Search

The PMAI-based PSCs form multiple NH⋯I hydrogen bonds, which can passivate interface defects and suppress ion migration and diffusion.

Black-phase formamidinium lead iodide (FAPbI

To investigate the relationship between blood pressure variability (BPV) and incidence of post-traumatic stress disorder (PTSD) in trauma patients.Patients admitted to the department of emergency medicine of the Affiliated Hospital of Xuzhou Medical University for acute trauma from January 2018 to December 2021 were enrolled. The clinical data and blood pressure at admission (T1), 10 minutes before anesthesia (T2), 60 minutes after surgery (T3), and 24 hours after surgery (T4) were collected. Coefficient of variation of blood pressure variation [CV-BP, including coefficient of variation of systolic blood pressure (CV-SBP), coefficient of variation of diastolic blood pressure (CV-DBP), coefficient of variation of mean arterial pressure (CV-MAP)] and its quartile were calculated. Patients were divided into Q1 group (CV-MAP ≤ 7.27), Q2 group (7.27CV-MAP ≤ 9.50), Q3 group (9.50CV-MAP ≤ 14.05) and Q4 group (CV-MAP14.05) according to CV-MAP quartile. The PTSD symptoms of the patients were evaluated using the PTSD scale (PCL-5) one month later, and the patients were divided into the PTSD group and the non-PTSD group according to whether PCL-5 score higher than 38. Then the differences of the above indicators were compared and analyzed. Spearman correlation analysis was used to analyze the relationship between each index and PCL-5 score; the risk factors of PTSD were analyzed by univariate binary Logistic regression. Variables with P0.05 were included in the multivariate binary Logistic regression model. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of CV-MAP on the incidence of PTSD.A total of 112 patients were enrolled, including 24 in PTSD group and 88 in non-PTSD group. Compared with non-PTSD group, the proportion of women, T1 shock index, proportion of intraoperative and postoperative blood transfusion in PTSD group was higher. Besides, PTSD group also had longer PT, more intraoperative and postoperative blood transfusion, and lower postoperative hemoglobin (Hb) level (all P0.05). The T1 SBP, DBP, MAP and T4 MAP of patients in PTSD group were significantly lower than those in non-PTSD group [T1 SBP (mmHg, 1 mmHg ≈ 0.133 kPa): 105.0 (86.3, 121.3) vs. 122.0 (112.0, 132.8), T1 DBP (mmHg): 62.5 (50.0, 77.3) vs. 76.0 (68.5, 82.8), T1 MAP (mmHg): 77.8 (60.4, 91.3) vs. 93.3 (82.5, 99.0), T4 MAP (mmHg): 83.8±9.1 vs. 88.7±10.4, all P0.05], CV-SBP, CV-DBP and CV-MAP were higher than those in the non-PTSD group [CV-SBP: 12.80 (10.12, 19.16) vs. 9.30 (6.07, 12.95), CV-DBP: 16.62±6.47 vs. 12.40±5.61, CV-MAP: 14.10 (9.25, 18.85) vs. 8.90 (6.93, 13.29), all P0.05]. Spearman correlation analysis showed that there was a positive correlation between CV-MAP and PCL-5 scores in patients with acute trauma (r = 0.429, P0.001); multivariate binary Logistic regression analysis showed that only CV-MAP [odds ratio (OR) = 1.128, 95% confidence interval (95%CI) was 1.015-1.254, P = 0.025] and CV-DBP (OR = 1.114, 95% confidence interval (95%CI) was 1.016-1.221, P = 0.022) was the risk factor for PTSD in acute trauma patients. Compared with Q1 group, Q4 group was significantly more likely to develop PTSD (OR = 18.6, 95%CI was 1.9-179.1, P = 0.012). CV-SBP, CV-DBP and CV-MAP had certain predictive value on PTSD diagnosis in patients with acute trauma according to ROC curve analysis results [area under the ROC curve (AUC) was 0.713, 0.682 and 0.726, respectively], among which CV-MAP has the highest predictive value. When the cut-off value of CV-MAP was 12.158, the sensitivity was 75.0% and the specificity was 69.3%.Higher BPV after trauma is a risk factor for PTSD. Maintaining stable blood pressure in trauma patients is of great significance for prevention and treatment of PTSD.

Poly (ADP-ribose) polymerase-1 (PARP1), a DNA repair gene, is the crucial player in the maintenance of genome integrity. T2285C polymorphism in coding region of PARP1 has been reported to be associated with susceptibility to tumours. We explored the relationship and mechanism of T2285C polymorphism of PARP1 to its expression and activity along with risk and prognosis in non-small cell lung cancer (NSCLC). mRNA expression was measured using quantitative RT–PCR assay or collected from TCGA dataset. Protein expression was examined with immunoblotting assay. Genotypes were determined by PCR-RFLP and sequencing approaches. PARP1 activity was determined with enzyme activity assay. Regulation of SIRT7 to PARP1 was determined by overexpression and small interference experiment. Association of PARP1 T2285C polymorphism with NSCLC risk was evaluated via multiple logistic regression analysis. Comparison of treatment response and progression-free survival (PFS) of NSCLC patients among different genotypes or regimens was made by chi-square test. Results indicated that mRNA and protein expression of PARP1 dramatically increased in NSCLC tissues in comparison with paired para-carcinoma tissues (P < 0.05). TC/CC mutant genotypes were associated with markedly enhanced PARP1 mRNA level compared with TT genotype (P = 0.011). No significant difference was discovered in PARP1 protein expression among TT, TC or CC genotypes (P > 0.05). Subjects with variant allele C had higher risk of NSCLC in comparison with allele T carriers [odds ratio = 1.560; P = 0.000]. NSCLC patients carrying mutational TC or CC genotypes were correlated with unfavourable response to platinum-based chemotherapy (TT vs. TC vs. CC, P = 0.010), and shorter PFS compared with TT genotype (TT vs. TC vs. CC, P = 0.009). T2285C mutation of PARP1 resulted in the enhancement of its mRNA, but the decrease of enzyme activity in tumour cell. Overexpression of SIRT7 attenuated PARP1 expression and activity. These findings suggest the variant allele C of T2285C polymorphism of PARP1 linked to an increase of NSCLC risk, and unfavourable efficacy and prognosis of NSCLC patients with platinum-based chemotherapy, which might be associated with enhancement of its mRNA expression and the diminishment of activity. Identification of PARP1 T2285C polymorphism and mRNA expression may be the promising way for the individualised treatment of NSCLC.

In recent years, perovskite solar cells (PSCs) have been attracting more and more attention. Although perovskite materials have high defect tolerance, defects remain the main factor that seriously affects the efficiency and stability of PSCs. Herein, the ionic liquid of 1-butyl, 3-methylimidazolium acetate ([BMIM][ACO]) was introduced into the SnO2/perovskite interface for the first time. Thanks to the dipoles formed by ILs spontaneously, the work function of SnO2 was reduced and the transport ability of carriers was improved as well. Moreover, the Lewis acidity and lone pair electrons of [BMIM][ACO] contribute to the passivation of I– defects, Pb2+ defects, or Pb-I anti site defects. In addition, the presence of dipoles will repel the approach of photogenerated holes and the reverse transport of electrons, reducing the recombination of defect sites through field-effect passivation. The solar cell with efficiency of 19.43% was obtained under such a dual passivation effect, and the best device maintained 75.21% of the initial efficiency after 80 h of continuous illumination.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe syndrome lacking efficient therapy and resulting in high morbidity and mortality. Although resveratrol (RES), a natural phytoalexin, has been reported to protect the ALI by suppressing the inflammatory response, the detailed mechanism of how RES affected the immune system is poorly studied. Pulmonary conventional dendritic cells (cDCs) are critically involved in the pathogenesis of inflammatory lung diseases including ALI. In this study, we aimed to investigate the protective role of RES via pulmonary cDCs in lipopolysaccharide (LPS)-induced ALI mice. Murine ALI model was established by intratracheally challenging with 5 mg/kg LPS. We found that RES pretreatment could mitigate LPS-induced ALI. Additionally, proinflammatory-skewed cytokines decreased whereas anti-inflammatory-related cytokines increased in bronchoalveolar lavage fluid by RES pretreatment. Mechanistically, RES regulated pulmonary cDCs’ maturation and function, exhibiting lower level of CD80, CD86, major histocompatibility complex (MHC) II expression, and IL-10 secretion in ALI mice. Furthermore, RES modulated the balance between proinflammation and anti-inflammation of cDCs. Moreover, in vitro RES pretreatment regulated the maturation and function of bone marrow derived dendritic cells (BMDCs). Finally, the adoptive transfer of RES-pretreated BMDCs enhanced recovery of ALI. Thus, these data might further extend our understanding of a protective role of RES in regulating pulmonary cDCs against ALI.

Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury.Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis.SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3'-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes.SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury.

Human cytomegalovirus (HCMV) infection in the respiratory tract leads to pneumonitis in immunocompromised hosts without available vaccine. Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV‐specific pulmonary mucosal vaccine development that provides a long‐lasting protection against CMV challenge gains our attention. In this study, N‐terminal domain of GP96 (GP96‐NT) was used as a mucosal adjuvant to enhance the induction of pulmonary‐resident CD8 T cells elicited by MCMV glycoprotein B (gB) vaccine. Mice were intranasally co‐immunized with 50 μg pgB and equal amount of pGP96‐NT vaccine 4 times at 2‐week intervals, and then i.n. challenged with MCMV at 16 weeks after the last immunization. Compared with pgB immunization alone, co‐immunization with pgB/pGP96‐NT enhanced a long‐lasting protection against MCMV pneumonitis by significantly improved pneumonitis pathology, enhanced bodyweight, reduced viral burdens and increased survival rate. Moreover, the increased CD8 T cells were observed in lung but not spleen from pgB/pGP96‐NT co‐immunized mice. The increments of pulmonary CD8 T cells might be mainly due to non‐circulating pulmonary‐resident CD8 T‐cell subset expansion but not circulating CD8 T‐cell populations that home to inflammation site upon MCMV challenge. Finally, the deterioration of MCMV pneumonitis by depletion of pulmonary site‐specific CD8 T cells in mice that were pgB/pGP96‐NT co‐immunization might be a clue to interpret the non‐circulating pulmonary‐resident CD8 T subset expansion. These data might uncover a promising long‐lasting prophylactic vaccine strategy against MCMV‐induced pneumonitis.

Background NEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown. Methods We detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR. Results We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression. Conclusions Our results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.

p21-activated kinase 6 (PAK6), a member of the serine/threonine kinase family, has been reported to be involved in numerous types of cancers. The present study aimed to investigate the role of PAK6 in cervical cancer. In the present study, PAK6 expression was evaluated in tissue microarrays and cell lines by using immunohistochemistry and western blotting. The mRNA level of PAK6 was evaluated by reverse transcription quantitative PCR. The Wnt/β-catenin signaling-related protein expression was detected by western blotting following short hairpin (sh)RNA-mediated PAK6 knockdown or PAK6 overexpression. Cell proliferation was determined using Cell Countink Kit-8. Migration, invasion and colony formation were further assessed following PAK6 knockdown or overexpression. Co-immunoprecipitation (Co-IP) and fluorescence colocalization microscopy were used to detect the interaction between PAK6 and GSK3β. The results from tissue microarray revealed that the expression levels of PAK6 in cervical cancer tissues were upregulated. The downregulation of PAK6 expression levels using shRNA not only decreased cell growth and proliferation, but it also inhibited the migration and invasion of HeLa cells. Conversely, the overexpression of PAK6 promoted the proliferation, migration and invasion of HeLa cells. In addition, the expression levels of proteins involved in the Wnt/β-catenin signaling pathway were modified in the PAK6 knockdown group, including downregulation of GSK3β phosphorylation and Cyclin D1 protein, and upregulation of β-catenin phosphorylation and E-cadherin. In contrast, following the overexpression of PAK6, the Wnt/β-catenin signaling pathway was activated. Further investigation using fluorescence microscopy and Co-IP assays indicated that PAK6 may interact with GSK3β. In conclusion, the findings of the present study suggested that PAK6 may serve a role in promoting cervical cancer through activating the Wnt/β-catenin signaling pathway.

In native bone tissue regeneration, blood vessels, providing oxygen and nutrition for tissues, can promote the regeneration of bone and accelerate the repair of a defected area. In this study, Poly(D, L-lactic-co-glycolic acid) (PLGA) inverse opal scaffolds with high pore interconnectivity were fabricated and further modified with vascular endothelial growth factor (VEGF). The rat bone marrow derived mesenchymal stem cells (rMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured onto the scaffolds to enhance vascularization for bone tissue regeneration. Cell attachment, viability, proliferation, and morphology were detected by cell counting kit-8 (CCK-8) assay, live and dead staining and scanning electron microscopy (SEM). Hydrostatic pressure with 0-279 KPa and 1 Hz one hour per day for 7 days was applied to tissue engineered bone constructs to investigate whether the loading stimulation can promote osteogenesis and angiogenesis mutually evaluated in parallel by multiple in vitro assays and in an in vivo chicken chorioallantoic membrane (CAM) model. The results indicated that the immobilization of VEGF can improve biocompatibility of PLGA scaffolds and promote cell attachment and proliferation. The cell-scaffold constructs showed higher CD31 expression because of the angiogenic differentiation of rMSCs in hydrostatic loading culture condition in vitro. The in vivo CAM model experiment demonstrated that hydrostatic loading stimulated angiogenic differentiation of rMSCs can accelerate tubulogenesis. Furthermore, the new capillaries formed in cell-scaffold constructs were conducive to calcium deposition in vivo.

Posttraumatic stress disorder (PTSD) and other anxiety disorders stem from dysregulated fear memory in which the basolateral amygdala (BLA) plays an integral role. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergic neurons. However, definitive evidence for the involvement of the SK2 channel in the BLA in fear extinction is lacking. Here, we discovered that fear conditioning decreased the levers of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levers of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane palmitoylated protein 2 (MPP2). Collectively, our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of fear memory. These findings expand our understanding of the neurobiological mechanism of PTSD and provide a new direction for PTSD treatment.

Black-phase formamidinium lead iodide (FAPbI3), with a narrow bandgap and high thermal stability, has emerged as an in-demand material for highly efficient perovskite solar cells (PSCs). In a two-step sequential deposition, the PbI2 film plays an important role in the formation of a perovskite film with desirable qualities. This paper explores using N-methyl-2-pyrrolidone (NMP), a strong Lewis base, and N,N-dimethylformamide (DMF) as a mixed precursor solvent (DMF/NMP) of PbI2 and reports on preparing PbI2 films with a porous morphology by thermal treatment. Porous PbI2 films ensure the diffusion and sufficient reaction of the formamidinium iodide solution to form a smooth perovskite film. In addition, a dynamic spin coating method is also introduced to improve the uniformity of the perovskite film. Both methods yield a pure α-phase FAPbI3 film immediately in the unannealed state, which is necessary for the perovskite film to maintain phase stability. Finally, PSCs with a power conversion efficiency of 21.20% (0.13 cm2) are fabricated and optimized. The unencapsulated PSCs retain 90% of the initial efficiency for 1000 hours in dry air and exhibit a good thermal stability when heated to 85 °C.

During the voyage, predicting fuel consumption of ships under different sea-states and weather conditions has been a challenging and far-reaching topic, because there are a great number of feature variables affecting the fuel consumption, including main-engine status, cargo weight, ship draft, sea-states and weather conditions, etc. Data driven statistical models have been employed to model the relationship between fuel consumption rate and these voyage parameters. However, some of the feature variables are highly correlated, e.g. wind speed and wave height, air pressure and wind force, cargo weight and draft etc., thus a typical multiple collinearity problem arises so that the fuel consumption cannot be accurately calculated by using the traditional multiple linear regression. In this study, the LASSO (Least Absolute Shrinkage and Selection Operator) regression algorithm is employed to implement the variable selection for these feature variables, additionally, it guides the trained predictor towards a generalizable solution, thereby improving the interpretability and accuracy of the model. On the basis of the LASSO, a novel ship fuel consumption prediction model is proposed. Experimentally, the superiority of the proposed method was confirmed by comparing it with some existing methods on predicting the fuel consumption. The proposed method is a promising development that improves the calculation of the fuel consumption.

An industrial volatile organic compounds (VOCs) emission inventory was developed in China in 2018. It was based on the emission factors method, using a revised and updated source classification system and emission factors of key industrial sources. Results showed that the total industrial VOCs emission in China in 2018 reached as high as 12698 kt. Processes using products containing VOCs were the largest contributors, accounting for 59% of the total emission. The industrial coating industry, printing, the basic organic chemical industry, gasoline storage and transport, and the oil refinery industry were the five largest emitters, accounting for 54% of the total emission. Guangdong, Shandong, Zhejiang, and Jiangsu were the four largest emission contributors, contributing to 41% of the total emission. Hainan, Ningxia, Tibet, Heilongjiang, and Xinjiang showed the largest VOCs emission intensities, with more than 80 t·(100 million yuan)

STUDY DESIGN Basic science. OBJECTIVE The aim of this study was to examine the effect of vascular endothelial growth factor (VEGF)-transfected bone marrow mesenchymal stem cells (BMSCs) on the recovery of motor and sensory functions of rats with spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA There is no effective treatment to protect against SCI. BMSCs have been widely applied to the treatment of nervous system damage due to the function of prompt neurite growth and inhibition of demyelination following injury. METHODS VEGF-transfected BMSCs were injected to rats with SCI and the recovery of motor and sensory functions was observed. The Basso, Beattie, and Bresnahan, mechanical withdrawal threshold and thermal withdraw latency grading was conducted to assess the recovery status of motor and sensory functions of the SCI rats. The expression of VEGF, CD31, and NF200 was detected by immunofluorescence. RESULTS The recovery of the rat motor and sensory functions in the VEGF-transfected BMSC (BMSC-VEGF) group was higher than those of the other groups with the exception of the Sham group (P < 0.05). The expression of the CD31 and NF200 proteins in the rat SCI regions was the highest in the BMSC-VEGF group, whereas the survival of BMSC in the BMSC-VEGF group was increased compared with that in the BMSC-Ad group. In addition, the injection of VEGF-transfected BMSCs can improve the angiogenesis of the injured area and retain the survival of injected cells and neurons. CONCLUSION The injection of BMSC-VEGF improved the recovery of motor function in SCI rats. LEVEL OF EVIDENCE N/A.

The purpose of this work was to investigate if the biomimetically conjugated VEGF and HUVECs co-culture could modulate the osteogenic and angiogenic differentiation of MSCs derived from rat and human bone marrow (rMSCs and hMSCs). After treated by ammonia plasma, Poly(lactic-co-glycolic acid) (PLGA) electrospun nanofibers were immobilized with VEGF through heparin to fulfil the sustained release. The proliferation capacity of rMSCs and hMSCs on neat PLGA nanofibers (NF) and VEGF immobilized NF (NF-VEGF) surfaces were assessed by CCK-8 and compared when MSCs were mono-cultured and co-cultured with HUVECs. The effect of VEGF and HUVECs co-culturing on osteogenic and angiogenic differentiation of rMSCs and hMSCs were investigated by calcium deposits and CD31 expression on NF and NF-VEGF surfaces. The results indicated that VEGF has been biomimetically immobilized onto PLGA nanofibers surface and kept sustained release successfully. The CD31 staining results showed that both VEGF and HUVECs co-culture could enhance the angiogenesis of rMSCs and hMSCs. However, the proliferation and osteogenic differentiation of MSCs when cultured with VEGF and HUVECs showed a species dependent response. Taken together, VEGF immobilization and co-culture with HUVECs promoted angiogenesis of MSCs, indicating a good strategy for vascularization in bone tissue engineering.

BackgroundAngiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer.MethodsWe searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events.ResultsFifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71–0.97) and no improved OS (HR, 0.95; 95% CI, 0.86–1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65–0.81) and OS (HR, 0.84; 95%CI, 0.74–0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52–0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79–0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63–1.01) or OS (HR, 1.06; 95% CI, 0.88–1.28) in the pure maintenance therapy.In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66–3.97), hypertension (RR, 7.60; 95% CI, 2.79–20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34–3.84), proteinuria (RR, 4.31; 95% CI, 2.15–8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12–2.63).ConclusionsCombination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.

This paper presents an introduction to a deformable plasma antenna excited by an alternating current power supply at a frequency of 12 kHz. The deformable discharge tube could be transformed into many types of shapes, such as a monopole, U-shape, loop, helix, or plane, by means of a simple mounting and rotating system. The characteristics of the antenna were studied for various discharge parameters and antenna shapes. Experimental results demonstrate that the antenna characteristics, such as impedance, radiation pattern, gain, and polarization, can be simply controlled by varying the discharge parameters and antenna shapes. Compared with a conventional plasma antenna made of hard materials, the reconfiguration scope of the deformable plasma antenna is considerably broader. Moreover, the antenna shape can be modified in a manner that is both flexible and easily implemented.

Vascular endothelial growth factor (VEGF) stimulation and bone marrow mesenchymal stem cell (BMSC) transplantation have been implicated in the treatment of acute cerebral infarction for their pivotal roles in behavioral recovery, neuroprotection, neurogenesis, and angiogenesis. However, the effects of BMSC transplants are likely limited because of low transplant survival after acute cerebral infarction, and delivery of VEGF alone also has limited effects on recovery because the protein is cleared quickly. This study attempted to explore whether VEGF could be transferred into BMSC via an adenovirus and whether transplanting VEGF-transfected BMSC into the rat brain provides sufficient neuroprotection after transient middle cerebral artery occlusion. The adenovirus carried VEGF into BMSC (Ad-VEGF-BMSC), and purified adenovirus was transferred into BMSC (Ad-BMSC). Western blots were used to detect the expression of VEGF protein after transfection. Rats exposed to 90-min middle cerebral artery occlusion (MCAO) were treated with Ad-VEGF-BMSC, Ad-BMSC, BMSC and Dulbecco's Modified Eagle's Medium (DMEM) after ischemia reperfusion for 24h. The Sham group only received surgery. After transplantation of Ad-VEGF-BMSC into the perifocal area of the ischemic rat brain, we found increased expression and secretion of VEGF and BDNF as well as a higher level of MAP2, increased microvascular density, improved behavioral function and enhanced BMSC survival. Our results indicated that transplantation of Ad-VEGF-BMSC improved ischemic neurological deficiency after MCAO in rats. This finding provides a potential valuable therapeutic intervention for cerebral ischemic diseases.

Action potentials, taking place over milliseconds, are the basis of neural computation. However, the dynamics of excitability over longer, behaviorally relevant timescales remain underexplored. A recent experiment used long-term recordings from single neurons to reveal multiple timescale fluctuations in response to constant stimuli, along with more reliable responses to variable stimuli. Here, we demonstrate that this apparent paradox is resolved if neurons operate in a marginally stable dynamic regime, which we reveal using a novel inference method. Excitability in this regime is characterized by large fluctuations while retaining high sensitivity to external varying stimuli. A new model with a dynamic recovery timescale that interacts with excitability captures this dynamic regime and predicts the neurons' response with high accuracy. The model explains most experimental observations under several stimulus statistics. The compact structure of our model permits further exploration on the network level.SIGNIFICANCE STATEMENTExcitability is the basis for all neural computations and its long-term dynamics reveal a complex combination of many timescales. We discovered that neural excitability operates under a marginally stable regime in which the system is dominated by internal fluctuation while retaining high sensitivity to externally varying stimuli. We offer a novel approach to modeling excitability dynamics by assuming that the recovery timescale is itself a dynamic variable. Our model is able to capture a wide range of experimental phenomena using few parameters with significantly higher predictive power than previous models.

Recently, several studies have demonstrated that reactive oxygen species are responsible for inducing multiple organ failure and septic shock. Particularly, mitochondrial dysfunction has been demonstrated in the pathogenesis of multiple organ dysfunction syndrome (MODS). In cytopathic hypoxia, impairment of mitochondrial oxidative phosphorylation decreases aerobic adenosine triphosphate (ATP) production and potentially induces MODS. Shen-Fu (SF) injections are widely used in the treatment of various diseases. SF exhibits cardiovascular protective effects. For example, it can stretch the coronary artery, stabilize blood pressure, regulate IRI, and improve the overall heart function. Clinical studies have demonstrated that SF injections have notable therapeutic effects on septic and hemorrhagic shocks. In the present study, the effects of SF injection on mitochondrial function in the intestinal epithelial cells of rats with endotoxemia were analyzed.

This study introduces a physical training evaluation method based on the analytic hierarchy process to solve the difficulty of quantifying the evaluation of the physical training of college students. First, this method establishes an evaluation index system and constructs the corresponding evaluation index judgement matrix. Second, it normalises and calculates the index combination weight for constructing the basic evaluation model. Finally, this evaluation model is comprehensively utilised to evaluate the physical training of college students. The results denote that the method proposed in this study can effectively evaluate the physical training of college students. When compared with the traditional assessment method, the proposed method can better reflect the real physical condition and highlight the physical characteristics of the college students as well as conduct targeted training for the college students.

Repeated traumatic brain injury, leads to cumulative neuronal injury and neurological impairments. There are currently no effective treatments to prevent these consequences. Growing interest is building in the use of transcranial photobiomodulation (PBM) therapy to treat traumatic brain injury. Here, we examined PBM in a repeated closed head injury (rCHI) rat model. Rats were administered a total of three closed head injuries, with each injury separated by 5 days. PBM treatment was initiated 2 hours after the first injury and administered daily for a total of 15 days. We found that PBM-treated rCHI rats had a significant reduction in motor ability, anxiety and cognitive deficits compared to CHI group. PBM group showed an increase of synaptic proteins and surviving neurons, along with a reduction in reactive gliosis and neuronal injury. These findings highlight the complexity of gliosis and neuronal injury following rCHI and suggest that PBM may be a viable treatment option to mitigate these effects and their detrimental consequences.

Having advantageous biocompatibility and osteoconductive properties known to enhance the osteogenic differentiation of mesenchymal stem cells (MSCs), hydroxyapatite (HA) is a commonly used material for bone tissue engineering. What remains unclear, however, is whether HA holds a similar potential for stimulating the osteogenic differentiation of MSCs to that of a more frequently used osteogenic-inducing medium (OIM). To that end, we used PHBV electrospun nanofibrous scaffolds to directly compare the osteogenic capacities of HA with OIM over MSCs. Through the observation of cellular morphology, the staining of osteogenic markers, and the quantitative measuring of osteogenic-related genes, as well as microRNA analyses, we not only found that HA was as capable as OIM for differentiating MSCs down an osteogenic lineage; albeit, at a significantly slower rate, but also that numerous microRNAs are involved in the osteogenic differentiation of MSCs through multiple pathways involving the inhibition of cellular proliferation and stemness, chondrogenesis and adipogenesis, and the active promotion of osteogenesis. Taken together, we have shown for the first time that PHBV electrospun nanofibrous scaffolds combined with HA have a similar osteogenic-inducing potential as OIM and may therefore be used as a viable replacement for OIM for alternative in vivo-mimicking bone tissue engineering applications.

With the wide use of AIS system in the world, especially in ports and the waters with heavy traffic, AIS message loss may be related to environmental conditions, obstacle, limitation of VHF technology and AIS network overload, thereby reducing the AIS signal successful reception rate. This paper selected typical AIS data received by Yagi and Omni antennas at the same time in specific waters, uses grid and AIS data recovery technology, establishes the AIS signal coverage model, analyzes signal reception rate of Yagi antenna and Omni antenna of AIS base station, and verified the superiority of Yagi antenna in AIS signal reception rate.

This study analyses risk-return trade-off and behaviour of various volatility dynamics including: volatility, its persistence, mean reversion and speed of mean reversion along with asymmetry and leverage effect on the Pakistani stock market by employing aggregate (aggregate market level) and disaggregate (sectoral level) monthly data for the period from 1998 to 2012. Three generalised autoregressive conditional heteroscedasticity models were applied: GARCH (1,1) for various volatility dynamics; EGARCH for asymmetric and leverage effect and GARCH-M for pricing of risk. The outcomes of the study are as follows: first, the volatility shocks are quite persistent but with varying degrees across the sectors. Both the ARCH effect (short-term effect) and GARCH effect (long-term effect) play their role in generating conditional future stock returns volatility. Further, overall the volatility process is mean reverting; however, the speed of mean reversion varies across the sectors. Secondly, the current study finds little evidence of asymmetry and leverage effect at both aggregate and disaggregates data. Thirdly, the pricing of risk (positive risk premium) is also evident, particularly at the disaggregate data in the Pakistani stock market. Finally, this research study sets the implications for both the policy makers and investors.

In view of the influence of Metro under construction on the foundation pit excavation of the new commercial service project in the city and in order to ensure the safety of subway in the process of foundation pit excavation, combined with the geographical location and geological conditions of the project in this paper, the corresponding monitoring points were set up to protect and monitor the Metro near the project, so as to ensure the minimum impact on the Metro under the premise of normal construction of the foundation pit. The monitoring results were in line with the requirements of the specification, providing guarantee for the subsequent construction.

OBJECTIVE To screen for mutations in a Chinese pedigree affected with hypokalemic periodic paralysis. METHODS The proband and nine family members were enrolled for the analysis of CACNA1S and SCN4A gene mutations. Genomic DNA was extracted from peripheral blood samples. The coding regions of the two genes were amplified with PCR and subjected to Sanger sequencing. Potential impact of suspected mutations was predicted with Bioinformatics software. The mutations were also verified among 100 healthy controls. RESULTS The proband and 5 family members (including 5 males and 1 female) had presented with episodes of flaccid paralysis accompanied by low serum potassium. Genetic testing has identified a c.664CT (p.Arg222Trp) mutation in the proband, which has been reported previously. The same mutation was identified in other 5 affected members from the family. No mutation of the CACNA1S gene was detected. CONCLUSION The c.664CT mutation of the SCN4A gene probably underlies the hypokalemic periodic paralysis in this family. All patients from the family have shown a complete penetrance of the disease.

Previous studies have demonstrated that activation of proline-rich tyrosine kinase 2 (PYK2) in cerebral ischemia is involved in the modulation of N-methyl-d-aspartate-type (NMDA) glutamate receptor activity and Ca(2+) dynamics, resulting in ischemic neuron death ultimately. A number of reports indicate that PYK2 is a redox sensitive kinase that must be activated by an estrogen-induced reactive oxygen species (ROS). However, the mechanism of PYK2 activation remains incompletely illustrated. Accumulating attention is focused on nitric oxide (NO, a free radical) which plays a critical role in cellular signal transduction through stimulus-coupled S-nitrosylation of cysteine residues. Here we reported that PYK2 over-expressed in human embryonic kidney (HEK293) cells was S-nitrosylated (forming SNO-PYK2) by reacting with GSNO, an exogenous NO donor, at one critical cysteine residue (Cys534) with a biotin switch assay. Moreover, our results showed that S-nitrosylation and phosphorylation of PYK2 over-expressed in SH-SY5Y cells was significantly increased after oxygen-glucose deprivation (OGD). We further investigated whether the activation (phosphorylation) of PYK2 was associated with S-nitrosylation following SH-SY5Y cells OGD. Our results showed that the cysteine534 residue (site of S-nitrosylation) mutant PYK2 over-expressed in SH-SY5Y cells diminished S-nitrosylation of PYK2 and inhibited its phosphorylation induced by OGD. In addition, overexpression of the mutant PYK2 protein could prevent nuclear accumulation and abrogate neuronal cell death compared to wild type PYK2 in SH-SY5Y cells induced by OGD. These data suggest that the activation of PYK2 following OGD may be modulated by S-nitrosylation, which provides a new avenue for stroke therapy by targeting the post-translational modification machinery.