AC breakdown and decomposition products detection characteristics of eco-friendly insulating medium in gas insulated switchgear.

Gas Insulated Switchgear (GIS) was a crucial electrical equipment that provides the safety and security of power systems, and finding the eco-friendly alternatives of sulphur hexafluoride (SF6) as insulating medium in GIS has been an urgent demand in past decades. However, few studies reported the specific dielectric strength under various electrodes and partial discharge (PD) decomposition products detection of applying the eco-friendly gas in GIS. In this paper, the insulation properties among C4F7N/CO2 mixtures, dry air and CO2 were explored under the reduced-scale gas-insulated experimental device. The relationship between AC breakdown voltage and gas pressure was gained under the different electrodes and gap distances, and 0.6 MPa 7% C4F7N/93% CO2, 0.9 MPa dry air, 0.9 MPa CO2 all possess the capacity to be the insulating medium in eco-friendly gas insulated switchgear. Furthermore, the partial discharge experimental was also carried out to realize the decomposition products detection of dry air, which designs three common defect types including metal protrusion defects, air gap defects, and metal contamination defects. The decomposition products detection result shows that the contains of CO2, CO, and NO2 linearly increase with the increasing applied voltages and times, and the partial discharge defects are distinguished according to the ratios of c(CO2 + CO)/c(NO2) and c(CO2)/c(CO). The results can provide the basis for the further development of eco-friendly gas insulated switchgear.

How far has the globe gone in achieving One Health? Current evidence and policy implications based on global One Health index.

Background: In the 21st century, as globalization accelerates and global public health crises occur, the One Health approach, guided by the holistic thinking of human-animal-environment and emphasizing interdisciplinary collaboration to address global health issues, has been strongly advocated by the international community. An immediate requirement exists for the creation of an assessment tool to foster One Health initiatives on both global and national scales. Methods: Built upon extensive expert consultations and dialogues, this follow-up study enhances the 2022 global One Health index (GOHI) indicator system. The GOHI framework is enriched by covering three indices, e.g. external drivers index (EDI), intrinsic drivers index (IDI), and core drivers index (CDI). The comprehensive indicator system incorporates 13 key indicators, 50 indicators, and 170 sub I-indicators, utilizing a fuzzy analytic hierarchy process to ascertain the weight for each indicator. Weighted and summed, the EDI, IDI, and CDI scores contribute to the computation of the overall GOHI 2022 score. By comparing the ranking and the overall scores among the seven regions and across 160 countries/territories, we have not only derived an overall profile of the GOHI 2022 scores, but also assessed the GOHI framework. We also compared rankings of indicators and sub I-indicators to provide greater clarity on the strengths and weaknesses of each region within the One Health domains. Results: The GOHI 2022 performance reveals significant disparities between countries/territories ranged from 39.03 to 70.61. The global average score of the GOHI 2022 is 54.82. The average score for EDI, IDI, and CDI are 46.57, 58.01, and 57.25, respectively. In terms of global rankings, countries from North America, Europe and Central Asia, East Asia and Pacific present higher scores. In terms of One Health domains of CDI, the lowest scores are observed in antimicrobial resistance (median: 43.09), followed by food security (median: 53.78), governance (median: 54.77), climate change (median: 64.12) and zoonotic diseases (median: 69.23). Globally, the scores of GOHI vary spatially, with the highest score in North America while lowest in sub-Saharan Africa. In addition, evidence shows associations between the socio-demographic profile of countries/territories and their GOHI performance in certain One Health scenarios. Conclusion: The objective of GOHI is to guide impactful strategies for enhancing capacity building in One Health. With advanced technology and an annually updated database, intensifying efforts to refine GOHI's data-mining methodologies become imperative. The goal is to offer profound insights into disparities and progressions in practical One Health implementation, particularly in anticipation of future pandemics.

Metabolome evidence of CKDu risks after chronic exposure to simulated Sri Lanka drinking water in zebrafish.

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.

Effect of transglutaminase on ovalbumin emulsion gels as carriers of encapsulated probiotic bacteria.

BACKGROUND: The use of emulsion gels to protect and deliver probiotics has become an important topic in the food industry. This study used transglutaminase (TGase) to regulate ovalbumin (OVA) to prepare a novel emulsion gel. The effects of OVA concentration and the addition of TGase on the microstructure, rheological properties, water-holding capacity, and stability of the emulsion gels were investigated. RESULTS: With the addition of TGase and the increasing OVA, the particle size of the emulsion gels decreased significantly (P < 0.05). The gels with TGase exhibited greater water holding, hardness, and chewiness to some extent by forming a more uniform and stable system. After simulated digestion, the survival rate of Bifidobacterium lactis embedded in OVA emulsion gels improved significantly in comparison with the oil-water mixture as a result of the protective effect of the emulsion gel encapsulation. CONCLUSION: By increasing the OVA content and adding TGase, the rheological characteristics, stability, and encapsulation capability of the OVA emulsion gel could be enhanced, providing a theoretical basis for the use of emulsion gels to construct probiotic delivery systems. © 2023 Society of Chemical Industry.

Multi-omics reveal mechanisms underlying chronic kidney disease of unknown etiology (CKDu) pathogenesis using zebrafish.

Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F-, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with Comamonas (rho = 0.72) and significantly negatively correlated with Plesiomonas (rho = -0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.

Assessing food security performance from the One Health concept: an evaluation tool based on the Global One Health Index.

BACKGROUND: Food systems instantiate the complex interdependencies across humans, physical environments, and other organisms. Applying One Health approaches for agri-food system transformation, which adopts integrated and unifying approaches to optimize the overall health of humans, animals, plants, and environments, is crucial to enhance the sustainability of food systems. This study develops a potential assessment tool, named the global One Health index-Food Security (GOHI-FS), aiming to evaluate food security performance across countries/territories from One Health perspective and identify relevant gaps that need to be improved for sustainable food systems. METHODS: We comprehensively reviewed existing frameworks and elements of food security. The indicator framework of GOHI-FS was conceptualized following the structure-process-outcome model and confirmed by expert advisory. Publicly available data in 2020 was collected for each indicator. The weighting strategy was determined by the Fuzzy Analytical Hierarchy Process. The data for each indicator was normalized and aggregated by weighted arithmetic mean. Linear regressions were performed to evaluate the associations of GOHI-FS with health and social-economic indicators. RESULTS: The GOHI-FS includes 5 first-level indicators, 19 second-level indicators and 45 third-level indicators. There were 146 countries/territories enrolled for evaluation. The highest average score of first-level indicators was Nutrition (69.8) and the lowest was Government Support and Response (31.3). There was regional heterogeneity of GOHI-FS scores. Higher median scores with interquartile range (IQR) were shown in North America (median: 76.1, IQR: 75.5-76.7), followed by Europe and Central Asia (median: 66.9, IQR: 60.1-74.3), East Asia and the Pacific (median: 60.6, IQR: 55.5-68.7), Latin America and the Caribbean (median: 60.2, IQR: 57.8-65.0), Middle East and North Africa (median: 56.6, IQR: 52.0-62.8), South Asia (median: 51.1, IQR: 46.7-53.8), and sub-Saharan Africa (median: 41.4, IQR: 37.2-46.5). We also found significant associations between GOHI-FS and GDP per capita, socio-demographic index, health expenditure and life expectancy. CONCLUSIONS: GOHI-FS is a potential assessment tool to understand the gaps in food security across countries/territories under the One Health concept. The pilot findings suggest notable gaps for sub-Saharan Africa in numerous aspects. Broad actions are needed globally to promote government support and response for food security.

Probiotics mitigate kidney damage after exposure to Sri Lanka's local groundwater from chronic kidney disease with uncertain etiology (CKDu) prevalent area in zebrafish.

Groundwater in Sri Lanka, contaminated with environmental toxins, is suspected to potentially induce chronic kidney disease of uncertain etiology (CKDu) in humans. This study aims to elucidate the potential mitigating effects of probiotics on kidney damage induced by exposure to this local groundwater (LW) in zebrafish. We used zebrafish as a model organism and exposed them to local groundwater to evaluate the risk of CKDu. Probiotics were then added at a concentration of 108 colony-forming units per milliliter (CFU/mL). Our findings revealed that exposure to local groundwater resulted in abnormalities, such as tail deletion and spinal curvature in zebrafish larvae. However, the addition of probiotics mitigated these effects, improving the hatching rate, heart rate, length, weight, deformity rate, survival rate, and abnormal behavior of zebrafish. It also positively influenced the differential expression levels of kidney development and immunity-related genes (dync2h1, foxj1, pkd2, gata3, slc20a1, il1ß, and lyso). Furthermore, exposure to LW decreased both the diversity and abundance of microbiota in zebrafish larvae. However, treatment with probiotics, such as L. plantarum and L. rhamnosus partially restored the disrupted gut microbiota and significantly impacted the cellular process pathways of the microbial community, as determined by KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. In conclusion, this study highlights the risks associated with Sri Lanka's local groundwater from a CKDu prevalent area and confirms the beneficial effects of different probiotics. These findings may provide new insights into bacterial function in host kidney health.

A novel peptide P1-121aa encoded by STK24P1 regulates vasculogenic mimicry via ELF2 phosphorylation in glioblastoma.

Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Vasculogenic mimicry (VM) is a hematological system composed of tumor cells that exert blood perfusion without relying on vascular endothelial cells. The current poor results of anti-vascular therapy for clinical GBM are associated with the presence of VM; therefore, it is important to investigate VM formation in GBM. Our results demonstrate that STK24P1 encodes P1-121aa with a kinase structural domain, and in vitro kinase assays demonstrated that P1-121aa mediates modification of ELF2 phosphorylation. ChIP and dual luciferase reporter gene assays demonstrated that the transcription factor ELF2 binds to VE-cadherin and the VEGFR2 promoter region, thereby promoting VM formation in glioma cells. P1-121aa, encoded by the pseudogene STK24P1, phosphorylates ELF2 at S107, increasing the stability of the ELF2 protein. ELF2 promotes VEGFR2 and VE-cadherin expression at the transcriptional level, which in turn promotes VM in GBM. This study demonstrates the important roles of STK24P1, P1-121aa, and ELF2 in regulating VM in GBM, which could provide potential targets for GBM treatment.

Elucidating environmental factors and their combined effects on CKDu in Sri Lanka using zebrafish.

Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas, Paracoccus, and ZOR0006, etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on "bio-markers" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu.

Parasites as ecosystem modulators: foliar pathogens suppress top-down effects of large herbivores.

Parasites can catalyze or inhibit interactions between their hosts and other species, but the ecosystem-level effects of such interaction modifications are poorly understood. We conducted a large-scale field experiment in temperate grasslands of China to understand how foliar fungal pathogens influenced top-down effects of cattle on plant diversity and productivity. When foliar pathogens were suppressed, cattle grazing strongly reduced biomass of the dominant grass, Leymus chinensis, generating competitive release that significantly increased community-level species richness and evenness. In the absence of grazing, pathogen attack on L. chinensis had no measurable effect on host biomass. However, pathogens disrupted top-down effects of herbivory by inhibiting grazing effects on plant biomass and species richness. Mechanistically, fungal pathogens were linked to increased alkaloid and reduced nitrogen levels in leaf tissue, which appeared to deter cattle grazing on L. chinensis. In conclusion, foliar pathogens can suppress top-down effects of large herbivores on grassland community composition and ecosystem function by modifying the strength of their host's interactions with dominant consumers. Parasites may act as modulators of ecosystem function when their direct effects on host abundance are overshadowed by powerful influences on host traits that modify their interactions with competitors, herbivores, or predators.

Modulation Recognition of Communication Signals Based on Multimodal Feature Fusion.

Modulation recognition is the indispensable part of signal interception analysis, which has always been the research hotspot in the field of radio communication. With the increasing complexity of the electromagnetic spectrum environment, interference in signal propagation becomes more and more serious. This paper proposes a modulation recognition scheme based on multimodal feature fusion, which attempts to improve the performance of modulation recognition under different channels. Firstly, different time- and frequency-domain features are extracted as the network input in the signal preprocessing stage. The residual shrinkage building unit with channel-wise thresholds (RSBU-CW) was used to construct deep convolutional neural networks to extract spatial features, which interact with time features extracted by LSTM in pairs to increase the diversity of the features. Finally, the PNN model was adapted to make the features extracted from the network cross-fused to enhance the complementarity between features. The simulation results indicated that the proposed scheme has better recognition performance than the existing feature fusion schemes, and it can also achieve good recognition performance in multipath fading channels. The test results of the public dataset, RadioML2018.01A, showed that recognition accuracy exceeds 95% when the signal-to-noise ratio (SNR) reaches 8dB.

Exposure to Sri Lanka's local groundwater in a CKDu prevalent area causes kidney damage in zebrafish.

How local groundwater induces chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is still elusive. This study aims to elucidate the impacts of Sri Lanka's local groundwater in a CKDu prevalent area and reveal the possible pathogenic mechanism of CKDu using zebrafish models. The drinking water from the local underground well in Vavuniya was sampled and the water quality parameters including Na+, Mg2+, K+, Ca2+, Cl-, NO3-, SO42-, and F- were analyzed. Then, local groundwater exposure to zebrafish larvae and 293T cells was performed, and water with high hardness and fluoride was prepared as parallel groups. Our result showed that exposure to Sri Lanka's local groundwater caused developmental toxicity, kidney damage, and pronephric duct obstruction as well as abnormal behavior in zebrafish. Similar results were also found after exposure to water with high hardness and fluoride in zebrafish. Further, the expression levels of marker genes related to renal development and functions (foxj1a, dync2h1, pkd2, gata3, and slc20a1) were significantly altered, which is also confirmed in the 293T cells. Taken together, those results indicated that Sri Lanka's local groundwater in a CKDu prevalent area could cause kidney damage, implying that high water hardness and fluorine might be the inducible environmental factors for the etiological cause of CKDu.

Chinese interpreting students' learning motivation and performance in the Covid-19 context: a quasi-experimental study.

Covid-19 has brought about profound changes and challenges to the interpreting profession, and this study aims to explore Chinese students' learning motivation and performance in the new context. Motivation is a main determinant of performance. Referring to the studies on intrinsic motivation, ideal self, and Maslow's needs theory as well as the characteristics of interpreting, we have summarized six motivation dimensions, including safety, social, esteem, cognitive, actualization, and transcendence ones. A questionnaire was designed to address the six motivation dimensions. Experimental teaching was carried out on two undergraduate classes. The Covid-19 context was incorporated into the experimental group but not the control group. Three parallel tests were organized, and students completed the motivation questionnaire after each test. Data analyses showed that the experimental group's actualization and transcendence motivation dimensions increased significantly after the experimental teaching, but not the control group, and the experimental group also had a significantly higher score in the final test. It implied that the actualization and transcendence dimensions were closely related to students' performance.

Large herbivores facilitate a dominant grassland forb via multiple indirect effects.

While large herbivores are critically important components of terrestrial ecosystems and can have pronounced top-down effects on plants, our understanding of the underlying mechanisms driving these effects remains incomplete. Large herbivores can alter plant growth, reproduction, and abundance through direct effects (predominantly consumption) and through indirect effects via altered interactions with abiotic factors and other species. We know considerably less about these indirect effects than the direct effects. Here, we integrate medium- and small-scale field experiments to investigate how a large vertebrate herbivore, cattle (Bos taurus), affects the aboveground biomass of a dominant forb species, Artemisia scoparia, via diverse direct and indirect pathways in a temperate grassland in northeast China. Although cattle consumed this forb, its biomass increased significantly in response to grazing, due to multiple indirect positive effects that outweighed the direct negative effects of consumption. Cattle preferentially consumed the competing grass Leymus chinensis, and altered Artemisia microhabitats by reducing total plant cover and litter biomass and by increasing the abundance of co-occurring ant species (e.g., Formica spp. and Lasius spp.). This led to additional indirect positive effects on A. scoparia likely due to (1) increased light availability in understory layers and other limiting resources (e.g., soil nutrients and moisture) caused by removal of competitors and plant litter at the soil surface and (2) the changes in resource availability (e.g., soil nutrients and moisture) associated with ant colonies. Our results show that large herbivores can affect plant growth not only via direct consumption, but also via multiple indirect effects. Focusing on the causes and consequences of herbivore-induced indirect effects will not only help us to better understand the influence of these animals in ecological systems, but will also lead to more effective land management and conservation practices in the regions they inhabit.

Two-stage inventory management with financing under demand updates.

Considered is a retailer (she) facing non-stationary stochastic demand. Demand can be fully observed and backlogged, consequently the retailer can update the initial demand information using a Bayesian approach. To alleviate the demand risk, the retailer may use a secondary opportunity to replenish through an option contract. In addition, the retailer also has access to an immediate loan if she faces capital constraints and to a risk-free investment if she has surplus funds. The paper presents a recourse approach to solve the two-stage optimization problem and derive the optimal inventory/financing policies. The results show that the option procurement policy has a two-threshold base-stock structure depending on the first procurement, demand update and also the retailer's financial state. The initial procurement can be computed subsequently. A sufficiently large initial demand will induce the retailer to seize the secondary procurement opportunity. Finally, a series of numerical examples demonstrate the resulting policy under various inventory/financial situations. This research incorporates the financial and operational decisions into demand updates, and brings new managerial results and insights.

Disulfonated Poly(arylene ether sulfone) Random Copolymers Containing Hierarchical Iptycene Units for Proton Exchange Membranes.

Two series of disulfonated iptycene-based poly(arylene ether sulfone) random copolymers, i.e., TRP-BP (triptycene-based) and PENT-BP (pentiptycene-based), were synthesized via condensation polymerization from disulfonated monomer and comonomers to prepare proton exchange membranes (PEMs) for potential applications in electrochemical devices such as fuel cell. To investigate the effect of iptycene units on membrane performance, these copolymers were systematically varied in composition (i.e., iptycene content) and the degree of sulfonation (i.e., 30-50%), which were characterized comprehensively in terms of water uptake, swelling ratio, oxidative stability, thermal and mechanical properties, and proton conductivity at various temperatures. Comparing to copolymers without iptycene units, TRP-BP and PENT-BP ionomers showed greatly enhanced thermal and oxidative stabilities due to strong intra- and inter-molecular supramolecular interactions induced by hierarchical iptycene units. In addition, the introduction of iptycene units in general provides PEMs with exceptional dimensional stability of low volume swelling ratio at high water uptakes, which is ascribed to the supramolecularly interlocked structure as well as high fractional free volume of iptycene-based polymers. It is demonstrated that the combination of high proton conductivity and good membrane dimension stability is the result of the synergistic effects of multiple factors including free volume (iptycene content), sulfonation degree, hydrophobicity, and swelling behavior (supramolecular interactions).

Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy.

PURPOSE: Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of TP53 mutations leading to dysfunctional G1 cell-cycle checkpoint, which likely makes esophageal cancer cells highly reliant upon G2-M checkpoint for adaptation to DNA replication stress and DNA damage after radiation. We aim to explore whether targeting Wee1 kinase to abolish G2-M checkpoint sensitizes esophageal cancer cells to radiotherapy. EXPERIMENTAL DESIGN: Cell viability was assessed by cytotoxicity and colony-forming assays, cell-cycle distribution was analyzed by flow cytometry, and mitotic catastrophe was assessed by immunofluorescence staining. Human esophageal cancer xenografts were generated to explore the radiosensitizing effect of AZD1775 in vivo. RESULTS: The IC50 concentrations of AZD1775 on esophageal cancer cell lines were between 300 and 600 nmol/L. AZD1775 (100 nmol/L) as monotherapy did not alter the viability of esophageal cancer cells, but significantly radiosensitized esophageal cancer cells. AZD1775 significantly abrogated radiation-induced G2-M phase arrest and attenuation of p-CDK1-Y15. Moreover, AZD1775 increased radiation-induced mitotic catastrophe, which was accompanied by increased γH2AX levels, and subsequently reduced survival after radiation. Importantly, AZD1775 in combination with radiotherapy resulted in marked tumor regression of esophageal cancer tumor xenografts. CONCLUSIONS: Abrogation of G2-M checkpoint by targeting Wee1 kinase with AZD1775 sensitizes esophageal cancer cells to radiotherapy in vitro and in mouse xenografts. Our findings suggest that inhibition of Wee1 by AZD1775 is an effective strategy for radiosensitization in esophageal cancer and warrants clinical testing.

LCL161, a SMAC-mimetic, Preferentially Radiosensitizes Human Papillomavirus-negative Head and Neck Squamous Cell Carcinoma.

Targeting inhibitor of apoptosis proteins (IAP) with second mitochondria-derived activator of caspase (SMAC) mimetics may promote cancer cell death. We tested whether cIAP1 predicts poor prognosis in head and neck squamous cell carcinoma (HNSCC) and whether a novel Smac-mimetic, LCL161, could radiosensitize human papillomavirus-positive (HPV+) and -negative (HPV-) HNSCC. The association of BIRC2 (encoding cIAP1) mRNA level with HPV status in HNSCC was analyzed using The Cancer Genome Atlas (TCGA) database. cIAP1 was assessed by IHC on an HNSCC tissue microarray (TMA, n = 84) followed by correlation analysis with HPV status and patient outcomes. Human cell culture and animal models of HNSCC were used to analyze the outcome and molecular characteristics following radiotherapy in combination with LCL161. cIAP1 expression is increased in HPV- compared with HPV+HNSCC tumors in the TCGA database. In our TMA, cIAP1 was overexpressed in HNSCC compared with normal tissues (P = 0.0003) and associated with a poor overall survival (P = 0.0402). cIAP1 levels were higher in HPV- than that in HPV+HNSCC tumors (P = 0.004) and patients with cIAP1+/HPV- HNSCC had the worst survival. LCL161 effectively radiosensitized HPV- HNSCC cells, which was accompanied with enhanced apoptosis, but not HPV+ HNSCC cells. Importantly, LCL161 in combination with radiotherapy led to dramatic tumor regression of HPV- HNSCC tumor xenografts, accompanied by cIAP1 degradation and apoptosis activation. These results reveal that cIAP1 is a prognostic and a potential therapeutic biomarker for HNSCC, and targeting cIAP1 with LCL161 preferentially radiosensitizes HPV- HNSCC, providing justification for clinical testing of LCL161 in combination with radiation for patients with HPV- HNSCC.

[Analysis of schistosomiasis endemic status of national surveillance sites in Yunnan Province, 2014].

OBJECTIVE: To master the dynamic endemic status and influencing factors of schistosomiasis in Yunnan Province, so as to provide the evidence for making the control and prevention measures. METHODS: Four villages of four schistosomiasis heavy endemic counties were selected as survey sites. Then, the serological screening and etiological tests were carried out in the residents, and the basic situations of the survey sites were investigated. The infection status of the livestock and relevant information of Oncomelania hupensis snails were surveyed. All the results were analyzed statistically. RESULTS: Totally 4310 residents were surveyed by the indirect hemagglutination assay with the examination rate of 79.68% and serum positive rate of 8.40%. The positive rate reached upwards 12.53% in Qiandian Village of Eryuan County. The serum positive rate of the female was higher than that of the male, and the positive rates of the 30 years and older age groups were higher than those of the other age groups. The serum positive rates of the peasants, migrant labourers and residents with the junior high school education level were higher. No positive feces were found. A total of 24 advanced cases were reported. No positive livestock and snails were found, and the average density of living snails was 0.023 3-0.056 6/0.1 m2. CONCLUSION: Right now, the schistosomiasis is at a low prevalence status in Yunnan Province, and the endemic situation has been effectively controlled.