Identification of Hydrolyzable Tannins (Punicalagin, Punicalin and Geraniin) as Novel inhibitors of Hepatitis B Virus Covalently Closed Circular DNA

The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication. Furthermore, punicalagin did not affect precore/core promoter activity, pgRNA transcription, core protein expression, or HBsAg secretion. By employing the cell-based cccDNA accumulation and stability assay, we found that these tannins significantly inhibited the establishment of cccDNA and modestly facilitated the degradation of preexisting cccDNA. Collectively, our results suggest that hydrolyzable tannins inhibit HBV cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay, although the latter effect is rather minor. These hydrolyzable tannins may serve as lead compounds for the development of new agents to cure HBV infection

Decreased Connection Between Reward Systems and Paralimbic Cortex in Depressive Patients

Despite decades of research on depression, the underlying pathophysiology of depression remains incompletely understood. Emerging evidence from task-based studies suggests that the abnormal reward-related processing contribute to the development of depression. It is unclear about the function pattern of reward-related circuit during resting state in depressive patients. In present study, seed-based functional connectivity was used to evaluate the functional pattern of reward-related circuit during resting state. Selected seeds were two key nodes in reward processing, medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAcc). Fifty depressive patients and 57 healthy participants were included in present study. Clinical severity of participants was assessed with Hamilton depression scale and Hamilton anxiety scale. We found that compared with healthy participants, depressive patients showed decreased connectivity of right mOFC with left temporal pole (TP_L), right insula extending to superior temporal gyrus (INS_R/STG) and increased connectivity of right mOFC with left precuneus. Similarly, decreased connectivity of left mOFC with TP_L and increased connectivity with cuneus were found in depressive patients. There is also decreased connectivity of right NAcc with bilateral temporal pole, as well as decreased connectivity of left NAcc with INS_R/STG. In addition, the functional connectivity of right nucleus accumbens with right temporal pole (TP_R) was negatively correlated with clinical severity. Our results emphasize the role of communication deficits between reward systems and paralimbic cortex in the pathophysiology of depression

MiR-539 inhibited the malignant behaviors of breast cancer cells by targeting SP1

The aberrant expression of microRNAs (miRNAs) is involved in the initiation and progression of human cancers. In our study, we found that miR-539 was down-regulated in breast cancer tissues and cell lines. Decreased expression of miR-539 was significantly associated with lymph node metastasis in patients with breast cancer. Overexpression of miR-539 inhibited the proliferation and promoted apoptosis of breast cancer cells. Moreover, highly expressed miR-539 significantly suppressed the epithelial–mesenchymal transition (EMT) and sensitized cells to cisplatin treatment. Mechanistically, miR-539 was found to target the specificity protein 1 (SP1) and down-regulated the expression of SP1 in breast cancer cells. Knockdown of miR-539 consistently increased the expression of SP1. The expression of miR-539 in breast cancer tissues was negatively correlated with the expression of SP1. Restoration of SP1 significantly attenuated the inhibitory effect of miR-539 on the proliferation of breast cancer cells. Taken together, our results indicate that miR-539 has a tumor suppressive role in breast cancer via targeting SP1, suggesting miR-539 as a promising target for the diagnosis of breast cancer.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Rational Design of Amorphous Indium Zinc Oxide/Carbon Nanotube Hybrid Film for Unique Performance Transistors

Here we report unique performance transistors based on sol gel processed indium zinc oxide/single-walled carbon nanotube (SWNT) composite thin films. In the composite, SWNTs provide fast tracks for carrier transport to significantly improve the apparent field effect mobility. Specifically, the composite thin film transistors with SWNT weight concentrations in the range of 0-2 wt % have been investigated with the field effect mobility reaching as high as 140 cm(2)/V.s at 1 wt SWNTs while maintaining a high on/off ratio similar to 10(7). Furthermore, the introduction SWNTs into the composite thin film render excellent mechanical flexibility for flexible electronics. The dynamic loading test presents evidently superior mechanical stability with only 17% variation at a bending radius as small as 700 mu m, and the repeated bending test shows only 8% normalized resistance variation after 300 cycles of folding and unfolding, demonstrating enormous improvement over the basic amorphous indium zinc oxide thin film. The results provide an important advance toward high-performance flexible electronics applications

Hypoxia-Induced HIF-1α Expression Promotes Neurogenic Bladder Fibrosis via EMT and Pyroptosis

Background: Neurogenic bladder (NB) patients exhibit varying degrees of bladder fibrosis, and the thickening and hardening of the bladder wall induced by fibrosis will further affect bladder function and cause renal failure. Our study aimed to investigate the mechanism of bladder fibrosis caused by a spinal cord injury (SCI). Methods: NB rat models were created by cutting the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves. RNA-seq, Western blotting, immunofluorescence, cell viability and ELISA were performed to assess the inflammation and fibrosis levels. Results: The rats showed bladder dysfunction, upper urinary tract damage and bladder fibrosis after SCI. RNA-seq results indicated that hypoxia, EMT and pyroptosis might be involved in bladder fibrosis induced by SCI. Subsequent Western blot, ELISA and cell viability assays and immunofluorescence of bladder tissue confirmed the RNA-seq findings. Hypoxic exposure increased the expression of HIF-1α and induced EMT and pyroptosis in bladder epithelial cells. Furthermore, HIF-1α knockdown rescued hypoxia-induced pyroptosis, EMT and fibrosis. Conclusion: EMT and pyroptosis were involved in the development of SCI-induced bladder fibrosis via the HIF-1α pathway. Inhibition of the HIF-1α pathway may serve as a potential target to alleviate bladder fibrosis caused by SCI

High Performance Amorphous ZnMgO/Carbon Nanotube Composite Thin-film Transistors with a Tunable Threshold Voltage

Here we report the fabrication and characterization of high mobility amorphous ZnMgO/single-walled carbon nanotube composite thin film transistors (TFTs) with a tunable threshold voltage. By controlling the ratio of MgO, ZnO and carbon nanotubes, high performance composite TFTs can be obtained with a field-effect mobility of up to 135 cm(2) V-1 s(-1), a low threshold voltage of 1 V and a subthreshold swing as small as 200 mV per decade, making it a promising new solution-processed material for high performance functional circuits. A low voltage inverter is demonstrated with a functional frequency exceeding 5 kHz, which is only limited by parasitic capacitance rather than the intrinsic material speed. The overall device performance of the composite TFTs greatly surpasses not only that of the solution-processed TFTs, but also that of the conventional amorphous or polycrystalline silicon TFTs. It therefore has the potential to open up a new avenue to high-performance, solution-processed flexible electronics which could significantly impact the existing applications, and enable a whole new generation of flexible, wearable, or disposable electronics

Rational Design of Amorphous Indium Zinc Oxide/Carbon Nanotube Hybrid Film for Unique Performance Transistors

Here we report unique performance transistors based on sol–gel processed indium zinc oxide/single-walled carbon nanotube (SWNT) composite thin films. In the composite, SWNTs provide fast tracks for carrier transport to significantly improve the apparent field effect mobility. Specifically, the composite thin film transistors with SWNT weight concentrations in the range of 0–2 wt % have been investigated with the field effect mobility reaching as high as 140 cm²/V·s at 1 wt % SWNTs while maintaining a high on/off ratio ∼10⁷. Furthermore, the introduction SWNTs into the composite thin film render excellent mechanical flexibility for flexible electronics. The dynamic loading test presents evidently superior mechanical stability with only 17% variation at a bending radius as small as 700 μm, and the repeated bending test shows only 8% normalized resistance variation after 300 cycles of folding and unfolding, demonstrating enormous improvement over the basic amorphous indium zinc oxide thin film. The results provide an important advance toward high-performance flexible electronics applications