Oxidative Tandem Cyclization of Aromatic Acids with (Benzo)thiophenes: One-Pot Access to Planar Sulfur-Containing Polycyclic Heteroarenes for Lipid-Droplet-Targeted Probes.

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

Effect of Remimazolam on Emergence Delirium in Children Undergoing Laparoscopic Surgery: A Double-Blinded Randomized Trial.

BACKGROUND: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children. METHODS: A hundred and twenty children aged 1-6 years old were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg kg -1 h -1; group RB, which received a single bolus of remimazolam at 0.2 mg kg -1 at the beginning of wound closure; and group C, which received a continuous infusion of saline at 1 mL kg -1 h -1 and single bolus of saline at 0.2 mL kg -1 at the beginning of sutures. The primary outcome was the incidence of emergence delirium assessed by pediatric anesthesia emergence delirium (PAED) scale. Secondary outcomes included the number of rescues propofol administrations in the post-anesthesia care unit (PACU), recovery time, end-tidal sevoflurane concentration when maintaining BIS within the range of 40-60, and adverse events. RESULTS: The incidence of emergence delirium in group RC (5%, vs. group C, risk ratio, 0.14; 95% CI, 0.04 to 0.59; P=0.001) and group RB (7.7%, vs. group C, risk ratio, 0.22; 95% CI, 0.07 to 0.71; P=0.003) was significantly lower compared with group C (32.5%). Propofol was given to 2 patients in each of groups RC and RB to treat delirium and to 10 patients in group C (group RC vs. group C, risk ratio, 0.20; 95% CI, 0.05 to 0.86; P=0.012; group RB vs. group C, risk ratio, 0.21; 95% CI, 0.05 to 0.88; P=0.014). No differences in the recovery time and adverse effects were detected. CONCLUSIONS: Both continuous infusion and single bolus administration of remimazolam can effectively reduce the occurrence of emergence delirium in children.

Preoperative Anxiolytic and Sedative Effects of Intranasal Remimazolam and Dexmedetomidine: A Randomized Controlled Clinical Study in Children Undergoing General Surgeries.

Purpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries. Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg-1), Group D (intranasal dexmedetomidine 2 mcg kg-1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS). Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010). Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation. Trial Registration: NCT04720963, January 22, 2021, ClinicalTrials.Gov.

Comparison of postoperative analgesia and side effects in pediatric laparoscopic surgery with morphine and nalbuphine.

There is currently no consensus on the optimal perioperative pain management strategy involving specific opioids. This study aims to compare the postoperative analgesia, the associated side effects between nalbuphine and morphine in children undergoing laparoscopic surgery. One hundred ninety children were randomly assigned to nalbuphine (0.2 mg/kg) or morphine (0.2 mg/kg). Nalbuphine's analgesic effect was non-inferior to morphine, with similar total rescue analgesic consumption during PACU stay (0.03 ± 0.05mg vs. 0.04 ± 0.06 mg, p > 0.05). Nalbuphine group had a lower incidence of respiratory depression (RR ≤ 10/min) (4.8% vs. 38.6%, p < 0.001), PONV (2.4% vs. 18.1%, p = 0.002), and pruritus (0% vs. 16.9%, p < 0.001) than morphine. Additionally, nalbuphine showed a shorter laryngeal mask airway removal time (13.9 [12.7, 15.1]) compared with morphine (17.0 [15.1, 18.9], p = 0.011). Nalbuphine provides equipotent analgesia with significantly lower incidences of respiratory depression, PONV, and pruritus compared with morphine in pediatric laparoscopic surgery.

Retraction Notice to: TNFAIP8 Promotes Cisplatin Chemoresistance in Triple-Negative Breast Cancer by Repressing p53-Mediated miR-205-5p Expression.

[This retracts the article DOI: 10.1016/j.omtn.2020.09.025.].

Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats.

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Trend of research on the medical use of molecular hydrogen: a bibliometric analysis.

The medical use of molecular hydrogen, including hydrogen-rich water and hydrogen gas, has been extensively explored since 2007. This article aimed to demonstrate the trend in medical research on molecular hydrogen. A total of 1126 publications on hydrogen therapy were retrieved from the PubMed database until July 30, 2021. From 2007 to 2020, the number of publications in this field had been on an upward trend. Medical Gas Research, Scientific Report and Shock have contributed the largest number of publications on this topic. Researchers by the name of Xue-Jun Sun, Ke-Liang Xie and Yong-Hao Yu published the most studies in the field. Analysis of the co-occurrence of key words indicated that the key words "molecular hydrogen," "hydrogen-rich water," "oxidative stress," "hydrogen gas," and "inflammation" occurred most frequently in these articles. "Gut microbiota," "pyroptosis," and "COVID-19" occurred the most recently among the keywords. In summary, the therapeutic application of molecular hydrogen had attracted much attention in these years. The advance in this field could be caught up by subscribing to relevant journals or following experienced scholars. Oxidative stress and inflammation were the most important research directions currently, and gut microbiota, pyroptosis, and coronavirus disease 2019 might become hotspots in the future.

Novel predictors and a predictive model of cerebrovascular atherosclerotic ischemic stroke based on clinical databases.

BACKGROUND AND PURPOSE: Early identification of cerebrovascular atherosclerotic ischemic stroke is necessary for accurate treatment and clinical research. AIMS: To identify novel predictors and build a predictive model of ischemic strokes due to cerebrovascular atherosclerosis. METHOD: MIMIC-IV database was used to search for clinical data of patients with ischemic stroke. Included patients were divided into two groups according to their etiologies. Univariate and multivariate logistic regressions were used to build the predictive model, and the model reliability parameters were calculated. The cut-off value for the model was selected according to the Youden index. Clinical data from the Neurovascular Center of Changhai Hospital were used to verify the predictive model. RESULTS: Logistical regressions showed a positive correlation between advanced age, peripheral atherosclerosis, history of transient ischemia, and the diagnosis of ischemic strokes due to cerebrovascular atherosclerosis. The history of atrial fibrillation, levels of the National Institutes of Health Stroke Scale, serum potassium, and activated partial thromboplastin time were negatively correlated to the diagnosis of cerebrovascular atherosclerotic ischemic stroke. The predictive model was constructed from logistic regression results, and the area under the curve was 0.764. The cut-off value for the model was set at 0.089 to achieve the highest Youden index, with sensitivity and specificity of 75.9% and 64.1%. Clinical verification of the model revealed that the sensitivity and specificity of the model were 52.5% and 93.0% respectively. CONCLUSION: The efficacy of the predictive model was acceptable as an aid in predicting cerebrovascular atherosclerotic ischemic stroke.

Prevention of polycystic ovary syndrome and postmenopausal osteoporosis by inhibiting apoptosis with Shenling Baizhu powder compound.

Objective: Shenling Baizhu powder (SBP) has been shown to reverse the abnormal expression of the aromatic hydrocarbon receptor (AHR) mediated by air pollution. Our study aimed to understand the main ingredient of SBP and investigate its action mechanism in preventing polycystic ovary syndrome (POCS) and postmenopausal osteoporosis (PMO). Methods: The active ingredients of SBP with the highest binding affinity to AHR were screened using a Chinese medicine database, and their binding mechanism was simulated using molecular dynamics simulation (MDS). Rutin was utilized to treat ovarian granulosa cell lines and osteoblast cell lines. The cell lines were treated with a gradient of rutin concentration (0.01 mmol/L, 0.05 mmol/L and 0.1 mmol/L) to find the optimal drug dose. PCR was used to detect AHR and apoptosis-related proteins, and WB to detect the expression of AHR, caspase-3 and cleaved-caspase-3. Finally, the CCK-8 cell proliferation assay detected the proliferation of cells. Results: We obtained Rutin through the Chinese medicine database, and dynamics simulation determined its binding sites. Ovarian granulosa cell lines and osteoblast cell lines were treated with Rutin. RT-PCR and western blotting revealed that the expression of apoptosis-associated protein Bcl-2 was elevated, and the expression of AHR, Bax, caspase-3 and PARP were decreased. CCK-8 results showed accelerated proliferation in both cell types. Conclusion: Rutin, the main ingredient of SBP compound, works by binding to AHR, which can improve POCS and PMO by inhibiting cell apoptosis and by promoting cell proliferation.

Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data.

Aims: This study aimed to build a prediction model to early diagnose intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) in acute ischemic stroke patients before digital subtractive angiography. Methods: Patients enrolled in the DIRECT-MT trial (NCT03469206) were included in our secondary analysis and distributed into ICAS-LVO and non-ICAS-LVO groups. We also retrieved demographic data, medical histories, clinical characteristics, and pre-operative imaging data. Hypothesis testing was used to compare data of the two groups, and univariate logistic regression was used to identify the predictors of ICAS-LVO primarily. Then, we used multivariate logistic regression to determine the independent predictors and formulate the prediction model. Model efficacy was estimated by the area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic parameters generated from internal and external validations. Results: The subgroup analysis included 45 cases in the ICAS-LVO group and 611 cases in the non-ICAS-LVO group. Variates with p < 0.1 in the comparative analysis were used as inputs in the univariate logistic regression. Next, variates with p < 0.1 in the univariate logistic regression were used as inputs in the multivariate logistic regression. The multivariate logistic regression indicated that the atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score were related to the diagnosis of ICAS-LVO. Then, we constructed a prediction model based on multivariate logistics regression. The sensitivity and specificity of the model were 84.09 and 74.54% in internal validation and 73.11 and 71.53% in external validation. Conclusion: Our current prediction model based on clinical data of patients from the DIRECT-MT trial might be a promising tool for predicting ICAS-LVO.

A framework from point clouds to workpieces.

Combining computer-aided design and computer numerical control (CNC) with global technical connections have become interesting topics in the manufacturing industry. A framework was implemented that includes point clouds to workpieces and consists of a mesh generation from geometric data, optimal surface segmentation for CNC, and tool path planning with a certified scallop height. The latest methods were introduced into the mesh generation with implicit geometric regularization and total generalized variation. Once the mesh model was obtained, a fast and robust optimal surface segmentation method is provided by establishing a weighted graph and searching for the minimum spanning tree of the graph for extraordinary points. This method is easy to implement, and the number of segmented patches can be controlled while preserving the sharp features of the workpiece. Finally, a contour parallel tool-path with a confined scallop height is generated on each patch based on B-spline fitting. Experimental results show that the proposed framework is effective and robust.

SpCrus2 Glycine-Rich Region Contributes Largely to the Antiviral Activity of the Whole-Protein Molecule by Interacting with VP26, a WSSV Structural Protein.

Crustins are cysteine-rich cationic antimicrobial peptides with diverse biological functions including antimicrobial and proteinase inhibitory activities in crustaceans. Although a few crustins reportedly respond to white spot syndrome virus (WSSV) infection, the detailed antiviral mechanisms of crustins remain largely unknown. Our previous research has shown that SpCrus2, from mud crab Scylla paramamosain, is a type II crustin containing a glycine-rich region (GRR) and a cysteine-rich region (CRR). In the present study, we found that SpCrus2 was upregulated in gills after WSSV challenge. Knockdown of SpCrus2 by injecting double-stranded RNA (dsSpCrus2) resulted in remarkably increased virus copies in mud crabs after infection with WSSV. These results suggested that SpCrus2 played a critical role in the antiviral immunity of mud crab. A GST pull-down assay showed that recombinant SpCrus2 interacted specifically with WSSV structural protein VP26, and this result was further confirmed by a co-immunoprecipitation assay with Drosophila S2 cells. As the signature sequence of type II crustin, SpCrus2 GRR is a glycine-rich cationic polypeptide with amphipathic properties. Our study demonstrated that the GRR and CRR of SpCrus2 exhibited binding activities to VP26, with the former displaying more potent binding ability than the latter. Interestingly, pre-incubating WSSV particles with recombinant SpCrus2 (rSpCrus2), rGRR, or rCRR inhibited virus proliferation in vivo; moreover, rSpCrus2 and rGRR possessed similar antiviral abilities, which were much stronger than those of rCRR. These findings indicated that SpCrus2 GRR contributed largely to the antiviral ability of SpCrus2, and that the stronger antiviral ability of GRR might result from its stronger binding activity to the viral structural protein. Overall, this study provided new insights into the antiviral mechanism of SpCrus2 and the development of new antiviral drugs.

Integrated Microbiome-Metabolome Analysis Reveals Stage-Dependent Alterations in Bacterial Degradation of Aromatics in Leptinotarsa decemlineata.

To avoid potential harm during pupation, the Colorado potato beetle Leptinotarsa decemlineata lives in two different habitats throughout its developmental excursion, with the larva and adult settling on potato plants and the pupa in soil. Potato plants and agricultural soil contain a specific subset of aromatics. In the present study, we intended to determine whether the stage-specific bacterial flora plays a role in the catabolism of aromatics in L. decemlineata. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the operational taxonomic units (OTUs) obtained by sequencing of culture-independent 16S rRNA region enriched a group of bacterial genes involved in the elimination of mono- and polycyclic aromatics at the pupal stage compared with those at the larval and adult periods. Consistently, metabolome analysis revealed that dozens of monoaromatics such as styrene, benzoates, and phenols, polycyclic aromatics, for instance, naphthalene and steroids, were more abundant in the pupal sample. Moreover, a total of seven active pathways were uncovered in the pupal specimen. These ways were associated with the biodegradation of benzoate, 4-methoxybenzoate, fluorobenzoates, styrene, vanillin, benzamide, and naphthalene. In addition, the metabolomic profiles and the catabolism abilities were significantly different in the pupae where their bacteria were removed by a mixture of three antibiotics. Therefore, our data suggested the stage-dependent alterations in bacterial breakdown of aromatics in L. decemlineata.

Resolvin Conjugates in Tissue Regeneration 1 Promote Alveolar Fluid Clearance by Activating Alveolar Epithelial Sodium Channels and Na, K-ATPase in Lipopolysaccharide-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser473-phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner.

Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway.

BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects. METHODS: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6-8). Rosuvastatin (0.3 µmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h. RESULTS: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway. CONCLUSION: In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.

LXA4 Inhibits Lipopolysaccharide-Induced Inflammatory Cell Accumulation by Resident Macrophages in Mice.

INTRODUCTION: Alveolar macrophages that regulate the inflammatory response in lungs are the main target cell for the treatment of inflammatory pulmonary pathologies, such as acute respiratory distress syndrome (ARDS). Yolk sac derived alveolar resident macrophages play an important role in the pulmonary inflammatory response. With regards to anti-inflammatory actions, lipoxin A4 (LXA4) has been identified as an inflammatory "braking signal". METHODS: In vivo, LXA4 (0.1 µg/mouse) was injected intraperitoneally after intratracheal (1 mg/kg) lipopolysaccharide (LPS) administration; flow cytometry was used to measure peripheral blood monocyte derived recruited macrophage and neutrophil numbers; resident alveolar macrophage was depleted by liposome clodronate; CXCL2, CCL2, MMP9 level was detected by RT-PCR and ELISA. In vitro, sorted resident macrophages (1×106) were cultured with LPS (1 µg/mL) and LXA4 (100 nmol/mL) with or without BOC-2 (10 µM) for 24 h to gain a better understanding of the mechanisms of LXA4. RESULTS: LXA4 inhibited tumor necrosis factor-a (TNF-a) and interleukin-1ß (IL-1ß) production induced by LPS. LXA4 also mediated LPS-induced macrophage recruitment and showed that this was dependent on CCL2 secretion and release by resident macrophages. LXA4 protects lung tissue by inhibiting neutrophil recruitment, partly through the CXCL2/MMP-9 signaling pathway. CXCL2 and MMP-9 are mainly expressed by resident macrophages and neutrophils, respectively. Finally, LXA4's beneficial effects were abrogated by BOC-2, an LXA4 receptor inhibitor. CONCLUSION: These results suggest that LXA4 may be a promising therapy for preventing and treating ARDS.

Comparison of four markers of hepatic fibrosis and hepatic function indices in patients with liver cirrhosis and hepatoma.

BACKGROUND: The present study aimed to compare four hepatic fibrosis markers [i.e., hyaluronic acid (HA), laminin (LN), procollagen III N-terminal peptide (PIIINP), and collagen type IV (CIV)] and 16 hepatic function indices in patients with liver cirrhosis of varying etiology. METHODS: The hepatic function indices and hepatic fibrosis markers were measured in 108 patients with liver cirrhosis and hepatoma using an automatic biochemical analyzer and luminescent immune analyzer. Twenty healthy controls were enrolled to compare the differences between liver cirrhosis and hepatoma of varying etiology and to analyze the correlations between the hepatic function indices and fibrosis markers. RESULTS: There was no correlation between alanine aminotransferase (ALT), total protein (TP), alkaline phosphatase (ALP), or the four markers of hepatic fibrosis in liver cirrhosis caused by hepatitis B (P>0.05). Aspartate aminotransferase (AST) was positively correlated with HA (r=0.428, P=0.007), LN (r=0.458, P=0.004), and CIV (r=0.374, P=0.021). Total bilirubin (TBIL) and direct bilirubin (DBIL) were positively correlated with LN (TBIL: r=0.480, P=0.002; DBIL: r=0.457, P=0.004), PIIINP (TBIL: r=0.380, P=0.017; DBIL: r=0.406, P=0.011), and CIV (TBIL: r=0.415, P=0.010; DBIL: r=0.400, P=0.013). Total bile acid (TBA) and γ-glutamyltranspeptidase (GGT) were positively correlated with PIIINP (TBA: r=0.363, P=0.025; GGT: r=0.353, P=0.029) and CIV (TBA: r=0.419, P=0.009; GGT: r=0.335, P=0.040). Leucine aminopeptidase (LAP) was positively correlated with LN (r=0.482, P=0.002). Cholinesterase (CHE) (HA: r=-0.452, P=0.004, LN: r=-0.336, P=0.039; PIIINP: r=-0.468, P=0.003; CIV: r=-0.485, P=0.002), prealbumin (PA) (HA: r=-0.575, P=0.000, LN: r=-0.413, P=0.010; PIIINP: r=-0.344, P=0.035; CIV: r=-0.371, P=0.022), albumin (ALB) (HA: r=-0.541, P=0.000, LN: r=-0.373, P=0.021; PIIINP: r=-0.353, P=0.030; CIV: r=-0.415, P=0.010), and superoxide dismutase (SOD) (HA: r=-0.334, P=0.040, LN: r=-0.347, P=0.033; PIIINP: r=-0.487, P=0.002; CIV: r=-0.536, P=0.001) were negatively correlated with the four markers of hepatic fibrosis. There was no correlation between ALT, AST, TBIL, TP, ALP, GGT, or the four hepatic fibrosis markers in hepatoma caused by hepatitis B (P>0.05). Meanwhile, DBIL and TBA were positively correlated with CIV (DBIL: r=0.519, P=0.023; TBA: r=0.563, P=0.012), while CHE (r=-0.604, P=0.006), ALB (r=-0.564, P=0.012), and SOD (r=-0.489, P=0.034) were negatively correlated with CIV. Moreover, PA was negatively correlated with LN (r=-0.510, P=0.026) and CIV (r=-0.696, P=0.001). CONCLUSIONS: The concentrations of the serological indices differed significantly based on the specific liver cirrhosis etiology. There was a strong correlation between the hepatic function indices and four hepatic fibrosis markers. Thus, the detection of these markers might improve the diagnosis and treatment of hepatoma.

TNFAIP8 Promotes Cisplatin Chemoresistance in Triple-Negative Breast Cancer by Repressing p53-Mediated miR-205-5p Expression.

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is implicated in the tumor progression and prognosis of triple-negative breast cancer (TNBC), but the detailed regulatory mechanism of TNFAIP8 in cisplatin tolerance in TNBC has not yet been investigated. TNFAIP8 was evidently upregulated in TNBC tumor tissues and cell lines. Knocking down TNFAIP8 led to impaired proliferation and elevated apoptosis of TNBC cells upon cisplatin (DDP) treatment. Mechanistic studies revealed that TNFAIP8 repressed the expression of p53 and p53-promoted microRNA (miR)-205-5p; moreover, miR-205-5p targeted multiple genes required for the cell cycle and repressed Akt phosphorylation, which thus inhibited the proliferation of TNBC cells. In addition, silencing of TNFAIP8 led to the upregulation of miR-205-5p and the restraint of the TRAF2-NF-κB pathway, which thus enhanced the suppressive effects of DDP on tumor growth in nude mice. This study revealed that TNFAIP8 was essential in the DDP tolerance formation of TNBC cells by reducing p53-promoted miR-205-5p expression. Thus, targeting TNFAIP8 might become a promising strategy to suppress TNBC progression.

Amino acid compounds released by the giant freshwater prawn Macrobrachium rosenbergii during ecdysis: a factor attracting cannibalistic behaviour?

Ecdysis is a common phenomenon that happens throughout the life phase of the giant freshwater prawn Macrobrachium rosenbergii. It is vital to better understand the correlation between cannibalism and biochemical compound that exists during the moulting process. The objective of the present study was to determine the amino acid profile released by M. rosenbergii during the ecdysis process that promotes cannibalism. To accomplish this, changes in amino acid levels (total amino acid (TAA) and free amino acid (FAA)) of tissue muscle, exoskeleton, and sample water of culture medium from the moulting (E-stage) and non-moulting (C-stage) prawns were analysed using high-performance liquid chromatography (HPLC). Comparison study revealed that among the TAA compounds, proline and sarcosine of tissues from moulting prawn were found at the highest levels. The level of FAA from water that contains moulting prawns (E-stage) was dominated by tryptophan and proline. Significant values obtained in the present study suggested that these amino acid compounds act as a chemical cue to promote cannibalism in M. rosenbergii during ecdysis. The knowledge of compositions and compounds that were released during the moulting process should be helpful for better understanding of the mechanism and chemical cues that play roles on triggering cannibalism, and also for future dietary manipulation to improve feeding efficiencies and feeding management, which indirectly impacts productivity and profitability.

LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway.

BACKGROUND: Long non-coding RNA H19 (lncRNA H19) has been implicated in tumorigenesis and metastasis of breast cancer through regulating epithelial to mesenchymal transition (EMT); however, the underlying mechanisms remain elusive. METHODS: LncRNA H19 and TNFAIP8 were identified by qRT-PCR and western blotting. CCK-8 assay, clone formation assay, transwell assay, and flow cytometry assay were performed to determine cell proliferation, migration, invasion and cell cycle of breast cancer respectively. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the protein expression levels of p53, TNFAIP8, and marker proteins of EMT cascades in vivo. Dual luciferase reporter assay and RNA pull down assay were conducted to evaluate the interactions of lncRNA H19, p53 and TNFAIP8. RESULTS: The expression of lncRNA H19 and TNFAIP8 was up-regulated in breast cancer tissues and cell lines, especially in triple-negative breast cancer (TNBC). Functionally, knockdown of lncRNA H19 or TNFAIP8 coused the capacities of cell proliferation, migration, and invasion were suppressed, and cell cycle arrest was induced, as well as that the EMT markers were expressed abnormal. Mechanistically, lncRNA H19 antagonized p53 and increased expression of its target gene TNFAIP8 to promote EMT process. Furthermore, silencing of lncRNA H19 or TNFAIP8 also could inhibit tumorigenesis and lymph node metastases of MDA-MB-231 cells in xenograft nude mouse models. CONCLUSIONS: Our findings provide insight into a novel mechanism of lncRNA H19 in tumorigenesis and metastases of breast cancer and demonstrate H19/p53/TNFAIP8 axis as a promising therapeutic target for breast cancer, especially for TNBC.