Nucleophilic Organocatalyst for Photochemical Carbon Radical Generation via SN2 Substitution.

Photochemical generation of radicals is a powerful way to construct various molecules. But most of these methods rely on initiators or the redox properties of radical precursors. Herein, we report a photochemical organic catalyst that reacts with benzyl halide to generate carbon radical via an SN2 pathway. This nucleophilic catalyst can be easily prepared and is bench-stable. The SN2 process does not rely on the redox properties of halides, showing potential synthetic utility. Control experiments and UV-vis spectroscopic analysis indicate that the SN2 substitution adduct is the key intermediate.

Elevated serum mitochondrial DNA levels were associated with the progression and mortality in idiopathic pulmonary fibrosis.

Circulating mitochondrial DNA (mtDNA) was implicated in idiopathic pulmonary fibrosis (IPF), but the association between circulating mtDNA levels with clinical parameters in IPF was unclear. In this study, we investigate the relationship between serum mtDNA levels with the progression and mortality of IPF. Eighty-three patients with clinical diagnoses of IPF and fifty-three healthy controls were enrolled. Clinical data were collected and IPF patients were classified as stable disease (SD) and progressive disease (PD) based on the diagnostic criteria. Serum mtDNA levels were measured by real-time quantitative PCR and were compared between the two groups. Associations of the mtDNA levels with pulmonary function data and clinical parameters were assessed. Cox regression was performed to access the association between serum mtDNA levels with mortality in IPF. The serum mtDNA levels were significantly higher in IPF patients compared to those in healthy controls (P < 0.001), and further higher in patients with PD than those with SD (P < 0.001). Serum mtDNA levels were significantly inverse correlated with carbon monoxide diffusing capacity percent predicted (DLCO% predicted) (P = 0.030) and serum albumin levels (P = 0.008). During follow-up, 36 patients (43.4 %) died with a median survival of 46.00 (IQR: 25.00-69.75) months. Multivariate analysis showed that higher serum mtDNA levels were a significant predictor of mortality in IPF. In conclusion, elevated serum mtDNA levels were associated with the progression and mortality of IPF, which provided new insights that mitochondrial metabolism might have a potential role in the pathogenesis of IPF.

The Application of circRNA-016901 in Improving the Diagnostic Accuracy of Osteoarthritis.

In clinical practice, osteoarthritis (OA) is frequently misdiagnosed as rheumatoid arthritis (RA) and osteonecrosis (ON), leading to wrong treatment and disease progression. Circular RNA- (circRNA-) 016901 affects the recovery of irradiation-induced injury in the bone, while its role in OA is unclear. This study is aimed at exploring the role of circRNA-016901 in improving the diagnostic accuracy of OA. The present study included patients with OA (n = 80), patients with RA (n = 80), patients with ON (n = 80), and healthy controls (HCs, n = 80) to collect plasma samples before and after treatment. RT-qPCR was performed to detect RNA accumulation of circRNA-016901 in plasma samples from all participants. The role of plasma expression of circRNA-016901 in predicting OA was studied with ROC curve analysis. Association between plasma expression of circRNA-016901 and patients' clinical features was analyzed with the chi-squared test. Compared to HCs, increased accumulation of circRNA-016901 was only observed in the OA group, but not in the RA and ON groups before treatment. OA patients were effectively separated from the RA, ON, and HC groups using plasma expression of circRNA-016901 before treatment as a biomarker. Plasma expression of circRNA-016901 was closely associated with OA patients' disease severity. After treatment, decreased plasma expression levels of circRNA-016901 were only observed in OA patients, while no alteration in plasma circRNA-016901 accumulation was observed in the RA and ON groups. In conclusion, circRNA-016901 is accumulated to high levels in OA and may be applied to improve the diagnostic accuracy of OA.

KLF4 regulates TERT expression in alveolar epithelial cells in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) was considered as a telomere-mediated disease. TERT and TERC correlated with telomere length. Although telomerase gene mutations were associated with IPF, majority patients did not carry mutations. The mechanism by which telomerase expression was regulated in IPF are still unclear. In this study, we aimed to delineate the mechanisms that how TERT protein expression were regulated in alveolar epithelial cells (AECs) in pulmonary fibrosis. Here, we found that P16, P21 and fibrosis markers (αSMA and Collagen-I) were prominently increased in lung tissues of IPF patients and bleomycin-induced mouse models, while the expression of KLF4 and TERT were decreased in AECs. In vivo experiments, AAV-6 vectors mediated KLF4 over-expression with specific SP-C promoter was constructed. Over-expression of KLF4 in AECs could protect TERT expression and suppress the development of pulmonary fibrosis in bleomycin-induced mouse models. In the mechanism exploration of TERT regulation, KLF4 and TERT were both down-regulated in bleomycin-induced senescent MLE-12 and BEAS-2B cells. Compared with control group, small-interfering RNA targeting KLF4 significantly reduced the TERT expression and telomerase activity, while overexpression of KLF4 can increased the expression of TERT and telomerase activity in senescent AECs. Furthermore, ChIP showed that KLF4 protein could bind to the TERT promoter region in MLE-12 cells, suggesting that KLF4 could implicate in pathogenesis of lung fibrosis through regulating TERT transcription in AECs. Taken together, this study identified that KLF4 might be a promising potential target for further understanding the mechanism and developing novel strategy for the treatment of lung fibrosis in IPF.

Signal Detection for GSTFIM Systems with Carrier Frequency Offset.

Generalized space-time-frequency index modulation (GSTFIM) inherits the drawbacks of the conventional orthogonal frequency-division multiplex (OFDM), such as being sensitive to carrier frequency offset (CFO). For a robust design against this problem, in this contribution, a novel construction of a message passing (MP)-aided detector is developed for GSTFIM systems to combat the influence of CFO, while offering a flexible tradeoff between transmission performance and computational complexity. Through complexity analysis and simulation results, we demonstrate that, in the context of CFO, with a careful design, the developed MP detector is capable of approaching traditional GSTFIM with maximum likelihood (ML) detection, and of offering better performance at lower complexity compared to its minimum mean-square-error (MMSE)-aided counterpart.

Isoflurane post-conditioning attenuates cerebral ischemia/reperfusion injury by reducing apoptotic through activating the BMP7/SMAD signaling pathway in rats.

The expressions of different temporal patterns of bone morphogenetic proteins (BMPs) have changed after ischemic strokes, and ischemic preconditioning-induced neuroprotection was attenuated when BMP7 was inhibited. In the previous study, the neuroprotection of isoflurane postconditioning (ISPOC) against cerebral ischemia-reperfusion (I/R) injury has been addressed, with particular relevance to the role of BMP7. Consequently, in the present study, we continued to explore the mechanisms involved in the BMP7 signal mediated the neuroprotection of ISPOC. A rat model of the middle cerebral artery occlusion was used in this study. Rats were administered 1.5 % isoflurane, 60 min after 90 min of ischemia, followed by a 24 h reperfusion period. The 1.5 % ISPOC significantly ameliorated the cerebral infarct volumes, neurologic deficit scores, damaged neurons, and apoptotic neurons. Moreover, ISPOC unregulated the expressions of BMP7, p-Smad1/5/9, and p-p38. Whereas, the neuroprotective effect was weakened by LDN-193189 and SB203580, respectively, a BMP7/Smad1/5/9 and p38MAPK signaling pathway inhibitor. Furthermore, LDN-193189 downregulated the expression of p-p38. The present results of this study indicated that the neuroprotection of 1.5 % isoflurane postconditioning to cerebral ischemia-reperfusion injury is related to the activating of BMP7/Smad1/5/9 and p38MAPK signal pathway.

SNHG14 induces osteogenic differentiation of human stromal (mesenchymal) stem cells in vitro by downregulating miR-2861.

BACKGROUND: The differentiation of human stromal (mesenchymal) stem cells (hMSCs) is a critical procedure for the development of osteoblast. SNHG14 is a newly discovered lncRNA that has been barely studied. Our preliminary experiments showed that SNHG14 may be dysregulated in the differentiation of hMSCs. In this study, we focused on elucidating the relationships among SNGH14, miR-2861, and osteoblastic differentiation of hMSCs. METHOD: To investigate the roles of SNHG14 and miR2861 in hMSCs differentiation, qRT-PCR, luciferase activity, cell transfections, the detections of ALP activity, and Alizarin Red staining were performed. RESULT: We found that the expression of SNHG14 was enhanced, while the expression of miR-2861 was suppressed in serum and hMSCs from patients with osteoporosis. SNHG14 could target miR-2861, and shSNHG14 suppressed osteoblast differentiation of hMSC. MiR-2861 suppressed osteoblast differentiation of hMSC. In addition, the effects of SNHG14 on osteoblast differentiation of hMSC were attenuated by miR-2861. CONCLUSION: In conclusion, our experimental data showed that the induction effects of SNHG14 on osteoblast differentiation of hMSC were attenuated by miR-2861. SNHG14 could induce osteogenic differentiation of hMSC in vitro by targeting miR-2861.

Correlation between Preoperative Anxiety and ABO Blood Types: Evidence from a Clinical Cross-Sectional Study.

Gene-environment interaction is identified as the determinant in anxiety. ABO blood types represent a part of the genetic phenotype. Therefore, we assume ABO blood types correlate with preoperative anxiety. This cross-sectional study enrolled 352 patients with different ABO blood types, scheduled for elective surgery between 2018 and 2019 in the First Affiliated Hospital of Shihezi University. HADS (hospital anxiety and depression scale) scores and VA (visual analogue scales for anxiety) scores were all used to assess the preoperative anxiety in the A, B, AB, and O groups. Bivariate correlation and logistic regression were performed to identify relationships between preoperative anxiety and related variables. A significant difference in VA and HADS-A (anxiety) scores was found between the AB and other groups. The ratio of preoperative anxiety was 3.73 (95% CI [confidence interval]: 2.32-6.00, P < 0.001) times in female than in male; 0.36 (95% CI: 0.21-0.63, P < 0.001) times in ASA (American Society of Anesthesiologists) grade II than in grade I; 0.41 (95% CI: 0.20-0.86, P < 0.05) times in ASA grade III than in grade I; 1.25 (95% CI: 1.1-1.41, P < 0.001) times in higher VAS (visual analogue scales for pain) scores than in lower VAS scores; and 0.28 (95% CI: 0.16-0.49, P < 0.01) times in non-AB blood type than in AB blood type. Differences in ABO blood types were found in preoperative anxiety, and the AB group displayed a high preoperative anxiety level. ABO blood types, sex, ASA grade, and VAS were associated with preoperative anxiety. This trial is registered with ChiCTR1800019390.

Paper-like Foldable Nanowave Circuit with Ultralarge Curvature and Ultrahigh Stability.

Highly foldable conducting interconnects are fundamental elements for multipurpose flexible electronic circuits, including wearable electronics and biomedical devices. Traditional metalized thin-film interconnects demonstrate stable electronic performances in rigid devices but low deformation tolerance in flexibility. Recently, several remarkable research studies on flexible electronics have been carried out, as interconnect structures of serpentine, wavy, and nanowire networks. However, all of the reported flexible interconnects possess either mechanical instability or fabrication difficulty, which restrict their practical applications. Here, we report a new flexible circuit system, which consists of nanowave structure metal interconnects with highly foldable and large-scale manufactured features. This kind of nanowave interconnects presents both stable and prominent electrical performances under mechanical deformation (down to 0.2 mm bending radius with interconnecting resistance variation less than 10%). Further, a highly flexible paper-like wireless accelerometer based on the nanowave interconnects is fabricated and characterized under several extreme strain situations. Our approach affords a comprehensive direction for constitutional realization of new flexible designs and implements the assembly of next-generation foldable electronic equipment.

Size-dependent Young's modulus in ZnO nanowires with strong surface atomic bonds.

The mechanical properties of size-dependent nanowires are important in nano-electro-mechanical systems (NEMSs), and have attracted much research interest. Characterization of the size effect of nanowires in atmosphere directly to broaden their practical application instead of just in high vacuum situations, as reported previously, is desperately needed. In this study, we systematically studied the Young's modulus of vertical ZnO nanowires in atmosphere. The diameters ranged from 48 nm to 239 nm with a resonance method using non-contact atomic force microscopy. The values of Young's modulus in atmosphere present extremely strong increasing tendency with decreasing diameter of nanowire due to stronger surface atomic bonds compared with that in vacuum. A core-shell model for nanowires is proposed to explore the Young's modulus enhancement in atmosphere, which is correlated with atoms of oxygen occurring near the nanowire surface. The modified model is more accurate for analyzing the mechanical behavior of nanowires in atmosphere compared with the model in vacuum. Furthermore, it is possible to use this characterization method to measure the size-related elastic properties of similar wire-sharp nanomaterials in atmosphere and estimate the corresponding mechanical behavior. The study of the size-dependent Young's modulus in ZnO nanowires in atmosphere will improve the understanding of the mechanical properties of nanomaterials as well as providing guidance for applications in NEMSs, nanogenerators, biosensors and other related areas.