The role and mechanism of miR-425-3p regulating neuronal pyroptosis -mediated inorganic arsenic-induced generalized anxiety disorder.

Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO2 (50, 100 µg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO2 to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Treating with different concentrations of NaAsO2 showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.

Theoretical Prediction of Electrocatalytic Reduction of CO2 Using a 2D Catalyst Composed of 3 d Transition Metal and Hexaamine Dipyrazino Quinoxaline.

Transition metals and organic ligands combine to form metal-organic frameworks (MOFs), which possess distinct active sites, large specific surface areas and stable porous structures, giving them considerable promise for CO2 reduction electrocatalysis. In the present study, using spin polarisation density-functional theory, a series of 2D MOFs constructed from 3d transition metal and hexamethylene dipyrazoline quinoxaline(HADQ) were investigated. The calculated binding energies between HADQ and metal atoms for the ten TM-HADQ monolayers were strong sufficient to stably disperse the metal atoms in the HADQ monolayers. Of the ten catalysts tested, seven (Sc, Ni, Cu, Zn, Ti, V and Cr) exhibited high CO2 reduction selectivity, while Mn, Fe and Co required pH values above 2.350, 6.461 and 6.363, respectively, to exhibit CO2 reduction selectivity. HCOOH was the most important producer for Sc, Zn, Ni and Mn, while CH4 was the main producer for Ti, Cr, Fe and V. Cu and Co were less selective, producing HCHO, CH3 OH, and CH4 simultaneously at the same rate-determining step and limiting potential. The Cu-HADQ catalyst had a high overpotential for the HCHO product (1.022 V), while the other catalysts had lower overpotentials between 0.016 V and 0.792 V. Thus, these results predict TM-HADQ to show excellent activity in CO2 electrocatalytic reduction and to become a promising electrocatalyst for CO2 reduction.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Synthesis and biological evaluation of novel pentanediamide derivatives as S-adenosyl-l-homocysteine hydrolase inhibitors.

A series of novel pentanediamide derivatives were designed, synthesized and evaluated as S-adenosyl-l-homocysteine hydrolase (SAHase) inhibitors in this study. Some compounds showed good inhibitory activity against SAHase. The optimal compound 7i showed good inhibitory activity against SAHase with IC50 value of 3.58 ± 0.19 µM, cytotoxicity with IC50 values ranging from 13.16 ± 1.44 to 21.23 ± 0.73 µM against four tumor cell lines (MCF-7, A549, MGC-803, Hela) and very weak cytotoxicity (IC50 = 84.22 ± 1.89 µM) on normal LO2 cells. In addition, compound 7i showed potency against respiratory syncytial virus with EC50 value of 27.4 µM and selectivity index of 6.84. Further molecular simulation study suggested that compound 7i had good ADMET properties, and strongly binds to the active site of SAHase. In summary, compound 7i could serve as a new lead compound for further screening novel non-adenosine SAHase inhibitors.

Natural dynamics and residues of pymetrozine for typical rice-growing areas of China.

Pymetrozine has replaced toxic organophosphate pesticides previously used for controlling pests of rice crops in China. Existing data on its environmental behavior are usually related to studies on artificial plots that do not adequately address the natural dynamics and residues in actual field conditions. Therefore, studies under field conditions were carried out to investigate the natural dynamics and residues of pymetrozine in two typical rice-growing areas in China - Hunan and Guangxi provinces. Samples of paddy soil and water were collected in relation to spraying events in the study areas. The quick, easy, cheap, effective, rugged and safe (QuEChERS) method was used to extract pymetrozine residues from the samples by a Waters ACQUITY UPLC (Milford, MA, USA) system interfaced with a triple-quadrupole mass spectrometer (Xevo TQ-D, Waters Corp., USA). The initial deposition of pymetrozine in paddy soils was higher than in paddy waters in both areas. The decay of pymetrozine followed an exponential trend consistent with the first order kinetics. The half-life of pymetrozine in paddy water was determined to be 3.0 and 3.8 days, whereas the half-life in soil was 3.8 and 3.5 days in the Guangxi and Hunan samples, respectively. The decline rates of pymetrozine in paddy soil and paddy water in this field study were faster than those conducted under non-field conditions reported in previous studies. Compared to other pesticides used in China as reported in previous studies, the environmental persistence of pymetrozine in both paddy water and soils in Guangxi and Hunan provinces is very low. This has important implications for the use of pymetrozine in agricultural systems globally.

Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer.

OBJECTIVES: Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell-free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients. METHODS: The status of THBS1 methylation was detected by quantitative methylation-specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve. RESULTS: Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non-atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001). CONCLUSION: Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients.

Toxicological effects of hypoxanthine on Heterosigmaakashiwo: Mechanism of growth inhibition and change in hemolytic toxin content.

Heterosigmaakashiwo is an algal species that causes harmful algal blooms (HABs) with strong hemolytic toxicity on coastal aquatic organisms. This study investigated the mechanism of growth inhibition and changes in hemolytic toxin contents in algal culture after exposure to hypoxanthine, a compound secreted by algicidal bacterium Bacillus sp.strain B1. An algal inhibition rate of 86% was observed with 1.0 mM hypoxanthine treatment on day 15. The levels of superoxide dismutase and catalase in algal cell culture increased while that of glutathione decreased during the treatment. In addition,the level of hemolytic toxin contents increased on day 3 under hypoxanthine treatment, and significantly decreased on days 6, 9, 12, and 15. Twelve fatty acids in H.akashiwo were detected by GC-MS, and the changes in the contents of C16, C18, C18:4ω3, and C20:5ω3 in the treatment group were consistent with the change in hemolytic toxin content. The four fatty acids were tested for hemolysis and it was observed that the hemolysis rate of 25 µg/mL C18:4ω3 and 5 µg/mL C20:5ω3 reached more than 80%, but C16 and C18 exhibited no hemolytic capability.Therefore, our results showed that hypoxanthine inhibited the growth of H. akashiwo through the changes of levels of antioxidants and hemolytic toxin content in the cultures, and fatty acids C18:4ω3 and C20:5ω3 were contributors to hemolytic toxins. The results confirmed that hypoxanthine is a potential algal inhibitor to prevent HABs.

Bioconversion of steviol glycosides into steviol by Microbacterium barkeri.

The strain which degraded steviol glycosides to steviol (STE) was screened and isolated from soil samples. A phylogenetic tree was constructed and used to determine the taxonomic status of the strain. 16S rDNA sequence was ultimately used to identify the strain as Microbacterium barkeri XJ. The transformation product was detected and identified as STE by HPLC/LC-MS/IR analysis. The bioconversion rate of 1% (v/v) steviol glycosides (stevioside, rebaudioside A, rebaudioside C) into STE in basic medium were 100% within 24 h, 84 h and 144 h, respectively. The results indicated XJ was more effective than mixed flora in the bioconversion of steviol glycosides to STE.

Integrated Assessment of Bioconcentration, Toxicity, and Hazards of Chlorobenzenes in the Aquatic Environment.

The evaluation of bioconcentration, toxicity, and hazard (BTH) of persistent lipophilic organic compounds (LOCs) are generally performed as separate rather than integrated assessments. There are adequate data sets in the literature for chlorobenzenes (CBs) consisting of (a) concentrations in aquatic biota (CB) and water (Cw) in the natural environment, (b) laboratory-derived bioconcentration factors (KB) and field concentration ratios (CR), the field equivalent factor of KB, (c) measured internal lethal concentrations (ILC50) and model estimated ILC50 calculated from KB and lethal concentrations (LC50), and (d) calculated hazard quotients in aquatic biota (HQB) and in water (HQW). However, there have been no integrated studies of those parameter values based on the respective lipid-based parameters (CBL, KBL, CRL, ILC50L, HQBL) performed. This study utilized the lipid-based parameters for CBs; a group of widely occuring, bioaccumulative, and toxic LOCs, and integrated those parameters into a bioconcentration-toxicity-hazard (BTHL) index. The values of the parameters were obtained from selected literature with known lipid contents of the aquatic biota. The results showed that the laboratory derived bioconcentration factors, KBLs, were comparable to the corresponding field based factors, CRLs, and the measured internal lethal concentrations, ILC50L, showed comparable values with the estimated ones. The integrated BTHL index was less than an order of magnitude or moderately acceptable for the assessment of variability, uncertainty, and predictive power of the index. This integrated assessment can be used to support decision making dealing with CBs in specific and LOCs in general, both in regional and global aquatic environments.

Performance and kinetics analysis of an aerobic sequencing batch flexible fibre biofilm reactor for milk processing wastewater treatment.

In this study, a sequencing batch flexible fibre biofilm reactor (SB-FFBR) is used for efficient and cost-effective treatment of milk processing wastewater (MPW). The SB-FFBR, modified type of a typical sequencing batch reactor (SBR), is made up of eight bundles of flexible fibre as a supporting media for microorganisms'growth. The working volume and the cycle length of the bioreactor are 8 L and 24 h, respectively. The biological performance of the bioreactor is studied at 10, 3 and 10 various levels of the influent chemical oxygen demand (CODin; 610-8193 mg L-1), retention time (RT; 1, 1.6 and 2 days), and organic loading rate (OLR; 0.38-8.19 gCOD m-3d-1), respectively. From the results, the minimum COD and total suspended solids (TSS) removal efficiency of 86.8% and 77.3% were achieved at OLR of 8.2 kg COD m-3d-1, CODin of 8193 mg L-1 and RT of 1 day. While, an excellent COD and TSS removal efficiency were found to be 97.5% and 99.3%, respectively, at low OLR of 0.4 kg COD m-3d-1, CODin of 945 mg L-1 and RT of 2 days. Furthermore, the kinetic coefficients of COD removal were computed using a first order substrate removal model at different COD concentrations. The first order kinetic constant, (k), was 0.60, 0.65 and 0.357 h-1 for 500, 810 and 2000 mg COD L-1, respectively. The use of the flexible fibre as a packing material provided a huge surface area for more microorganism attachment. Therefore, the results demonstrated the SB-FFBR has acted as a suitable and effective strategy in treatment of milk processing industrial wastewater.

Electro-assisted adsorption of heavy metals from aqueous solutions by biochar.

Electro-assisted adsorption was investigated for Pb2+, Cu2+ and Ni2+ removal using date seed biochar (DSB-Electro). Compared with pristine biochar, the results showed that DSB-Electro effectively increased the adsorption capacity of Pb2+, Cu2+ and Ni2+ by 21% to 94%. Significant differences were observed between Pb2+ and Cu2+ adsorption compared with Ni2+, which could be explained based on ion polarizing power. Under the same voltage, Ni2+ solution shows the highest electric conductivity; thereby more Ni2+ is transported to the biochar anode, giving them a greater chance to interact with the surface groups. Electro-assisted adsorption occurred rapidly as around 88% of Pb2+ and Ni2+ adsorbed within the first 3 h, while 96% of Cu2+ occurred within the first hour of contact. Reversing the polarity did not seem to cause significant desorption of the adsorbed ions as the amount released from reversing polarity was less than 38%, indicating that only a small fraction of the ions was held by the electrostatic charge introduced by the current. It was likely that the enhanced charge facilitated other adsorption mechanisms by bringing the ions in contact with the biochar initially via electrostatic force. Electro-assisted adsorption can improve the biochar economic feasibility for metals removal (particularly Ni2+) from industrial streams.

Surgical treatment of huge hepatocarcinoma with invasion or severe adhesion of diaphragm using the technique of orthotopic liver resection.

BACKGROUND/AIMS: To explore the clinical application and significance of the technique of orthotopic liver resection. METHODOLOGY: From January 2004 to December 2011, five patients with huge hepatocellular carcinoma with invasion or severe adhesion of diaphragm were undergone right semi-liver resection using the technique of orthotopic liver resection. The right hemi-liver was isolated from the first liver portal, second liver portal and third liver portal, then isolated from the normal liver, finally the tumor and the invaded diaphragm were resected or removed from the severe adhesion. The approach to hepatic resection involved routine use of Peng's multifunctional operative dissector, selective control of in and out-flow of liver, control of inferior vena cava (IVC) and liver hanging maneuver, anterior approach, etc. RESULTS: The operations were successfully performed in 5 patients. Operative time was 120, 180, 150, 150 and 160 min, respectively. The amount of blood loss were 350, 350, 400, 450, 600 ml, respectively. Postoperative complications were pleural effusion in 3 cases, and other 2 cases recovered without complications. CONCLUSIONS: Although the technique of orthotopic liver resection has a high technical requirement for surgeons, it provides a surgical method and operative opportunity for the patients whose tumor has invaded diaphragm or has been severe adhesion with diaphragm and conventional liver resection cannot be performed.

Spatial-temporal distribution of phthalate esters from riverine outlets of Pearl River Delta in China.

The aquatic environments of the Pearl River Delta (PRD) in China have been contaminated by various industrial chemicals from local industries. In this study, the spatial-temporal distribution of six priority phthalate esters (PAEs) in surface water and sediments from the PRD was investigated. The PAEs were detected with total concentrations (Σ6PAEs) ranging from 0.35 to 20.70 µg L⁻¹ in surface water and dry weight ranging from 0.88 to 5.69 µg g⁻¹ in sediments. The Σ6PAEs concentrations in surface water were higher in the wet season than those in the dry season, while the opposite pattern was observed in sediments. Di(2-ethylhexyl) phthalate (DEHP) was the most abundant congener, which was higher than those reported in the literature. Risk quotients for relevant aquatic organisms were obtained and showed that most of these PAEs, in particular, butyl benzyl phthalate, DEHP and di-n-octyl phthalate, have significant potential health and ecological risks for the aquatic environment studied.

Spatial and Seasonal Variations of Total Petroleum Hydrocarbon in Surface Water and Sediment in Pearl River Delta.

A field study in the Pearl River Delta of China was conducted in order to describe to the spatial and seasonal variation of occurrence and concentrations of total petroleum hydrocarbon (TPH) in surface water and sediments. Petroleum hydrocarbons and isoprenoid alkanes were quantified by UV spectroscopy and gas chromatography with a mass selective detector. The concentrations of TPH ranged from 4.3 to 68.7 µg L(-1) in surface water, and from 66.6 to 1445 µg g(-1) in surface sediments. The ratios of pristine to phytane suggested that the main sources of TPH in the sediment were petroleum importation. The highest concentrations of TPH were present in the spring season. When compared with results from previous studies, it can be concluded that the Pearl River Delta was moderately polluted by TPH. No statistically significant correlations were observed between the concentrations of TPH in surface water and sediments.

Circulating methylated MINT2 promoter DNA is a potential poor prognostic factor in gastric cancer.

BACKGROUND AND AIM: Aberrant DNA methylation has been shown to be associated with the growth, development, metastasis, and prognosis of tumors. Methylated DNAs may be suitable biomarkers for cancer patients. Here, we investigated whether circulating methylated MINT2 DNAs represent a potential poor prognostic factor in gastric cancer (GC). METHODS: MINT2 methylation was detected by real-time methylation-specific PCR in tumor tissues, pairing preoperative peritoneal lavage fluid (PPLF) and blood from 92 GC patients. The theory meaning and clinical practicality value of MINT2 methylation in different specimens were analyzed. RESULTS: The methylation status of the MINT2 gene was found to be significantly higher in tumor tissues (44.6%, 41/92) than in adjacent normal tissues (3.3%, 3/92). No MINT2 methylation was found in healthy controls, and partial MINT2 methylation was observed in three (6.25%, 3/48) patients with chronic atrophic gastritis. The frequency of MINT2 methylation in pairing PPLF and blood samples from 92 GC patients was 40.2% (37/92) and 39.1% (36/92), respectively. Methylated MINT2 in tumor tissues, pairing PPLF, and blood samples were very approximate. Aberrant MINT2 methylation in tumor tissues and pairing PPLF or blood samples were closely related to peritoneal dissemination, tumor progression, and poor prognosis (all P < 0.0001). CONCLUSIONS: Aberrant MINT2 methylation in PPLF/blood may predict peritoneal micrometastasis for GC patients, which is a potential poor prognostic factor in GC.

Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer.

BACKGROUND: Adjuvant chemotherapy could reduce residual tumor cells and prevent relapse, however, not all patients are suitable for adjuvant chemotherapy. Screening appropriate patients based on molecular markers for individualized adjuvant chemotherapy is necessary. METHODS: Between June 2002 and June 2004, 119 patients who underwent radical gastrectomy were retrospectively analyzed. Some patients had adjuvant chemotherapy based on platinum and 5-FU for four to six cycles. Topoisomerase II (ToPo II) negative, multidrug resistance protein (MRP) positive and glutathione S-transferase π (GST-π) positive were regarded as three risk factors that may be associated with chemotherapy resistance and poor prognosis. Patients were divided into two groups: a high-risk group (≥2 risk factors) and a low-risk group (<2 risk factors), and tumor recurrence and patient survival time of the two groups were analyzed. RESULTS: The average recurrence time of the low-risk group was significantly longer than that of the high-risk group (21.29 ± 11.10 versus 15.16 ± 8.05 months, P < 0.01). The 3-year and 5-year survival rates of the high-risk group were 57.4% and 42.6%, however, it had no significant difference compared to 66.2% and 58.5% of the low-risk group (P >0.05). In the high-risk group, the 3-year survival rates of patients with/without chemotherapy were 62.1% and 52.0% and the 5-year survival rates were 44.8% and 40.0%, respectively, but the difference was not statistically significant (P > 0.05). In the low-risk group, the 3-year survival rates of patients with/without chemotherapy were 81.2% and 51.5%, and the 5-year survival rates were 71.9% and 45.5%, respectively, these differences were statistically significant (P < 0.05). CONCLUSIONS: Combined detection of the multidrug resistance (MDR)-related proteins ToPo II, MRP and GST-π may be prospectively valuable for postoperative individualized chemotherapy and in further predicting the outcomes of gastric cancer patients.

Spatial-temporal distribution and potential ecological risk assessment of nonylphenol and octylphenol in riverine outlets of Pearl River Delta, China.

The aquatic environments of the Pearl River Delta in Southern China are subjected to contamination with various industrial chemicals from local industries. In this paper, the occurrence, seasonal variation and spatial distribution of alkylphenol octylphenol (OP) and nonylphenol (NP) in river surface water and sediments in the runoff outlets of the Pearl River Delta were investigated. NP and OP were detected in all water and sediment samples and their mean concentrations in surface water during the dry season ranged from 810 to 3366 ng/L and 85.5 to 581 ng/L, respectively, and those in sediments ranged from 14.2 to 95.2 ng/g dw and 0.4 to 3.0 ng/g dw, respectively. In surface water, much higher concentrations were detected in the dry season than those in the wet season. In sediments, the concentrations in the dry season were also mostly higher. High concentrations of NP and OP were found in Humen outlet, likely due to high levels of domestic and industrial wastewater discharges. An ecological risk assessment with the use of hazard quotient (HQ) was also carried out and the HQ values ranged from 3.6×10(-5) to 35 and 64% of samples gave a HQ>1, indicating that the current levels of NP and OP pose a significant risk to the relevant aquatic organisms in the region.

Discovery of 4-aminophenylacetamide derivatives as intestine-specific farnesoid X receptor antagonists for the potential treatment of nonalcoholic steatohepatitis.

Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, lipid and glucose metabolism and is emerging as a promising therapeutic target for nonalcoholic steatohepatitis (NASH). Emerging evidence suggested that intestine-specific FXR antagonists exhibited remarkable metabolic improvements and slowed NASH progression. In this study, we discovered several potent FXR antagonists using a multistage ligand- and structure-based virtual screening approach. Notably, compound V023-9340, which possesses a 4-aminophenylacetamide scaffold, emerged as the most potent FXR antagonist with an IC50 value of 4.27 µM. In vivo, V023-9340 demonstrated selective accumulation in the intestine, substantially ameliorating high-fat diet (HFD)-induced NASH in mice by mitigating hepatic steatosis and inflammation. Mechanistic studies revealed that V023-9340 strongly inhibited intestinal FXR while concurrently feedback-activated hepatic FXR. Further structure-activity relationship optimization employing V023-9340 has resulted in the synthesis of a more efficacious compound V02-8 with an IC50 value of 0.89 µM, which exhibited a 4.8-fold increase in FXR antagonistic activity compared to V023-9340. In summary, 4-aminophenylacetamide derivative V023-9340 represented a novel intestine-specific FXR antagonist and showed improved effects against HFD-induced NASH in mice, which may serve as a promising lead in discovering potential therapeutic drugs for NASH treatment.

DesTrans: A medical image fusion method based on Transformer and improved DenseNet.

Medical image fusion can provide doctors with more detailed data and thus improve the accuracy of disease diagnosis. In recent years, deep learning has been widely used in the field of medical image fusion. The traditional method of medical image fusion is to operate by superimposing and other methods of pixels. The introduction of deep learning methods has improved the effectiveness of medical image fusion. However, these methods still have problems such as edge blurring and information redundancy. In this paper, we propose a deep learning network model based on Transformer and an improved DenseNet network module integration that can be applied to medical images and solve the above problems. At the same time, the method can be moved to natural images. The use of Transformer and dense concatenation enhances the feature extraction capability of the method by limiting the feature loss which reduces the risk of edge blurring. We compared several representative traditional methods and more advanced deep learning methods with this method. The experimental results show that the Transformer and the improved DenseNet network module have a strong capability of feature extraction. The method yields good results both in terms of visual quality and objective image evaluation metrics.