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The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c‐FOS/c‐JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine‐pre‐treated macrophage or Bafilomycin A1 (an autophagy inhibitor)‐pre‐treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK‐glutamine‐autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To evaluate accuracy and feasibility of a handheld ultrasound machine for measuring carotid artery intima-media thicknesses (CIMT) and hemodynamic parameters by different expertise levels of ultrasound operators. Methods: : The operators were divided into three groups based on the level of their medical expertise: ultrasound technician, sonographer, and nursing staff. Operators from each group measured the CIMT and hemodynamic parameters of 25 volunteers using both handheld ultrasound and a conventional ultrasound machine. The reliability and reproducibility of handheld ultrasound measurements of CIMT and hemodynamic parameters (peak systolic velocity (PSV), end-diastolic velocity (EDV)) in operators were analyzed. Results: After a period of training, there was no statistically significant difference between the mean CIMT measured using handheld ultrasound among the three operators (0.45 ± 0.09 mm, 0.50 ± 0.07 mm, 0.46 ± 0.08 mm, P > 0.05, respectively), as well as PSV (83.30 ± 15.42 cm/s, 76.28 ± 13.26 cm/s, 81.12 ± 21.21 cm/s, P > 0.05, respectively) and EDV (21.04 ± 4.12 cm/s, 21.87 ± 5.05 cm/s, 20.17 ± 5.90 cm/s, respectively, P > 0.05). Furthermore, there was a good repeatability and consistent of handheld ultrasound device in measuring mean CIMT in the ultrasound technician and sonographer groups (r = 0.662, 0.691, respectively, P < 0.01). Conclusions: Under the premise of proper training, handheld ultrasound systems are feasible for rapid and primary assessment of carotid artery by operators with different levels of expertise. [ABSTRACT FROM AUTHOR]

Background: Arterial pressure volume index (API) offers a non-invasive measurement of brachial artery residual stress. This study investigated API distribution characteristics and correlations with cardiovascular disease risk (CVD) factors in a large Chinese population sample. Methods: This cross-sectional study surveyed a total of 7620 participants. We analyzed the relationships between API and factors influencing CVD, using regression-based stepwise backward selection and restrictive cubic spline models to express relationships as standardized beta values. Results: Multiple linear regression analysis identified many independent factors influencing API including age, sex, body mass index (BMI), pulse pressure (PP), heart rate (HR), hemoglobin, uric acid (UA), estimated glomerular filtration rate (eGFR), triglyceride (TC), and a history of hypertension. Notably, API values increased at 33 and escalated with advancing age. Increases in API were associated with rises in PP and UA increases, particularly when PP reached 60 mmHg and the UA reached 525 units. Conversely, API was found to decrease with elevated HR and eGFR. Furthermore, there was a significant inverted U-shaped relationship between API and BMI. Conclusions: This study was the first to describe API distribution characteristics in a large sample of the Chinese population, providing references for evaluating API changes in the assessment of residual stress variations in diverse diseases. Notably, API displayed a U-shaped relationship with age and was closely related to traditional CVD risk factors, underscoring its potential as a non-invasive tool for risk assessment in vascular health. [ABSTRACT FROM AUTHOR]

Background: This study investigated the correlation in parameters of arterial stiffness and cardiovascular disease (CVD) risk on age and body mass index (BMI) in Chinese females. Methods: This cross-sectional study enrolled 2220 females. Arterial stiffness was assessed by the measurement of arterial velocity pulse index (AVI) and arterial pressure volume index (API). Individual 10-year cardiovascular risk was calculated for each patient using the Framingham cardiovascular risk score (FCVRS). Results: API and AVI had a significant J-shaped relationship with age. Beginning at the age of 30 years, the API started to increase, while after 49 years, the increase in API was even steeper. AVI increased from the age of 32 years, and increased more rapidly after 56 years. The linear association between API and BMI following adjustment for age was significant (ß = 0.324, 95% CI 0.247-0.400, p < 0.001). In the total study cohort, FCVRS scores increased by 0.16 scores for every 1 kg/m2 increase in BMI and by 0.11 scores for each 1 value increase in API in the age adjusted model. Conclusions: API and BMI correlate with 10-year cardiovascular risk at various ages in females. Regardless of age, overweight females have a higher risk of increased API. Therefore API can be used for the early detection of CVD so that preventive therapy can be instituted in these high risk patients. Clinical Trial Registration: Registered on the official website of the China Clinical Trial Registration Center (20/08/2020, ChiCTR2000035937). [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the renal protective effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) on improving renal tubular damage in diabetic kidney disease (DKD) and to explore the potential mechanism of GLP-1RA on renal tubular protection. Methods: Long-acting GLP-1RA was used to treat DKD mice for 12 weeks. The label-free quantitative proteomic analysis of renal proteins was conducted to explore the differentially expressed proteins (DEPs) in the renal tissues of the control, DKD and GLP-1RA groups. The DEPs and markers of renal tubular injury were verified by qPCR in vivo and in vitro. The expression of glucagon-likepeptide-1 receptor (GLP-1R) in renal tubules was determined by immunofluorescence staining. Results: GLP-1RA treatment significantly improved the tubular damages in kidney tissues of DKD mice and mTEC cells stimulated by high glucose (HG). Proteomics analysis revealed that 30 proteins in kidney tissue were differentially expressed among three groups. Seminal vesicle secretory protein 6 (SVS6) was the most differentially expressed protein in kidney tissues among three groups of mice. The expression changes of Svs6 mRNA in vitro and in vivo detected by qPCR were consistent with the results of proteomic analysis. Furthermore, reduction of Svs6 expression by SVS6 siRNA could attenuate HG-stimulated tubular injury in mTEC cells. Immunofluorescence staining also found that GLP-1R was widely expressed in renal tubules in vitro and in vivo. Conclusion: GLP-1RA significantly improved renal tubular damage in DKD mice. SVS6 may be a potential therapeutic target for GLP-1RA in the treatment of DKD. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the four major tumors in the world and the second leading cause of cancer-related death. It was reported that Substance P (SP), as an oncogenic factor, could regulate the expression of miRNAs in gastric cancer progression. Here, we focused on the role of miR-877-5p in gastric cancer development and the miR-877-5p involvement in the SP-mediated gastric cancer development. The mRNA expression level and cell proliferation were assessed by quantitative real-time PCR and cell counting kit-8 assay, respectively. Flow cytometry was conducted to detect apoptosis, followed by assessing the expression of related apoptosis factors. Dual-luciferase reporter assay was performed to validate the interaction between miR-877-5p and Forkhead cassette M1 (FOXM1). Our results showed that SP treatment significantly increased cell proliferation in gastric cancer. Moreover, the miR-877-5p expression was dose-dependently decreased by SP, whereas FOXM1 expression was markedly increased by SP in gastric cancer cells. miR-877-5p negatively regulated gastric cancer development via inhibiting cell proliferation and promoting apoptosis accompanied by increased cleaved caspase-3, cleaved caspase-9, and Bax protein levels and decreased Bcl-2 level. We confirmed that miR-877-5p could target FOXM1 and negatively regulate its expression. Furthermore, we demonstrated that SP could promote cell proliferation and inhibit apoptosis, while miR-877-5p overexpression reversed the effect of SP on cell proliferation and apoptosis. These results suggest that miR-877-5p overexpression can antagonize the promoting effect of SP on the development of gastric cancer, indicating that miR-877-5p may serve as a promising therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Corncob, a renewable biomass waste, has been successfully explored as a low-cost crude carbon source to prepare controlled morphology, and result in higher value-added carbons through a ZnCl2/NaCl treatment and direct pyrolysis process. The synthesis route is simple, green, and results in carbons with different morphology and porous structures by varying the ratio of the eutectic salt ZnCl2/NaCl. Moreover, the adsorption capacities of different carbon materials for formaldehyde and butyraldehyde were tested further. It was demonstrated that NaCl and ZnCl2 could be utilized as a mesopore template, and as a micropore activation agent for carbon materials, respectively. Although the mesopores can provide a fast diffusion channel, and the micropores can enhance adsorption ability, the specific surface area originating from the mesopores was proportional to the amount of butyraldehyde adsorption, and the specific surface area of the micropores was beneficial to the amount of formaldehyde adsorption taking place. The adsorption isotherms follow Langmuir and pseudo first-order kinetic modeling. Additionally, the whole process belongs to physical adsorption. [ABSTRACT FROM AUTHOR]

Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies. Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cholangitis, but its effects on the enterohepatic circulation of bile acid (BA) have been under-investigated. Therefore, we studied the influence of UDCA on BA enterohepatic circulation in vivo and the mechanisms by which UDCA affects the BA kinetics.Experimental Approach: Mice were treated with UDCA and other BAs to observe changes in BA pool and BA transporters involved in enterohepatic circulation. Isotope dilution techniques and biochemical analyses were applied to study BA kinetics after oral administration of UDCA, and the mechanism involved.Key Results: Oral administration of UDCA in mice reduced the overall BA pool and produced a unique BA profile with high-abundance conjugated UDCA species, including tauroursodeoxycholic acid (TUDCA) and GUDCA. We found increased expression of several main BA transporters in the ileum and liver. BA kinetic experiment showed that feeding UDCA shortened cycling time of BA and accelerated BA enterohepatic circulation. Additionally, we found evidence that the effect of UDCA administration on accelerating BA enterohepatic circulation was due to the inhibition of farnesoid X receptor (FXR) signalling in the ileum and FGF15/19 in the liver.Conclusion and Implications: Oral administration of UDCA produced a unique BA profile with high-abundance TUDCA and GUDCA and significantly accelerated BA enterohepatic circulation through the inhibition of intestinal FXR signalling and reduced level of FGF15/19, which in turn, induced the expression of BA transporters in the liver. These findings highlight a critical role for UDCA in maintaining the homeostasis of BA enterohepatic circulation in vivo. [ABSTRACT FROM AUTHOR]

Pu-erh tea has been extensively reported to possess lipid lowering effects but the underlying mechanisms remained unclear. Free fatty acids (FFAs) are generally correlated with the development of obesity, leading to increased risk for type 2 diabetes mellitus and cardiovascular diseases. To investigate whether Pu-erh tea treatment alters FA metabolism, we treated HFD induced obese mice with Pu-erh tea for 22 weeks and analyzed FFA profiles of experimental mice using a UPLC-QTOF-MS platform. Results showed remarkable changes in metabolic phenotypes and FFA compositions in mice treated with or without Pu-erh tea. HFD induced a marked obese phenotype in mice as revealed by significantly increased body weight, liver and adipose tissue weight, lipid levels in serum and liver, and these parameters were markedly reduced by Pu-erh tea treatment. Several FFA or FFA ratios, such as DGLA, palmitoleic acid, and OA/SA ratio, were significantly increased while the levels of SA/PA and AA/DGLA were significantly reduced in HFD-induced obese mice. Interestingly, these differential FFAs or FFA ratios were previous identified as key markers in human obese subjects, and their changes observed in the HFD group were reversed by Pu-erh tea treatment. Moreover, a panel of FFA markers including C20:3 n6/C18:3 n6 and C20:3 n6/C20:2 n6, C18:3 n6/C18:2 n6, C18:3 n3/C18:2 n6 and C24:1 n9/C22:1 n9, which were previously identified as biomarkers in predicting the remission of obesity and diabetes in human subjects who underwent metabolic surgery procedures, were reversed by Pu-erh tea intervention. Pu-erh tea significantly improved glucose homeostasis and insulin tolerance compared to the HFD group. Additionally, Pu-erh tea treatment significantly decreased FFA synthesis genes and increased the expression of genes involved in FFA uptake and β-oxidation including FATP2, FATP5, PPARα, CPT1α, and ACOX-1. These finding confirmed the beneficial effects of Pu-erh tea on regulating lipid and glucose metabolism, and further validated a panel of FFA markers with diagnostic and prognostic value for obesity and diabetes. [ABSTRACT FROM AUTHOR]

Lomefloxacin (LOM) and pefloxacin (PEF) are synthetic antibiotics that have been used in the treatment of infectious diseases in both human and animals. In the People’s Republic of China, the use of LOM and PEF in livestock has been prohibited because of the concern that the residues of these drugs may pose a risk to public health. Despite this prohibition, these drugs are still being used in the poultry industry illegally, and so far there has been no systematic study of the persistence of LOM and PEF residues in chickens. In this study, laying hens were treated with a daily dose (10 mg/kg of body weight) of LOM or PEF for five consecutive days, and the drug residues in various tissues and eggs were determined over a 15-day period after the last drug administration. The highest LOM and PEF residual concentrations were found in the tissues 4 h after the last drug administration, and concentrations gradually decreased over time. Plasma had the lowest and liver had the highest residual concentrations throughout the 15-day study period. At the end of the 15 days, 3.64 6 0.74 lg/kg LOM and 1.78 6 0.28 lg/kg PEF were detected in the liver, with slightly lower residual concentrations in the kidney. No LOM or PEF residue was detected in the ovarian follicle, plasma, and muscle at the end of the 15 days. In eggs, the depletion rate of LOM was slower than that of PEF. LOM and PEF residues were detected in whole eggs for up to 10 and 8 days, respectively, after drug administration ceased. These findings suggest that the liver and, to a lesser extent, the kidney may be the sites where LOM or PEF residues would persist. This information can be a reliable reference for governmental agencies with respect to the screening of LOM and PEF residues in food products derived from laying hens. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk factors for postoperative fever and to identify the value of preoperative procalcitonin (PCT) in predicting postoperative fever after percutaneous nephrolithotomy (PNL). Patients and Methods: Patients who underwent PNL between January 2014 and March 2017 were studied. In total, 363 medical records with complete data were determined to be eligible for analysis. Patients were classified into a control or febrile group according to the presence of a body temperature over 38°C. Demographic and perioperative data were compared between the groups. Variables found to be statistically significant were included in a binary logistic regression analysis. Results: Ninety-one (25.1%) patients experienced postoperative fever. Univariate analysis revealed a statistically significant difference between postoperative fever and factors, such as sex (p = 0.009), preoperative fever (p < 0.001), stone burden (p < 0.001), pyuria (p = 0.013), urine culture (p < 0.001), and serum levels of Creactive protein (CRP) (p = 0.003), PCT (p < 0.001), and interleukin-6 (IL-6) (p = 0.003). Binary logistic regression analysis indicated the presence of preoperative fever (p = 0.037), stone burden >353mm² (p = 0.002), PCT >0.05 ng/mL (p < 0.001), or positive urine culture (p = 0.004) as independent risk factors for postoperative fever following PNL. Conclusions: We concluded that patients with preoperative fever, stone burden >353mm², PCT >0.05 ng/mL, or positive urine culture were more likely to develop postoperative fever and that routinely detecting PCT levels before PNL would be helpful in predicting postoperative fever. [ABSTRACT FROM AUTHOR]

Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. [ABSTRACT FROM AUTHOR]

Fatty liver syndrome is a metabolic disorder that occurs in mink (Mustela vison). The aim of this study was to compare the effects of dietary fat sources (chicken oil, fish oil and soybean oil) on the recovery fatty liver syndrome in female mink in response to short term fasting for 5 days and subsequent re-feeding for 7-28 days. Food deprivation resulted in the rapid mobilization of body fat, causing an elevated hepatosomatic index and increased liver lipid content. Re-feeding resulted in a more pronounced recovery of liver health in the mink fed the fish oil diet than chicken oil or soybean oil diet. The fish oil diet was found to be useful to relieve the severity of hepatic lipidosis in mink. [ABSTRACT FROM AUTHOR]

American mink (Neovison vison) develop fatty liver quickly in response to food deprivation, which results in preferential mobilisation of n-3 PUFA. The altered n-3:n-6 PUFA ratio in the liver may activate the endocannabinoid system resulting in increased lipid synthesis. The objective of the present study was to investigate the effects of feeding intensity (80 or 120 % RDA), dietary fat source (n-3, n-6 or n-9 fatty acids (FA)) and short-term fasting (1–7 d) on hepatic de novo lipogenesis (DNL) and the development of fatty liver in mink. Significantly elevated expression of mRNA encoding for acetyl-CoA carboxylase-1 (ACC-1) and FA synthase (FAS) was observed in the liver of mink fasted for 5–7 d, while upon re-feeding for 28 d after a 7 d food deprivation, DNL returned to pre-fasting levels. The females had a higher expression of ACC-1 and FAS mRNA than the males. In the non-fasted animals, dietary fat source and feeding intensity had significant effects on ACC-1 mRNA. The highest levels were observed in the mink fed the rapeseed oil (n-9) diet at 80 % RDA, while the lowest levels were seen when the same diet was fed at 120 % RDA. For FAS, the highest gene expression was seen in the fasted mink fed at 80 % RDA and the lowest in the non-fasted mink fed at 80 %. It is concluded that short-term food deprivation induces hepatic lipidosis in mink and that during this process, hepatic DNL further exacerbates liver fat accumulation. [ABSTRACT FROM PUBLISHER]

Hydrogen sulfide (H2S) is produced endogenously by l-cysteine metabolism. H2S modulates several ion channels with an unclear mechanism of action. A possible mechanism is through reduction-oxidation reactions attributable to the redox potential of the sulfur moiety. The aims of this study were to determine the effects of the H2S donor NaHS on NaV1.5, a voltage-dependent sodium channel expressed in the gastrointestinal tract in human jejunum smooth muscle cells and interstitial cells of Cajal, and to elucidate whether H2S acts on NaV1.5 by redox reactions. Whole cell Na+ currents were recorded in freshly dissociated human jejunum circular myocytes and NaV1.5-transfected human embryonic kidney-293 cells. RT-PCR amplified mRNA for H2S enzymes cystathionine β-synthase and cystathionine γ-lyase from the human jejunum. NaHS increased native Na+ peak currents and shifted the half-point (V1/2) of steady-state activation and inactivation by +21 ± 2 mV and +15 ± 3 mV, respectively. Similar effects were seen on the heterologously expressed NaV1.5 α subunit with EC50s in the 10-4 to 10-3 M range. The reducing agent dithiothreitol (DTT) mimicked in part the effects of NaHS by increasing peak current and positively shifting steady-state activation. DTT together with NaHS had an additive effect on steady-state activation but not on peak current, suggesting that the latter may be altered via reduction. Pretreatment with the Hg2+-conjugated oxidizer thimerosal or the alkylating agent N-ethylmaleimide inhibited or decreased NaHS induction of NaV1.5 peak current. These studies show that H2S activates the gastrointestinal Na+ channel, and the mechanism of action of H2S is partially redox independent. [ABSTRACT FROM AUTHOR]

The aims of this study were to quantify the change in resting membrane potential (RMP) across the thickness of the circular muscle layer in the mouse and human small intestine and to determine whether the gradient in RMP is dependent on the endogenous production of carbon monoxide (CO). Conventional sharp glass microelectrodes were used to record the RMPs of circular smooth muscle cells at different depths in the human small intestine and in wild-type, HO2-KO, and W/Wv mutant mouse small intestine. In the wild-type mouse and human intestine, the RMP of circular smooth muscle cells near the myenteric plexus was -65.3 ± 2 mV and -58.4 ± 2 mV, respectively, and -60.1 ± 2 mV and -49.1 ± I mV, respectively, in circular smooth muscle cells at the submucosal border. Oxyhemoglobin (20 µM), a trapping agent for CO, and chromium mesoporphyrin IX, an inhibitor of heme oxygenase, abolished the transwall gradient. The RMP gradients in mouse and human small intestine were not altered by NG-nitro-L-arginine (200 µM). No transwall RMP gradient was found in HO2-KO mice and W/Wv mutant mice. TTX (1 µM) and lH-[1,2,4-]oxadiazolo[4,3-a]-quinoxalin-1-one (10 µM) had no effect on the RMP gradient. These data suggest that the gradient in RMP across the thickness of the circular muscle layer of mouse and human small intestine is CO dependent. [ABSTRACT FROM AUTHOR]

Autoimmune autonomic neuropathy (AAN) is an acquired, often severe, form of dysautonomia. Many patients with AAN have serum antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (AChR). Rabbits immunized with a fusion protein corresponding to the N-terminal extracellular domain of the ganglionic AChR α3 subunit produce ganglionic AChR antibodies and develop signs of experimental AAN (EAAN) that recapitulate the cardinal autonomic features of AAN in man. We now demonstrate that EAAN is an antibody-mediated disorder by documenting sympathetic, parasympathetic, and enteric autonomic dysfunction in mice injected with rabbit IgG containing ganglionic AChR antibodies. Recipient mice develop transient gastrointestinal dysmotility, urinary retention, dilated pupils, reduced heart rate variability, and impaired catecholamine response to stress. The autonomic signs are associated with a reversible failure of nicotinic cholinergic synaptic transmission in superior mesenteric ganglia. Mice injected with IgG from two patients with AAN (of three tested) demonstrated a milder phenotype with evidence of urinary retention and gastrointestinal dysmotility. The demonstration that ganglionic AChR-specific IgG causes impaired autonomic synaptic transmission and autonomic failure in mice implicates an antibody-mediated pathogenesis for AAN. The antibody effect is potentially reversible, justifying early use of immunomodulatory therapy directed at lowering IgG levels and abrogating IgG production in patients with AAN. [ABSTRACT FROM AUTHOR]

Problem: Decidual stromal cells (DSCs) are important origins of cytokines to modulate maternal‐fetal immunotolerance and provide a feasible environment for embryo implantation and development. Interleukin (IL)‐24 is a multifunctional cancer killing cytokine and a pleiotropic immunoregulator with complex potency according to tissue or cell types. Its role in establishment and maintenance of normal pregnancy is largely unknown. The aim of our study was to investigate the function and significance of IL‐24 and its receptor in the coordination between DSCs and natural killer cells (NK) in early pregnancy. Method of study : The levels of IL‐24 in DSC, endometrial stromal cell (ESC), peripheral blood NK cells (pNK), or decidual NK cells (dNK) culture supernatants were detected by enzyme‐linked immunosorbent assay (ELISA), and the levels of IL‐24 receptors were determined by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) and flow cytometry assays. The effect of IL‐24 on the functions of decidual NK cells was analyzed by flow cytometry assays in vitro. Results : The concentration of IL‐24 in culture supernatant of DSCs was significantly higher than that of ESCs. Both eNK (endometrial NK cells) and dNK highly expressed IL‐24 receptors (IL‐20R1 and IL‐22R1), especially on CD56dim eNK. However, there were extremely low levels of IL‐20R1 and IL‐22R1 on pNK. Recombinant human IL‐24 or DSCs‐secreted IL‐24 downregulated the levels of CD16, Granzyme B, perforin, and interferon (IFN)‐γ and upregulated the levels of inhibitory receptors killer‐cell immunoglobulin‐like receptor (KIR)2DL1 and KIR3DL1, or immunotolerant or angiogenic cytokines (eg, transforming growth factor (TGF)‐β, IL‐10, and IL‐8), and elevated the percentage of CD56brightCD16−dNK in vitro. Conclusion : These data suggest that DSCs promote the differentiation of CD56brightCD16−NK with high levels of inhibitory receptors, immunotolerant, and angiogenic cytokines by secreting IL‐24 during decidualization in early pregnancy. [ABSTRACT FROM AUTHOR]

We report a new member to the family of tungsten nitrides, WN6, predicted from the structure search. Ground-state convex hull calculation reveals that crystalline WN6 is thermodynamically stable at pressures above 16 GPa, but remains dynamically stable at ambient conditions. The predicted high-pressure WN6 structure contains chaired rings isoelectronic to cyclo-hexasulfur (S6), which is unprecedented in nitrogen. In the unit all nitrogen atoms are singly bonded and therefore contain a high energy density. By means of efficiently packing the covalent-bonded species, WN6 is estimated to have extremely high Vickers hardness greater than 40 GPa at ambient conditions, placing it as one of the hardest materials. The present results reveal that WN6 may be used as a superhard material but simultaneously maintaining other desirable properties, which represents an interesting example of multifunctional materials. [ABSTRACT FROM AUTHOR]

Emerging evidence points to a strong association between sex and gut microbiota, bile acids (BAs), and gastrointestinal cancers. Here, we investigated the mechanistic link between microbiota and hepatocellular carcinogenesis using a streptozotocin-high fat diet (STZ-HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) murine model and compared results for both sexes. STZ-HFD feeding induced a much higher incidence of HCC in male mice with substantially increased intrahepatic retention of hydrophobic BAs and decreased hepatic expression of tumor-suppressive microRNAs. Metagenomic analysis showed differences in gut microbiota involved in BA metabolism between normal male and female mice, and such differences were amplified when mice of both sexes were exposed to STZ-HFD. Treating STZ-HFD male mice with 2% cholestyramine led to significant improvement of hepatic BA retention, tumor-suppressive microRNA expressions, microbial gut communities, and prevention of HCC. Additionally the sex-dependent differences in BA profiles in the murine model can be correlated to the differential BA profiles between men and women during the development of HCC. These results uncover distinct male and female profiles for gut microbiota, BAs, and microRNAs that may contribute to sex-based disparity in liver carcinogenesis, and suggest new possibilities for preventing and controlling human obesity-related gastrointestinal cancers that often exhibit sex differences. [ABSTRACT FROM AUTHOR]