Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.

Metabolic (dysfunction)-associated steatohepatitis (MASH) is the advanced stage of metabolic (dysfunction)-associated fatty liver disease (MAFLD) lacking approved clinical drugs. Adenosine A1 receptor (A1R), belonging to the G-protein-coupled receptors (GPCRs) superfamily, is mainly distributed in the central nervous system and major peripheral organs with wide-ranging physiological functions; however, the exact role of hepatic A1R in MAFLD remains unclear. Here, we report that liver-specific depletion of A1R aggravates while overexpression attenuates diet-induced metabolic-associated fatty liver (MAFL)/MASH in mice. Mechanistically, activation of hepatic A1R promotes the competitive binding of sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) to sequestosome 1 (SQSTM1), rather than protein kinase A (PKA) leading to SCAP degradation in lysosomes. Reduced SCAP hinders SREBP1c/2 maturation and thus suppresses de novo lipogenesis and inflammation. Higher hepatic A1R expression is observed in patients with MAFL/MASH and high-fat diet (HFD)-fed mice, which is supposed to be a physiologically adaptive response because A1R agonists attenuate MAFL/MASH in an A1R-dependent manner. These results highlight that hepatic A1R is a potential target for MAFL/MASH therapy.

Modelling tomato pericarp microstructure as force control reference for harvesting robot.

BACKGROUND: The harvest of fruit can be significantly advanced with the thriving development of intelligent and automated robot technologies. Nevertheless, the picking success rate of tomato fruit still requires improvement as some fruits are unexpectedly damaged inside, which is imperceptible by machine vision. Herein, a modelling method based on modified Voronoi algorithm is proposed to reconstruct the cellular structure of tomato pericarp. RESULTS: Based on the reconstructed micro-model, the compression physical behaviour of the pericarp cells is simulated to observe internal local stress and potential damage. It is revealed that the simulation result for pericarps of tomatoes with different ripeness is highly consistent to the experimental tests, which has well validated the feasibility of this modelling and simulation method. CONCLUSION: A Voronoi-based modelling method is proposed for micro-reconstruction of tomato pericarp, and the corresponding compression simulation results agree well with the experimental tests. Such result can be utilized as reference to improve the grasping force control for harvesting robot to avoid invisible damage induced by accident overload issue. With the predicting result, superior success rate can be achieved to enhance robot performance. © 2024 Society of Chemical Industry.

Intestinal Flora Imbalance Induced by Antibiotic Use in Rats.

Aim: This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum. Methods: Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-ß and TNF-α. Results: Our findings revealed that the initial average weight of the rats did not differ between groups (p>0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, <0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p<0.001). There were no difference in nine microbiota at day 1 (all p>0.05); at day 4 A/B (p=0.044), A/D (p<0.001), A/E (p=0.029); at day 8, all p<0.01, at day 11, only A/F exist significant difference (p<0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-ß and TNF-α (p<0.001). Conclusion: This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon.

Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight.

BACKGROUND: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. METHODS: Bile samples from 20 patients (10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by further bioinformatic analysis. RESULTS: Among the differentially-expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially-expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor (PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APOA-I and APOA-II, were confirmed using enzyme-linked immunosorbent assay. CONCLUSIONS: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

Loop Closure Detection Based on Residual Network and Capsule Network for Mobile Robot.

Loop closure detection based on a residual network (ResNet) and a capsule network (CapsNet) is proposed to address the problems of low accuracy and poor robustness for mobile robot simultaneous localization and mapping (SLAM) in complex scenes. First, the residual network of a feature coding strategy is introduced to extract the shallow geometric features and deep semantic features of images, reduce the amount of image noise information, accelerate the convergence speed of the model, and solve the problems of gradient disappearance and network degradation of deep neural networks. Then, the dynamic routing mechanism of the capsule network is optimized through the entropy peak density, and a vector is used to represent the spatial position relationship between features, which can improve the ability of image feature extraction and expression to optimize the overall performance of networks. Finally, the optimized residual network and capsule network are fused to retain the differences and correlations between features, and the global feature descriptors and feature vectors are combined to calculate the similarity of image features for loop closure detection. The experimental results show that the proposed method can achieve loop closure detection for mobile robots in complex scenes, such as view changes, illumination changes, and dynamic objects, and improve the accuracy and robustness of mobile robot SLAM.

The Innate and Adaptive Immune Cells in Alzheimer's and Parkinson's Diseases.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders of the central nervous system (CNS). Increasing evidence supports the view that dysfunction of innate immune cells initiated by accumulated and misfolded proteins plays essential roles in the pathogenesis and progression of these diseases. The TLR family was found to be involved in the regulation of microglial function in the pathogenesis and progression of AD or PD, making it as double-edged sword in these diseases. Altered function of peripheral innate immune cells was found in AD and PD and thus contributed to the development and progression of AD and PD. Alteration of different subsets of T cells was found in the peripheral blood and CNS in AD and PD. The CNS-infiltrating T cells can exert both neuroprotective and neurotoxic effects in the pathogenesis and progression. Here, we review recent evidences for the roles of innate and adaptive immune cells in the pathogenesis and progression of AD and PD.

Largest Amplitude of Glycemic Excursion Calculating from Self-Monitoring Blood Glucose Predicted the Episodes of Nocturnal Asymptomatic Hypoglycemia Detecting by Continuous Glucose Monitoring in Outpatients with Type 2 Diabetes.

Aims: Nocturnal asymptomatic hypoglycemia (NAH) is a serious complication of diabetes, but it is difficult to be detected clinically. This study was conducted to determine the largest amplitude of glycemic excursion (LAGE) to predict the episodes of NAH in outpatients with type 2 diabetes. Methods: Data were obtained from 313 outpatients with type 2 diabetes. All subjects received continuous glucose monitoring (CGM) for consecutive 72 hours. The episodes of NAH and glycemic variability indices (glucose standard deviation [SD], mean amplitude of plasma glucose excursion [MAGE], mean blood glucose [MBG]) were accessed via CGM. LAGE was calculated from self-monitoring blood glucose (SMBG). Results: A total of 76 people (24.3%) had NAH. Compared to patients without NAH, patients with NAH showed higher levels of glucose SD (2.4 ± 0.9 mmol/L vs 1.7 ± 0.9 mmol/L, p <0.001), MAGE (5.2 ± 2.1 mmol/L vs 3.7 ± 2.0, p<0.001) and LAGE (4.6 ± 2.3 mmol/L vs 3.8 ± 1.9 mmol/L, p=0.007), and lower level of MBG (7.5 ± 1.5 mmol/L vs 8.4 ± 2.2 mmol/L, p=0.002). LAGE was significantly associated with the incidence of NAH and time below rang (TBR) in model 1 [NAH: 1.189 (1.027-1.378), p=0.021; TBR: 0.008 (0.002-0.014), p=0.013] with adjustment for age, BMI, sex, work, hyperlipidemia, complication and medication, and in model 2 [NAH: 1.177 (1.013-1.367), p=0.033; TBR: 0.008 (0.002-0.014), p=0.012] after adjusting for diabetes duration based on model 1, as well as in model 3 [NAH: 1.244 (1.057-1.464), p=0.009; TBR: 0.009 (0.002-0.016), p=0.007] with further adjustment for HbA1c based on model 2. In addition, no significant interactions were found between LAGE and sex, age, HbA1c, duration of diabetes, BMI and insulin therapy on the risk of NAH. The receiver operator characteristic (ROC) curve shows the ideal cutoff value of LAGE for the prediction of NAH was 3.48 mmol/L with 66.7% sensitivity, 50% specificity and 0.587 (95% CI: 0.509-0.665) of area under the ROC curve. Conclusions: High glycemic variability is strongly associated with the risk of NAH. The LAGE based on SMBG could be an independent predictor of NAH for outpatients with type 2 diabetes, and LAGE greater than 3.48 mmol/L could act as a warning alarm for high risk of NAH in daily life.

Expression of Tspan8 in Patients with Intrahepatic Cholangiocarcinoma and Its Relationship with Clinicopathological Features and Prognosis.

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. High invasion and metastasis are one of the main causes of death in patients. The selection of reasonable and effective molecular markers to evaluate the prognosis of patients with ICC has important clinical guiding significance. In this study, the expression of Tspan protein in ICC and normal tissues was compared, the correlation between Tspan expression and pathological features of patients was analyzed by the logistic regression model using multivariate analysis, and the relationship between Tspan8 expression and prognosis of ICC patients was analyzed by the Kaplan-Meier survival curve. The results showed that Tspan8 is highly positive in ICC tissues, TNM stage, degree of tumor differentiation, lymph node metastasis, and Tspan8 protein expression were independently correlated, and the overexpression of Tspan was associated with the prognosis of ICC invasion and metastasis. This provides a new idea for clinical treatment.

Migration of Chlorine in Plant-Soil-Leaching System and Its Effects on the Yield and Fruit Quality of Sweet Orange.

Chlorine (Cl) is indispensable for the growth of plants. While rarely systematic reports are available for the effect of Cl-containing fertilizers on citrus production. This study aimed to investigate the impacts of various Cl-containing fertilizers on the nutrients in the leaves, the yield and quality of sweet orange, and the Cl migration in the plant-soil-leaching system. A 5-year field experiment (2016-2020) with five Cl treatments (0, 75, 150, 450, and 900 kg ha-1), and soil core lysimeter test with five Cl levels (0, 150, 225, 300, and 450 kg ha-1) were carried out. The results showed that 77.0% of Cl leached into above 60 cm deeper soil layer, with calcium as the main accompanying ions, resulting in less Cl being absorbed by the citrus plants. The content of Cl in the leaves and soil was enhanced by the increasing input of Cl-containing fertilizer, without yearly increased characteristics, under a mean annual rainfall of 1,474 mm. Chlorine significantly increased the yield (13.24-37.8 9%), fruit weight, and vitamin C (Vc), in addition to enhancing the flavor and the juice yield of sweet orange via improving the absorption of N and K. Moreover, the long-term application of potassium sulfate has elevated the accumulation of sulfur in the soil and in leaves; it is becoming a potential risk factor for citrus production. Taken together, the application of Cl-containing fertilizer in sweet orange is feasible, and trace absorbance of Cl could improve the yield and fruit quality of sweet orange.

Migration of Hem-o-lok clip into the common hepatic duct after laparoscopic bile duct exploration: A case report.

Hem-o-lok clip migration into the bile duct can lead to stone formation and granulation tissue hyperplasia. This report discusses a case wherein four clips migrated into the bile duct after laparoscopic bile duct exploration.

Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid.

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan-Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.

Hidden blood loss and the influencing factors after laparoscopic cholecystectomy.

BACKGROUND: A small amount of bleeding usually occurs during laparoscopic cholecystectomy (LC), but the occurrence of perioperative hidden blood loss (HBL) is ignored. So our objective is to investigate the amount of HBL and find out the influential factors in LC. METHODS: From January 2017 to May 2019, 139 patients scheduled for LC were enrolled in the study. The data of patients' sex, age, height, weight, body mass index (BMI), form of gallbladder bed, gallbladder status, hypertension, diabetes, liver cirrhosis, drainage volume and operation time were recorded. The patients' height, weight and preoperative and postoperative haematocrit and haemoglobin were recorded and applied to the Gross formula to determine the amount of blood loss. The data of sex, age, BMI, hypertension, diabetes, gallbladder status, liver cirrhosis and operation time were analysed by multivariate linear regression analysis. One-way analysis of variance was performed to find out the relative correlation between HBL and the type of gallbladder bed. RESULTS: The HBL was 259.3 ± 188.5 mL. On the basis of multivariate linear regression analysis and analysis of variance, the gallbladder bed, hypertension and the operation time are influential factors of HBL in patients with LC. However, sex, age, BMI, gallbladder status, liver cirrhosis and diabetes are not significantly correlated with HBL. CONCLUSIONS: HBL should not be overlooked during the perioperative period of LC, especially in patients with hypertension, gallbladder bed >50% gallbladder surface or operation time >60 min.

Clinical analysis of prophylactic cholecystectomy during gastrectomy for gastric cancer patients: a retrospective study of 1753 patients.

BACKGROUND: Performance of gastrectomy in gastric cancer patients can lead to an increased incidence of cholecystolithiasis (CL) and a higher morbidity rate. However, the value of prophylactic cholecystectomy performed during gastric cancer surgery is still being debated. METHODS: We carried out a retrospective study on patients with gastric cancer who underwent subtotal or total gastrectomy, with preservation of the gallbladder or simultaneous cholecystectomy from January 2010 to March 2018. RESULTS: Cholecystolithiasis occurred in 152 of 1691 (8.98%) patients after gastric cancer surgery, with 45 (2.67%) patients undergoing subsequent cholecystectomy. Postoperative body mass index (BMI) decrease > 5% in 3 months was an independent risk factor for cholecystolithiasis [BMI decrease > 5%/≤5%: OR (95%CI): 1.812 (1.225-2.681), p = 0.003). Gastrectomy method and diabetes mellitus were independent risk factors for both cholecystolithiasis [gastrectomy method (no-Billroth I/Billroth I): OR (95%CI): 1.801 (1.097-2.959), p = 0.002; diabetes mellitus (yes/no): OR (95%CI): 1.544 (1.030-2.316), p = 0.036] and subsequent cholecystectomy [gastrectomy method (no-Billroth I/Billroth I): OR (95%CI): 5.432 (1.309-22.539), p = 0.020; diabetes mellitus (yes/no): OR (95%CI): 2.136 (1.106-4.125), p = 0.024]. Simultaneous cholecystectomy was performed in 62 of 1753 (3.5%) patients. The mortality and morbidity rates did not differ significantly between the combined surgery group and the gastrectomy only group (8.1% vs. 8.9 and 1.6% vs. 2.2%, respectively, p > 0.05). CONCLUSIONS: Prophylactic cholecystectomy may be necessary in gastric cancer patients without Billroth I gastrectomy and with diabetes mellitus. Simultaneous cholecystectomy during gastric cancer surgery does not increase the postoperative mortality and morbidity rates.

Telomerase insufficiency induced telomere erosion accumulation in successive generations in dyskeratosis congenita family.

BACKGROUND: Dyskeratosis congenita (DC) is a rare heritable bone marrow failure syndrome that is associated with telomere dysfunction, and has high genetic heterogeneity and varied features. OBJECTIVE: This study aimed to identify the underlying genetic etiology of a DC family with more severe symptoms in the younger generation and to explore the relationship between the genetic causes and the severity of DC phenotype. METHODS: Whole-exome sequencing was performed on the proband to screen the candidate causative gene. The protein structure was then predicted by SWISS-MODEL software. Telomere length (TL) assay was performed on family members along with large-scale population controls. The prenatal diagnosis (PND) was performed on the fetus of parents with secondary pregnancy. RESULTS: Novel heterozygous mutations in TERT (NM_198253.2), c.1796G>A (p.Arg599Gln), c.2839T>C (p.Ser947Pro), and c.3346G>C (p.Glu1116Gln) were identified in the proband. His TL was below the first percentile of the peers, which also appeared on the fetus with epidermal dyskeratosis through PND. The TL data of large-scale population and members of the DC family implied the accumulation of telomere erosion in successive generations in this family. CONCLUSIONS: Our study identified three clinical pathologic TERT mutations and implied that telomere erosion might be accumulated through successive generations, contributing to the severity of DC in the younger generation.

A Case Study on Attribute Recognition of Heated Metal Mark Image Using Deep Convolutional Neural Networks.

Heated metal mark is an important trace to identify the cause of fire. However, traditional methods mainly focus on the knowledge of physics and chemistry for qualitative analysis and make it still a challenging problem. This paper presents a case study on attribute recognition of the heated metal mark image using computer vision and machine learning technologies. The proposed work is composed of three parts. Material is first generated. According to national standards, actual needs and feasibility, seven attributes are selected for research. Data generation and organization are conducted, and a small size benchmark dataset is constructed. A recognition model is then implemented. Feature representation and classifier construction methods are introduced based on deep convolutional neural networks. Finally, the experimental evaluation is carried out. Multi-aspect testings are performed with various model structures, data augments, training modes, optimization methods and batch sizes. The influence of parameters, recognitio efficiency and execution time are also analyzed. The results show that with a fine-tuned model, the recognition rate of attributes metal type, heating mode, heating temperature, heating duration, cooling mode, placing duration and relative humidity are 0.925, 0.908, 0.835, 0.917, 0.928, 0.805 and 0.92, respectively. The proposed method recognizes the attribute of heated metal mark with preferable effect, and it can be used in practical application.

A novel chloroplast-localized pentatricopeptide repeat protein involved in splicing affects chloroplast development and abiotic stress response in rice.

Pentatricopeptide repeat (PPR) proteins comprise a large family in higher plants and modulate organellar gene expression by participating in various aspects of organellar RNA metabolism. In rice, the family contains 477 members, and the majority of their functions remain unclear. In this study, we isolated and characterized a rice mutant, white stripe leaf (wsl), which displays chlorotic striations early in development. Map-based cloning revealed that WSL encodes a newly identified rice PPR protein which targets the chloroplasts. In wsl mutants, PEP-dependent plastid gene expression was significantly down-regulated, and plastid rRNAs and translation products accumulate to very low levels. Consistently with the observations, wsl shows a strong defect in the splicing of chloroplast transcript rpl2, resulting in aberrant transcript accumulation and its product reduction in the mutant. The wsl shows enhanced sensitivity to ABA, salinity, and sugar, and it accumulates more H2O2 than wild-type. These results suggest the reduced translation efficiency may affect the response of the mutant to abiotic stress.