Ultrafast removal of toxic Cr(VI) by the marine bacterium Vibrio natriegens.

The fastest-growing microbe Vibrio natriegens is an excellent platform for bioproduction processes. Until now, this marine bacterium has not been examined for bioremediation applications, where the production of substantial amounts of biomass would be beneficial. V. natriegens can perform extracellular electron transfer (EET) to Fe(III) via a single porin-cytochrome circuit conserved in Vibrionaceae. Electroactive microbes capable of EET to Fe(III) usually also reduce toxic metals such as carcinogenic Cr(VI), which is converted to Cr(III), thus decreasing its toxicity and mobility. Here, the performance of V. natriegens was explored for the bioremediation of Cr(VI). At a density of 100 mg/mL, V. natriegens removed 5-20 mg/L Cr(VI) within 30 s and 100 mg/L Cr(VI) within 10 min. In comparison, the model bacterium Escherichia coli grown to a comparable cell density removed Cr(VI) 36 times slower. To eliminate Cr(VI), V. natriegens had to be metabolically active, and functional outer-membrane c-type cytochromes were required. At the end of the Cr(VI) removal process, V. natriegens had reduced all of it into Cr(III) while adsorbing more than half of the metallic ions. These results demonstrate that V. natriegens, with its fast metabolism, is a viable option for the rapid treatment of aqueous pollution with Cr.

A Propolis-Derived Small Molecule Tectochrysin Ameliorates Type 2 Diabetes in Mice by Activating Insulin Receptor ß.

SCOPE: Propolis has been found to decrease glucose levels and increase insulin sensitivity in type 2 diabetes. However, the active ingredient responsible for these effects and its regulating mechanism are not fully understood. METHODS AND RESULTS: To address this, molecular docking screening is used to screen the effective hypoglycemic ingredient in propolis and found that tectochrysin (TEC) has a high affinity to the insulin receptor (IR), highlighting its potential for glycemic control. In vivo tests show that TEC decreases glucose levels and enhances insulin sensitivity in db/db mice. By hyperinsulinemic euglycemic clamp test, this study further finds that TEC promotes glucose uptake in adipose tissue and skeletal muscle, as well as inhibits hepatic gluconeogenesis. Moreover, it finds that TEC promotes glucose uptake and adipocytes differentiation in 3T3-L1 cells like insulin, suggesting that TEC exerts an insulin mimetic effect. Mechanistically, pharmacology inhibition of IRß abolishes the effects of TEC on glucose uptake and the phosphorylation of IR. The study further demonstrates that TEC binds to and activates IRß by targeting its E1077 and M1079. CONCLUSION: Therefore, this study sheds light on the mechanism underlying propolis' potential for ameliorating type 2 diabetes, offering a natural food-derived compound as a promising therapeutic option.

Fumarate disproportionation by Geobacter sulfurreducens and its involvement in biocorrosion and interspecies electron transfer.

The model electroactive bacterium Geobacter sulfurreducens can acquire electrons directly from solid donors including metals and other species. Reports on this physiology concluding that solid donors are the only electron sources were conducted with fumarate believed to serve exclusively as the terminal electron acceptor (TEA). Here, G. sulfurreducens was repeatedly transferred for adaptation within a growth medium containing only fumarate and no other solid or soluble substrate. The resulting evolved strain grew efficiently with either the C4-dicarboxylate fumarate or malate acting simultaneously as electron donor, carbon source, and electron acceptor via disproportionation. Whole-genome sequencing identified 38 mutations including one in the regulator PilR known to repress the expression of the C4-dicarboxylate antiporter DcuB essential to G. sulfurreducens when growing with fumarate. Futhermore, the PilR mutation was identical to the sole mutation previously reported in an evolved G. sulfurreducens grown in a co-culture assumed to derive energy solely from direct interspecies electron transfer, but cultivated with fumarate as the TEA. When cultivating the fumarate-adapted strain in the presence of stainless steel and fumarate, biocorrosion was observed and bacterial growth was accelerated 2.3 times. These results suggest that G. sulfurreducens can conserve energy concomitantly from C4-dicarboxylate disproportionation and the oxidation of a solid electron donor. This co-metabolic capacity confers an advantage to Geobacter for survival and colonization and explains in part why these microbes are omnipresent in different anaerobic ecosystems.

Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans.

Genetic variants in the asialoglycoprotein receptor 1 (ASGR1) are associated with a reduced risk of cardiovascular disease (CVD) in humans. However, the underlying molecular mechanism remains elusive. Given the cardiovascular similarities between pigs and humans, we generated ASGR1-deficient pigs using the CRISPR/Cas9 system. These pigs show age-dependent low levels of non-HDL-C under standard diet. When received an atherogenic diet for 6 months, ASGR1-deficient pigs show lower levels of non-HDL-C and less atherosclerotic lesions than that of controls. Furthermore, by analysis of hepatic transcriptome and in vivo cholesterol metabolism, we show that ASGR1 deficiency reduces hepatic de novo cholesterol synthesis by downregulating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and increases cholesterol clearance by upregulating the hepatic low-density lipoprotein receptor (LDLR), which together contribute to the low levels of non-HDL-C. Despite the cardioprotective effect, we unexpectedly observed mild to moderate hepatic injury in ASGR1-deficient pigs, which has not been documented in humans with ASGR1 variants. Thus, targeting ASGR1 might be an effective strategy to reduce hypercholesterolemia and atherosclerosis, whereas further clinical evidence is required to assess its hepatic impact.

Sonographic features of the lateral femoral cutaneous nerve in meralgia paresthetica.

BACKGROUND: The diagnosis of meralgia paresthetica (MP) is usually based on clinical symptoms and physical examination. Therefore, the present study aimed to investigate the lateral femoral cutaneous nerve (LFCN) sonographic features in MP patients. METHODS: A total of 86 clinically suspected MP patients and 40 asymptomatic volunteers were prospectively recruited in the study. The sonographic features of the LFCN were observed by 18 MHz high-frequency ultrasound. At the level of the anterior superior iliac spine, the cross-sectional area of the LFCN was measured. RESULTS: Of the 86 clinically suspected MP patients, 82 (95.3%) had sonographic findings positive for MP. There were 54, 63, and 44 cases of abrupt caliber change, indistinct perineurium, and abnormal intraneural vascularity. The average value of the cross-sectional area of the LFCN at the level of the anterior superior iliac spine was 4.47±2.64 mm2, and the cut-off value was 2.65 mm2. CONCLUSIONS: The sonographic diagnosis of MP may be achieved based on the following signs: nerve abrupt caliber change, indistinct perineurium of the nerve, intraneural vascularity, or increased cross-sectional area.

Diosmetin Protects Against Obesity and Metabolic Dysfunctions Through Activation of Adipose Estrogen Receptors in Mice.

SCOPE: Obesity is a major public health and economic problem of global significance. Here, we investigate the role of diosmetin, a natural flavonoid presents mainly in citrus fruits, in the regulation of obesity and metabolic dysfunctions in mice. METHODS AND RESULTS: Eight-week-old male C57BL/6 mice fed a high-fat diet (HFD) or 5-week-old male ob/ob mice fed a normal diet are treated with diosmetin (50 mg kg-1 daily) or vehicle for 8 weeks. Diosmetin treatment decreases body weight and fat mass, improves glucose tolerance and insulin resistance in obese mice. These metabolic benefits are mainly attributed to increase energy expenditure via enhancing thermogenesis in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Mechanistically, diosmetin acts as an agonist for estrogen receptors (ERs), and subsequently elevates adipose expressions of ERs in mice and in cultured adipocytes. When ERs are blocked by their antagonist fulvestrant in mice, diosmetin loses its beneficial effects, suggesting that ERs are indispensable for the metabolic benefits of diosmetin. CONCLUSION: The results indicate that diosmetin may be a potential anti-obesity nutritional supplement and could be explored for low ERs-related obesity populations.

Improved robustness of microbial electrosynthesis by adaptation of a strict anaerobic microbial catalyst to molecular oxygen.

Microbial electrosynthesis (MES) and other bioprocesses such as syngas fermentation developed for energy storage and the conversion of carbon dioxide into valuable chemicals often employs acetogens as microbial catalysts. Acetogens are sensitive to molecular oxygen, which means that bioproduction reactors must be maintained under strict anaerobic conditions. This requirement increases cost and does not eliminate the possibility of O2 leakage. For MES, the risk is even greater since the system generates O2 when water splitting is the anodic reaction. Here, we show that O2 from the anode of a MES reactor diffuses into the cathode chamber where strict anaerobes reduce CO2. To overcome this drawback, a stepwise adaptive laboratory evolution (ALE) strategy is used to develop the O2 tolerance of the acetogen Sporomusa ovata. Two heavily-mutated S. ovata strains growing well autotrophically in the presence of 0.5 to 5% O2 were obtained. The adapted strains were more performant in the MES system than the wild type converting electrical energy and CO2 into acetate 1.5 fold faster. This study shows that the O2 tolerance of acetogens can be increased, which leads to improvement of the performance and robustness of energy-storage bioprocesses such as MES where O2 is an inhibitor.

Fast removal of toxic hexavalent chromium from an aqueous solution by high-density Geobacter sulfurreducens.

Hexavalent chromium (Cr(VI)) is a carcinogenic compound that can be removed from contaminated sites by the activity of metal-reducing bacteria. The model bacterium Geobacter sulfurreducens reduces Cr(VI) to less toxic Cr(III) and accumulates Cr ions intracellularly. However, this process is usually slow with small concentrations of Cr(VI) removed in a matter of days. Here, high-density G. sulfurreducens cultures were tested for the capacity to remove Cr(VI) readily. With an initial G. sulfurreducens density of 5.8 × 108 cells ml-1, 99.0 ± 0.8% of 100 mg l-1 Cr(VI) was removed after 20 min. With a higher starting Cr(VI) concentration of 200 mg l-1, G. sulfurreducens with a density of 11.4 × 108 cells ml-1 removed 99.0 ± 0.4% Cr(VI) after 2 h. Experiments performed with cell-free spent medium indicate that extracellular proteins are major contributors for the reduction of Cr(VI) to Cr(III). Furthermore, results show that most Cr(III) ions ultimately end up inside the bacterial cells where they are less susceptible to re-oxidation. The fast Cr(VI) removal rates observed with high-density G. sulfurreducens demonstrate the potential of this bacterium for bioremediation applications such as the cleaning of industrial wastewaters.

Primary external iliac vein leiomyosarcoma in a young female diagnosed by contrast-enhanced ultrasound: A case report.

RATIONALE: Venous leiomyosarcoma (LMS) is a malignant tumor arising from the smooth muscle cell of the vein wall. The diagnosis of venous LMS is usually delayed owing to its rarity, absence of serological markers, and mimicry with deep vein thrombosis (DVT). Herein, we report a case of a primary external ilian vein LMS characterized by long-term, unexplained DVT in the left lower limb. Contrast-enhanced ultrasound (CEUS) played a crucial role in the preoperative diagnosis. No improvement was observed in the lower limb status; a rapid, high-level, heterogeneous wash-in and wash-out mass of the vein, as seen with CEUS, could indicate angiogenic malignancy. CEUS also helped evaluate the percent of intratumoral necrosis, which is an important parameter for predicting the prognosis. PATIENT CONCERNS: A 37-year-old Chinese women presented to the Vascular Surgery Department of our hospital for accurate diagnosis of her condition. She began experiencing edema and pain in her left leg 2 years ago. She was diagnosed with DVT in the left lower extremity and was administered anticoagulant therapy since then. However, her symptoms started to aggravate 8 months ago. DIAGNOSES: The laboratory results including D-dimer, prothrombin time (PT), activated partial thrombin time (APTT), and prothrombotic conditions screening were within normal ranges. A pelvic ultrasound detected a heterogeneous, hypoechoic mass compressing the external iliac vein and obstructing the venous drain of the lower extremity. The mass showed a rapid, high-level, heterogeneous wash-in and wash-out on CEUS, which suggested angiogenic malignancy. Contrast-enhanced CT (CECT) confirmed the result of CEUS but revealed no metastasis. INTERVENTIONS: She underwent complete surgical removal of the tumor, which was resected successfully. There was no infiltration in the inguinal nodes sent for the study. OUTCOMES: Pathological examination and immunohistochemistry confirmed that the mass was a well-differentiated LMS originating from the external iliac vein. There was no sign of local recurrence or distant metastasis during a 12-month follow-up. LESSONS: Effective imaging techniques and differential diagnosis of venous LMS is vital and should be considered for patients with chronic thrombosis presenting with normal laboratory results.

Crystalline CdS/MoS2 shape-controlled by a bacterial cellulose scaffold for enhanced photocatalytic hydrogen evolution.

The conversion of sunlight into H2 by noble-metal-free photocatalysts is a promising approach for the production of easy-to-store chemical energy. For this purpose, higher efficiency is achieved by photocatalysts with heterojunctions preventing fast charge recombination. Most processes for the synthesis of high-performance heterojunction photocatalysts require solvents harmful to living organisms. Here, berry-shaped (b)-CdS/MoS2 particles were fabricated instead by a hydrothermal process where non-toxic bacterial cellulose was used to mold b-CdS into nanostructures with enhanced spatial arrangement. Subsequently, MoS2 was combined with b-CdS resulting in a composite with suitable shape and intimate semiconductor contacts beneficial for charge transfer. The photocatalytic H2 evolution (PHE) of b-CdS/1%MoS2 was 63.59 mmol g-1 h-1. It was 61.1 times, 397 times, and 10.2 times higher than PHE with b-CdS, CdS fabricated without BC scaffold, and b-CdS doped with Pt, respectively. These results show the high potential of b-CdS/MoS2 and the associated synthesis method for PHE.

The hidden chemolithoautotrophic metabolism of Geobacter sulfurreducens uncovered by adaptation to formate.

Multiple Fe(III)-reducing Geobacter species including the model Geobacter sulfurreducens are thought to be incapable of carbon dioxide fixation. The discovery of the reversed oxidative tricarboxylic acid cycle (roTCA) for CO2 reduction with citrate synthase as key enzyme raises the possibility that G. sulfurreducens harbors the metabolic potential for chemolithoautotrophic growth. We investigate this hypothesis by transferring G. sulfurreducens PCA serially with Fe(III) as electron acceptor and formate as electron donor and carbon source. The evolved strain T17-3 grew chemolithoautotrophically with a 2.7-fold population increase over 48 h and a Fe(III) reduction rate of 417.5 µM h-1. T17-3 also grew with CO2 as carbon source. Mutations in T17-3 and enzymatic assays point to an adaptation process where the succinyl-CoA synthetase, which is inactive in the wild-type, became active to complete the roTCA cycle. Deletion of the genes coding for the succinyl-CoA synthetase in T17-3 prevented growth with formate as substrate. Enzymatic assays also showed that the citrate synthase can perform the necessary cleavage of citrate for the functional roTCA cycle. These results demonstrate that G. sulfurreducens after adaptation reduced CO2 via the roTCA cycle. This previously hidden metabolism can be harnessed for biotechnological applications and suggests hidden ecological functions for Geobacter.

Isoimperatorin enhances 3T3-L1 preadipocyte differentiation by regulating PPARγ and C/EBPα through the Akt signaling pathway.

Lipodystrophic patients have an adipose tissue triglyceride storage defect that causes ectopic lipid accumulation, leading to severe insulin resistance. The present study investigated the potential role of isoimperatorin on 3T3-L1 adipocyte differentiation. mRNA and protein levels of differentiation- and lipid accumulation-associated genes, as well as the adipogenesis-related signaling pathway were analyzed in control and isoimperatorin-treated differentiated 3T3-L1 adipocytes using reverse transcription-quantitative PCR and western blot analysis. Results determined that isoimperatorin promoted 3T3-L1 fibroblast adipogenesis in a dose-dependent manner compared with standard differentiation inducers. Isoimperatorin significantly increased mRNA and protein expression of the crucial adipogenic transcription factors peroxisome proliferator activated receptor-γ (PPARγ) and CCAAT enhancer binding protein-α (C/EBPα). mRNA expression of the downstream adipogenesis-related genes sterol regulatory element-binding transcription factor 1c, adipocyte protein 2, fatty acid synthase, adiponectin and diacylglycerol O-acyltransferase 2 were also significantly increased following isoimperatorin treatment. The underlying mechanism likely involved activation of the Akt signaling pathway. Taken together, the present findings indicated that isoimperatorin may alter PPARγ and C/EBPα expression via the Akt signaling pathway, resulting in promotion of adipogenesis. The results highlighted the potential use of isoimperatorin as a therapeutic agent for preventing diabetes.

Escherichia coli adaptation and response to exposure to heavy atmospheric pollution.

90% of the world population is exposed to heavy atmospheric pollution. This is a major public health issue causing 7 million death each year. Air pollution comprises an array of pollutants such as particulate matters, ozone and carbon monoxide imposing a multifactorial stress on living cells. Here, Escherichia coli was used as model cell and adapted for 390 generations to atmospheric pollution to assess its long-term effects at the genetic, transcriptomic and physiological levels. Over this period, E. coli evolved to grow faster and acquired an adaptive mutation in rpoB, which encodes the RNA polymerase ß subunit. Transcriptomic and biochemical characterization showed alteration of the cell membrane composition resulting in lesser permeability after the adaptation process. A second significant change in the cell wall structure of the adapted strain was the greater accumulation of the exopolysaccharides colanic acid and cellulose in the extracellular fraction. Results also indicated that amino acids homeostasis was involved in E. coli response to atmospheric pollutants. This study demonstrates that adaptive mutation with transformative physiological impact can be fixed in genome after exposure to atmospheric pollution and also provides a comprehensive portrait of the cellular response mechanisms involved.

The TRAPs From Microglial Vesicles Protect Against Listeria Infection in the CNS.

Previous studies have demonstrated that T cells and microglia could fight against cerebral Listeria monocytogenes (Listeria); however, their synergistic anti-Listeria mechanisms remain unknown. Following Listeria infection in a culture system, we found that microglia, but not nerve cells, could release extracellular traps (ETs) which originated from microglial vesicles. Specific inhibitor analysis showed that extracellular DNA (eDNA), matrix metallopeptidases (MMP9 and MMP12), citrullinated histone H3, and peptidyl arginine deiminase 2 were the major components of microglial ETs (MiETs) and were also the components of vesicles. Systematic analysis indicated that Listeria-induced MiETs were cytosolic reactive oxygen species (ROS)- and NADPH oxidase (NOX)-dependent and involved ERK. MiETs were exhibited in Listeria-infected mouse brain and might protected against Listeria infection via bacterial killing in a mouse meningitis model, and MiETs existed in cerebrospinal fluid (CSF) from Listeria meningitis patients in vivo and in vitro. Additionally, interferon-γ could induce MiET formation in Listeria-infected microglia in vitro that was mediated by NOX, and there was a positive relationship between the elevated level of IFN-γ and eDNA and nucleosomes in the brain homogenates and CSF of Listeria meningitis model mice and in the CSF before treatment in clinical Listeria meningitis patients. Together, this is the first report of MiET formation, these findings pave the way for deeper exploration of the innate immune response to pathogens in CNS.

Ameliorative effect of docosahexaenoic acid on hepatocyte apoptosis and inflammation induced by oleic acid in grass carp, Ctenopharyngodon idella.

Our previous study has shown that overload of lipid accumulation results in cell apoptosis and inflammation in grass carp (Ctenopharyngodon idella). In this study, we investigated the potential protective effects of docosahexaenoic acid (DHA) on inhibiting oleic acid (OA)-induced apoptosis and inflammation in grass carp hepatocytes. Firstly, the hepatocyte of grass carp were treated with OA (800 µM) and different concentration (0, 50, 100 and 200 µM) of DHA for 24 h, the apoptotic ratio, gene expression levels of apoptosis such as caspase 3, caspase 8, and caspase 9, protein levels of Caspase3, and mRNA levels of inflammation genes such as nf-kb, tnf-α, and il-8 were detected. Furthermore, the mRNA levels of lipogenesis genes srebp1c, fas, acc, and scd and a key enzyme of lipolysis Atgl were also detected. These results showed that the cell apoptosis and the inflammation increased by OA were significantly attenuated by DHA (P < 0.05). Furthermore, DHA could significantly decrease fatty acid synthesis gene expression levels which were induced by OA (P < 0.05). However, the hepatocytes exposed with DHA had no significant influence on the expression of Atgl. Taken together, the study indicated that DHA protects the hepatocytes against apoptosis and inflammation induced by OA might via inhibiting fatty acid synthesis, instead of promoting lipolysis. These results call for further studies to assess the effectiveness of DHA.

The protein-sparing effect of α-lipoic acid in juvenile grass carp, Ctenopharyngodon idellus: effects on lipolysis, fatty acid ß-oxidation and protein synthesis.

To investigate the protein-sparing effect of α-lipoic acid (LA), experimental fish (initial body weight: 18·99 (sd 1·82) g) were fed on a 0, 600 or 1200 mg/kg α-LA diet for 56 d, and hepatocytes were treated with 20 µm compound C, the inhibitor of AMP kinase α (AMPKα), treated for 30 min before α-LA treatment for 24 h. LA significantly decreased lipid content of the whole body and other tissues (P0·05). Consistent with results from the experiment in vitro, LA activated phosphorylation of AMPKα and notably increased the protein content of adipose TAG lipase in intraperitoneal fat, hepatopancreas and muscle in vivo (P<0·05). Meanwhile, LA significantly up-regulated the mRNA expression of genes involved in fatty acid ß-oxidation in the same three areas, and LA also obviously down-regulated the mRNA expression of genes involved in amino acid catabolism in muscle (P<0·05). Besides, it was observed that LA significantly activated the mammalian target of rapamycin (mTOR) pathway in muscle of experimental fish (P<0·05). LA could promote lipolysis and fatty acid ß-oxidation via increasing energy supply from lipid catabolism, and then, it could economise on the protein from energy production to increase protein deposition in grass carp. Besides, LA might directly promote protein synthesis through activating the mTOR pathway.

Cytochrome P450 2AA molecular clone, expression pattern, and different regulation by fish oil and lard oil in diets of grass carp (Ctenopharyngodon idella).

Cytochrome P450 enzymes (CYP enzymes) catalyze important metabolic reactions of exogenous and endogenous substrates, including fatty acid. In this study, we cloned the complete CDS of the cytochrome P450 2AA (CYP2AA) gene from the grass carp (Ctenopharyngodon idella) for the first time. CYP2AA consisted of 1500 bp, which encoded a predicted protein of 499 amino acids. The identities of CYP2AA between C. idella and zebrafish were 86%. It consists of the conserved heme-binding motif FXXGXXXCXG. Quantitative real-time PCR analysis indicated that CYP2AA mRNA in C. idella was highly expressed in liver and adipose tissue. The effects of fish oil and lard oil in diets on expression of CYP2AA mRNA in vivo were also investigated. The fish oil (FO) group exhibited significantly higher CYP2AA expression in adipose tissue than the lard oil (LO) group (P < 0.01), whereas the mRNA expression of CYP2AA was not notably different in liver. It suggested that the high abundance of CYP2AA mRNA expression in adipose tissue could be induced by fish oil. Our findings provided molecular characterization and expression profile of CYP2AA, and enhanced our understanding of CYP2AA in fish lipid metabolism.

Docosahexaenoic acid induces PPARγ-dependent preadipocytes apoptosis in grass carp Ctenopharyngodon idella.

Our previous study showed that docosahexaenoic acid (DHA) plays an important role in decreasing lipid accumulation by inducing apoptosis of the adipocytes in grass carp. However, the mechanism involved remains unclear. DHA has been reported as the natural ligand of PPARγ. The present study aimed to assess whether PPARγ mediates the pro-apoptotic effects by DHA. Adipocytes of grass carp were cultured until 2 days post-confluence and were treated with DHA at various concentrations-0, 25, 50, 100, 200, and 400 µmol/L for 24 h and at 200 µmol/L for various time periods (0, 12, 24, and 48 h, respectively). Besides, the adipocytes were exposed to 200 µM DHA and PPARγ antagonist or inhibitor of certain key enzymes of apoptosis, following which the expression levels of key genes of the cell apoptotic and mitochondrial apoptotic pathways were detected. We found that DHA induced apoptosis of grass carp adipocytes in a time- and dose-dependent manner (P < 0.05). In addition, DHA treatment significantly increased the protein and gene expression levels of PPARγ (P < 0.05), but the PPARγ antagonist significantly abolished this effect and the DHA pro-apoptotic effect (P < 0.05). Moreover, treatment with caspase 9 inhibitor significantly attenuated the DHA-induced preadipocytes apoptosis effects, while treatment with caspase 8 inhibitor showed no influence. These observations suggest that the DHA-induced apoptosis in adipocytes might be mediated by PPARγ and via the intrinsic apoptotic pathway in grass carp.

Triclosan Enhances the Clearing of Pathogenic Intracellular Salmonella or Candida albicans but Disturbs the Intestinal Microbiota through mTOR-Independent Autophagy.

Triclosan (TCS) is a broad-spectrum antimicrobial agent, whose well-known antibacterial mechanism is inhibiting lipid synthesis. Autophagy, an innate immune response, is an intracellular process that delivers the cargo including pathogens to lysosomes for degradation. In this study, we first demonstrated that TCS induced autophagy in a dose-dependent manner in non-phagocytic cells (HeLa) and in macrophages (Raw264.7) and in vivo. The western blot results also revealed that TCS induced autophagy via the AMPK/ULK1 and JNK/ERK/p38 pathways independent of mTOR. The immunofluorescence results indicated that TCS up-regulated the expression of the ubiquitin receptors NDP52 and p62 and strengthened the co-localization of these receptors with Salmonella enterica Typhimurium (S. typhimurium) or Candida albicans (C. albicans) in infected MΦ cells. In addition, sub-lethal concentrations of TCS enhanced the clearing of the pathogens S. typhimurium or C. albicans in infected MΦ and in corresponding mouse infection models in vivo. Specifically, we found that a sub-inhibitory concentration of TCS induced autophagy, leading to an imbalance of the intestinal microflora in mice through the analysis of 16s rRNA Sequencing. Together, these results demonstrated that TCS induced autophagy, which enhanced the killing against pathogenic S. typhimurium or C. albicans within mammal cells but broke the balance of the intestinal microflora.

Contrast-enhanced ultrasound imaging characteristics of malignant transformation of a localized type gallbladder adenomyomatosis: A case report and literature review.

Gallbladder adenomyomatosis (GAM) is an acquired, reactive, tumor-like condition. Malignant transformation is extremely rare, and imaging features during contrast-enhanced ultrasound (CEUS) have not been described before. Herein, we describe a 73-year-old Asian man who had been diagnosed with gallbladder carcinoma by conventional ultrasonography (US). Based on additional radiological findings, we believed that it was a localized adenomyomatosis. However, the histopathological diagnosis was adenocarcinoma originate from adenomyomatosis with serosal invasion. We believe this is the first case of adenocarcinoma derived from GAM with characteristics of CEUS findings. This case is presented to indicate a clinical awareness of malignant transformation of GAM and discuss the radiology significance with an emphasis on CEUS.