bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance evaluation of compound parabolic solar collector using different nanofluids: An experimental study
Authors: Farhan Muhammad , Shahid Muhammad Ihsan , Jamil Furqan , Usman Muhammad , Mujtaba M. A. , Saleem Muhammad Wajid , Nasir Shah Syed , Saghir Shahid , Yusuf Abdulfatah Abdu , Mousa Mohamed , El-Shafay A.S.
Published: September 2022

The article reports an experimental study on a non-tracking compound parabolic collector (CPC) with nanofluid and hybrid nanofluids (NFs). An experimental setup was fabricated having a concentration ratio of 4.17, 0.828 m2 collector area, 24° of half acceptance angle, and an evacuated tube receiver having 1.85 m length. Fluids like water and NFs have been investigated in CPC performance improvement, but current research deals with NFs and hybrid NFs in a CPC as rare studies are found on a CPC using NFs. The 0.010 and 0.015 wt% concentration were used of nanofluids (NFs) which were silica/water + ethylene glycol (SiO2)/(H2O + EG), and hybrid nanofluids of magnesium oxide + carbon black/water (MgO + CB/H2O) and carbon black + graphene nanoplatelets/water (CB + GNPs/H2O) at flow rates of 0.020, 0.015, and 0.010 kg/s. The experimentation was performed under real climate conditions of Taxila, Pakistan, and solar irradiance and ambient temperature were measured to determine the performance of the CPC in comparison to a simple base fluid which was water. The experimental results revealed that a maximum temperature difference of 8.5°C with an around thermal efficiency of 38.51% was achieved for hybrid pair of MgO + CB at a flow rate of 0.010 kg/s and volumetric concentration of 0.015 wt%. The efficiency variation using NFs (SiO2/EG + H2O) varies from 12.8% to 59.1% from lowest 0.010 kg/s to highest 0.020 kg/s flow rates, and volumetric concentrations (0.010 and 0.015 wt%) of nanoparticles. For similar experimental conditions, efficiency variation for (CB + GNPs) pair varies from 14.2% to 65.6% for aforementioned conditions. Efficiency variation from 15.3% to 66.3% was attained using MgO + CB in the base fluid of water for said flow rates and volumetric concentrations of nanoparticles. In addition, an efficiency enhancement of 24.3%, 30.8%, and 31.5% was observed for SiO2/EG + H2O, CB + GNPs/H2O, and MgO + CB/H2O, respectively, at maximum flow rates and volumetric concentration of nanoparticles as compared to water. Therefore, the usage of hybrid-based NF in the CPC is beneficial in terms of efficiency enhancement, and it will bring young research workers to get deep into this field to bring revolution in the area of solar energy.
Gearbox fault diagnosis using improved feature representation and multitask learning
Authors: Sohaib Muhammad , Munir Shahid , Islam M. M. Manjurul , Shin Jungpil , Tariq Faisal , Ar Rashid S. M. Mamun , Kim Jong-Myon
Published: September 2022

A gearbox is a critical rotating component that is used to transmit torque from one shaft to another. This paper presents a data-driven gearbox fault diagnosis system in which the issue of variable working conditions namely uneven speed and the load of the machinery is addressed. Moreover, a mechanism is suggested that how an improved feature extraction process and data from multiple tasks can contribute to the overall performance of a fault diagnosis model. The variable working conditions make a gearbox fault diagnosis a challenging task. The performance of the existing algorithms in the literature deteriorates under variable working conditions. In this paper, a refined feature extraction technique and multitask learning are adopted to address this variability issue. The feature extraction step helps to explore unique fault signatures which are helpful to perform gearbox fault diagnosis under uneven speed and load conditions. Later, these extracted features are provided to a convolutional neural network (CNN) based multitask learning (MTL) network to identify the faults in the provided gearbox dataset. A comparison of the experimental results of the proposed model with that of several already published state-of-the-art diagnostic techniques suggests the superiority of the proposed model under uneven speed and load conditions. Therefore, based on the results the proposed approach can be used for gearbox fault diagnosis under uneven speed and load conditions.
Technological innovation evolution and industrial modernization driven by green factors: Case of combined heat and power (CHP) industry in Yangtze River Delta, China
Authors: Su Chenqing , Wang Chengsi , Wang Zhanao , Zhang Lu , Tian Yaqi
Published: September 2022

China’s Yangtze River Delta region has banned the approval of new thermal power projects except for combined heat and power (CHP) generation and is promoting technological innovation in CHP. However, technological innovation of energy technology has been evidenced to be often affected by spatial elements. The role of spatial agglomeration in the energy industry on technological innovation has not been discussed in the context of CHP. Therefore, this article studied the spatial agglomeration and evolution characteristics of CHP technological innovation point elements through the Global Moran's index, kernel density analysis, and thermal map analysis and analyzed the influencing factors and changes by the spatial regression model. The results show that environmental regulation and high-tech park agglomeration are the key factors influencing CHP technological innovation. This indicates that future policy making needs to consider the economic factors of green development and the role of high-tech parks in innovation.
Production- and consumption-based carbon emission decoupling and decomposition of the Belt and Road countries
Authors: Zhang Jianpeng , Han Mengyao
Published: September 2022

The Belt and Road Initiative (BRI) provides a platform for developing countries with huge growth potentials, which may also face huge carbon emission pressure while achieving rapid economic growth. Given certain similarities in economic patterns and resource endowments, this study aims to trace carbon emission decoupling and decomposition of different countries/regions within the Belt and Road area and provide new insights into the drivers of carbon emission decoupling from both production- and consumption-based perspectives. Based on the multi-regional input-output modelling and Tapio decoupling decomposition, this study quantitatively analyzes the decoupling evolution and decomposition drivers of economic activities and carbon emissions in countries along the Belt and Road. From the results, the production-based carbon emissions of the Belt and Road countries was significantly higher than the consumption-based carbon emissions. The increasing rate in the production-based carbon emissions was also faster than the consumption-based one, with an increasing huge gap between the two sides. Regarding the spatial distribution of carbon emissions, the regions with huge amounts of carbon emissions mainly distributed in Russia, Iran, South Korea, and Saudi Arabia. When compared, the consumption-based carbon emissions of China and Russia were the highest, followed by those of the countries in Central Asia and West Asia. Compared with the production-based side, the decoupling rate of the Belt and Road countries was slower than the consumption-based one. The Belt and Road countries mainly maintained in the weak decoupling status, with the economic effect as the main driver in carbon emission growth, and the energy intensity effect as the dominated contributor in carbon emission reduction. Through exploring the decoupling and decomposition of production- and consumption-based carbon emissions within the Belt and Road countries, this study attempts to provide certain implications for the low-carbon transition and sustainable development within the countries along the Belt and Road.
Stable isotopes in monitoring terrestrial arthropods
Authors: Komonen Atte , Torniainen Jyrki , Kiljunen Mikko
Published: September 2022

Monitoring of arthropods focuses typically on changes in population and range size over time. Yet, there are a myriad of other aspects that could and should be monitored under the ongoing global and local environmental change. Stable isotope analysis, widely employed in short-term ecological studies, has potential in long-term monitoring of arthropods. Here we discuss the use of stable isotopes in monitoring terrestrial arthropods, provide some empirical examples of the use of bulk tissue samples in stable isotope analysis, and outline future directions in using compound-specific stable isotope analysis in monitoring. We performed a literature search for 2012–2021 to see if stable isotopes have been specifically used in monitoring of terrestrial arthropods. The literature shows that stable isotopes have been successfully used to reveal ecological phenomena (dispersal, trophic interactions, resource use) that would have been difficult or impossible to detect by other means. Yet, stable isotopes have been underused in arthropod monitoring programs, but the growing number of basic studies on stable isotope ecology and methodology provides crucial basis needed for developing monitoring programs. Stable isotopes provide technically, economically and ecologically feasible addition to the traditional monitoring methods of terrestrial arthropods.
Ascertaining yield and grain protein content stability in wheat genotypes having the Gpc-B1 gene using univariate, multivariate, and correlation analysis
Authors: Tanin Mohammad Jafar , Sharma Achla , Saini Dinesh Kumar , Singh Satinder , Kashyap Lenika , Srivastava Puja , Mavi G. S. , Kaur Satinder , Kumar Vijay , Kumar Vineet , Grover Gomti , Chhuneja Parveen , Sohu V. S.
Published: September 2022

The high performance and stability of wheat genotypes for yield, grain protein content (GPC), and other desirable traits are critical for varietal development and food and nutritional security. Likewise, the genotype by environment (G × E) interaction (GEI) should be thoroughly investigated and favorably utilized whenever genotype selection decisions are made. The present study was planned with the following two major objectives: 1) determination of GEI for some advanced wheat genotypes across four locations (Ludhiana, Ballowal, Patiala, and Bathinda) of Punjab, India; and 2) selection of the best genotypes with high GPC and yield in various environments. Different univariate [Eberhart and Ruessll’s models; Perkins and Jinks’ models; Wrike’s Ecovalence; and Francis and Kannenberg’s models], multivariate (AMMI and GGE biplot), and correlation analyses were used to interpret the data from the multi-environmental trial (MET). Consequently, both the univariate and multivariate analyses provided almost similar results regarding the top-performing and stable genotypes. The analysis of variance revealed that variation due to environment, genotype, and GEI was highly significant at the 0.01 and 0.001 levels of significance for all studied traits. The days to flowering, plant height, spikelets per spike, grain per spike, days to maturity, and 1000-grain weight were specifically affected by the environment, whereas yield was mainly affected by the environment and GEI. Genotypes, on the other hand, had a greater impact on the GPC than environmental conditions. As a result, a multi-environmental investigation was necessary to identify the GEI for wheat genotype selection because the GEI was very significant for all of the evaluated traits. Yield, 1000-grain weight, spikelet per spike, and days to maturity were observed to have positive correlations, implying the feasibility of their simultaneous selection for yield enhancement. However, GPC was observed to have a negative correlation with yield. Patiala was found to be the most discriminating environment for both yield and GPC and also the most effective representative environment for GPC, whereas Ludhiana was found to be the most effective representative environment for yield. Eventually, two NILs (BWL7508, and BWL7511) were selected as the top across all environments for both yield and GPC.
Microfluidic devices: The application in TME modeling and the potential in immunotherapy optimization
Authors: Li Yuting , Fan Honghong , Ding Junli , Xu Junying , Liu Chaoying , Wang Huiyu
Published: September 2022

With continued advances in cancer research, the crucial role of the tumor microenvironment (TME) in regulating tumor progression and influencing immunotherapy outcomes has been realized over the years. A series of studies devoted to enhancing the response to immunotherapies through exploring efficient predictive biomarkers and new combination approaches. The microfluidic technology not only promoted the development of multi-omics analyses but also enabled the recapitulation of TME in vitro microfluidic system, which made these devices attractive across studies for optimization of immunotherapy. Here, we reviewed the application of microfluidic systems in modeling TME and the potential of these devices in predicting and monitoring immunotherapy effects.
A ferroptosis associated gene signature for predicting prognosis and immune responses in patients with colorectal carcinoma
Authors: Yan Lijun , Chen Xi , Bian Zhaolian , Gu Chunyan , Ji Hanzhen , Chen Liyan , Xu Haifeng , Tang Qiyun
Published: September 2022

Background: Colorectal carcinoma (CRC) is one of the most prevalent malignancies globally. Ferroptosis, a novel type of cell death, is critical in the development and treatment of tumors.

Objective: This study was designed to establish a genetic signature for ferroptosis which has a predictive effect on the outcomes and immunotherapeutic response of CRC.

Methods: Data of CRC patients were retrieved from TCGA and GEO databases. The genes associated with ferroptosis were obtained from GeneCards. The genetic signature for ferroptosis was identified by performing Cox regression analysis. Kaplan–Meier and ROC analysis were performed to assess the prognosis role of the genetic signature. CIBERSORT tool was used to identify a potential association of the genetic signature with the immune cells. The potential immunotherapeutic signatures and drug sensitivity prediction targeting this signature were also discussed. Immunohistochemistry was used to detect expression of ferroptosis-associated genes in CRC tissues and adjacent tissues.

Results: A ferroptosis-associated gene signature comprised of three genes (CDKN2A, FDFT1, and ACSL6) was developed for prediction of prognosis and evaluation of immune responses in CRC. Patients in the high-risk group tended to have a poor prognosis. In CRC, the ferroptosis-associated gene signature may function as independent predictors. Additionally, the expressional levels of the immune checkpoint proteins PD-L1 and CTLA-4 were substantially increased in the high-risk group. Moreover, we can distinguish between patients based on their immunotherapeutic responses more effectively if we categorize them by this signature. Additionally, candidate compounds were identified for the differentiation of CRC subtypes.

Conclusion: The ferroptosis-associated gene signature identified in this study is effective in predicting the prognosis and evaluating immunotherapeutic response in CRC patients, and provides us with novel insights into the potential effect of ferroptosis targeted treatment on CRC.
Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions
Authors: Lachén-Montes Mercedes , Mendizuri Naroa , Ausín Karina , Echaide Miriam , Blanco Ester , Chocarro Luisa , de Toro María , Escors David , Fernández-Irigoyen Joaquín , Kochan Grazyna , Santamaría Enrique
Published: September 2022

One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tagged SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells. Transcriptomic and proteomic trajectories uncovered a widespread metabolic remodeling commonly converging in extracellular matrix organization, lipid metabolism and signaling by receptor tyrosine kinases. The molecular singularities and specific interactome expression modules were also characterized for each viral structural factor. The intracellular molecular imbalance induced by each SARS-CoV-2 structural protein was accompanied by differential activation dynamics in survival and immunological routes in parallel with a differentiated secretion profile of chemokines in OB cells. Machine learning through a proteotranscriptomic data integration uncovered TGF-beta signaling as a confluent activation node by the SARS-CoV-2 structural proteome. Taken together, these data provide important avenues for understanding the multifunctional immunomodulatory properties of SARS-CoV-2 M, N, S and E proteins beyond their intrinsic role in virion formation, deciphering mechanistic clues to the olfactory inflammation observed in COVID-19 patients.
Pan-cancer analysis reveals interleukin-17 family members as biomarkers in the prediction for immune checkpoint inhibitor curative effect
Authors: Han Xiaying , Ye Jianxin , Huang Runzhi , Li Yongai , Liu Jianpeng , Meng Tong , Song Dianwen
Published: September 2022

Background

The interleukin-17 (IL-17) family contains six homologous genes, IL-17A to IL-17F. Growing evidence indicates that dysregulated IL-17 family members act as major pathogenic factors in the early and late stages of cancer development and progression. However, the prevalence and predictive value of IL-17 for immune checkpoint inhibitor (ICI) therapeutic effectiveness in multiple tumor types remain largely unknown, and the associations between its expression levels and immunotherapy-associated signatures also need to be explored.

Methods

The pan-cancer dataset in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (http://xena.ucsc.edu/). The immunotherapeutic cohorts included IMvigor210, which were obtained from the Gene Expression Omnibus database and included in a previously published study. Other datasets, namely, the GEO dataset and PRECOG, GEO, and METABRIC databases, were also included. In 33 TCGA tumor types, a pan-cancer analysis was carried out including their expression map, clinical risk assessment, and immune subtype analysis, along with their association with the stemness indices, tumor microenvironment (TME) in pan-cancer, immune infiltration analysis, ICI-related immune indicators, and drug sensitivity. RT-PCR was also carried out to verify the gene expression levels among MCF-10A and MCF-7 cell lines.

Results

The expression of the IL-17 family is different between tumor and normal tissue in most cancers, and consistency has been observed between gene activity and gene expression. RT-PCR results show that the expression differences in the IL-17 family of human cell (MCF-10A and MCF-7) are consistent with the bioinformatics differential expression analysis. Moreover, the expression of the IL-17 family can be a sign of patients’ survival prognosis in some tumors and varies in different immune subtypes. Moreover, the expression of the IL-17 family presents a robust correlation with immune cell infiltration, ICI-related immune indicators, and drug sensitivity. High expression of the IL-17 family is significantly related to immune-relevant pathways, and the low expression of IL-17B means a better immunotherapeutic response in BLCA.

Conclusion

Collectively, IL-17 family members may act as biomarkers in predicting the prognosis of the tumor and the therapeutic effects of ICIs, which provides new guidance for cancer treatment.
Improvement of gut microbiome and intestinal permeability following splenectomy plus pericardial devascularization in hepatitis B virus-related cirrhotic portal hypertension
Authors: Zhao Yang , Zhou Rui , Guo Ying , Chen Xi , Zhang Aiyu , Wang Jiayin , Ji Fanpu , Qin Bowen , Geng Jing , Kong Guangyao , Li Zongfang
Published: September 2022

The gut microbiome is an essential component of the intestinal mucosal barrier, critical in regulating intestinal permeability. Microbiome dysbiosis and intestinal permeability changes are commonly encountered conditions in patients with cirrhosis and are closely related to its development and further complications. However, alterations in the gut microbiome and intestinal permeability in chronic hepatitis B virus (HBV) patients with cirrhotic portal hypertension after undergoing a splenectomy plus pericardial devascularization (SPD) have not been investigated. This study recruited 22 patients who were measured against themselves on the study parameters before and after an SPD, along with 20 healthy controls. Methodologically, fecal samples were collected for gut microbiome analysis by 16S ribosomal DNA sequencing, and peripheral blood samples were obtained to examine the liver function and intestinal permeability. This study showed that the community structure of the gut microbiomes in patients before the SPD exhibited obvious differences from those in the healthy control group. They also exhibited a decreased bacterial community richness, increased intestinal permeability, and enhanced inflammation compared with the healthy controls. These issues were further aggravated two weeks after the SPD. There was also evidence of significantly higher abundances of Streptococcaceae, Enterobacteriaceae, and Enterococcaceae than those in the healthy control group. However, 12 months after the surgery, 12 of the 16 patient-associated genera recovered, of which 10 reached normal levels. Additionally, the microbiome diversity increased; the bacterial composition was back to a level similar to the healthy controls. Liver function, intestinal permeability, and inflammation levels all improved compared with preoperative levels. Furthermore, correlation analyses indicated that the five recovered bacterial taxa and the Shannon diversity index were correlated with several improved clinical indicators. Altogether, the improvements in the liver function and intestinal permeability in HBV-related cirrhotic patients may be related to the restoration of the gut microbiome after an SPD.
Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH
Authors: Maretti-Mira Ana C. , Salomon Matthew P. , Hsu Angela M. , Kanel Gary C. , Golden-Mason Lucy
Published: September 2022

Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However, the impact of cholesterol on these cells in the setting of NASH remains elusive. Here, we demonstrate that the dietary cholesterol content directly affects hepatic macrophage global gene expression. Our findings suggest that the modifications triggered by prolonged high cholesterol intake induce long-lasting hepatic damage and support the expansion of a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction. The present work expands the understanding of the modulatory effects of cholesterol on innate immune cell transcriptome and may help identify novel therapeutic targets for NASH intervention.
Affinity capillary electrophoresis – mass spectrometry permits direct binding assessment of IgG and FcγRIIa in a glycoform-resolved manner
Authors: Gstöttner Christoph , Knaupp Alexander , Vidarsson Gestur , Reusch Dietmar , Schlothauer Tilman , Wuhrer Manfred , Domínguez-Vega Elena
Published: September 2022

The impact of antibody glycoforms on FcγRIIa activation and immune responses is poorly understood. Yet, glycoform binding assessment remains one of the major analytical challenges requiring long enrichment or glycoengineering steps. Here, we developed and applied an affinity capillary electrophoresis-mass spectrometry approach to selectively assess the binding of different antibody glycoforms to the FcγIIa receptor without the need of glycoengineering. The approach required only low microgram amounts of antibody and receptor and enables assessing the binding of high and low-abundance glycoforms. The approach indicated clear differences in binging between doubly-, hemi-glycosylated and non-glycosylated antibodies as well as for mutated (Leu234Ala, Leu235Ala – Pro329-Gly (LALA-PG)) IgG1 antibodies silenced for Fcγ binding. The LALA-PG mutated antibody showed no binding to the FcγIIa receptor (excluding potential non-specific binding effects) while the non-glycosylated IgG1 showed a strongly reduced, but still minor binding. The highest binding affinity was for the antibody carrying two complex-type glycans. Man5 glycans resulted in decreased binding compared to complex-type glycans, with the lowest binding for the IgG containing two Man5. For complex-type glycans, galactosylation showed a subtle increase in binding to the FcγIIa receptor, and sialylation showed an increase in binding for lower sialylated species. Fucosylation did not influence binding to the FcγIIa receptor. Finally, the assay was evaluated for the two variants of the FcγRIIa receptor (allotypes H131 and R131) showing highly comparable glycoform selectivity. Overall, the proposed approach allows the direct comparison of binding affinities of different antibody species in mixtures promising a fast establishment of their structure-function relationships.
Immune depletion of the methylated phenotype of colon cancer is closely related to resistance to immune checkpoint inhibitors
Authors: Zhong Chengqian , Xie Tingjiang , Chen Long , Zhong Xuejing , Li Xinjing , Cai Xiumei , Chen Kaihong , Lan Shiqian
Published: September 2022

Background

Molecular typing based on single omics data has its limitations and requires effective integration of multiple omics data for tumor typing of colorectal cancer (CRC).

Methods

Transcriptome expression, DNA methylation, somatic mutation, clinicopathological information, and copy number variation were retrieved from TCGA, UCSC Xena, cBioPortal, FireBrowse, or GEO. After pre-processing and calculating the clustering prediction index (CPI) with gap statistics, integrative clustering analysis was conducted via MOVICS. The tumor microenvironment (TME) was deconvolved using several algorithms such as GSVA, MCPcounter, ESTIMATE, and PCA. The metabolism-relevant pathways were extracted through ssGSEA. Differential analysis was based on limma and enrichment analysis was carried out by Enrichr. DNA methylation and transcriptome expression were integrated via ELMER. Finally, nearest template or hemotherapeutic sensitivity prediction was conducted using NTP or pRRophetic.

Results

Three molecular subtypes (CS1, CS2, and CS3) were recognized by integrating transcriptome, DNA methylation, and driver mutations. CRC patients in CS3 had the most favorable prognosis. A total of 90 differentially mutated genes among the three CSs were obtained, and CS3 displayed the highest tumor mutation burden (TMB), while significant instability across the entire chromosome was observed in the CS2 group. A total of 30 upregulated mRNAs served as classifiers were identified and the similar diversity in clinical outcomes of CS3 was validated in four external datasets. The heterogeneity in the TME and metabolism-related pathways were also observed in the three CSs. Furthermore, we found CS2 tended to loss methylations while CS3 tended to gain methylations. Univariate and multivariate Cox regression revealed that the subtypes were independent prognostic factors. For the drug sensitivity analysis, we found patients in CS2 were more sensitive to ABT.263, NSC.87877, BIRB.0796, and PAC.1. By Integrating with the DNA mutation and RNA expression in CS3, we identified that SOX9, a specific marker of CS3, was higher in the tumor than tumor adjacent by IHC in the in-house cohort and public cohort.

Conclusion

The molecular subtypes based on integrated multi-omics uncovered new insights into the prognosis, mechanisms, and clinical therapeutic targets for CRC.
Identification and validation of SNHG gene signature to predict malignant behaviors and therapeutic responses in glioblastoma
Authors: Fan Yang , Gao Zijie , Xu Jianye , Wang Huizhi , Guo Qindong , Xue Hao , Zhao Rongrong , Guo Xing , Li Gang
Published: September 2022

Glioblastoma (GBM) patients exhibit high mortality and recurrence rates despite multimodal therapy. Small nucleolar RNA host genes (SNHGs) are a group of long noncoding RNAs that perform a wide range of biological functions. We aimed to reveal the role of SNHGs in GBM subtypes, cell infiltration into the tumor microenvironment (TME), and stemness characteristics. SNHG interaction patterns were determined based on 25 SNHGs and systematically correlated with GBM subtypes, TME and stemness characteristics. The SNHG interaction score (SNHGscore) model was generated to quantify SNHG interaction patterns. The high SNHGscore group was characterized by a poor prognosis, the mesenchymal (MES) subtype, the infiltration of suppressive immune cells and a differentiated phenotype. Further analysis indicated that high SNHGscore was associated with a weaker response to anti-PD-1/L1 immunotherapy. Tumor cells with high SNHG scores were more sensitive to drugs targeting the EGFR and ERK-MAPK signaling pathways. Finally, we assessed SNHG interaction patterns in multiple cancers to verify their universality. This is a novel and comprehensive study that provides targeted therapeutic strategies based on SNHG interactions. Our work highlights the crosstalk and potential clinical utility of SNHG interactions in cancer therapy.
Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines
Authors: Pazos-Castro Diego , Margain Clémence , Gonzalez-Klein Zulema , Amores-Borge Marina , Yuste-Calvo Carmen , Garrido-Arandia Maria , Zurita Lucía , Esteban Vanesa , Tome-Amat Jaime , Diaz-Perales Araceli , Ponz Fernando
Published: September 2022

Virus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived from Turnip mosaic virus (TuMV) have proven to present a tridimensional structure suited to display molecules of interest on their surface, making them interesting tools to be studied in theragnostic strategies. Here, we study their potential in the treatment of food allergy by genetically coupling TuMV-derived VLPs to Pru p 3, one of the most dominant allergens in Mediterranean climates. VLPs-Pru p 3 were generated by cloning a synthetic gene encoding the TuMV coat protein and Pru p 3, separated by a linker, into a transient high-expression vector, followed by agroinfiltration in Nicotiana benthamiana plants. The generated fusion protein self-assembled in planta to form the VLPs, which were purified by exclusion chromatography. Their elongated morphology was confirmed by electron microscopy and their size (~400 nm), and monodispersity was confirmed by dynamic light scattering. Initial in vitro characterization confirmed that they were able to induce proliferation of human immune cells. This proliferative capability was enhanced when coupled with the natural lipid ligand of Pru p 3. The resultant formulation, called VLP-Complex, was also able to be transported by intestinal epithelial cells, without affecting the monolayer integrity. In light of all these results, VLP-Complex was furtherly tested in a mouse model of food allergy. Sublingual administration of VLP-Complex could effectively reduce some serological markers associated with allergic responses in mice, such as anti-Pru p 3 sIgE and sIgG2a. Noteworthy, no associated macroscopic, nephritic, or hepatic toxicity was detected, as assessed by weight, blood urea nitrogen (BUN) and galectin-3 analyses, respectively. Our results highlight the standardized production of allergen-coated TuMV-VLPs in N. benthamiana plants. The resulting formula exerts notable immunomodulatory properties without the need for potentially hazardous adjuvants. Accordingly, no detectable toxicity associated to their administration was detected. As a result, we propose them as good candidates to be furtherly studied in the treatment of immune-based pathologies.
Microstructure degradation of service-exposed turbine blades made of directionally solidified DZ125 superalloy
Authors: Xie Yadan , Zhao Jianjiang , Wang Jiangwei , Wei Hua
Published: September 2022

The investigation about the degradation behavior of turbine blades exposed to complex and extreme environments for long-term service is of great importance to assess the remaining life of the blades. In our work, the microstructure at different positions of the service-exposed turbine blade was characterized from the micron scale to the nanoscale. The results showed that there are noticeable differences in the microstructure at different positions of the blade and the blade has a complex service history. These conclusions suggest that the most severely damaged part of the blade should be responsible for assessing the remaining life of the blade, moreover, the mechanical properties of materials should not be limited to life at constant temperature and stress, rather non-isothermal and variable stress tests are more instructive in assessing the performance or life of aircraft engine blade materials.
Population genomics in neglected malaria parasites
Authors: Brashear Awtum M. , Cui Liwang
Published: September 2022

Malaria elimination includes neglected human malaria parasites Plasmodium vivax, Plasmodium ovale spp., and Plasmodium malariae. Biological features such as association with low-density infection and the formation of hypnozoites responsible for relapse make their elimination challenging. Studies on these parasites rely primarily on clinical samples due to the lack of long-term culture techniques. With improved methods to enrich parasite DNA from clinical samples, whole-genome sequencing of the neglected malaria parasites has gained increasing popularity. Population genomics of more than 2200 P. vivax global isolates has improved our knowledge of parasite biology and host-parasite interactions, identified vaccine targets and potential drug resistance markers, and provided a new way to track parasite migration and introduction and monitor the evolutionary response of local populations to elimination efforts. Here, we review advances in population genomics for neglected malaria parasites, discuss how the rich genomic information is being used to understand parasite biology and epidemiology, and explore opportunities for the applications of malaria genomic data in malaria elimination practice.
Expert workshop summary: Advancing toward a standardized murine model to evaluate treatments for antimicrobial resistance lung infections
Authors: Arrazuria Rakel , Kerscher Bernhard , Huber Karen E. , Hoover Jennifer L. , Lundberg Carina Vingsbo , Hansen Jon Ulf , Sordello Sylvie , Renard Stephane , Aranzana-Climent Vincent , Hughes Diarmaid , Gribbon Philip , Friberg Lena E. , Bekeredjian-Ding Isabelle
Published: September 2022

The rise in antimicrobial resistance (AMR), and increase in treatment-refractory AMR infections, generates an urgent need to accelerate the discovery and development of novel anti-infectives. Preclinical animal models play a crucial role in assessing the efficacy of novel drugs, informing human dosing regimens and progressing drug candidates into the clinic. The Innovative Medicines Initiative-funded “Collaboration for prevention and treatment of MDR bacterial infections” (COMBINE) consortium is establishing a validated and globally harmonized preclinical model to increase reproducibility and more reliably translate results from animals to humans. Toward this goal, in April 2021, COMBINE organized the expert workshop “Advancing toward a standardized murine model to evaluate treatments for AMR lung infections”. This workshop explored the conduct and interpretation of mouse infection models, with presentations on PK/PD and efficacy studies of small molecule antibiotics, combination treatments (β-lactam/β-lactamase inhibitor), bacteriophage therapy, monoclonal antibodies and iron sequestering molecules, with a focus on the major Gram-negative AMR respiratory pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Here we summarize the factors of variability that we identified in murine lung infection models used for antimicrobial efficacy testing, as well as the workshop presentations, panel discussions and the survey results for the harmonization of key experimental parameters. The resulting recommendations for standard design parameters are presented in this document and will provide the basis for the development of a harmonized and bench-marked efficacy studies in preclinical murine pneumonia model.
Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents
Authors: Arrazuria Rakel , Kerscher Bernhard , Huber Karen E. , Hoover Jennifer L. , Lundberg Carina Vingsbo , Hansen Jon Ulf , Sordello Sylvie , Renard Stephane , Aranzana-Climent Vincent , Hughes Diarmaid , Gribbon Philip , Friberg Lena E. , Bekeredjian-Ding Isabelle
Published: September 2022

Antimicrobial resistance has become one of the greatest threats to human health, and new antibacterial treatments are urgently needed. As a tool to develop novel therapies, animal models are essential to bridge the gap between preclinical and clinical research. However, despite common usage of in vivo models that mimic clinical infection, translational challenges remain high. Standardization of in vivo models is deemed necessary to improve the robustness and reproducibility of preclinical studies and thus translational research. The European Innovative Medicines Initiative (IMI)-funded “Collaboration for prevention and treatment of MDR bacterial infections” (COMBINE) consortium, aims to develop a standardized, quality-controlled murine pneumonia model for preclinical efficacy testing of novel anti-infective candidates and to improve tools for the translation of preclinical data to the clinic. In this review of murine pneumonia model data published in the last 10 years, we present our findings of considerable variability in the protocols employed for testing the efficacy of antimicrobial compounds using this in vivo model. Based on specific inclusion criteria, fifty-three studies focusing on antimicrobial assessment against Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii were reviewed in detail. The data revealed marked differences in the experimental design of the murine pneumonia models employed in the literature. Notably, several differences were observed in variables that are expected to impact the obtained results, such as the immune status of the animals, the age, infection route and sample processing, highlighting the necessity of a standardized model.
Nitric oxide reversibly binds the reduced [2Fe-2S] cluster in mitochondrial outer membrane protein mitoNEET and inhibits its electron transfer activity
Authors: Fontenot Chelsey R. , Cheng Zishuo , Ding Huangen
Published: September 2022

MitoNEET is a mitochondrial outer membrane protein that regulates energy metabolism, iron homeostasis, and production of reactive oxygen species in cells. Aberrant expression of mitoNEET in tissues has been linked to type II diabetes, neurodegenerative diseases, and several types of cancer. Structurally, the N-terminal domain of mitoNEET has a single transmembrane alpha helix that anchors the protein to mitochondrial outer membrane. The C-terminal cytosolic domain of mitoNEET hosts a redox active [2Fe-2S] cluster via an unusual ligand arrangement of three cysteine and one histidine residues. Here we report that the reduced [2Fe-2S] cluster in the C-terminal cytosolic domain of mitoNEET (mitoNEET45-108) is able to bind nitric oxide (NO) without disruption of the cluster. Importantly, binding of NO at the reduced [2Fe-2S] cluster effectively inhibits the redox transition of the cluster in mitoNEET45-108. While the NO-bound [2Fe-2S] cluster in mitoNEET45-108 is stable, light excitation releases NO from the NO-bound [2Fe-2S] cluster and restores the redox transition activity of the cluster in mitoNEET45-108. The results suggest that NO may regulate the electron transfer activity of mitoNEET in mitochondrial outer membrane via reversible binding to its reduced [2Fe-2S] cluster.
Dexamethasone reduces vascular endothelial growth factor in comparison to placebo in post-operative chronic subdural hematoma samples: A target for future drug therapy?
Authors: Edlmann Ellie , Giorgi-Coll Susan , Thelin Eric P. , Hutchinson Peter J. , Carpenter Keri L. H.
Published: September 2022

Background

Chronic subdural hematoma (CSDH) is a collection of blood and fluid that arises on the brain surface due to a combination of trauma and/or inflammation. The mainstay of treatment is surgical drainage, but CSDH can recur. Dexamethasone has been shown to reduce CSDH recurrence, but its mechanism of action has not been fully elucidated. Understanding the inflammatory mediators driving CSDH formation and recurrence and how dexamethasone alters this can help develop new therapeutic strategies.

Methods

A subgroup of adult patients recruited to the Dex-CSDH trial, randomized to dexamethasone or placebo, who had surgery for their CSDH, were included. CSDH fluid and peripheral blood were collected intraoperatively, from post-operative drains and operated recurrences. Samples were analyzed using a 12-plex panel of inflammatory mediators. Clinical patient data were also reviewed.

Results

A total of 52 patients, with a mean age of 76 years, were included. Five recurrent CSDHs occurred. Vascular endothelial growth factor (VEGF) had the highest concentration across all CSDHs, and only matrix metalloproteinase (MMP)-9 had lower concentrations in CSDH compared to plasma but was increased in recurrent CSDHs. The interleukin (IL)-10 concentration was significantly lower in primary CSDHs that recurred. Most inflammatory mediators increased post-operatively, and dexamethasone significantly reduced the post-operative peak in VEGF on day 2, compared to placebo.

Conclusion

It is evident that VEGF plays a critical role in the inflammatory response in CSDH. The post-operative reduction with dexamethasone could signal the mechanism by which it reduces recurrence. Novel therapies with a better side-effect profile than dexamethasone should be targeted at VEGF or potential alternatives such as IL-10 supplementation.
Determinants of functioning and health-related quality of life after vestibular stroke
Authors: Schuhbeck Franziska , Strobl Ralf , Conrad Julian , Möhwald Ken , Jaufenthaler Patricia , Jahn Klaus , Dieterich Marianne , Grill Eva , Zwergal Andreas
Published: September 2022

Background

Stroke accounts for 5–10% of all presentations with acute vertigo and dizziness. The objective of the current study was to examine determinants of long-term functioning and health-related quality of life (HRQoL) in a patient cohort with vestibular stroke.

Methods

Thirty-six patients (mean age: 66.1 years, 39% female) with an MRI-proven vestibular stroke were followed prospectively (mean time: 30.2 months) in the context of the EMVERT (EMergency VERTigo) cohort study at the Ludwig-Maximilians Universität, Munich. The following scores were obtained once in the acute stage (<24 h of symptom onset) and once during long-term follow-up (preferably >1 year after stroke): European Quality of Life Scale-five dimensions-five levels questionnaire (EQ-5D-5L) and Visual Analog Scale (EQ-VAS) for HRQoL, Dizziness Handicap Inventory (DHI) for symptom severity, and modified Rankin Scale (mRS) for general functioning and disability. Anxiety state and trait were evaluated by STAI-S/STAI-T, and depression was evaluated by the Patient Health Questionnaire-9 (PHQ-9). Voxel-based lesion mapping was applied in normalized MRIs to analyze stroke volume and localization. Multiple linear regression models were calculated to determine predictors of functional outcome (DHI, EQ-VAS at follow-up).

Results

Mean DHI scores improved significantly from 45.0 in the acute stage to 18.1 at follow-up (p < 0.001), and mean mRS improved from 2.1 to 1.1 (p < 0.001). Mean HRQoL (EQ-5D-5L index/EQ-VAS) changed from 0.69/58.8 to 0.83/65.2 (p = 0.01/p = 0.11). Multiple linear regression models identified higher scores of STAI-T and DHI at the time of acute vestibular stroke and larger stroke volume as significant predictors for higher DHI at follow-up assessment. The effect of STAI-T was additionally enhanced in women. There was a significant effect of patient age on EQ-VAS, but not DHI during follow-up.

Conclusion

The average functional outcome of strokes with the chief complaint of vertigo and dizziness is favorable. The most relevant predictors for individual outcomes are the personal anxiety trait (especially in combination with the female sex), the initial symptom intensity, and lesion volume. These factors should be considered for therapeutic decisions both in the acute stage of stroke and during subsequent rehabilitation.
Graft-versus-host disease complicated with small bowel obstruction in children: A case report
Authors: Wang Yizhong , Liu Jiangbin , Jiang Bingxin , Yuan Chenling , Chen Licai , Zhang Ting , Lv Zhibao
Published: September 2022

Graft-versus-host disease (GvHD) is a severe complication following hematopoietic cell transplantation (HCT). The clinical manifestations of GvHD can affect multiple systems. Although gastrointestinal (GI) GvHD is common, GI obstruction complications are rare. Here, we present a case of GI-GvHD after HCT for acute myeloid leukemia (AML) in a young girl from China. The patient suffered from watery diarrhea, which progressed to bloody diarrhea 40 days after HCT. She experienced prolonged and repeated mucous or bloody stool after the withdrawal of cyclosporine and the gradual reduction in methylprednisolone. The plain abdominal radiography and computed tomographic (CT) scan showed apparent bowel wall thickening and intestinal stenosis 10 months after HCT. Finally, the patient underwent surgery to remove the small intestinal stenosis at the age of 26 months. The patient recovered with the help of appropriate medical therapies and nutritional support during hospitalization. She remained stable, and there was no recurrence of GI symptoms 16 months after the surgery. In summary, surgery may be an optimal treatment for GvHD patients with persistent bowel obstruction and failure of appropriate immunosuppressive therapies.
Inhibition and potential treatment of colorectal cancer by natural compounds via various signaling pathways
Authors: Wang Mingchuan , Liu Xianjun , Chen Tong , Cheng Xianbin , Xiao Huijie , Meng Xianglong , Jiang Yang
Published: September 2022

Colorectal cancer (CRC) is a common type of malignant digestive tract tumor with a high incidence rate worldwide. Currently, the clinical treatment of CRC predominantly include surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Some natural compounds found in plants, fungi, marine animals, and bacteria have been shown to inhibit the occurrence and development of CRC. Although the explicit molecular mechanisms underlying the therapeutic effects of these compounds on CRC are not clear, classical signaling transduction pathways such as NF-kB and Wnt/β-catenin are extensively regulated. In this review, we have summarized the specific mechanisms regulating the inhibition and development of CRC by various types of natural compounds through nine signaling pathways, and explored the potential therapeutic values of these natural compounds in the clinical treatment of CRC.