bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Volcanic Activity on Hydrocarbon-Forming Organisms in Organic-Rich Shale: A Case Study of Dalong Formation in Northwestern Sichuan Basin, China
Authors: Zhang Chuanwen , Meng Qingqiang , Tang Xuan , Sun Zuoyu , Pang Qian , Lyu Dawei , Zhu Dongya , Liu Jiayi , Li Jiachun , Jiang Bin
Published: August 2022

Hydrocarbon-generating material determines the elemental composition and hydrocarbon-generating potential of kerogens in a source rock, and it is the key material basis to control the hydrocarbon-generating capacity of the source rock. Previous studies have shown that many intervals of high-quality source rocks generally contain a varying number of volcanic ash layers. The impact of these volcanic ash layers on the development of high-quality source rocks has attracted extensive attention. However, these studies mainly focused on the development of hydrocarbon-forming organisms and the preservation of organic matters but rarely dealt with the differential development of hydrocarbon-forming organisms between multiple volcanic ash layers. The Permian Dalong Formation in the northwestern Sichuan Basin, China, is a set of high-quality source rocks with multiple volcanic sedimentary layers. To understand the differential development of hydrocarbon-forming organisms between volcanic ash layers, with the Dalong Formation in the Longfeng quarry section, Guangyuan, the Sichuan Basin as an example, this study analyzes the types of hydrocarbon-generating materials of high-quality source rocks of the Dalong Formation and the reasons why volcanic activities affected the growth of hydrocarbon-forming organisms and explores the impact of volcanic activities on the development of different types of hydrocarbon-forming organisms. The results show that the TOC of the Longfeng quarry section is 0.05%–15.46%, with an average of 4.76%, and the average TOC of the Dalong Formation is as high as 5.16%, which belongs to high-quality source rocks. The hydrocarbon-forming organism association in the Dalong Formation source rocks is mainly composed of floating algae and benthic algae and vertically divided into three parts: a few radiolarians and trace fossils occasionally in the lower part; a large number of radiolarians, calcium spheres, and algal debris in the middle part; and mainly foraminifera and gastropods in the upper part. There are 36 volcanic ash layers in the Dalong Formation of the study area. In the process of volcanic activity, the “fertilization” effect of volcanic ash made the nutrient elements in the volcanic ash enter water, increasing the number of hydrocarbon-forming organisms, causing the differential development of various hydrocarbon-forming organisms, and promoting the formation of reducing water to support the preservation of organic matters. The development of hydrocarbon-forming organisms is controlled by the changes of element types and abundances caused by magmatic properties. The time interval of volcanic activities also has an important impact on the development of hydrocarbon-forming organisms.
Modeling of soil–rock mixture landslides with the generalized interpolation material point method
Authors: Li Xia , Xie Peng-Fei , Zheng Yong , Liu Jie , Wang Lie-Jian , He Kai-Yuan , Jiang Tao
Published: August 2022

The new numerical model for studying the dynamic evolution of soil–rock mixture landslides is presented in this article. The numerical model based on the generalized interpolation material point method analyzes a simplified slope. The gravity is linearly loaded, and the linear elastic model is used to update the stress to obtain the initial state of the slope. A small soil cohesion is set to trigger the slope sliding until the equilibrium state is reached again. During this period, the elastic–plastic material model based on the Drucker–Prager criterion is adopted for soil and stones. The differences in dynamic evolution between the homogeneous soil slope and soil–rock mixture slope are studied. Under the same stone content, the influence of the size and shape of stone on the dynamic evolution of slope is studied.
The use of virtual and augmented reality in science and math education in Arab countries: A survey of previous research studies
Authors: Abutayeh Khaled A. , Kraishan Osamah M. , Kraishan Eman Q.
Published: August 2022

The aim of this study was to present a survey of research relating to the use of virtual and augmented reality in science and math education in Arab countries after 2012. The research studies were collected from several sources that include a set of common Arabic research database, a set of English research database, and popular search engines. Thirty three research studies were found related to the use of virtual and augmented reality in science and math education in Arab countries. These studies were examined based on four variables: focus, research method, data collection tools, and geographical distribution. The results showed that most of the research related to uses of virtual and augmented reality in science and math education in Arab countries focused on students and their teachers and most of the researches followed the two-group experimental design, and the quantitative descriptive research. Regarding the methods of data collection most of the studies used test and questionnaires. In addition, most of the research studies were conducted in Saudi Arabia and Egypt. Based on the findings, a set of recommendations were presented.
Exploring the concept of pedagogical resilience during the COVID-19 pandemic: Teachers’ perspectives from Thailand and the Philippines
Authors: Zara Celso G. , Balazon Francis , Wangdi Thinley , Perales William Franco , Praditson Pavirasa , Ulla Mark Bedoya
Published: August 2022

This brief research report aimed to explore the concept of pedagogical resilience and how teachers in Thailand and the Philippines build resilience in pedagogy during the COVID-19 pandemic. Employing the qualitative research design, the data were obtained from the focus group discussion (FGD) and semi-structured interviews with 12 teachers, 8 of whom were from 1 of the universities in the Philippines and another four teachers from a university in Thailand. The thematic analysis revealed that pedagogical resilience is influenced by teachers’ personal, professional, and social attitudes toward teaching and learning during the COVID-19 pandemic. Although teachers acknowledged that they had no experience in remote and online teaching, they demonstrated resiliency by being flexible and adaptive to the situation. Such an attitude allowed them to build a relationship with their colleagues and design teaching and learning pedagogy that addresses the issues in their online and remote teaching. The findings provide a clear understanding of the conceptualization of pedagogical resilience from the perspectives of teachers in the Philippines and Thailand.
A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model
Authors: Lu I-Cheng , Tan Hao , Wu Sheng-Hua , Huang Tzu-Yen , Tseng Hsin-Yi , Wang Jia-Joanna , Dionigi Gianlorenzo , Chai Young Jun , Chiang Feng-Yu , Chang Pi-Ying , Wu Che-Wei
Published: August 2022

Background

Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium.

Methods

Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value.

Results

Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium.

Conclusions

This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.
Gender differences in pancreatic neuroendocrine neoplasms: A retrospective study based on the population of Hubei Province, China
Authors: Fu Mengfei , Yu Li , Yang Liu , Chen Yang , Chen Xiao , Hu Qinyu , Sun Hui
Published: August 2022

Objective

The aims of the present study were to investigate gender differences in the clinicopathological features, distant metastasis and prognosis of pancreatic neuroendocrine neoplasms (pNENs) in a Chinese population, and to identify any important gaps in the classification and management of pNENs relative to gender.

Methods

Retrospective collection of the clinicopathological data of 193 patients with pathologically confirmed pNENs were analyzed and follow up was extended to observe the prognosis of the disease. Differences between genders in basic characteristics, clinical symptoms, comorbidities, and tumor parameters were analyzed.

Results

There was no significant difference in females and males, however, moderately higher for females (52.8% vs. 47.2%), with the largest subgroup being 40~60 years of age (54.9%). Age at onset (P=0.002) and age at diagnosis (P=0.005) were both younger in females compared to males. Males lived more in urban areas and females lived more in rural areas (P=0.047). The proportion of smokers and alcohol drinkers was significantly higher in males than in females (P < 0.001). Non-functional pNENs were more frequent in males and functional pNENs in females (P=0.032). In women, functional status of the tumor was significantly associated with metastatic outcome (P=0.007) and functional tumors proved to be a protective factor compared to non-functional tumors (OR=0.090,95% CI: 0.011~ 0.752). There were no gender differences in tumor size, location, grade, stage or prognosis.

Conclusions

Gender differences in some clinicopathological features, and distant metastasis in patients with pNENs were identified, which suggested certain management details that justified emphasis based on gender.
Primary aldosteronism: Pathophysiological mechanisms of cell death and proliferation
Authors: Tetti Martina , Gong Siyuan , Veglio Franco , Reincke Martin , Williams Tracy Ann
Published: August 2022

Primary aldosteronism is the most common surgically curable form of hypertension. The sporadic forms of the disorder are usually caused by aldosterone overproduction from a unilateral adrenocortical aldosterone-producing adenoma or from bilateral adrenocortical hyperplasia. The main knowledge-advances in disease pathophysiology focus on pathogenic germline and somatic variants that drive the excess aldosterone production. Less clear are the molecular and cellular mechanisms that lead to an increased mass of the adrenal cortex. However, the combined application of transcriptomics, metabolomics, and epigenetics has achieved substantial insight into these processes and uncovered the evolving complexity of disrupted cell growth mechanisms in primary aldosteronism. In this review, we summarize and discuss recent progress in our understanding of mechanisms of cell death, and proliferation in the pathophysiology of primary aldosteronism.
Associations between rs3480 and rs16835198 gene polymorphisms of FNDC5 with type 2 diabetes mellitus susceptibility: a meta-analysis
Authors: Yang Xianqin , Ni Li , Sun Junyu , Yuan Xiaolu , Li Dezhong
Published: August 2022

Background

FNDC5 is a novel and important player in energy regulation related to glucose metabolism and insulin levels. Thus, it may affect the incidence of type 2 diabetes mellitus (T2DM). Nevertheless, the association between FNDC5 single nucleotide polymorphisms (SNPs) and susceptibility to T2DM remains unclear. The aim of this meta-analysis was to explore whether the SNPs, rs3480 and rs16835198, are associated with the risk of T2DM.

Methods

Studies published before February 1st, 2022 were screened to identify the included studies. R software was also applied for calculation of odds ratio (OR), 95% confidence interval (95% CI), heterogeneity, and sensitivity analysis.

Results

Seven studies for rs3480 (involving 5475 patients with T2DM and 4855 healthy controls) and five studies for rs16835198 (involving 4217 patients with T2DM and 4019 healthy controls) were included in this meta-analysis. The results revealed a statistically significant association of rs3480 with T2DM under homozygote (GG vs AA: OR = 1.76, 95% CI = 1.31–2.37, P = 0.0002, I2 = 59%) genetic model. However, there was no statistically significant correlation between rs16835198 and susceptibility to T2DM under allelic (G vs T: OR = 1.33, 95% CI = 0.94–1.89, P = 0.11, I2 = 84%), heterozygote (GT vs TT: OR = 1.17, 95% CI = 0.80–1.69, P = 0.42, I2 = 71%), homozygote (GG vs TT: OR = 1.35, 95% CI = 0.95–1.94, P = 0.10, I2 = 62%), recessive (GG+GT vs TT: OR = 1.25, 95% CI = 0.88–1.79, P = 0.22, I2 = 72%), and dominant (GG vs GT+GG: OR = 1.20, 95% CI = 0.96–1.50, P = 0.11, I2 = 46%) genetic models.

Conclusions

The present meta-analysis revealed that rs3480 in FNDC5 is significantly associated with susceptibility to T2DM, while rs16835198 does not show such an association.
A novel extraction method enhanced the osteogenic and anti-osteoporosis effect of tea extract without any hepatotoxicity in ovariectomized rats
Authors: Kulkarni Chirag , Sharma Shivani , Bora Prateek Singh , Verma Saurabh , Rajput Swati , Porwal Konica , Rath Srikanta Kumar , Gayen Jiaur Rahaman , Sharma Upendra , Chattopadhyay Naibedya
Published: August 2022

Tea (Camellia sinensis) has several reported health benefits, including that on bone health attributed to catechins of which the most abundant is epigallocatechin-3-gallate (EGCG). However, several preclinical and clinical studies raise safety concerns about EGCG in tea extract causing acute liver failure. Tea also contains kaempferol, albeit scanty, and it has hepatoprotective and osteogenic effects. Here, we utilized a novel extraction procedure of acid hydrolysis to enhance the osteogenic effect of tea extract while reducing its hepatotoxicity. The resultant extract (USKECSE) has a ~40-fold increase in kaempferol and a 2.5-fold reduction in EGCG content compared with the hydroethanolic extract (USCSE). In a female Sprague Dawley (SD) rat femur osteotomy model, USKECSE (100 mg/kg) but not USCSE promoted bone regeneration. In a rat postmenopausal osteoporosis model induced by bilateral ovariectomy (OVX), USKECSE through an osteogenic mechanism maintained bone mass, strength, and microarchitecture to the levels of ovary-intact rats with no hepatotoxic effect. After a single oral dose (100 mg/kg) of USKECSE to adult rats, kaempferol was detectable for 48 hours, suggesting its significant absorption and distribution in plasma. Peak kaempferol concentration in plasma (Cmax) was 483 ng/ml (2 μM), and at this concentration, kaempferol induces osteoblast differentiation. USKECSE had no genotoxicity, and its safety index assessed by preclinical toxicity studies, including safety pharmacology, was >20-fold. Taken together, we report a novel extraction process that enhanced the osteogenicity and concomitantly reduced hepatotoxicity of tea extract with significant kaempferol bioavailability and a favorable systemic safety profile. Based on these data, we propose assessing the USKECSE effect for postmenopausal osteoporosis treatment.
A patient with an ectopic sphenoid bone TSH secretory adenoma: Case report and review of the literature
Authors: Kumar Shejil , Phang Cun An , Ni Huajing , Diamond Terrence
Published: August 2022

Ectopic thyroid-stimulating hormone (TSH)oma located outside the sella turcica is exceedingly rare and can be associated with significant diagnostic delay. The clinical presentation depends on the anatomical location and size of the ectopic tumor and the degree of thyrotoxicosis. A 71-year-old woman presented with goiter and thyrotoxicosis. Initial investigations revealed elevated free thyroxine (fT4) and tri-iodothyronine (fT3) with inappropriately high-normal TSH. Assay interference was unlikely, pituitary magnetic resonance imaging (MRI) scan was reported as “normal,” and germline sequencing was negative for thyroid hormone receptor ß pathogenic variants. One year later, total thyroidectomy for enlarging symptomatic goiter and suspicious nodule revealed multifocal microscopic papillary thyroid carcinoma. Six years later, she presented to an ear, nose, and throat surgeon with nasal congestion, and a sphenoid bone mass was discovered on nasoendoscopy and imaging. Ectopic TSHoma was confirmed on surgical resection, and a review of the initial pituitary MRI scan revealed the mass which had initially been missed. This is the first reported case of an ectopic TSHoma located in the sphenoid bone. Ectopic TSHoma should be considered in patients with inappropriate TSH secretion when more common differentials are excluded including thyroid hormone resistance or pituitary TSHoma.
Total tumor diameter is a better indicator of multifocal papillary thyroid microcarcinoma: A propensity score matching analysis
Authors: Jiang Ke-cheng , Lin Bei , Zhang Yu , Zhao Ling-qian , Luo Ding-cun
Published: August 2022

Background

Accurate evaluation of the risk of papillary thyroid microcarcinoma (PTMC) is the key to treatment. However, the maximum diameter (MD), which is currently used in various staging systems, may not truly reflect the aggressiveness of multifocal tumors.

Methods

Clinical and pathological data for 1001 patients with papillary thyroid carcinoma who underwent surgery at the Hangzhou First People’s Hospital were retrospectively analyzed. First, the relationship between total tumor diameter (TTD) and clinicopathological features in multifocal PTMC was explored. Then, patients were divided into subgroups according to the TTD. The baseline was consistent after using the propensity score matching method, and the differences between groups were compared. In addition, the effectiveness of TTD and MD in evaluating central lymph node metastasis (CLNM) was analyzed and compared.

Results

TTD is associated with a range of clinicopathological features, including lymph node metastasis, extrathyroidal extension, and risk stratification. Assuming the same MD and number of foci, the invasiveness of multifocal PTMC with TTD >1 cm was significantly higher than that with TTD <1 cm, and even higher than unifocal non-PTMC. Moreover, the efficiency of TTD in predicting CLNM was also significantly higher than that of MD.

Conclusion

For multifocal PTMC, TTD is a more realistic indicator of tumor biological characteristics than MD. The aggressiveness of PTMC with TTD >1 cm was significantly enhanced, and surgical treatment should be actively sought in such cases.
Numerical study on the release and migration behavior of fission gas in a molten LBE pool
Authors: Mai Zijun , Zhao Zichen , Cheng Hui , Cheng Songbai , Zhao Jiyun
Published: August 2022

The lead-cooled fast reactor (LFR) is one of the most promising fast neutron reactors using molten lead or the lead–bismuth eutectic (LBE) alloy as a coolant. Under postulated severe accidents, the fuel rod of LFR may be damaged, which would cause the release of fission gas, and the migration of fission gas bubbles in the reactor molten pool will affect the release and absorption of radioactive substances in the reactor. In this paper, a three-dimensional numerical study on the release and migration behavior of fission gas in the molten LBE pool of LFR is carried out based on the volume of fluid method. The bubbles are continuously released by gas injection, and the research mainly focuses on the detachment time, the rising velocity, and the size of the bubble when it detaches at the orifice. The coalescence of bubbles is observed, and the acceleration effect of the bubble wake is confirmed. The distribution of the bubble terminal rising velocity with diameter has no simple or linear relationship. The effects of the gas injection velocity, the release depth, and the gas injection angle are studied. A lower gas injection velocity will delay the detachment and reduce the size of the bubble. The increase of release depth tends to release smaller bubbles. The bubbles released from a vertical surface will attach to the wall. The simulations and theoretical analysis are comparable and have similar tendencies. The distribution of the bubble terminal rising velocity with equivalent diameter may predict the migration behavior of bubbles in molten LBE.
Research on situation assessment of active distribution networks considering cyberattacks
Authors: Li Jun’e , Liang Jiaqi , Liu Quanying , Qi Donglian , Zhang Jianliang , Chen Yangrong
Published: August 2022

With the rapid development of integrated energy system, the large-scale and high-permeability access of distributed generations (DGs) is making the distribution networks develop into active distribution networks (ADNs). The increased complexity of ADNs also increases the vulnerabilities for cyberattacks. It is a new challenge how to evaluate the situation of an ADN so as to support the decision-making of grid control policies in the condition of cyberattacks probably occur. Hence, in this paper, we proposed a method of situation assessment for ADNs considering cyberattacks. This method is aggregated by two parts. 1) An index system is presented, which includes the indexes of DGs stability, the indexes of security risk considering cyberattacks along with the traditional safety indexes. 2) The entropy weight method is used to assign weights to each index, and taking the normal operation status of ADNs as the reference scenario, an operating situation assessment method for ADNs is proposed based on grey correlation analysis method. Finally, in order to verify the effectiveness of the proposed index system and assessment method, 12 attack scenarios are established from three categories: attacks on DGs, attacks on controllable loads and attacks on both of them, and the situation of the ADN, a case based on IEEE 33-node standard distribution system, is evaluated under each scenario.
Research on the spatiotemporal distribution and evolution of remote sensing: A data-driven analysis
Authors: Liu Yu , Kuai Xi , Su Fei , Wang Shaochen , Wang Kaifeng , Xing Lijun
Published: August 2022

The development of remote sensing technology largely reflects the scientific research level of a country or region. Given that the quantity and quality of research works are important indicators for scientific prowess evaluation, exploratory spatial data analysis and scientometric analysis of remote sensing work published from 2012 to 2021 were performed in this study, utilizing the Web of Sciences database. This study probed the spatial distribution and spatiotemporal evolution at the country/regional level to reveal the spatiotemporal characteristics of knowledge spillover in remote sensing. According to the results, the global spatial distribution of research output in remote sensing presented a significant dispersion; the United States and China were the most active countries. During the study period, Transferring Deep Convolutional Neural Networks for the Scene Classification of High-Resolution Remote Sensing Imagery was one of the most influential studies, both in the field of remote sensing and in the whole scientific community. With respect to the spatial evolution of research output in remote sensing, the gap between continents and the regional imbalance showed a downward trend, while Asia ranked first in the intracontinental disparity and Europe ranked last. For relevant countries/regions and institutions trying to optimize the spatial allocation of scientific and technological resources to narrow regional disparities, this study provides fundamental data and decision-making references.
Development of a polyphagous leaf beetle on different host plant species and its detoxification of glucosinolates
Authors: Friedrichs Jeanne , Schweiger Rabea , Geisler Svenja , Neumann Judith M. , Sadzik Sullivan J. M. , Niehaus Karsten , Müller Caroline
Published: August 2022

Herbivores face a broad range of defences when feeding on plants. By mixing diets, polyphagous herbivores are assumed to benefit during their development by gaining a better nutritional balance and reducing the intake of toxic compounds from individual plant species. Nevertheless, they also show strategies to metabolically cope with plant defences. In this study, we investigated the development of the polyphagous tansy leaf beetle, Galeruca tanaceti (Coleoptera: Chrysomelidae), on mono diets consisting of one plant species [cabbage (Brassica rapa), Brassicaceae; lettuce (Lactuca sativa), or tansy (Tanacetum vulgare), Asteraceae] vs. two mixed diets, both containing tansy. Leaves of the three species were analysed for contents of water, carbon and nitrogen, the specific leaf area (SLA) and trichome density. Furthermore, we studied the insect metabolism of two glucosinolates, characteristic defences of Brassicaceae. Individuals reared on cabbage mono diet developed fastest and showed the highest survival, while the development was slowest for individuals kept on tansy mono diet. Lettuce had the highest water content and SLA but the lowest C/N ratio and no trichomes. In contrast, tansy had the lowest water content and SLA but the highest C/N ratio and trichome density. Cabbage was intermediate in these traits. Analysis of insect samples with UHPLC-DAD-QTOF-MS/MS revealed that benzyl glucosinolate was metabolised to N-benzoylglycine, N-benzoylalanine and N-benzoylserine. MALDI-Orbitrap-MS imaging revealed the localisation of these metabolites in the larval hindgut region. 4-Hydroxybenzyl glucosinolate was metabolised to N-(4-hydroxybenzoyl)glycine. Our results highlight that G. tanaceti deals with toxic hydrolysis products of glucosinolates by conjugation with different amino acids, which may enable this species to develop well on cabbage. The high trichome density and/or specific plant chemistry may lower the accessibility and/or digestibility of tansy leaves, leading to a poorer beetle development on pure tansy diet or diet mixes containing tansy. Thus, diet mixing is not necessarily beneficial, if one of the plant species is strongly defended.
Association of cardiovascular risk factors and lifestyle behaviors with aortic aneurysm: A Mendelian randomization study
Authors: Zhou Jiawei , Lin Jianfeng , Zheng Yuehong
Published: August 2022

Objective: To examine the causality between hypertension, diabetes, other cardiovascular risk factors, lifestyle behaviors, and the aortic aneurysm among patients of European ancestry.

Methods: We performed two-sample Mendelian randomization (MR) analysis to investigate the causality of 12 modifiable risk factors with aortic aneurysm, including hypertension, body mass index (BMI), waist–hip ratio (WHR), diabetes, tobacco smoking, alcohol and coffee consumption, physical activity, and sleep duration. Genome-wide significant genetic instruments (p < 5 × 10–8) for risk factors were extracted from European-descent genome-wide association studies, whereas aortic aneurysm genetic instruments were selected from the UK Biobank and FinnGen cohort. The inverse-variance weighted MR was used as the main analysis, and MR-Egger (MRE), weighted median MR, MR pleiotropy residual sum and outlier, and Phenoscanner searching were performed as sensitivity analyses. Furthermore, we calculated MRE intercept to detect pleiotropy and Cochran’s Q statistics to assess heterogeneity and conducted bidirectional MR and MR Steiger tests to exclude the possibility of reverse causality.

Results: We observed significantly higher risks for the aortic aneurysm in hypertension [pooled OR: 4.30 (95% CI 2.84–6.52)], BMI [OR: 1.58 (95% CI 1.37–1.81)], WHR [OR: 1.51 (95% CI 1.21–1.88)], WHR adjusted for BMI (WHRadjBMI) [OR: 1.35 (95% CI 1.12–1.63)], age of smoking initiation [OR: 1.63 (95% CI 1.18–2.26)], and tobacco use (initiation, cessation, and heaviness) [OR: 2.88 (95% CI 1.85–2.26)]. In sensitivity analysis, the causal effects of hypertension, BMI, WHRadjBMI, and tobacco use (initiation, cessation, and heaviness) remained robust.

Conclusion: There was a positive causal relationship between hypertension, BMI, WHR, and WHRadjBMI and aortic aneurysm.
A systematic pan-cancer analysis of the gasdermin (GSDM) family of genes and their correlation with prognosis, the tumor microenvironment, and drug sensitivity
Authors: Zheng Yufu , Yuan Didi , Zhang Fei , Tang Renkuan
Published: August 2022

Background: Pyroptosis is a programmed cell death process mediated by the gasdermin (GSDM) protein. However, limited research has been conducted to comprehensively analyze the contribution of the GSDM family in a pan-cancer setting.

Methods: We systematically evaluated the gene expression, genetic variations, and prognostic values of the GSDM family members. Furthermore, we investigated the association between the expression of GSDM genes and immune subtypes, the tumor microenvironment (TME), the stemness index, and cancer drug sensitivities by means of a pan-cancer analysis.

Results: GSDM genes were highly upregulated in most of the tested cancers. Low-level mutation frequencies within GSDM genes were common across the examined types of cancer, and their expression levels were associated with prognosis, clinical characteristics, TME features, and stemness scores in several cancer types, particularly those of the urinary system. Importantly, we found that the expressions of GSDMB, GSDMC, and GSDMD were higher in kidney carcinomas, and specifically kidney renal clear cell carcinoma (KIRC); which adversely impacted the patient outcome. We showed that GSDMD was potentially the most useful biomarker for KIRC. The drug sensitivity analysis demonstrated that the expressions of GSDM genes were correlated with the sensitivity of tumor cells to treatment with chemotherapy drugs nelarabine, fluphenazine, dexrazoxane, bortezomib, midostaurin, and vincristine.

Conclusion: GSDM genes were associated with tumor behaviors and may participate in carcinogenesis. The results of this study may therefore provide new directions for further investigating the role of GSDM genes as therapeutic targets in a pan-cancer setting.
The regulatory effect and molecular mechanism of lncRNA Gm10451 on islet cell dysfunction in children with diabetes
Authors: Wang Jiao , Zhang Li-hai , Kang Yu-ming , Wang Xian-he , Jiang Chun-yu
Published: August 2022

The dysfunction of islet β-cells is one of the causes of diabetes, and lncRNA Gm10451 is also a participant in the occurrence and the development of various diseases. This study was carried out to reveal the correlation within β-cells and Gm10451. Our study was started with the cellular cultivation of MIN6 cells in vitro, where this islet β-cell line was randomly divided into the groups of control, hyperglycemia, Gm10451 siRNA tansfection, and Gm10451 tansfection. Of all these treatments, cells in the groups of Gm10451 siRNA tansfection and Gm10451 tansfection were given with lentiviral transfection under hyperglycemia condition. Further explorations were established using PCR assay and MTT method to evaluate Gm10451 expression and estimate cellular proliferation. It ended up with the enzyme-linked immunosorbent assay (ELISA) to assess Caspase 3 activity, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) content and the secretion of IL-10 and IL-1. It was found that Gm10451 expression in MIN6 cells under hyperglycemia cultivation was notably higher than the control group; likewise, a transfection with the lentivirus of Gm10451 also resulted in the upregulation of Gm10451 expression, succeeded with inhibiting cellular proliferation, enhancing Caspase 3 activity, and decreasing SOD activity. In the lentivirus transfection groups, transfection of Gm10451 elevated the ROS content and promoted IL-1 expression, and it also decreased both IL-10 expression and insulin secretion, leading to a consequence of statistically significant difference in contrast to the high-glucose group; on the contrary, transfection of Gm10451 siRNA in a high-glucose environment downregulated the expression of Gm10451 and inversed those change before, whose results were statistically significant when compared with the high-glucose group. Hyperglycemia promotes the expression of Gm10451. Targeting inhibition toward Gm10451 alleviates cellular apoptosis and the oxidative stress of islet cells, promoting proliferation and insulin secretion of islet cells.
Identification of the first congenital ichthyosis case caused by a homozygous deletion in the ALOX12B gene due to chromosome 17 mixed uniparental disomy
Authors: Zhang Lei , Hu Yanqiu , Lu Jingjing , Zhao Peiwei , Zhang Xiankai , Tan Li , Li Jun , Xiao Cuiping , Zeng Linkong , He Xuelian
Published: August 2022

Uniparental disomy (UPD) is a rare genetic event caused by errors during gametogenesis and fertilization leading to two copies of a chromosome or chromosomal region inherited from one parent. MixUPD is one type of UPD that contains isodisomic and heterodisomic parts because of meiotic recombination. Using whole-exome sequencing (WES), we identified the first case of ichthyosis due to a maternal mixUPD on chromosome 17, which results in a homozygous deletion of partial intron 8 to exon 10 in ALOX12B, being predicted to lead to an internal protein deletion of 97 amino acids. We also performed a retrospective analysis of 198 patients with ALOX12B mutations. The results suggested that the exon 9 and 10 are located in the mutational hotspots of ALOX12B. In addition, our patient has microtia and congenital stenosis of the external auditory canals, which is very rare in patients with ALOX12B mutations. Our study reports the first case of autosomal recessive congenital ichthyosis (ARCI) due to a mixUPD of chromosome 17 and expands the spectrum of clinical manifestations of ARCI caused by mutations in the ALOX12B gene.
A novel pyroptosis-related prognostic lncRNAs signature, tumor immune microenvironment and the associated regulation axes in bladder cancer
Authors: Mo Xiaocong , Hu Di , Li Yin , Nai Aitao , Ma Feng , Bashir Shoaib , Jia Guoxia , Xu Meng
Published: August 2022

Bladder cancer (BC) is the most common malignancy of the urinary system. Pyroptosis is a host programmed cell death. However, the effects of pyroptosis-related lncRNAs (PRLs) on BC have not yet been completely elucidated. In this study, a prognostic PRLs model and two ceRNA networks were established using sufficient bioinformatics analysis and preliminary RT-qPCR validation in vitro. 6 PRLs were identified to construct a prognostic model. Then, the prognostic model risk score was verified to be an effective independent factor (Training cohort: Univariate analysis: HR = 1.786, 95% Cl = 1.416-2.252, p < 0.001; multivariate analysis: HR = 1.664, 95% Cl = 1.308-2.116, p < 0.001; testing cohort: Univariate analysis: HR = 1.268, 95% Cl = 1.144-1.405, p < 0.001; multivariate analysis: HR = 1.141, 95% Cl = 1.018-1.280, p = 0.024). Moreover, ROC and nomogram were performed to assess the accuracy of this signature (1-year-AUC = 0.764, 3-years-AUC = 0.769, 5-years-AUC = 0.738). Consequently, we evaluated the survival curves of these 6 lncRNAs using Kaplan–Meier survival analysis, demonstrating that MAFG-DT was risk lncRNA, while OCIAD1-AS1, SLC25A25-AS1, SNHG18, PSMB8-AS1 and TRM31-AS1 were protective lncRNAs. We found a strong correlation between PRLs and tumor immune microenvironment by Pearson’s correlation analysis. As for sensitivity of anti-tumor drugs, the high-risk group was more sensitive to Sorafenib, Bicalutamide and Cisplatin, while the low-risk group was more sensitive to AKT.inhibitor.VIII, Salubrinal and Lenalidomide, etc. Meanwhile, we identified lncRNA OCIAD1-AS1/miR-141-3p/GPM6B and lncRNA OCIAD1-AS1/miR-200a-3p/AKAP11 regulatory axes, which may play a potential role in the progression of BC.
Th2A cells: The pathogenic players in allergic diseases
Authors: Huang Ziyu , Chu Ming , Chen Xi , Wang Ziyuan , Jiang Lin , Ma Yinchao , Wang Yuedan
Published: August 2022

Proallergic type 2 helper T (Th2A) cells are a subset of memory Th2 cells confined to atopic individuals, and they include all the allergen-specific Th2 cells. Recently, many studies have shown that Th2A cells characterized by CD3+ CD4+ HPGDS+ CRTH2+ CD161high ST2high CD49dhigh CD27low play a crucial role in allergic diseases, such as atopic dermatitis (AD), food allergy (FA), allergic rhinitis (AR), asthma, and eosinophilic esophagitis (EoE). In this review, we summarize the discovery, biomarkers, and biological properties of Th2A cells to gain new insights into the pathogenesis of allergic diseases.
Mesenchymal stem cell spheroids alleviate neuropathic pain by modulating chronic inflammatory response genes
Authors: Lee Nayeon , Park Gyu Tae , Lim Jae Kyung , Choi Eun Bae , Moon Hye Ji , Kim Dae Kyoung , Choi Seong Min , Song Young Cheol , Kim Tae Kyun , Kim Jae Ho
Published: August 2022

Chronic neuropathic pain is caused by dysfunction of the peripheral nerves associated with the somatosensory system. Mesenchymal stem cells (MSCs) have attracted attention as promising cell therapeutics for chronic pain; however, their clinical application has been hampered by the poor in vivo survival and low therapeutic efficacy of transplanted cells. Increasing evidence suggests enhanced therapeutic efficacy of spheroids formed by three-dimensional culture of MSCs. In the present study, we established a neuropathic pain murine model by inducing a chronic constriction injury through ligation of the right sciatic nerve and measured the therapeutic effects and survival efficacy of spheroids. Monolayer-cultured and spheroids were transplanted into the gastrocnemius muscle close to the damaged sciatic nerve. Transplantation of spheroids alleviated chronic pain more potently and exhibited prolonged in vivo survival compared to monolayer-cultured cells. Moreover, spheroids significantly reduced macrophage infiltration into the injured tissues. Interestingly, the expression of mouse-origin genes associated with inflammatory responses, Ccl11/Eotaxin, interleukin 1A, tumor necrosis factor B, and tumor necrosis factor, was significantly attenuated by the administration of spheroids compared to that of monolayer. These results suggest that MSC spheroids exhibit enhanced in vivo survival after cell transplantation and reduced the host inflammatory response through the regulation of main chronic inflammatory response-related genes.
PTPRO-related CD8+ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer
Authors: Dong Hongmei , Xie Chaoyu , Yao Zhimeng , Zhao Ruijun , Lin Yusheng , Luo Yichen , Chen Shuanglong , Qin Yanfang , Chen Yexi , Zhang Hao
Published: August 2022

Background

Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers.

Methods

ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets.

Results

High PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs).

Conclusion

PTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients.
Dynamics of PD-1 expression are associated with treatment efficacy and prognosis in patients with intermediate/high-risk myelodysplastic syndromes under hypomethylating treatment
Authors: Geng Suxia , Xu Ruohao , Huang Xin , Li Minming , Deng Chengxin , Lai Peilong , Wang Yulian , Wu Ping , Chen Xiaomei , Weng Jianyu , Du Xin
Published: August 2022

Hypomethylating agents (HMAs) are widely used in patients with higher-risk MDS not eligible for stem cell transplantation. However, the general response rate by HMAs is lesser than 50% in MDS patients, while the relapse rate is high. Emerging evidence indicates that demethylating effects committed by HMAs may facilitate the up-regulation of a range of immune checkpoints or cancer suppressor genes in patients with MDS, among which the programmed death protein 1 (PD-1) and its ligands are demonstrated to be prominent and may contribute to treatment failure and early relapse. Although results from preliminary studies with a limited number of enrolled patients indicate that combined administration of PD-1 inhibitor may yield extra therapeutic benefit in some MDS patients, identifications of this subgroup of patients and optimal timing for the anti-PD-1 intervention remain significant challenges. Dynamics of immune checkpoints and associated predictive values during HMA-treatment cycles remained poorly investigated. In this present study, expression levels of immune checkpoints PD-1 and its ligands PD-L1 and PD-L2 were retrospectively analyzed by quantitative PCR (Q-PCR) in a total of 135 myelodysplastic syndromes (MDS) cohort with higher-risk stratification. The prognostic value of dynamics of these immune checkpoints during HMA cycles was validated in two independent prospective cohorts in our center (NCT01599325 and NCT01751867). Our data revealed that PD-1 expression was significantly higher than that in younger MDS patients (age ≤ 60) and MDS with lower IPSS risk stratification (intermediate risk-1). A significantly up-regulated expression of PD-1 was seen during the first four HMA treatment cycles in MDS patients, while similar observation was not seen concerning the expression of PD-L1 or PD-L2. By utilizing binary logistic regression and receiver operating characteristic (ROC) models, we further identified that higher or equal to 75.9 PD-1 expressions after 2 cycles of HMA treatment is an independent negative prognostic factor in predicting acute myeloid leukemia (AML) transformation and survival. Collectively, our data provide rationales for monitoring the expression of PD-1 during HMA treatment cycles, a higher than 75.9 PD-1 expression may identify patients who will potentially benefit from the combined therapy of HMA and PD-1 inhibitors.
Application of lipid-based nanoparticles in cancer immunotherapy
Authors: Zhang Zhongkun , Yao Siyu , Hu Yingwen , Zhao Xiaobin , Lee Robert J.
Published: August 2022

Immunotherapy is revolutionizing the clinical management of patients with different cancer types by sensitizing autologous or allogenic immune cells to the tumor microenvironment which eventually leads to tumor cell lysis without rapidly killing normal cells. Although immunotherapy has been widely demonstrated to be superior to chemotherapies, only a few populations of patients with specific cancer types respond to such treatment due to the failure of systemic immune activation. In addition, severe immune-related adverse events are rapidly observed when patients with very few responses are given higher doses of such therapies. Recent advances of lipid-based nanoparticles (NPs) development have made it possible to deliver not only small molecules but also mRNAs to achieve systemic anticancer immunity through cytotoxic immune cell activation, checkpoint blockade, and chimeric antigen receptor cell therapies, etc. This review summarized recent development and applications of LNPs in anticancer immunotherapy. The diversity of lipid-based NPs would encapsulate payloads with different structures and molecular weights to achieve optimal antitumor immunity through multiple mechanisms of action. The discussion about the components of lipid-based NPs and their immunologic payloads in this review hopefully shed more light on the future direction of anticancer immunotherapy.