Dynamic Reconstruction of Yttrium Oxide-Stabilized Cobalt-Loaded Carbon-Based Catalysts During Thermal Ammonia Decomposition.

Hydrogen production from the decomposition of ammonia is considered an effective approach for addressing challenges associated with hydrogen storage and transportation. However, their relatively high energy consumption and low efficiency hinder practical multi-scenario applications. In this study, Y2O3-stabilized catalysts with Co-loaded onto porous nitrogen-doped carbon (Y2O3-Co/NC) are synthesized by pyrolysis of Y(NO3)3-modified ZIF-67 under an inert atmosphere, followed by annealing in a reducing environment. The introduction of Y2O3 enhanced the recombination and desorption of N atoms and facilitated the gradual dehydrogenation of NHx on the catalyst surface, resulting in improved catalytic activity for the thermal decomposition of ammonia. Benefitting from the electron-donating properties of Y2O3 and N-doped carbon, the optimized catalyst achieved a remarkable NH3 conversion efficiency of 92.3% at a high gas hourly space velocity of 20 000 cm3· g cat - 1 ${\mathrm{g}}_{{\mathrm{cat}}}^{ - {\mathrm{1}}}$ ·h-1 with an encouraging H2 production rate of 20.6 mmol· g cat - 1 ${\mathrm{g}}_{{\mathrm{cat}}}^{ - {\mathrm{1}}}$ ·min-1 at 550 °C. Moreover, the synthesized catalyst undergoes a fast-dynamic reconstruction process, resulting in exceptionally stable catalytic activity during the thermal decomposition of ammonia, rendering it a promising candidate for carbon-free energy thermocatalytic conversion technology.

Porous Transport Layers with Laser Micropatterning for Enhanced Mass Transport in PEM Water Electrolyzers.

Efficient electrochemical energy conversion technologies, such as fuel cells and water electrolyzers, require high current densities to lower the capital cost for large-scale commercialization but are often limited by mass transport. In this study, we demonstrated exceptional electrochemical performances in proton electrolyte membrane water electrolyzers (PEMWEs) creating micropatterned pore channels in the porous transport layer (MPC PTL) using a picosecond laser. This approach yielded an impressive performance of 1.82 V @ 2 A·cm-2, which is better than commercial PTL of 1.90 V @ 2 A cm-2. The significant performance enhancement is attributed to the micropatterned porous channel structure, facilitating the efficient expulsion of oxygen bubbles and input of reactant water. This work provides valuable insights for the design of PTL responsible for biphasic transport in electrochemical energy conversion technologies.

Study of hydraulic cutting as a method to prevent coal burst disasters.

This study explores the causes of coal bursts in the Xinzhou Kiln Mine, identifying key factors such as residual pillars, hard coal seams and/or roofs, stress concentration due to complex geological structures, and the stress distribution characteristics of the primary rock. A significant finding is that hydraulic cutting not only diminishes and redistributes the stress concentration region inside the coal seam but also mitigates the burst potential of the coal-rock mass, fundamentally reducing the likelihood of coal bursts. By taking Face No. 8937 in Xinzhou Kiln Mine as the test object, a coal burst prevention test was performed using hydraulic cutting. In combination with theoretical analysis and numerical simulation, the mechanism of hydraulic cutting for preventing coal burst was discussed, and reasonable cutting parameters were established. Onsite monitoring revealed that hydraulic cutting disrupts the integrity of the coal-rock mass, releases internal stress, and increases its water content, thereby weakening its burst tendency. Additionally, the deformation and fracturing of the cutting slots and the closure of boreholes shifted the stress concentration from the coal seam to deeper areas and to the two ribs. Post-cutting observations showed a significant reduction in both the frequency and impact energy of coal bursts; there was also a noticeable increase in the convergence of the roadway in the cutting area compared to non-cutting areas. Furthermore, displacement of the roof and floor increased by 78.9 % and that of the two ribs increased by 47.4 % after cutting, preventing the coal-rock mass from accumulating high stress. In conclusion, hydraulic cutting is a promising method for effectively preventing coal bursts and enhancing the safety of mining operations.

A Review of the Use of Native and Engineered Probiotics for Colorectal Cancer Therapy.

Colorectal cancer (CRC) is a serious global health concern, and researchers have been investigating different strategies to prevent, treat, or support conventional therapies for CRC. This review article comprehensively covers CRC therapy involving wild-type bacteria, including probiotics and oncolytic bacteria as well as genetically modified bacteria. Given the close relationship between CRC and the gut microbiota, it is crucial to compile and present a comprehensive overview of bacterial therapies used in the context of colorectal cancer. It is evident that the use of native and engineered probiotics for colorectal cancer therapy necessitates research focused on enhancing the therapeutic properties of probiotic strains.. Genetically engineered probiotics might be designed to produce particular molecules or to target cancer cells more effectively and cure CRC patients.

Long-term PM2.5 exposure and early-onset diabetes: Does BMI link this risk?

OBJECTIVE: Limited studies investigated the association between high-level fine particulate matter (PM2.5) pollution and early-onset diabetes, leaving the possible metabolic mechanisms unclear. We assessed the association of cumulative PM2.5 exposure with diabetes, including early-onset, in high-pollution areas of China and explored whether metabolic factors mediated this association. METHODS: 124,204 participants (≥18 years) from 121 counties in Hunan province, China, were enrolled between 2005 and 2020, with follow-up until 2021. The ground-level air pollution concentrations at each participant's residence were calculated using a high-quality dataset in China. The independent association of PM2.5 with incident diabetes and early-onset diabetes was assessed by Cox proportional hazards models. Restricted cubic splines were utilized to establish the exposure-response relationships. The role of metabolism-related mediators was estimated by mediation analysis. RESULTS: During a median follow-up of 8.47 (IQR, 6.65-9.82) years, there were 3650 patients with new-onset diabetes. Each 1 µg/m3 increase in the level of cumulative PM2.5 exposure was positively related to an increased incidence of diabetes (HR 1.177, 95 % CI 1.172-1.181) among individuals in the PM2.5 > 50 µg/m3 group after adjusting for multiple variables. The relationship of the PM2.5 dose-response curve for diabetes was non-linear. Significant associations between PM2.5 exposure and early-onset diabetes risk were observed, with this risk showing an increase with the earlier age of early diabetes onset. Males, young individuals (≤45 years), and those with a lower body mass index (BMI <24 kg/m2) appeared to be more susceptible to diabetes. Moreover, change in BMI significantly mediated 31.06 % of the PM2.5-diabetes relationship. CONCLUSIONS: Long-term cumulative PM2.5 exposure increased the risk of early-onset diabetes, which is partially mediated by BMI. Sustained air pollution control measures, priority protection of vulnerable individuals, and effective management of BMI should be taken to reduce the burden of diabetes.

Enhancing tumor-specific recognition of programmable synthetic bacterial consortium for precision therapy of colorectal cancer.

Probiotics hold promise as a potential therapy for colorectal cancer (CRC), but encounter obstacles related to tumor specificity, drug penetration, and dosage adjustability. In this study, genetic circuits based on the E. coli Nissle 1917 (EcN) chassis were developed to sense indicators of tumor microenvironment and control the expression of therapeutic payloads. Integration of XOR gate amplify gene switch into EcN biosensors resulted in a 1.8-2.3-fold increase in signal output, as confirmed by mathematical model fitting. Co-culturing programmable EcNs with CRC cells demonstrated a significant reduction in cellular viability ranging from 30% to 50%. This approach was further validated in a mouse subcutaneous tumor model, revealing 47%-52% inhibition of tumor growth upon administration of therapeutic strains. Additionally, in a mouse tumorigenesis model induced by AOM and DSS, the use of synthetic bacterial consortium (SynCon) equipped with multiple sensing modules led to approximately 1.2-fold increased colon length and 2.4-fold decreased polyp count. Gut microbiota analysis suggested that SynCon maintained the abundance of butyrate-producing bacteria Lactobacillaceae NK4A136, whereas reducing the level of gut inflammation-related bacteria Bacteroides. Taken together, engineered EcNs confer the advantage of specific recognition of CRC, while SynCon serves to augment the synergistic effect of this approach.

The miR-3074/BMP7 axis regulates TGF-ß-caused activation of hepatic stellate cells in vitro and CCl4-caused murine liver fibrosis in vivo.

Continuously progressive hepatic fibrosis might cause chronic liver diseases, resulting in hepatic failure. The activation of hepatic stellate cells (HSCs) residing in the liver might induce and influence hepatic fibrosis. In the present study, microRNA 3074 (miR-3074) was found increased within transforming growth factor-ß (TGF-ß)-activated HSCs and enriched within the TGF-ß signaling. In activated HSCs by TGF-ß, miR-3074 overexpression aggravated TGF-ß-induced fibrotic changes, whereas miR-3074 inhibition exerted opposite effects. miR-3074 directly targeted bone morphogenetic protein 7 (BMP7) and inhibited BMP7 expression. Under TGF-ß induction, overexpressed BMP7 notably attenuated the promotive roles of miR-3074 overexpression in TGF-ß-activated HSCs. Within carbon tetrachloride (CCl4)-caused liver fibrosis murine model, miR-3074 agomir administration promoted, while LV-BMP7 administration alleviated CCl4-induced fibrotic changes; LV-BMP7 significantly attenuated the effects of miR-3074 agomir. Lastly, mmu-miR-3074 also targeted mouse BMP7 and inhibited mouse BMP7 expression. In conclusion, the miR-3074/BMP7 axis regulates TGF-ß-caused activation of HSCs in vitro and CCl4-caused murine liver fibrosis in vivo. BMP7-mediated Smad1/5/8 activation might be involved.

Why more successful? An analysis of participants' self-monitoring data in an online weight loss intervention.

BACKGROUND: Self-monitoring is crucial for behavioral weight loss. However, few studies have examined the role of self-monitoring using mixed methods, which may hinder our understanding of its impact. METHODS: This study examined self-monitoring data from 61 Chinese adults who participated in a 5-week online group intervention for weight loss. Participants reported their baseline Body Mass Index (BMI), weight loss motivation, and engaged in both daily quantitative self-monitoring (e.g., caloric intake, mood, sedentary behavior, etc.) and qualitative self-monitoring (e.g., daily log that summarizes the progress of weight loss). The timeliness of participants' daily self-monitoring data filling was assessed using a scoring rule. One-way repeated measurement ANOVA was employed to analyze the dynamics of each self-monitoring indicator. Correlation and regression analyses were used to reveal the relationship between baseline data, self-monitoring indicators, and weight change. Content analysis was utilized to analyze participants' qualitative self-monitoring data. Participants were categorized into three groups based on their weight loss outcomes, and a chi-square test was used to compare the frequency distribution between these groups. RESULTS: After the intervention, participants achieved an average weight loss of 2.52 kg (SD = 1.36) and 3.99% (SD = 1.96%) of their initial weight. Daily caloric intake, weight loss satisfaction, frequency of daily log, and the speed of weight loss showed a downward trend, but daily sedentary time gradually increased. Moreover, regression analysis showed that baseline BMI, weight loss motivation, and timeliness of daily filling predicted final weight loss. Qualitative self-monitoring data analysis revealed four categories and nineteen subcategories. A significant difference in the frequency of qualitative data was observed, with the excellent group reporting a greater number of daily logs than expected in all categories and most subcategories, and the moderate and poor groups reporting less than expected in all categories and most subcategories. CONCLUSION: The self-monitoring data in short-term online group intervention exhibited fluctuations. Participants with higher baseline BMI, higher levels of weight loss motivation, and timely self-monitoring achieved more weight loss. Participants who achieved greater weight loss reported a higher quantity of qualitative self-monitoring data. Practitioners should focus on enhancing dieters' weight loss motivation and promote adherence to self-monitoring practices.

Insulin resistance levels predicted metabolic improvement and weight loss after metabolic surgery in Chinese patients with type 2 diabetes.

BACKGROUND: The causes for failure of metabolic improvement and inadequate weight loss after metabolic surgery (MS) in Chinese patients with type 2 diabetes (T2D) have not been fully elucidated. The effect of insulin resistance (IR) on the outcome of T2D, hypertension, hyperlipidemia, and obesity after MS in Chinese patients with T2D and a body mass index (BMI) of 25-32.5 kg/m2 warrants further study. OBJECTIVES: Patients with T2D and a BMI of 25-32.5 kg/m2 who underwent MS between July 2019 and June 2021 were included. SETTING: University hospital, China. METHODS: IR levels were evaluated with the glucose disposal rate (GDR). Improvement of T2D, hypertension, and hyperlipidemia was assessed with the composite triple endpoint (CTEP), and weight loss was assessed with the percent of total weight loss (%TWL). Partial correlation analysis, binary logistic regression analysis, multiple linear regression analysis, receiver operating characteristic curve (ROC) analysis, and subgroup analysis were used to analyze the relationship between the CTEP, %TWL at 1 year postoperative, and GDR preoperative. RESULTS: This study analyzed the data of 51 patients with T2D and a BMI of 25-32.5 kg/m2 (30 men and 21 women) with a mean preoperative GDR of 3.72 ± 1.48 mg/kg/min. Partial correlation coefficients between CTEP, %TWL, and GDR were .303 (P = .041) and .449 (P = .001), respectively. The preoperative GDR was significantly positively correlated with CTEP (OR = 1.610, P = .024) and %TWL (ß = 1.38, P = .003). The preoperative GDR predicted cutoff values of 4.36 and 5.35 mg/kg/min for CTEP attainment and %TWL ≥ 20%, respectively. CONCLUSION: IR levels predicted metabolic improvement and weight loss 1 year after MS in Chinese patients with T2D and a BMI of 25-32.5 kg/m2.

Nonselective beta-adrenoceptor blocker use and risk of Parkinson's disease: from multiple real-world evidence.

BACKGROUND: People with hypertension have a higher risk of developing Parkinson's disease (PD), epidemiological evidence suggests that multiple antihypertensives may affect the occurrence and development of PD with inconsistent results. With multisource data, we sought to determine whether specific antihypertensive classes elevated or reduced the risk for PD. METHODS: We used a mixed methods approach that combines 4 methodologies. First, we conducted a disproportionality analysis using the reports causing adverse events in the US Food and Drug Administration Adverse Events Reporting System (FAERS) to explore the effect of different classes of antihypertensive medications on the risk of PD; based on the findings from FAERS, a meta-analysis and a UK Biobank cohort analysis were used to further assess the association of drug use with PD; finally, we employed Mendelian randomization (MR) analysis to validate the causal relationship between the drug target and the occurrence of PD. RESULTS: In the disproportionality analysis using the FAERS (N = 187,266), nonselective beta-adrenoceptor blockers (NBBs) were demonstrated to have a significant association with PD (reporting odds ratio (ROR) = 3.13; 95% CI 2.33-4.22). In the meta-analysis of 12 studies with 12,183,809 participants, PD risk was elevated in NBBs (RR, 1.64; 95% CI, 1.19-2.09) when stratified by subtypes of BBs. Among the 105,763 participants included in the cohort analysis using data from the UK Biobank, individuals who used NBBs had a significantly increased risk of PD compared to nonusers (HR, 1.47; 95% CI 1.04-2.06). The MR analysis revealed a significant association between higher expression of the ß2 adrenergic receptor (ADRB2) gene, a drug target blocked by NBBs, and a reduced risk of PD (OR, 0.85; 95% CI 0.73-0.99). CONCLUSIONS: Our comprehensive study indicated that regular NBB use is associated with an increased risk of PD. In light of the detrimental effects of NBBs on PD, some people should choose alternative antihypertensive treatments.

Clinical factors associated with remission of obese acanthosis nigricans after laparoscopic sleeve gastrectomy: a prospective cohort study.

BACKGROUND: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. METHODS: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n =178) or OB with AN (OB_AN, n =141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. RESULTS: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels ( P <0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery ( P <0.01). CONCLUSION: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer.

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.

Epilepsy and long-term risk of arrhythmias.

BACKGROUND AND AIMS: Previous evidence has mainly supported transient changes in cardiac function during interictal or peri-ictal phases in people with epilepsy, but the long-term risk of cardiac arrhythmias is poorly described. This study aimed to assess the long-term association of epilepsy with cardiac arrhythmias, considering the potential role of genetic predisposition and antiseizure medications (ASMs) in any associations observed. METHODS: This population-based study evaluated UK Biobank data for individuals recruited between 2006 and 2010. Cox proportional hazards models and competing risk models were used to examine the association of epilepsy history with the long-term incidence risk of cardiac arrhythmias and arrhythmias subtypes. Polygenic risk scores (PRS) were calculated to investigate the effect of genetic susceptibility. The role of ASMs was also evaluated by integrating observational and drug target Mendelian randomization (MR) evidence. RESULTS: The study included 329 432 individuals, including 2699 people with epilepsy. Compared with those without epilepsy, people with epilepsy experienced an increased risk of all cardiac arrhythmias [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.21-1.53], atrial fibrillation (HR 1.26, 95% CI 1.08-1.46), and other cardiac arrhythmias (HR 1.56, 95% CI 1.34-1.81). The associations were not modified by genetic predisposition as indicated by PRS. Competing and sensitivity analyses corroborated these results. Individuals with epilepsy using ASMs, especially carbamazepine and valproic acid, were at a higher risk for cardiac arrhythmias. This observation was further supported by drug target MR results (PSMR < .05 and PHEIDI > .05). CONCLUSION: This study revealed the higher risk of cardiac arrhythmias persists long term in people with epilepsy, especially among those using carbamazepine and valproic acid. These findings highlight the need for regular heart rhythm monitoring and management in people with epilepsy in order to reduce the risk of further cardiovascular complications.

Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.

AIMS/HYPOTHESIS: This study aimed to assess the causal relationship between visceral obesity and type 2 diabetes and subsequently to screen visceral adipose tissue (VAT)-specific targets for type 2 diabetes. METHODS: We examined the causal relationship between VAT and type 2 diabetes using bidirectional Mendelian randomisation (MR) followed by multivariable MR. We conducted a transcriptome-wide association study (TWAS) leveraging prediction models and a large-scale type 2 diabetes genome-wide association study (74,124 cases and 824,006 controls) to identify candidate genes in VAT and used summary-data-based MR (SMR) and co-localisation analysis to map causal genes. We performed enrichment and single-cell RNA-seq analyses to determine the cell-specific localisation of the TWAS-identified genes. We also conducted knockdown experiments in 3T3-L1 pre-adipocytes. RESULTS: MR analyses showed a causal relationship between genetically increased VAT mass and type 2 diabetes (inverse-variance weighted OR 2.48 [95% CI 2.21, 2.79]). Ten VAT-specific candidate genes were associated with type 2 diabetes after Bonferroni correction, including five causal genes supported by SMR and co-localisation: PABPC4 (1p34.3); CCNE2 (8q22.1); HAUS6 (9p22.1); CWF19L1 (10q24.31); and CCDC92 (12q24.31). Combined with enrichment analyses, clarifying cell-type specificity with single-cell RNA-seq data indicated that most TWAS-identified candidate genes appear more likely to be associated with adipocytes in VAT. Knockdown experiments suggested that Pabpc4 likely contributes to regulating differentiation and energy metabolism in 3T3-L1 adipocytes. CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.

Astaxanthin protects the radiation-induced lung injury in C57BL/6 female mice.

Radiation-induced lung injury (RILI) is one of the common complications of radiotherapy for chest tumors and nuclear radiation accidents. The excessive reactive oxygen species induced by radiation is the main mediator. So far, the effective prevention and treatment for RILI are still lacking. Astaxanthin is a carotenoid that belongs to red natural lutein family and is commonly found in Marine organisms such as shrimp, oysters and salmon. It has been confirmed that astaxanthin has strong antioxidant and anti-inflammatory properties, therefore we speculated that astaxanthin may be a potential treatment for RILI. First, with a mice model of RILI, the protected effects of astaxanthin were observed. Furthermore, the experiments in vitro were performed by detecting apoptosis. As a result, astaxanthin protects the RILI, inhibits the process of pulmonary fibrosis, and reduces the elevation of inflammatory factors. The experiments in vitro demonstrated that astaxanthin could reduce radiation-induced apoptosis and especially inhibit activation of apoptosis pathway. In conclusion, astaxanthin could protect RILI of mice, which is mediated by inhibiting activation of apoptosis pathway.

Sex-Specific Changes in Body Composition Following Metabolic and Bariatric Surgery Are Associated with the Remission of Metabolic Syndrome.

PURPOSE: Metabolic and bariatric surgery (MBS) is the most effective treatment for metabolic syndrome (MetS). However, the mechanism of MetS remission after MBS remains unclear. We aimed to explore the relationship between sex differences, body composition, and the remission of MetS after MBS. MATERIALS AND METHODS: Cross-sectional study of 80 patients with obesity and MetS who underwent MBS with case-control design. The International Diabetes Federation criteria were used to define MetS. Body composition was measured using dual-energy X-ray absorptiometry before and 1 year after the operation. In addition to calculating changes in MetS and its prevalence, we performed a multiple logistic regression to determine predictors of MetS remission. RESULTS: There were significant differences in body composition between males and females after MBS. Both males and females had significant improvements in the overall prevalence of MetS, decreasing from 100 to 21.74% (P <0.001) and from 100 to 35.29% (P <0.001), respectively. A higher percentage of visceral adipose tissue (VAT) reduction tends to be associated with a higher chance of MetS remission in men. In females, the MetS nonremission subgroup had a higher %Trunk lean body mass (LBM), and %Android LBM reduction than the remission subgroup, but the multiple logistic regression analysis result was not statistically significant. CONCLUSION: After MBS, reduced VAT might be related to MetS reversibility in males, while reduced LBM may result in MetS nonremission in females.

Effect of laparoscopic sleeve gastrectomy on mobilization of site-specific body adipose depots: a prospective cohort study.

BACKGROUND: Effect of bariatric surgery on mobilization of site-specific body adipose depots is not well investigated. Herein, the authors conducted a prospective cohort study to assess whether bariatric surgery can differentially affect specific fat storage pools and to further investigate correlations between site-specific fat mobilization and clinical outcomes. MATERIALS AND METHODS: In this single-centre prospective cohort study, 49 participants underwent laparoscopic sleeve gastrectomy (LSG) from 24 May 2022 to 20 October 2022 and underwent MRI to estimate subcutaneous fat area, visceral fat area (VFA), hepatic and pancreatic proton density fat fraction (PDFF) at baseline and 3 months after surgery. The protocol for this study was registered on clinicaltrials.gov. RESULTS: Among 49 patients who met all inclusion criteria, the median [interquartile range (IQR)] age was 31.0 (23.0-37.0) years, the median (IQR) BMI was 38.1 (33.7-42.2) kg/m 2 and 36.7% were male. Median (IQR) percentage hepatic PDFF loss was the greatest after bariatric surgery at 68.8% (47.3-79.7%), followed by percentage pancreatic PDFF loss at 51.2% (37.0-62.1%), percentage VFA loss at 36.0% (30.0-42.4%), and percentage subcutaneous fat area loss at 22.7% (17.2-32.4%) ( P <0.001). By calculating Pearson correlation coefficient and partial correlation coefficient, the positive correlations were confirmed between change in VFA and change in glycated haemoglobin ( r =0.394, P =0.028; partial r =0.428, P =0.042) and between change in hepatic PDFF and change in homoeostatic model assessment of insulin resistance ( r =0.385, P =0.025; partial r =0.403, P =0.046). CONCLUSIONS: LSG preferentially mobilized hepatic fat, followed by pancreatic fat and visceral adipose tissue, while subcutaneous adipose tissue was mobilized to the least extent. Reduction in visceral adipose tissue and hepatic fat is independently associated with the improvement of glucose metabolism after LSG.

Tumor-targeting engineered probiotic Escherichia coli Nissle 1917 inhibits colorectal tumorigenesis and modulates gut microbiota homeostasis in mice.

AIMS: Preliminary studies have identified the use of probiotics as a potential treatment strategy against colorectal cancer (CRC). However, natural probiotics lack direct tumor-targeting and tumor-killing activity in the intestine. This study aimed to construct a tumor-targeting engineered probiotic to combat CRC. MAIN METHODS: Standard adhesion assay was performed to analyze the adherence ability of tumor-binding protein HlpA to CT26 cells. CCK-8 assay, Hoechst 33258 staining and flow cytometry analysis were used for examining cytotoxicity of tumoricidal protein azurin toward CT26 cells. An engineered probiotic Ep-AH harboring azurin and hlpA genes was developed using Escherichia coli Nissle 1917 (EcN) chassis. Antitumor effects of Ep-AH were evaluated in the azoxymethane (AOM) and dextran sodium sulfate salt (DSS)-induced CRC mice. Moreover, analysis of gut microbiota was conducted via fecal 16S rRNA gene sequencing and shotgun metagenomic sequencing. KEY FINDINGS: Azurin caused a dose-dependent increase of apoptosis in CT26 cells. Ep-AH treatment reversed weight loss (p < 0.001), fecal occult blood (p < 0.01), and shortening of colon length (p < 0.001) than model group, as well as reducing tumorigenesis by 36 % (p < 0.001). Both Ep-H and Ep-A (EcN expressing HlpA or azurin) were less effective than Ep-AH. Furthermore, Ep-AH enriched the members of beneficial bacteria (e.g., Blautia and Bifidobacterium) and reversed abnormal changes of genes associated with several metabolic pathways (e.g., lipopolysaccharide biosynthesis). SIGNIFICANCE: These results demonstrated that Ep-AH had excellent therapeutic benefits on cancer remission and gut microbiota modulation. Our study provides an effective strategy for anti-CRC treatment.

Temporal Relationship Between Insulin Resistance and Lipid Accumulation After Bariatric Surgery: a Multicenter Cohort Study.

PURPOSE: Insulin resistance (IR) is closely associated with lipid accumulation. Here, we investigated the temporal relationship between the two conditions after bariatric surgery. MATERIALS AND METHODS: In total, 409 participants were enrolled from three bariatric centers in China from 2009 to 2018. We evaluated whether baseline IR (proxied by homeostasis model assessment of insulin resistance (HOMA-IR)) and lipid accumulation (proxied by visceral adiposity index (VAI) and lipid accumulation product (LAP)) were associated with follow-up IR and lipid accumulation (3 months postoperatively) using linear regression models. We then conducted a cross-lagged panel analysis model to simultaneously examine the bidirectional relationship between IR and lipid accumulation. RESULTS: Multivariable linear regression analyses showed that baseline HOMA-IR was associated with follow-up VAI (ß = 0.430, 95% CI: 0.082-0.778, p = 0.016) and LAP (ß = 0.070, 95% CI: 0.010-0.130, p = 0.022). There was no relationship between baseline lipid accumulation and follow-up IR. Further cross-lagged panel analyses indicated that the path coefficient from baseline HOMA-IR to follow-up VAI (ß2 = 0.145, p = 0.003) was significantly greater than the coefficient from baseline VAI to follow-up HOMA-IR (ß1 = - 0.013, p = 0.777). Similarly, the path coefficient from baseline HOMA-IR to follow-up LAP (ß2 = 0.141, p = 0.003) was significantly greater than the coefficient from baseline LAP to follow-up HOMA-IR (ß1 = 0.041, p = 0.391). CONCLUSION: Our study demonstrated a unidirectional relationship from HOMA-IR to VAI and LAP, suggesting that the change in IR may precede lipid accumulation after surgery.