bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttranslational Regulation of Inflammasomes, Its Potential as Biomarkers and in the Identification of Novel Drugs Targets
Authors: Nanda Sambit K. , Vollmer Stefan , Perez-Oliva Ana B.
Published: June 2022

In this review, we have summarized classical post-translational modifications (PTMs) such as phosphorylation, ubiquitylation, and SUMOylation of the different components of one of the most studied NLRP3, and other emerging inflammasomes. We will highlight how the discovery of these modifications have provided mechanistic insight into the biology, function, and regulation of these multiprotein complexes not only in the context of the innate immune system but also in adaptive immunity, hematopoiesis, bone marrow transplantation, as well and their role in human diseases. We have also collected available information concerning less-studied modifications such as acetylation, ADP-ribosylation, nitrosylation, prenylation, citrullination, and emphasized their relevance in the regulation of inflammasome complex formation. We have described disease-associated mutations affecting PTMs of inflammasome components. Finally, we have discussed how a deeper understanding of different PTMs can help the development of biomarkers and identification of novel drug targets to treat diseases caused by the malfunctioning of inflammasomes.
Two Sides of the Same Coin: Protein Kinase C γ in Cancer and Neurodegeneration
Authors: Pilo Caila A. , Newton Alexandra C.
Published: June 2022

Protein kinase C (PKC) isozymes transduce myriad signals within the cell in response to the generation of second messengers from membrane phospholipids. The conventional isozyme PKCγ reversibly binds Ca2+ and diacylglycerol, which leads to an open, active conformation. PKCγ expression is typically restricted to neurons, but evidence for its expression in certain cancers has emerged. PKC isozymes have been labeled as oncogenes since the discovery that they bind tumor-promoting phorbol esters, however, studies of cancer-associated PKC mutations and clinical trial data showing that PKC inhibitors have worsened patient survival have reframed PKC as a tumor suppressor. Aberrant expression of PKCγ in certain cancers suggests a role outside the brain, although whether PKCγ also acts as a tumor suppressor remains to be established. On the other hand, PKCγ variants associated with spinocerebellar ataxia type 14 (SCA14), a neurodegenerative disorder characterized by Purkinje cell degeneration, enhance basal activity while preventing phorbol ester-mediated degradation. Although the basis for SCA14 Purkinje cell degeneration remains unknown, studies have revealed how altered PKCγ activity rewires cerebellar signaling to drive SCA14. Importantly, enhanced basal activity of SCA14-associated mutants inversely correlates with age of onset, supporting that enhanced PKCγ activity drives SCA14. Thus, PKCγ activity should likely be inhibited in SCA14, whereas restoring PKC activity should be the goal in cancer therapies. This review describes how PKCγ activity can be lost or gained in disease and the overarching need for a PKC structure as a powerful tool to predict the effect of PKCγ mutations in disease.
The Role of ZAP and TRIM25 RNA Binding in Restricting Viral Translation
Authors: Yang Emily , Nguyen LeAnn P. , Wisherop Carlyn A. , Kan Ryan L. , Li Melody M.H.
Published: June 2022

The innate immune response controls the acute phase of virus infections; critical to this response is the induction of type I interferon (IFN) and resultant IFN-stimulated genes to establish an antiviral environment. One such gene, zinc finger antiviral protein (ZAP), is a potent antiviral factor that inhibits replication of diverse RNA and DNA viruses by binding preferentially to CpG-rich viral RNA. ZAP restricts alphaviruses and the flavivirus Japanese encephalitis virus (JEV) by inhibiting translation of their positive-sense RNA genomes. While ZAP residues important for RNA binding and CpG specificity have been identified by recent structural studies, their role in viral translation inhibition has yet to be characterized. Additionally, the ubiquitin E3 ligase tripartite motif-containing protein 25 (TRIM25) has recently been uncovered as a critical co-factor for ZAP’s suppression of alphavirus translation. While TRIM25 RNA binding is required for efficient TRIM25 ligase activity, its importance in the context of ZAP translation inhibition remains unclear. Here, we characterized the effects of ZAP and TRIM25 RNA binding on translation inhibition in the context of the prototype alphavirus Sindbis virus (SINV) and JEV. To do so, we generated a series of ZAP and TRIM25 RNA binding mutants, characterized loss of their binding to SINV genomic RNA, and assessed their ability to interact with each other and to suppress SINV replication, SINV translation, and JEV translation. We found that mutations compromising general RNA binding of ZAP and TRIM25 impact their ability to restrict SINV replication, but mutations specifically targeting ZAP CpG-mediated RNA binding have a greater effect on SINV and JEV translation inhibition. Interestingly, ZAP-TRIM25 interaction is a critical determinant of JEV translation inhibition. Taken together, these findings illuminate the contribution of RNA binding and co-factor interaction to the synergistic inhibition of viral translation by ZAP and TRIM25.
Variability in Susceptibility to Type I Interferon Response and Subgenomic RNA Accumulation Between Clinical Isolates of Dengue and Zika Virus From Oaxaca Mexico Correlate With Replication Efficiency in Human Cells and Disease Severity
Authors: Castro-Jiménez Tannya Karen , Gómez-Legorreta Laura Cristina , López-Campa Laura Alejandra , Martínez-Torres Valeria , Alvarado-Silva Marcos , Posadas-Mondragón Araceli , Díaz-Lima Nallely , Angulo-Mendez Hilda Arcelia , Mejía-Domínguez Nancy R. , Vaca-Paniagua Felipe , Ávila-Moreno Federico , García-Cordero Julio , Cedillo-Barrón Leticia , Aguilar-Ruíz Sergio Roberto , Bustos-Arriaga José
Published: June 2022

Dengue and Zika viruses cocirculate annually in endemic areas of Mexico, causing outbreaks of different magnitude and severity every year, suggesting a continuous selection of Flavivirus variants with variable phenotypes of transmissibility and virulence. To evaluate if Flavivirus variants with different phenotypes cocirculate during outbreaks, we isolated dengue and Zika viruses from blood samples of febrile patients from Oaxaca City during the 2016 and 2019 epidemic years. We compared their replication kinetics in human cells, susceptibility to type I interferon antiviral response, and the accumulation of subgenomic RNA on infected cells. We observed correlations between type I interferon susceptibility and subgenomic RNA accumulation, with high hematocrit percentage and thrombocytopenia. Our results suggest that Flaviviruses that cocirculate in Oaxaca, Mexico, have variable sensitivity to the antiviral activity of type I interferons, and this phenotypic trait correlates with the severity of the disease.
Within-Speaker Perception and Production of Two Marginal Contrasts in Illinois English
Authors: Zhang Jennifer , Graham Lindsey , Barlaz Marissa , Hualde José Ignacio
Published: June 2022

The notion of marginal contrasts and other gradient relations challenges the classification of phones as either contrastive phonemes or allophones of the same phoneme. The existence of “fuzzy” or “intermediate” contrasts has implications for language acquisition and sound change. In this research, we examine production and perception of two marginal contrasts [ɑ-ɔ] (“cot-caught”), where two original phonemes are undergoing a merger, and [ʌi-aɪ] (“writer-rider”), where a single original phoneme has arguably split into two contrastive sounds, albeit in a limited manner. Participants born and raised in Illinois were asked to provide recordings ofcot-caughtandwriter-riderpairs embedded in sentences, followed by the target word in isolation. They then completed ABX and two-alternative forced choice two-alternative forced choice (2FC) perception tasks with stimuli produced by two native speakers from the Chicagoland area. Results showed that the [ʌi-aɪ] contrast, which has been defined as marginal in other work, is actually currently more phonetically and phonologically stable than [ɑ-ɔ] for the group of speakers that we have tested, with a more robust link between production and perception. Thecot-caughtmerger appears to have progressed further, compared to what had previously been documented in the region. Our results and analysis suggest different sound change trajectories for phonological mergers, regarding the coupling of production and perception, as compared with phonemic splits.
Association Between Familial Hypercholesterolemia and Risk of Cardiovascular Events and Death in Different Cohorts: A Meta-Analysis of 1.1 Million Subjects
Authors: Yu Yani , Chen Lei , Zhang Honghong , Fu Zihao , Liu Qi , Zhao Haijing , Liu Yuqi , Chen Yundai
Published: June 2022

Background and Aims

The association of familial hypercholesterolemia (FH) with risk of cardiovascular events (CVE) and death in different cohorts is controversial. We aimed to assess the risk of CVE and death in patients with FH in different cohorts, including CHD and ACS patients, White and Asian, different diagnostic criteria.

Methods

We searched PubMed, MEDLINE, and Web of Science electronic databases through May 2021 to identify cohort studies of CVE and death in patients with FH.

Results

We found 18 eligible studies with 1,139,788 participants, including 34,261 patients. There were 31,287 ACS patients, of whom 2,338 were combined with FH. Randomized-effects meta-analysis showed that in patients with FH, relative risk (RR) of CVE and death was 1.87 (95% CI 1.21–2.88), among which CVE was 2.14 (95%CI 1.26–3.64), all-cause of death RR = 1.12 (95% CI 0.89–1.41), and cardiac death RR = 1.03 (95% CI 0.59–1.79). Risk of CVE and death in general population with FH was 2.85 (95% CI 0.72–11.21), hyperlipidemia population RR = 1.59 (95% CI 1.05–2.41), coronary heart disease patients (CHD) RR = 1.46 (95% CI 1.24–1.72), and acute coronary syndrome patients (ACS) RR = 1.71 (95% CI 1.19–2.46). Among ACS patients, the RR of CVE in patients with FH was 1.91 (95% CI 1.55–2.35), the RR of all-cause of death was 1.03 (95% CI 0.80–1.32), and the RR of cardiac death was 1.03 (95% CI 0.59–1.79). The risk of CVE and death in ACS patients with FH in White was 1.69 (95% CI 1.09–2.64) and Asian 1.90 (95% CI 1.31–2.75). RR in patients with Dutch Lipid Network criteria (DLCN) ≥6 vs. <3 points was higher (RR = 2.24, 95% CI 1.69–2.97). RR for long-term follow-up was 1.68 (95% CI 1.09–2.61) and for short-term follow-up was 1.80 (95% CI 1.16–2.78). The results of the overall population were similar, but RR for overall population during a short-term follow-up was 1.49 (95% CI 0.81–2.73). We followed PRISMA checklist to complete meta-analysis.

Conclusions

The risk of CVE and death was increased in patients with CHD, especially in patients with ACS. DLCN ≥ 6 points was suggested for clinical diagnosis of FH. The risk of long-term and short-term CVE and death increased in ACS patients with FH.

Registration Number

INPLASY2021110010.
Multi-Slice Computed Tomography Analysis in Patients Undergoing Transcatheter Aortic Valve Replacement – Impact of Workflows on Measurement of Virtual Aortic Annulus and Valve Size
Authors: Piayda Kerstin , Hellhammer Katharina , Veulemans Verena , Afzal Shazia , Klein Kathrin , Berisha Nora , Leuders Pia , Erkens Ralf , Kirchner Julian , Heidari Houtan , Kelm Malte , Antoch Gerald , Zeus Tobias , Quast Christine
Published: June 2022

Exact and reliable measurements of anatomical dimensions in pre-procedural multi-slice computed tomography (MSCT) scans are crucial for optimal valve sizing and clinical results of transcatheter aortic valve replacement (TAVR). This study aimed to investigate interrater reliability between routinely used workflows for pre-procedural analysis. MSCT scans of 329 patients scheduled for TAVR were analyzed using both a 3mensio and SECTRA IDS7 platform. The results were retrospectively compared using the intraclass correlation coefficient, revealing excellent correlation in the analysis of simple diameters and poor correlation in the assessment of more complex structures with impact on calculated valve size.
Efficacy of Drug-Coated Balloon Approaches for de novo Coronary Artery Diseases: A Bayesian Network Meta-Analysis
Authors: Zhong Peng-Yu , Ma Ying , Shang Yao-Sheng , Niu Ying , Bai Nan , Wang Zhi-Lu
Published: June 2022

Background and Objective

The de novo coronary lesions are the most common form of coronary artery disease, and stent implantation still is the main therapeutic strategy. This network meta-analysis aims to evaluate the efficacy of drug-coated balloons only (DCB only) and DCB combined with bare-metal stents (DCB+BMS) strategies vs. drug-eluting stents (DES) and BMS approaches in coronary artery de novo lesion.

Method

PubMed, EMBASE, and Cochrane Library databases were retrieved to include the relevant randomized controlled trials that compared DCB approaches and stents implantation in patients with de novo coronary artery diseases. The primary outcome was major adverse cardiac events (MACE). The clinical outcomes included target lesion revascularization (TLR), all-cause death, and myocardial infarction. The angiographic outcomes consisted of in-segment late lumen loss (LLL) and binary restenosis. The odds ratio (OR) and 95% confidence intervals (95% CIs) for dichotomous data, and weighted mean differences for continuous data were calculated in the Bayesian network frame.

Result

A total of 26 randomized controlled trials and 4,664 patients were included in this study. The DCB-only strategy was comparable with the efficacy of MACE, clinical outcomes, and binary restenosis compared with DES. In addition, this strategy can significantly reduce the in-segment LLL compared with the first-generation (MD −0.29, −0.49 to −0.12) and the second-generation DES (MD −0.15, −0.27 to −0.026). However, subgroup analysis suggested that DCB only was associated with higher in-segment LLL than DES (MD 0.33, 0.14 to 0.51) in patients with acute coronary syndrome. Compared with DES, the DCB+BMS strategy had a similar incidence of myocardial infarction and all-cause death, but a higher incidence of MACE, TLR, and angiographic outcomes. In addition, DCB+BMS was associated with a similar incidence of myocardial infarction and all-cause death than BMS, with a lower incidence of MACE, TLR, and angiographic outcomes.

Conclusion

The DCB only is associated with similar efficacy and lower risk of LLL compared with DES. In addition, the DCB+BMS strategy is superior to BMS alone but inferior to DES (PROSPERO, CRD 42021257567).

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
Predicting Late Recurrence of Atrial Fibrillation After Radiofrequency Ablation in Patients With Atrial Fibrillation: Comparison of C2HEST and HATCH Scores
Authors: Han Jingjing , Li Guangling , Zhang Demei , Wang Xiaomei , Guo Xueya
Published: June 2022

Objective

This study was aimed to investigate the risk of recurrence in patients with atrial fibrillation (AF) after radiofrequency ablation and predict risk of recurrence using C2HEST and HATCH scores.

Methods

We retrospectively included 322 patients with AF from Second Hospital of Lanzhou University, and 261 patients were included in the analysis finally. They had AF and were admitted for radiofrequency catheter ablation. We compared the ability of C2HEST and HATCH scores to predict recurrence after radiofrequency ablation of AF. The predictive ability of C2HEST and HATCH scores for AF recurrence was estimated by the area under the receiver operating characteristic curve (AUROC). The difference in receiver operating characteristic curve between the two models was compared using the DeLong test.

Results

Of the 261 patients included in the analysis, 83 (31.6%) patients suffered a late recurrence of AF after radiofrequency ablation. The risk of postoperative recurrence of AF increased with increasing C2HEST and HATCH scores. The AUROC of C2HEST and HATCH scores in predicting postoperative recurrence of AF was 0.773 (95%CI, 0.713–0.833) and 0.801 (95% CI, 0.740–0.861), respectively. There was no significant difference between the two models in their ability to evaluate patients for postoperative recurrence of AF (DeLong test p-value = 0.36). Among the risk factors in both models, hypertension and heart failure (HF) contributed the most to postoperative recurrence after AF, and higher blood pressure and lower cardiac ejection fraction (EF) were associated with a higher risk of recurrence.

Conclusion

Both C2HEST and HATCH scores were significantly associated with the risk of late recurrence after radiofrequency ablation of AF. Besides hypertension and HF contributed the most to postoperative recurrence after AF.
Investigation Into Deformation and Failure Characteristics of the Soft-Hard Interbedded Rock Mass Under Multiaxial Compression
Authors: Li Ang , Shao Guojian , Li Yaodong , Sun Yang , Su Jingbo , Liu Juncheng
Published: June 2022

The influence of loading path, intermediate principal stress and weak layers on the deformation property and failure characteristics of soft-hard interbedded rock mass is initially discussed in this study. First, the laboratory experiments of multiaxial compression failure are carried out to soft-hard interbedded rock samples of Jinping. Three failure modes of rock samples caused by different distribution forms of weak layers under uniaxial compression and deformation property and failure characteristics of rock samples in different loading paths under biaxial compression are analyzed. Then, considering the property of strain softening, numerical models are established based on the elastic-brittle-plastic constitutive relation. The effect of weak layer dip angle, quantity, distribution form, and volume ratio on strength characteristics is further investigated. The results reveal that the failure mode of Jinping soft-hard interbedded rock samples generally follows the pattern of multi-fracture splitting under uniaxial compression, and the pattern of tension-shear damage under biaxial compression. The intermediate principal stress is positively correlated with the vertical failure loading. The number of weak layers has no significant effect on the “U” type strength characteristics of samples. However, as the number of weak layers increases, there is a tendency for the minimum of vertical failure loading to move forward in the direction of smaller dip.
Psychological Detachment as a Mediator Between Successive Days' Job Stress and Negative Affect of Teachers
Authors: Aulén Anna-Mari , Pakarinen Eija , Feldt Taru , Tolvanen Asko , Lerkkanen Marja-Kristiina
Published: June 2022

The study investigated the mediating role of teachers' psychological detachment between successive days' job stress and negative affect. Fifty-seven Finnish teachers answered to a mobile diary four times a day on two successive workdays assessing their negative affect, three times a day assessing their job stress and once a day after work assessing their psychological detachment from work. Two-level modeling on both the between individual level and within day level was used to test the mediational model. The data supported the mediational model where teachers' job stress hinders their psychological detachment, which again increases their negative affect and job stress on the subsequent day. On the basis of our results teachers' occupational health interventions intended to reduce their job stress and support their psychological detachment from work are desirable. In addition, robust work-home segmentation norms within schools are suggested to support teachers' psychological detachment from work.
Three Decades of Research on Individual Teacher-Child Relationships: A Chronological Review of Prominent Attachment-Based Themes
Authors: Spilt Jantine L. , Koomen Helma M. Y.
Published: June 2022

Attachment theory has played a prominent role in the study of affective relationships between teachers and individual children in school settings. This review synthesizes three decades of attachment-based research on teacher-child relationships roughly covering the period between 1992 and 2022. Five key themes were discussed: (1) conceptualization and assessment, (2) secure base and autonomous exploration, (3) safe haven and self-regulation, (4) attachment history and relationship (dis)continuity, and (5) teacher sensitivity and mentalization. Following a narrative review approach, a selection of pivotal research studies was made and chronologically presented to illustrate research developments per theme. The results indicated that the conceptualization and assessment of teacher-child relationships holds largely, but not completely, across different developmental phases, cultural contexts, measurement methods, and informants. In addition, research confirmed the role of the secure base and safe haven functions of teacher-child relationships in promoting children’s emotional security at school. Furthermore, progression has been made through the development of multiple measurement methods for both teachers and children, by expanding research from early childhood education up to secondary education, and by more recent cross-cultural studies. However, there is still limited insight in mechanisms that explain (dis)continuity in relationships over time, and a striking lack of research on dyadic teacher sensitivity and mentalization as antecedents of teacher-child relationships. Research directions for the following decade(s) of research are discussed per theme.
Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis
Authors: Li Yixuan , Cao Shan , Gaculenko Anastasia , Zhan Yifan , Bozec Aline , Chen Xiaoxiang
Published: June 2022

Bone marrow adipocytes (BMAs) represent 10% of the total fat mass of the human body and serve as an energy reservoir for the skeletal niche. They function as an endocrine organ by actively secreting fatty acids, cytokines, and adipokines. The volume of BMAs increases along with age, osteoporosis and/or obesity. With the rapid development of multi-omic analysis and the advance in in vivo imaging technology, further distinct characteristics and functions of BMAs have been revealed. There is accumulating evidence that BMAs are metabolically, biologically and functionally unique from white, brown, beige and pink adipocytes. Bone metastatic disease is an uncurable complication in cancer patients, where primary cancer cells spread from their original site into the bone marrow. Recent publications have highlighted those BMAs could also serve as a rich lipid source of fatty acids that can be utilized by the cancer cells during bone metastasis, particularly for breast, prostate, lung, ovarian and pancreatic cancer as well as melanoma. In this review, we summarize the novel progressions in BMAs metabolism, especially with multi-omic analysis and in vivo imaging technology. We also update the metabolic role of BMAs in bone metastasis, and their potential new avenues for diagnosis and therapies against metastatic cancers.
Experimental Study on the Influence of Particle Diameter, Mass Concentration, and Impeller Material on the Wear Performance of Solid–Liquid Two-Phase Centrifugal Pump Blade
Authors: Wang Yanping , Li Weiqin , He Tielin , Liu Hao , Han Chuanfeng , Zhu Zucao
Published: June 2022

A centrifugal pump is an important solid–liquid mixture conveying machinery, which is widely used in mineral mining, water conservancy engineering, and other fields. Solid particles will wear the impeller of the centrifugal pump in the process of transportation, resulting in lower service life of the impeller, especially in the transportation of a high concentration of solid particles. Many scholars use numerical simulation to study the wear of centrifugal pumps, but few efforts have been made in the wear experiment. In this study, the effect of three factors, namely, diameter of solid particles, mass concentration of particles, and material of impellers on the wear of a solid–liquid two-phase centrifugal pump was studied by the wear experiment. The solid particles are SiO2 with irregular shapes, and the diameter ranges are 0.125–0.212 mm, 0.212–0.425 mm, and 0.425–0.710 mm. The mass concentration of solid particles is 15%, 20%, and 30%. The material of impellers is carbon structural steel (Q235), gray cast iron (HT200), and low-alloy high-strength steel (16 Mn). The amount of wear is determined by measuring the thickness of the impeller material before and after wear experiments. The wear morphology of the impeller was observed by using a digital microscope. The results showed that the wear mainly concentrated on the middle and trailing edges of the blade. Impellers of different materials suffer different wear forms, among which the impeller made of HT200 has the best erosion resistance. The increase of solid mass concentration will aggravate the wear of the impeller. The change of particle diameters also has a great influence on impeller wear.
Inertia Optimization Control and Transient Stability Analysis of Wind Power Grid-Connected System
Authors: Song Wenle , Wang Lei , Zhao Wei , Zhang Xiangyu , Wang Zhiwei
Published: June 2022

The virtual inertia control effectively makes up for the insufficient inertia caused by the high penetration wind power grid connection. However, it has an impact on the mechanical part of the wind turbine and greatly increases the difficulty of the dynamic stability analysis of the system, resulting in limited engineering practicability. Therefore, the state equation of the wind power grid-connected system is established in this paper, and the influence of virtual inertia control on wind turbine shafting oscillation is analyzed based on the small-signal theory. Secondly, the nonlinear extended disturbance observer is designed as the compensation signal of inertia control to improve its dynamic stability supportability. Based on the integral manifold method, the shafting model of the wind turbine is reduced, and the transient energy function of shafting is established, which provided the basis for the design of the shafting stability controller. Finally, a grid-connected wind power system with high permeability is installed, and the results demonstrate that under the proposed control strategy, the swing stability of power angle is significantly improved, and the wind turbine shafting oscillation is suppressed.
Carbon Emission Characteristics and Reduction Pathways of Urban Household in China
Authors: Li Zhi , Liu Yuze , Zhang Zuo
Published: June 2022

With China’s rapid urbanization and rising living standards, the household sector has become the second largest contributor to urban carbon emissions and important pathway to achieve China’s carbon reduction targets. Based on data of Chinese Residential Energy Consumption Survey in 2014, this paper establishes standard households in 54 cities to identify the carbon emission characteristics and explores the emission reduction paths of urban households. We present evidence that rich households tend to increase their use of clean energy, low-income households will not completely abandon inferior energy because of their usage habits and costs and they always live in suburban areas and urban villages. Cities with high household carbon emissions are almost located in north of Huai River/Qinling Mountains line, while cities with low carbon emissions are mostly located around the line and which are mainly on the south side. Monocentric urban development patterns and frigid climates are easy to increase higher household carbon emissions. In this regard, policy makers should help low-income households to escape from inferior energy dependence, encourage the use of new energy vehicles and green housing technologies, introduce a two-part pricing system for central heating services and maintain relative balance of residential and public resources in urban planning.
Effect of Large-Scale Mining Drainage on Groundwater Hydrogeochemical Evolution in Semi-Arid and Arid Regions
Authors: Luo Ankun , Wang Guangcai , Dong Shuning , Wang Hao , Shi Zheming , Ji Zhongkui , Xue Jiankun
Published: June 2022

Groundwater evolution and circulation in coal mining areas will be significantly affected by natural processes and human activities. However, the impacts of large-scale mining drainage on groundwater hydrochemistry are unclear in the semi-arid and arid inland coalfields in northwest China. In particular, for shallow buried areas, the spontaneous combustion of coal seam outcrops forms burnt rock that is rich in fractures. Being a strong water-yield aquifer after receiving recharge, burnt rock has become a potential source of mine water inrush hazards. Therefore, drainage from this aquifer is necessary to eliminate potential hazards, which also leads to the deterioration of the local ecological diversity and sustainability. The hydrogeochemical method is an effective way to study the source and evolution of groundwater in mining areas and to determine the long-term cumulative effect of mining and drainage on the hydrogeochemical evolution of burnt rock areas. It is, however, still poorly understood. In this study, we employed the hydrochemical and isotope (2H, 3H, and 18O) to investigate the long-term effects of drainage on the hydrogeochemical evolution in the coalfield of southern Xinjiang, China. The results showed that the hydrochemical environment became more complex as the effect of recharge of different tritium-based groundwater ages in multiple-layered aquifer system and leads to the changes in the concentration of the chemical components. Before large-scale mining drainage, groundwater flowed from west to east and was finally discharged into the Kuqa River. The major water–rock interactions that occurred were the dissolution of halite, carbonate and gypsum dissolution, cation exchange, and dedolomitization. After large-scale and long-term mining drainage from the burnt rock aquifer, the groundwater flow field had changed, and the Kuqa river turned to recharge into the burn rock aquifer, the hydrochemical evolution also changed from water–rock interaction to mixture. This was caused by the significant decline in the groundwater level and changes in groundwater circulation in the mining area, which further led to the loss of valuable surface water resources in this arid area. Based on the characteristics and recharge conditions of burnt rock, we suggested that grouting can effectively cut off the hydraulic connection between the river and burnt rock and thus protect water resources.
Gastric Microplastics in Clarias gariepinus of the Upper Vaal River, South Africa
Authors: Dahms Heinrich T. J. , Tweddle Gavin P. , Greenfield Richard
Published: June 2022

Microplastics are defined as plastics smaller than 5 mm down to 0.05 mm. These plastics enter the environment and undergo certain physical changes, most notably density changes and a relative increase of surface size. Microplastics can then release or absorb toxicants from the surrounding environment. These plastics may then enter the food chain from producers to top predators. In this study, microplastics were investigated in four study sites in the upper Vaal River, South Africa. The goal of the study was to determine the levels of plastics in water, sediment and a top predator, the benthic fish Clarias gariepinus. In this study, a 10% KOH digestion of water and fish, and density separation of sediment with NaCl (1.2 g cm3) was used to extract microplastics for identification. Microplastics were detected in water (3, 300 particles m−³), fish (7.47 particles per fish) and sediment (46.7 particles kg−1). Microplastic intake was not attributed to the microplastic shape or size of the fish that ingested it. This highlights the need to understand how niche-specific microplastic concentrations are, which will not only aid in quantifying microplastics accurately in the environment but to better understand how they may influence various ecosystems.
The Immune Cell Infiltration Patterns and Characterization Score in Bladder Cancer to Identify Prognosis
Authors: Zhang Yongsheng , Wang Yunlong , Wang Jichuang , Zhang Kaixiang
Published: June 2022

Background: Bladder cancer (BLCA) is among the most frequent types of cancer. Patients with BLCA have a significant recurrence rate and a poor post-surgery survival rate. Recent research has found a link between tumor immune cell infiltration (ICI) and the prognosis of BLCA patients. However, the ICI’s picture of BLCA remains unclear.

Methods: Common gene expression data were obtained by combining the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) expression databases. Two computational algorithms were proposed to unravel the ICI landscape of BLCA patients. The R package “limma” was applied to find differentially expressed genes (DEGs). ICI patterns were defined by the unsupervised clustering method. Principal-component analysis (PCA) was used to calculate the ICI score. In addition, the combined ICI score and tumor burden mutation (TMB) were utilized to assess BLCA patients’ prognosis. The predictive value of ICI scores was verified by different clinical characteristics.

Results: A total of 569 common gene expression data were retrieved from TCGA and GEO cohorts. CD8+ T cells were found to have a substantial positive connection with activated memory CD4+ T cells and immune score. On the contrary, CD8+ T cells were found to have a substantial negative connection with macrophages M0. Thirty-eight DEGs were selected. Two ICI patterns were defined by the unsupervised clustering method. Patients of BLCA were separated into two groups. The high ICI score group exhibited a better outcome than the low ICI score one (p < 0.001). Finally, the group with a high tumor mutation burden (TMB) as well as a high ICI score had the best outcome. (p < 0.001).

Conclusions: Combining TMB and ICI scores resulted in a more accurate survival prediction, suggesting that ICI scores could be used as a prognostic marker for BLCA patients.
Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis
Authors: Liu Wenjie , Huo Gengwei , Chen Peng
Published: June 2022

Objective

Atezolizumab is becoming a significant therapy for non-small cell lung cancer (NSCLC), but its efficacy needs to be further improved. The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features, and to choose a better therapeutic regimen of atezolizumab to achieve more precise treatment in immunotherapy.

Methods

Randomized clinical trials (RCTs) in the Cochrane Library, PubMed, Embase Science Direct, and Google Scholar, together with major oncology conferences that compared atezolizumab with chemotherapy-based treatment for individuals with advanced NSCLC published prior to February 2022, were searched. Studies, bias risk assessment, and data extraction were selected by two independent authors. We extracted the basic features of the included studies, together with the 95% confidence interval (CI) and hazard ratios (HRs), from all patients and subgroups. The combined treatment data were assessed using the inverse variance weighting method.

Results

Seven RCTs including 4,859 patients were included. Our meta-analysis findings indicated that atezolizumab substantially enhanced OS (HR 0.82; 95% CI, 0.77–0.88; p < 0.00001) and PFS (HR 0.72; 95% CI, 0.61–0.85; p < 0.0001) in patients with advanced NSCLC compared with chemotherapy-based treatment. Atezolizumab substantially enhanced OS in patients aged <65 years old and 65–74 years old, those with wild-type EGFR, those without liver metastases, active or previous smokers, white patients and those with TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3, and TC0 and IC0, but not in patients aged ≥75 years, never smokers, those with liver metastases, those with EGFR mutant, Asians, Black or African Americans, or those with TC1/2 or IC1/2. Patients with advanced NSCLC who received atezolizumab showed OS improvement regardless of sex (male or female), histological type (non-squamous or squamous NSCLC), performance status (0 or 1), and line of treatment (1st-line therapy or ≥2nd-line therapy). Subgroup analysis revealed that male individuals, those with non-squamous NSCLC, those with PS 1, active or previous smokers, and those with wild-type EGFR, TC3 or IC3, and TC1/2/3 or IC1/2/3 achieved OS benefit from atezolizumab treatment not related to the treatment line and treatment regimen.

Conclusions

Age group, smoking history, liver metastasis status, EGFR mutation status, race, and PD-L1 expression can be used to predict the potency of atezolizumab and provide a better treatment regimen for patients with advanced NSCLC to achieve accurate and personalized treatment.
Comparison of IgA, IgG, and Neutralizing Antibody Responses Following Immunization With Moderna, BioNTech, AstraZeneca, Sputnik-V, Johnson and Johnson, and Sinopharm’s COVID-19 Vaccines
Authors: Adjobimey Tomabu , Meyer Julia , Sollberg Leander , Bawolt Michael , Berens Christina , Kovačević Peđa , Trudić Anika , Parcina Marijo , Hoerauf Achim
Published: June 2022

In an ongoing multinational trial, we obtained blood samples from 365 volunteers vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from Sinopharm. After collecting reactogenicity data, the expression of S-Protein binding IgG and IgA was analyzed using an automated sandwich ELISA system. Serum neutralizing potentials were then investigated using an ACE-2-RBD neutralizing assay. Moderna’s vaccine induced the highest amounts of SARS-CoV-2 specific neutralizing antibodies compared to the other groups. In contrast, Sinopharm and Johnson and Johnson’s vaccinees presented the lowest SARS-CoV-2-specific antibody titers. Interestingly, moderate to high negative correlations between age and virus-specific IgG expression were observed in the Johnson and Johnson (ρ =-0.3936) and Sinopharm (ρ =-0.6977) groups according to Spearman’s rank correlation analysis. A negative correlation was seen between age and IgA expression in the Sputnik-V group (ρ =-0.3917). The analysis of virus neutralization potentials in age categories demonstrated that no significant neutralization potential was observed in older vaccinees (61and 80 years old) in the Sputnik-V Johnson and Johnson and Sinopharm vaccinees’ groups. In contrast, neutralization potentials in sera of Moderna, BioNTech, and AstraZeneca vaccinees were statistically comparable in all age categories. Furthermore, while the AstraZeneca vaccine alone induced moderate IgG and IgA expression, the combination with Moderna or BioNTech mRNA vaccines induced significantly higher antibody levels than a double dose of AstraZeneca and similar IgG expression and neutralization potential compared to Moderna or BioNTech vaccines used alone. These results suggest that mRNA vaccines are the most immunogenic after two doses. DNA vectored vaccines from AstraZeneca and Sputnik-V presented lower but significant antibody expression and virus neutralizing properties after two doses. The lowest antibody and neutralization potential were observed in the Sinopharm or Johnson and Johnson vaccinees. Especially elderly over 60 presented no significant increase in neutralizing antibodies after vaccination. The data also indicate that heterologous vaccination strategies combining the AstraZeneca DNA vectored vaccines and mRNA vaccines are more effective in the induction of neutralizing antibodies compared to their homologous counterparts.
Recipient Tregs: Can They Be Exploited for Successful Hematopoietic Stem Cell Transplant Outcomes?
Authors: Copsel Sabrina N. , Wolf Dietlinde , Pfeiffer Brent , Barreras Henry , Perez Victor L. , Levy Robert B.
Published: June 2022

Human and mouse CD4+FoxP3+ T cells (Tregs) comprise non-redundant regulatory compartments which maintain self-tolerance and have been found to be of potential therapeutic usefulness in autoimmune disorders and transplants including allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is substantial literature interrogating the application of donor derived Tregs for the prevention of graft versus host disease (GVHD). This Mini-Review will focus on the recipient’s Tregs which persist post-transplant. Although treatment in patients with low dose IL-2 months post-HSCT are encouraging, manipulating Tregs in recipients early post-transplant is challenging, in part likely an indirect consequence of damage to the microenvironment required to support Treg expansion of which little is understood. This review will discuss the potential for manipulating recipient Tregs in vivo prior to and after HSCT (fusion proteins, mAbs). Strategies that would circumvent donor/recipient peripheral blood harvest, cell culture and ex-vivo Treg expansion will be considered for the translational application of Tregs to improve HSCT outcomes.
Thermal Fluctuations Yield Sex-Specific Differences of Ingestion Rates of the Littoral Mysid Neomysis integer
Authors: Hennigs Laura M. , Bergunder Konstanze , Sperfeld Erik , Wacker Alexander
Published: June 2022

Shallow aquatic environments are characterized by strong environmental variability. For ectotherms, temperature is the main driver of metabolic activity, thus also shaping performance. Ingestion rates in mysids are fast responses, influenced by metabolic and behavioral activity. We examined ingestion rates of the mysid Neomysis integer, collected in the Baltic Sea, after one-week exposure to different constant and fluctuating temperature regimes (5, 10, 15, 20°C and 9 ± 5, 14 ± 5°C, respectively). To investigate possible differences between sexes, thermal performance curves (TPCs) were established for female and male mysids based on ingestion rates measured at constant temperatures. TPCs of ingestion rates at constant temperatures differed between sexes, with female mysids showing a higher total ingestion rate as well as a higher thermal optimum compared to male mysids. Females showed reduced ingestion rates when exposed to fluctuating temperatures around their thermal optimum, whereas ingestion of male mysids was not reduced when exposed to fluctuating temperatures. The observed sex-specific differences might be related to potentially higher lipid and energy demands of the females. We suggest future studies should investigate males and females to improve our understanding about impacts of environmental variability on natural populations.
Evidence for Carbonate System Mediated Shape Shift in an Intertidal Predatory Gastropod
Authors: Mayk Dennis , Peck Lloyd S. , Harper Elizabeth M.
Published: June 2022

Phenotypic plasticity represents an important first-line organism response to newly introduced or changing environmental constraints. Knowledge about structural responses to environmental stressors could thus be an essential measure to predict species and ecosystem responses to a world in change. In this study, we combined morphometric analyses with environmental modelling to identify direct shape responses of the predatory gastropod Nucella lapillus to large-scale variability in sea surface temperature and the carbonate system. Our models suggest that the state of the carbonate system and, more specifically, the substrate inhibitor ratio ([HCO3−][H+]−1) (SIR) has a dominant effect on the shell shape of this intertidal muricid. Populations in regions with a lower SIR tend to form narrower shells with a higher spire to body whorl ratio, whereas populations in areas with a higher SIR form wider shells with a much lower spire to body whorl ratio. These results indicate that a widespread phenotypic response of N. lapillus to continuing ocean acidification can be expected, potentially altering the phenotypic response pattern to predator or wave exposure regimes with profound implications for North Atlantic rocky shore communities.
Single-Cell Sequencing on Marine Life: Application and Future Development
Authors: Li Jing , Wang Hao , Li Chaolun
Published: June 2022

Single-cell RNA-sequencing (scRNA-seq) is the genomic approach that directly examines gene expression information from individual cells and provides a higher resolution of cellular differences than bulk RNA-seq. In the past decade, with the rapid development of microfluid, barcoding, and next-generation sequencing (NGS) technologies, scRNA-seq has revolutionized transcriptomic studies and gained great success and broad prospects. However, compared with the wide use in the few model animals, the application of scRNA-seq in marine organisms is limited due to the high cost of early scRNA-seq and the immature of single-cell methods for marine organisms. Recently, with the increase of genomic data, maturation of scRNA-seq platform and downstream bioinformatics algorithms, the scRNA-seq has been successfully applied in several marine model animals with great success, which demonstrated that the scRNA-seq could be the ideal and powerful tool to extend our understanding of marine organisms’ evolutionary and physiological processes and their adaptation to ecological niches. Here, we review the state-of-the-art improvements of single-cell sequencing techniques and new studies that apply single-cell methods to marine organisms. We also summarize the opportunities and challenges scientists may face in further single-cell research and propose several appealing prospects that may benefit from the combination of single-cell techniques and marine organisms.
Amelioration of Flesh Quality in Hybrid Grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu) Fed With Oxidized Fish Oil Diet by Supplying Lactobacillus pentosus
Authors: Yan Xiaobo , Pan Simiao , Li Zhihao , Dong Xiaohui , Tan Beiping , Long Shuisheng , Li Tao , Suo Xiangxiang , Yang Yuanzhi
Published: June 2022

The objective was to investigate the improvement of the flesh quality and nutritional value of hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu) by Lactobacillus pentosus (BL-15). The two diets were prepared with 9% oxidized fish oil (OFO negative control group) or 9% fresh fish oil (FFO positive control group) as the major lipid source, and the OFO diet were sprayed with L. pentosus at 1.0×107, 1.0×108, 1.0×109 CFU/g, respectively. Five kinds of diets were fed to hybrid grouper with initial weight of 21.36 ± 0.03 g for 60 days. The results showed that (1) consumption of OFO diet significantly increased muscle crude lipid, total cholesterol, and total monounsaturated fatty acids contents and significantly decreased muscle C20:5n3, C22:6n3, ∑PUFA levels of grouper (p < 0.05), whereas the addition of L. pentosus to OFO diet significantly reduced muscle crude lipid, malondialdehyde, reactive oxygen radicals, total cholesterol concentration, increased C20:5n3, C22:6n3, ∑PUFA levels, increased muscle crude protein content, and enhanced muscle hardness, gumminess, and chewiness compared with FFO or OFO group (p < 0.05). (2) In addition, ingestion of OFO diet significantly increased muscle phenylalanine content and significantly decreased aspartic acid content (p < 0.05), while the addition of L. pentosus restored aspartic acid to the level not significantly different from that of FFO group (p > 0.05). The addition of L. pentosus also increased tyrosine, lysine, leucine, phenylalanine, arginine, and alanine content compared to FFO group at the same time (p < 0.05). (3) Furthermore, the intake of OFO diet would lead to deterioration in muscle flavor quality and increase in noxious odors in grouper, and the addition of L. pentosus can mitigate or rectify these detrimental consequences. In further analysis, consumption of OFO group significantly downregulated the mRNA expression of muscle growth factors and caused serious damage to the muscle antioxidant system (p < 0.05), which was protected against by the potent antioxidant properties of L. pentosus. We recommend the supplementation level of L. pentosus to be 1.0×109 CFU/g under the highly oxidized conditions of the present trial fish oil.