ROLE OF MICRORNA LET-7 IN PANCREATIC BETA CELLS

MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression at transcriptional or post-transcriptional level. Let-7 family is among the first identified human miRNAs and regulates multiple cellular processes including glucose metabolism in multiple organs. It has been reported that overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance through repressing insulin signaling pathway in both muscle and liver. However, the role and mechanism underlying let-7 function in pancreatic beta-cells have yet to be elucidated. Let-7 family contains nine members, which poses a significant challenge in complete deletion of this miRNA family. To study the function of let-7 and to overcome the functional redundancies of various let-7 members in pancreatic beta-cells, the highly expressed let-7a and let-7b were blocked simultaneously using short tandem target mimic (STTM) approach developed in our laboratory. Introducing STTM-let7 into beta-cells markedly increased the expression of Caspase 3, a direct target of let-7, confirming a sufficient functional knockdown of let-7a/b by STTM-let7. STTM-let7 enhanced apoptotic cell death induced by cytokine, indicating that let-7a/b is able to protect from apoptosis through attenuating Caspase 3 expression in pancreatic beta-cells. In contrast to the previous observation that let-7 silencing increases insulin signaling in muscle and liver, inhibition of let-7 with STTM-let7 significantly repressed glucose-stimulated insulin signaling in pancreatic beta-cells, leading to impaired insulin secretion and reduced beta-cell proliferation. Taken together, an appropriate level of let-7 is essential in maintaining beta-cell function and viability. Dysregulation of let-7 may contribute to the pathogenesis of type 2 diabetes

Disruption of CD40 Results in Significantly Attenuated Renal Inflammation Following Glycerol-Induced Acute Kidney Injury

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The role of connectivity in significant bandgap narrowing for fused-pyrene based non-fullerene acceptors toward high-efficiency organic solar cells

Great attention has been paid to developing low bandgap non-fullerene acceptors (NFAs) for matching wide bandgap donor polymers to increase the photocurrent and therefore the power conversion efficiencies (PCEs) of NFA organic solar cells, while pyrene-core based acceptor-donor-acceptor (A-D-A) NFAs have been mainly reported via the 2,9-position connection due to their bisthieno[3′,2′-b']thienyl[a,h]pyrene fused via a five-membered ring bridge at the ortho-position of pyrene as the representative one named FPIC5, which has prohibited further narrowing their energy gap. Herein, an acceptor FPIC6 was exploited by creating the 1,8-position connection through fusing as bisthieno[3′,2′-b′]thienyl[f-g,m-n]pyrene linked at the bay-position via a six-membered bridge, with enhanced push-pull characteristics within such A-D-A structure. As a structural isomer of FPIC5, FPIC6 exhibited a much lower bandgap of 1.42 eV (1.63 eV for FPIC5). Therefore, the photocurrent and PCE of PTB7-Th:FPIC6 cells were improved to 21.50 mA cm-2 and 11.55%, respectively, due to the balanced mobilities, better photoluminescence quenching efficiency and optimized morphology, which are both ∼40% better than those of PTB7-Th:FPIC5 cells. Our results clearly proved that a pyrene fused core with 1,8-position connection with electron-withdrawing end groups instead of 2,9-position connection is an efficient molecular design strategy to narrow the optical bandgap and improve the photovoltaic performance of NFA based OSCs

MicroRNAs as pharmacological targets in diabetes

Diabetes is characterized by high levels of blood glucose due to either the loss of insulin-producing beta-cells in the pancreas, leading to a deficiency of insulin in type 1 diabetes, or due to increased insulin resistance, leading to reduced insulin sensitivity and productivity in type 2 diabetes. There is an increasing need for new options to treat diabetes, especially type 2 diabetes at its early stages due to an ineffective control of its development in patients. Recently, a novel class of small noncoding RNAs, termed microRNAs (miRNAs), is found to play a key role as important transcriptional and posttranscriptional inhibitors of gene expression in fine-tuning the target messenger RNAs (mRNAs). miRNAs are implicated in the pathogenesis of diabetes and have become an intriguing target for therapeutic intervention. This review focuses on the dysregulated miRNAs discovered in various diabetic models and addresses the potential for miRNAs to be therapeutic targets in the treatment of diabetes

Ancient mitochondrial genomes from Chinese cave hyenas provide insights into the evolutionary history of the genus Crocuta

Cave hyenas (genus Crocuta) are extinct bone-cracking carnivores from the family Hyaenidae and are generally split into two taxa that correspond to a European/Eurasian and an (East) Asian lineage. They are close relatives of the extant African spotted hyenas, the only extant member of the genus Crocuta. Cave hyenas inhabited a wide range across Eurasia during the Pleistocene, but became extinct at the end of the Late Pleistocene. Using genetic and genomic datasets, previous studies have proposed different scenarios about the evolutionary history of Crocuta. However, causes of the extinction of cave hyenas are widely speculative and samples from China are severely understudied. In this study, we assembled near-complete mitochondrial genomes from two cave hyenas from northeastern China dating to 20 240 and 20 253 calBP, representing the youngest directly dated fossils of Crocuta in Asia. Phylogenetic analyses suggest a monophyletic clade of these two samples within a deeply diverging mitochondrial haplogroup of Crocuta. Bayesian analyses suggest that the split of this Asian cave hyena mitochondrial lineage from their European and African relatives occurred approximately 1.85 Ma (95% CI 1.62–2.09 Ma), which is broadly concordant with the earliest Eurasian Crocuta fossil dating to approximately 2 Ma. Comparisons of mean genetic distance indicate that cave hyenas harboured higher genetic diversity than extant spotted hyenas, brown hyenas and aardwolves, but this is probably at least partially due to the fact that their mitochondrial lineages do not represent a monophyletic group, although this is also true for extant spotted hyenas. Moreover, the joint female effective population size of Crocuta (both cave hyenas and extant spotted hyenas) has sustained two declines during the Late Pleistocene. Combining this mitochondrial phylogeny, previous nuclear findings and fossil records, we discuss the possible relationship of fossil Crocuta in China and the extinction of cave hyenas

Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity

Abnormal microRNA functions are closely associated with pancreatic β-cell loss and dysfunction in type 2 diabetes. Dysregulation of miR-30d has been reported in the individuals with diabetes. To study how miR-30d affects pancreatic β-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in β-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected β-cell function. Elevated miR-30d at low-level (TgL, 2-fold) had mild effects on signaling pathways and displayed no significant changes to metabolic homeostasis. In contrast, transgenic mice with high-level of miR-30d expression (TgH, 12-fold) exhibited significant diet-induced hyperglycemia and β-cell dysfunction. In addition, loss of β-cell identity was invariably accompanied with increased insulin/glucagon-double positive bihormonal cells and excess plasma glucagon levels. The transcriptomic analysis revealed that miR-30d overexpression inhibited β-cell-enriched gene expression and induced α-cell-enriched gene expression. These findings implicate that an appropriate miR-30d level is essential in maintaining normal β-cell identity and function

Nonfullerene acceptors from thieno[3,2-b]thiophene-fused naphthalene donor core with six-member-ring connection for efficient organic solar cells

Comprehensive design ideas on the fused-ring donor-core in state-of-the-art acceptor-donor-acceptor (A-D-A) nonfullerene acceptors (NFAs) are still of great importance for regulating the electron push-pull effect for the sake of optimal light-harvesting, frontier molecular orbital levels, and finally their photovoltaic properties. Herein, thieno[3,2-b]thiophenes were fused in bay-area of naphthalene via six-member-ring connection, resulting in the formation of dihydropyrenobisthieno[3,2-b]thiophene based octacyclic ladder-type donor core, which was flanked by two 1,1-dicyanomethylene-3-indanone (IC) acceptor motifs with and without 5,6-diflourination, namely PTT-IC and PTT-2FIC, respectively, as novel efficient A-D-A fused-ring electron acceptors (FREAs). Compared with PTT-IC, fluorinated PTT-2FIC possesses narrower optical bandgap of 1.48 eV, better π-π stacking, and its PBDB-T:PTT-2FIC blend film exhibited better morphology, and better hole and electron mobility. As a result, nonfullerene solar cells using PBDB-T:PTT-2FIC as the active layer achieved a decent PCE of 10.40%, with an open-circuit voltage (VOC) of 0.87 V, a fill factor (FF) of 0.65, and a much higher short-circuit current (JSC) of 18.26 mA/cm2. Meanwhile, the PBDB-T:PTT-IC cells delivered a lower JSC of 12.58 mA/cm2 but a higher VOC of 0.99 V, thus resulting in a PCE of 7.39% due to its wider optical bandgap of 1.58 eV and higher LUMO energy level. These results demonstrated that NFAs based on fused-ring donor core from fusing thieno[3,2-b]thiophenes with naphthalene via six-member-ring connection are promising for organic photovoltaic applications