macrophages and activating nuclear factor erythroid 2-related factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 significantly different genes, and subsequent bioinformatics research revealed that ferroptosis and IDH1 play essential roles in foam cell production. We also confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reduced ox-LDL-induced elevated Fe2+ levels, lipid peroxidation (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, inhibiting IDH1 reduced Fe2+ overload, lipid peroxidation, LDH, and glutathione depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and foam cell formation in macrophages, implying that IDH1 may be an important molecule regulating foam cell formation and may be a promising molecular target for the treatment of atherosclerosis.

Exposure to the environmentally toxic pesticide maneb induces Parkinson's disease-like neurotoxicity in mice: A combined proteomic and metabolomic analysis.

Maneb is a typical dithiocarbamate fungicide that has been extensively used worldwide. Epidemiological evidence shows that exposure to maneb is an environmental risk factor for Parkinson's disease (PD). However, the mechanisms underlying maneb-induced neurotoxicity have yet to be elucidated. In this study, we exposed SH-SY5Y cells to maneb at environmentally relevant concentrations (0, 0.1, 5, 10 mg/L) and found that maneb dose-dependently decreased the cell viability. Furthermore, maneb (60 mg/kg) induced PD-like motor impairment in α-synuclein A53T transgenic mice. The results of tandem mass tag (TMT) proteomics and metabolomics studies of mouse brain and serum revealed significant changes in proteins and metabolites in the pathways involved in the neurotransmitter system. The omics results were verified by targeted metabolomics and Western blot analysis, which demonstrated that maneb induced disturbance of the PD-related pathways, including the phenylalanine and tryptophan metabolism pathways, dopaminergic synapse, synaptic vesicle cycle, mitochondrial dysfunction, and oxidative stress. In addition, the PD-like phenotype induced by maneb was attenuated by the asparagine endopeptidase (AEP) inhibitor compound #11 (CP11) (10 mg/kg), indicating that AEP may play a role in maneb-induced neurotoxicity. To the best of our knowledge, this is the first study to investigate the molecular mechanisms underlying maneb-induced PD-like phenotypes using multiomics analysis, which identified novel therapeutic targets for PD associated with pesticides and other environmental pollutants.

Multimodal Imaging Response after the Singular or Combination Treatments of Vascular Endothelial Growth Factor Inhibitor and Immune Checkpoint Inhibitor.

This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and 18F-FDG PET/CT in a hepatocellular carcinoma (HCC) mice model. Based on different treatments, 24 mice were randomly divided into four groups: control (isotype-matched IgG antibody 10 mg/kg), VEGF inhibitor (sorafenib 50 mg/kg), ICI (anti-PD-L1 antibody 10 mg/kg), and combination groups (sorafenib 50 mg/kg + anti-PD-L1 antibody 10 mg/kg). Quantitative imaging assessments, including volume transfer constant (Ktrans), apparent diffusion coefficient (ADC), lactate/choline ratio, and the maximum standardized 18F-FDG uptake value ratio of tumor to muscle (SUVtumor/SUVmuscle ratio), were acquired at different time points (before treatment and 7, 14, and 21 days after treatment). Quantitative data were presented as the mean ± standard errors and two-way repeated-measure ANOVA tests were performed for intergroup and intertime point comparisons. After 21 days from the initiation of therapies, combination group showed the lowest tumor volume and weight, followed by ICI, VEGF inhibitor, and control group, with no significance between the VEGF inhibitor and control groups. In addition, Ktrans values significantly decreased, and the lactate/choline ratio and SUVtumor/SUVmuscle ratio were significantly elevated in the VEGF inhibitor group. ADC significantly increased in the ICI and combination groups, with no significant differences in ADC observed between the control and VEGF inhibitor groups, which showed a similar dynamic change to the tumor volume. Furthermore, Ktrans, lactate/choline ratio, and ADC were significantly correlated with CD31+ area, hypoxyprobe+ area, and apoptosis, respectively. Our results suggest that the singular treatment and combination of the VEGF inhibitor and ICI treatments for HCC present different multimodal imaging changes in accordance with the specific histopathological features. These findings might facilitate the formulation of better treatment response criteria; besides, we find ADC is probably an indicator easily to obtain for treatment response evaluation.

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling.

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.

Sea urchin-like CoNi2S4materials derived from nickel hexamyanocobaltate for high-performance asymmetric hybrid supercapacitor.

In this work, a mild chemical precipitation method and simple hydrothermal treatment of the nickel hexamyanocobaltate precursor strategy are developed to prepare a sea urchin-like CoNi2S4compound with remarkable specific capacity and excellent cycling stability. The prepared CoNi2S4has an outstanding specific capacity of 149.1 mA h g-1at 1 A g-1and an initial capacity of 83.1% after 3000 cycles at 10 A g-1. Moreover, the porous carbon nanospheres (PCNs) with exhibit cycling stability (94.7% of initial specific capacity after 10 000 cycles at 10 A g-1) are selected as negative electrode to match CoNi2S4positive electrode for assembly of CoNi2S4//PCNs asymmetric supercapacitor (ASC). Satisfactorily, the as-assembled CoNi2S4//PCNs ASC exhibits an impressive energy density of 41.6 Wh kg-1at 797 W kg-1, as well as the suitable capacity retention of 82.8% after 10 000 cycles. The superior properties of the device demonstrated that the as-prepared material is potential energy storage material.

Systematic Investigations on the Metabolic and Transcriptomic Regulation of Lactate in the Human Colon Epithelial Cells.

Lactate, primarily produced by the gut microbiota, performs as a necessary "information transmission carrier" between the gut and the microbiota. To investigate the role of lactate in the gut epithelium cell-microbiota interactions as a metabolic signal, we performed a combinatory, global, and unbiased analysis of metabolomic and transcriptional profiling in human colon epithelial cells (Caco-2), using a lactate treatment at the physiological concentration (8 mM). The data demonstrated that most of the genes in oxidative phosphorylation were significantly downregulated in the Caco-2 cells due to lactate treatment. Consistently, the levels of fumarate, adenosine triphosphate (ATP), and creatine significantly decreased, and these are the metabolic markers of OXPHOS inhibition by mitochondria dysfunction. The one-carbon metabolism was affected and the polyol pathway was activated at the levels of gene expression and metabolic alternation. In addition, lactate significantly upregulated the expressions of genes related to self-protection against apoptosis. In conclusion, lactate participates in gut-gut microbiota communications by remodeling the metabolomic and transcriptional signatures, especially for the regulation of mitochondrial function. This work contributes comprehensive information to disclose the molecular mechanisms of lactate-mediated functions in human colon epithelial cells that can help us understand how the microbiota communicates with the intestines through the signaling molecule, lactate.

Perioperative Myocardial Injury/Infarction After Non-cardiac Surgery in Elderly Patients.

At present, we have entered an aging society. Many diseases suffered by the elderly, such as malignant tumors, cardiovascular diseases, fractures, surgical emergencies and so on, need surgical intervention. With the improvement of Geriatrics, surgical minimally invasive technology and anesthesia level, more and more elderly patients can safely undergo surgery. Elderly surgical patients are often complicated with a variety of chronic diseases, and the risk of postoperative myocardial injury/infarction (PMI) is high. PMI is considered to be the increase of cardiac troponin caused by perioperative ischemia, which mostly occurs during operation or within 30 days after operation, which can increase the risk of short-term and long-term death. Therefore, it is suggested to screen troponin in elderly patients during perioperative period, timely identify patients with postoperative myocardial injury and give appropriate treatment, so as to improve the prognosis. The pathophysiological mechanism of PMI is mainly due to the increase of myocardial oxygen consumption and / the decrease of myocardial oxygen supply. Preoperative and postoperative risk factors of myocardial injury can be induced by mismatch of preoperative and postoperative oxygen supply. The treatment strategy should first control the risk factors and use the drugs recommended in the guidelines for treatment. Application of cardiovascular drugs, such as antiplatelet ß- Receptor blockers, statins and angiotensin converting enzyme inhibitors can effectively improve postoperative myocardial ischemia. However, the risk of perioperative bleeding should be fully considered before using antiplatelet and anticoagulant drugs. This review is intended to describe the epidemiology, diagnosis, pathophysiology, risk factors, prognosis and treatment of postoperative myocardial infarction /injury.

Management of Postoperative Myocardial Injury After Non-cardiac Surgery in Patients Aged ≥ 80 Years: Our 10 Years' Experience.

Background: Postoperative myocardial injury (PMI) is associated with short- and long-term mortality. The incidence of PMI in very old patients is currently unknown. There is currently neither known effective prophylaxis nor a uniform strategy for the elderly with PMI. Objective: To share our 10 years of experience in the comprehensive management of PMI after non-cardiac surgery in patients aged ≥ 80 years. Methods: In this case series, we retrospectively collected and assessed the 2,984 cases aged ≥ 80 years who accepted non-cardiac surgery from 2011 to 2021 at the second Medical Center, Chinese PLA General Hospital. The incidence, risk factors, management strategy, and prognosis of surgical patients with PMI were analyzed. Results: A total of 2,984 patients met our inclusion criteria. The overall incidence of PMI was 14%. In multivariable analysis, coronary artery disease, chronic heart failure, and hypotension were independently associated with the development of PMI. The patients with PMI were at a higher risk of death (OR, 2.69; 95% CI, 1.78-3.65). They were more likely to have received low molecular heparin, anti-plantlet therapy, beta-blocker, early coronary angiography, and statin than patients without PMI. The 30-day (0.96% vs. 0.35%; OR 3.46; 95% CI, 1.49-7.98; P < 0.001) and 1-year mortality (5.37% vs. 2.60%; OR 2.35; 95% CI, 1.12-6.53; P < 0.001) was significantly higher in patients with PMI compared with those without PMI. Conclusions: The incidence of PMI in very old patients was high. The PMI is associated with an increased risk of 30 days and 1-year mortality. These patients can benefit from intensification of assessment and individualized care of multi-morbidities during the perioperative period. Especially cardiovascular medical treatments, such as antiplatelet, anticoagulation, ß-blockers, and statins are very important for patients with PMI.