Genome-directed discovery of antiproliferative bafilomycins from a deepsea-derived Streptomyces samsunensis.

Genomic bioinformatics analysis identified a bafilomycin biosynthetic gene cluster (named bfl) in the deepsea-derived S. samsunensis OUCT16-12, from which two new (1 and 2, named bafilomycins R and S) along with four known (3-6) bafilomycins were targetly obtained. The structure of 3 was clearly identified for the first time, thus named bafilomycin T herein. Differ from the fumarate substitution at C-21 of known bafilomycins, its location on C-23 is a unique feature of 1 and 2. The stereochemistry of the compounds was established based on NOE correlations, ketoreductase (KR)-types in PKS modules of bfl, and ECD calculations. Moreover, a detailed biosynthetic model of 1-6 in S. samsunensis OUCT16-12 was provided based on the gene function prediction and sequence identity. Compared with the positive control doxorubicin, 1-6 showed more potent antiproliferative activities against drug-resistant lung cancer cell line A549-Taxol, with IC50 values ranging from 0.07 µM to 1.79 µM, which arrested cell cycle in G0/G1 phase to hinder proliferation.

New Olimycins from a Cold-Seep-Derived Streptomyces olivaceus.

Cold-seeps are areas of the ocean floor in which hydrogen sulfide and methane are released into the open water. The cold-seep microbes are an emerging source of novel bioactive natural products. Four new ansa-ring opened linear ansamycin analogues, named olimycins E-H (1-4) were isolated from the cold-seep-derived Streptomyces olivaceus OUCLQ19-3. The planar and stereochemical structures of the isolated compounds were elucidated based on extensive MS and NMR spectroscopic analyses together with ECD calculations.

Electroacupuncture Ameliorates Cognitive Impairment by Regulating γ-Amino Butyric Acidergic Interneurons in the Hippocampus of 5 Familial Alzheimer's Disease Mice.

OBJECTIVES: γ-amino butyric acid (GABA)-ergic dysfunction in excitatory and inhibitory (E/I) imbalance drives the pathogenesis of Alzheimer's disease (AD). Inhibitory interneurons play an important role in the regulation of E/I balance, synaptic transmission, and network oscillation through manipulation of GABAergic functions, showing positive outcomes in AD animal models. Mice expressing 5 familial AD mutation (5xFAD) exhibited a series of AD-like pathology and learning and memory deficits with age. Because electroacupuncture (EA) treatment has been used for a complementary alternative medicine therapy in patients with AD, we aimed to examine any usefulness of EA therapy in GABA interneuron function and its associated synaptic proteins, to determine whether EA could effectively improve inhibitory transmission and network oscillation and eventually alleviate cognitive impairments in 5xFAD mice, and to further elucidate the GABAergic system function underlying the antidementia response of EA. MATERIALS AND METHODS: 5xFAD mice were used to evaluate the potential neuroprotective effect of electroacupuncture at Baihui (DU 20) and Dazhui (DU 14) through behavioral testing, immunofluorescence staining, electrophysiology recording, and molecular biology analysis. RESULTS: First, we observed that EA improved memory deficits and inhibitory synaptic protein expression. Second, EA treatment alleviated the decrease of somatostatin-positive interneurons in the dorsal hippocampus. Third, EA attenuated E/I imbalance in 5xFAD mice. Last, EA treatment enhanced theta and gamma oscillation in the hippocampus of 5xFAD mice. CONCLUSIONS: EA stimulation at DU20 and DU14 acupoints may be a potential alternative therapy to ameliorate cognitive deficits in AD through the regulation of the function of the GABAergic interneuron.

Acupuncture for swallowing disorder after recovery from COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: Swallowing disorder is a common sequela after recovery from COVID-19. Acupuncture is an important traditional therapy for treating swallowing disorder. However, the efficacy of acupuncture for swallowing disorder after recovery from COVID-19 lacks evidence-based medicine. METHODS: All randomized controlled trials of acupuncture for swallowing disorder after recovery from COVID-19 will be retrieved and collected from December 2019 to November 2022 with no language restrictions. PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, Chinese Biomedical Database, Chinese Science and Technology Journal Database (VIP), and the Wanfang Database will be searched. Two researchers will independently select studies, extract data, and evaluate study quality. The Cochrane risk of bias tool for randomized trials will be used to assess the risk of bias in the included studies. Statistical analyses will be performed using Review Manager version 5.3. RESULTS: This study will provide a high-quality and convincing assessment of the efficacy and safety of acupuncture for swallowing disorder after recovery from COVID-19 and will be published in peer-reviewed journals. CONCLUSION: Our findings will provide a reference for future clinical decisions and guidance development.

Acupuncture for dry eye disease after recovery from COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Dry eye disease (DED) is a condition occurring worldwide. Studies have found that coronavirus disease 2019 (COVID-19) patients may have persistent dry eye symptoms for weeks and months after recovery, and the prevalence of dry eye is higher in COVID-19 patients than in people without COVID-19 infection. As one of the common ophthalmic diseases, the clinical application of acupuncture in the treatment of DED is not widely used nowadays. METHODS: According to the retrieval strategies, randomized controlled trials (RCT) on the acupuncture for DED after recovery from COVID-19 were obtained from Embase, The Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure database, Chinese Biomedical Database, Chinese Science and Technology Periodical database, The WanFang database. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.3) and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: The study will provide a high-quality and convincing assessment of the efficacy and safety of acupuncture for DED after recovery from COVID-19 and will be published in peer-reviewed journals. CONCLUSION: Our findings will provide references for future clinical decision and guidance development.

Pocket Dietitian: Automated Healthy Dish Recommendations by Location.

A root cause of chronic disease is a lack of timely informed decision power in everyday lifestyle choices, such as in diets. Users are unable to clearly delineate and demand healthy food in a quantitative manner. To scale the benefit of health nutrition coaching in broad real-world scenarios, we need a technological solution that is constantly able to interpret nutrition information. We ingest nutritional facts about products to efficiently calculate which items are healthiest. We deliver these results to users based on their location context. Our ranking algorithm outperforms major nutrition score metrics, and is more consistent than human dietitians in real world scenarios. Most importantly, our system gives the user a rapid way to connect with healthy food in their vicinity, reducing the barriers to a healthy diet.