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Stem cell‐derived pancreatic progenitors (SC‐PPs), as an unlimited source of SC‐derived β (SC‐β) cells, offers a robust tool for diabetes treatment in stem cell‐based transplantation, disease modeling, and drug screening. Whereas, PDX1+/NKX6.1+ PPs enhances the subsequent endocrine lineage specification and gives rise to glucose‐responsive SC‐β cells in vivo and in vitro. To identify the regulators that promote induction efficiency and cellular function maturation, single‐cell RNA‐sequencing is performed to decipher the transcriptional landscape during PPs differentiation. The comprehensive evaluation of functionality demonstrated that manipulating LINC MIR503HG using CRISPR in PP cell fate decision can improve insulin synthesis and secretion in mature SC‐β cells, without effects on liver lineage specification. Importantly, transplantation of MIR503HG−/− SC‐β cells in recipients significantly restored blood glucose homeostasis, accompanied by serum C‐peptide release and an increase in body weight. Mechanistically, by releasing CtBP1 occupying the CDH1 and HES1 promoters, the decrease in MIR503HG expression levels provided an excellent extracellular niche and appropriate Notch signaling activation for PPs following differentiation. Furthermore, this exhibited higher crucial transcription factors and mature epithelial markers in CDH1High expressed clusters. Altogether, these findings highlighted MIR503HG as an essential and exclusive PP cell fate specification regulator with promising therapeutic potential for patients with diabetes. [ABSTRACT FROM AUTHOR]

To avoid CO2 pneumoperitoneum-associated cardiopulmonary side-effects during conventional laparoscopic surgeries, we have developed a gasless laparoscopic operation field formation (LOFF) device for laparoendoscopic single-site surgery. The aim of this study is to analyze the safety and efficacy of the LOFF device for laparoendoscopic single-site cholecystectomy and to verify its advantage of avoiding CO2 pneumoperitoneum-associated complications. In this prospective, randomized, observer-blinded clinical trial, eligible participants were randomized in a 1:1 ratio to undergo either conventional CO2 pneumoperitoneum assisted laparoendoscopic single-site cholecystectomy (LESS) or the new gasless LOFF device assisted laparoendoscopic single-site cholecystectomy (LOFF-LESS). Outcomes including intra-operative respiratory and hemodynamic parameters, operation time, conversion rate, complication rate, et al were compared between the two groups. A total of 100 patients were randomized to the LESS group [n = 50; mean (SD) age, 49.5 (13.9) years; 24 (48.0%) women] and the LOFF-LESS group [n = 50, mean (SD) age, 47.4 (13.3) years; 27 (54.0%) women]. Compared with the LOFF-LESS group, the LESS group witnessed significant fluctuations in intra-operative respiratory and hemodynamic parameters. The tracheal extubation time of the LESS group was significantly longer (P = 0.001). The gasless LOFF device is safe and feasible for simple laparoscopic cholecystectomy and has a predominance of avoiding CO2 pneumoperitoneum-associated cardiopulmonary side-effects. Trial registration number: ChiCTR2000033702 [ABSTRACT FROM AUTHOR]

Background: Hepatic lipid metabolism regulates biliary composition and influences the formation of cholesterol gallstones. The genes Hmgcr and Cyp7a1 , which encode key liver enzymes, are regulated by circadian rhythm-related transcription factors. We aimed to investigate the effect of circadian rhythm disruption on hepatic cholesterol and bile acid metabolism and the incidence of cholesterol stone formation. Methods: Adult male C57BL/6J mice were fed either a lithogenic diet (LD) only during the sleep phase (time-restricted lithogenic diet feeding, TRF) or an LD ad libitum (non-time-restricted lithogenic diet feeding, nTRF) for 4 weeks. Food consumption, body mass gain, and the incidence of gallstones were assessed. Circulating metabolic parameters, lipid accumulation in the liver, the circadian expression of hepatic clock and metabolic genes, and the gut microbiota were analyzed. Results: TRF caused a dysregulation of the circadian rhythm in the mice, characterized by significant differences in the circadian expression patterns of clock-related genes. In TRF mice, the circadian rhythms in the expression of genes involved in bile acid and cholesterol metabolism were disrupted, as was the circadian rhythm of the gut microbiota. These changes were associated with high biliary cholesterol content, which promoted gallstone formation in the TRF mice. Conclusion: Disordered circadian rhythm is associated with abnormal hepatic bile acid and cholesterol metabolism in mice, which promotes gallstone formation. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that cholecystectomy is an independent risk factor for non‐alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms that lead to hepatic lipid deposition after cholecystectomy are unclear. In this study, adult male C57BL/6J mice that underwent a cholecystectomy or sham operation were fed either a high‐fat diet (HFD) or a chow diet for 56 days. Significantly increased steatohepatitis, liver/body weight ratio, hepatic triglycerides, and glucose intolerance were observed in postcholecystectomy mice fed the HFD. Notable alterations in the composition of gut microbiota after cholecystectomy were observed in both HFD‐ and chow‐diet‐fed mice. Our results indicate that cholecystectomy alters the gut microbiota profile, which might contribute to the development of NAFLD in mice. [ABSTRACT FROM AUTHOR]

The optimization of bulk heterojunction morphology is one of the most challenging topics in all‐small‐molecule organic solar cells. Herein, three small molecular donors based on dithieno[2,3‐d;2′,3′‐d′]benzo[1,2‐b;4,5‐b′]dithiophene (DTBDT) unit by systematically moving the branching point of the alkyl chain have been designed, synthesized, and applied in organic solar cells. Modifying the branching points enables the properties of the aggregation state to be tuned, and an efficient nanofiber‐based hierarchical morphology is successfully demonstrated by combining with different nonfullerene acceptors. The molecules with far branching points can form nanofibers in active layers, and theses nanofibers help the charge separation and charge transport in a large donor‐rich or acceptor‐rich domain of approximately 100 nm. Using nonfullerrene Y6 as an acceptor, the highest power conversion efficiency of 14.78% is obtained, which is one of the highest efficiencies in all‐small‐molecule organic solar cells. The strategy of modification of alkyl side chain branching points can be a practical way to actualize crystallinity control and active layer morphology for improving the performance of all‐small‐molecule organic solar cells. [ABSTRACT FROM AUTHOR]

Abstract: Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different aromatic rings as π bridges and different core side substitutions are designed and synthesized (PzNDT‐T‐1,3‐bis(4‐(2‐ethylhexyl)‐thiophen‐2‐yl)‐5,7‐bis(2‐ethylhexyl)benzo[1,2‐c:4,5‐c′]‐dithiophene‐4,8‐dione (BDD), PzNDT‐TT‐BDD, and PzNDTP‐T‐BDD, respectively). The 2D conjugation structure and molecular planarity of the polymers can be effectively altered through the modification of conjugated side chains and π‐bridges. These alterations contribute to the variation in energy levels, light absorption capacity, and morphology compatibility of the polymers. When blended with the nonfullerene acceptor (2,2′‐[(4,4,9,9‐tetrahexyl‐4,9‐dihydro‐sindaceno[1,2‐b:5,6‐b′]dithiophene‐2,7‐diyl)bis[methylidyne(3‐oxo‐1H‐indene‐2,1(3H)‐diylidene)]]bis‐propanedinitrile) (IDIC), PzNDT‐T‐BDD exhibits the highest power conversion efficiency (PCE) of 9.72% among the three polymers. This result can be attributed to its superior crystallinity and more obvious face‐on orientation in blending film. PzNDT‐TT‐BDD and PzNDTP‐T‐BDD present PCE values of 8.20% and 4.62%, respectively. The alteration of polymer structure, particularly the modification of conjugated side chains and π‐bridges, is an effective strategy for designing NDT‐based polymers with high photovoltaic performance and potential applications in fullerene‐free solar cells. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p’-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human. [ABSTRACT FROM AUTHOR]

Global prevalence of obesity has been increasing dramatically in all ages. Although traditional causes for obesity development have been studied widely, it is unclear whether environmental exposure of substances such as trace heavy metals affects obesity development among children and adolescents so far. Data from the National Health and Nutrition Examination Survey (1999-2011) were retrieved, and 6602 US children were analyzed in this study. Urinary level of nine trace heavy metals, including barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, and tungsten, was analyzed for their association with the prevalence of obesity among children aged 6-19 years. Multiple logistic regression was performed to assess the associations adjusted for age, race/ethnicity, gender, urinary creatinine, PIR, serum cotinine, and television, video game, and computer usage. A remarkable association was found between barium exposure (OR 1.43; 95% CI 1.09-1.88; P < 0.001) and obesity in children aged 6-19 years. Negative association was observed between cadmium (OR 0.46; 95% CI 0.33-0.64; P < 0.001), cobalt (OR 0.56; 95% CI: 0.41-0.76; P < 0.001), and lead (OR 0.57; 95% CI 0.41-0.78; P = 0.018), and obesity. All the negative associations were stronger in the 6-12 years group than in the 13-19 years group. The present study demonstrated that barium might increase the occurrence of obesity, but cadmium, cobalt, and lead caused weight loss among children. The results imply that trace heavy metals may represent critical risk factors for the development of obesity, especially in the area that the state of metal contamination is serious. [ABSTRACT FROM AUTHOR]

Two novel asymmetric thiophene/pyridine flanked diketopyrrolopyrrole (DPP) based polymers, named PPyTDPP-TT and PPyTDPP-BT were designed, synthesized and applied in organic field-effect transistors (OFETs) and polymer solar cells (PSCs). In contrast to the reported bipyridine flanked DPP, the asymmetric DPP polymers incorporating thiophene/pyridine flankers exhibited narrower bandgaps of ∼1.5 eV and deeper HOMO energy levels, thus leading to a broadened absorption from 500 to 850 nm and were potentially beneficial for low-energy photon harvesting. Both polymers displayed promising ambipolar semiconducting properties. The hole and electron mobilities of PPyTDPP-TT reach 0.48 cm2 V−1 s−1 and 0.18 cm2 V−1 s−1; and PPyTDPP-BT reach 0.55 cm2 V−1 s−1 and 0.08 cm2 V−1 s−1, respectively. Intriguingly, due to their ambipolar properties, two polymers can play an ambipolar role, both as electron donors and acceptors with PC71BM and P3HT in PSCs. Photovoltaic devices based on PPyTDPP-BT as the donor material reach PCEs of 7.56% and achieve 0.59% as the acceptor material, while those based on PPyTDPP-TT reach 5.48% with PC71BM and 0.82% with P3HT, respectively. These results suggest that the adoption of asymmetric flanker DPP polymers can effectively tune the absorption properties of polymers as excellent ambipolar transporting polymers towards high performance in both OFETs and PSCs. [ABSTRACT FROM AUTHOR]

Objective: The gut microbiome is essential for human health due to its effects on disease development, drug metabolism and the immune system. It may also play a role in the interaction with environmental toxicants. However, the effect of epoxiconazole, a fungicide active ingredient from the class of azoles developed to protect crops, on the abundance and composition of the gut microbiome has never been studied. We put forward the hypothesis that changes in gut microbiota may be early signs of toxicity induced by epoxiconazole. Methods: In this study, female rats were fed with epoxiconazole-adulterated diets (0, 4 and 100 mg/kg/day) for 90 days. The gut microbiome was determined by 16S rRNA gene sequencing. Body and organ weight, and blood biochemistry were also measured after 90 days of oral epoxiconazole exposure. Results: Interestingly, the abundance of gut Firmicutes decreased, and Bacteroidetes and Proteobacteria increased. At family level, Lachnospiraceae and Enterobacteriaceae were selectively enriched following epoxiconazole exposure. Our results indicate that epoxiconazole exposure may induce changes in the gut microbiome and potential liver toxicity. Conclusion: Changes in the gut microbiome may be used as early indicators for monitoring the health risk of the host. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Associations between polycyclic aromatic hydrocarbons (PAHs) and respiratory diseases have been widely studied, but the effects of PAH on liver toxicity in adolescents are unclear. Here, 3194 adolescents with NHANES data from 2003 to 2016 were selected. PAH exposure was assessed by measuring PAH metabolites in urine. The outcome variables were the levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transpeptidase (GGT). The association between PAH exposure and liver function was evaluated by the weighted quantile sum (WQS) and logistic regression, and the associations between PAHs and inflammation and blood lipids were evaluated by linear regression. Covariates were adjusted for age, ethnicity, BMI, physical activity, family income, cotinine, and urinary creatinine. The results showed that for females, mixed PAH exposure was related to an increased ALT level (OR = 2.33, 95% CI 1.15, 4.72), and 2-fluorene contributed the most (38.6%). Urinary 2-fluorene was positively associated with an elevated ALT level (OR = 2.19 95% 1.12, 4.27, p for trend = 0.004). Mechanistically, 2-fluorene can cause a 3.56% increase in the white blood cell count, a 6.99% increase in the triglyceride level, and 1.70% increase in the total cholesterol level. PAHs may have toxic effects, possibly mediated by inflammation and blood lipids, on the adolescent female liver. Additional confirmatory studies are needed. [Display omitted] • Urinary PAHs mixtures may be risk factors for hepatotoxicity. • Urinary 2-fluorene positively associated with increased risk of ALT. • Each increment of one unit (ng/L) in the 2-fluorene was associated with a 3.56% increase in white blood cells count. Exposure to a mixture of polycyclic aromatic hydrocarbons (PAHs) is positively related to elevated alanine aminotransferase (ALT) level. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is an emerging organic pollutant (EOP) hazardous to human health. Effects of maternal PFOA exposure on offspring as well as the underlying mechanisms remain unclear. In this study, ICR mouse models of gestational low PFOA exposure (0.05 mg/kg/day) were established to investigate the roles on metabolic disorders of offspring. Body weight, body composition, hepatic lipid levels, transcriptome and metabolome were analyzed. Expression of genes related to lipid metabolism, inflammasome formation and gut barrier integrity were measured. Furthermore, oral administration of chlorogenic acid (CGA) (100 mg/kg/day) was performed to observe the rescue effect on lipid disorders caused by PFOA exposure. Our findings demonstrated that gestational exposure to PFOA resulted in obesity, hepatic inflammation, disorders of lipid metabolism, and disruption of gut barrier integrity in male offspring. Notably, these adverse effects were attenuated by CGA supplementation. These data suggested that PFOA exposure during early life stage induced potential risks for later onset of obesity and metabolic disorder which could be ameliorated by CGA treatment. Image 1 • Low-dose gestational perfluorooctanoic acid (PFOA) exposure induces obesity in male offspring. • Low-dose gestational PFOA exposure impairs hepatic lipid metabolism and gut barrier integrity in male offspring. • Chlorogenic acid (CGA) attenuates adverse effects in male offspring induced by PFOA. Chlorogenic acid (CGA) ameliorates gestational PFOA exposure induced obesity and metabolic disorder in male offspring. [ABSTRACT FROM AUTHOR]

p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p'-DDE and β-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and β-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p'-DDE and β-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid β-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid β-oxidation and aggravated disorders of fatty acid metabolism. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below: 4,4′-thiodiphenol (TDP) < bisphenol S (BPS) < 4,4′-dihydroxybenzophenone (DHBP) < tetrabromobisphenol A (TBBPA) < tetrachlorobisphenol A (TCBPA) < bisphenol E (BPE) < bisphenol F (BPF) < bisphenol B (BPB) < bisphenol AF (BPAF) < bisphenol A (BPA) < bisphenol C (BPC) < tetramethylbisphenol A (TMBPA) < bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid β-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs. • A high-content screening assay was performed to evaluate the hepatic lipid accumulation of 13 bisphenols in vitro. • BPE, BPF, BPB, BPAF, BPA, BPC, TMBPA, and BPAP exhibited the significant effects on lipid deposition. • BPAP, BPA, and BPAF significantly regulated genes involved in lipid β-oxidation, lipogenesis and nuclear receptor genes. [ABSTRACT FROM AUTHOR]

In recent years, the security of deep learning models achieves more and more attentions with the rapid development of neural networks, which are vulnerable to adversarial examples. Almost all existing gradient-based attack methods use the sign function in the generation to meet the requirement of perturbation budget on L ∞ norm. However, we find that the sign function may be improper for generating adversarial examples since it modifies the exact gradient direction. Instead of using the sign function, we propose to directly utilize the exact gradient direction with a scaling factor for generating adversarial perturbations, which improves the attack success rates of adversarial examples even with fewer perturbations. At the same time, we also theoretically prove that this method can achieve better black-box transferability. Moreover, considering that the best scaling factor varies across different images, we propose an adaptive scaling factor generator to seek an appropriate scaling factor for each image, which avoids the computational cost for manually searching the scaling factor. Our method can be integrated with almost all existing gradient-based attack methods to further improve their attack success rates. Extensive experiments on the CIFAR10 and ImageNet datasets show that our method exhibits higher transferability and outperforms the state-of-the-art methods.

The role and mechanism of insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) in the metastasis of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, IGF2BP3 mRNA and protein expression levels were evaluated in ESCC tissues. Small interfering RNAs (siRNAs), plasmid overexpression, and stable lentivirus transfection were used to manipulate intracellular IGF2BP3 expression levels. The role of IGF2BP3 in ESCC tumorigenesis was investigated in vitro and in vivo. IGF2BP3 target transcripts were detected, and the acetylation effect ratios of the IGF2BP3 promoter region by H3K27ac were determined. IGF2BP3 mRNA expression levels were significantly higher in ESCC tissues than in normal esophageal tissues. Increased IGF2BP3 expression levels were detected in node-negative ESCC tissues and correlated with greater lesion depth in ESCC. Overexpression of IGF2BP3 promoted ESCC development in vitro and in vivo, and IGF2BP3 knockdown caused an opposite effect. IGF2BP3 was found to directly bind to the zinc finger E-box-binding homeobox 1 (Zeb1) mRNA, and the downregulation of IGF2BP3 reduced the stability of Zeb1 mRNA. IGF2BP3 induced epithelial-mesenchymal transition in ESCC cells in a Zeb1-dependent manner. IGF2BP3 was transcriptionally activated in ESCC cell lines via H3K27 acetylation. Our results demonstrate that IGF2BP3 plays a vital role in ESCC cell proliferation, invasion, and metastasis and is a potential therapeutic target for treating ESCC., (© 2023 Wiley Periodicals LLC.)

Objective: For patients with gallstones, laparoscopy combined with choledochoscopic lithotomy is a therapeutic surgical option for preservation rather than the removal of the gallbladder. However, postoperative recurrence of gallstones is a key concern for both patients and surgeons. This prospective study was performed to investigate the risk factors for early postoperative recurrence of gallstones. Methods: The clinical data of 466 patients were collected. Each patient was followed up for up to 2 years. The first follow-up visit occurred 4 months after the operation, and a follow-up visit was carried out every 6 months thereafter. The main goal of each visit was to confirm the presence or absence of gallbladder stones. The factors associated with gallstone recurrence were analyzed by univariate analysis and Cox regression. Results: In total, 466 eligible patients were included in the study, and 438 patients (180 men and 258 women) completed the 2-year postoperative follow-up. The follow-up rate was 94.0%. Recurrence of gallstones was detected in 5.71% (25/438) of the patients. Univariate analysis revealed five risk factors for the recurrence of gallstones. Multivariate Cox regression analysis showed that multiple gallstones, a gallbladder wall thickness of ≥4 mm, and a family history of gallbladder stones were the three predictive factors for postoperative recurrence of gallstones ( P < 0.05). Conclusion: The overall 2-year recurrence rate of gallstones after the operation was 5.71%. Multiple gallstones, a gallbladder wall thickness of ≥4 mm, and a family history of gallstones were the three risk factors associated with early postoperative recurrence of gallstones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Huang, Jiang, Li, Bao, Ding, Jiang, Zhao and Hu.)

Gallstone disease is a worldwide common disease. However, the knowledge concerning the gallbladder in the pathogenesis of cholesterol gallstone formation remains limited. In this study, using single-cell RNA sequencing (scRNA-seq) to obtain the transcriptome of gallbladder cells, we showed cellular heterogeneity and transcriptomic dynamics in murine gallbladder cells during the process of lithogenesis. Our results indicated gallbladder walls were subjected to remodeling during the process of lithogenesis. The major molecular events that happened included proliferation of epithelial cells, infiltration of immune-cells, activation of angiogenesis, and extracellular matrix modulation. Furthermore, we observed partial reversal of gallbladder cell transcriptomes by ursodeoxycholic acid treatment. This work thus provides novel and integral knowledges on the cellular changes during lithogenesis, which is of great significance to the understanding of pathogenesis and treatment of cholesterol gallstone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liang, Shao, Liu, Lu, Gu and Jiang.)

This paper presents detailed methods on detecting hepatic mitochondrial function for a better understanding the cause of metabolic disorders caused by environmental organochlorine pesticides (OCPs) in hepatocytes. HepG2 cells were exposed to β-hexachlorocyclohexane (β-HCH) for 24 h at an equivalent dose of internal exposure in general population. Ultrastructure in hepatocytes was examined by transmission electron microscopy (TEM) to show the damage of mitochondria. Mitochondrial function was further evaluated by mitochondrial fluorescence intensity, adenosine 5'-triphosphate (ATP) levels, oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP) in HepG2 cells incubated with β-HCH. The mitochondria fluorescence intensity after stained by mitochondrial green fluorescent probe was observed with a fluorescence microscopy. The luciferin-luciferase reaction was used to determine ATP levels. The MMP was detected by the cationic dye JC-1 and analyzed under flow cytometry. OCR was measured with an extracellular flux analyzer. In summary, these protocols were used in detecting mitochondrial function in hepatocytes with to investigate mitochondria damages.

Cisplatin is widely used as the standard gastric cancer treatment, but the relapse and metastasis are common as intrinsic or acquired drug resistance. CD133 has been widely known to be associated with chemoresistance in various cancer cells. In this study, we focused on investigating the function and mechanism of CD133 underlying cisplatin resistance in gastric cancer cell line KATO-III. We detected CD133 expression by using quantitative real-time polymerase chain reaction and Western blot and found that expression of CD133 was upregulated in cisplatin resistance of KATO-III cells (Cis-KATO-III) compared with KATO-III cells, indicating the role of CD133 in regulating cisplatin resistance of KATO-III cells. Then we sorted the Cis-KATO-III cells into CD133-positive (CD133 + ) pools and measured the proliferation and apoptosis after the cell is transfected with pc-CD133 and sh-CD133 by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry. The results showed that the inhibition of CD133 inhibited the cell viability and promoted the cell apoptosis after cisplatin treatment. Furthermore, we found that inhibition of CD133 downregulated the expression of PI3K/AKT and promoted the expression of mammalian target of rapamycin, thus inhibited the autophagic activity in the Cis-KATO-III cells after cisplatin treatment. Besides, we also verified the effects of CD133 in vivo . The results indicated that inhibition of CD133 enhanced the Cis-KATO-III cell sensitivity to cisplatin by regulating PI3K/AKT/mTOR signaling pathway. In summary, our data provide new insight that CD133 activates the PI3K/AKT/mTOR signaling transduction pathway, resulting in activation of autophagy and cisplatin resistance of Cis-KATO-III cells. These results may offer a novel therapeutic target in cisplatin-resistant gastric cancer.

Introduction: Traditional laparaendoscopic surgery using CO2 pneumoperitoneum is associated with complications and the existing gasless laparaendoscopic surgery has shortcomings such as poor visibility in the operation field. To overcome the disadvantages of the current lifting gasless laparaendoscopic operation platforms, we developed an inflatable device for gasless laparoscopic operation field formation (LOFF) that can be internally installed and applied in practice., Methods: We initially designed operation platforms for gasless laparaendoscopic single-port (GLESP) surgery. Subsequently, a triangular prismatic LOFF device was selected and applied successfully to GLESP cholecystectomy of five pigs. Ultimately, using pigs as a model, three surgical approaches (LOFF-assisted laparaendoscopic single-site (LOFF-LESS), LESS surgery, and traditional lifting (GLESP) were compared, and the advantages and drawbacks of inflatable devices for gasless laparoscopic operation field assessed., Results: The use of the LOFF device in GLESP cholecystectomy was first evaluated. The time for surgical space formation (4.4 ± 1.2 and 4.8 ± 1.0), the operating time for gallbladder removal (25.2 ± 4.8 and 25.4 ± 2.7), and the loss of blood (9.4 ± 3.1and 9.2 ± 2.4) was similar between LESS and LOFF, respectively (Table 2). In contrast these parameters were higher in GLESP (6.6 ± 1.0, 30.3 ± 4.4 and 10.1 ± 2.0, respectively. The LOFF-LESS surgery exhibited a clearer exposure of the surgical field and shorter operating time than the GLESP surgery. LESS technology showed less postoperation pain, fast recovery, and extremely high cosmetic satisfaction., Conclusion: The LOFF device provides a safe, effective, and feasible operation platform that can be internally installed and inflated for GLESP surgery during cholescytectomy in animal models.

Background: Mounting evidence shows that microRNAs may be useful as prognostic biomarkers of gastric cancer. The aim of this meta-analysis was to summarize the predictive role of miR-21 for survival in patients with gastric cancer and to verify the association between expression of miR-21 and clinical characteristics., Material and Methods: All the eligible studies were searched by PubMed and EMBASE and clinical characteristics and survival results were extracted. Then a meta-analysis was carried out to clarify the prognostic role of the miR-21 expression in different subgroups., Results: We included 8 studies dealing with gastric cancer in this meta-analysis. For overall survival, the pooled hazard ratio of higher miR-21 expression in tumor tissue was 2.00 (95% CI: 1.39-2.88, P<0.01), which could significantly predict poorer survival in gastric cancer patients. Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with tumor differentiation 0.42 (95% CI: 0.25-0.70 p<0.01), lymph node metastasis 6.39(95% CI: 3.11-13.14, P<0.01), and TNM stage 0.38 (95% CI: 0.21-0.67, P<0.01)., Conclusions: This meta-analysis indicates that miR-21 detection has a prognostic value in patients with gastric cancer. In addition, overexpression of miR-21 is associated with worse tumor differentiation, lymph node metastasis, and TNM stage.

Objective: The gut microbiome is essential for human health due to its effects on disease development, drug metabolism and the immune system. It may also play a role in the interaction with environmental toxicants. However, the effect of epoxiconazole, a fungicide active ingredient from the class of azoles developed to protect crops, on the abundance and composition of the gut microbiome has never been studied. We put forward the hypothesis that changes in gut microbiota may be early signs of toxicity induced by epoxiconazole., Methods: In this study, female rats were fed with epoxiconazole-adulterated diets (0, 4 and 100 mg/kg/day) for 90 days. The gut microbiome was determined by 16S rRNA gene sequencing. Body and organ weight, and blood biochemistry were also measured after 90 days of oral epoxiconazole exposure., Results: Interestingly, the abundance of gut Firmicutes decreased, and Bacteroidetes and Proteobacteria increased. At family level, Lachnospiraceae and Enterobacteriaceae were selectively enriched following epoxiconazole exposure. Our results indicate that epoxiconazole exposure may induce changes in the gut microbiome and potential liver toxicity., Conclusion: Changes in the gut microbiome may be used as early indicators for monitoring the health risk of the host., (© 2015 S. Karger AG, Basel)