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

Genome-Wide Characterization and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Cinnamomum camphora ('Gantong 1')

Cinnamomum camphora is one of the most commonly used tree species in landscaping. Improving its ornamental traits, particularly bark and leaf colors, is one of the key breeding goals. The basic helix-loop-helix (bHLH) transcription factors (TFs) are crucial in controlling anthocyanin biosynthesis in many plants. However, their role in C. camphora remains largely unknown. In this study, we identified 150 bHLH TFs (CcbHLHs) using natural mutant C. camphora 'Gantong 1', which has unusual bark and leaf colors. Phylogenetic analysis revealed that 150 CcbHLHs were divided into 26 subfamilies which shared similar gene structures and conserved motifs. According to the protein homology analysis, we identified four candidate CcbHLHs that were highly conserved compared to the TT8 protein in A. thaliana. These TFs are potentially involved in anthocyanin biosynthesis in C. camphora. RNA-seq analysis revealed specific expression patterns of CcbHLHs in different tissue types. Furthermore, we verified expression patterns of seven CcbHLHs (CcbHLH001, CcbHLH015, CcbHLH017, CcbHLH022, CcbHLH101, CcbHLH118, and CcbHLH134) in various tissue types at different growth stages using qRT-PCR. This study opens a new avenue for subsequent research on anthocyanin biosynthesis regulated by CcbHLH TFs in C. camphora

Improved Estimation of the Gross Primary Production of Europe by Considering the Spatial and Temporal Changes in Photosynthetic Capacity from 2001 to 2016

The value of leaf photosynthetic capacity (Vcmax) varies with time and space, but state-of-the-art terrestrial biosphere models rarely include such Vcmax variability, hindering the accuracy of carbon cycle estimations on a large scale. In particular, while the European terrestrial ecosystem is particularly sensitive to climate change, current estimates of gross primary production (GPP) in Europe are subject to significant uncertainties (2.5 to 8.7 Pg C yr−1). This study applied a process-based Farquhar GPP model (FGM) to improve GPP estimation by introducing a spatially and temporally explicit Vcmax derived from the satellite-based leaf chlorophyll content (LCC) on two scales: across multiple eddy covariance tower sites and on the regional scale. Across the 19 EuroFLUX sites selected for independent model validation based on 9 plant functional types (PFTs), relative to the biome-specific Vcmax, the inclusion of the LCC-derived Vcmax improved the model estimates of GPP, with the coefficient of determination (R2) increased by 23% and the root mean square error (RMSE) decreased by 25%. Vcmax values are typically parameterized with PFT-specific Vcmax calibrated from flux tower observations or empirical Vcmax based on the TRY database (which includes 723 data points derived from Vcmax field measurements). On the regional scale, compared with GPP, using the LCC-derived Vcmax, the conventional method of fixing Vcmax using the calibrated Vcmax or TRY-based Vcmax overestimated the annual GPP of Europe by 0.5 to 2.9 Pg C yr−1 or 5 to 31% and overestimated the interannually increasing GPP trend by 0.007 to 0.01 Pg C yr−2 or 14 to 20%, respectively. The spatial pattern and interannual change trend of the European GPP estimated by the improved FGM showed general consistency with the existing studies, while our estimates indicated that the European terrestrial ecosystem (including part of Russia) had higher carbon assimilation potential (9.4 Pg C yr−1). Our study highlighted the urgent need to develop spatially and temporally consistent Vcmax products with a high accuracy so as to reduce uncertainties in global carbon modeling and improve our understanding of how terrestrial ecosystems respond to climate change

Analysis of Patents Issued in China for Antihyperglycemic Therapies for Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is prevalent, with a dramatic increase in recent years. Moreover, its microvascular and macrovascular complications cause significant societal issues. The demand for new and effective antidiabetic therapies grows with each passing day and motivates organizations and individuals to pay more attention to such products. In this article, we focused on oral antihyperglycemic drugs patented in China and introduced them according to their antihyperglycemic mechanisms. By searching the website of State Intellectual Property Office of the People’s Republic of China (http://www.sipo.gov.cn), 2,500 antihyperglycemic patents for T2DM were identified and analyzed. These consisted of 4 patents for derivatives of herbal extracts (0.2%), 162 patents for herbal extracts (6.5%), 61 compositions for traditional Chinese medicine (TCM) (2.4%), 2,263 patents for synthetic compounds (90.5%), and 10 (0.4%) patents of the combination of synthetic compounds and TCM. As the most common drugs for diabetes mellitus, synthetic compounds can also be classified into several categories according to their working mechanisms, such as insulin secretion promotor agents, insulin sensitizer agents, α-glucosidase inhibitors, and so forth. This article discussed the chemical structure, potential antihyperglycemic mechanism of these antihyperglycemic drugs in patents in China.Expert opinion: Insulin sensitivity and β-cell function could be improved by weight loss to prevent prediabetes into T2DM. However, 40–50% patients with impaired glucose tolerance (IGT) still progress to T2DM, even after successful long-term weight loss.Antihyperglycemic remedies provide a treatment option to improve insulin sensitivity and maintain β-cell function. Combination therapy is the best treatment for diabetes. Combination therapy can reduce the dosage of each single drug option, and avoid the side effects. Drugs with different mechanisms are complementary, and are better adapted to patients with changing conditions. Classical combination therapies include combinations such as sulfonylureas plus biguanides or glucosidase inhibitors, biguanide plus glucosidase inhibitors or insulin sensitizers, insulin treatment plus biguanides or glucosidase inhibitors. The general principle of combination therapy is that two drugs with different mechanisms are selected jointly, and the combination of three types of hypoglycemic drugs is not recommended. After reading a large amount of literature, we have rarely found a case of three oral hypoglycemic agents, which may mean that the combination of three oral hypoglycemic agents is unnecessary and has unpredictable risks. There is no objection to the idea of multi-drug therapy. But multiple drugs can only be used when it shows a significant benefit to the patients. Combined use of multiple antidiabetic drugs poses a risk to patients due to drug interactions and overtreatment

Dye-enhanced graphene oxide for photothermal therapy and photoacoustic imaging

National Basic Research Program of China [2010CB732403]; National Natural Science Foundation of China [21125524, 20975023]; Program for New Century Excellent Talents in the University of China [09-0014]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1116]; National Science Foundation of Fujian Province [2010J06003]Graphene oxide (GO) has many exciting advantages such as easy preparation, low toxicity, good solubility and stability in aqueous solution. However, GO itself has a low near-infrared (NIR) absorption, and thus is not suitable for photothermal therapy and photoacoustic imaging. To overcome this limitation, a novel dye-enhanced GO is prepared utilizing the pi-pi stacking interactions between GO and indocyanine green (ICG). The ICG-GO complex has a high optical absorbance in the NIR region and exhibits excellent photothermal properties under NIR irradiation. In order to improve the cancer-targeting activity, GO was modified with folic acid (FA). In vitro experiments showed that the ICG-GO-FA nanocomposite could be used for targeted photothermal cancer cell destruction. Moreover, the application of the ICG-GO-FA nanocomposite for photoacoustic imaging was also demonstrated