SEIPIN Regulates Lipid Droplet Expansion and Adipocyte Development by Modulating the Activity of Glycerol-3-phosphate Acyltransferase

Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) is caused by loss-of-function mutations in SEIPIN, a protein implicated in both adipogenesis and lipid droplet expansion but whose molecular function remains obscure. Here, we identify physical and functional interactions between SEIPIN and microsomal isoforms of glycerol-3-phosphate acyltransferase (GPAT) in multiple organisms. Compared to controls, GPAT activity was elevated in SEIPIN-deficient cells and tissues and GPAT kinetic values were altered. Increased GPAT activity appears to underpin the block in adipogenesis and abnormal lipid droplet morphology associated with SEIPIN loss. Overexpression of Gpat3 blocked adipogenesis, and Gpat3 knockdown in SEIPIN-deficient preadipocytes partially restored differentiation. GPAT overexpression in yeast, preadipocytes, and fly salivary glands also formed supersized lipid droplets. Finally, pharmacological inhibition of GPAT in Seipin-/- mouse preadipocytes partially restored adipogenesis. These data identify SEIPIN as an evolutionarily conserved regulator of microsomal GPAT and suggest that GPAT inhibitors might be useful for the treatment of human BSCL2 patients

Effect of Transcutaneous Electrical Acupoint Stimulation on One-Lung Ventilation-Induced Lung Injury in Patients Undergoing Esophageal Cancer Operation

Objective. To investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) on one-lung ventilation-induced injury in patients undergoing esophageal cancer operation. Methods. The participants (n = 121) were randomly assigned into TEAS and sham groups. The TEAS group was given transcutaneous electrical stimulation therapy. The acupoints selected were Feishu (BL13), Hegu (L14), and Zusanli (ST36) and were treated 30 minutes before induction of anesthesia; treatment lasts 30 minutes. The sham group was connected to the electrode on the same acupoints, but electronic stimulation was not applied. The levels of oxygenation index (PaO2/FiO2) and alveolar-arterial oxygen tension difference (A-aDO2) before one-lung ventilation (T1), 30 minutes after one-lung ventilation (T2), 2 hours after one-lung ventilation (T3), and 1 hour after the operation (T4) and the levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) at T1, T2, T3, and 24 hours after the operation (T5) were taken as the primary endpoints. The incidence of postoperative pulmonary complications, removal time of thoracic drainage tube, and length of hospital stay were taken as the secondary endpoints. Results. Compared with that, in the sham group, the level of PaO2/FiO2 in the TEAS group was significantly increased at T2, T3, and T4, and the level of A-aDO2 was significantly reduced at T2 and T3 (P<0.05). Besides, compared with that, in the sham group, the level of serum TNF-α at T2, T3, and T5, as well as the level of serum IL-6 at T3 and T5, was significantly reduced, whereas the level of serum IL-10 at T3 was significantly increased (P<0.05). The incidences of pulmonary infection and pleural effusion in the TEAS group were significantly lower than that in the sham group, and the removal time of thoracic drainage tube and the length of hospital stay in the TEAS group were significantly shorter than that in the sham group (P<0.05). Conclusions. TEAS could effectively increase the levels of PaO2/FiO2 and IL-10, reduce the levels of A-aDO2, TNF-α, and IL-6, and reduce the incidence of pulmonary complications. Moreover, it could also contribute to shorten the removal time of thoracic drainage tube and the length of hospital stay

Antiobesity, Antidiabetic, Antioxidative, and Antihyperlipidemic Activities of Bioactive Seaweed Substances

Bioactive seaweed substances such as alginate, carrageenan, agar, fucoidan, polyphenols, polyunsaturated fatty acids, amino acids, and protein have many physiological functions. They have been widely used in consumer products such as functional foods, marine nutraceuticals, biomedical materials, cosmetics, and many other products that offer health benefits, which are unique and different to those obtained from other sources. This chapter summarizes the antiobesity, antidiabetic, antioxidative, and antihyperlipidemic activities of various bioactive seaweed substances

Randomized Efficacy Trial of Conventional, TCM Herb, and TEAS on Bone Marrow Suppression in Patients with Small Cell Lung Cancer after Initial Chemotherapy

Objective. To compare the efficiency of transcutaneous electrical acupoint stimulation (TEAS) with those of conventional and TCM herb on bone marrow suppression in small cell lung cancer (SCLC) patients after initial chemotherapy. Methods. We recruited 139 participants with pathologically confirmed SCLC who had not received chemotherapy. The conventional group (n = 37) received gemcitabine and cisplatin chemotherapy and routine care. The TCM herb group (n = 35) received 3 Diyushengbai tablets thrice a day for one day prior to chemotherapy and maintained during the trial. The TEAS group (n = 42) received TEAS at a frequency of 65–100 Hz with a pulse width of 100–200 μsec. Acupoints were selected from Dazhui (DU14), Geshu (BL17), Zusanli (ST36), Sanyinjiao (SP6), and Hegu (LI4) and were treated on days 1, 2, 3, 5, 8, 14, 21, and 28 of chemotherapy for 30 min each day. All three groups underwent a 28-day treatment for a total of one treatment course. Changes in the white blood cell, neutrophil, platelet, and hemoglobin indices on day 1 before chemotherapy and days 5, 8, 11, 14, 21, and 28 days after chemotherapy were compared among the groups. Comfort levels of patients on day 1 before chemotherapy and days 5, 11, and 21 after chemotherapy were observed. Results. Compared with the conventional group, the white blood cell counts in the TEAS group on days 8 (7.07 ± 2.11 vs. 5.97 ± 2.10 × 109/L) and 14 (6.14 ± 1.51 vs. 5.07 ± 2.41 × 109/L) of chemotherapy and that in the TCM herb group on day 14 (6.63 ± 3.44 vs. 5.07 ± 2.41 × 109/L) of chemotherapy were increased (P<0.05). Compared with the conventional group, the neutrophil count in the TEAS group on days 5 (4.28 ± 1.54 vs. 3.01 ± 1.41 × 109/L), 8 (3.75 ± 1.21 vs. 2.77 ± 1.17 × 109/L), 11 (3.46 ± 1.31 vs. 2.31 ± 1.24 × 109/L), 14 (3.18 ± 1.29 vs. 2.07 ± 1.14 × 109/L), and 21 (4.67 ± 1.31 vs. 3.58 ± 1.23 × 109/L) of chemotherapy and that in the TCM herb group on day 5 (3.88 ± 1.05 vs. 3.01 ± 1.41 × 109/L) of chemotherapy were increased (P<0.05). Compared with the conventional group, the platelet count of patients in the TEAS group increased on days 5 (264.7 ± 64.1 vs. 201.0 ± 55.7 × 109/L), 8 (251.3 ± 74.9 vs. 188.2 ± 65.8 × 109/L), 11 (236.7 ± 74.9 vs. 181.3 ± 84.3 × 109/L), and 14 (238.3 ± 75.9 vs. 192.8 ± 95.8 × 109/L) of chemotherapy (P<0.05). Compared with the TCM herb group, the platelet count in the TEAS group increased on days 5 (264.7 ± 64.1 vs. 216.3 ± 57.9 × 109/L), 8 (251.3 ± 74.9 vs. 213.7 ± 70.3 × 109/L), 11 (236.7 ± 74.9 vs. 181.3 ± 84.3 × 109/L), and 21 (254.8 ± 81.8 vs. 213.9 ± 82.6 × 109/L) of chemotherapy (P<0.05). Compared with the conventional group, the hemoglobin level in the TCM herb group increased on day 14 (135.03 ± 28.06 vs. 122.09 ± 12.63 g/L) of chemotherapy (P<0.05). Compared with the conventional group, the comfort score of the TEAS group increased on days 5 (78.31 ± 10.21 vs. 70.18 ± 9.34 score) and 11 (80.07 ± 10.44 vs. 72.11 ± 9.47 score) of chemotherapy (P<0.05). Conclusion. TEAS is an effective and safe treatment modality for improving bone marrow suppression in SCLC patients after initial chemotherapy. TEAS improved comfort levels more effectively than did conventional and TCM herb

Table_1_Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma.docx

Lactic acid, once considered as an endpoint or a waste metabolite of glycolysis, has emerged as a major regulator of cancer development, maintenance, and progression. However, studies about lactic acid metabolism-related genes (LRGs) in lung adenocarcinoma (LUAD) remain unclear. Two distinct molecular subtypes were identified on basis of 24 LRGs and found the significant enrichment of subtype A in metabolism-related pathways and had better overall survival (OS). Subsequently, a prognostic signature based on 5 OS-related LRGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. Then, a highly accurate nomogram was cosntructed to improve the clinical application of the LRG_score. By further analyzing the LRG_score, higher immune score and lower stromal score were found in the low LRG_score group, which presented a better prognosis. Patients with low LRG_score also exhibited lower somatic mutation rate, tumor mutation burden (TMB), and cancer stem cell (CSC) index. Three more independent cohorts (GSE126044: anti-PD-1, GSE135222: anti-PD-1, and IMvigor210: anti-PD-L1) were analyzed, and the results showed that patients in the low LRG_score category were more responsive to anti-PD-1/PD-L1 medication and had longer survival times. It was also determined that gefitinib, etoposide, erlotinib, and gemcitabine were more sensitive to the low LRG_score group. Finally, we validated the stability and reliability of LRG_score in cell lines, clinical tissue samples and HPA databases. Overall, the LRG_score may improve prognostic information and provide directions for current research on drug treatment strategies for LUAD patients.</p

Table_2_Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma.docx

Lactic acid, once considered as an endpoint or a waste metabolite of glycolysis, has emerged as a major regulator of cancer development, maintenance, and progression. However, studies about lactic acid metabolism-related genes (LRGs) in lung adenocarcinoma (LUAD) remain unclear. Two distinct molecular subtypes were identified on basis of 24 LRGs and found the significant enrichment of subtype A in metabolism-related pathways and had better overall survival (OS). Subsequently, a prognostic signature based on 5 OS-related LRGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. Then, a highly accurate nomogram was cosntructed to improve the clinical application of the LRG_score. By further analyzing the LRG_score, higher immune score and lower stromal score were found in the low LRG_score group, which presented a better prognosis. Patients with low LRG_score also exhibited lower somatic mutation rate, tumor mutation burden (TMB), and cancer stem cell (CSC) index. Three more independent cohorts (GSE126044: anti-PD-1, GSE135222: anti-PD-1, and IMvigor210: anti-PD-L1) were analyzed, and the results showed that patients in the low LRG_score category were more responsive to anti-PD-1/PD-L1 medication and had longer survival times. It was also determined that gefitinib, etoposide, erlotinib, and gemcitabine were more sensitive to the low LRG_score group. Finally, we validated the stability and reliability of LRG_score in cell lines, clinical tissue samples and HPA databases. Overall, the LRG_score may improve prognostic information and provide directions for current research on drug treatment strategies for LUAD patients.</p

A Review of Recent Developments in Preparation Methods for Large-Area Perovskite Solar Cells

The recent rapid development in perovskite solar cells (PSCs) has led to significant research interest due to their notable photovoltaic performance, currently exceeding 25% power conversion efficiency for small-area PSCs. The materials used to fabricate PSCs dominate the current photovoltaic market, especially with the rapid increase in efficiency and performance. The present work reviews recent developments in PSCs&rsquo; preparation and fabrication methods, the associated advantages and disadvantages, and methods for improving the efficiency of large-area perovskite films for commercial application. The work is structured in three parts. First is a brief overview of large-area PSCs, followed by a discussion of the preparation methods and methods to improve PSC efficiency, quality, and stability. Envisioned future perspectives on the synthesis and commercialization of large-area PSCs are discussed last. Most of the growth in commercial PSC applications is likely to be in building integrated photovoltaics and electric vehicle battery charging solutions. This review concludes that blade coating, slot-die coating, and ink-jet printing carry the highest potential for the scalable manufacture of large-area PSCs with moderate-to-high PCEs. More research and development are key to improving PSC stability and, in the long-term, closing the chasm in lifespan between PSCs and conventional photovoltaic cells

Protective Effect of Hydroxysafflor Yellow A on Nephropathy by Attenuating Oxidative Stress and Inhibiting Apoptosis in Induced Type 2 Diabetes in Rat

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing all over the world, which is also the leading cause of end-stage renal failure. Hydroxysafflor yellow A (HSYA) is the main active chemical component of Carthamus tinctorius L., and it is commonly used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the renal protective effects and molecular mechanisms of HSYA on high-fat diet (HFD) and streptozotocin- (STZ-) induced DN in rats. The DN rats were treated with HSYA for eight weeks. We assessed creatinine (CR), urea nitrogen (UN), glomerular volume, podocyte number, renal inflammation, oxidative stress, and cells apoptosis markers after HSYA treatment. The number of apoptotic cells was measured by the TUNEL assay, and apoptosis-related proteins BAX, caspase-3, and BCL-2 in the renal tissue were analyzed by western blot. The treatment with HSYA significantly decreased fasting blood glucose, CR, UN, and blood lipid profile, including triglyceride and total and low-density lipoprotein cholesterol, even though it did not change the rats’ body weights. The western blot results indicated that HSYA reversed the upregulation of BAX and caspase-3 and significantly increased BCL-2 in renal tissue. Moreover, the levels of TNF-α and the inflammatory products, including free fatty acids (FFA) and lactic dehydrogenase (LDH) in the HSYA group, were significantly decreased. For the oxidative stress marker, the superoxide dismutase (SOD) markedly increased in the HSYA treatment group, while the malondialdehyde (MDA) in the serum and kidney tissue evidently decreased. In conclusion, HSYA treatment preserved kidney function in diabetic nephropathy in the HFD- and STZ-induced rats. The potential mechanism of renal protective effect of HSYA might be through inhibiting oxidative stress, reducing inflammatory reaction, and attenuating renal cell apoptosis. Our studies present a promising use for Hydroxysafflor yellow A in the treatment of type 2 diabetes mellitus

SEIPIN regulates lipid droplet expansion and adipocyte development by modulating the activity of glycerol-3-phosphate acyltransferase

Summary Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) is caused by loss-of-function mutations in SEIPIN, a protein implicated in both adipogenesis and lipid droplet expansion but whose molecular function remains obscure. Here, we identify physical and functional interactions between SEIPIN and microsomal isoforms of glycerol-3-phosphate acyltransferase (GPAT) in multiple organisms. Compared to controls, GPAT activity was elevated in SEIPIN-deficient cells and tissues and GPAT kinetic values were altered. Increased GPAT activity appears to underpin the block in adipogenesis and abnormal lipid droplet morphology associated with SEIPIN loss. Overexpression of Gpat3 blocked adipogenesis, and Gpat3 knockdown in SEIPIN-deficient preadipocytes partially restored differentiation. GPAT overexpression in yeast, preadipocytes, and fly salivary glands also formed supersized lipid droplets. Finally, pharmacological inhibition of GPAT in Seipin−/− mouse preadipocytes partially restored adipogenesis. These data identify SEIPIN as an evolutionarily conserved regulator of microsomal GPAT and suggest that GPAT inhibitors might be useful for the treatment of human BSCL2 patients