bluuebunny/crossref_metadata_2025 huggingface dataset:
Holocene paleotemperature reconstruction based on phytolith records of lacustrine sediments in the Badain Jaran Desert, northwestern China
Authors: Wang Yixin , Ning Kai , He Qinghua , Jie Dongmei , Guan Qingyu
Published: September 2022

Quantitative reconstruction of regional paleotemperature is the key to understanding temperature change and its driving mechanisms. In this study, 133 phytolith samples were collected as proxy indicators from lacustrine sediments of the Zhunzhahanjilin (ZZH) profile in the hinterland of the Badain Jaran Desert, China. The phytolith samples were then analyzed to quantitatively reconstruct the Holocene paleotemperature at the millennial scale. Based on accelerator mass spectrometry (AMS), 14C dates and an ordered clustering method were used to divide the phytoliths into five assemblage zones with environmental significance. The quantitative reconstruction results indicated that the paleotemperature in the Badain Jaran Desert was relatively high during the early Holocene (11,040–8,200 cal a BP), and the average paleotemperature was approximately 9.5°C. This may have led to increased melt water near the surrounding area and recharged the lakes in the Badain Jaran Desert, resulting in the expansion of the lakes during the early Holocene. The average paleotemperature during the middle Holocene (8,200–3,100 cal a BP) was approximately 7.9°C. This period was warm and the environment was humid, with extensive precipitation from summer monsoons and low evaporation leading to higher water levels in the lakes. The paleotemperature decreased during the late Holocene (3,100 cal a BP to the present), and lakes retreated or dried up because of the decreased summer monsoon rains. The Holocene paleotemperature in the Badain Jaran Desert may have been related to July insolation in the Northern Hemisphere and had a range of impacts on the hydrological cycle in this arid region.
Migration law of different top coal thicknesses in top coal caving
Authors: Nan Hua , Wang Shuai
Published: September 2022

Top coal caving has become one of the main mining methods for thick and extrathick coal seams. Because of coal seam conditions, the top coal thickness is not constant. It is necessary to study the influence of top coal thickness changes on the top-coal-caving mining process. To explore the migration law of top coal failure, the experimental means of similar simulation experiment, numerical simulation experiment and field monitoring data were used. Through a similar simulation test of three different top coal thicknesses, the change rule of top coal migration was analyzed. Moreover, the stress and displacement changes of a 14 m coal seam over a thick top coal caving face were monitored and analyzed comprehensively with the simulation results. The results show that when the top coal thickness is unchanged, the top coal vertical displacement in the upper part is larger than that in the middle part due to the top plate rotation in front of the working face, and the stress change follows an opposite trend. The simulation results were the same as the field test results. When the top coal thickness is changed, whether it is upper top coal or middle top coal, the top coal displacement and stress changes will increase. The top coal migration will be more obvious, and thus the crushing will be more serious.
Associations between serum copper, zinc, selenium level and sex hormones among 6–19 years old children and adolescents in NHANES 2013–2016
Authors: Xiao Lishun , Yang Chengcheng , Gu Wen , Liu Rong , Chen Ding
Published: September 2022

Copper, zinc, and selenium are essential trace elements for human and have important effects on sex hormones. There are few studies on the relationships between the three trace elements and sex hormones. Therefore, our study aimed to investigate the relationships between serum copper, zinc, selenium and testosterone, estradiol, SHBG using data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 in participants 6-19 years. 1097 participants were enrolled and stratified into male/female children and adolescents. Weighted linear regression models combined regression diagnosis were used to estimate the relationships between trace elements and sex hormones according to the different stratifications. Our results showed that copper was inversely associated with testosterone and estradiol but positively correlated with SHBG. Zinc had positive relationships with testosterone in male adolescents and female children but an inverse relationship with testosterone in female adolescents. Furthermore, a negative association was observed between zinc and SHBG. With the rise of selenium level, testosterone and estradiol were increased but SHBG was decreased. In general, this study used more standardized statistical methods to investigate the relationships between copper, zinc, selenium and testosterone, estradiol, SHBG. Further study should pay attention to some details in statistical methods.
Inverse association between blood ethylene oxide levels and obesity in the general population: NHANES 2013–2016
Authors: Cheang Iokfai , Zhu Xu , Zhu Qingqing , Li Menghuan , Liao Shengen , Zuo Zhi , Yao Wenming , Zhou Yanli , Zhang Haifeng , Li Xinli
Published: September 2022

Background

Ethylene oxide (EO) has been shown to associate with increased cardiovascular risk. This study aimed to explore the relationship and its meditating factors between EO exposure and the major cardiovascular risk factor of obesity among the general adult population.

Methods

Cross-sectional data of 3,220 participants from National Health and Nutritional Examination Survey (NHANES) 2013–2016 were enrolled. Obesity was defined as body mass index (BMI) ≥30 kg/m2, and abdominal obesity was defined as waist circumference (WC) ≥102 cm in men and ≥88 cm in women. The association among hemoglobin adduct of EO (HbEO), inflammatory biomarkers, and obesity was evaluated using restricted cubic splines and the multivariable linear regression model. Mediation analysis was used to further assess their association.

Results

The increased quartiles of HbEO were inversely associated with BMI and WC [Q1 vs. Q4, BMI: β = −2.98 (−3.74, −2.22), WC: β = −6.50 (−8.60, −4.39); all p for trend < 0.05], and were inversely associated with obesity after full adjustment [obesity: OR = 0.43 (0.31, 0.58), abdominal obesity: OR = 0.42 (0.27, 0.65); all p for trend < 0.05]. The levels of alkaline phosphatase, white blood cells, lymphocytes, and neutrophils were also positively associated with BMI and WC (all p < 0.05). Mediation analysis showed that exposure of EO not only had a negative direct effect on BMI and WC, but also generated an inverse indirect effect.

Conclusions

Current findings showed an inverse association between HbEO and obesity, and suggested that systemic inflammation may not be their only mediator. Additional research is required to explore the underlying link of EO and system metabolism.
The role of protein acetylation in carcinogenesis and targeted drug discovery
Authors: Yang Jingru , Song Cong , Zhan Xianquan
Published: September 2022

Protein acetylation is a reversible post-translational modification, and is involved in many biological processes in cells, such as transcriptional regulation, DNA damage repair, and energy metabolism, which is an important molecular event and is associated with a wide range of diseases such as cancers. Protein acetylation is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) in homeostasis. The abnormal acetylation level might lead to the occurrence and deterioration of a cancer, and is closely related to various pathophysiological characteristics of a cancer, such as malignant phenotypes, and promotes cancer cells to adapt to tumor microenvironment. Therapeutic modalities targeting protein acetylation are a potential therapeutic strategy. This article discussed the roles of protein acetylation in tumor pathology and therapeutic drugs targeting protein acetylation, which offers the contributions of protein acetylation in clarification of carcinogenesis, and discovery of therapeutic drugs for cancers, and lays the foundation for precision medicine in oncology.
Long-term survival outcomes of pediatric adrenal malignancies: An analysis with the upstaged SEER registry during 2000-2019
Authors: Lv Zemin , Yu Yunyun , Luo Yangmei , Lin Song , Xiang Xuang , Mao Xiaowen , Cheng Shigang
Published: September 2022

Objective

To investigate the clinicopathological characteristics and long-term survival outcomes of pediatric adrenal malignancies.

Method

This study retrospectively analyzed children with pathologically confirmed pediatric adrenal malignancies from Surveillance, Epidemiology, and End Results Database from 2000 to 2019. Kaplan-Meier curve was used to assess the overall survival (OS) and cancer-special survival (CSS), and the Log-Rank method was used to calculate statistical differences. Cox proportional hazards model and Fine-and-Grey model were used to calculate the hazard ratio (HR) of all-cause mortality risk and the sub-distribution HR (sHR) of disease-specific mortality risk, respectively, and their corresponding 95% confidence intervals (CI).

Results

1601 children were included in the study in which 1335 (83.4%) neuroblastoma, 151 (9.4%) ganglioneuroblastoma, 89 (5.6%) adrenocortical carcinoma, and 26 (1.6%) were diagnosed with other types malignancies. Metastatic disease accounted for the largest proportion (69.3%), and the proportion of metastases diagnosed by neuroblastoma was higher than that of adrenocortical carcinoma and ganglioneuroblastoma (73.9% vs. 45.7% vs. 47.2%). The 5-year OS and CSS of all cohort were 69.5% and 70.5%, respectively. Adrenal cortical carcinoma had the worst prognosis, with 5-year OS and CSS of 52.5% and 53.1%, respectively. Patients in recent years had no better OS and CSS than in previous years at diagnosis. The tumor stage remained the main prognostic predictor. Compared to metastatic adrenal tumors, the risk of all-cause mortality (adjusted HR: 0.12, 95% CI: 0.06-0.25, P < 0.001) and the risk of disease-specific mortality (adjusted sHR: 0.11, 95% CI: 0.05-0.25, P<0.001) was significantly lower for patients with localized diseases. Additionally, higher age, adrenal cortical carcinoma, and lack of complete tumor resection are independent risk factors for poor prognosis. Furthermore, it was found that the prognosis of patients who received chemotherapy was worse than those who did not, mainly because the former mostly had metastasis at the presentation and complete resection of the tumor cannot be achieved.

Conclusion

The clinicopathological characteristics of pediatric adrenal malignancies have not changed significantly in the past two decades, while the prognosis of patients has improved. Early diagnosis of disease and complete resection of local tumors are the keys to improving prognosis.
A study on the path of improving the performance of China’s provincial circular economy—An empirical study based on the fsQCA method
Authors: Zhu Fangyang , Lai Liangrong , Zhu Zhidong , Zhang Xiaojie
Published: September 2022

Circular economy is an important trend in the development of the world economy. The establishment of a sound green and low-carbon circular economy system is an important way and method for China to promote sustainable development. Based on the Technology-Organization-Environment (TOE) framework, this paper investigates the linkage effects of technological, organizational, and environmental conditions on the performance of the circular economy and their configuration paths using the fuzzy set qualitative comparative analysis method (fsQCA) with 30 provincial-level circular economy development levels in China as a case study. The study found that: 1) China’s circular economy performance in 2019 shows regional differences of “high in the east, medium in the centre and low in the west,” and there are also imbalances in development between different dimensions. 2) There is no single necessary condition that affects the circular economy, but rather the result of the combined influence of multiple condition variables. And the combination of different conditions has the characteristic of “different ways and the same way”. 3) There are obvious differentiations in the performance-driven paths of circular economy in eastern, central and western regions of China. Based on the research results, policy recommendations are provided for the development of China’s circular economy to promote the balanced development of the circular economy in the east, central and west.
Provincial ecological well-being performance level measurement and its spatial-temporal evolution analysis in China
Authors: Deng Yuanjian , Ma Yan , Yang Xu
Published: September 2022

Based on the panel data of 30 provinces (autonomous regions and municipalities) in China from 2004 to 2017, this paper used the three-stage super-efficiency SBM-DEA model to calculate the ecological well-being performance (EWP) of provincial capital cities and analyzed its temporal and spatial evolution. The results show that: (①) the improvement of China’s technological level and opening-up level can promote the improvement of ecological well-being performance, while the improvement of environmental regulation, urbanization level, and economic development level can inhibit the improvement of ecological well-being performance (②). After excluding the influence of external environment and random interference, the ecological health performance of the whole country and the eastern, central and western regions has been improved, with the eastern region having the greatest improvement and the central region having the smallest improvement. The performance level of national ecological well-being presents a spatial pattern of “strong in the eastern region, secondary in the central region and weak in the western region” (③). The ecological well-being performance levels of Beijing, Hainan, and Shanghai had always been at the forefront of the country, while those of Ningxia, Inner Mongolia, and Liaoning had been in the bottom three for a long time. The gap between provinces is obvious, but the gap between provinces within the same region is smaller.
Impact of green human resource management on organizational reputation and attractiveness: The mediated-moderated model
Authors: Merlin Matumona Lubabu , Chen Yinfei
Published: September 2022

There is increasing global concern for environmental sustainability, with firms being monitored by different stakeholders: customers, government, suppliers, and current and potential employees. This research aims to explore the impacts of green human resource management (GHRM) on organizational reputation (OR) and organizational attractiveness (OA). The conceptual model of the study is derived from social identity theory. A close-ended questionnaire was administered to collect data through a web-based survey link which was shared with 331 employees in a Democratic Republic of Congo hospitality organization. A partial least-square structural equation modeling approach was employed to run data analysis through SmartPLS 3.0 software. The findings of the study reflect that all of the hypotheses were supported. In particular, GHRM has a strong influence on both OR and OA. An OR of green culture and personal environmental orientation strongly affected OA, while it positively and significantly mediated the relationship between GHRM and OA. Personal environmental orientation significantly moderated the link between GHRM and OA. We could find no support for a positive moderating effect of green culture on the connection between GHRM and OA. This study enhanced the scope of social identity theory by proposing that OA can be improved by GHRM, OR, green culture, and personal environmental orientation. In addition, this research suggests that managers in the hospitality sector must incorporate green practices, promote green behavior and initiative, and increase environmental awareness so that employees feel pride in being part of the organization and are attracted to it.
Digital economy and ecological performance: Evidence from a spatial panel data in China
Authors: Shen Xiaomeng , Zhao Haoxiang , Yu Jingyue , Wan Zhicheng , He Taiyi , Liu Jiawei
Published: September 2022

The rapid development of information and communication technologies has brought the concept of digital economy into the limelight. Data elements have played a more important role in economic production. As an environmentally friendly economic model, the data factor-driven economy, compared to the traditional one, has low energy consumption and less pollution emissions. Hence, the effect of digital economy development on ecological performance is worth exploring. We measured the digital economy index and the ecological performance index for 30 provinces in China. Furthermore, the relationship between the two was analyzed with the help of a dynamic spatial Durbin model. The results showed the following: 1) closely related to the regional economic foundation, the development level of the digital economy showed obvious spatial characteristics that were high in the eastern region and low in the western region in China. 2) Over time, the pattern of ecological performance in China has changed markedly, showing a high level in the south and a low level in the north. 3) The digital economy showed a significant promoting effect on ecological performance, with a strong externality in space that could have a spillover effect on the surrounding areas. 4) The effect of the digital economy on ecological performance had a significant positive effect, although it lagged behind over time. In addition, the effect has regional heterogeneity and was more obvious in developed regions. Based on these findings, we recommend that the role of ICT in economic activity be strengthened in some developed regions. However, in some developing regions, a balance needs to be struck between digitalization and environmental benefits. At the same time, developed regions should be encouraged to realize economic collaboration with developing regions, with the help of data elements in an effort to narrow the regional gap.
Environmental dilemma and sustainable development of resource-based cities: A case study from northeast china
Authors: Qing Yiting , Guo Wei , Cao Gaohang , Qin Yu , Nie Xin , Wang Han
Published: September 2022

With ambitious carbon peak and carbon neutral targets, China has to realize it relies heavily on significant reductions in energy-related carbon emissions. Therefore, as the largest contributing region, resource-based cities (RBCs) must achieve an energy transition. Unfortunately, these cities are facing serious environmental problems. The aim of this study is to analyze the development history and problems of RBCs by using the example of the Northeast region. The results show the reasons blocking the green development of these cities include management policies and life cycles. This implies the management of RBCs needs to develop toward a win-win situation of industrial transformation and ecological protection. Finally, some policy recommendations are proposed to achieve emission reduction and sustainable development.
Machine learning identification of cuproptosis and necroptosis-associated molecular subtypes to aid in prognosis assessment and immunotherapy response prediction in low-grade glioma
Authors: Miao Ye , Liu Jifeng , Liu Xishu , Yuan Qihang , Li Hanshuo , Zhang Yunshu , Zhan Yibo , Feng Xiaoshi
Published: September 2022

Both cuproptosis and necroptosis are typical cell death processes that serve essential regulatory roles in the onset and progression of malignancies, including low-grade glioma (LGG). Nonetheless, there remains a paucity of research on cuproptosis and necroptosis-related gene (CNRG) prognostic signature in patients with LGG. We acquired patient data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and captured CNRGs from the well-recognized literature. Firstly, we comprehensively summarized the pan-cancer landscape of CNRGs from the perspective of expression traits, prognostic values, mutation profiles, and pathway regulation. Then, we devised a technique for predicting the clinical efficacy of immunotherapy for LGG patients. Non-negative matrix factorization (NMF) defined by CNRGs with prognostic values was performed to generate molecular subtypes (i.e., C1 and C2). C1 subtype is characterized by poor prognosis in terms of disease-specific survival (DSS), progression-free survival (PFS), and overall survival (OS), more patients with G3 and tumour recurrence, high abundance of immunocyte infiltration, high expression of immune checkpoints, and poor response to immunotherapy. LASSO-SVM-random Forest analysis was performed to aid in developing a novel and robust CNRG-based prognostic signature. LGG patients in the TCGA and GEO databases were categorized into the training and test cohorts, respectively. A five-gene signature, including SQSTM1, ZBP1, PLK1, CFLAR, and FADD, for predicting OS of LGG patients was constructed and its predictive reliability was confirmed in both training and test cohorts. In both the training and the test datasets (cohorts), higher risk scores were linked to a lower OS rate. The time-dependent ROC curve proved that the risk score had outstanding prediction efficiency for LGG patients in the training and test cohorts. Univariate and multivariate Cox regression analyses showed the CNRG-based prognostic signature independently functioned as a risk factor for OS in LGG patients. Furthermore, we developed a highly reliable nomogram to facilitate the clinical practice of the CNRG-based prognostic signature (AUC > 0.9). Collectively, our results gave a promising understanding of cuproptosis and necroptosis in LGG, as well as a tailored prediction tool for prognosis and immunotherapeutic responses in patients.
Pleistocene climate and geomorphology drive the evolution and phylogeographic pattern of Triplophysa robusta (Kessler, 1876)
Authors: Zhong Hui , Sun Yaxian , Wu Huihui , Li Shengnan , Shen Zhongyuan , Yang Conghui , Wen Ming , Chen Peng , Gu Qianhong
Published: September 2022

Montane systems provide excellent opportunities to study the rapid radiation influenced by geological and climatic processes. We assessed the role of Pleistocene climatic oscillations and mountain building on the evolution history of Triplophysa robusta, a cold-adapted species restricted to high elevations in China. We found seven differentiated sublineages of T. robusta, which were established during the Mid Pleistocene 0.87–0.61 Mya. The species distribution modeling (SDM) showed an expansion of T. robusta during the Last Glacial Maximum (LGM) and a considerable retraction during the Last Interglacial (LIG). The deep divergence between Clade I distributed in Qinling Mountains and Clade II in Northeastern Qinghai-Tibet Plateau (QTP) was mainly the result of a vicariance event caused by the rapid uplifting of Qinling Mountains during the Early Pleistocene. While the middling to high level of historical gene flow among different sublineages could be attributed to the dispersal events connected to the repetition of the glacial period during the Pleistocene. Our findings suggested that frequent range expansions and regressions due to Pleistocene glaciers likely have been crucial for driving the phylogeographic pattern of T. robusta. Finally, we urge a burning question in future conservation projection on the vulnerable cold-adapted species endemic to high elevations, as they would be negatively impacted by the recent rapid climate warming.
G × EBLUP: A novel method for exploring genotype by environment interactions and genomic prediction
Authors: Song Hailiang , Wang Xue , Guo Yi , Ding Xiangdong
Published: September 2022

Genotype by environment (G × E) interaction is fundamental in the biology of complex traits and diseases. However, most of the existing methods for genomic prediction tend to ignore G × E interaction (GEI). In this study, we proposed the genomic prediction method G × EBLUP by considering GEI. Meanwhile, G × EBLUP can also detect the genome-wide single nucleotide polymorphisms (SNPs) subject to GEI. Using comprehensive simulations and analysis of real data from pigs and maize, we showed that G × EBLUP achieved higher efficiency in mapping GEI SNPs and higher prediction accuracy than the existing methods, and its superiority was more obvious when the GEI variance was large. For pig and maize real data, compared with GBLUP, G × EBLUP showed improvement by 3% in the prediction accuracy for backfat thickness, while our findings indicated that the trait of days to 100 kg of pig was not affected by GEI and G × EBLUP did not improve the accuracy of genomic prediction for the trait. A significant advantage was observed for G × EBLUP in maize; the prediction accuracy was improved by ∼5.0 and 7.7% for grain weight and water content, respectively. Furthermore, G × EBLUP was not influenced by the number of environment levels. It could determine a favourable environment using SNP Bayes factors for each environment, implying that it is a robust and useful method for market-specific animal and plant breeding. We proposed G × EBLUP, a novel method for the estimation of genomic breeding value by considering GEI. This method identified the genome-wide SNPs that were susceptible to GEI and yielded higher genomic prediction accuracies and lower mean squared error compared with the GBLUP method.
Case Report: The third-generation sequencing confirmed a novel 7.2 Kb deletion at β-globin gene in a patient with rare β-thalassemia
Authors: Zhong Guoxing , Zhong Zeyan , Guan Zhiyang , Chen Dina , Wu Zhiyong , Yang Kunxiang , Chen Dan , Liu Yinyin , Xu Ruofan , Chen Jianhong
Published: September 2022

Background: Thalassemia was the most common monogenic diseases worldwide, which was caused by mutations, deletions or duplications in human globin genes which disturbed the synthesis balance between α- and β-globin chains of hemoglobin. There were many classics methods to diagnose thalassemia, but all of them had limitations. Although variations in the human β-globin gene cluster were mainly point mutations, novel large deletions had been described in recent years along with the development of DNA sequencing technology.

Case report: We present a case of 32-year-old male with abnormal hematological results. However, 23 genotypes of the most common thalassemia were not detected by two independent conventional platforms. Finally, using multiplex ligation-dependent probe amplification (MLPA), third-generation sequencing (TGS) and Gap PCR detection methods, we first confirmed the case with a novel 7.2 Kb deletion (Chr11:5222800-5230034, hg38) located at HBB gene.

Conclusion: Our results showed that TGS technology was a powerful tool for thalassemia breakpoint detection, had promising potentiality in genetic screening of novel thalassemia, especially for the novel deletions in globin genes.
Systematic analysis of inheritance pattern determination in genes that cause rare neurodevelopmental diseases
Authors: Park Soojin , Jang Se Song , Lee Seungbok , Kim Minsoo , Sim Hyungtai , Jeon Hyeongseok , Hong Sung Eun , Lee Jean , Lee Jeongeun , Jeon Eun Young , Lee Jeongha , Lee Cho-Rong , Kim Soo Yeon , Kim Man Jin , Yoon Jihoon G. , Lim Byung Chan , Kim Woo Joong , Kim Ki Joong , Ko Jung Min , Cho Anna , Lee Jin Sook , Choi Murim , Chae Jong-Hee
Published: September 2022

Despite recent advancements in our understanding of genetic etiology and its molecular and physiological consequences, it is not yet clear what genetic features determine the inheritance pattern of a disease. To address this issue, we conducted whole exome sequencing analysis to characterize genetic variants in 1,180 Korean patients with neurological symptoms. The diagnostic yield for definitive pathogenic variant findings was 50.8%, after including 33 cases (5.9%) additionally diagnosed by reanalysis. Of diagnosed patients, 33.4% carried inherited variants. At the genetic level, autosomal recessive-inherited genes were characterized by enrichments in metabolic process, muscle organization and metal ion homeostasis pathways. Transcriptome and interactome profiling analyses revealed less brain-centered expression and fewer protein-protein interactions for recessive genes. The majority of autosomal recessive genes were more tolerant of variation, and functional prediction scores of recessively-inherited variants tended to be lower than those of dominantly-inherited variants. Additionally, we were able to predict the rates of carriers for recessive variants. Our results showed that genes responsible for neurodevelopmental disorders harbor different molecular mechanisms and expression patterns according to their inheritance patterns. Also, calculated frequency rates for recessive variants could be utilized to pre-screen rare neurodevelopmental disorder carriers.
Identification of diagnostic mRNA biomarkers in whole blood for ankylosing spondylitis using WGCNA and machine learning feature selection
Authors: Han Yaguang , Zhou Yiqin , Li Haobo , Gong Zhenyu , Liu Ziye , Wang Huan , Wang Bo , Ye Xiaojian , Liu Yi
Published: September 2022

Ankylosing spondylitis (AS) is a common inflammatory spondyloarthritis affecting the spine and sacroiliac joint that finally results in sclerosis of the axial skeleton. Aside from human leukocyte antigen B27, transcriptomic biomarkers in blood for AS diagnosis still remain unknown. Hence, this study aimed to investigate credible AS-specific mRNA biomarkers from the whole blood of AS patients by analyzing an mRNA expression profile (GSE73754) downloaded Gene Expression Omnibus, which includes AS and healthy control blood samples. Weighted gene co-expression network analysis was performed and revealed three mRNA modules associated with AS. By performing gene set enrichment analysis, the functional annotations of these modules revealed immune biological processes that occur in AS. Several feature mRNAs were identified by analyzing the hubs of the protein-protein interaction network, which was based on the intersection between differentially expressed mRNAs and mRNA modules. A machine learning-based feature selection method, SVM-RFE, was used to further screen out 13 key feature mRNAs. After verifying by qPCR, IL17RA, Sqstm1, Picalm, Eif4e, Srrt, Lrrfip1, Synj1 and Cxcr6 were found to be significant for AS diagnosis. Among them, Cxcr6, IL17RA and Lrrfip1 were correlated with severity of AS symptoms. In conclusion, our findings provide a framework for identifying the key mRNAs in whole blood of AS that is conducive for the development of novel diagnostic markers for AS.
Effectiveness and safety of Belimumab combined with standard therapy in severe active lupus nephritis requiring kidney replacement therapy: A case report and literature review
Authors: Zhang Chengning , Zeng Ming , Ge Yifei , Liu Kang , Xing Changying , Mao Huijuan
Published: September 2022

Lupus Nephritis (LN) is the most common manifestation of severe organ damage for systemic lupus erythematosus (SLE) patients. Severe active LN could result in acute kidney injury (AKI), which could even require Kidney Replacement Therapy (KRT). Therefore, there needs to be a more proactive and safe induction therapy to quickly and effectively control renal immune inflammation, maintain kidney function or reverse kidney damage. While multiple clinical studies have proven the efficacy and safety of Belimumab in treating SLE and LN, these studies have not included cases of severe LN requiring KRT. We observed the effectiveness and safety of Belimumab in treating four severe active LN patients undergoing KRT. With Belimumab administered at a dosage of 10mg/kg, all four patients were able to discontinue KRT with no adverse events (AEs) to date ultimately. These cases provided an excellent basis for the application of Belimumab combined with standard therapy to LN patients with a medium to severe kidney injury.
Role of RGC-32 in multiple sclerosis and neuroinflammation – few answers and many questions
Authors: Tatomir Alexandru , Cuevas Jacob , Badea Tudor C. , Muresanu Dafin F. , Rus Violeta , Rus Horea
Published: September 2022

Recent advances in understanding the pathogenesis of multiple sclerosis (MS) have brought into the spotlight the major role played by reactive astrocytes in this condition. Response Gene to Complement (RGC)-32 is a gene induced by complement activation, growth factors, and cytokines, notably transforming growth factor β, that is involved in the modulation of processes such as angiogenesis, fibrosis, cell migration, and cell differentiation. Studies have uncovered the crucial role that RGC-32 plays in promoting the differentiation of Th17 cells, a subtype of CD4+ T lymphocytes with an important role in MS and its murine model, experimental autoimmune encephalomyelitis. The latest data have also shown that RGC-32 is involved in regulating major transcriptomic changes in astrocytes and in favoring the synthesis and secretion of extracellular matrix components, growth factors, axonal growth molecules, and pro-astrogliogenic molecules. These results suggest that RGC-32 plays a major role in driving reactive astrocytosis and the generation of astrocytes from radial glia precursors. In this review, we summarize recent advances in understanding how RGC-32 regulates the behavior of Th17 cells and astrocytes in neuroinflammation, providing insight into its role as a potential new biomarker and therapeutic target.
Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation
Authors: Neyrinck-Leglantier Déborah , Tamagne Marie , L’honoré Sasha , Cagnet Léonie , Pakdaman Sadaf , Marchand Alexandre , Pirenne France , Vingert BenoÎt
Published: September 2022

Extracellular vesicles (EVs), which are generated by cell membrane budding in diverse cells, are present in variable numbers in the blood. An immunoregulatory role has been demonstrated principally for heterologous EVs, but the function of the EVs present naturally in blood remains unknown. We hypothesize that these autologous EVs might also modulate the phenotype and function of immune system cells, especially CD4+T lymphocytes (TLs), as previously described for heterologous EVs. Several membranes and soluble immunoregulatory molecules were studied after the treatment of CD4+TLs with autologous EVs. No direct activation was detected with autologous EVs, contrasting with the findings for heterologous EVs. However, following treatment with autologous EVs, a soluble form of CD27 (sCD27) was detected. sCD27 is strongly associated with lymphoproliferation. Autologous EVs have been shown to increase TL proliferation only after T-cell receptor (TcR) engagement due to polyclonal or specific-antigen stimulation. Our results therefore suggest that the EVs present in the blood have an immunomodulatory role different from that of heterologous EVs. These findings should be taken into account in future studies, particularly those focusing on infectious diseases, autotransfusion or doping practices.
Efficacy of Metarhizium anisopliae and (E)–2–hexenal combination using autodissemination technology for the management of the adult greenhouse whitefly, Trialeurodes vaporariorum Westwood (Hemiptera: Aleyrodidae)
Authors: Paradza Vongai M. , Khamis Fathiya M. , Yusuf Abdullahi A. , Subramanian Sevgan , Akutse Komivi S.
Published: September 2022

The efficiency of an autodissemination technique in controlling adult whiteflies, Trialeurodes vaporariorum Westwood (Hemiptera: Aleyrodidae) on tomato, Solunum lycopersicum was investigated with previously identified potent fungal isolates of Metarhizium anisopliae ICIPE 18, ICIPE 62 and ICIPE 69 under screenhouse or semi-field conditions. The autodissemination device was inoculated with dry conidia of the M. anisopliae isolates, while control insects were exposed to a fungus–free device. Sampling for conidia uptake, conidial viability and persistence, and insect mortality was done at 1, 2, 3, 5 and 8 days post–exposure, and collected insects were monitored for mortality over ten days. Overall, mortality was higher in insects exposed to ICIPE 18 (62.8%) and ICIPE 69 (61.8%) than in those exposed to ICIPE 62 (42.6%), with median lethal times, (LT50) ranging between 6.73–8.54 days. The control group recorded the lowest mortality rates (18.9%). A general linear reduction in conidial viability with exposure time was observed, although this was more pronounced with M. anisopliae ICIPE 62. Insects exposed to M. anisopliae ICIPE 69 also recorded the highest conidia uptake, hence selected for further evaluation with a T. vaporariorum attractant volatile organic compound, (E)–2–hexenal. The volatile inhibited fungal germination in laboratory compatibility tests, therefore, spatial separation of M. anisopliae ICIPE 69 and (E)–2–hexenal in the autodissemination device was conducted. The inhibitory effects of the volatile were significantly reduced by spatial separation at a distance of 5 cm between the fungus and the volatile, which was found to be more suitable and chosen for the subsequent experiments. Results showed that (E)–2–hexenal did not influence conidia uptake by the insects, while fungal viability and the subsequent mortality variations were more related to duration of exposure. The fungus–volatile compatibility demonstrated with spatial separation provides a basis for the optimisation of the volatile formulation to achieve better T. vaporariorum suppression with an excellent autodissemination efficiency when used in the management of whiteflies under screenhouse conditions.
Geochemical characteristics of gases associated with natural gas hydrate
Authors: Li Yuanyuan , Chang Jingyi , Lu Hailong
Published: September 2022

With more natural gas hydrate samples recovered and more research approaches applied to hydrate-associated gas studies, data concerning the geochemical characteristics of hydrate-associated gases have been increased significantly in the past decades. Although systematic reviews of hydrocarbons are available, fewer studies have focused on the systematic classification of gas hydrates, yet. In this study, the primary origins and secondary processes that affect the geochemical characteristics of the gases are discussed. The primary origins are affected mainly by the type and /or maturity of the organic matter, which determine the main signature of the gas is microbial gas or thermogenic gas in a broad scheme. Apart from primary origins, secondary processes after gas generation such as migration, mixing, biodegradation and oxidation occur during the migration and/or storage of gases can significantly alter their primary features. Traditional methods such as stable isotope and molecular ratios are basic proxies, which have been widely adopted to identify these primary origins and secondary processes. Isotopic compositions of C2+ gases have been employed to identify the precursor of the gases or source rocks in recent years. Data from novel techniques such as methane clumped isotope and noble gases bring additional insights into the gas origins and sources by providing information about the formation temperature of methane or proxies of mantle contribution. A combination of these multiple geochemical approaches can help to elucidate an accurate delineation of the generation and accumulation processes of gases in a gas hydrate reservoir.
Medium-term observations of salt marsh morphodynamics
Authors: Jin Chuang , Gong Zheng , Shi Lei , Zhao Kun , Tinoco Rafael O. , San Juan Jorge E. , Geng Liang , Coco Giovanni
Published: September 2022

Salt marshes play a key role in attenuating wave energy and promoting sedimentation necessary to potentially adapt to sea level rise. The changes in the soil surface elevation, as a result of spatially and temporally varied sedimentation pattern, affect the hydrodynamics, marsh edge extension and so the sedimentation rate. Little attention has yet been paid to the medium-term sedim\entation under the influence of marsh extension. To fill this gap, we performed a 6-year (from 2012 to 2018) field observation to obtain the soil surface elevation of the cross-shore tidal flats in the center Jiangsu Coast (China). The salt marsh edge is extracted from remote sensing images using NVDI technique, which allows us to quantify the seaward extension of salt marshes. Results highlight that soil surface elevation in the salt marsh region varies spatially and temporally as a function of marsh topography, inundation frequency and distance to the salt marsh edge. The sedimentation rate reduces linearly shoreward as a result of increasing soil surface elevation in the marsh region. At the transition of salt marshes and bare flats, the sedimentation rate follows a parabolic relationship with the increase in distance to the salt marsh edge but decreases linearly at the more landward sites. The maximum sedimentation rate is initially located around the mean high-water level and moves towards the edge of the salt marsh as a result of marsh extension and increasing soil surface elevation. Our field observations reveal these medium-term marsh dynamics and provide a unique dataset for development, testing and validation of numerical simulations to enhance predictions of the overall evolution of tidal flats.
Comparison of intravitreal ranibizumab monotherapy vs. ranibizumab combined with dexamethasone implant for macular edema secondary to retinal vein occlusion
Authors: Liang Xuemei , Shen Baiyun , Ou Zuguo , An Hongmei , Li Li
Published: September 2022

Purpose

To compare the efficacy and the injection number of intravitreal ranibizumab (IVR) monotherapy vs. intravitreal ranibizumab plus dexamethasone (IVR + DEX) implants for macular edema (ME) secondary to retinal vein occlusion (RVO).

Methods

This prospective, control trial comprised 96 eyes of 96 patients with ME due to non-ischemic RVO divided into two groups. The IVR monotherapy group consisted of 61 patients (29 with CRVO and 32 with BRVO) treated with ranibizumab with three consecutive loading doses at a monthly + pro re nata (three + PRN) regimen. The IVR + DEX implant group consisted of 35 patients (19 with CRVO and 16 with BRVO) treated with intravitreal ranibizumab plus DEX implant. All eyes underwent best-corrected visual acuity (BCVA, log MAR), central foveal thickness (CFT), and intraocular pressure (IOP). In case of recurrence, each group received initial medication.

Results

At the 12-month visit, the mean log MAR BCVA that was improved from baseline was 0.23 with the IVR group and 0.30 with the IVR + DEX group. CFT decreased on average by 420 ± 292 μm with the IVR group and 393 ± 259 μm with the IVR + DEX implant group. No significant differences were detected in BCVA improvement and CFT reduction between the two groups (p > 0.05). The mean number of injections was 5.4 in the IVR group and 3.9 in the IVR + DEX implant group (p < 0.001). The mean reinjection interval for patients with the IVR + DEX implant was 131.2 ± 8.9 days (range: 98–150). The incidence of high IOP and cataract progression were significantly higher in the IVR + DEX implant group than in the IVR group (both p < 0.001).

Conclusion

In RVO-ME, the IVR + DEX implant did not have synergistic efficacy, providing further improvement in BCVA and a reduction in CFT. However, the IVR + DEX implant still had an advantage in reducing the number of injections and prolonging the time between injections.
Protective effect of Limosilactobacillus fermentum HFY06 on dextran sulfate sodium-induced colitis in mice
Authors: Liu Bihui , Yang Lei , Wu Ya , Zhao Xin
Published: September 2022

Ulcerative colitis is one of the main gastrointestinal diseases that threaten human health. This study investigated the effect of Limosilactobacillus fermentum HFY06 (LF-HFY06) on dextran sulfate sodium (DSS)-induced murine colitis. The protective effect of LF-HFY06 was evaluated by examining the length and histopathological sections of colon, related biochemical indicators, and genes related to inflammation. Direct and microscopic observations showed that LF-HFY06 increased the length of the colon and ameliorated the pathological damage induced by DSS. The biochemical indicators showed that LF-HFY06 enhanced the activities of antioxidant enzymes total superoxide dismutase (T-SOD) and catalase (CAT) in serum, while reducing the level of malondialdehyde (MDA). It was also observed that the serum inflammatory cytokines levels of tumor necrosis factor-α (TNF-α), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and IL-12 were decreased, and the anti-inflammatory cytokine IL-10 level was increased. The qPCR experiment revealed that LF-HFY06 downregulated the mRNA expression levels of nuclear factor-κB-p65 (Rela), Tnf, Il 1b, Il 6, and prostaglandin-endoperoxide synthase 2 (Ptgs2) in colon tissues, and upregulated the mRNA expression of NF-κB inhibitor-α (Nfkbia) and Il 10. These data indicated that LF-HFY06 inhibited inflammation through the NF-κB signaling pathway to prevent the occurrence and development of colitis. This research demonstrates that probiotics LF-HFY06 have the potential to prevent and treat colitis.
Strategies for dispersion of cariogenic biofilms: applications and mechanisms
Authors: Chen Rourong , Du Minquan , Liu Chang
Published: September 2022

Bacteria residing within biofilms are more resistant to drugs than planktonic bacteria. They can thus play a significant role in the onset of chronic infections. Dispersion of biofilms is a promising avenue for the treatment of biofilm-associated diseases, such as dental caries. In this review, we summarize strategies for dispersion of cariogenic biofilms, including biofilm environment, signaling pathways, biological therapies, and nanovehicle-based adjuvant strategies. The mechanisms behind these strategies have been discussed from the components of oral biofilm. In the future, these strategies may provide great opportunities for the clinical treatment of dental diseases.

Graphical Abstract
3-Dimensional coculture of breast cancer cell lines with adipose tissue–Derived stem cells reveals the efficiency of oncolytic Newcastle disease virus infection via labeling technology
Authors: Salman Marwa Ibrahim , Al-Shammari Ahmed Majeed , Emran Mahfodha Abbas
Published: September 2022

Oncolytic virotherapy is one of the emerging biological therapeutics that needs a more efficient in vitro tumor model to overcome the two-dimensional (2D) monolayer tumor cell culture model’s inability to maintain tissue-specific structure. This is to offer significant prognostic preclinical assessment findings. One of the best models that can mimic the in vivo model in vitro are the three-dimensional (3D) tumor–normal cell coculture systems, which can be employed in preclinical oncolytic virus therapeutics. Thus, we developed our 3D coculture system in vitro using two types of breast cancer cell lines showing different receptor statuses cocultured with adipose tissue–derived mesenchymal stem cells. The cells were cultured in a floater tissue culture plate to allow spheroids formation, and then the spheroids were collected and transferred to a scaffold spheroids dish. These 3D culture systems were used to evaluate oncolytic Newcastle disease virus AMHA1 strain infectivity and antitumor activity using a tracking system of the Newcastle disease virus (NDV) labeled with fluorescent PKH67 linker to follow the virus entry into target cells. This provides evidence that the NDV AMHA1 strain is an efficient oncolytic agent. The fluorescently detected virus particles showed high intensity in both coculture spheres. Strategies for chemically introducing fluorescent dyes into NDV particles extract quantitative information from the infected cancer models. In conclusion, the results indicate that the NDV AMHA1 strain efficiently replicates and induces an antitumor effect in cancer–normal 3D coculture systems, indicating efficient clinical outcomes.