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Background: Next-generation sequencing of the metagenome (mNGS) is increasingly used in pathogen diagnosis for infectious diseases due to its short detection time. The time for Oxford Nanopore Technologies (ONT) sequencing-based etiology detection is further shortened compared with that of mNGS, but only a few studies have verified the time advantage and accuracy of ONT sequencing for etiology diagnosis. In 2022, a study confirmed that there was no significant difference in sensitivity and specificity between ONT and mNGS in suspected community-acquired pneumonia patients, which there was no clinical study verified in patients with SHAP., Methods: From October 24 to November 20, 2022, 10 patients with severe hospital-acquired pneumonia (SHAP) in the Nanfang Hospital intensive care unit (ICU) were prospectively enrolled. Bronchoalveolar lavage fluid (BALF) was collected for ONT sequencing, mNGS, and traditional culture. The differences in pathogen detection time and diagnostic agreement among ONT sequencing, mNGS, traditional culture method, and clinical composite diagnosis were compared., Results: Compared with mNGS and the traditional culture method, ONT sequencing had a significant advantage in pathogen detection time (9.6±0.7 h versus 24.7±2.7 h versus 132±58 h, P <0.05). The agreement rate between ONT sequencing and the clinical composite diagnosis was 73.3% (kappa value=0.737, P <0.05)., Conclusion: ONT sequencing has a potential advantage for rapidly identifying pathogens., Competing Interests: All authors declare that they have no potential conflicts of interest in this work., (© 2023 Zhao et al.)

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver function remains unclear. We show that APAP disturbance is associated with a distinct gut microbial community, with notable decreases in Lactobacillus vaginalis. Mice receiving L. vaginalis showed resistance to APAP hepatotoxicity due to the liberation of the isoflavone daidzein from the diet by bacterial β-galactosidase. The hepatoprotective effects of L. vaginalis in APAP-exposed germ-free mice were abolished with a β-galactosidase inhibitor. Similarly, β-galactosidase-deficient L. vaginalis produced poorer outcomes in APAP-treated mice than the wild-type strain, but these differences were overcome with daidzein administration. Mechanistically, daidzein prevented ferroptotic death, which was linked to decreased expression of farnesyl diphosphate synthase (Fdps) that activated a key ferroptosis pathway involving AKT-GSK3β-Nrf2. Thus, liberation of daidzein by L. vaginalis β-galactosidase inhibits Fdps-mediated hepatocyte ferroptosis, providing promising therapeutic approaches for DILI., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Sepsis, a critical condition resulting from the systemic inflammatory response to a severe microbial infection, represents a global public health challenge. However, effective treatment or intervention to prevent and combat sepsis is still lacking. Here, we report that hyodeoxycholic acid (HDCA) has excellent anti-inflammatory properties in sepsis. We discovered that the plasma concentration of HDCA was remarkably lower in patients with sepsis and negatively correlated with the severity of the disease. Similar changes in HDCA levels in plasma and cecal content samples were observed in a mouse model of sepsis, and these changes were associated with a reduced abundance of HDCA-producing strains. Interestingly, HDCA administration significantly decreased systemic inflammatory responses, prevented organ injury, and prolonged the survival of septic mice. We demonstrated that HDCA suppressed excessive activation of inflammatory macrophages by competitively blocking lipopolysaccharide binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 receptor complex, a unique mechanism that characterizes HDCA as an endogenous inhibitor of inflammatory signaling. Additionally, we verified these findings in TLR4 knockout mice. Our study highlights the potential value of HDCA as a therapeutic molecule for sepsis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Sepsis-induced acute kidney injury (AKI) is known to result from the inflammatory responses. MiRNAs participate in the development of sepsis-induced AKI. Nevertheless, the function of miR-527 in sepsis-induced AKI remains unclear., Methods: Cell viability was evaluated by CCK8 assay, and TUNEL staining was applied to assess cell apoptosis. Pro-inflammatory cytokine (TNF-α, IL-6 and IL-1β) levels were evaluated by ELISA. Meanwhile, the relation among miR-527 and Beclin1 was detected by dual luciferase report assay. Western blot and RT-qPCR were used to examine the protein and mRNA levels, respectively. Furthermore, an in vivo model was constructed to assess the function of miR-527 in sepsis-induced AKI., Results: MiR-527 downregulation significantly alleviated the symptoms of sepsis-induced AKI in mice. MiR-527 level in HK-2 cells was significantly upregulated by LPS, and downregulation of miR-527 notably reversed LPS-induced inhibition of HK-2 cell viability by inhibiting apoptosis. In addition, LPS greatly increased TNF-α, IL-6 and IL-1β levels in supernatant of HK-2 cells, while miR-527 inhibitor partially restored this phenomenon. Meanwhile, Beclin1 was found to be the downstream mRNA of miR-527, and miR-527 inhibitor notably upregulated the level of LC3. MiR-527 downregulation reversed LPS-induced HK-2 cell injury through suppression of TGF-β pathway., Conclusion: Downregulation of miR-527 alleviated sepsis-induced AKI via targeting Beclin1. Thus, miR-527 might act as a vital mediator in sepsis-induced AKI., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Abstract: Background : Our previous studies have shown that ameliorating mitochondrial damage in renal tubular epithelial cells (RTECs) can alleviate septic acute kidney injury (SAKI). It is reported that AMPK phosphorylation (p-AMPK) could ameliorate mitochondrial damage in renal tissue and Sirtuin 5 (SIRT5) overexpression significantly enhanced the level of p-AMPK in bovine preadipocytes. However, the role of SIRT5-mediated phosphorylation of AMPK in SAKI needs to be clarified. Methods : WT/SIRT5 gene knockout mouse model of cecal ligation and puncture-induced SAKI and a human kidney 2 cell model of LPS-induced SAKI were constructed. An AMPK chemical activator and SIRT5 overexpression plasmid were used. Indexes of mitochondrial structure and function, level of p-AMPK, and expression of SIRT5 protein in renal tissue and RTECs were measured. Results : After sepsis stimulation, the p-AMPK level was decreased, mitochondrial structure was disrupted, and ATP content was decreased. Notably, an AMPK activator alleviated SAKI. Sirtuin 5 gene knockout significantly aggravated SAKI, while SIRT5 overexpression alleviated mitochondrial dysfunction after LPS stimulation, as manifested by the increase of p-AMPK level, the alleviation of mitochondrial structure damage, the restoration of ATP content, the decrease of proapoptotic protein expression, as well as the reduction of reactive oxygen species generation. Conclusions : Upregulation of SIRT5 expression can attenuate mitochondrial dysfunction in RTECs and alleviate SAKI by enhancing the phosphorylation of AMPK., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 by the Shock Society.)

Background: Previous studies have shown that dexmedetomidine (DEX) may be associated with reduced vasopressor requirements in septic shock patients, however, long-term DEX-only sedation in reducing vasopressor requirements is still controversial., Methods: A retrospective study was conducted among patients with septic shock on mechanical ventilation using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary outcome was the ratio of norepinephrine equivalent dose to mean arterial pressure (NEq/MAP) in the first 72 h after DEX or other sedatives for sedation. The secondary outcomes were key organ function parameters, 28-day mortality, and 90-day mortality. Univariate, propensity score matching (PSM), and generalized linear mixed model (GLMM) analyses were performed., Results: DEX was associated with decreased NEq/MAP in the first 72 h (difference = 0.05, 95% CI = -0.02-0.08, p  = 0.002) after adjusting for confounders in the GLMM analysis. The DEX group was also associated with a lower heart rate, cardiac output (CO), lactate level, aspartate transaminase (AST) level, and higher PaO 2 /FiO 2 ratio ( p  < 0.0125). Moreover, DEX only sedation was associated with reduced 90-day mortality (OR = 0.60, 95% CI = 0.37-0.94, p  = 0.030)., Conclusion: DEX may be associated with decreased vasopressor requirements, improved AST and PaO 2 /FiO 2 levels, and reduced 90-day mortality in patients with septic shock, which warrants further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Shi, Xiong, Kong, Chen, Zhou, Zeng, An and Xu.)

Strategies to generate high-valence metal species capable of oxidizing water often employ composition and coordination tuning of oxide-based catalysts, where strong covalent interactions with metal sites are crucial. However, it remains unexplored whether a relatively weak "non-bonding" interaction between ligands and oxides can mediate the electronic states of metal sites in oxides. Here we present an unusual non-covalent phenanthroline-CoO 2 interaction that substantially elevates the population of Co 4+ sites for improved water oxidation. We find that phenanthroline only coordinates with Co 2+ forming soluble Co(phenanthroline) 2 (OH) 2 complex in alkaline electrolytes, which can be deposited as amorphous CoO x H y film containing non-bonding phenanthroline upon oxidation of Co 2+ to Co 3+/4+ . This in situ deposited catalyst demonstrates a low overpotential of 216 mV at 10 mA cm -2 and sustainable activity over 1600 h with Faradaic efficiency above 97%. Density functional theory calculations reveal that the presence of phenanthroline can stabilize CoO 2 through the non-covalent interaction and generate polaron-like electronic states at the Co-Co center., (© 2023. The Author(s).)

The aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) are critical contributors to the pulmonary vascular remodeling that occurs during the development of Pulmonary arterial hypertension (PAH). Krüppel-like Factor 7 (KLF7) has been reported to be involved in the development of certain cardiovascular diseases. However, the role of KLF7 in PAH remains unknown. Here, we aimed to explore whether KLF7 mediates the proliferation and migration of PASMCs and its underlying mechanism. In this study, Sprague Dawley rats were exposed to 60 mg/kg monocrotaline (MCT) for 3 weeks to induce PAH and human PASMCs were stimulated with 20 ng/ml platelet-derived growth factor-BB (PDGF-BB) for 24 h to induce proliferation and migration. The mRNA and protein expression of KLF7 were significantly down-regulated in MCT-induced PAH rats and PDGF-BB-treated PASMCs. Under normal conditions, KLF7 knockdown obviously promoted PASMCs proliferation and migration, whereas KLF7 overexpression exhibited the opposite effects. Furthermore, PDGF-BB promoted the PASMCs proliferation and migration, increased the cell proportion in S phase, which was significantly attenuated by overexpression of KLF7. Mechanistic investigation indicated that KLF7 through activation its target protein, the cell cycle inhibitor p21, which finally leading to the inhibition of PASMCs growth. Consistently, UC2288, a specific inhibitor of p21, partially reversed the PASMCs proliferation inhibited by KLF7 overexpression. Taken collectively, the data suggested that KLF7 inhibits PASMCs proliferation and migration via p21 pathway and it may be used as a new therapeutic target for the PAH., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The properties of ultrathin (1-2 monolayer) (hydroxy)oxide films on transition metal substrates have been extensively studied as models of the celebrated Strong Metal-Support Interaction (SMSI) and related phenomena. However, results from these analyses have been largely system specific, and limited insights into the general principles that govern film/substrate interactions exist. Here, using Density Functional Theory (DFT) calculations, we analyze the stability of ZnO x H y films on transition metal surfaces and show that the formation energies of these films are related to the binding energies of isolated Zn and O atoms via linear scaling relationships (SRs). Such relationships have previously been identified for adsorbates on metal surfaces and have been rationalized in terms of bond order conservation (BOC) principles. However, for thin (hydroxy)oxide films, SRs are not governed by standard BOC relationships, and a generalized bonding model is required to explain the slopes of these SRs. We introduce such a model for the ZnO x H y films and confirm that it also describes the behavior of reducible transition metal oxide films, such as TiO x H y , on metal substrates. We demonstrate how the SRs may be combined with grand canonical phase diagrams to predict film stability under conditions relevant to heterogeneous catalytic reactions, and we apply these insights to estimate which transition metals are likely to exhibit SMSI behavior under realistic environmental conditions. Finally, we discuss how SMSI overlayer formation for irreducible oxides, such as ZnO, is linked to hydroxylation and is mechanistically distinct from the overlayer formation for reducible oxides such as TiO 2 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background and Aims: Esmolol is a common short-acting drug to control ventricular rate. This study aimed to evaluate the association between use of esmolol and mortality in critically ill patients., Methods: This is a retrospective cohort study from MIMIC-IV database containing adult patients with a heart rate of over 100 beats/min during the intensive care unit (ICU) stay. Multivariable Cox proportional hazard models and logistic regression were used to explore the association between esmolol and mortality and adjust confounders. A 1:1 nearest neighbor propensity score matching (PSM) was performed to minimize potential cofounding bias. The comparison for secondary outcomes was performed at different points of time using an independent t -test., Results: A total of 30,332 patients were reviewed and identified as critically ill. There was no significant difference in 28-day mortality between two groups before (HR = 0.90, 95% CI = 0.73-1.12, p  = 0.343) and after PSM (HR = 0.84, 95% CI = 0.65-1.08, p  = 0.167). Similar results were shown in 90-day mortality before (HR = 0.93, 95% CI = 0.75-1.14, p  = 0.484) and after PSM (HR = 0.85, 95% CI = 0.67-1.09, p  = 0.193). However, esmolol treatment was associated with higher requirement of vasopressor use before (HR = 2.89, 95% CI = 2.18-3.82, p  < 0.001) and after PSM (HR = 2.66, 95% CI = 2.06-3.45, p  < 0.001). Esmolol treatment statistically reduced diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (all p  < 0.001) and increased fluid balance at 24 hours ( p  < 0.05) but did not significantly lower SBP ( p  = 0.721). Patients in esmolol group showed no significant difference in lactate levels and daily urine output when compared with those in non-esmolol group when adjusted for confounders (all p  > 0.05)., Conclusion: Esmolol treatment was associated with reduced heart rate and lowered DBP and MAP, which may increase vasopressor use and fluid balance at the timepoint of 24 hours in critically ill patients during ICU stay. However, after adjusting for confounders, esmolol treatment was not associated with 28-day and 90-day mortality.

Background: Amnestic mild cognitive impairment (aMCI) is regarded as a transitional state of Alzheimer's disease, with working memory (WM) impairment., Objective: To investigate the brain activity in aMCI patients during WM tasks with the functional near-infrared spectroscopy (fNIRS) technique, as well as explore the association between brain activity and cognitive function in multiple domains., Methods: This study is a case-control study of 54 aMCI patients and 33 cognitively healthy elderly (NC). All participants underwent neuropsychological assessments. fNIRS was applied to examine the brain activation during the WM task. Multivariable linear regression analysis was applied to evaluate associations between brain activation and cognitive function in multiple domains., Results: Compared to NC subjects, aMCI patients had lower activation in the bilateral prefrontal, parietal, and occipital cortex during the WM task. Additionally, activation in the left prefrontal, bilateral parietal, and occipital cortex during the encoding and maintenance phase was positively associated with memory function. During memory retrieval, higher activity in the left prefrontal, parietal, and occipital cortex were correlated with higher memory scores. Besides, a positive association also formed between attention function and the activation in the left prefrontal, parietal, and occipital cortex during the WM task., Conclusion: These findings demonstrated that reduced activation in the prefrontal, parietal and occipital cortex during WM might reflect the risk of cognitive impairment, especially memory and attention function in aMCI patients. Given the brain activation visualization, fNIRS may be a convenient and alternative tool for screening the risk of Alzheimer's disease.

Cardiovascular disease (CVD) is a group of systemic disorders threatening human health with complex pathogenesis, among which mitochondrial energy metabolism reprogramming has a critical role. Mitochondria are cell organelles that fuel the energy essential for biochemical reactions and maintain normal physiological functions of the body. Mitochondrial metabolic disorders are extensively involved in the progression of CVD, especially for energy-demanding organs such as the heart. Therefore, elucidating the role of mitochondrial metabolism in the progression of CVD is of great significance to further understand the pathogenesis of CVD and explore preventive and therapeutic methods. In this review, we discuss the major factors of mitochondrial metabolism and their potential roles in the prevention and treatment of CVD. The current application of mitochondria-targeted therapeutic agents in the treatment of CVD and advances in mitochondria-targeted gene therapy technologies are also overviewed.

It is a new advertising marketing method for commodity companies to use vloggers to endorse their products, and to influence consumers' attitudes and decisions. In view of this phenomenon, there are few studies on the relationship between vloggers and consumers, and this study aims to explore how the persuasive strategies used by vloggers to promote products influence consumers' purchase intentions. Based on the concepts of Aristotle's persuasion theory, this study extracts two specific persuasive approaches, "two-sided messages" and "emotional appeal," to explore consumers' perceptions of them and the effectiveness of these two strategies. At the same time, para-social interaction and perceived value as intermediary factors are also included in the study for further discussion. The study empirically analyzed a sample of 511 questionnaires from participants who had purchased products recommended by vloggers and came to the following conclusions: (1) vloggers can enhance consumers' purchase intention by adopting two-sided messages persuasion when promoting products; (2) vloggers' emotional persuasion can enhance consumers' purchase intention; (3) as an intermediary variable, para-social interaction plays a more obvious role in vloggers' persuasion by appealing to emotions. The audience can have common feelings with vloggers, and they are more connected with each other, thus increasing their willingness to buy; (4) Perceived value, as an intermediary variable, plays a more obvious role in vloggers' persuasion with the two-sided messages. The two-sided messages can show vloggers' credibility and more abundant information about products, so that consumers have a positive perception of product value, and the direct persuasion effect of the two-sided messages is greater. Based on the results of the study, this paper helps vloggers to adopt different persuasive approaches for different types of audiences, choose the proper marketing methods, attract the potential customers, and achieve such purposes as enriching product marketing forms and increasing market share., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sheng, Zeng, Zhang and Hu.)

Background: Recombinant human thrombopoietin (rhTPO) is reported to stimulate platelet production and increase peripheral platelet counts; it is primarily used to manage chemotherapy-induced thrombocytopenia and idiopathic thrombocytopenic purpura. However, the effect of rhTPO in patients with pneumonia and thrombocytopenia remains uncertain. Objective: To assess the association of rhTPO and platelet counts in ICU patients with pneumonia and thrombocytopenia. Materials and Methods: A retrospective cohort study was performed in the ICU department, Nanfang Hospital, Southern Medical University, Guangzhou, China. From January 2016 to April 2021, patients with pneumonia and thrombocytopenia were allocated to two groups-the rhTPO and no-rhTPO groups-according to whether they received rhTPO treatment or not during their ICU stay. Demographical and clinical data were collected and analyzed using statistical software; p < 0.05 was considered statistically significant. Results: Out of 327 patients, 149 were in the rhTPO group and 178 were in the no-rhTPO group. Within the first 7 days, platelet counts increased more for patients in the rhTPO group compared with those in the no-rhTPO group (99.21 ± 102.613 vs. 2.08 ± 43.877, p = 0.000). The clinical recovery rate of platelets increased within 7 days (65.8 vs. 18.5%, p = 0.000) and, after 7 days of enrollment, hemorrhagic scores decreased more apparently in the rhTPO group (2.81 ± 2.856 vs. 1.16 ± 2.123, p = 0.000). Further, bleeding events ceased in 66.7% of the patients in the rhTPO group compared with 37.3% of the patients in the no-rhTPO group ( p = 0.000). Less red-blood-cells transfusions were needed in the rhTPO group (3.639 ± 4.630 vs. 5.818 ± 6.858, p = 0.009). Furthermore, through logistic regression, rhTPO administration was found to be an independent indicator that affected the platelet recovery rate within 7 days. Conclusion: This study finds that rhTPO administration is associated with increased platelet counts, alleviated bleeding, and reduced blood transfusion. For patients with pneumonia and thrombocytopenia, rhTPO may be an effective therapeutic drug; however, more RCT trails are needed to confirm our observation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Xuan, Wu, Shi, Dai, Cai, An, Huang, Huang, Chen and Zeng.)

Background: Many studies demonstrated no improved survival in patients with pulmonary artery catheter placement. However, no consistent conclusions have been drawn regarding the impact of pulmonary artery catheter in critically ill patients with heart disease. This study aimed to investigate the association of early pulmonary artery catheter use with 28-day mortality in that population., Methods: The Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database, a single-center critical care database, was employed to investigate this issue. This study enrolled a total of 11,887 critically ill patients with cardiac disease with or without pulmonary artery catheter insertion. The primary outcome was 28-day mortality. The multivariate regression was modeled to examine the association between pulmonary artery catheter and outcomes. Additionally, we examined the effect modification by cardiac surgeries. Propensity score matching was conducted to validate our findings., Results: No improvement in 28-day mortality was observed among the pulmonary artery catheter group compared to the non-pulmonary artery catheter group (odds ratio 95% confidence interval: 1.18 [1.00-1.38], P = .049). When stratified by cardiac surgeries, the results were consistent. The patients in the pulmonary artery catheter group had fewer ventilation-free days and vasopressor-free days than those in the nonpulmonary artery catheter group after surgery stratification. In the surgical patients, pulmonary artery catheter insertion was not associated with the occurrence of acute kidney injury, and it was associated with a higher daily fluid input (mean difference 95% confidence interval: 0.13 [0.05-0.20], P = .001). In nonsurgical patients, the pulmonary artery catheter group had a higher risk of acute kidney injury occurrence (odds ratio 95% confidence interval: 1.94 [1.32-2.84], P = .001)., Conclusion: Early pulmonary artery catheter placement is not associated with survival benefits in critically ill patients with cardiac diseases, either in surgical or nonsurgical patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: Sepsis is a fatal health issue induced by an aberrant host response to infection, and it correlates with organ damage and a high mortality rate. Endothelial barrier dysfunction and subsequent capillary leakage play major roles in sepsis-induced multiorgan dysfunction. Anaerobic glycolysis is the primary metabolic mode in sepsis and the pyruvate dehydrogenase complex (PDHC) serves as a critical hub in energy regulation. Therefore, it is important to understand the role of PDHC in metabolic regulation during the development of sepsis-induced endothelial barrier dysfunction.In present study, human umbilical vein endothelial cells (HUVECs) and C57 BL/6 mice were treated with lipopolysaccharide (LPS) as models of endotoxemia. LPS increased basal glycolysis, compensatory glycolysis, and lactate secretion, indicating increased glycolysis level in endothelial cells (ECs). Activation of PDHC with dichloroacetate (DCA) reversed LPS-induced glycolysis, allowing PDHC to remain in the active dephosphorylated state, thereby preventing lactic acid production and HUVECs monolayers barrier dysfunction, as assessed by transendothelial electrical resistance and Fluorescein Isothiocyanate-labeled dextran. The in vivo study also showed that the lactate level and vascular permeability were increased in LPS-treated mice, but pretreatment with DCA attenuated these increases. The LPS-treated HUVEC model showed that DCA reversed LPS-induced phosphorylation of pyruvate dehydrogenase E1α Ser293 and Ser300 to restore PDHC activity. Immunoprecipitation results showed that LPS treatment increased the acetylation level of PDH E1α in HUVECs.Our study suggested that activation of PDHC may represent a therapeutic target for treatment of LPS-induced endothelial barrier dysfunction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Heat stroke (HS) is a severe condition characterized by increased morbidity and high mortality. Acute liver injury (ALI) is a well-documented complication of HS. The tumor suppressor p53 plays an important role in regulation of mitochondrial integrity and mitophagy in several forms of ALI. However, the role of p53-regulated mitophagy in HS-ALI remains unclear. In our study, we discovered the dynamic changes of mitophagy in hepatocytes and demonstrated the protective effects of mitophagy activation on HS-ALI. Pretreatment with 3-MA or Mdivi-1 significantly exacerbated ALI by inhibiting mitophagy in HS-ALI mice. Consistent with the animal HS-ALI model results, silencing Parkin aggravated mitochondrial damage and apoptosis by inhibiting mitophagy in HS-treated normal human liver cell line (LO2 cells). Moreover, we described an increase in the translocation of p53 from the nucleus to the cytoplasm, and cytosolic p53 binds to Parkin in LO2 cells following HS. p53 overexpression using a specific adenovirus or Tenovin-6 exacerbated HS-ALI through Parkin-dependent mitophagy both in vivo and in vitro , whereas inhibition of p53 using siRNA or PFT-α effectively reversed this process. Our results demonstrate that cytosolic p53 binds to Parkin and inhibits mitophagy by preventing Parkin's translocation from the cytosol to the mitochondria, which decreases mitophagy activation and leads to hepatocyte apoptosis in HS-ALI. Overall, pharmacologic induction of mitophagy by inhibiting p53 may be a promising therapeutic approach for HS-ALI treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Xie, Zhong, Cai, Huang, Liu, Zeng and Liu.)

β-elemene (Bel) is a sesquiterpene compound that has shown potential in the antinociceptive treatment. This study focused on the function of Bel in neuropathic pain relief in mice. A murine model with spared nerve injury (SNI) was established and treated with Bel. The paw withdrawal thresholds in response to mechanical and thermal stimulations were examined using von Frey filaments. The L4-L6 spinal dorsal horn tissue samples were collected for histological examination. Bel treatment reduced the sensitivities of model mice to mechanical and thermal stimulations, and it inhibited activation of microglia and the secretion of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in tissues. Bel treatment reduced the expression of nociceptor excitatory N-methyl-D-aspartate receptor (NMDAR), whereas it enhanced the expression of nociceptor inhibitory gamma-aminobutyric acid A (GABAA) receptor to relieve the nociception of mice. The C-X-C motif chemokine receptor 3 (CXCR3) is a downstream molecule mediated by Bel. Either overexpression of CXCR3 or downregulation of GABAA receptor in the tissues aggravated the neuropathic pain in SNI mice which was initially relieved by Bel. In conclusion, this study suggested that Bel might serve as a drug for nociception management by inhibiting CXCR3 and upregulating GABAA receptor. This study may offer novel insights into the field of neuropathic pain relief.

Background: Synovial mesenchymal stem cells (SMSCs) have been discussed as promising tools for protecting chondrocytes from loss and inhibiting osteoarthritis (OA). This work infocuses on the function of SMSC-derived extracellular vesicles (EVs) in chondrocytes during OA and the molecular mechanism., Methods: EVs were extracted from SMSCs and identified. Chondrocytes were treated with interleukin (IL)-1β to induce an OA-like condition in vitro and then treated with EVs. The proliferation, apoptosis, migration, extracellular matrix (ECM) degradation and inflammation in chondrocytes were examined. Key microRNAs (miRNAs) carried by EVs were screened using a microarray analysis, and the downstream molecules involved were explored using bioinformatic analysis. Rescue experiments were performed to validate the involvements of these molecules in EV-mediated events., Results: EVs restored proliferation and migration while reduced apoptosis, ECM degradation and the secretion of pro-inflammatory cytokines in chondrocytes induced by IL-1β. miR-130b-3p was significantly elevated in chondrocytes after EVs treatment. Knockdown of miR-130b-3p blocked the protective roles of EVs against IL-1β-induced damage to chondrocytes. miR-130b-3p was found to target LDL receptor related protein 12 (LRP12) mRNA in chondrocytes. Overexpression of LRP12 counteracted the effects of EVs as well and activated the AKT/β-catenin signaling pathway., Conclusion: This study provided evidence that EVs alleviate chondrocyte damage during OA through miR-130b-3p-mediated inhibition of the LRP12/AKT/β-catenin axis. This study may offer novel thoughts into the protection of chondrocytes and the management of OA.

Background: Most prostate cancer patients are already in the middle/advanced stages of the disease at the time of detection. Whether brucine can regulate apoptosis in prostate cancer cells through the expression of heat shock protein 70 (HSP70) has not been reported. We preliminarily investigated the effects of brucine on the mitochondrial apoptosis and HSP70 expression of prostate cancer cells and analyzed brucine's possible mechanisms in the hope of providing an experimental basis for its clinical application., Methods: The effect of brucine on the activity of PC-3 cells was determined by the methodology of tetrazolium (MTT) assay method. The effect of brucine on apoptosis was measured by Hoechst 33258 staining and flow cytometry, and western blotting was used to detect the expression levels of the apoptosis-related heat shock protein 70 (HSP70), anti-apoptotic protease activating factor 1 (Apaf-1) and anti-cysteine protease-3 (caspase-3)., Results: At 24 and 48 h, the activity of human prostate cancer PC-3 cells in the low, medium, and high dose brucine groups was significantly lower than that of the control group, with a dose-dependent difference (P<0.01). The nuclei of the control group fluoresced uniformly with intact nuclei, whereas the nuclei of the brucine group appeared crinkled, and dense granular masses of strong blue fluorescence were visible. The apoptosis rate of human prostate cancer PC-3 cells in the low, medium, and high dose brucine groups was significantly higher than that in the control group (P<0.01) and was dose-dependent. The expression levels of the HSP70 protein in the human prostate cancer PC-3 cells in the low, medium, and high dose brucine groups were significantly lower than those in the control group, while the expression levels of the Apaf-1 and caspase-3 proteins were significantly higher than those in the control group (P<0.01) and showed a dose-dependent relationship., Conclusions: Brucine downregulated HSP70 expression in human prostate cancer PC-3 cells and inhibited the mitochondrial apoptotic signaling pathway, thus acting as an anti-apoptotic agent., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-209/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

To identify the risk factors related to the patient's 28-day mortality, we retrospectively reviewed the records of patients with intra-abdominal infections admitted to the ICU of Nanfang Hospital, Southern Medical University from 2011 to 2018. Multivariate Cox proportional hazard regression analysis was used to identify independent risk factors for mortality. Four hundred and thirty-one patients with intra-abdominal infections were analyzed in the study. The 28-day mortality stepwise increased with greater severity of disease expression: 3.5% in infected patients without sepsis, 7.6% in septic patients, and 30.9% in patients with septic shock ( p < 0.001). In multivariate analysis, independent risk factors for 28-day mortality were underlying chronic diseases (adjusted HR 3.137, 95% CI 1.425-6.906), high Sequential Organ Failure Assessment (SOFA) score (adjusted HR 1.285, 95% CI 1.160-1.424), low hematocrit (adjusted HR 1.099, 95% CI 1.042-1.161), and receiving more fluid within 72 h (adjusted HR 1.028, 95% CI 1.015-1.041). Compared to the first and last 4 years, the early use of antibiotics, the optimization of IAT strategies, and the restriction of positive fluid balance were related to the decline in mortality of IAIs in the later period. Therefore, underlying chronic diseases, high SOFA score, low hematocrit, and receiving more fluid within 72 h after ICU admission were independent risk factors for patients' poor prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Li, Ou, Zeng and Chen.)

Sensitivity is an important parameter for a molecular probe. Hill-type pH probes exhibit improved detection sensitivity compared to the traditional pH probes following the Henderson-Hasselbalch equation. Exploiting positive cooperativity, we recently devised a novel molecular scaffold ( PHX ) to offer such an unconventional Hill-type pH titration profile. We previously confirmed that PHX is not a pure Hill-type probe yet. Only 64% of its absorbance/fluorescence turn-on is the result of a Hill-type pathway. The remaining 36% is from an undesired Henderson-Hasselbalch-type pathway (HH pathway). In this work, the Thorpe-Ingold dialkylation was harnessed to further suppress the percent contribution of the HH pathway down to 16%. We also propose that PHX is a viable molecular model for assessing the efficacy of the steric compressing effect induced by different Thorpe-Ingold dialkylations.

Maternal obesity has been reported to be related to neurodevelopmental disorders in the offspring. However, the underlying mechanisms and effective interventions remain unclear. This cross-sectional study with 778 children aged 7-14 years in China indicated that maternal obesity is strongly associated with children's lower cognition and sociality. Moreover, it has been demonstrated that maternal obesity in mice disrupted the behavior and gut microbiome in offspring, both of which were restored by a high-fiber diet in either dams or offspring via alleviating synaptic impairments and microglial maturation defects. Co-housing and feces microbiota transplantation experiments revealed a causal relationship between microbiota and behavioral changes. Moreover, treatment with the microbiota-derived short-chain fatty acids also alleviated the behavioral deficits in the offspring of obese dams. Together, our study indicated that the microbiota-metabolites-brain axis may underlie maternal obesity-induced cognitive and social dysfunctions and that high dietary fiber intake could be a promising intervention., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Fluid therapy is a cornerstone in the treatment of sepsis. Recently, the guidelines have recommended the combined administration that using crystalloids plus albumin for septic patients, but the optimal timing for albumin combined is still unclear. The objective of this study was to investigate the association of timing of albumin combined with 28-day mortality in patients with sepsis., Methods: We involved septic patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and these patients were categorized into crystalloids group (crystalloids alone) and early combination group (crystalloids combined albumin at 0-24 h). The primary outcome was 28-day mortality. We used propensity score matching (PSM) to adjust confounding and restricted mean survival time (RMST) analysis was conducted to quantify the beneficial effect on survival due to the combination group., Results: We categorized 6597 and 920 patients in the "crystalloids alone" and "early combination", respectively. After PSM, compared to the crystalloids group, the combination group was associated with the increased survival among 28-day (increased survival: 3.39 days, 95% CI 2.53-4.25; P < 0.001) after ICU admission. Patients who received albumin combination at the first 24-h was associated with prolonged LOS in ICU (10.72 days vs. 8.24 days; P < 0.001) but lower risk of 28-day mortality (12.5% vs 16.4%, P = 0.003) than those received crystalloids alone., Conclusion: In septic patients, receiving albumin combined within the first 24-h after crystalloids administration was associated with an increment of survival in 28 days.

Our previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

Objective: To assess the predictors and outcomes of acute kidney injury (AKI) among patients with coronavirus disease 2019 (COVID-19)., Objective: This retrospective observational study was conducted among patients with a confirmed diagnosis of COVID-19 admitted to Hankou Hospital between January, 5 and March 8, 2020. We evaluated the association of AKI with the demographic and biochemical parameters and clinical outcomes of the patients using univariate regression analysis., Objective: Atotal of 287 COVID-19 patients, including 55 with AKI and 232 without AKI, were included in the analysis. Compared with the patients without AKI, the patients with AKI were older, predominantly male, and were more likely to have hypoxia and pre-existing hypertension and cerebrovascular diseases. The patients with AKI also had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3% and that of stage 2 or 3 AKI was 4.9%. The patients with AKI had much higher mortality rate than those without AKI., Objective: AKI is an important complication of COVID-19. An older age, a male gender, multiple pre- existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions are all potential risk factors ofAKI. COVID- 19 patients with AKI that progresses into stages 2 or 3 AKI have a high mortality rate. Prevention of AKI and monitoring kidney function is critical in the care of COVID-19 patients.

Introduction: Resveratrol plays a protective role against sepsis development, and the long noncoding RNA (lncRNA) MALAT1 is an inflammation-relevant biomarker. This investigation attempted to reveal whether resveratrol attenuated inflammation of sepsis-induced acute kidney injury (AKI) by regulating MALAT1., Material and Methods: In total 120 rats were divided into a control group (n = 20), a Sham group (n = 20), a sepsis group (n = 40) and a resveratrol group (n = 40), and serum levels of inflammatory cytokines and AKI biomarkers were determined. An equal number of rats under identical treatments were, additionally, tracked for their survival, and the serum level of lncRNA MALAT1 was measured by RT-PCR. Moreover, septic cell models were constructed by treating HK-2 cells with lipopolysaccharide (LPS), and tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 levels released by the cells were determined with ELISA., Results: Resveratrol treatment significantly brought down serum levels of inflammatory cytokines (i.e. TNF-α, IL-1β and IL-6), kidney function indicators (i.e. Scr, blood urea nitrogen [BUN] and Scys C), AKI biomarkers (i.e. NGAL and KIM-1) and MALAT1 in cecal ligation and puncture (CLP)-induced septic model rats (all p < 0.05), and the life span of septic rats was elongated by resveratrol treatment (p < 0.05). Viability and cytokine release of LPS-treated HK2 cells were rescued by resveratrol (p < 0.05), which was accompanied by a marked fall of MALAT1 expression (p < 0.05). In addition, si-MALAT1 diminished viability and suppressed cytokine release of HK2 cells, while pcDNA3.1-MALAT1 hindered the impact of resveratrol on the inflammatory response of HK2 cells (p < 0.05). Ultimately, miR-205, a protective molecule in sepsis-relevant AKI, was down-regulated by resveratrol and si-MALAT1 (p < 0.05)., Conclusions: Resveratrol relieved sepsis-induced AKI by restraining the lncRNA MALAT1/miR-205 axis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Objective: To explore the clinical characteristics and outcomes of adult critically ill patients with COVID-19 and identify the risk factors correlated with in-hospital deaths., Methods: This study was conducted among 20 confirmed adult cases of COVID-19 in the Intensive Care Unit (ICU) of Honghu People's Hospital in Jingzhou City, Hubei Province. According to the final outcome, the patients were divided into survivor group and death group with 10 patients each. The demographic data, clinical manifestations and signs, laboratory findings, treatment measures and clinical outcomes were obtained from electronic medical records to compare the clinical characteristics and outcomes between the two groups. Univariate logistic analysis was used to analyze the risk factors associated with in-hospital death., Results: The mean age of patients with confirmed COVID-19 was 70 ± 12 years, and 40% of them were male. The patients were admitted to ICU 11 ± 9 days after symptom onset. The most common symptoms on admission were cough (19 cases), fatigue or myalgia (18 cases), fever (17 cases) and dyspnea (16 cases). Eleven (55%) of the patients had underlying diseases, among which hypertension was the most common (11 cases), followed by cardiovascular disease (4 cases) and diabetes (3 cases). Six (30%) of the patients received invasive mechanical ventilation and continued renal replacement therapy but eventually died. Acute cardiac injury was the most common complication (19 cases). Half of the patients died between the 2nd and 19th day after ICU admission. Compared with dead patients, the surviving patients had a lower average body weight (61.70±2.36 vs 68.60±7.15 kg, P =0.01) and a higher Glasgow Coma Index (14.69 ± 0.70 vs 12.70 ± 2.45, P =0.03), and were less likely to develop shock (2 vs 10, P =0.001) or acute respiratory distress syndrome (2 vs 10, P =0.001)., Conclusions: Critically ill patients with COVID-19 are generally older. A higher body weight and a lower lymphocyte count are potentially associated with a greater likeliness of fatality in ICU patients with COVID-19.

NiFe and CoFe (MFe) layered double hydroxides (LDHs) are among the most active electrocatalysts for the alkaline oxygen evolution reaction (OER). Herein, we combine electrochemical measurements, operando X-ray scattering and absorption spectroscopy, and density functional theory (DFT) calculations to elucidate the catalytically active phase, reaction center and the OER mechanism. We provide the first direct atomic-scale evidence that, under applied anodic potentials, MFe LDHs oxidize from as-prepared α-phases to activated γ-phases. The OER-active γ-phases are characterized by about 8% contraction of the lattice spacing and switching of the intercalated ions. DFT calculations reveal that the OER proceeds via a Mars van Krevelen mechanism. The flexible electronic structure of the surface Fe sites, and their synergy with nearest-neighbor M sites through formation of O-bridged Fe-M reaction centers, stabilize OER intermediates that are unfavorable on pure M-M centers and single Fe sites, fundamentally accounting for the high catalytic activity of MFe LDHs.

In a previous study, we demonstrated the role of polydatin (PD) in protecting against multiple organ dysfunction in sepsis. The aim of this study is to investigate whether PD protects against lipopolysaccharide (LPS)-induced endothelial barrier disruption through SIRT3 activation and to disclose the underlying mechanisms. Wild-type mice were injected with LPS and Evans Blue assay was performed to evaluate vascular permeability. Primary human umbilical vein endothelial cells (HUVECs) were stimulated with LPS. Endothelial permeability was evaluated by transendothelial electrical resistance (TER) and FITC-dextran leakage. SIRT3 activity was determined by a Deacetylase Fluorometric kit, and protein expression level of SIRT3 was detected by western blotting. Mitochondrial function was evaluated by determination of ROS level, mitochondrial membrane potential and mPTP opening. In endotoxemic mice, PD pretreatment attenuated vascular leakage in multiple organs while SIRT3 inhibition with 3-TYP reversed the effects of PD. PD treatment in late sepsis also exhibited barrier protective effects. In HUVECs, PD alleviated LPS-induced F-actin rearrangement, cadherin-catenin complex dissociation and endothelial hyperpermeability, whereas 3-TYP or SIRT3 siRNA attenuated the protective effects of PD. PD enhanced SIRT3 deacetylase activity, and attenuated LPS-induced decrease in SIRT3 expression as well. Furthermore, gain-of-function and loss-of-function strategies also confirmed the role of SIRT3 in enhancing endothelial barrier integrity. It was further ascertained that PD enhanced SIRT3-mediated deacetylation of SOD2 and cyclophilin D (CypD), thus suppressing mitochondrial dysfunction and subsequent endothelial barrier dysfunction. In addition, it was revealed that RAGE was involved in LPS-regulated SIRT3 signaling. Our results suggest that polydatin protects against LPS-induced endothelial barrier disruption dependent on SIRT3 and can be applied as a potential therapy for sepsis.

We review the experience with the diagnosis and treatment of secondary cerebral infarction in an elderly patient with coronavirus disease 2019 (COVID-19). COVID-19 has rapid disease progression with a high mortality rate in elderly patients, and physicians should be alert to secondary bacterial infection that may result in coagulation dysfunction and cerebral infarction. Early anti-infection therapy, immune regulation and appropriate anticoagulation intervention may help improve the prognosis of the patients.

Necroptosis, a form of regulated necrosis, has been reported to be involved in numerous pathologies, including sepsis. However, a protective effect of the selective inhibitor of necroptosis, necrostatin-1 (Nec-1), against sepsis remains to be confirmed. Animals (rats and mice) were subjected to cecal ligation and puncture (CLP) to mimic clinical sepsis. Nec-1 or its vehicle (control) was administered 20 min before CLP. Survival time was observed up to 72 h after CLP. Specimens of liver tissue and serum were obtained at 6 h, 12 h, and 18 h. Expression of necroptosis-related proteins [receptor-interacting protein kinase (RIP)1, RIP3, and mixed lineage kinase domain-like (MLKL)] was determined by Western blot analysis. The RIP1/RIP3 interaction and the recruitment of MLKL to RIP3 were also analyzed. Liver function, histopathological changes, serum inflammation cytokines, TUNEL staining, and the expression of apoptosis-related protein, including caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (Bax), was determined. As expected, Nec-1 administration reduced the expression of necroptosis-related proteins and the RIP1/RIP3 interaction, indicating inhibited necroptosis. Surprisingly, Nec-1 treatment exacerbated the liver injury and shortened survival time of septic rats with increased TUNEL-positive cells, cleaved caspase-3 protein content, and Bax/Bcl-2 ratio. Collectively, these findings show that Nec-1 administration inhibited the hepatocyte necroptosis pathway but accelerated apoptosis via the apoptotic pathway in CLP-induced sepsis rat. NEW & NOTEWORTHY The present study demonstrated that a chemical inhibitor necrostatin-1 (Nec-1) or receptor-interacting protein kinase(RIP1) knock down targeted at necroptosis inhibition accelerated liver injury of following sepsis. For fundamental research, these results warrant further investigation of the potential link between Nec-1 administration and the cellular apoptosis following sepsis induced liver injury. For applied research, these results suggest the potential harmful effect of Nec-1 on future sepsis treatment.

Sepsis is the leading cause of death in the intensive care unit and continues to lack effective treatment. It is widely accepted that high-mobility group box 1 (HMGB1) is a key inflammatory mediator in the pathogenesis of sepsis. Moreover, some studies indicate that the functions of HMGB1 depend on its molecular localization and posttranslational modifications. Our previous study confirms that sirtuin 1, silent information regulator 2-related enzyme 1 (SIRT1), a type III deacetylase, can ameliorate sepsis-associated acute kidney injury (SA-AKI). We explored the effect and mechanism of SIRT1 on HMGB1 using a mouse model of cecal ligation and puncture-induced sepsis and LPS-treated human kidney (HK-2) cell line. We found that HMGB1 is elevated in the serum but is gradually reduced in kidney cells in the later stages of septic mice. The acetylation modification of HMGB1 is a key process before its nucleus-to-cytoplasm translocation and extracellular secretion in kidney cells, accelerating the development of SA-AKI. Moreover, SIRT1 can physically interact with HMGB1 at the deacetylated lysine sites K28, K29, and K30, subsequently suppressing downstream inflammatory signaling. Thus the SIRT1-HMGB1 signaling pathway is a crucial mechanism in the development of SA-AKI and presents a novel experimental perspective for future SA-AKI research.

Objective: Sepsis, life-threatening organ dysfunction caused by a dysregulated host response to infection, is a major public health concern. To date, the mechanism of sepsis is not completely understood, which is still a huge task ahead of numerous clinical and laboratory researchers. Recently, increasing evidences show that deacetylase sirtuins play an important role in sepsis and the function of sirtuins are varied in different stages of sepsis. More importantly, the mechanism of sirutins is not fully understood. The sirtuins family is composed by sirtuin 1-7 members. Among them, sirtuin 1 is widely reported. In addition to sirtuin 1, other members of sirtuins are also involved in the regulation of inflammation or metabolism signaling following sepsis. Of note, the sirtuins may interact with each other and form a precious control mechanism. Herein, we tried to summarize the recent paper from PubMed, to explain the possible mechanism of distinct role of sirtuin 1/2, to generalize the downstream effects of sirtuin 3 action, and to describe the interactions among sirtuins members on sepsis, which might be helpful for our future research and potential clinical applications.

Lumbar disc herniation is usually managed with conservative treatment or surgery. However, conservative therapy seldom yields good results, and surgery is associated with multiple complications. This study aimed to assess bipolar radiofrequency thermocoagulation for the treatment of lumbar disc herniation. A total of 168 patients with lumbar disc herniation suitable for radiofrequency thermocoagulation were enrolled and randomized to monopolar radiofrequency thermocoagulation (control group, n=84) or bipolar radiofrequency thermocoagulation (experimental group, n=84) treatment groups. Ablation sites were targeted under CT scan guidance, and consecutive radiofrequency therapy was used. One and two probes were used for monopolar and bipolar thermocoagulation, respectively. Thermocoagulation was achieved at 50°C, 60°C, and 70°C for 60s each, 80°C for 90s, and 92°C for 100s. Symptoms and complications were evaluated using the modified Macnab criteria and Visual Analog Scale at 7, 30, and 180days postoperatively. At 180days, a significantly higher efficacy rate was obtained in the experimental group compared with control patients (91.6% versus 79.7%, P<0.05). No severe complications were occurred in either group. Targeted ablation via bipolar radiofrequency thermocoagulation is efficient for lumbar disc herniation treatment, and should be further explored for broad clinical application., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Object: Recent studies have suggested that intrinsic apoptotic signaling cascade is involved in endothelial barrier dysfunction following hemorrhagic shock (HS), which results in vascular hyperpermeability. Our previous study demonstrated that ulinastatin (UTI) inhibits oxidant-induced endothelial hyperpermeability and apoptotic signaling. In present study, we hypothesized that UTI would improve HS-induced vascular hyperpermeability by regulating the intrinsic apoptotic signaling cascade., Methods: Hemorrhagic shock was induced in rats by withdrawing blood to reduce the mean arterial pressure to 40-45 mmHg for 60 min, followed by reperfusion. Mesenteric postcapillary venules were examined for changes in hyperpermeability by intravital microscopy. In vitro, Rat lung microvascular endothelial cells (RLMVECs) were exposed in hemorrhagic shock serum for 120 min, followed by transendothelial electrical resistance (TER) estimation. Mitochondrial release of cytochrome c and caspase-3 activation was estimated in vivo. In vitro, ratio of cell apoptosis was evaluated by Annexin-V/PI double stain assay; mitochondrial membrane potential (∆Ψm) was determined with JC-1; intracellular ATP content was assayed by a commercial kit; reactive oxygen species (ROS) was measured by DCFH-DA; adherens junction protein β-catenin was detected by immunofluorescense staining., Results: In vivo, UTI attenuated HS-induced vascular hyperpermeability versus the HS group (P < 0.05); In vitro, UTI attenuated shock serum induced RLMEC monolayer hyperpermeability (P < 0.05). In vivo, UTI inhibited HS-induced cytochrome c release and caspase-3 activation (P < 0.05). In vitro, shock serum induced cell apoptosis, low ATP level, ∆Ψm depolarization, ROS increase were improved by UTI pre-treatment (P < 0.05). UTI improved shock serum induced disruption of endothelial cell adherens junction., Conclusions: UTI inhibits vascular hyperpermeability following HS. UTI regulates oxidative stress and intrinsic apoptotic signaling following HS.

Anti-inflammatory and anti-apoptotic effects of polydatin (PD) have been demonstrated in our previous studies. Recently, we have found that PD treatment can ameliorate burn-induced acute lung injury (ALI). In the present study, we hypothesized that PD may provide protective effect against LPS-induced ALI through reducing inflammation and apoptosis. Rats were respectively pretreated with PD at doses of 15, 30 and 45 mg/kg weight, followed by intratracheal administration of lipopolysaccharide (LPS). LPS-challenged rats exhibited significant lung injury characterized by the deterioration of histopathology, pulmonary microvascular hyperpermeability, wet-to-dry weight ratio, and oxygenation index, which was attenuated by PD (30 and 45 mg/kg) treatment. Moreover, PD (30 and 45 mg/kg) treatment inhibited LPS-induced inflammatory response, as evidenced by the downregulation of lung myeloperoxidase activity, total cells and PMNs in bronchoalveolar lavage fluid, and the systemic levels of the pro-inflammatory cytokines. Furthermore, PD (30 and 45 mg/kg) treatment remarkably improved LPS-induced increase in TUNEL (deoxynucleotidyl transferase dUTP nick end labeling) staining-positive cells, caspase 3 activity, Bax over-expression and Bcl-2 down-expression. In conclusion, these results demonstrate that PD (30 and 45 mg/kg) treatment attenuates LPS-induced ALI through reducing lung inflammation and apoptosis.

Oxidants are important signaling molecules known to increase endothelial permeability. Studies implicate reactive oxygen species (ROS) and the intrinsic apoptotic signaling cascades as mediators of vascular hyperpermeability. Here we report the protective effects of ulinastatin, a serine protease inhibitor with antiapoptotic properties, against oxidant-induced endothelial monolayer hyperpermeability. HUVECs were respectively pretreated with 10,000 and 50,000 u/l ulinastatin, followed by stimulation of 0.6 mM H₂O₂. Monolayer permeability was determined by transendothelial electrical resistance (TER); Mitochondrial release of cytochrome c was determined by enzyme-linked immunosorbent assay; Caspase-3 activity was measured by fluorometric assay; Adherens junction protein β-catenin was detected by immunofluorescense staining; Ratio of cell apoptosis was evaluated by Annexin-V/PI double stain assay; Mitochondrial membrane potential (Δψm) was determined with JC-1; Intracellular ATP content was assayed by a commercial kit; Bax and Bcl-2 expression were estimated by western blotting; Intracellular reactive oxygen species (ROS) level was measured by DCFH-DA. H₂O₂ exposure resulted in endothelial hyperpermeability and ROS formation (P < 0.05). The activation of mitochondrial intrinsic apoptotic signaling pathway was evidenced from BAX up-regulation, Bcl-2 down-regulation, mitochondrial depolarization, an increase in cytochrome c release, and activation of caspase-3 (P < 0.05). UTI (50,000 u/l) attenuated endothelial hyperpermeability, ROS formation, mitochondrial dysfunction, cytochrome c release, activation of caspase-3, and disruption of cell adherens junctions (P < 0.05). Together, these results demonstrate that UTI provides protection against vascular hyperpermeability by modulating the intrinsic apoptotic signaling.