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MicroRNAs (miRNAs) consist of a large family of small, non-coding RNAs with the ability to result in gene silencing post-transcriptionally. With recent advances in research technology over the past several years, the physiological and pathological potentials of miRNAs have been gradually uncovered. MiR-149-5p, a conserved miRNA, was found to regulate physiological processes, such as inflammatory response, adipogenesis and cell proliferation. Notably, increasing studies indicate miR-149-5p may act as an important regulator in solid tumors, especially cancers in reproductive system and digestive system. It has been acknowledged that miR-149-5p can function as an oncogene or tumor suppressor in different cancers, which is achieved by controlling a variety of genes expression and adjusting downstream signaling pathway. Moreover, the levels of miR-149-5p are influenced by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there is blank about systematic function and mechanism of miR-149-5p in human cancers. In this review, we firstly summarize the present comprehension of miR-149-5p at the molecular level, its vital role in tumor initiation and progression, as well as its potential roles in monitoring diverse reproductive and digestive malignancies.

Background Recent studies have revealed that vitamin D deficiency may increase the risk of Alzheimer's disease, and vitamin D supplementation may be effective strategy to ameliorate the neurodegenerative process in Alzheimer's disease patients. Paricalcitol (PAL), a low-calcemic vitamin D receptor agonist, is clinically used to treat secondary hyperparathyroidism. However, the potential application of PAL for treating neurodegenerative disorders remains unexplored. Methods The APP/PS1 mice were intraperitoneally injected with PAL or vehicle every other day for 15 weeks. The β-amyloid (Aβ) production was confirmed using immunostaining and enzyme linked immunosorbent assay. The underlying mechanism was verified by western blot and immunostaining in vivo and in vitro. Findings Long-term PAL treatment clearly reduced β-amyloid (Aβ) generation and neuronal loss in APP/PS1 transgenic mouse brains. PAL stimulated the expression of low-density lipoprotein receptor-related protein 1 (LRP1) possibly through inhibiting sterol regulatory element binding protein-2 (SREBP2); PAL also promoted LRP1-mediated β-site APP cleavage enzyme 1 (BACE1) transport to late endosomes, thus increasing the lysosomal degradation of BACE1. Furthermore, PAL diminished 8-hydroxyguanosine (8-OHdG) generation in neuronal mitochondria via enhancing base excision repair (BER), resulting in the attenuation of calpain-1-mediated neuronal loss. Interpretation The present data demonstrate that PAL can reduce Aβ generation through accelerating BACE1 lysosomal degradation and can inhibit neuronal loss through suppressing mitochondrial 8-OHdG generation. Hence, PAL might be a promising agent for treating Alzheimer's disease. Fund This study was financially supported by the Natural Science Foundation of China (U1608282).

Stratifin (SFN) is a member of the 14-3-3 family of highly conserved soluble acidic proteins, which regulates a variety of cellular activities such as cell cycle, cell growth and development, cell survival and death, and gene transcription. Acute kidney injury (AKI) is prevalent disorder characterized by inflammatory response, oxidative stress, and programmed cell death in renal tubular epithelial cells, but there is still a lack of effective therapeutic target for AKI. In this study, we investigated the role of SFN in AKI and the underlying mechanisms. We established ischemic and nephrotoxic AKI mouse models caused by ischemia-reperfusion (I/R) and cisplatin, respectively. We conducted proteomic and immunohistochemical analyses and found that SFN expression levels were significantly increased in AKI patients, cisplatin- or I/R-induced AKI mice. In cisplatin- or hypoxia/reoxygenation (H/R)-treated human proximal tubule epithelial cells (HK2), we showed that knockdown of SFN significantly reduced the expression of kidney injury marker Kim-1, attenuated programmed cell death and inflammatory response. Knockdown of SFN also significantly alleviated the decline of renal function and histological damage in cisplatin-caused AKI mice in vivo. We further revealed that SFN bound to RIPK3, a key signaling modulator in necroptosis, to induce necroptosis and the subsequent inflammation in cisplatin- or H/R-treated HK2 cells. Overexpression of SFN increased Kim-1 protein levels in cisplatin-treated MTEC cells, which was suppressed by RIPK3 knockout. Taken together, our results demonstrate that SFN that enhances cisplatin- or I/R-caused programmed cell death and inflammation via interacting with RIPK3 may serve as a promising therapeutic target for AKI treatment.

The mitochondrial genome of Fejervarya kawamurai is a circular molecule of 17,650 bp in length, containing 13 protein-coding genes, two rRNA genes, 23 tRNA genes (including an extra tRNA-Met), and the control region. The AT content of the whole genome is 56.9%. In Bayesian inference (BI) and Maximum likelihood (ML) analyses, we found that F. kawamurai is a sister clade to F. multistriata and F. limnocharis. The monophyly of Fejervarya, Quasipaa, Nanorana was well supported (1.00 in BI and 100% in ML).

The complete mitochondrial genome sequence of the hybrid of Hoplobatrachus chinensis (♀) × H. rugulosus (♂) was obtained in this study. The circular mitochondrial genome was 20,282 bp in length (including extra ND5 genes). Compared with the complete mitogenome of the parents, the results indicated that the mitochondria of the hybrid tiger frog was consistent with a maternal inheritance. Phylogenetic analyses using concatenated nucleotide sequences of the 11 protein-coding genes with two different methods (maximum likelihood and MrBayes analysis) both highly supported a close relationship of the hybrid frogs with the Chinese tiger frog (=H. chinensis).

The incidence and severity of acute kidney injury (AKI) is increased yearly in diabetic patients. Although the mechanisms for this remain unclear, the prevention of AKI in diabetic nephropathy is feasible and of value. As we detected highly activation of TGF-β/Smad3 signaling in both human biopsy and mouse model of diabetic nephropathy, we hypothesized that Smad3 activation in diabetic kidneys may increase AKI sensitivity. We tested our hypothesis in vitro using TGF-β type II receptor (TGF-βRII) disrupted tubular epithelial cells (TECs) and in vivo in mice with streptozotocin (STZ)-induced diabetic nephropathy before the induction of ischemia/reperfusion (I/R) injury. We found that high glucose (HG)-cultured TECs showed increased inflammation, apoptosis and oxidative stress following hypoxia/reoxygenation (H/R) injury. Disruption of TGF-βRII attenuated cell injury induced by H/R in HG-treated TECs. Consistently, Smad3 knockdown in diabetic kidney attenuated I/R-induced AKI. Mechanistically, Smad3 binds to p53 and enhances p53 activity in cells treated with HG and H/R, which may lead to TECs apoptosis. Additionally, ChIP assay showed that Smad3 bound with the promoter region of NOX4 and induced ROS production and inflammation. In conclusion, our results demonstrate that Smad3 promotes AKI susceptibility in diabetic mice by interacting with p53 and NOX4., Graphical abstract Image 1, Highlights • Smad3 activation in diabetic kidneys may increase AKI sensitivity. • Blockade of Smad3 in diabetic kidney may both prevent AKI and CKD progression. • Smad3 interacts with p53 to enhance TECs apoptosis. • Smad3 binds with promoter region of NOX4 to induce ROS production and inflammation.

The mitochondrial genome of Fejervarya kawamurai is a circular molecule of 17,650 bp in length, containing 13 protein-coding genes, two rRNA genes, 23 tRNA genes (including an extra tRNA-Me...

Acute kidney injury (AKI) is a destructive clinical condition induced by multiple insults including ischemic reperfusion, nephrotoxic drugs and sepsis. It is characterized by a sudden decline in renal function, in addition to excessive inflammation, oxidative stress and programmed cell death of renal tubular epithelial cells. RIPK1-mediated necroptosis plays an important role in AKI. In the present study, we evaluated the treatment effects of Compound-71 (Cpd-71), a novel RIPK1 inhibitor, by comparing with Necrostatin-1 (Nec-1), a classic RIPK1 inhibitor, which has several drawbacks like the narrow structure–activity relationship (SAR) profile, moderate potency and non-ideal pharmacokinetic properties, in vivo and in vitro. Our results showed that pretreatment of Cpd-71 attenuated cisplatin-induced renal injury, restored renal function and suppressed renal inflammation, oxidative stress and cell necroptosis. In addition, Cpd-71 inhibited renal damage while reducing the up-regulated serum creatinine (Cr) and blood urea nitrogen (BUN) levels in established AKI mice model. Consistently, we confirmed that Cpd-71 exhibited more effectively suppressive effect on cisplatin-induced renal tubular cell necroptosis than Nec-1, by physically binding to the allosteric type III ligand binding site of RIPK1, thereby reduced RIPK1 kinase activity, RIPK1/RIPK3 complex formation and phosphor-MLKL membrane translocation by molecular docking, Western blot, co-immunoprecipitation and cellular thermal shift assay (CETSA). Taken together, we currently showed that targeting RIPK1 with Cpd-71 may serve as a promising clinical candidate for AKI treatment.

Both Sys1 and Sygdh, two codon-optimized genes encoding SyS1 and SyGDH, were synthesized based on the carbonyl reductase (S1) and glucose 1-dehydrogenase (GDH) gene sequences, respectively, from Candida magnoliae and Thermoplasma acidophilum, and co-expressed in Escherichia coli BL21(DE3) using two strategies. One strategy involved a recombinant E. coli strain (E. coli/Sygdh-Sys1) constructed by transforming a recombinant plasmid, pETDuet-Sygdh-Sys1, into E. coli BL21. The other strategy involved another recombinant E. coli strain (E. coli/Sys1/Sygdh) obtained by co-transforming the recombinant plasmids pET-22b-Sys1 and pET-28a-Sygdh into E. coli BL21. The enzyme activity assays indicated that the activities of recombinant SyS1 and SyGDH (3.7 and 56.3 U/g wet cells) expressed in E. coli/Sygdh-Sys1 were higher than those (2.8 and 44.1 U/g wet cells) in E. coli/Sys1/Sygdh. Accordingly, E. coli/Sygdh-Sys1 was chosen, and its whole cells were used as catalysts for the asymmetric reduction of m-chlorophenacyl chloride (m-CPC) to the corresponding (R)-2-chloro-1-(3-chlorophenyl)ethanol [(R)-CCE] coupled with the regeneration of NADPH in situ. Under the optimized reaction conditions of 30 mM m-CPC, 50 mg/ml wet cells, 40 mM glucose and 0.2 mM NADP+ at pH 7.0 and 35 °C for 3 h, (R)-CCE was obtained with a molar yield of 99.2 % and an enantiomeric excess (e.e.) value of more than 99 %.

A compact LTCC filter using LC resonators is presented. The resonator is made up of the multilayer capacitors and inductors, which are printed on multilayer ceramic. Four resonators are exploited, which makes the filter have wide passband. By properly controlling the coupling elements of each resonator, two transmission zeros can be located at both sides of the passband for better selectivity. Measured results show a bandwidth of more than 47.2%, where the centre frequency is 1.25GHz. The whole size of the filter is 4.5×3.2×1.7mm3.

The complete mitochondrial genome sequence of the hybrid of Hoplobatrachus chinensis (♀) × H. rugulosus (♂) was obtained in this study. The circular mitochondrial genome was 20,282 bp in length (in...

A visual management platform is designed for wireless temperature and humidity sensor network. The platform offers a multifunctional visual interface, including data management, curve plotting of sensor node, display of topology and data sending and receiving situation, etc, so that the receiving data from sensors can be accessed more conveniently to be used for optimization of network performance. Since ZigBee is specially developed for wireless network of low-rate, low power and low cost, and the platform has been operated efficiently with good compatibility, which is promising for wireless sensor network.

In this study, electrochemical investigation of corrosion protection and electrochromic properties of aniline-pentamer-based electroactive polyurea (EPU) coating prepared by oxidative coupling polymerization is presented. Monitoring of the in situ chemical oxidation process for the reduced form of soluble EPU in N-methyl-2-pyrrolidone (NMP) by the incorporation of an oxidant was performed by measuring UV-Visible absorption spectra. Moreover, the electroactivity of EPU was evaluated by performing electrochemical cyclic voltammetry (CV) studies. The EPU coating was found to exhibit enhanced corrosion protection effect on cold-rolled steel (CRS) electrodes as compared to a corresponding non-electroactive polyurea (NEPU) coating based on a series of electrochemical measurements in 3.5 wt% NaCl electrolyte. The electrochromic performance of EPU was investigated by measuring electrochromic photographs and UV absorption spectra.