Harnessing the benefits of physical exercise-induced melatonin: a potential promising approach to combat Alzheimer's disease by targeting beta-amyloid (Aß).

Alzheimer's disease (AD) is a chronic neurogenerative disease that impairs cognition, learning, behavior, and memory. The aberrant accumulation of extracellular amyloid-ß (Aß) plaques is a characteristic of AD. It has been demonstrated that melatonin exerts a significant role in AD prevention and treatment via its antioxidant effects, reducing neuroinflammation, and Aß. Moreover, studies have shown that physical exercise (PE) is not only a promising non-pharmacological strategy for AD prevention and treatment but can also lead to an increase in melatonin levels. Hence, we hypothesized that PE can contribute to AD prevention and treatment by increasing melatonin levels and reducing Aß accumulation, enhancing Aß clearance, and modulating inflammation in these patients. However, the mechanisms by which PE increases melatonin synthesis and the cellular and molecular mechanisms of actions of melatonin in AD prevention and treatment have not to date been completely understood. Therefore, in the future, further investigations are required to elucidate the underlying mechanisms, optimize intervention strategies, identify biomarkers, and validate findings through clinical trials. Understanding the potential of exercise-induced melatonin in AD holds promise for innovative therapeutic interventions and future directions in AD research.

Constructing a interfacial electric field for efficient reduction of nitrogen to ammonia.

Electrochemical nitrogen reduction (eNRR) is a cost-effective and environmentally sustainable approach for ammonia production. MoS2, as a typical layered transition metal compound, holds significant potential as an electrocatalyst for the eNRR. Nevertheless, it suffers from a limited number of active sites and low electron transfer efficiency. In this study, we constructed a heterostructure by depositing SnO2 (an n-type semiconductor) nanoparticles on MoS2 (a p-type semiconductor). This unique interfacial structure not only generates abundant interfacial contacts but also facilitates the transfer of electrons from SnO2 to MoS2, leading to the formation of an interfacial electric field. Theoretical calculations demonstrate that this electric field increases the number of active electrons, facilitating N2 adsorption and NN bond activation. Moreover, it increases the degree of orbital overlap between N2 and SnO2/MoS2, effectively reducing the energy barrier of the rate-determining step. Benefiting from the interfacial electric field effect, the SnO2/MoS2 catalyst exhibits significant catalytic activity and selectivity towards eNRR, with an ammonia yield of 47.1 µg h-1 mg-1 and a Faraday efficiency of 19.3 %, surpassing those reported for the majority of MoS2- and SnO2-based catalysts.

Anti-Inflammatory and α-Glucosidase Inhibitory Triterpenoid with Diverse Carbon Skeletons from the Fruits of Rosa roxburghii.

The fruits of Rosa roxburghii Tratt. are edible nutritional food with high medicinal value and have been traditionally used as Chinese folk medicine for a long time. In this study, 26 triterpenoids including four new pentacyclic triterpenoids, roxbuterpenes A-D (1, 4, 5, and 24), along with 22 known analogues (2, 3, 6-23, 25, and 26), were isolated from the fruits of R. roxburghii. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, HRESIMS and NMR spectroscopy). The absolute configuration of roxbuterpene A (1) was determined by an X-ray crystallographic analysis. This is the first report of the crystal structure of 5/6/6/6/6-fused system pentacyclic triterpenoid. Notably, roxbuterpenes A and B (1 and 4) possessed the A-ring contracted triterpenoid and nortriterpenoid skeletons with a rare 5/6/6/6/6-fused system, respectively. Compounds 1-7, 11, 13-15, 18-20, 24, and 25 exhibited moderate or potent inhibitory activities against α-glucosidase. Compounds 2, 4, 6, 11, and 14 showed strong activities against α-glucosidase with IC50 values of 8.4 ± 1.6, 7.3 ± 2.2, 13.6 ± 1.4, 0.9 ± 0.4, and 12.5 ± 2.4 µM, respectively (positive control acarbose, 10.1 ± 0.8 µM). Compounds 13, 14, and 16 moderately inhibited the release of NO (nitric oxide) with IC50 values ranging from 25.1 ± 2.0 to 51.4 ± 3.1 µM. Furthermore, the expressions of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) were detected by ELISA (enzyme-linked immunosorbent assay), and compounds 13, 14, and 16 exhibited moderate inhibitory effects on TNF-α and IL-6 release in a dose-dependent manner ranging from 12.5 to 50 µM.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Grevillosides R-S: glucosides of 5-alkylresorcinol derivatives from roots of Ardisia crispa (Thunb.) A. DC.

Grevillosides R-S (1-2), two new glucosides of 5-alkylresorcinol derivatives, were isolated from the roots of Ardisia crispa (Thunb.) A. DC. The structures of grevillosides R-S (1-2) were determined by 1D and 2D NMR, HR-MS, UV, IR experiments and by comparison of their spectroscopic and physical data with literature values. In this paper, grevillosides R-S (1-2) were tested for their radical-scavenging activity (DPPH and ABTS) and α-glucosidase inhibitory activity in vitro. Grevillosides R-S (1-2) exhibited weak DPPH radical-scavenging activity with IC50 values of 72.3 and 485.2 µM, respectively. Grevillosides R-S (1-2) exhibited no inhibitory activity against α-glucosidase.

Characterisation and sequencing of the novel phage Abp95, which is effective against multi-genotypes of carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii has become one of the most challenging conditional pathogens in health facilities. It causes various infectious diseases in humans, such as wound or urinary tract infections and pneumonia. Phage therapy has been used as an alternative strategy for antibiotic-resistant A. baumannii infections and has been approved by several governments. Previously, we have reported two potential phage therapy candidates, Abp1 and Abp9, both of which are narrow-host-range phages. In the present study, we screened and isolated 22 A. baumannii bacteriophages from hospital sewage water and determined that Abp95 has a wide host range (29%; 58/200). The biological and genomic characteristics and anti-infection potential of Abp95 were also investigated. Abp95 belongs to the Myoviridae family, with a G+C content of 37.85% and a genome size of 43,176 bp. Its genome encodes 77 putative genes, none of which are virulence, lysogeny, or antibiotic resistance genes. Abp95 was found to accelerate wound healing in a diabetic mouse wound infection model by clearing local infections of multidrug-resistant A. baumannii. In conclusion, the lytic phage Abp95, which has a wide host range, demonstrates potential as a candidate for phage therapy against multiple sequence types of carbapenem-resistant A. baumannii.

CRISPRi-Mediated Gene Suppression Reveals Putative Reverse Transcriptase Gene PA0715 to Be a Global Regulator of Pseudomonas aeruginosa.

Purpose: Pseudomonas aeruginosa is a common pathogen of infection in burn and trauma patients, and multi-drug resistant P. aeruginosa has become an increasingly important pathogen. Essential genes are key to the development of novel antibiotics. The PA0715 gene is a novel unidentified essential gene that has attracted our interest as a potential antibiotic target. Our study aims to determine the exact role of PA0715 in cell physiology and bacterial pathogenicity, providing important clues for antibiotic development. Patients and Methods: The shuttle vector pHERD20T containing an arabinose inducible promoter was used to construct the CRISPRi system. Alterations in cellular physiology and bacterial pathogenicity of P. aeruginosa PAO1 after PA0715 inhibition were characterized. High-throughput RNA-seq was performed to gain more insight into the mechanisms by which PA0715 regulates the vital activity of P. aeruginosa. Results: We found that down-regulation of PA0715 significantly reduced PAO1 growth rate, motility and chemotaxis, antibiotic resistance, pyocyanin and biofilm production. In addition, PA0715 inhibition reduced the pathogenicity of PAO1 to the greater galleria mellonella larvae. Transcriptional profiling identified 1757 genes including those related to amino acid, carbohydrate, ketone body and organic salt metabolism, whose expression was directly or indirectly controlled by PA0715. Unexpectedly, genes involved in oxidative phosphorylation also varied with PA0715 levels, and these findings support a hitherto unrecognized critical role for PA0715 in oxidative respiration in P. aeruginosa. Conclusion: We identified PA0715 as a global regulator of the metabolic network that is indispensable for the survival and reproduction of P. aeruginosa. Our results provide a basis for future studies of potential antibiotic targets for P. aeruginosa and offer new ideas for P. aeruginosa infection control.

Simultaneous Recognition of Atrophic Gastritis and Intestinal Metaplasia on White Light Endoscopic Images Based on Convolutional Neural Networks: A Multicenter Study.

INTRODUCTION: Patients with atrophic gastritis (AG) or gastric intestinal metaplasia (GIM) have elevated risk of gastric adenocarcinoma. Endoscopic screening and surveillance have been implemented in high incidence countries. The study aimed to evaluate the accuracy of a deep convolutional neural network (CNN) for simultaneous recognition of AG and GIM. METHODS: Archived endoscopic white light images with corresponding gastric biopsies were collected from 14 hospitals located in different regions of China. Corresponding images by anatomic sites containing AG, GIM, and chronic non-AG were categorized using pathology reports. The participants were randomly assigned (8:1:1) to the training cohort for developing the CNN model (TResNet), the validation cohort for fine-tuning, and the test cohort for evaluating the diagnostic accuracy. The area under the curve (AUC), sensitivity, specificity, and accuracy with 95% confidence interval (CI) were calculated. RESULTS: A total of 7,037 endoscopic images from 2,741 participants were used to develop the CNN for recognition of AG and/or GIM. The AUC for recognizing AG was 0.98 (95% CI 0.97-0.99) with sensitivity, specificity, and accuracy of 96.2% (95% CI 94.2%-97.6%), 96.4% (95% CI 94.8%-97.9%), and 96.4% (95% CI 94.4%-97.8%), respectively. The AUC for recognizing GIM was 0.99 (95% CI 0.98-1.00) with sensitivity, specificity, and accuracy of 97.9% (95% CI 96.2%-98.9%), 97.5% (95% CI 95.8%-98.6%), and 97.6% (95% CI 95.8%-98.6%), respectively. DISCUSSION: CNN using endoscopic white light images achieved high diagnostic accuracy in recognizing AG and GIM.

Volatile Organic Compounds in Human Exhaled Breath to Diagnose Gastrointestinal Cancer: A Meta-Analysis.

INTRODUCTION: Human exhaled volatile organic compounds (VOCs) are being extensively studied for the purposes of noninvasive cancer diagnoses. This article was primarily to assess the feasibility of utilizing exhaled VOCs analysis for gastrointestinal cancer (GIC) diagnosis. METHODS: PRISMA-based system searches were conducted for related studies of exhaled VOCs in GIC diagnosis based on predetermined criteria. Relevant articles on colorectal cancer and gastroesophageal cancer were summarized, and meta analysis was performed on articles providing sensitivity and specificity data. RESULTS: From 2,227 articles, 14 were found to meet inclusion criteria, six of which were on colorectal cancer (CRC) and eight on Gastroesophageal cancer(GEC). Five articles could provide specific data of sensitivity and specificity in GEC, which were used for meta-analysis. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated based on the combination of these data, and were 85.0% [95% confidence interval (CI): 79.0%-90.0%], 89.0% (95%CI: 86.0%-91.0%), 41.30 (21.56-79.10), and 0.93, respectively. CONCLUSION: VOCs can distinguish gastrointestinal cancers from other gastrointestinal diseases, opening up a new avenue for the diagnosis and identification of gastrointestinal cancers, and the analysis of VOCs in exhaled breath has potential clinical application in screening. VOCs are promising tumor biomarkers for GIC diagnosis. Furthermore, limitations like the heterogeneity of diagnostic VOCs between studies should be minded.

Therapeutic Efficacy of the Combination Therapy of Corticosteroids and 5-Aminosalicylic Acid for Treatment of Pyoderma Gangrenosum with Ulcerative Colitis.

BACKGROUND: Pyoderma gangrenosum (PG) in inflammatory bowel disease (IBD) is a rare cutaneous condition and its treatment remains controversial due to limited data. AIMS AND OBJECTIVES: The purpose of this study was to investigate the characteristics and treatment response to specific therapies of IBD-associated PG. METHODS: In this retrospective study, we reviewed a series of cases of IBD-associated PG patients who presented at our institution, and collected clinical data, such as demographics, characteristics, subtype, and disease activity of IBD and specific therapies used and their treatment response. RESULTS: In total, 42 cases were identified: 69% female and 92.9% with ulcerative colitis (UC). At PG diagnosis, 93% had active and 7% inactive IBD. PG ulcers occurred predominantly on the legs (33.3%); 14.3% had multiple lesions. In total, 20/39 UC patients received the combination therapy of systemic corticosteroids and 5-aminosalicylic acid (5-ASA) with a good response in 19 patients (95%). Seven patients received the monotherapy of 5-ASA with a response rate of 43%. Five patients were successfully treated with systemic corticosteroids alone. Other patients were treated with intravenous immunoglobulin, infliximab, or cyclophosphamide alone or in combination with corticosteroids and all showed a good response. CONCLUSION: Our study indicates the therapeutic efficacy of corticosteroids in combination with 5-ASA, which may be considered as the first-line therapy for UC-associated PG.

The Diagnostic Accuracy of Conventional Forceps Biopsy Compared to ESD.

OBJECTIVE: conventional forceps biopsy (CFB) is the most popular way to screen for gastric epithelial neoplasia (GEN). Our study aimed to compare the diagnostic accuracy between conventional forceps biopsy and endoscopic submucosal dissection (ESD). METHODS: 105 patients diagnosed GEN finally undertook ESD in our hospital were enrolled. We retrospectively assessed the characteristics of pathological results of CFB and ESD. RESULTS: The overall pathologic concordance rate between the CFB and ESD specimens was 68.57%. 55 cases of CFB maintained low-grade intraepithelial neoplasia (LGIN) under ESD,18 cases (23.1%) diagnosis for high-grade intraepithelial neoplasia (HGIN), 5 cases (6.4%) diagnosis for cancer. Moreover, 10 cases of CFB maintained HGIN under ESD. Lesions with surface hyperemia (44.4% vs. 27.54%) or surface ulcer (57.14% vs.26.76%) were more likely to cancerate (P<0.05). CONCLUSION: endoscopic biopsy in the diagnosis of low-grade intraepithelial neoplasia, may exist or progression to high-grade intraepithelial neoplasia, some may have cancer, should take active treatment measures.

Epidemiological characterization of Acinetobacter baumannii bloodstream isolates from a Chinese Burn Institute: A three-year study.

Acinetobacter baumannii infection is a serious threat to burn patients. Bacteremia due to A. baumannii is becoming the most common cause of mortality following burn. However, the epidemiology of A. baumannii causing burn-related bloodstream infections has rarely been reported. We retrospectively collected 81 A. baumannii isolates from the bloodstream of burn patients over a three-year period. Antibiotic susceptibility tests, the prevalence of antibiotic-resistant genes and sequence typing (ST) were conducted to characterize these strains. Most of the isolates showed an extensive drug-resistant phenotype. The resistance frequencies to imipenem and meropenem were 94% and 91%, respectively. The blaOXA-23-like gene, AmpC, IS-AmpC, PER and SIM are the five most prevalent resistant genes, and their prevalence rates are 93% (75/81), 86% (70/81), 73% (59/81), 73% (59/81) and 52% (42/81), respectively. The 81 isolates were grouped into 10 known and 18 unknown ST types, with ST368 (38%) being the most prevalent. Except for ST457 and four new types (STn2, STn6, STn11 and STn14), the remaining 23 ST types belonged to one clonal complex 92, which is most common among clinical isolate in China. The above results indicated that ST368 isolates possessing both the blaOXA-23-like gene and ampC gene were the main culprits of the increasing nosocomial A. baumannii infection in this study. More attention should be paid to monitoring the molecular epidemiology of A. baumannii isolates from burn patients to prevent further distribution. Such information may help clinicians with therapeutic decisions and infection control in the Burns Institute.

[Investigation on mental health of residents living in a mineral area in Hubei province].

OBJECTIVE: To study the effect of mining operations on the mental health of residents living in a mining area in Hubei province. METHODS: Villagers (n = 93) living in the mining area were compared with a control group of residents (n = 101) in mental health status, and knowledge of environment and health. The mental health status of villagers was assessed using the Symptom Checklist 90 (SCL-90), State-Trait Anxiety Inventory (STAI); The knowledge of environment and health was evaluated using a self-designed questionnaire. The urine and hair samples were collected from some subjects. The lead, cadmium, arsenic, copper and zinc contents were detected as well as the total protein, NAG, d-ALA in the urine. RESULTS: The occurrence rate of lead, cadmium, arsenic exposure symptoms was significantly higher in the exposed group than in the control group. The urine cadmium, the hair cadmium, the hair arsenic and hair lead were significantly higher in the exposed group than in the control group (P < 0.05). The positive symptom detection rate of SCL-90 in the exposed group was 8.60% compared with 0.99% of the control group. For the SCL-90, the total scale, somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, paranoid ideation, psychoticism, other symptom in the exposed groups were significantly higher than those in the control group (P < 0.05), indicating the status of the psychological hygiene of the exposed group was worse than the control group. The total S-AI (anxiety) score and the sex-specific value in the exposed group were higher than the control group (P < 0.05, P < 0.01), which showed that the anxiety of the exposed group was more evident. The total T-AI score and the sex-specific value in women of the exposed group were significantly higher than the control group (P < 0.01), showing that the anxiety were more significant in the exposed group, especially the women of the exposed group. CONCLUSION: The mental health status of the residents who living in a mining area is affected and they have a higher S-AI and T-AI scale than those living a non-mining area.