Prohexadione-calcium improves grape quality by regulating endogenous hormones, sugar and acid metabolism and related enzyme activities in grape berries.

Prohexadione-Calcium (Pro-Ca) plays key roles in improving fruit quality and yield by regulating various aspects of plant growth. However, the effects of how Pro-Ca regulates the regulation of sugar and acid balance and its impact on the production of volatile aroma substances during fruit growth and development are poorly understood. In this study, the Pro-Ca solutions developed at concentrations of 200, 400, 600 and 800 mg·L-1 were sprayed on the entire "Chardonnay" grape tree 22, 42, 62 and 82 days after initial flowering. The values of endogenous hormones, sugar and acid content, enzyme activities and flavor content were then measured in grapes 45, 65, 85 and 105 days (ripeness stage) after the initial flowering. The results showed that Pro-Ca had significant effects on fruits during development, including reducing ABA content, increasing ZT, GA3 and IAA levels, promoting fruit ripening and enhancing enzymes, which are involved in sugar and acid synthesis. Consequently, these effects led to an increase in sugar and acid content in the berries. Particularly during the ripening phase, the application of 600 mg L-1 Pro-Ca resulted in an increase in soluble sugar content of 11.28% and a significant increase in citric acid and malic acid content of 97.80% and 68.86%, respectively. Additionally, Pro-Ca treatment enhanced both the variety and quantity of aroma compounds present in the berries, with the 600 mg·L-1 Pro-Ca treatment showcasing the most favorable impact on volatile aroma compounds in 'Chardonnay' grapes. The levels of aldehydes, esters, alcohols, phenols, acids, ketones, and terpenes were significantly higher under the 600 mg·L-1 Pro-Ca treatment compared to those of control with 51.46 - 423.85% increase. In conclusion, Pro-Ca can regulate the content of endogenous hormones and the activities of enzymes related to sugar and acid metabolism in fruit, thereby increasing the content of soluble sugar and organic acid in fruit and the diversity and concentration of fruit aroma substances. Among them, foliar spraying 600 mg · L-1 Pro-Ca has the best effect. In the future, we need to further understand the molecular mechanism of Pro-Ca in grape fruit to lay a solid foundation for quality improvement breeding.

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification.

BACKGROUND: Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise. METHODS: Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments. RESULTS: In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain. CONCLUSION: The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

Glycyrrhizic Acid Protects Glomerular Podocytes Induced by High Glucose by Modulating SNARK/AMPK Signaling Pathway.

OBJECTIVE: Diabetic nephropathy is one of the most important microvascular complications of diabetes, which mainly refers to glomerular capillary sclerosis. Podocytes are an important part of glomerular capillaries. Previous clinical and basic studies have shown that fibrosis is the main factor of diabetic nephropathy. This study aimed to assess the protective mechanism of glycyrrhizic acid (GA) on glomerular podocytes induced by high glucose as we hypothesized that GA may have antifibrotic and anti-inflammatory effects on podocytes through regulation of the adenosine 5'-monophosphate-activated protein kinase (AMPK)/sucrose nonfermenting AMPK-related kinase (SNARK) signaling pathway. METHODS: SNARK siRNA was used to transfect podocytes. Real-time quantitative polymerase chain reaction and immunofluorescence staining assays were used for molecular and pathological analysis. The expression levels of key pathway proteins (including TGF-ß1, α-SMA, SITR1, AMPKα, LKB1, PGC-1α, NF-κB, IL-6, and TNF-α) were verified by Western blotting. The expression of inflammatory factors in podocytes was detected by ELISA. RESULTS: We demonstrated that GA decreased the expression of podocyte fibrosis signaling pathway-related factors by upregulating the AMPK pathway and its related factors. However, after transfection of podocytes with SNARK siRNA, there was an increased expression of fibrosis-related factors and inflammation-related factors. CONCLUSION: GA can protect podocytes and alleviate fibrosis and inflammation induced by high glucose, which is related to the AMPK signaling pathway. Meanwhile, knockdown of SNARK protein can inhibit the AMPK signaling pathway, aggravate fibrosis, and increase inflammation.

Exploring the targets and molecular mechanism of glycyrrhetinic acid against diabetic nephropathy based on network pharmacology and molecular docking.

BACKGROUND: Diabetic nephropathy (DN) stands as the most prevalent chronic microvascular complication of diabetes mellitus. Approximately 50% of DN patients progress to end-stage renal disease, posing a substantial health burden. AIM: To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid (GA) treats DN, subsequently validating these predictions through experimental means. METHODS: The study initially identified GA targets using Pharm Mapper and the TCMSP database. Targets relevant to DN were obtained from the Genecards, OMIM, and TTD databases. The Venny database facilitated the acquisition of intersecting targets between GA and DN. The String database was used to construct a protein interaction network, while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. Molecular docking experiments were performed using Autodock software with selected proteins. Experimental validation was conducted using renal proximal tubular cells (HK-2) as the study subjects. A hyperglycemic environment was simulated using glucose solution, and the effect of GA on cell viability was assessed through the cell counting kit-8 method. Flow cytometry was employed to detect cell cycle and apoptosis, and protein immunoblot (western blot) was used to measure the expression of proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and insulin resistance pathway, including insulin receptor (INSR), PI3K, p-PI3K, AKT, p-AKT, and glycogen synthase kinase-3 (GSK3). RESULTS: A total of 186 intersecting targets between GA and DN were identified, which were associated with 144 KEGG-related enrichment pathways, 375 GO biological process entries, 45 GO cellular component entries, and 112 GO cellular function entries. Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase (MAPK)-1, SRC, PIK3R1, HSP90AA1, CASPASE9, HARS, KRAS, and MAPK14. In vitro experiments revealed that GA inhibited HK-2 cell viability, induced cell cycle arrest at the G2/M phase, and reduced apoptosis with increasing drug concentration. Western blot analysis showed that GA differentially up-regulated GSK3 protein expression, up-regulated AKT/p-AKT expression, down-regulated INSR, AKT, p-AKT, PI3K, and p-PI3K protein expression, and reduced p-PI3K/PI3K levels under high glucose conditions. CONCLUSION: GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway, thereby inhibiting HK-2 cell viability, reducing HK-2 cell apoptosis, and inducing cell cycle arrest at the G0/G1 phase.

Digestive Tract Injuries Caused by Ingested Foreign Bodies Containing Magnets.

We report on 16 children with ingestion of magnetic foreign bodies, who were identified by a medical record review of our hospital data for the time period between January, 2017 and May, 2018. Digestive tract wall was sandwiched in 13 (75%) children and 11 (74%) had gaptic intestinal perforation.

Detection and localization of image forgeries using improved mask regional convolutional neural network.

The research on forgery detection and localization is significant in digital forensics and has attracted increasing attention recently. Traditional methods mostly use handcrafted or shallow-learning based features，but they have limited description ability and heavy computational costs. Recently, deep neural networks have shown to be capable of extracting complex statistical features from high-dimensional inputs and efficiently learning their hierarchical representations. In order to capture more discriminative features between tampered and non-tampered regions，we propose an improved mask regional convolutional neural network (Mask R-CNN) which attach a Sobel filter to the mask branch of Mask R-CNN in this paper. The Sobel filter acts as an auxiliary task to encourage predicted masks to have similar image gradients to the groundtruth mask. The overall network is capable of detecting two different types of image manipulations, including copy-move and splicing. The experimental results on two standard datasets show that the proposed model outperforms some state-of-the-art methods.

[Study on trace elements in wuji baifeng wan and its preparation].

We studied the amount of trace elements in the traditional Chinese medicine Wuji Baifeng Wan by cluster analysis, and found that the clustering results of the trace elements in Twelve Wuji Baifeng Wan (the southern preparation) and Wuji Baifeng Wan (the northern preparation) were not in the same group. In this paper, AAS was used for the determination of trace elements in Wuji Baifeng Wan and its preparation. The results showed that there were great differences between Twelve Wuji Baifeng Wan and Wuji Baifeng Wan , while the difference between Chinese Taihe Chicken and Native Chicken was slight. So we drew a conclusion that the great differences between Twelve Wuji Baifeng Wan and Wuji Baifeng Wan were caused by other medicine, not in its preparation.

Effectiveness and safety profile of S-1-based chemotherapy compared with capecitabine-based chemotherapy for advanced gastric and colorectal cancer: A meta-analysis.

The aim of the present analysis was to compare the efficacy and safety profile of S-1-based chemotherapy (SBCT) versus capecitabine-based chemotherapy (CBCT) for advanced gastric cancer (AGC) and advanced colorectal cancer (ACRC). A meta-analysis was performed, which included eligible randomized controlled trials (RCTs) that were identified using RevMan 5.1.0 software. A total of 1,064 patients from 11 RCTs, comprising of 527 patients in the SBCT group and 537 patients in the CBCT group, were included in the analysis. For AGC, the meta-analysis of overall survival (OS) [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.85-1.12], time to progression (HR, 0.95; 95% CI, 0.80-1.12) and overall response rate (ORR) [odds ratio (OR), 1.06; 95% CI, 0.72-1.55] of patients in the SBCT group indicated no statistical significance when compared with those in the CBCT group. Furthermore, for ACRC, a pooled analysis demonstrated no significant difference between the SBCT and CBCT groups (OS: HR, 0.82; 95% CI, 0.61-1.10; progression-free survival: HR, 0.79; 95% CI=0.60-1.04; ORR: OR, 1.27; 95% CI, 0.91-1.78). The statistically significant differences identified in the overall meta-analysis indicated a low incidence of grade 3-4 hand-foot-syndrome (OR, 0.15; 95% CI, 0.06-0.36) in the SBCT group; however no statistically significant difference was observed in the incidence of grade 3-4 anemia, thrombocytopenia, leucopenia, neutropenia, diarrhea, stomatitis or nausea/vomiting. The SBCT treatment exhibited similar efficacy and an approximately equivalent safety profile compared with the CBCT treatment and was an alternative to CBCT for patients with AGC or ACRC; however, further investigation is required to provide confirmation.

Ameliorative effects of diammonium glycyrrhizinate on inflammation in focal cerebral ischemic-reperfusion injury.

The present study investigated the neuroprotective potential of Diammonium Glycyrrhizinate (DG) in focal cerebral ischemic-reperfusion (IR) injury in mice. The middle cerebral artery occlusion (MCAO) model of the mouse was used. Mice were treated with DG (20mg/kg per day, intraperitoneal injection) or saline as control, from the beginning of the reperfusion to 7 days. The focal cerebral IR injury resulted in significant neurological deficits, infarct size, and brain water content (BWC) at 1 day, 3 days and 7 days after MCAO. A significant increase in various inflammatory mediators like interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) and astrocytic glial fibrillary acidic protein (GFAP) was also observed in the IR challenged brains. The DG treatment significantly improved neurofunction, decreased infarct size, and suppressed edema in the focal cerebral IR injury. The neuroprotective effect of DG was found to be associated with significant reduction in the IL-1, TNF-α, COX-2, iNOS, NF-κB and GFAP levels. In summary, this study suggested that DG has a neuroprotective effect on cerebral IR injury and this effect is likely related to DG's anti-inflammatory function.

Bietti crystalline dystrophy with bilateral macular holes.

OBJECTIVE: Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. DESIGN: Case report and literature review. RESULTS: Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. CONCLUSION: Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear.

[Dose-effect relationship of para-toluenesulfonamide for treatment of hepatocellular carcinoma in rats].

OBJECTIVE: To investigate the dose-effect relationship of para-toluenesulfonamide (PTS) for treatment of hepatocellular carcinoma in rats. METHODS: Forty-two SD rats bearing subcutaneous transplanted hepatocellular carcinoma were randomly divided into 6 groups (n=7), in which 0.02, 0.04, 0.06, 0.08, and 0.10 ml PTS and 0.10 ml normal saline were injected into the tumor, respectively. All of the rats were executed 24 h after the injection to observe the pathological changes in the tumor. RESULTS: In rats with saline injection, the tumor tissues exhibited no obvious changes and the tumor cells retained the active proliferation. PTS, in contrast, caused coagulation necrosis of the tumor tissue, and the necrotic area expanded with the increase of the injected doses. The necrotic volume of the tumor was in roughly linear correlation with the dose of PTS injected, with the linear regression equation of V (cm(3))=-0.018+2.595Y (where V represents tumor necrosis volume, and Y the injected dose of PTS). CONCLUSION: The dose-effect relationship of PTS is roughly linear, and the PTS dose for injection can be estimated according to the diameter of the tumor.

[Association of single nucleotide polymorphism at interleukin-10 gene 1082 nt with the risk of gastric cancer in Chinese population].

OBJECTIVE: To study the association of single nucleotide polymorphism at interleukin-10 gene 1082 locus with Helicobacter pylori (Hp) infection and the risk of gastric cancer in high prevalent region (Shaanxi Province)aand low prevalence region (Guangdong Province) in China. METHODS: The genomic DNA was extracted from the peripheral blood of 104 healthy individuals, 104 gastric cancer patients from Guangdong Province, and from 102 healthy volunteers and 102 gastric cancer patients in Shaanxi Province, China. The single nucleotide polymorphism at IL-10 gene 1082 locus was analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The serum levels of anit-Hp IgG was measured by enzyme-linked immunosorbent assay. RESULTS: The frequencies of IL-10-1082 A/A, A/G and G/G genotypes in the 412 subjects were 86.7%, 10.7% and 2.4%, respectively. In the low prevalence region, the number of carriers of IL-10-1082 G* was much greater in the cancer patients than in the healthy controls (14.4% vs 7.7%, Chi2=4.02, P<0.05, OR=1.01, 95% CI=1.08-3.10). The presence of IL-10-1082 G* was associated with significantly increased risk of gastric cancer following Hp infection (Chi(2)=5.36, P<0.05, OR=6.0, 95% CI=1.23-17.52). In the high prevalence region, the frequency of IL-10-1082 G* was slightly higher among the cancer patients than in the healthy controls, but this difference was not statistically significant (12.7% vs 16.6%, P>0.05). CONCLUSION: The G* genotype of IL-10 gene 1082 locus may be associated with increased risk of gastric cancer in China.