INFLUENCING FACTORS OF THE DIABETES DISTRESS AMONG CHINESE PATIENTS WITH TYPE 2 DIABETES MELLITUS

Background: Patients with Diabetes Mellitus (DM) are required to have long-term treatment regimen and strict selfmanagement, which thus might lead to the Diabetes Distress (DD). Patients’ DD varies in different regions with different levels of medical conditions. For improving the treatment effect of the patients with the Type-2-Diabetes-Mellitus (T2DM), this study explores the influencing factors of the patients’ DD in the regions where the medical treatment are at low level. Subjects and methods: In this study, 167 adult patients with T2DM were selected from the People’s Hospital of Jinhua city, an A-grade hospital of a small-mid-sized city in Eastern China. Based on these samples, the Diabetes Distress Scale with 17 items (DDS17) was adopted to measure the degree of patients’ DD, and then regression analyses were carried out to investigate the influencing factors for their DD. Results: The T2DM patients with moderate and high levels of DD take up 54.5% of the samples investigated in this study. According to the Spearman correlation analysis, sleep time, physical exercise, diet control, treatment regimen, TG and HbA1c significantly affect the patients’ DD. Through the multivariate linear regression analysis, this study shows that (1) sleep time significantly influences the T2DM patients’ DD (????=-0.213, P=0.034); (2) sleep time also impacts emotional burden (????=-0.379, P=0.027); (3) physical exercise (????=-0.195, P=0.002), treatment regimen (????=0.158, P=0.026) and diet control (????=0.158, P=0.026) are the three major influencing factors for regimen-related distress. Conclusion: In the small-mid-sized city where the treatment regimen is not highly advanced, to alleviate the T2DM patients’ DD, the medical staff should suggest the patients to improve sleep quality and exercise more, help them positively understand the insulin infusion therapy and take proper diet control

Full-length transcriptome analysis provides insights into larval shell formation in Mulinia lateralis

Mollusca is the second largest animal phylum and represents one of the most evolutionarily successful animal groups. Mulinia lateralis, a small bivalve, is a promising model organism to facilitate studies of mollusc development. However, because of the lack of published genomic and transcriptomic resources, integrated research on the formation of larval shells in this species, which is a representative developmental process of molluscs and of great importance for larva survival, is hindered. In this study, the blastula, gastrula, trochophore larva, and D-shaped larva of M. lateralis were utilized for generating a comprehensive full-length transcriptome through Pacific BioSciences (PacBio) isoform sequencing (Iso-seq) and Illumina RNA-Seq. A total of 238,919 full-length transcripts with an average length of 3,267 bp and 121,424 annotated genes were obtained. Illumina RNA-Seq data analysis showed that 4,512, 10,637, and 17,829 differentially expressed genes (DEGs) were obtained between the two adjacent developmental stages. Functional annotation and enrichment analysis revealed the specific function of genes in shell biomineralization during different developmental stages. Twelve genes that may be involved in the formation of the larval shell of M. lateralis were identified, including insoluble shell matrix protein-encoding gene 1 (ISMP1), ISMP2, ISMP5, chitin synthase, tyrosinase, chitin-binding protein, collagen and pu14 involved in shell matrix deposition, and carbonic anhydrase, solute carrier family 4 member 8 (slc4a8), EF-hand, and a calmodulin coding gene C-2442 participated in ion transportation. In addition, calcium ion binding function, calcium signaling pathway, and endocrine and other factor-regulated calcium reabsorption pathways were significantly enriched. Weighted gene correlation network analysis (WGCNA) identified two modules related to biomineralization and larval shell formation, and slc4a8 and ring finger protein 41 (rnf41) were key hub genes that may be involved in this process. Moreover, it could be implied that the process of ion transport occurs earlier than the deposition of the shell matrix. This work provided a clear view of the transcriptome for M. lateralis and will be valuable in elucidating the mechanisms of larval shell formation as well as other developmental processes in molluscs

Cocaine Exposure Increases Blood Pressure and Aortic Stiffness via the miR-30c-5p–Malic Enzyme 1–Reactive Oxygen Species Pathway

Cocaine abuse increases the risk of cardiovascular mortality and morbidity; however, the underlying molecular mechanisms remain elusive. By using a mouse model for cocaine abuse/use, we found that repeated cocaine injection led to increased blood pressure and aortic stiffness in mice associated with elevated levels of reactive oxygen species (ROS) in the aortas, a phenomenon similar to that observed in hypertensive humans. This ROS elevation was correlated with downregulation of Me1 (malic enzyme 1), an important redox molecule that counteracts ROS generation, and upregulation of microRNA (miR)-30c-5p that targets Me1 expression by directly binding to its 3'UTR (untranslated region). Remarkably, lentivirus-mediated overexpression of miR-30c-5p in aortic smooth muscle cells recapitulated the effect of cocaine on Me1 suppression, which in turn led to ROS elevation. Moreover, in vivo silencing of miR-30c-5p in smooth muscle cells resulted in Me1 upregulation, ROS reduction, and significantly suppressed cocaine-induced increases in blood pressure and aortic stiffness-a similar effect to that produced by treatment with the antioxidant N-acetyl cysteine. Discovery of this novel cocaine-↑miR-30c-5p-↓Me1-↑ROS pathway provides a potential new therapeutic avenue for treatment of cocaine abuse-related cardiovascular disease

Dynamic transcriptome analysis reveals the gene network of gonadal development from the early history life stages in dwarf surfclam Mulinia lateralis

Highlights Mulinia lateralis reaches sexual maturation within 2 months, facilitating comprehensive studies of gonadal development. A combined morphological and molecular analysis reveals the timing of gonad formation, sex differentiation and gametogenesis. WGCNA on 40 transcriptomes identifies key modules and molecular drivers of clam gonadal development. SOX2, FOXZ, HSFY, FOXL2 and HES1 are hub transcription factors for gonadal development of Mulinia lateralis

K252a inhibition of sperm viability for efficient crossbreeding of hermaphroditic bivalves

Bivalve mollusks are economically important shellfish, representing 56.3% of aquaculture production. Cross-breeding is a popular approach for the genetic improvement of aquaculture species, including bivalves. However, it is difficult for simultaneous hermaphrodites due to the difficulty in collecting unfertilized oocytes. Male infertility or subfertility could be a solution. Considering that protein phosphorylation is critical in spermato-genesis, we investigated the effects of the protein kinase inhibitor K252a on germ cell development, gamete quality and embryonic/larval development of the simultaneously hermaphroditic scallop Argopecten irradians and evaluated its feasibility in crossbreeding. The results showed that 20% K252a injection at the gonad growth stage led to significant decreases in sperm number and progressive motility rate. Abnormal axoneme arrange-ment in flagella may have caused reduced sperm motility. Normal oocytes fertilized with K252a-treated sperm showed significant decreases in fertilization rate (38.24%), cleavage rate (83.42%) and D-stage survival rate (15.93%), and K252a-treated oocytes did not show obvious defects in early development. Interspecific hybrid-ization using K252a-treated A. irradians fertilized with Argopecten purpuratus sperm resulted in a 3.19-fold in-crease in the hybrid ratio (67%) over that of the control group (16%). Our study indicated that K252a influenced sperm development without affecting oocytes in A. irradians, indicating that K252a treatment may facilitate the mass production of crossbreeds and hybrids for simultaneous hermaphrodites. The approach reported here will greatly assist in genetic improvement programs for mollusk hermaphrodites

Genetic and Biochemical Analysis of High Iron Toxicity in Yeast: IRON TOXICITY IS DUE TO THE ACCUMULATION OF CYTOSOLIC IRON AND OCCURS UNDER BOTH AEROBIC AND ANAEROBIC CONDITIONS*

Iron storage in yeast requires the activity of the vacuolar iron transporter Ccc1. Yeast with an intact CCC1 are resistant to iron toxicity, but deletion of CCC1 renders yeast susceptible to iron toxicity. We used genetic and biochemical analysis to identify suppressors of high iron toxicity in Δccc1 cells to probe the mechanism of high iron toxicity. All genes identified as suppressors of high iron toxicity in aerobically grown Δccc1 cells encode organelle iron transporters including mitochondrial iron transporters MRS3, MRS4, and RIM2. Overexpression of MRS3 suppressed high iron toxicity by decreasing cytosolic iron through mitochondrial iron accumulation. Under anaerobic conditions, Δccc1 cells were still sensitive to high iron toxicity, but overexpression of MRS3 did not suppress iron toxicity and did not result in mitochondrial iron accumulation. We conclude that Mrs3/Mrs4 can sequester iron within mitochondria under aerobic conditions but not anaerobic conditions. We show that iron toxicity in Δccc1 cells occurred under both aerobic and anaerobic conditions. Microarray analysis showed no evidence of oxidative damage under anaerobic conditions, suggesting that iron toxicity may not be solely due to oxidative damage. Deletion of TSA1, which encodes a peroxiredoxin, exacerbated iron toxicity in Δccc1 cells under both aerobic and anaerobic conditions, suggesting a unique role for Tsa1 in iron toxicity

Rural Residents in China Are at Increased Risk of Exposure to Tick-Borne Pathogens Anaplasma phagocytophilum and Ehrlichia chaffeensis

As emerging tick born rickettsial diseases caused by A. phagocytophilum and E. chaffeensis, anaplasmosis and ehrlichiosis have become a serious threat to human and animal health throughout the world. In particular, in China, an unusual transmission of nosocomial cases of human granulocytic anaplasmosis occurred in Anhui Province in 2006 and more recent coinfection case of A. phagocytophilum and E. chaffeensis was documented in Shandong Province. Although the seroprevalence of human granulocytic anaplasmosis (former human granulocytic ehrlichiosis, HGE) has been documented in several studies, these data existed on local investigations, and also little data was reported on the seroprevalence of human monocytic ehrlichiosis (HME) in China. In this cross-sectional epidemiological study, indirect immunofluorescence antibody assay (IFA) proposed by WHO was used to detect A. phagocytophilum and E. chaffeensis IgG antibodies for 7,322 serum samples from agrarian residents from 9 provinces/cities and 819 urban residents from 2 provinces. Our data showed that farmers were at substantially increased risk of exposure. However, even among urban residents, risk was considerable. Seroprevalence of HGA and HME occurred in diverse regions of the country and tended to be the highest in young adults. Many species of ticks were confirmed carrying A. phagocytophilum organisms in China while several kinds of domestic animals including dog, goats, sheep, cattle, horse, wild rabbit, and some small wild rodents were proposed to be the reservoir hosts of A. phagocytophilum. The broad distribution of vector and hosts of the A. phagocytophilum and E. chaffeensis, especially the relationship between the generalized susceptibility of vectors and reservoirs and the severity of the disease’s clinical manifestations and the genetic variation of Chinese HGA isolates in China, is urgently needed to be further investigated