Fat body and cardiomyocyte apoLpp regulate systemic lipid metabolism differently on normal food diet and high fat diet.

<p>(A) Whole-body TG levels of newly-eclosed flies with <i>Gal4</i> driver only (control) or with fat body-specific knockdown of <i>apoLpp</i> using <i>ppl-Gal4</i> (A) on NFD (blue) or HFD (red). (B, C) Whole-body TG levels of newly-eclosed flies with <i>Gal4</i> drivers only (controls) or with cardiomyocyte-specific knockdown of <i>apoLpp</i> using <i>Hand-Gal4</i> (B), or <i>TinC-Gal4</i> (C) on NFD (blue) or HFD (red). (D) RT-PCR analysis of <i>mtp</i> mRNA levels in whole flies with <i>Arm-Gal4</i> driver only (control) or with <i>Arm-Gal4</i>-induced overexpression of full-length <i>mtp</i> (<i>mtp</i>^<i>+</i>). Actin serves as an internal control. (E) Whole-body TG levels of newly-eclosed flies with <i>Gal4</i> driver only (control), with cardiomyocyte-specific overexpression of <i>mtp</i>^<i>+</i> using <i>TinC-Gal4</i>, or with cardiomyocyte-specific overexpression of <i>mtp</i>^<i>+</i> and <i>apoLppRNAi</i> using <i>TinC-Gal4</i> on NFD (blue) or HFD (red). In A-C and E, TG levels (μg/μl) were normalized to total protein (μg/μl). Results are expressed as the fold change in whole fly normalized TG compared with that of the <i>Gal4</i> control flies on NFD (set to 1.0). Results are the mean ± SEM of the indicated number of flies (N) analyzed over at least 5 independent experiments. <i>P</i>-values are from Student’s <i>t</i>-test and are between <i>Gal4</i> control and <i>Gal4</i>-mediated RNAi lines within NFD or HFD, or between NFD and HFD for the same genotype.</p

Genetic screening identifies Mtp as a gene for determining systemic lipid metabolism.

<p>(A) Schematic of the results of the genetic screen showing the location of the <i>mtp</i> gene (blue symbol) on chromosome 2L. Red bars indicate deletions in the three deficiency lines investigated here: <i>Df(2L)ED1378</i>, <i>Df(2L)BSC333</i>, and <i>Df(2L)Exel7080</i>. (B) Whole-body TG levels of newly eclosed control (<i>w</i>^<i>1118</i>) flies and deficiency lines on NFD or HFD. For each genotype, a 1:1 ratio of males:females was analyzed. <i>P</i>-values are from Student’s <i>t</i>-test and are between control <i>w</i>^<i>1118</i> and deficiency lines within NFD or HFD, or between NFD and HFD for the same genotype. (C) Whole-body TG levels of newly eclosed control flies (<i>Arm-Gal4</i>), and flies with whole-body KD of <i>mtp</i> (<i>Arm-Gal4>mtp</i>^<i>RNAi</i>) on NFD and HFD. For each genotype, a 1:1 ratio of males:females was analyzed. <i>P</i>-values are from Student’s <i>t</i>-test and are between <i>Gal4</i> control and <i>Gal4</i>-mediated RNAi lines within NFD or HFD, or between NFD and HFD for the same genotype. (D) Whole-body TG levels of newly eclosed control flies (<i>Da-Gal4</i>), and flies with whole-body KD of <i>mtp</i> (<i>Da-Gal4>mtp</i>^<i>RNAi</i>) on NFD and HFD. For each genotype, a 1:1 ratio of males:females was analyzed. <i>P</i>-values are from Student’s <i>t</i>-test and are between <i>Gal4</i> control and <i>Gal4</i>-mediated RNAi lines within NFD or HFD, or between NFD and HFD for the same genotype. In (B), (C) and (D), TG levels (μg/μl) were normalized to total protein (μg/μl). Results are expressed as the fold change in whole fly normalized TG compared with that of the wild-type <i>w</i>^<i>1118</i> or <i>Gal4</i> control flies on NFD (set to 1.0). Results are the mean ± SEM of the indicated number of flies (N) analyzed over at least 5 independent experiments. (E) Colorimetric assay of food intake in control <i>w</i>^<i>1118</i> third instar larvae and third instar larvae with <i>Gal4</i> driver only (<i>Arm-Gal4</i>) or with whole body knockdown of <i>mtp</i> using <i>Arm-Gal4</i> (<i>Arm-Gal4>mtp</i>^<i>RNAi</i>). Results are the mean ± SEM of the indicated number of larvae (N) analyzed over 3 independent experiments. <i>P</i>-values are from Student’s <i>t</i>-test.</p

Identification of Small Molecules That Protect Pancreatic β Cells against Endoplasmic Reticulum Stress-Induced Cell Death

Endoplasmic reticulum (ER) stress plays an important role in the decline in pancreatic β cell function and mass observed in type 2 diabetes. Here, we developed a novel β cell-based high-throughput screening assay to identify small molecules that protect β cells against ER stress-induced cell death. Mouse βTC6 cells were treated with the ER stressor tunicamycin to induce ER stress, and cell death was measured as a reduction in cellular ATP. A collection of 17600 compounds was screened for molecules that promote β cell survival. Of the approximately 80 positive hits, two selected compounds were able to increase the survival of human primary β cells and rodent β cell lines subjected to ER stressors including palmitate, a free fatty acid of pathological relevance to diabetes. These compounds also restored ER stress-impaired glucose-stimulated insulin secretion responses. We show that the compounds promote β cell survival by reducing the expression of key genes of the unfolded protein response and apoptosis, thus alleviating ER stress. Identification of small molecules that prevent ER stress-induced β cell dysfunction and death may provide a new modality for the treatment of diabetes

Discovery of a Benzamide Derivative That Protects Pancreatic β‑Cells against Endoplasmic Reticulum Stress

Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing β-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of β-cell protective agents against ER stress-induced dysfunction and death. Through structure–activity relationship optimization, a 3-(<i>N</i>-piperidinyl)­methylbenzamide derivative <b>13d</b> markedly protects β-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC₅₀ of 0.032 μM. Compound <b>13d</b> alleviates ER stress in β-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that <b>13d</b> significantly lowers blood glucose levels and increases concomitant β-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of β-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes

DataSheet1_Social network and villagers’ willingness to adopt residential rooftop PV products: A multiple mediating model based on TAM/PR theory.pdf

Facing the promise of “carbon neutrality” and “carbon peak”, China’s vast rural areas will be the main front of energy conservation and emission reduction in the future. From the perspective of social capital, this paper combined TAM and perceived risk theory to construct a hypothesis model. Based on 617 rural survey data, structural equation model was used to reveal the influencing factors of the willingness to adopt residential rooftop PV products in rural China. The results show that: 1) social network has a significant impact on the willingness of villagers to adopt rooftop PV products. 2) Perceived usefulness, perceived ease of use and perceived risk play multiple mediating roles. 3) The parallel mediating effect of villagers’ perceived risk on the relationship between social network and adoption intention is much higher than the other two paths. 4) The chain mediating effect of perceived risk and perceived ease of use on the relationship between social network and villagers’ adoption intention is much higher than the other two paths. This study provides rich policy implications for rural renewable energy promotion and energy transition in China and other developing countries.</p

Table_2_The combination of a seven-autoantibody panel with computed tomography scanning can enhance the diagnostic efficiency of non-small cell lung cancer.docx

BackgroundNon-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC.MethodsWe retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel.ResultsThe strategy of a “both-positive rule” combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (PConclusionThis study shows that combination of a 7-AAB panel with CT has can significantly enhance the diagnostic efficiency of lung cancer. Moreover, the 7-AAB panel also has potential prognostic value and has reference significance for the formulation of the treatment plan.</p

Table_1_The combination of a seven-autoantibody panel with computed tomography scanning can enhance the diagnostic efficiency of non-small cell lung cancer.docx

BackgroundNon-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC.MethodsWe retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel.ResultsThe strategy of a “both-positive rule” combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (PConclusionThis study shows that combination of a 7-AAB panel with CT has can significantly enhance the diagnostic efficiency of lung cancer. Moreover, the 7-AAB panel also has potential prognostic value and has reference significance for the formulation of the treatment plan.</p