Performance on inhibitory tasks does not relate to handedness in several small groups of Callitrichids.

Brain lateralization, a trait ubiquitous in vertebrates and invertebrates, refers to structural differences between the left and right sides of the brain or to the left and right sides controlling different functions or processing information in different ways. Many studies have looked into the advantages of lateralized brains and discovered that cerebral lateralization confers a fitness advantage. Enhancing cognitive ability has been proposed as one of the potential benefits of the lateralized brain, however, this has not been widely validated. In this study, we investigated the handedness of 34 subjects from four groups of Callitrichids, as well as their performance in two inhibitory control tasks (the revised A-not-B task and the cylinder task). The subjects had strong individual hand preferences, and only a few zoo-born individuals were ambidextrous. Sex and generation influence the strength of hand preference. In the cylinder task, the subjects showed differences between groups, and the performance of the second-generation was better than that of the first-generation. We found that neither the strength of hand preferences (ABS-HI) or direction of hand preferences (HI) was linked with success on the two inhibitory tasks. That is, we were unable to support the enhanced cognitive function hypothesis. We believe that individual ontogeny and the type of cognitive task have an impact on the support of this hypothesis. The advantages of lateralized brain may be reflected in tests that require multiple cognitive abilities.

Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells.

BACKGROUND: Intestinal epithelial barrier disruption and bacterial translocation exacerbates the progression of alcoholic liver disease. Lactobacillus rhamnosus GG (LGG), a probiotic, has been shown benefits in chronic liver disease and in regulating gut dysbiosis. Previous studies showed the protective roles of LGG in ethanol-disrupted gut barrier functions and liver injury. Inosine, a metabolite produced by intestinal bacteria, has the anti-inflammatory and immunregulatory functions. In this study, the synergistic effect of LGG and inosine was investigated in a mouse model of alcohol-induced liver disease (ALD). METHODS: Male C57BL/6 mice were fed with a Lieber-DeCarli diet containing 5% alcohol for four weeks to establish a model of alcohol-induced liver injury. LGG or a combination of LGG and inosine were administrated orally to explore a new therapeutic method for alcohol-induced liver disease and to investigate the underlying mechanisms. Liver damage was evaluated by transaminases and pathological changes. Tight junction proteins, composition of the gut microbiome, cytokines, lipopolysaccharides (LPS), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), F4/80+ macrophages, as well as p38, Jun N-terminal kinase (JNK), were determined by qRT-PCR, RNAseq, ELISA, IHC and western blot. Regulatory T (Treg) cells were characterized by positive staining of CD4, CD25 and Foxp3 using flow cytometry. IFN-γ-producing CD4+ T (Th1) cells were examined by intracellular cytokine staining. RESULTS: Alcohol consumption induced elevated liver enzymes, steatosis and inflammation, while LGG combined with inosine treatment was more significant to ameliorate these symptoms compared with LGG alone. When LGG combined with inosine were administered to ALD mice, intestinal microecology significantly improved reflected by intestinal villi and tight junction proteins recovery and the restoration of intestinal flora. Combined therapy inhibited phosphorylation of p38 and JNK to alleviate hepatic inflammation. Moreover, flow cytometry analysis showed that long-term excessive alcohol consumption reduced Tregs population while increased Th1 population, which was restored by a combination of LGG and inosine treatment. CONCLUSIONS: The findings from the study indicate that the combined LGG and inosine treatment ameliorates ALD by improving the gut ecosystem, intestinal barrier function, immune homeostasis and liver injury.

Tussilagone protects acute lung injury from PM2.5 via alleviating Hif-1α/NF-κB-mediated inflammatory response.

Environmental pollution, especially particulate matter in the air, is a serious threat to human health. Long-term inhalation of particulate matter with a diameter < 2.5 µm (PM2.5) induced irreversible respiratory and lung injury. However, it is not clear whether temporary exposure to massive PM2.5 would result in epithelial damage and lung injury. More importantly, it is urgent to clarify the mechanisms of PM2.5 cytotoxicity and develop a defensive and therapeutic approach. In this study, we demonstrated that temporary exposure with PM2.5 induced lung epithelial cell apoptosis via promoting cytokines expression and inflammatory factors secretion. The cytotoxicity of PM2.5 could be alleviated by tussilagone (TSL), which is a natural compound isolated from the flower buds of Tussilago farfara. The mechanism study indicated that PM2.5 promoted the protein level of Hif-1α by reducing its degradation mediated by PHD2 binding, which furtherly activated NF-κB signaling and inflammatory response. Meanwhile, TSL administration facilitated the interaction of the Hif-1α/PHD2 complex and restored the Hif-1α protein level increased by PM2.5. When PHD2 was inhibited in epithelial cells, the protective function of TSL on PM2.5 cytotoxicity was attenuated and the expression of cytokines was retrieved. Expectedly, the in vivo study also suggested that temporary PM2.5 exposure led to acute lung injury. TSL treatment could effectively relieve the damage and decrease the expression of inflammatory cytokines by repressing Hif-1α level and NF-κB activation. Our findings provide a new therapeutic strategy for air pollution-related respiratory diseases, and TSL would be a potential preventive medicine for PM2.5 cytotoxicity.

Menstrual blood-derived mesenchymal stem cells attenuate inflammation and improve the mortality of acute liver failure combining with A2AR agonist in mice.

BACKGROUND AND AIM: Acute liver failure (ALF) poses a serious public health issue. The menstrual blood-derived mesenchymal stem cells (MenSCs) have been applied to cure various liver-related diseases. However, the efficacy and mechanism are far from clear. This study aims to explore the efficacy and potential mechanism of MenSCs to cure ALF. METHODS: We investigate the potential mechanism of MenSCs on the ALF in vitro and in vivo. A2A adenosine receptor (A2AR) activation was investigated as the potential reinforcer for MenSCs treatment. Lipid polysaccharide/d-galactosamine (d-GalN) was employed to induce ALF. Diverse techniques were used to measure the inflammatory cytokines and key signaling molecules. Hematoxylin-eosin stain and aminotransaminases were applied to evaluate the liver injury. Flow cytometry was employed to assess the T cells. RESULTS: The MenSCs can decrease the lipid polysaccharide-induced inflammatory cytokine elevation and related signaling molecules in ALF, including TLR4, phosphorylated-NF-kBp65 (p-NF-kBp65), PI3K, and p-AKT, p-mTOR and p-IKK in vitro. Moreover, MenSCs also can significantly reverse the liver injury, inflammatory cytokines elevation and related signaling molecules increase, and Treg/Th17 ratio decrease in vivo. In addition, MenSCs plus A2AR agonist can enhance the above changes. CONCLUSIONS: The MenSCs can attenuate the ALF-induced liver injury via inhibition of TLR4-mediated PI3K/Akt/mTOR/IKK signaling. Then, this inhibits the p-NF-κBp65 translocate into nuclear, which causes a decrease of inflammatory cytokines release. Moreover, A2AR agonist can play a synergic role with MenSCs and enhance the above-mentioned effects.

microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation.

Autoimmune hepatitis (AIH) is a chronic liver disease due to autoimmune system attacks hepatocytes and causes inflammation and fibrosis. Intracellular signalling and miRNA may play an important role in regulation of liver injury. This study aimed to investigate the potential roles of microRNA 143 in a murine AIH model and a hepatocyte injury model. Murine AIH model was induced by hepatic antigen S100, and hepatocyte injury model was induced by LPS. Mice and AML12 cells were separated into six groups with or without the treatment of miRNA-143. Inflammation and fibrosis as well as gene expression were examined by different cellular and molecular techniques. The model was successfully established with the elevation of ALT and AST as well as inflammatory and fibrotic markers. Infection or transfection of mir-143 in mice or hepatocytes significantly attenuated the development of alleviation of hepatocyte injury. Moreover, the study demonstrated phosphorylation of TAK1-mediated miRNA-143 regulation of hepatic inflammation and fibrosis as well as hepatocyte injury. Our studies demonstrated a significant role of miRNA-143 in attenuation of liver injury in AIH mice and hepatocytes. miRNA-143 regulates inflammation and fibrosis through its regulation of TAK1 phosphorylation, which warrants TAK1 as a target for the development of new therapeutic strategy of autoimmune hepatitis.

LIGHT-INDUCED RICE1 Regulates Light-Dependent Attachment of LEAF-TYPE FERREDOXIN-NADP+ OXIDOREDUCTASE to the Thylakoid Membrane in Rice and Arabidopsis.

LIR1 (LIGHT-INDUCED RICE1) encodes a 13-kD, chloroplast-targeted protein containing two nearly identical motifs of unknown function. LIR1 is present in the genomes of vascular plants, mosses, liverworts, and algae, but not in cyanobacteria. Using coimmunoprecipitation assays, pull-down assays, and yeast two-hybrid analyses, we showed that LIR1 interacts with LEAF-TYPE FERREDOXIN-NADP(+) OXIDOREDUCTASE (LFNR), an essential chloroplast enzyme functioning in the last step of photosynthetic linear electron transfer. LIR1 and LFNR formed high molecular weight thylakoid protein complexes with the TIC62 and TROL proteins, previously shown to anchor LFNR to the membrane. We further showed that LIR1 increases the affinity of LFNRs for TIC62 and that the rapid light-triggered degradation of the LIR1 coincides with the release of the LFNR from the thylakoid membrane. Loss of LIR1 resulted in a marked decrease in the accumulation of LFNR-containing thylakoid protein complexes without a concomitant decrease in total LFNR content. In rice (Oryza sativa), photosynthetic capacity of lir1 plants was slightly impaired, whereas no such effect was observed in Arabidopsis thaliana knockout mutants. The consequences of LIR1 deficiency in different species are discussed.

Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Alkaline phosphatase (ALP) has been implicated to be associated with poor outcome in ischemic stroke patients, yet its role in aneurysmal subarachnoid hemorrhage (aSAH) patients is unknown. The current study aimed to investigate the on-admission and short-term variation trend of ALP levels in aSAH patients as well as its associations with vasospasm, delayed cerebral ischemia (DCI), and outcome after aSAH. METHODS: Between January 2014 and May 2018, all consecutive aSAH patients were prospectively enrolled. Blood samples from patients and 78 healthy individuals were obtained. Baseline information, clinical data, and radiologic data were collected, and serum ALP levels during hospitalization were measured. Patients were followed up for 6 months. RESULTS: One hundred and ninety-six aSAH patients were included. The serum ALP levels in aSAH patients were significantly higher compared to controls (71 vs. 61 U/L, p = 0.0002), yet did not differ significantly between patients with severe (WFNS 4-5) and mild clinical condition (72 vs. 63 U/L, p = 0.3362). However, ALP was significantly higher in patients with severe radiologic status (modified Fisher 3-4) compared to those with mild radiologic status (77 vs. 61.5 U/L, p = 0.0005). A significant correlation emerged between modified Fisher score and ALP level (r = 0.246, p = 0.001). Multivariable analysis found that higher ALP level was associated with angiographic vasospasm (OR 1.019, 95% CI 1.002-1.036, p = 0.026) and DCI-caused clinical deterioration (OR 1.019, 95% CI 1.001-1.037, p = 0.037), while higher WFNS score, modified Fisher score, and ALP level were independently associated with unfavorable outcome (serum ALP level, OR 1.083, 95% CI 1.041-1.127, p < 0.001). Trend analysis of ALP level based on 103 patients' data revealed a significant decrease in ALP level on post-admission day 7-9 (median; on-admission day vs. post-admission day 7-9, 72 vs. 60 U/L, p = 0.0012; post-admission day 3-5 vs. day 7-9, 70 vs. 60 U/L, p = 0.0052) and subsequent increase in ALP level on post-admission day 12-14 (median, 84 U/L, p < 0.0001). Higher ALP levels were observed in patients with unfavorable outcome on on-admission day, post-admission day 3-5, and 12-14 (median; unfavorable vs. favorable; on-admission day, 86 vs. 67 U/L, p = 0.0122; post-admission day 3-5, 80 vs. 64 U/L, p = 0.0044; post-admission day 7-9, 75 vs. 53.5 U/L, p < 0.0001) but not on post-admission day 12-14. CONCLUSIONS: Elevated serum ALP level is associated with vasospasm, DCI-caused clinical deterioration, and functional outcome after aSAH. Further studies are required to examine the potential role of serum ALP as an outcome predictor for aSAH patients.

OsCLT1, a CRT-like transporter 1, is required for glutathione homeostasis and arsenic tolerance in rice.

Arsenic (As) contamination in a paddy environment can cause phytotoxicity and elevated As accumulation in rice (Oryza sativa). The mechanism of As detoxification in rice is still poorly understood. We isolated an arsenate (As(V))-sensitive mutant of rice. Genomic resequencing and complementation identified OsCLT1, encoding a CRT-like transporter, as the causal gene for the mutant phenotype. OsCLT1 is localized to the envelope membrane of plastids. The glutathione and γ-glutamylcysteine contents in roots of Osclt1 and RNA interference lines were decreased markedly compared with the wild-type (WT). The concentrations of phytochelatin PC2 in Osclt1 roots were only 32% and 12% of that in WT after As(V) and As(III) treatments, respectively. OsCLT1 mutation resulted in lower As accumulation in roots but higher As accumulation in shoots when exposed to As(V). Under As(III) treatment, Osclt1 accumulated a lower As concentration in roots but similar As concentration in shoots to WT. Further analysis showed that the reduction of As(V) to As(III) was decreased in Osclt1. Osclt1 was also hypersensitive to cadmium (Cd). These results indicate that OsCLT1 plays an important role in glutathione homeostasis, probably by mediating the export of γ-glutamylcysteine and glutathione from plastids to the cytoplasm, which in turn affects As and Cd detoxification in rice.

Functional loops: Monitoring functional organization of deep neural networks using algebraic topology.

Various topological methods have emerged in recent years to investigate the inner workings of deep neural networks (DNNs) based on the structural and weight information. However, their effectiveness is restricted due to the stratified structure and volatile weight information. In this study, we explore the relationship between functional organizations and network performance using algebraic topology. Our results indicate that functional loops reveal functional interaction patterns of multiple neurons in DNNs. We also propose functional persistence as a measure of functional complexity and develop an early stopping criterion that achieves competitive results without requiring a validation set.

Forward looking statement, investor sentiment and stock liquidity.

Information is a critical element of capital markets, and liquidity is the lifeblood of capital markets. Relative to historical information, forward-looking information is of significant value to investors. Based on textual analysis calculations, we selected Chinese A-share listed companies as a research sample to explore the impact of forward-looking information disclosure level on stock liquidity. It is found that the higher the level of forward-looking information disclosure, the better the stock liquidity. Investor sentiment is the transmission mechanism through which the forward looking statement disclosure level affects stock liquidity. The heterogeneity analysis shows that the level of forward-Looking statement disclosure has a more significant effect on stock liquidity improvement for state-owned enterprises and enterprises in low-market regions than those in regions with high marketization levels. The article expands and enriches the research on forward-looking information disclosure, and also has some reference value for regulators to formulate laws and regulations and regulate forward-looking information disclosure.

The energy conservation and emission reduction co-benefits of China's emission trading system.

Emission Trading System (ETS) is an innovative practice under the progress of green development in China. It is also an important method for China to achieve market-oriented environmental governance in ecological civilization construction. The ETS pilot policy has implemented for more than 10 years. However, the co-benefits of ETS pilot policy by the integration of energy consumption, carbon and sulfur dioxide emissions, and wastewater has not been evaluated. In order to fill this gap, we use the 2003-2017 annual data of 30 China's provinces (municipalities and autonomous regions), and utilize the Difference-in-Differences (DID) model and Propensity Score Matching (PSM-DID) methodology to evaluate the co-benefits of ETS pilot policy on energy conservation and emission reduction. We find that the ETS pilot policy significantly promote energy conservation and emission reduction. Eastern and central China have significantly benefited from the policy, while the western China has not due to the limited technology and innovation as well as an imbalance of the industrial structure. The results provide the policy reference for China's government and institutions as well as the governments and institutions around the world to fulfill their commitments to save energy and reduce emissions, and early achieve the carbon peaking and carbon neutralization.

Polymeric immunoglobulin receptor deficiency exacerbates autoimmune hepatitis by inducing intestinal dysbiosis and barrier dysfunction.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease with unclear pathogenesis. The gut microbiota and intestinal barrier play an essential role in AIH. Polymeric immunoglobulin receptor (pIgR) is a central component of mucosal immunity. Herein, we aimed to test the hypothesis that pIgR plays a pivotal role in maintaining gut microbiota homeostasis and gut barrier integrity in an AIH mouse model. The expression of intestinal pIgR shows the variation tendency of falling after rising with the aggravation of experimental AIH (EAH). The deletion of Pigr exacerbates liver damage in EAH. Furthermore, we identified a distinct microbiota profile of Pigr-deficient EAH mice, with a significant increased aboundance in the Oscillospiraceae family, particularly the Anaeromassilibacillus genus. Such a situation occurs because the loss of Pigr inhibits MEK/ERK, a key signal pathway whereby pIgR transports immunoglobulin A (IgA), resulting in reduced IgA secretion, which leads to the destruction of intestinal epithelial tight junction proteins and intestinal flora disturbance. Increased intestinal leakage causes increased translocation of bacteria to the liver, thus aggravating liver inflammation in EAH. Treatment with the Lactobacillus rhamnosus GG supernatant reverses liver damage in EAH mice but loses its protective effect without pIgR. Our study identifies that intestinal pIgR is a critical regulator of the adaptive response to S100-induced alterations in gut flora and the gut barrier function, which closely correlates with liver injury. Intestinal upregulation of pIgR could be a novel approach for treating AIH.

Scoring model to predict postoperative neurological deterioration in spinal schwannoma.

Background: Spinal schwannomas (SSs) are benign tumors affecting the nerve sheath, accounting for 25% of spinal nerve root tumors. Surgery represents the mainstay of treatment for SS patients. Following surgery, approximately 30% of patients experienced developed new or worsening neurological deterioration, which probably represented an inevitable complication of nerve sheath tumor surgery. The objective of this study was to identify the rates of new or worsening neurological deterioration in our center and accurately predict the neurological outcomes of patients with SS by developing a new scoring model. Methods: A total of 203 patients were retrospectively enrolled at our center. Risk factors associated with postoperative neurological deterioration were identified by multivariate logistic regression analysis. ß-coefficients for independent risk factors were used to define a numerical score to generate a scoring model. The validation cohort at our center was used to verify the accuracy and reliability of the scoring model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the scoring model. Results: In this study, five measured variables were selected for the scoring model: duration of preoperative symptoms (1 point), radiating pain (2 points), tumor size (2 points), tumor site (1 point), and dumbbell tumor (1 point). The scoring model divided the spinal schwannoma patients into three categories: low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-7 points), with predicted risks of neurological deterioration of 8.7%, 36%, and 87.5%, respectively. And the validation cohort confirmed the model with the predicted risks of 8.6%, 46.4%, and 66.6%, respectively. Conclusion: The new scoring model might intuitively and individually predict the risk of neurological deterioration and may aid individualized treatment decision-making for SS patients.

FGF4 improves hepatocytes ferroptosis in autoimmune hepatitis mice via activation of CISD3.

Autoimmune hepatitis (AIH) is increasingly affecting human health but pharmacotherapies remain to be identified. Growing evidence reveals that ferroptosis, a newly recognized form of programmed cell death, is critical for AIH. However, the exact mechanisms of the ferroptotic cascade remain elusive. Data in this study showed that ferroptosis aggravation was associated with protectively-elevated fibroblast growth factor 4 (FGF4) expression in Concanavalin A (ConA)-induced AIH liver injury, with these effects being effectively reversed by Ferrostatin-1 (Fer-1). Moreover, hepatic Fgf4 depletion was more susceptible to lipid peroxidation and iron accumulation, as well as hepatic lesion and inflammation caused by ConA administration. Conversely, treatment with non-mitogenic recombinant FGF4 (rFGF4) mitigated liver damage and hepatocellular ferroptosis while being accompanied by the upregulation of CDGSH iron-sulfur domain-containing protein 3 (CISD3) in vivo and in vitro. Furthermore, CISD3 overexpression exhibited stronger resistance to ferroptosis while CISD3 knockdown reduced ferroptotic biomarkers cystine/glutamate transporter (xCT) and glutathione peroxidase 4（GPX4) in rFGF4-treated Erastin-induced AML12 cells. In addition, rFGF4 significantly enhanced the levels of heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in ConA-induced AIH mice. Overall, this study showed that FGF4 can act as a phylactic role in AIH progression, with rFGF4 treatment inhibiting ferroptosis of hepatocytes by increasing CISD3 levels and activating Nrf2/HO-1 signaling.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Mitochondrial toxicants in Xian-Ling-Gu-Bao induce liver injury by regulating the PI3K/mTOR signaling pathway: an in vitro study.

BACKGROUND: Drug-induced mitochondrial toxicity is thought to be a common mechanism of drug hepatotoxicity. Xian-Ling-Gu-Bao (XLGB) oral preparation is a commonly used drug for osteoporosis in China. Classical safety evaluation studies have shown that the entire preparation and six Chinese herbal medicines have high safety, but the incidence of drug-induced liver damage due to XLGB remains high, the mechanism and toxic substances causing liver injury are still unclear. The purpose of this study is to identify compounds with potential mitochondrial liabilities in XLGB, and to clarify their underlying mechanisms and related pathways. METHODS: The mitochondrial function analysis was performed using an extracellular flux assay, which simultaneously monitored both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Through network pharmacology and in vitro experimental verification, the potential protein targets, signaling pathways and molecular mechanism of mitochondrial toxicity have been studied. RESULTS: We observed a significant decrease in mitochondrial respiration of Psoraleae Fructus and its five compounds in fundamental bioenergetics parameters such as basal respiration, ATP-linked production and maximal respiration, indicating mitochondrial dysfunction. The network pharmacology results showed that the influence of XLGB on mitochondrial dysfunction was closely related to PI3K-Akt signaling pathway, mTOR signaling pathway and Apoptosis. Western blot showed that the levels of mTOR, p-mTOR (Ser2448), Raptor, PI3K (p110α), Beclin 1, ATG5 and Caspase-9 were up-regulated after treatment with psoralidin, psoralen and bavachin, and the expression of Bcl-2 was down-regulated after bavachinin treatment. CONCLUSIONS: The hepatotoxicity of XLGB is associated with mitochondrial dysfunction. Five compounds in Psoraleae Fructus showed mitochondrial damage, they are psoralidin, isobavachalcone, bavachinin, bavachin and psoralen, especially psoralidin showed significant reduction in reserve capacity and respiratory control ratios. The molecular mechanism is related to the activation of PI3K/mTOR signaling pathway to inhibit autophagy and induce mitochondrial apoptosis.

Simulation and Optimization of Connection-Strength Performance of Axial Extrusion Joint.

Axial extrusion-connection technology is one of the important connection technologies for hydraulic piping systems, with high sealing performance and mechanical strength. In this paper, the finite-element-modeling method is used to simulate the experimental process of the connection strength of the axial extrusion joint. The generation mechanism and calculation method of the connection strength are analyzed. To optimize the joint strength, orthogonal testing and grey correlation analysis are used to analyze the influencing factors of joint strength. The key factors affecting joint strength are obtained as the friction coefficient µ1, µ2 between joint components and the groove angle θ1 of the fittings body. The back-propagation (BP) neural-network algorithm is used to establish the connection-strength model of the joint and the genetic algorithm is used to optimize it. The optimal connection strength is 8.237 kN and the optimal combination of influencing factors is 0.2, 0.4 and 76.8°. Compared with the prediction results of the neural-network genetic algorithm, the relative error of the finite-element results is 3.9%, indicating that the method has high accuracy. The results show that the extrusion-based joining process offers significant advantages in the manufacture of high-strength titanium tubular joints.

Elevated Serum CCL23 Levels at Admission Predict Delayed Cerebral Ischemia and Functional Outcome after Aneurysmal Subarachnoid Hemorrhage.

(1) Background: CC chemokine ligand 23 (CCL23) is a chemokine implicated in the inflammatory response following brain damage. The aim of this study is to identify the change in serum CCL23 levels within 24 h after aSAH and whether serum CCL23 levels are associated with initial clinical severity, delayed cerebral ischemia (DCI), and functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). (2) Methods: 102 patients with aSAH and 61 controls were included in this prospective observational study. All clinical data were collected prospectively, and their serum CCL23 levels were measured. Initial clinical severity was reflected by the Hunt-Hess score and mFisher score. Functional outcome was evaluated in terms of the Glasgow Outcome Scale (GOS) score at 6-month follow-up. (3) Results: Patients with aSAH had higher serum CCL23 levels than controls. The temporal profile of serum CCL23 levels and neutrophils count exhibited a sustained increase within 24 h after aSAH. Serum CCL23 levels were related to blood neutrophils count, blood CRP levels, and initial clinical severity. Serum CCL23 level was an independent predictor of DCI and 6-month poor outcome in aSAH patients. (4) Conclusions: Serum CCL23 levels emerged as an independent predictor for DCI and poor outcome in patients with aSAH.

Serum CCL23 emerges as a biomarker for poor prognosis in patients with intracerebral hemorrhage.

BACKGROUND: CCL23 is involved in the inflammatory response and associated with the progression of brain injury. Herein, we assessed the relationship between serum CCL23 levels and inflammation, hematoma severity, and unfavorable outcome after intracerebral hemorrhage (ICH). METHODS: In this prospective observational study of 94 ICH patients and 47 controls, serum CCL23 levels were measured. Hemorrhage severity was reflected by the National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume. An unfavorable outcome was defined as a modified Rankin Scale > 2 at 6 months after ICH. Its association with clinical outcome was confirmed using the binary logistic regression analysis. Predictive efficiency was verified under receiver operating characteristic (ROC) curve. RESULTS: Significantly increased serum CCL23 levels were observed in ICH patients, as compared to controls. Serum CCL23 levels were highly related to NIHSS score, hematoma volume, ICH score, Glasgow coma scale score, serum C-reactive protein levels, blood leucocyte count, and neutrophil count. CCL23 ≥ 62.95 pg/ml served as an independent predictor of 6-month unfavorable outcome and death, and its validity was confirmed by ROC analysis. CONCLUSION: CCL23 may be implicated in the inflammatory response and serve as a potential marker for predicting the prognosis of patients with ICH.

COA3 overexpression promotes non-small cell lung cancer metastasis by reprogramming glucose metabolism.

Recent advances in cancer research have revealed a close relationship between mitochondrial dysfunction and cancer development. Human COX assembly factor 3 (COA3), also known as CCDC56, is a mitochondrial transmembrane protein responsible for cytochrome c oxidase (COX) protein complex assembly. However, the clinical implication and biological functions of COA3 remain unexplored in human cancers, including non-small cell lung cancer (NSCLC). Here, we found that COA3 is overexpressed at both mRNA and protein levels in human NSCLC cells, mainly as a result of decreased miR-338-3p level. The protein expression level of COA3 is positively associated with lymph node metastasis and predicts poor survival in patients with NSCLC. Silencing of COA3 significantly attenuated, while forced COA3 expression enhanced the migration and invasiveness of NSCLC cells. Mechanistically, we found that aerobic glycolysis, induced at least in part by dynamic-related protein 1 (DRP1) phosphorylation-mediated mitochondrial fragmentation, contributed to COA3-promoted NSCLC metastasis. Together, our study illustrates that COA3 plays a crucial role in NSCLC carcinogenesis, implying COA3 as a prognostic marker and treatment target in NSCLC.