Nanosecond pulsed electric field inhibits malignant melanoma growth by inducing the change of systemic immunity

Nanosecond pulsed electric fields (nsPEFs) showed an inhibitory effect on proliferation of malignant melanoma. In this study, the growth of melanoma were inhibited by changing the systemic immunity. C57BL/6 mice with B16 malignant were exposed to 200 pulses of 100 ns duration, 30kV/cm. The mice were executed four days later. T lymphocyte has been extracted from spleen. Cell viability was evaluated by CCK-8 assay. CD3+CD4+ T cells, CD3+CD8+ T cells, regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) were analyzed by flow cytometry. TNF-?, IL-2, IL-10, TGF-?, IFN? ? levels in supernatants were assessed by ELISA. C57 malignant melanoma model were established successfully. After the treatment of nsPEFs(30 kV/cm 100 ns 200p), the numbers of T lymphocytes were increased.CD3+ CD4+ T cells changed from 48% to 51.2%;CD3+CD8+T lymphocytes increased from 39.6% to 40.4%.Treg cells reduced from 4.3% to 2.4%,MDSC decreased by 39.0% to 19.7% . In addition, the level of TNF-?, IL-2 were increased (P0.05). Tumor growth can be effectively inhibited by nsPEFs in vivo, which activate targets of immune respones, accumulation of inflammatory cells and immune cytokines

Organizational Network Evolution and Governance Strategies in Megaprojects

The organization is the key factor for megaprojects in which thousands of connections and relations intertwine and influence the project performance. However, organizational evolution in megaprojects has not been fully studied. This study investigates the evolution of the organizational network of a megaproject in China using social network analysis (SNA), and then proposes corresponding governance strategies. The result shows that megaproject organizations evolve towards more connected networks but are differentiated for various investors. For government invested projects, the organizational network is well connected, cooperative, yet unstable and require strategic long-term governance policies; for private invested projects, the network is stable, but collaboration among participants is low, which indicates a need to establish collaborative governance structures. The result complements the organizational evolution theory for megaprojects and offers effective strategies for governing megaproject organizations. This study also helps practitioners better understand the nature and characteristics of megaproject organizations.

Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART

<p>Abstract</p> <p>Background</p> <p>CD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied.</p> <p>Methods</p> <p>Twenty-one asymptomatic treatment-naive HIV-infected patients with CD4 T+ cells less than 350 cells/μl were enrolled in the study. Naïve, central memory(CM), effective memory(EM) and terminally differentiated effector (EMRA) CD8+ cell subsets and their activation and proliferation subsets were evaluated in blood samples collected at base line, and week 2, 4, 8 and 12 of ART.</p> <p>Results</p> <p>The total CD8+ T cells declined and the Naïve and CM subsets had a tendency of increase. Activation levels of all CD8+ T cell subsets except EMRA subset decreased after ART. However, proliferation levels of total CD8+ T cells, EMRA, EM and CM subsets increased at the first 4 weeks of ART, then decreased. Proliferation level of the naïve cells decreased after ART.</p> <p>Conclusion</p> <p>The changes of CD8+ T cell subsets during initial ART are complex. Our results display a complete phenotypical picture of CD8+ cell subsets during initial ART and provide insights for understanding of immune status during ART.</p

Cryopreservation of human failed-matured oocytes followed by in vitro maturation: vitrification is superior to the slow freezing method

<p>Abstract</p> <p>Background</p> <p>Oocyte cryopreservation is an important method used in a number of human fertility circumstances. Here, we compared the survival, <it>in vitro </it>maturation, fertilization, and early embryonic development rates of frozen-thawed human immature oocytes using two different cryopreservation methods.</p> <p>Methods</p> <p>A total of 454 failed-matured oocytes [germinal vesicle (GV) and metaphase I (MI) stages] were collected from 135 patients (mean age 33.84 +/- 5.0 y) who underwent intracytoplasmic sperm injection (ICSI) cycles between February 2009 and December 2009 and randomly divided into a slow freezing group [1.5 mol/L-1, 2-propanediol (PROH) + 0.2 mol/l sucrose] and vitrification group [20% PROH + 20% ethylene glycol (EG) + 0.5 mol/l sucrose].</p> <p>Results</p> <p>The vitrification protocol yielded a better survival rate than the slow freezing protocol at each maturation stage assessed. Regardless of the maturation stage (GV + MI), the slow freezing protocol had a significantly lower survival rate than the vitrification protocol (p < 0.001). In addition, a significant difference was found in the survival rates between GV and MI oocytes regardless of the protocol used (90.1 vs. 64.7%, respectively; p < 0.01). We also found that the maturation rates of GV and MI oocytes from the slow freezing and vitrification groups were 16.7 vs. 24.4% and 50.8 vs. 55.4%, respectively. Regardless of the protocol used, the GV oocytes had significantly lower viability than MI oocytes after 36 h of <it>in vitro </it>maturation (21.2 vs. 54.0%, respectively; p < 0.01). In addition, the GV and MI oocytes from the slow freezing group had a markedly lower maturation rate than those from the vitrification group (33.6 vs. 43.1%, respectively), but no statistical difference was found between the two groups (P > 0.05). For the GV-matured oocytes, no fertilized eggs were obtained in the slow-freezing group, while a 19.0% (4/21) fertilization rate was observed in the vitrification group. For the MI-matured oocytes, fertilization rates for the slow freezing and vitrified groups were 36% and 61.1%, respectively, but no significant difference was found between the two groups (PIn the Methods section in the MS, all procedures were compliant with ethical guidelines, i.e. approved by the Ethical Committee of our university and Informed Consent signed by each patient. > 0.05). In the GV vitrification group, no embryo formed; however, in the MI slow freezing group, 12 oocytes were fertilized, but only two achieved cleavage and were subsequently blocked at the 2-cell stage. In the MI vitrification group, a total of 22 embryos were obtained, five of which developed to the blastocyst stage.</p> <p>Conclusions</p> <p>Vitrification is superior to the slow freezing method in terms of the survival and developmental rates for the cryopreservation of human failed-matured oocytes. In addition, GV oocytes appeared to be more resistant than MI oocytes to the low temperature and cryoprotectant used during cryopreservation.</p

A Novel Spatiotemporal Graph Convolutional Network Framework for Functional Connectivity Biomarkers Identification of Alzheimer’s Disease

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer\u27s disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD. METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, firstly, we optimized the STGC-GCAM model to enhance classification accuracy. Secondly, we identified novel AD-associated biomarkers using the optimized model. Thirdly, we validated the imaging biomarkers using Kaplan-Meier analysis. Lastly, we performed correlation analysis and causal mediation analysis to confirm the physiological significance of the identified biomarkers. RESULTS: The STGC-GCAM model demonstrated great classification performance (The average area under the curve (AUC) values for different categories were: CN vs MCI = 0.98, CN vs AD = 0.95, MCI vs AD = 0.96, stable MCI vs progressive MCI = 0.79). Notably, the model identified specific brain regions, including the sensorimotor network (SMN), visual network (VN), and default mode network (DMN), as key differentiators between patients and CN individuals. These brain regions exhibited significant associations with the severity of cognitive impairment (p \u3c 0.05). Moreover, the topological features of important brain regions demonstrated excellent predictive capability for the conversion from MCI to AD (Hazard ratio = 3.885, p \u3c 0.001). Additionally, our findings revealed that the topological features of these brain regions mediated the impact of amyloid beta (Aβ) deposition (bootstrapped average causal mediation effect: β = -0.01 [-0.025, 0.00], p \u3c 0.001) and brain glucose metabolism (bootstrapped average causal mediation effect: β = -0.02 [-0.04, -0.001], p \u3c 0.001) on cognitive status. CONCLUSIONS: This study presents the STGC-GCAM framework, which identifies FC biomarkers using a large multi-site fMRI dataset

Genetic Analysis and Molecular Breeding Applications of Malting Quality QTLs in Barley

Malting quality is an important determinant of the value of barley grain used in malting and brewing. With recent sequencing and assembling of the barley genome, an increasing number of quantitative trait loci (QTLs) and genes related to malting quality have been identified and cloned, which lays a good molecular genetic basis for barley quality improvement. In this review, we describe the following indicators of malting quality: malt extract (ME), diastatic power (DP), kolbach index (KI), wort viscosity (VIS), free amino nitrogen (FAN) content, soluble protein (SP) content, wort β-glucan (WBG) content, and protein content (PC), and have list related QTLs/genes with high phenotypic variation in multiple populations or environments. Meanwhile, the correlations among the quality parameters and parts of significant indicators suitable for improvement are discussed based on nutrient composition and content required for high-quality malt, which will provide reference for molecular marker-assisted selection (MAS) of malting quality in barley

Density-dependent prophylaxis in crowded Beet Webworm, Loxostege sticticalis (Lepidoptera: Pyralidae) larvae to a parasitoid and a fungal pathogen

Transmission of parasites and pathogens is generally positively density-dependent: as an insect population\u27s density increases, the risk of an individual becoming attacked or infected also increases. In some insect species, individuals experiencing crowded conditions are more resistant to natural enemies than those experiencing low density conditions, and they are predicted to divert resources to increase resistance. This phenomenon is called density-dependent prophylaxis. Here, possible expression of prophylaxis in fifth-instar larvae of Beet Webworm, Loxostege sticticalis, to biocontrol agents was investigated under rearing densities of 1, 10, and 30 larvae per jar (650 mL). Larvae reared at the moderate density and those reared in isolation displayed the greatest and lowest resistance, respectively, to an entomopathogenic fungus and a parasitoid. Moreover, larvae from the moderate density treatment exhibited elevated phenoloxidase, total haemocyte count and antibacterial activity in the haemolymph, whereas phenoloxidase levels in the midgut were not affected. The results suggest that larval rearing density significantly affects the immune system, and they provide evidence for density-dependent prophylaxis of larval L. sticticalis against its biocontrol agents. These results have implications for understanding the population dynamics and biocontrol of beet webworm

Imprints of tropical cyclone on three-dimensional structural characteristics of mesoscale oceanic eddies

The impact of tropical cyclones (TCs) on the three-dimensional characteristics of mesoscale oceanic eddies is investigated in this study on the basis of statistical analysis by satellite-based eddy information and Argo data. By comparing the three-dimensional structure of the temperature, salinity, and geostrophic velocity in the upper ocean above 1,000 m depth, it was found that there is a heat pump effect in the changes of eddy structure similar to that in tropical cyclones. Under the forcing of TC, the abnormal signals in the strong cold core (warm core) structure originally existing in the upper layer of the cyclonic eddy (anticyclonic eddy) are transmitted to the middle and lower layers of the eddy and form retention, making the eddy structure not recover to the original state in a short period of time. To a certain extent, this shows that the influence of TC on the eddy structure is not limited to the ocean surface. At the same time, the change of barrier layer in the eddy is explored, and it was found that the barrier layer thickness in both cyclonic eddy and anticyclonic eddy has increased, which also confirms the previous research