bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability Assessment of Multi-Stage Slopes Considering Local Failure
Authors: Wu Haochen , Sun Miaojun , Wang Jinnan
Published: June 2022

The analytical method for slope stability analysis requires a collapse mechanism in advance. The collapse mechanism for a multi-staged slope is generally assumed to be overall failure, whereas this kind of slope may suffer from local failure. However, a local failure is rarely reported in the previous research for multi-staged slopes, which may result in an overestimate for slope stability. To this end, local failure is incorporated into the collapse mechanism for the first time, so as to develop a complete approach to assess the stability of multi-stage slopes. The modified pseudo-dynamic method is conducted to properly account for seismic effects. Thanks to the limit analysis method and strength reduction technique, the safety factor of a multi-stage slope is obtained. The result obtained by the presented approach shows a good agreement with that of previous literature and numerical calculations. The collapse mechanism of multi-stage slopes is studied, and the safety factor is presented schematically for a wide range of parameters. The results show that the local failure for a multi-stage slope often manifests under the intense seismic effects.
Experimental Study on Moisture Migration in Unsaturated Sand Under Cyclic Diurnal Temperature Variation
Authors: Mao Xuesong , Zhang Jianxun , Wu Qian , Liu Feifei , Li Xiangyu , Wang Yueyue
Published: June 2022

The phenomenon of mixed migration of liquid water and water vapor appeared in subgrade covered with an impermeable semi-arid rigid base. The soil-water characteristic curves (SWCC) at different temperatures are a key factor in revealing the mechanism of liquid water migration. In particular, the matric suction of unsaturated soil is considerably affected by the change in temperature. A moisture migration laboratory experiment can visually observe the moisture migration process. Therefore, matric suction tests with different temperatures and moisture migration of the one-dimensional soil column were conducted. Then the non-isothermal SWCC model was extended based on the Van Genuchten (VG) model, and the validity was given. Based on the above results, the mechanism of the mixed migration of liquid water and water vapor in moisture migration of unsaturated soil under the effect of the cyclic diurnal temperature variation was revealed. The research demonstrated that the matric suction of unsaturated sand decreases with the increase in temperature. During the daytime, the temperature of the soil column gradually increases. Except for a part of liquid water transformed into water vapor, the liquid water migrated downward under the action of gravity and matric potential. At night, the water vapor accumulated beneath the lid condensed into liquid water under the action of the temperature sharply decreased, which was the main reason for the moisture aggregate beneath the closed layer. Meanwhile, the liquid water and water vapor mutually transformed and dynamically migrated in the soil column under the effect of the cyclic diurnal temperature variation. The moisture in the soil column dynamically migrates between daytime and night, which is named the “moisture circulation of covering effect” in this paper. The “moisture circulation of covering effect” would progressively attain a dynamic equilibrium and dynamic circulatory between the daytime and night with time.
Influence of Debris-Flow Impact on the Structural Stability of Check Dams
Authors: Eu Song , Im Sangjun
Published: June 2022

Small check dams are widely used in the Republic of Korea to mitigate and prevent sediment-driven damages by mountain torrents. This study aimed to quantify the combined effects of debris-flow impact forces and earth pressures from dam sedimentations on the structural stability of a dam by incorporating the change in the longitudinal profile of the channel bed owing to sediment deposition. A debris-flow simulation model (Hyper Kanako) was used to reproduce the debris-flow behavior from the 2011 Mt. Umyeon landslide (Seoul, The Republic of Korea). Finite element analysis was conducted to analyze the structural stability of the check dam under various debris discharge and sedimentation scenarios. The magnitudes of impact forces that were exerted on the check dam ranged from 81.76 kPa under a non-deposition scenario to 123.04 kPa under a 100% deposition scenario. The resultant tensile and compressive stresses were found to be up to 0.80 and 0.35 MPa, respectively, which were lower than the maximum allowable strengths of the dam, securing sufficient strength for the dam stability. Overall, the proposed approach can be applied to obtain a better understanding of the resultant internal stresses experienced during debris flow and sediment deposition, thereby providing valuable information for the structural analysis and safety assessment of check dams.
Genetic Analysis of Abnormally High Ground Temperature From the Existence of Magmatic Rock Beneath Pingdingshan Coalfield
Authors: Wang Qi , Liao Jiajia , Zhou Dongxu , Hou Quanlin , Wang Xinyi
Published: June 2022

Studies on the genetic mechanisms of abnormally high ground temperatures in coalfields are of great significance for the efficient mining of coal mines and the development and utilization of geothermal water. Therefore, we measured the temperature of 45 Cambrian limestone groundwater samples, thermal conductivity values of 11 Cambrian limestone samples, and the contents of uranium, thorium, and potassium-40 of 40 rock samples, aiming to ascertain the heat source of the abnormally high ground temperature in the Pingdingshan coalfield. The results show that the average geothermal gradient in the coalfield is about 3.32°C/100 m, and the calculated values of the average ground heat flow are about 104.28 mW/m2, which demonstrate the abnormally high ground temperature in Pingdingshan coalfield. We also concluded that the whole radiogenic heat generation in sedimentary and magmatic rocks is 1.53 mW/m2, whose contribution rate to the local geothermal flow is only 1.47%. Hence, we can infer that magmatic rocks exposed in or near the coalfield area may supply the heat source for the abnormally high ground temperature beneath Pingdingshan coalfield. A comprehensive analysis further shows that the latest intrusion time of the magmatic rock mass in the coalfield was 35 Ma; its lava temperature was 900°C, its cooling rate is 20.0°C/Ma, and the calculated residual temperature is more than 200.0°C. These values support the idea that the magmatic rocks may be the primary cause of the abnormally high ground temperature in the Pingdingshan coalfield.
Prediction Method of Sealing Capacity Distribution of Regional Mudstone Caprocks Damaged by Fault During the Hydrocarbon Accumulation Period
Authors: Han Xu , Fu Guang , Liang Mugui , Jin Fengming , Han Guomeng , Jiang Wenya
Published: June 2022

In order to study the distribution law of oil and gas above and below the regional mudstone caprocks damaged by fault in petroliferous basins, based on the study of the sealing mechanism and degree of regional mudstone caprocks damaged by fault during the hydrocarbon accumulation period, the paleo-juxtaposition thickness of regional mudstone caprock was calculated by determining the paleo-fault throw of faults and the paleo-thickness of regional mudstone caprocks during the hydrocarbon accumulation period. According to the relation between the paleo-juxtaposition thickness of regional mudstone caprocks at known well points in the study area and the distribution of oil and gas above and below the regional mudstone caprock, the maximum juxtaposition thickness required for the upper and lower connection of the fault-associated fracture zone in the regional mudstone caprock was determined. On this basis, a set of prediction methods for the sealing capacity of regional mudstone caprocks damaged by fault during the hydrocarbon accumulation period was established. Then, this method was applied to the prediction of the damage degree distribution of the Zhangdong Fault to the regional mudstone caprock of the middle sub-member of the first member of the Shahejie Formation in the middle and late depositional periods of the Minghuazhen Formations in Qikou Sag of the Bohai Bay Basin during the hydrocarbon accumulation period. The results show that the damage degree of the Zhangdong Fault to the regional mudstone caprock of the middle sub-member of the first member of the Shahejie Formation during the hydrocarbon accumulation period is large. The largest damage appears in the east, with an a-value greater than 1, followed by the west, with an a-value between 0.5 and 1. The relatively minor damage occurs in the middle west part, with an a-value less than 0.5. The middle part is conducive to the accumulation and preservation of oil and gas generated from the source rock of the underlying third member of the Shahejie Formation, which is consistent with the fact that oil and gas discovered in the lower sub-member of the first member of the Shahejie Formation near the Zhangdong Fault are mainly distributed in its middle part. It shows that this method is feasible to predict the damage degree distribution of regional mudstone caprocks during the hydrocarbon accumulation period.
Comparing Construction and Study of Concept Maps – An Intervention Study on Learning Outcome, Self-Evaluation and Enjoyment Through Training and Learning
Authors: Lenski Sina , Elsner Stefanie , Großschedl Jörg
Published: June 2022

Concept maps are graphical tools for organizing and representing knowledge. They are recommended for biology learning to support conceptual thinking. In this study, we compare concept map construction (CM-c, i.e., creating concept maps) and concept map study (CM-s, i.e., observing concept maps). Existing theories and indirect empirical evidence suggest distinct effects of both formats on cognitive, metacognitive and emotional aspects of learning. We developed a CM-c training, a CM-s training, and a brief introduction to concept maps (control training) for junior high school students. We investigated effects on learning performance, concept map quality, cognitive load (cognitive effects), accuracy of self-evaluation (metacognitive effects) and enjoyment (emotional effects) of these trainings in a subsequent learning phase (CM-c learning vs. CM-s learning) in a quasi-experimental two-factorial study with 3 × 2 groups (N = 167), involving the factors training type and learning type. Results reveal that CM-c training increased learning performance and concept map quality. Effects of CM-c training on learning performance transferred onto learning with CM-s. Self-evaluation was slightly more accurate after CM-c training than CM-s training. Students reported moderate, and highly varying enjoyment during CM-c and CM-s learning. The superiority of CM-c over CM-s in learning performance and concept map quality probably lies in its characteristic of being an active learning strategy. We recommend practitioners to favor CM-c training over CM-s training, and foster students’ active engagement and enjoyment.
Impact of Risk Factors on Short and Long-Term Maternal and Neonatal Outcomes in Women With Gestational Diabetes Mellitus: A Prospective Longitudinal Cohort Study
Authors: Corcillo Antonella , Quansah Dan Yedu , Kosinski Christophe , Benhalima Katrien , Puder Jardena J.
Published: June 2022

Aims

Universal screening of gestational diabetes mellitus (GDM) in women with no risk factors (RF) for GDM remains controversial. This study identified the impact of the presence of RF on perinatal and postpartum outcomes.

Methods

This prospective cohort study included 780 women with GDM. GDM RF included previous GDM, first grade family history of type 2 diabetes, high-risk ethnicity and pre-pregnancy overweight/obesity (OW/OB). Outcomes included obstetrical, neonatal and maternal metabolic parameters during pregnancy and up to 1 year postpartum.

Results

Out of 780 patients, 24% had no RF for GDM. Despite this, 40% of them needed medical treatment and they had a high prevalence of glucose intolerance of 21 and 27% at 6-8 weeks and 1-year postpartum, respectively. Despite similar treatment, women with RF had more neonatal and obstetrical complications, but they had especially more frequent adverse metabolic outcomes in the short- and long-term. The most important RF for poor perinatal outcome were previous GDM and pre-pregnancy OW/OB, whereas high-risk ethnicity and pre-pregnancy OW/OB were RF for adverse postpartum metabolic outcomes. Increasing number of RF were associated with worsened perinatal and long-term postpartum outcomes except for pregnancy-induced hypertension, C-section delivery and neonatal hypoglycaemia.

Conclusion

Women with no RF had a high prevalence of adverse perinatal and postpartum outcomes, while the presence of RF particularly increased the risk for postpartum adverse metabolic outcomes. This calls for a RF-based long-term follow-up of women with GDM.
Pharmacological Modulation of Melanocortin 1 Receptor Signaling by Mrap Proteins in Xenopus tropicalis
Authors: Tai Xiaolu , Zhang Yaqun , Yao Jindong , Li Xuan , Liu Jun , Han Jiazhen , Lyu Jianjun , Lin Gufa , Zhang Chao
Published: June 2022

The melanocortin system consists of five G protein–coupled receptors (MC1R-MC5R), the bidirectional endogenous ligands (MSH and Agouti families), and accessory proteins (MRAP1 and MRAP2). Accumulative studies of vertebrate species find high expression level of melanocortin 1 receptor (MC1R) in the dermal melanocyte and elucidate the essential roles in the skin and fur pigmentation, morphological background adaptation, and stress response. The diploid amphibian Xenopus tropicalis (xt) has been utilized as a fantastic animal model for embryonic development and studies of physiological cryptic colouring and environmental adaptiveness. However, the interaction of xtMc1r signaling with xtMrap proteins has not been assessed yet. In this study, we carried out in silico evolutionary analysis of protein alignment and genetic phylogenetic and genomic synteny of mc1r among various vertebrates. Ubiquitous expression of mrap1 and mrap2 and the co-expression with mc1r transcripts in the skin were clearly observed. Co-immunoprecipitation (ip) and fluorescent complementary approach validated the direct functional interaction of xtMc1r with xtMrap1 or xtMrap2 proteins on the plasma membrane. Pharmacological assay showed the improvement of the constitutive activity and alpha melanocyte-stimulating hormone (α-MSH) stimulated plateau without dramatic alteration of the cell surface translocation of xtMc1r in the presence of xtMrap proteins. Overall, the pharmacological modulation of xtMc1r by dual xtMrap2 proteins elucidated the potential role of this protein complex in the regulation of proper dermal function in amphibian species.
A Novel Inflammation and Insulin Resistance Related Indicator to Predict the Survival of Patients With Cancer
Authors: Ruan Guo-Tian , Xie Hai-Lun , Zhang He-Yang , Liu Chen-An , Ge Yi-Zhong , Zhang Qi , Wang Zi-Wen , Zhang Xi , Tang Meng , Song Meng-Meng , Zhang Xiao-Wei , Yang Ming , Chen Yong-Bing , Yu Kai-Ying , Deng Li , Gong Yi-Zhen , Hu Wen , Wang Kun-Hua , Cong Ming-Hua , Shi Han-Ping
Published: June 2022

Background

Systemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer.

Methods

The total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients’ inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer.

Results

The C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33–1.59; training cohort: HR = 1.36, 95% CI = 1.22–1.52; validation cohort: HR = 1.73, 95% CI = 1.47–2.04].

Conclusion

The CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.
Agroforestry in Shade Coffee Plantations as an Emission Reduction Strategy for Tropical Regions: Public Acceptance and the Role of Tree Banking
Authors: Nandakishor T. M. , Gopi Girigan , Champatan Vipin , Sukesh A. , Aravind P. V.
Published: June 2022

Support for the adoption of climate change mitigation measures in low-income regions depends on how such activities contribute to generating household income and gaining confidence from the local community. The planning of mitigation measures or pro-environmental activities need to consider the cost of deployment, customization of activities according to local conditions, and socio-cultural background and perceptions of people. This paper analyses the incentive induced “agroforestry” or “planting trees in farmland” as part of the Carbon Neutral Programme supported by the Government of Kerala in Meenangadi Grama Panchayath, Wayanad district. An increase in tree cover is proposed as a strategy for increasing carbon sequestration. Planting more trees in farmland (except grain cultivated areas) along with crops, according to farmers, may reduce crop yield and discourage farmers’ participation. The Government of Kerala put forward the concept of a tree banking/tree incentive program to attract farmers to expand tree cover. A survey was conducted among 100 individuals from the Meenangadi Grama Panchayath to assess the perceptions and concerns of farmers about the proposed “Agroforestry”/Tree Banking program. The sample size was chosen from the population assuming a 9.98% error tolerance. Tree Banking Programme designed to encourage farmers to plant trees has gained public interest, and the study also documented the factors influencing the willingness of farmers for planting trees. The study revealed that the majority of the individuals (93% of the survey participants) residing in the region are interested in supporting the activities for climate change mitigation. Financial incentives announced under tree banking generated interest among farmers. 89% of the survey participants consider the incentive scheme to be an attractive option, as it can compensate for the short-term loss in crop productivity. However, farmers were very selective in choosing the tree species to be planted on their farms. Incentivization helps to make sure that a large proportion of the planted saplings will grow into mature trees. Overall, it can be concluded that afforestation in the form of agroforestry could be potentially attractive to the farmers and contribute towards achieving carbon neutrality for tropical agricultural areas.
The Productivity Effects of Adopting Improved Organic Manure Practices in Nepal
Authors: Dhakal Chandra , Escalante Cesar L.
Published: June 2022

Owing to farmers’ issues on accessibility and affordability of chemical fertilizers in Nepal, organic manure has been advocated as a more environmentally sustainable fertilizer input alternative. Using household survey data from Nepal, we analyze the adoption and productivity effects of improved organic manure practices. Our empirical strategy utilizes a recently developed control function approach in the endogenous switching regression model that allows for substantial heterogeneities accounting for potential self-selection problem due to observables and unobservables. Findings reinforce the crucial role of social capital as farm households’ adoption decisions are significantly influenced by 1) having adopter neighbors or friends, 2) residing in proximity to the market, and 3) gaining easy access to agricultural extension services. Beyond environmental and social considerations, this study establishes economic motivations for the adoption decision. The results show that the adoption of improved organic manure practices increased crop yield by 17 percentage points. These practices did not only result in significantly higher yields among adopting farms, but counterfactual analyses indicate that non-adopting farms would have realized much better yield conditions had they implemented the technology. The study concludes with implications for policies and initiatives to expand the adoption and impacts of improved organic manure practices in Nepal.
Molecular Evidence of Chemical Disguise by the Socially Parasitic Spiny Ant Polyrhachis lamellidens (Hymenoptera: Formicidae) When Invading a Host Colony
Authors: Iwai Hironori , Mori Masaru , Tomita Masaru , Kono Nobuaki , Arakawa Kazuharu
Published: June 2022

While most ant species establish a colony independently, some socially parasitic ants build the foundation of their colony by invading other ant (host) colonies and utilizing their labor forces. Many socially parasitic ants disguise their cuticular hydrocarbon (CHC) profile, which is also known as signature mixture for nestmate discrimination, when invading the host colony. Since the strategy of chemical disguise is widespread in socially parasitic ants, elucidating the mechanism of chemical disguise will promote knowledge on the evolutionary history of social parasitism. However, detailed knowledge is still lacking, as the relevant information has only originated from circumstantial evidence, which was obtained from ecological observations. In this study, we investigated the mechanism of chemical disguise in a new queen of a temporary socially parasitic spiny ant (Polyrhachis lamellidens) by measuring its CHC profile, performing a tracing assay with labeled substances, and analyzing gene expression levels. First, after rubbing behavior was observed against the host workers, the CHC profile in P. lamellidens shifted to pronounced peaks that closely resembling that of the host workers. We also observed a reduction in aggressive behaviors by the host ant against P. lamellidens after rubbing behavior was performed. In addition, P. lamellidens acquired artificially-applied labeling substances from host workers through their rubbing behaviors, while gene expression profiling showed the expression of CHC synthesis-related genes did not change during this behavior. These results suggest that P. lamellidens directly obtains host CHCs through rubbing behavior, and these host CHCs enables P. lamellidens to remain disguised during colony invasion.
TextNetTopics: Text Classification Based Word Grouping as Topics and Topics’ Scoring
Authors: Yousef Malik , Voskergian Daniel
Published: June 2022

Medical document classification is one of the active research problems and the most challenging within the text classification domain. Medical datasets often contain massive feature sets where many features are considered irrelevant, redundant, and add noise, thus, reducing the classification performance. Therefore, to obtain a better accuracy of a classification model, it is crucial to choose a set of features (terms) that best discriminate between the classes of medical documents. This study proposes TextNetTopics, a novel approach that applies feature selection by considering Bag-of-topics (BOT) rather than the traditional approach, Bag-of-words (BOW). Thus our approach performs topic selections rather than words selection. TextNetTopics is based on the generic approach entitled G-S-M (Grouping, Scoring, and Modeling), developed by Yousef and his colleagues and used mainly in biological data. The proposed approach suggests scoring topics to select the top topics for training the classifier. This study applied TextNetTopics to textual data to respond to the CAMDA challenge. TextNetTopics outperforms various feature selection approaches while highly performing when applying the model to the validation data provided by the CAMDA. Additionally, we have applied our algorithm to different textual datasets.
MiR-142-5p/FAM134B Axis Manipulates ER-Phagy to Control PRRSV Replication
Authors: Guan Kaifeng , Su Qiuju , Kuang Kailin , Meng Xiangge , Zhou Xiang , Liu Bang
Published: June 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) can replicate its RNA genome in endoplasmic reticulum (ER) and utilize ER to facilitate its assembly and maturation. To maintain ER homeostasis, host cells initiate reticulophagy (known as ER-phagy) to effectively digest the stressed ER. In this study, we found that PRRSV infection subverted ER-phagy by downregulating ER-phagy receptor FAM134B. PRRSV-induced miR-142-5p directly targeted FAM134B and significantly promoted PRRSV replication. Meanwhile, siRNA-mediated depletion of FAM134B protein and overexpression of FAM134B mutant protein significantly disrupted ER-phagy and facilitated PRRSV replication. Furthermore, our results showed that FAM134B-mediated ER-phagy activated type I interferon signaling to inhibit PRRSV replication. Overall, this study reveals the important role of ER-phagy in PRRSV replication in a FAM134B-dependent manner. Our findings provide an insight into the pathogenesis of PRRSV and offer a theoretical basis for further development of antiviral therapeutic targets.
Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis
Authors: Li Xin-yu , Su Li-xin , Chen Wen-Xue , Liu Hui , Zhang Lu-yu , Shen Yu-Chen , You Jian-Xiong , Wang Jing-Bing , Zhang Liming , Wang Deming , Wen Ming-Zhe , Wang Zhenfeng , Shao Yu-hao , Chen De-Hu , Yang Xi-tao
Published: June 2022

Background

Necroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown.

Methods

The data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes.

Results

Necroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs.

Conclusion

Our study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.
Ferroptosis-Associated Molecular Features to Aid Patient Clinical Prognosis and Therapy Across Human Cancers
Authors: Cui Kaisa , Gong Liang , Wang Kang , Wang Yuanben , Huang Liuying , Liu Bingxin , Li Qilin , Zhang Qiang , Fei Bojian , Huang Zhaohui
Published: June 2022

Ferroptosis is a new non-apoptotic form that regulates cell death and is mainly dependent on iron-mediated oxidative damage and subsequent cell membrane damage. Ferroptosis may be a potential therapeutic strategy for immunotherapy, chemotherapy, and radiotherapy in human cancers. Numerous studies have analyzed ferroptosis-correlated signatures or genes, but a systematic landscape of associations among tumor ferroptosis, clinical outcomes, tumor microenvironment, and therapies in human cancers is lacking. Here, we developed a relative ferroptosis level (RFL) combined with drive/suppress regulators and validated it in the Gene Expression Omnibus datasets of ferroptotic drug treatment. Based on this effective evaluation method, we classified about 7,000 tumor samples into high and low RFL groups in each cancer type and observed that high RFL cases demonstrate favorable survival outcomes in nine cancer types from The Cancer Genome Atlas. Then, several RFL-correlated candidate genes that have not been reported to be ferroptosis-related were selected and experimentally validated in five cancer cell lines using Erastin treatment. We further showed that both immunostimulatory and immunosuppressive phenotypes were observed in high RFL tumors, suggesting that the consideration of ferroptosis could be a potential strategy in cancer immunotherapy. Moreover, we found that high RFL cases/cells showed responder or sensitivity to chemotherapy and radiotherapy. Our study provides a comprehensive molecular-level understanding of ferroptosis and may have practical implications for clinical cancer therapies, including immunotherapy, chemotherapy, and radiotherapy.
Gene Expression Signatures Reveal Common Virus Infection Pathways in Target Tissues of Type 1 Diabetes, Hashimoto’s Thyroiditis, and Celiac Disease
Authors: Yin Min , Zhang Yan , Liu Shanshan , Huang Juan , Li Xia
Published: June 2022

Type 1 diabetes (T1D) patients are at heightened risk for other autoimmune disorders, particularly Hashimoto’s thyroiditis (HT) and celiac disease (CD). Recent evidence suggests that target tissues of autoimmune diseases engage in a harmful dialogue with the immune system. However, it is unclear whether shared mechanisms drive similar molecular signatures at the target tissues among T1D, HT, and CD. In our current study, microarray datasets were obtained and mined to identify gene signatures from disease-specific targeted tissues including the pancreas, thyroid, and intestine from individuals with T1D, HT, and CD, as well as their matched controls. Further, the threshold-free algorithm rank-rank hypergeometric overlap analysis (RRHO) was used to compare the genomic signatures of the target tissues of the three autoimmune diseases. Next, promising drugs that could potentially reverse the observed signatures in patients with two or more autoimmune disorders were identified using the cloud-based CLUE software platform. Finally, microarray data of auto-antibody positive individuals but not diagnosed with T1D and single cell sequencing data of patients with T1D and HT were used to validate the shared transcriptomic fingerprint. Our findings revealed significant common gene expression changes in target tissues of the three autoimmune diseases studied, many of which are associated with virus infections, including influenza A, human T-lymphotropic virus type 1, and herpes simplex infection. These findings support the importance of common environmental factors in the pathogenesis of T1D, HT, and CD.
Human Platelet Lysate as Alternative of Fetal Bovine Serum for Enhanced Human In Vitro Bone Resorption and Remodeling
Authors: de Wildt Bregje W. M. , Ito Keita , Hofmann Sandra
Published: June 2022

Introduction

To study human physiological and pathological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3Rs), human in vitro bone remodeling models are being developed. Despite increasing safety-, scientific-, and ethical concerns, fetal bovine serum (FBS), a nutritional medium supplement, is still routinely used in these models. To comply with the 3Rs and to improve the reproducibility of such in vitro models, xenogeneic-free medium supplements should be investigated. Human platelet lysate (hPL) might be a good alternative as it has been shown to accelerate osteogenic differentiation of mesenchymal stromal cells (MSCs) and improve subsequent mineralization. However, for a human in vitro bone model, hPL should also be able to adequately support osteoclastic differentiation and subsequent bone resorption. In addition, optimizing co-culture medium conditions in mono-cultures might lead to unequal stimulation of co-cultured cells.

Methods

We compared supplementation with 10% FBS vs. 10%, 5%, and 2.5% hPL for osteoclast formation and resorption by human monocytes (MCs) in mono-culture and in co-culture with (osteogenically stimulated) human MSCs.

Results and Discussion

Supplementation of hPL can lead to a less donor-dependent and more homogeneous osteoclastic differentiation of MCs when compared to supplementation with 10% FBS. In co-cultures, osteoclastic differentiation and resorption in the 10% FBS group was almost completely inhibited by MSCs, while the supplementation with hPL still allowed for resorption, mostly at low concentrations. The addition of hPL to osteogenically stimulated MSC mono- and MC-MSC co-cultures resulted in osteogenic differentiation and bone-like matrix formation, mostly at high concentrations.

Conclusion

We conclude that hPL could support both osteoclastic differentiation of human MCs and osteogenic differentiation of human MSCs in mono- and in co-culture, and that this can be balanced by the hPL concentration. Thus, the use of hPL could limit the need for FBS, which is currently commonly accepted for in vitro bone remodeling models.
A Teleost CXCL10 Is Both an Immunoregulator and an Antimicrobial
Authors: Li Huili , Sun Yuanyuan , Sun Li
Published: June 2022

Chemokines are a group of cytokines that play important roles in cell migration, inflammation, and immune defense. In this study, we identified a CXC chemokine, CXCL10, from Japanese flounder Paralichthys olivaceus (named PoCXCL10) and investigated its immune function. Structurally, PoCXCL10 possesses an N-terminal coil, three β-strands, and a C-terminal α-helix with cationic and amphipathic properties. PoCXCL10 expression occurred in multiple tissues and was upregulated by bacterial pathogens. Recombinant PoCXCL10 (rPoCXCL10) promoted the migration, cytokine expression, and phagocytosis of flounder peripheral blood leukocytes (PBLs). rPoCXCL10 bound to and inhibited the growth of a variety of common Gram-negative and Gram-positive fish pathogens. rPoCXCL10 killed the pathogens by causing bacterial membrane permeabilization and structure destruction. When introduced in vivo, rPoCXCL10 significantly inhibited bacterial dissemination in fish tissues. A peptide derived from the C-terminal α-helix exhibited bactericidal activity and competed with rPoCXCL10 for bacterial binding. Deletion of the α-helix affected the in vitro bactericidal activity but not the chemotaxis or in vivo antimicrobial activity of PoCXCL10. Together, these results indicate that PoCXCL10 exerts the role of both an immunoregulator and a bactericide/bacteriostatic via different structural domains. These findings provide new insights into the immune function and working mechanism of fish CXC chemokines.
Comprehensive Pneumonitis Profile of Thoracic Radiotherapy Followed by Immune Checkpoint Inhibitor and Risk Factors for Radiation Recall Pneumonitis in Lung Cancer
Authors: Lu Xiaotong , Wang Jianyang , Zhang Tao , Zhou Zongmei , Deng Lei , Wang Xin , Wang Wenqing , Liu Wenyang , Tang Wei , Wang Zhijie , Wang Jie , Jiang Wei , Bi Nan , Wang Luhua
Published: June 2022

Purpose

Whilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer.

Methods and Materials

From January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables.

Results

With a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P=0.05), mean lung dose (MLD, P=0.038), percent volume of lung receiving ≥5 Gy (V5, P=0.012) and percent volume of lung receiving ≥20 Gy (V20, P=0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P=0.004).

Conclusions

Treatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice.
EZH2 Promotes T Follicular Helper Cell Differentiation Through Enhancing STAT3 Phosphorylation in Patients With Primary Sjögren’s Syndrome
Authors: He Chengmei , Yang Yanlei , Chen Zhilei , Liu Suying , Lyu Taibiao , Zeng Liuting , Wang Li , Li Yongzhe , Wang Mu , Chen Hua , Zhang Fengchun
Published: June 2022

Objectives

Enhancer of zeste homolog 2 (EZH2) is an epigenetic regulator that plays an essential role in immune system development and autoimmune diseases. This study aimed to characterize the role of EZH2 in the pathogenesis of primary Sjögren’s syndrome (pSS).

Methods

We analyzed EZH2 expression in two transcriptomic datasets of peripheral blood mononuclear cells (PBMCs) from pSS patients and healthy controls. We measured EZH2 expression in CD4+ T cells, CD8+ T cells, and CD19+ B cells from pSS patients and healthy controls and correlated EZH2 expression with clinical parameters. We also examined the activation, proliferation, and T-cell differentiation of CD4+ T cells using the EZH2 inhibitor GSK126, EZH2 siRNA, and EZH2-expressing vector. We further examined the STAT3 signaling pathway after EZH2 inhibition and detected Tfh differentiation in EZH2-overexpressed CD4+ T cells with STAT3 knocked down.

Results

EZH2 was upregulated in GSE164885 and GSE48378. EZH2 expression was higher in pSS CD4+ and CD8+ T cells, and EZH2 expression in circulating pSS CD4+ T cells was positively correlated with IgG, IgA, ESR, RF, and the circulating Tfh population. EZH2 inhibition and silencing EZH2 suppressed activation, proliferation, and Tfh differentiation. Furthermore, overexpressing EZH2 promoted activation, proliferation, and Tfh differentiation in CD4+ T cells. EZH2 inhibition attenuated STAT3 phosphorylation in CD4+ T cells. STAT3 knockdown abrogated EZH2-promoted Tfh differentiation.

Conclusions

EZH2 expression was abnormally elevated in pSS CD4+ T cells, which facilitated Tfh differentiation of CD4+ T cells by enhancing STAT3 phosphorylation. EZH2 promotes Tfh differentiation and might be implicated in pSS pathogenesis.
The Potential for Great Barrier Reef Regional Climate Regulation via Dimethylsulfide Atmospheric Oxidation Products
Authors: Swan Hilton B.
Published: June 2022

Research related to the potential for coral reef-derived dimethylsulfide (DMS) oxidation products to regulate the regional climate of the Great Barrier Reef (GBR) according to the CLAW hypothesis is summarized in this mini review. The GBR has been indicated as a region of high DMS production where atmospheric emissions may be increased when corals are subject to environmental stresses associated with low tide. During low wind speeds over aerially exposed coral reefs, plumes of atmospheric DMS and new sulfate-containing nano-particle production under photo-oxidative conditions have been detected on the GBR. Hygroscopic growth of these particles in combination with coagulation and condensation processes could potentially provide a coral-mediated mechanism of new aerosol for seeding low-level stratocumulus clouds. Fine mode aerosol optical depth over GBR coral reefs has been correlated with low wind speeds and a coral stress metric formulated as a function of irradiance, water clarity, and tide height. This correlation has been proposed as a possible mechanism by which the GBR might alter the optical properties of the overlying atmosphere to attenuate local insolation leading to regional climate regulation. However, recent regional-scale aerosol-climate modeling indicates that the potential for GBR regional climate regulationviaDMS atmospheric oxidation products is weak under current anthropogenic conditions which have instigated mass coral bleaching events along the entire length of the GBR between 1998 and 2022. This increased bleaching indicates that DMS oxidation products are insufficient to regulate the regional climate of the GBR according to the CLAW hypothesis under current global warming conditions.
Consequences of Atlantification on a Zooplanktivorous Arctic Seabird
Authors: Descamps Sébastien , Wojczulanis-Jakubas Katarzyna , Jakubas Dariusz , Vihtakari Mikko , Steen Harald , Karnovsky Nina J. , Welcker Jorg , Hovinen Johanna , Bertrand Philip , Strzelewicz Agnieszka , Skogseth Ragnheid , Kidawa Dorota , Boehnke Rafał , Błachowiak-Samołyk Katarzyna
Published: June 2022

Global warming, combined with an increasing influence of Atlantic Waters in the European Arctic, are causing a so-called Atlantification of the Arctic. This phenomenon is affecting the plankton biomass and communities with potential consequences for the upper trophic levels. Using long-term data (2005-2020) from a high Arctic zooplanktivorous seabird, the little auk (Alle alle), we tested the hypothesis that the Atlantification affects its diet, body condition and demography. We based our study on data collected in three fjords in West Spitsbergen, Svalbard, characterized by distinct oceanographic conditions. In all three fjords, we found a positive relationship between the inflow of Atlantic Waters and the proportion of Atlantic prey, notably of the copepod Calanus finmarchicus, in the little auk chick diet. A high proportion of Atlantic prey was negatively associated with adult body mass (though the effect size was small) and with chick survival (only in one fjord where chick survival until 21 days was available). We also found a negative and marginally significant effect of the average proportion of Atlantic prey in the chick diet on chick growth rate (data were available for one fjord only). Our results suggest that there are fitness costs for the little auk associated with the Atlantification of West Spitsbergen fjords. These costs seem especially pronounced during the late phase of the chick rearing period, when the energetic needs of the chicks are the highest. Consequently, even if little auks can partly adapt their foraging behaviour to changing environmental conditions, they are negatively affected by the ongoing changes in the Arctic marine ecosystems. These results stress the importance of long-term monitoring data in the Arctic to improve our understanding of the ongoing Atlantification and highlight the relevance of using seabirds as indicators of environmental change.
Oligotrophic Phytoplankton Community Effectively Adjusts to Artificial Upwelling Regardless of Intensity, but Differently Among Upwelling Modes
Authors: Ortiz Joaquin , Arístegui Javier , Hernández-Hernández Nauzet , Fernández-Méndez Mar , Riebesell Ulf
Published: June 2022

Artificial upwelling has been proposed as a means of enhancing oceanic CO2 sequestration and/or raising fishery yields through an increase in primary production in unproductive parts of the ocean. However, evidence of its efficacy, applicability and side effects is scarce. Here we present part of the results of a 37-day mesocosm study conducted in oligotrophic waters off the coast of Gran Canaria. The goal was to assess in situ the effects of artificial upwelling on the pelagic community. Upwelling was simulated via two modes: i) a singular deep-water pulse and ii) a recurring supply every 4 days; each mode at four different intensities defined by the total amount of nitrate added: approx. 1.5, 3, 5.7, and 11 µmol L-1. In this study we focus on the phytoplankton response through size-fractionated 14C primary production rates (PP), Chlorophyll a and biomass. We observed increases in PP, accumulated PP, Chlorophyll a and biomass that scaled linearly with upwelling intensity. Upwelling primarily benefitted larger phytoplankton size fractions, causing a shift from pico- and nano- to nano- and microphytoplankton. Recurring deep-water addition produced more biomass under higher upwelling intensities than a single pulse addition. It also reached significantly higher accumulated PP per unit of added nutrients and showed a stronger reduction in percentage extracellular release with increasing upwelling intensity. These results demonstrate that oligotrophic phytoplankton communities can effectively adjust to artificial upwelling regardless of upwelling intensity, but differently depending on the upwelling mode. Recurring supply of upwelled waters generated higher efficiencies in primary production and biomass build-up than a single pulse of the same volume and nutrient load.
A Dual-Polarized Frequency-Selective Rasorber With a Switchable Wide Passband Based on Characteristic Mode Analysis
Authors: Wang He , Kong Xiangkun , Zhang Xinyu
Published: June 2022

This study proposes a dual-polarized frequency-selective rasorber (FSR) with a switchable wide passband. The FSR is made up of two layers: the first is a lossy frequency-selective surface (FSS), which is made up of meander lines and lumped resistors that absorb energy. The position of the lumped resistors can be determined via characteristic mode analysis. Another layer is a lossless FSS with PIN diodes for the reconfigurable function. The lossless FSS is made up of three layers for a wide passband. When PIN diodes are turned off, the absorption bands in the lower band vary from 2.73 to 3.76GHz, while the upper band ranges from 6.07 to 7.94 GHz. Meanwhile, the reflect band with a value greater than −3 dB spans the frequency range from 4.21 to 5.88 GHz. When the PIN diodes are turned on, the passband with insertion loss less than −1 dB extends from 3.82 to 5.3 GHz. At the same time, the absorption band ranges from 5.9 to 7 GHz. Due to the nonlinearity of PIN diodes, there is a certain difference between the simulated and the measured results. Also, we analyzed the influence of the inductance value of PIN diodes on the whole structure.