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Objective Palliative care (PC) can improve the quality of life of Parkinson’s disease (PD) patients and their carers. However, the impact of PC services on patients with PD remains unclear. This research was conducted to identify the barriers and facilitators influencing PC services for patients with PD based on the Social Ecological Model (SEM) framework. Methods This research was conducted through semi-structured interviews, employing SEM to organize themes and identify potential solutions across multiple levels. Results A total of 29 interviewees (5 PD clinicians, 7 PD registered nurses, 8 patients, 5 caregivers, and 4 policy makers) completed the interviews. Facilitators and barriers were identified according to the levels of the SEM. Several facilitators were identified, i.e., (1) individual level: the critical needs among PD patients and their relatives and the desire for PC knowledge among health professionals; (2) interpersonal level: social support; (3) organizational level: the investments towards systematization of PC; and nurses are the bridge between patients and doctors; (4) community level: the convenience of community services; and hospital-community-family-based services; (5) culture and policy level: existing policy. Conclusion The social-ecological model proposed in this study helps illuminate the complex and multilevel factors that may influence PC delivery to PD patients.

Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes. Currently, the prevalence and mortality of DKD are increasing annually. However, with no effective drugs to prevent its occurrence and development, the primary therapeutic option is to control blood sugar and blood pressure. Therefore, new and effective drugs/methods are imperative to prevent the development of DKD in patients with diabetes. Mesenchymal stem cells (MSCs) with multi-differentiation potential and paracrine function have received extensive attention as a new treatment option for DKD. However, their role and mechanism in the treatment of DKD remain unclear, and clinical applications are still being explored. Given this, we here provide an unbiased review of recent advances in MSCs for the treatment of DKD in the last decade from the perspectives of the pathogenesis of DKD, biological characteristics of MSCs, and different molecular and signaling pathways. Furthermore, we summarize information on combination therapy strategies using MSCs. Finally, we discuss the challenges and prospects for clinical application.

Objective We investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN). Methods We selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients. Results Serum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people (P P > 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group (P P P P Conclusion Patients with DN were more likely to have zinc deficiency and lower expression of Nrf2. Additionally, DN patients with zinc deficiency were prone to have more severe clinical and pathological manifestations.

Glass-forming ability is a long-standing concern in the field of metallic glasses (MGs), which greatly limits their maximum casting size and extensive applications. In this work, we report an ultrasonic-assisted rapid cold welding of bulk MGs without using any additives. MGs with various compositions are welded together under a 20,000-Hz high-frequency ultrasonic vibration without losing their amorphous nature. The ultrasonic technology offers the advantages of rapid bonding (< 1 s) at low temperature (near room temperature) and low stress (< 1 MPa). According to the phenomenon observed in the experiment, the activated fresh atoms diffuse through the broken channel port under continuous rupture of the oxide layer, and the ultrasonic vibration accelerates the atomic-diffusion process. Finally, stable bonding of the MG interface is realized. This universal ultrasonic-assisted welding process can realize the composition design of dissimilar MGs as well as tuning of new materials with new performance.

Considering the influence of heat radiation, heat conduction, and plastic deformation, a novel temperature model of the injection-rolling zone during continuous injection direct rolling (CIDR) was developed through a mathematical analysis method. Numerical simulations based on the novel temperature model in the injection-rolling zone were performed under different injection temperatures, injection speeds, roller temperatures, roller speeds, and exit plate thicknesses. The novel temperature model was validated with actual CIDR experiments. The results showed that the polymer flow in the injection-rolling zone was laminar, and the injection speed and roller temperature had a substantial influence on the exit temperature of injection-rolling. The temperatures obtained through numerical simulations based on the novel temperature model were highly consistent with the measured temperatures with an average error of 2.4%. The microstructure ultrathin polymethyl methacrylate (PMMA) light guide plate with superior performance was manufactured through a CIDR experiment. The average height replication rate of microstructures with the aspect ratio 1:3 was 93.34%, and the average width replication rate was 101.13%. The average light transmittance was 88.32%, and the average reflectance was 8.7%.

An intermittent ultrasonic-assisted equal channel angular pressing (IU-ECAP) technique for grain refinement is proposed in this study. AZ31 Mg alloy samples were divided into two groups (IU-ECAP and ECAP) and processed using four passes along route BC, and the effects of ultrasonic vibration on the mechanical properties and microstructure were examined. Mechanical testing revealed that IU-ECAP significantly reduced the extrusion force relative to that for ECAP, whereas the microhardness and ultimate tensile strength were strengthened. The maximum true ultimate tensile strength and microhardness of the IU-ECAPed specimens were achieved using ultrasonic vibration with an amplitude of 35 μm and intermittent time of 2 s. In addition, the microstructures were the most homogeneous for the smallest grain sizes. The IU-ECAPed specimens also possessed less high-angle grain boundaries because of the lower temperature of the IU-ECAP die. Texture analysis revealed that after the 4th pass, the texture of the IU-ECAPed specimens along the (0001) crystal plane exhibited maximum reduction; furthermore, the textures along the (0001), ( $$01\bar{1}0$$ ), and ( $$\bar{1}2\bar{1}0$$ ) crystal planes were scattered homogeneously. These findings may be related to ultrasonic-induced grain boundary rotation.

To assess cancer survivors' unmet supportive care needs and associated factors. Limited evidence is available about the supportive care needs of Chinese cancer survivors to inform future service planning. A cross-sectional survey was conducted (STROBE cross-sectional checklist used for report). Standardized questionnaires were administered to 364 cancer survivors. Using the Supportive Care Framework as conceptual framework, factors concerning individuals' cognitive appraisals of their situation and social resources were examined to explore their association with unmet supportive care needs. The most common unmet supportive care needs included concern about the cancer coming back (51.5%), the need for up-to-date information (49.3%), collaborative management with the medical team (48.8%), and financial support (48.8%). Factors associated with greater strength of unmet supportive care needs included being female, having higher personal support, and higher self-efficacy pertaining to social relationship. Having lower support from family and friends was a contributing factor associated with greater strength of unmet needs in comprehensive cancer care and relationship, as was lower self-efficacy pertaining to uncertainty management associated with greater strength of unmet needs in quality of life, and lower self-efficacy pertaining to health professional interaction associated with greater strength of unmet needs in information. Chinese cancer survivors experience a number of unmet supportive needs. Female and rural cancer survivors, and those with lower social support level and self-efficacy are susceptible to having higher levels of unmet supportive care needs. Consistent information provision and peer support system establishment are two potentially beneficial approaches to meet cancer patients' long-term supportive care needs. Females and rural cancer survivors, those with less support from family and friends, and those with lower self-efficacy in interactions with health professionals and in managing uncertainty are especially at risk for unmet supportive care needs.

Background Gene therapy shows great promise for a broad array of diseases. However, we found that hypoxic tumor microenvironment (TME) exerted significant inhibitory effects on transfection efficiency of a variety of gene vectors (such as Lipo 2000 and PEI) in an oxygen-dependent manner. Solid tumors inevitably resulted in acute hypoxic areas due to the rapid proliferation of tumor cells and the aberrant structure of blood vessels. Thus, the hypoxic TME severely limited the efficiency and application of gene therapy. Methods In our previous study, we constructed endoplasmic reticulum-targeted cationic liposomes, PAR-Lipo, which could effectively deliver genes and ensure high transfection efficiency under normoxia. Unsatisfactorily, the transfection efficiency of PAR-Lipo was rather poor under hypoxia. We believed that reoxygenation was the most direct and effective means to rescue the low transfection under hypoxia. Hence, we fabricated liposomes modified with perfluorooctyl bromide (PFOB@Lipo) to load oxygen and deliver it to tumor sites, which effectively alleviated the hypoxic nature of tumor. Then PAR-Lipo were applied to mediate high-efficiency delivery of tumor suppressor gene pTP53 to inhibit tumor progression. Results The results showed that such staged strategy augmented the expression of P53 protein in tumors and extremely suppressed tumor growth. Conclusion This work was the first attempt to utilize an oxygen nanocarrier to assist the therapeutic effect of gene therapy under hypoxia, providing a new reference for gene therapy in malignant tumors. Graphical Abstarct

Background Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2. Methods We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated. Results After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs. Conclusions hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.

Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUCROC: 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUCROC: 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

Purposes: To assess the effects of Tai Chi on quality of life (QOL) of cancer survivors. Methods: The following databases were searched: PubMed, Cochrane CENTRAL, EBSCO (including MEDLINE, CINAHL, and other databases), ScienceDirect, CNKI, Wangfang Data, and CQVIP until April 25, 2018. Randomized controlled trials (RCTs) published in English or Chinese examining the effects of Tai Chi intervention for cancer survivors were included. The primary outcome was QOL; the secondary outcomes were limb function/muscular strength, immune function indicators, cancer-related fatigue (CRF), and sleep disturbance. Methodological quality was assessed using the Cochrane Risk of Bias tool. Results of RCTs were pooled with mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI). Quality of evidence for each outcome was assessed with the GRADE system. Results: Twenty-two RCTs were included in this review. Tai Chi improved the physical (SMD 0.34, 95%CI 0.09, 0.59) and mental health (SMD 0.60, 95%CI 0.12, 1.08) domains of quality of life. The intervention improved the limb/muscular function of breast cancer survivors (SMD 1.19, 95%CI 0.63, 1.75) and in mixed samples of cancer survivors reduced the levels of cortisol (MD − 0.09, 95%CI − 0.16, − 0.02), alleviated CRF (SMD − 0.37, 95%CI − 0.70, − 0.04), and promoted sleep (SMD − 0.37, 95%CI − 0.72, − 0.02). Conclusion: There is low-level evidence suggesting that Tai Chi improves physical and mental dimensions of QOL and sleep. There is moderate-level evidence suggesting Tai Chi reduces levels of cortisol and CRF and improves limb function. Additional studies with larger sample sizes and with higher-quality RCT designs comparing different regimens of Tai Chi are warranted.

In ultra-precision fly cutting (UPFC), steady tool wear progresses gradually when cutting ductile materials. The steady wear of diamond tools changes the tool geometry, and further affects the topography of the machined surface. In this study, a theoretical and experimental investigation was conducted on the forms of steady tool wear and their influence on the tool geometry in UPFC. The features of steady tool wear in UPFC were investigated, the displacement of the cutting edge under the effects of tool flank wear was modeled, and factors affecting the cutting edge roundness were investigated. The study results indicate the following: (1) the features of steady tool wear in UPFC include crater wear on the rake face, smooth and flat wear on the cutting edge, and flank wear on the tool clearance face. (2) A smooth wear-land on the cutting edge changes the top rake of the cutting tools, whereas flank wear on the tool clearance face affects the clearance angle and roundness of the cutting edge. (3) The maximum width of the tool material loss zone, the nose radius of the original fresh cutting edge, and the arc angle of the wear-land have a certain influence on the nose radius of the worn cutting edge. The results of this study will provide deep insight into steady tool wear and its influence on the tool geometry, which can potentially be used to predict or evaluate the finish of a machined surface under tool steady wear.

The high-frequency and high-speed printed circuit board (PCB) with lower transmission loss, higher heat resistance, and better processability play increasing significant roles in mobile communication technology. However, because the materials and micro drilling process of high-frequency and high-speed PCB are very different from the traditional printed board, there are still many of key techniques to be explored in the future study. In this paper, the characteristics of high-frequency and high-speed PCB were presented. Researches concerning the design and wear ability of micro drill, the analysis of micro drilling force and temperature, and the quality of micro holes were reviewed. Finally, several key techniques and challenges regarding materials and micro drilling were suggested.

The compression tests were carried out on a coarse-grained Mg-8Al-1.5Ca-0.2Sr magnesium alloy samples at temperatures from 300 to 450 °C and strain rates from 0.001 to 10 s−1. The flow stress curves were analyzed using the double-differentiation method, and double minima were detected on the flow curves. The first set of minima is shown to identify the critical strain for twinning, while the second set indicates the critical strain for the initiation of dynamic recrystallization (DRX). Twin variant selection was numerically identified by comprehensive analysis of the Schmid factors for different deformation modes and the accommodation strains imposed on neighboring grains. It was found that twinning is initiated before DRX. Dynamic recrystallization volume increases with strain rate at a given deformation temperature. At high strain rate, various twin variants are activated to accommodate deformation, leading to the formation of twin intersections and high DRX volume. Fully dynamic recrystallized structure can be obtained at both high and low strain rates due to the high mobility of the grain and twin boundaries at the temperature of 400 °C.

Equal-channel angular pressing (ECAP) is an efficient technique to achieve grain refinement in a wide range of materials. However, the extrusion process requires an excessive extrusion force, the microstructure of ECAPed specimens scatters heterogeneously because of considerable fragmentation of the structure and strain heterogeneity, and the resultant ultrafine grains exhibit poor thermal stability. The intermittent ultrasonic-assisted ECAP (IU-ECAP) approach was proposed to address these issues. In this work, ECAP and IU-ECAP were applied to produce ultrafine-grained Al-6061 alloys, and the differences in their mechanical properties, microstructural characteristics, and thermal stability were investigated. Mechanical testing demonstrated that the necessary extrusion force for IU-ECAP was significantly reduced; even more, the microhardness and ultimate tensile strength were strengthened. In addition, the IU-ECAPed Al alloy exhibited a smaller grain size with a more homogeneous microstructure. X-ray diffraction analysis indicated that the intensities of the textures were weakened using IU-ECAP, and a more homogeneous microstructure and larger dislocation densities were obtained. Investigation of the thermal stability revealed that the ultrafine-grained materials produced using IU-ECAP recrystallized at higher temperature or after longer time; the materials thus exhibited improved thermal stability.

Little information has been published in the literature regarding survival outcomes of patients with Ewing's sarcoma family tumors (ESFTs) of the spine. The purpose of this study is to explore factors that may affect the prognosis of patients with non-metastatic spinal ESFTs. A retrospective analysis of survival outcomes was performed in patients with non-metastatic spinal ESFTs. Univariate and multivariate analyses were employed to identify prognostic factors for recurrence and survival. Recurrence-free survival (RFS) and overall survival (OS) were defined as the date of surgery to the date of local relapse and death. Kaplan-Meier methods were applied to estimate RFS and OS. Log-rank test was used to analyze single factors for RFS and OS. Factors with p values ≤0.1 were subjected to multivariate analysis. A total of 63 patients with non-metastatic spinal ESFTs were included in this study. The mean follow-up period was 35.1 months (range 1-155). Postoperative recurrence was detected in 25 patients, and distant metastasis and death occurred in 22 and 36 patients respectively. The result of multivariate analysis suggested that age older than 25 years and neoadjuvant chemotherapy were favorable independent prognostic factors for RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis were favorable independent prognostic factors for OS. Age older than 25 years and neoadjuvant chemotherapy are favorable prognostic factors for both RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis are closely associated with favorable survival.

Ultrasonic-assisted microextrusion tests were performed on pure copper (Cu) with different amplitudes and dimensions to investigate the effects of amplitude and relative grain size L/D (i.e., the ratio of initial grain size L to dimension after extrusion D) on its rheological behavior. The ratio of average extrusion height H to dimension after extrusion D was used as a microformability evaluation parameter. Results showed that the extrusion stress, friction coefficient, and microhardness of Cu decrease with increasing vibration amplitude, whereas its microformability, surface quality, and deformation temperature increase. The effect of relative grain size on microformability could be divided into three sections under different amplitudes. Microformability decreases with increasing L/D when L/D ≤ 0.15 but gradually increases when L/D > 0.35. When 0.15 < L/D ≤ 0.35, experimental repeatability was the poorest and microformability was the worst among the three sections. Moreover, the results of the X-ray diffraction experiment indicated that ultrasonic vibration could effectively promote grain rotation to the (1 1 1) preferred orientation.

To investigate the correlation between protein expression of breast cancer susceptibility gene 1 (BRCA1) and topoisomerase IIβ-binding protein 1 (TopBP1) and clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy.Immunohistochemical staining was conducted to detect the protein expression of BRCA1 and TopBP1 in 101 cases of NSCLC and to correlate these with clinical features, disease progression, and patient survival. Chi-square test (χ (2)-test) was used to evaluate categorical variables. Spearman's rank order correlation was used to analyze continuous variables. Overall survival rate of NSCLC patients was analyzed by Kaplan-Meier survival curve and log-rank test. Relevant factors affecting the survival of patients with advanced NSCLC were analyzed by COX proportional hazards regression model.A total of 101 NSCLC patients were included in the present study. In tumor tissue specimens, positive expression rates of BRCA1 and TopBP1 proteins were 51.5 and 57.4 %, respectively. A significant correlation between the positive expression of BRCA1 and the positive expression of TopBP1 was observed (P 0.001, r = 0.326). No significant correlation between BRCA1/TopBP1 and age, gender, smoking status, performance status score, pathohistological type, or clinical stage was detected (P 0.05). During the follow-up period, 65 patients died, and 86 patients showed progression at the end of the study. The survival rate of patients with negative BRCA1 protein expression was higher than that in patients with positive BRCA1 protein expression [median overall survival (OS) 34 vs. 21 months, HR 1.913, 95 % CI 1.161-3.150, P = 0.011]. Similarly, the survival rate of patients with negative TopBP1 expression was higher than that in patients with positive TopBP1 (median OS 36 vs. 23 months, HR 1.931, 95 % CI 1.157-3.224, P = 0.012). No significant correlation between protein expression of BRCA1 or TopBP1 with NSCLC disease progression was observed (P 0.05).The present study indicates NSCLC patients with negative BRCA1 and TopBP1 expression showed better prognosis than those with positive protein expression.

Background The surgical treatment of upper cervical spine metastases are controversial up to now. By summarizing and analyzing the clinical data of the upper cervical spine involved metastases treated surgically in our center, we mainly aimed to investigate the surgical decisions and outcomes so as to provide more references for the clinical treatment of this special and complex spine metastasis. Methods We evaluated the patients’ pre- and post-operative neck pain and neurologic function with paired t test, followed by the statistics of the selection of surgical approaches, ways of reconstruction, and related complications. Moreover, the Kaplan–Meier survival analysis was adopted to analyze the patients’ survival according to different growth group (rapid, moderate, and slow). Results There were 39 patients with atlantoaxial metastases in this study. The most common symptom (94.87%) was occipital-cervical pain, which relieved greatly after surgical interventions (p

A novel microscale viscosity model was developed on the basis of molecular chain length (MCL). This MCL-viscosity model was validated by comparing the experimental filling ratio of 80- and 70-μm-thick sheets with the simulated filling ratio. In addition, the experimental pressure drops for 200- and 300-μm-long square columns were compared with the simulated pressure drops. The results showed that when the feature size decreased, the simulated filling ratio obtained using the MCL-viscosity model was much closer to experimental data than the macroscopic model. In addition, the simulated pressure drop by the MCL-viscosity model was closer to the experimental data than by the macroscopic model when the shear rate increased. The analysis of the impact of microviscosity on the micro flow process showed that, when the feature size decreased, the deviations in viscosity, injection pressure, and velocity values between the MCL-viscosity and macroviscosity models increased.

The hot deformation behaviors of extruded AZ80 Mg alloys were investigated using tension tests. True stress-true strain curves were obtained for deformation at temperatures from 250 to 450 °C with the strain rate range from 0.001 to 0.08 s−1. Optical microscopy analysis was performed to correlate microstructural changes to the flow behaviors. Based on the flow stress, the processing map at a strain of 0.18 was developed using the dynamic materials model theory and can be divided into three zones, including stability zones, change-over region, and instability zones. In stability zones, there are two dynamic recrystallization regions: one region with a peak efficiency of 58% at 350 °C and a strain rate of 0.001 s−1 called domain I; another region with a peak efficiency of 58% at 400 °C and a strain rate of 0.01 s−1 taken as domain II. The apparent activation energy for domain I was estimated to be 100.71 kJ/mol, indicating that short-circuit diffusion process is along the grain boundaries and falls at lower temperatures and lower strain rates. A lattice self-diffusion is considered to be rate controlling mechanism with the apparent activation energy estimated as 140.32 kJ/mol at higher temperatures and higher strain rates in domain II. The change-over region is the zone from domain I to domain II, in which the grains abnormally grow. In instability zones, twins, local deformation band, wedge cracking, and matrix cracking were observed, suggesting that these processing parameters for hot tension in this zone are inapplicable.

The aim of the present study was to investigate the effects of recombinant human anti-mullerian hormone (rhAMH) on Stem Cell Factor (SCF) expression in human granulosa cells (GCs). GCs were obtained from infertile patients undergoing IVF-ET cycles and cultured with 20 ng/ml of rhAMH. The levels of SCF mRNA and protein were detected in both matched and experimental group by real-time PCR, immunofluorescence, and ELISA, respectively, on day 4 of culture. We found that human GCs expressed SCF mRNA and protein, and SCF expression in the experimental group was significantly lower than that in the matched group (p < 0.05). We further showed that rhAMH inhibited SCF expression at mRNA and protein levels.

The spatiotemporal coherence properties of broadband Gaussian Schell-model (GSM) beams with different spectral bandwidths propagating through atmospheric turbulence are numerically calculated and analyzed. The results show that although the spatial coherence properties of an intermediate-broadband GSM beam almost do not depend on the spectral bandwidth, those of its ultra-broadband counterpart do. The temporal coherence of an ultra-broadband GSM beam not only has radial dependence in the observation plane, but also varies with the increasing propagation distance; however, the same behavior does not hold for an intermediate-broadband GSM beam of which the temporal coherence remains nearly invariable as the radial distance of the observation point or propagation distance changes.

Salinity and drought are two severe abiotic stresses that affect plant growth and decrease food production worldwide. Compared to the field plants, test-tube plantlets could be more direct and fast to investigate the mechanism of stress adaptation. In the present study, the ultrastructural and physiological differences of potato (Solanum tuberosum L. c.v. “Longshu No. 3”) plantlets in response to the gradient saline (0, 25, 50, 100, and 200 mM NaCl) and the modeling drought stresses with polyethylene glycol (PEG) at the concentrations of 0, 2, 4, 6, and 8 % were analyzed. The results show that the severe salt (200 mM NaCl) and the modeling drought stresses (8 % PEG) inhibited the plantlet growth. There are considerable differences in their ultrastructural alteration under salt and modeling drought adaptation: PEG caused the increase in the number of stacked chloroplast, plastoglobuli, and starch; NaCl induced the decrease in the number of chloroplast and plastoglobuli. Moreover, plantlet has higher free proline content, less malondialdehyde (MDA) content, and higher activities of catalase (CAT) and superoxide dismutase (SOD) under the gradient NaCl treatments than the gradient PEG treatments. The results of this study will provide theoretical and practical insights into characterizing the ultrastructural and physiological differences of plants adapting to various stressful environments.

The effect of the dynamic recrystallization (DRX) parameters are of prime importance to improve the accuracy of the numerical simulation of hot forming processes for metals. However, it is difficult to determine the values of DRX parameters from experiments because of the influence of various factors, such as temperature, etc. In the present study, the DRX parameters for AZ31 magnesium alloy are identified by using the method of inverse analysis based on measured stress, BP neural network algorithm, genetic algorithm (GA), orthogonal experiment, and numerical simulation. Then, by applying the identified parameters in finite element analysis, the comparison between the numerically calculated and the experimental results is made to verify the correctness of the method. The results show that the numerically calculated stress, strain, recrystallized fraction, and average grain size valus are in good agreement with the experimental ones. These results demonstrate that the method of inverse analysis is a feasible and an effective tool for determination of the AZ31 DRX parameters.

To explore an ideal approach for detecting the physical status of HPV-16 in clinic use and to investigate the integrated HPV-16 in CINs and cervical cancer. Multiplex real-time PCR method was established to quantify the copy numbers of E2 and E6 genes (E2/E6) for analysis of the physical status of HPV-16 DNA and this assay was compared to Southern blot analysis. HPV-16-containing paraffin-embedded tissues including 49 CINs and 51 cervical squamous cancers were detected using the method. (1) The cutoff ratio of E2/E6 to distinguish pure episomal from mixed HPV-16, was 0.81 in the multiplex real-time PCR; (2) The agreement rate between multiplex real-time PCR and Southern blot was 81.5% (the Kappa statistic was 0.844, P 70%) constituted the majority in CIN II and CIN III; HPV-16 DNA mostly integrated into the host chromosome (s) in squamous cervical cancers (68.6%); (4) The incidence of HPV-16 integration was increased with the degree of cervical lesions; (5) The frequency of pure integrated HPV-16 in stage II+III (88%) was significantly higher than that in stage I (33.3%). (1) Mutiplex real-time PCR provides a rapid, sensitive and reliable method for clinic detection of the physical state of HPV-16 DNA; (2) The integration of the HPV-16 DNA is a very early and important event in the progression from preinvasive to invasive cervical cancer; (3) The pure integrated status of HPV-16 in cervical cancer may be associated with poor prognosis of cervical cancer, but further study will be needed to prove its prognostic significance.

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.

A novel drug carrier for brain delivery, maleimide–poly(ethyleneglycol)–poly(lactide) (maleimide–PEG–PLA) nanoparticles (NPs) conjugated with mouse–anti-rat monoclonal antibody OX26 (OX26–NPs), was developed and its brain delivery property was evaluated. The diblock copolymers of maleimide–PEG–PLA were synthesized and applied to α-cobrotoxin (αCT)-loaded NPs which were characterized by transmission electron micrograph imaging, Fourier-transform IR, and X-ray diffraction. The NPs encapsulating αCT had a round and vesicle-like shape with a mean diameter around 100 nm, and the OX26 had covalently conjugated to the surface of NPs. MTT studies in brain microvascular endothelial cells (BMEC) revealed a moderate decrease in the cell viability of αCT, when incorporated in OX26–NPs compared to free αCT in solution. A higher affinity of the OX26–αCT–NPs to the BMEC was shown in comparison to αCT–NPs. Then, OX26–αCT–NPs were intranasally (i.n.) administered to rats, and αCT in the periaqueductal gray was monitored for up to 480 min using microdialysis technique in free-moving rats, with i.n. αCT–NPs, i.n. OX26–αCT–NPs, intramuscular injection (i.m.) αCT–NPs, and i.m. OX26–αCT–NPs. The brain transport results showed that the corresponding absolute bioavailability (F abs) of i.n. OX26–αCT–NPs were about 125 and 155 % with i.n. αCT–NPs and i.m. OX26–αCT–NPs, respectively, and it was found that both the C max and AUC of the four groups were as follows: i.n. OX26–αCT–NPs > i.n. αCT–NPs > i.m. OX26–αCT–NPs > i.m. αCT–NPs, while αCT solution, as control groups, could hardly enter the brain. These results indicated that OX26–NPs are promising carriers for peptide brain delivery.

It is commonly believed that paragangliomas are rare tumors arising from the neural crest-derived chromaffin cells. Although it has been speculated that paraganglioma is related to stem cell origin, there has been lack of direct evidence demonstrating the presence of (neural) stem cells in these tumor tissues. In this study, we found a subgroup of human paraganglioma from ten clinical samples displayed definitive markers of CD133 and/or nestin, the fundamental features of neural stem cell capable of self-renewal and differentiation. A panel of lineage-specific markers was also manifest in some of these tumors, consistent with the hierarchical and heterogeneous nature of these tumors. These observations strongly suggest that at least some forms of paraganglioma maintain tumor stem-like cells (TSCs) that potentially contribute to the histologic complexity of human paraganglioma. Finally, we found that the genomic DNA structure becomes highly unstable in tumor cells of paraganglioma, indicating the loss of tight control of genomic surveillance system be an important transitory event from normal multi-potent tissue stem cells to TSCs.