Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion

Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet. Mechanistically, TBC1D1 is located on insulin-like growth factor 1 (IGF1) storage vesicles, and the KI mutation increases endocrinal and paracrinal/autocrinal IGF1 secretion in an Rab8a-dependent manner. Hypersecretion of IGF1 causes increased expression of lipogenic genes via activating the protein kinase B (PKB; also known as Akt)–mammalian target of rapamycin (mTOR) pathway in adipose tissues, which contributes to the development of obesity, diabetes, and hepatic steatosis as the KI mice age. Collectively, these findings demonstrate that the AMPK–TBC1D1 signaling nexus interacts with the PKB–mTOR pathway via IGF1 secretion, which consequently controls expression of lipogenic genes in the adipose tissue. These findings also have implications for drug discovery to combat obesity

Prospective evaluation of a rapid clinical metagenomics test for bacterial pneumonia

Background: The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.  Objectives: To evaluate the clinical performance of a rapid nanopore-sequencing based metagenomics test for diagnosis of bacterial pathogens in common LRIs through a large-scale prospective study.  Methods: We enrolled 292 hospitalized patients suspected to have LRIs between November 2018 and June 2019 in a single-center, prospective cohort study. Rapid clinical metagenomics test was performed on-site, and the results were compared with those of routine microbiology tests.  Results: 171 bronchoalveolar lavage fluid (BAL) and 121 sputum samples were collected from patients with six kinds of LRIs. The turnaround time (from sample registration to result) for the rapid metagenomics test was 6.4 ± 1.4 hours, compared to 94.8 ± 34.9 hours for routine culture. Compared with culture and real-time PCR validation tests, rapid metagenomics achieved 96.6% sensitivity and 88.0% specificity and identified pathogens in 63 out of 161 (39.1%) culture-negative samples. Correlation between enriched anaerobes and lung abscess was observed by Gene Set Enrichment Analysis. Moreover, 38 anaerobic species failed in culture was identified by metagenomics sequencing. The hypothetical impact of metagenomics test proposed antibiotic de-escalation in 34 patients compared to 1 using routine culture.  Conclusions: Rapid clinical metagenomics test improved pathogen detection yield in the diagnosis of LRI. Empirical antimicrobial therapy could be de-escalated if rapid metagenomics test results were hypothetically applied to clinical management

Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives

A new series of 2-(5-methyl-2,3-dioxoindolin-1-yl)acetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ)-evoked convulsion model and antidepressant activity in the forced swimming test (FST) model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q) showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine

The Impact of Harvesting Mechanization on Oolong Tea Quality

Mechanization is the inevitable future of tea harvesting, but its impact on tea chemistry and quality remains uncertain. Our study examines untargeted metabolomic data from 185 oolong tea products (Tieguanyin) made from leaves harvested by hand or machine based on UPLC-QToF-MS analysis. The data revealed a minimum 50% loss for over half of the chemicals in the machine-harvested group, including catechins, theaflavin, gallic acid, chlorogenic acid, and kaempferol-3-gluocside. Integrating sensory evaluation, OPLS-DA identified the six most important metabolites as significant contributors to sensory decline caused by harvesting mechanization. Furthermore, our research validates the possibility of using DD-SIMCA modelling with untargeted metabolomic data for distinguishing handpicked from machine-harvested tea products. The model was able to achieve 93% accuracy. This study provides crucial insights into the chemical and sensory shifts during mechanization, along with tools to manage and monitor these changes

Rheological Properties, Drug Release Behavior and Cytocompatibility of Novel Hydrogels Prepared from Carboxymethyl Chitosan

International audienc

Identification and Comparative Analysis of CBS Domain-Containing Proteins in Soybean (Glycine max) and the Primary Function of GmCBS21 in Enhanced Tolerance to Low Nitrogen Stress

Nitrogen is an important macronutrient required for plant growth, and is a limiting factor for crop productivity. Improving the nitrogen use efficiency (NUE) is therefore crucial. At present, the NUE mechanism is unclear and information on the genes associated with NUE in soybeans is lacking. cystathionine beta synthase (CBS) domain-containing proteins (CDCPs) may be implicated in abiotic stress tolerance in plants. We identified and classified a CBS domain–containing protein superfamily in soybean. A candidate gene for NUE, GmCBS21, was identified. GmCBS21 gene characteristics, the temporal expression pattern of the GmCBS21 gene, and the phenotype of GmCBS21 overexpression in transgenic Arabidopsis thaliana under low nitrogen stress were analyzed. The phenotypes suggested that the transgenic Arabidopsis thaliana seedlings performed better under the nitrogen-deficient condition. GmCBS21-overexpressing transgenic plants exhibit higher low nitrogen stress tolerance than WT plants, and this suggests its role in low nitrogen stress tolerance in plants. We conclude that GmCBS21 may serve as an excellent candidate for breeding crops with enhanced NUE and better yield

Expression pattern of GmLAX genes under different stresses in soybean drought sensitive cultivar and tolerant cultivar

Auxin has been reported to regulate plant growth and development, as well as to mediate plant adaption to abiotic stresses, including drought. AUX/LAX family displays auxin uptake functions and comprises four highly conserved genes AUX1 and LIKE AUX1 (LAX1, LAX2, and LAX3) in Arabidopsis. There are fifteen GmLAX family genes in the soybean genomes and several members were regulated by dehydration stress. In this study, the sequence differences and expression pattern of GmLAXs-I were analyzed under stress treatment between the soybean drought-tolerant Jindou 21 and drought-sensitive varieties Zhongdou 33. Five homologous genes of AUX1 were all responsive to PEG, salt, ABA and IAA stimuli. There were two SNPs in the promoter region of GmLAX4 gene, and this gene was differentially expressed in two cultivars. Moreover, our results showed YFP-GmLAXs are predominantly localized in plasma membrane. Taken together, our results suggest that GmLAXs are involved in abiotic response, which can provide theoretical and technical support for the genetic improvement of soybean drought tolerance