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Recent studies have identified a genetic variant rs641738 near two genes encoding membrane bound O -acyltransferase domain-containing 7 ( MBOAT7 ) and transmembrane channel-like 4 ( TMC4 ) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017). Based on hepatic expression quantitative trait loci analysis, it has been suggested that MBOAT7 loss of function promotes liver disease progression (Buch et al., 2015; Mancina et al., 2016; Luukkonen et al., 2016; Thabet et al., 2016; Viitasalo et al., 2016; Krawczyk et al., 2017; Thabet et al., 2017), but this has never been formally tested. Here we show that Mboat7 loss, but not Tmc4 , in mice is sufficient to promote the progression of NAFLD in the setting of high fat diet. Mboat7 loss of function is associated with accumulation of its substrate lysophosphatidylinositol (LPI) lipids, and direct administration of LPI promotes hepatic inflammatory and fibrotic transcriptional changes in an Mboat7 -dependent manner. These studies reveal a novel role for MBOAT7-driven acylation of LPI lipids in suppressing the progression of NAFLD. Non-alcoholic fatty liver disease, or NAFLD for short, is a medical condition that develops when the liver accumulates excess fat. It can lead to complications such as diabetes and liver scarring. In humans, mutations that inactivate a protein called MBOAT7 increase the risk of fat accumulating in the liver. Genetic studies suggest that low levels of MBOAT7 in a human’s liver cells increase the severity of NAFLD. Yet the links between MBOAT7, NAFLD and obesity are not well understood. Helsley et al. used data from humans and from obese mice that had been fed a high-fat diet to investigate the relationship between NAFLD and MBOAT7. This revealed that people who are obese have lower levels of MBOAT7 in their livers. Next, obese mice were genetically manipulated to produce less MBOAT7, which led them to develop more severe NAFLD. Helsley et al. then grew human liver cells in the laboratory and lowered their levels of MBOAT7, which led to excess fat accumulating in the cells. This increase in fat accumulation was, at least in part, due to how these cells metabolize fats when MBOAT7 is reduced: they start making more new fats and consume fewer lipids to produce energy. These findings provide a link between obesity and liver damage in both humans and mice, and show how a decrease in MBOAT7 levels causes changes in fat metabolism that could lead to NAFLD. The results could drive new approaches to treating liver damage in patients with mutations in the gene that codes for MBOAT7.

Hepatic metabolism and elimination of endobiotics (for example, steroids, bile acids) and xenobiotics (for example, drugs, toxins) is essential for health. While the enzymatic (termed phase I–II) and transport machinery (termed phase III) controlling endobiotic and xenobiotic metabolism (EXM) is known, understanding of molecular nodal points that coordinate EXM function in physiology and disease remains incomplete. Here we show that the transcription factor Kruppel-like factor 15 (KLF15) regulates all three phases of the EXM system by direct and indirect pathways. Unbiased transcriptomic analyses coupled with validation studies in cells, human tissues, and animals, support direct transcriptional control of the EXM machinery by KLF15. Liver-specific deficiency of KLF15 (Li-KO) results in altered expression of numerous phase I–III targets, and renders animals resistant to the pathologic effects of bile acid and acetaminophen toxicity. Furthermore, Li-KO mice demonstrate enhanced degradation and elimination of endogenous steroid hormones, such as testosterone and glucocorticoid, resulting in reduced male fertility and blood glucose levels, respectively. Viral reconstitution of hepatic KLF15 expression in Li-KO mice reverses these phenotypes. Our observations identify a previously unappreciated transcriptional pathway regulating metabolism and elimination of endobiotics and xenobiotics. The transcription factor Klf15 controls various metabolic processes, including bile acid synthesis. Here the authors show that Klf15 acts as an upstream regulator of xenobiotic and endobiotic metabolism by controlling expression of a variety of phase I–III metabolic genes via direct and indirect mechanisms.

Objective To describe a decade of our experience with a neo‐urethral modification of ileal orthotopic neobladder (pitcher pot ONB). Multiple investigators have reported similar modifications. However, long‐term longitudinal functional and quality of life (QOL) outcomes are lacking. Methods Prospectively maintained hospital registry for 238 ONB patients comprising a mix of open and robotic surgery cohorts from 2007 to 2017, and minimum of 2 years of follow‐up was retrospectively queried. QOL was evaluated using Bladder Cancer Index (BCI). Longitudinal trends of QOL domain parameters were analysed. List of perioperative variables that have a biologically plausible association with continence, potency, and post‐operative BCI QOL sexual, urinary, and bowel domain scores was drawn. Variables included surgery type, Body Mass Index (BMI), T and N stage, neurovascular bundle (NVB) sparing, age, and related pre‐operative BCI QOL domain score. Prognostic associations were analysed using multivariable Cox proportional hazard models and multilevel mixed‐effects modeling. Results The study comprised 80 and 158 patients who underwent open and robotic sandwich technique cohorts, respectively. Open surgery was associated with significantly higher “any” complication (40% vs 27%, P‐value .050) and “major” complication rate (15% vs 11%, P‐value .048). All patients developed a bladder capacity >400 cc with negligible post‐void residual urine, and all but one patient achieved spontaneous voiding by the end of study period (<1% clean intermittent self‐catheterization [CISC] rate). By 15 months, QOL for all three domains had recovered to reach a plateau. About 45% of patients achieved potency, and the median time to achieve day and night time continence was 9 and 12 months respectively. Lower age and NVBs spared during surgery were found to be significantly associated with the earlier achievement of potency, day and night time continence, as well as better urinary and sexual summary QOL scores. Conclusions Pitcher pot neobladder achieves satisfactory long‐term functional and QOL outcomes with negligible CISC rate. Results were superior with incremental nerves spared during surgery.

Sterol 12α-hydroxylase (CYP8B1) is required for the synthesis of cholic acid in the classic bile acid synthesis pathway and plays a role in dyslipidemia and insulin resistance. However, the mechanism of the involvement of Cyp8b1 in dyslipidemia and insulin resistance is not known. CYP8B1 mRNA and protein expression are elevated in diabetic and obese (db/db) mouse liver. In this study adenovirus-mediated transduction of CYP8B1 was used to study the effect of Cyp8b1 on lipid metabolism in mice. Results show that Ad-Cyp8b1 increased 12α-hydroxylated bile acids and induced sterol regulatory element-binding protein 1c (Srebp-1c)-mediated lipogenic gene expression. Interestingly, Ad-Cyp8b1 increased ceramide synthesis and activated hepatic mechanistic target of rapamycin complex 1 (mTORC1)-p70S6K signaling cascade and inhibited AKT/insulin signaling in mice. Ad-Cyp8b1 increased free fatty acid uptake into mouse primary hepatocytes. Ceramides stimulated S6K phosphorylation in both mouse and human primary hepatocytes. In high-fat diet-fed mice, Ad-Cyp8b1 reduced fibroblast growth factor 21 (FGF21), activated intestinal farnesoid X receptor (FXR) target gene expression, increased serum ceramides, VLDL secretion, and LDL cholesterol. In high-fat diet-induced obese (DIO) mice, Cyp8b1 ablation by adenovirus-mediated shRNA improved oral glucose tolerance, increased FGF21, and reduced liver triglycerides, inflammatory cytokine expression, nuclear localization of Srebp-1c and phosphorylation of S6K. In conclusion, this study unveiled a novel mechanism linking CYP8B1 to ceramide synthesis and mTORC1 signaling in dyslipidemia and insulin resistance, via intestinal FXR-mediated induction of FGF15 and liver FGF21. Reducing cholic acid synthesis may be a potential therapeutic strategy to treat dyslipidemia and nonalcoholic fatty liver disease.

Fingerprint-which have been used for about 100 years are the oldest biometric signs of identity. Humans have used fingerprints for personal identification for centuries and the validity of fingerprint identification has been well established. In fact, fingerprint technology is so common in Human Identification that it has almost become the synonym of biometrics. Fingerprints are believed to be unique across individuals and across fingers of same individual. Even identical twins having similar DNA, are believed to have different fingerprints. The analysis of fingerprints for matching purposes generally requires the comparison of several features of the print pattern. These include patterns, which are aggregate characteristics of ridges, and minutia points, which are unique features found within the patterns. is also necessary to know the structure and properties of human skin in order to successfully employ some of the imaging technologies. A major approach for fingerprint recognition today is to extract minutiae from fingerprint images and to perform fingerprint matching based on the number of corresponding minutiae pairings. One of the most difficult problems in fingerprint recognition has been that the recognition performance is significantly influenced by fingertip surface condition, which may vary depending on environmental or personal causes. Addressing this problem this paper propose some extra features that can be used to strengthen the present approaches followed in developing Fingerprint recognition system. To increase security and accuracy we can use Infrared technique and technique to assign a score value to each of extracted minutiae. Key Terms- Biometric, Minutiae, Binarization, Thinning, Median Filter.

Sterol 12a-hydroxylase (CYP8B1) is involved in cholic acid synthesis and plays a role in intestinal cholesterol absorption and pathogenesis of cholesterol gallstone disease and dyslipidemia. In this study, we investigated the underlying mechanism of a fasting-induced and cholesterol activated nuclear receptor and core clock gene RORa in regulation of circadian rhythm and fasting induction of CYP8B1 expression. In free fed mice, CYP8B1 expression was reduced to the lowest level at the onset of the dark cycle when RORa expression was the lowest. However, fasting stimulated, while re-feeding reduced expression of CYP8B1 mRNA and protein expression. Interestingly, fasting and feeding had little effect on the diurnal rhythm of RORa mRNA expression, but fasting increased, whereas feeding decreased RORa protein levels in mouse liver. Adenovirus-mediated transduction of RORa to mice strongly induced CYP8B1 gene expression, increased 12a-hydroxylated bile acids in bile acid pool and serum and liver cholesterol. Reporter assay and mutagenesis analysis of the CYP8B1 promoter identified a functional RORa response element. Mammalian two-hybrid assay showed strong interaction of RORa with cAMP response element binding protein-binding protein (CBP). Chromatin immune-precipitation assay showed that RORa recruited CBP to the CYP8B1 promoter to stimulate histone acetylation. CAMP-activated protein kinase A phosphorylates RORa and increases its half-life. In conclusion, RORa is a key regulator of circadian expression and fasting induction of CYP8B1 to increase 12a-hydroxylated bile acids in the bile acid pool, and serum and liver cholesterol. This study contributes to our understanding of the molecular mechanism by which bile acid synthesis and composition regulates hepatic metabolic homeostasis. Overall this study sheds light on the mechanism of development of hypercholesterolemia in diabetic patients. Therefore, antagonizing RORa activity may be a therapeutic strategy for treating inflammatory diseases such as non-alcoholic fatty liver disease.

Primary liver cancer accounts for approximately 700,000 deaths worldwide annually ranking third in cancer-related mortality, with hepatocellular carcinoma (HCC) comprising the majority of these tumors. Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently a leading cause of HCC in the United States. We previously identified the lipid hydrolase alpha/beta hydrolase domain 6 (ABHD6) as a key mediator of the development of metabolic syndrome and intimately involved in cell signaling, making it a prime target for investigation in MASLD-related HCC. ABHD6 displays higher expression within HCC tumor cores when compared to adjacent non-tumor liver tissue in human subjects. Using an in vivo antisense oligonucleotide (ASO)-driven knockdown approach, we have shown the inhibition of ABHD6 prevents the development and progression of HCC in an obesity/MASLD-driven mouse model. Additionally, a xenograft model using the human Huh7 cell line displayed reduced tumor engraftment and growth with ABHD6 genetic deletion and small molecule inhibition. ABHD6 knockout cells demonstrated increased levels of bis(monoacylglycerol)phosphates (BMPs), lipids relevant to high fat diet-induced lysosomal dysfunction, and knockout cells also demonstrated altered autophagy and lysosomal activity using model of saturated fatty acid-induced lipotoxicity. These studies reveal novel lipid signaling mechanisms by which MASLD progresses towards HCC and provide support for ABHD6 as a therapeutic target in HCC. We have identified that alpha/beta hydrolase domain 6 (ABHD6) plays a role in lysosomal membrane lipid remodeling pathways that are relevant in obesity/MASLD-driven HCC. Inhibitors targeting ABHD6 reorganize lysosomal lipid homeostasis to improve outcomes in HCC.

TRPV1 channels have been linked to the development and progression of diabetes at multiple levels, including control of appetite and weight, regulation of pancreatic function, thermogenesis, metabolism and energy homeostasis. Despite this, little information is known regarding its role in liver homeostasis and nonalcoholic fatty liver disease (NAFLD). To better understand the role of TRPV1 in liver metabolism, we explored the effects of a high fat/sugar diet (Western, 24-week regimen) in male and female wild type (WT) and TRPV1-null (V1KO) mice. Our data reveal that loss of the TRPV1 gene makes mice susceptible to diet-induced obesity and induces NAFLD. V1KO mice displayed gross phenotypic and gross morphological changes including insulin resistance, glucose intolerance, increased body mass and central adiposity on a western diet compared to WT counterparts. Western fed V1KO mice exhibited gross changes in liver morphology and size compared to western fed WT mice, which were supported with histological H&E and Oil Red O staining. Accompanying the liver changes, Western fed V1KO mice exhibited altered lipid profiles as demonstrated by elevated hepatic triglyceride, cholesterol and free fatty acid levels compared to western fed WT mice. Interestingly, female V1KO mice fed a western diet displayed significant protection against diet-induced obesity and the progression of NAFLD compared to their male counterparts. Taken together, these data suggest that loss of TRPV1 promotes fat accumulation, NAFLD development and changes in liver lipid profiles in male mice, the extent to which is less severe in female V1KO mice. In conclusion, TRPV1 may be a protective therapeutic target for the prevention of NAFLD development in diet-induced obesity.

Graphite dual-ion batteries represent a potential battery concept for large-scale stationary storage of electricity, especially when constructed free of lithium and other chemical elements with limited natural reserves. Owing to their non-rocking-chair operation mechanism, however, the practical deployment of graphite dual-ion batteries is inherently limited by the need for large quantities of electrolyte solutions as reservoirs of all ions that are needed for complete charge and discharge of the electrodes. Thus far, lithium-free graphite dual-ion batteries have employed moderately concentrated electrolyte solutions (0.3–1 M), resulting in rather low cell-level energy densities of 20–70 Wh kg −1 . In this work, we present a lithium-free graphite dual-ion battery utilizing a highly concentrated electrolyte solution of 5 M potassium bis(fluorosulfonyl)imide in alkyl carbonates. The resultant battery offers an energy density of 207 Wh kg −1 , along with a high energy efficiency of 89% and an average discharge voltage of 4.7 V. Lithium-free graphite dual-ion battery offers a new means of energy storage. Here the authors show such device utilizing a highly concentrated electrolyte solution of KFSI in alkyl carbonates that exhibits a high energy density and high energy efficiency as well as an average discharge voltage of 4.7 V.

The therapeutic value of Aegle marmelos Correa (Rutaceae), commonly known as ‘‘Bael,’’ has been recognized as a component of traditional medication for the treatment of various human ailments. The plant, though, being highly explored, still lacks sufficient evidences for the best variety possessing the highest degree of medicinal values. The present study is focused on phytochemical screening of aqueous and methanolic leaf extracts of 18 varieties/accessions of A. marmelos. The crude extracts of A. marmelos revealed the presence of several biologically active phytochemicals with the highest quantity of alkaloids, flavonoids, and phenols in Pant Aparna variety. The antibacterial efficacy was investigated against pathogenic bacterial strains and the highest inhibitory activity of aqueous extract was obtained against S. epidermidis, whereas methanolic extract was found to be most potent against S. aureus at 40 mg/mL concentration. However, in aqueous : ethanol, the best results were observed against E. aerogenes followed by K. pneumonia and S. epidermidis. The MIC of aqueous and methanol extract of Aegle marmelos ranged from 10 mg/mL to 40 mg/mL whereas in aqueous : ethanol it ranged between 40 mg/mL and 160 mg/mL. The GC-MS analysis revealed the presence of many bioactive compounds such as flavonoids, alcohols, aldehydes, aromatic compounds, fatty acid methyl esters, terpenoids, phenolics, and steroids that can be postulated for antibacterial activity.