bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution Characteristics and Mechanism of the Load/Unload Response Ratio Based on Strain Observation Before the Jiuzhaigou MS7.0 Earthquake
Authors: Yue Chong , Ji Ping , Wang Yali , Yu Huaizhong , Cui Jin , Yu Chen , Ma Yuchuan
Published: June 2022

Strain observation is the most intuitive observation equipment to monitor stress change in the crust. Strain equipment near the epicenter area of the Jiuzhaigou earthquake (JZGEQ) provides a lot of reliable pre-seismic and post-seismic data for the study of stress change. In this study, the load/unload response ratio (LURR) method is used to study the stress state of rocks by calculating the ratio of strain observation during the loading phase and unloading phase. Results show that the LURR method based on strain observation is an effective method to describe the dynamic change of the constitutive relationship of the rocks in the crust. Different from the strain observation, the LURR anomaly evolution process is more continuous regardless of the time series curve or spatial and temporal distribution characteristics. The LURR curves of different stations begin to increase above 1.0 gradually from 6 months to 1 year prior to the occurrence of the JZGEQ, reaching the maximum value in 1–3 months before the JZGEQ, and subsequently return to a low level. The maximum value of the LURR anomalies decreases with the distance from the epicenters. At the same time, the spatial and temporal evolution characteristics of the LURR anomalies show us the process of “extension—enhance—weaken” in the epicenter of JZGEQ and its peripheral area prior to the earthquake. The concentration areas of the aforementioned LURR anomalies are all distributed in the pre-seismic normal stress-loading zone, which indicates that the faults are in the process of decoupling, and microfracture may exist in the stage of rock dilatancy.
Dolomite Origins of the Carbonate Successions From the Chihsia Formation, South China: A Case Study From the Pingdingshan Section
Authors: Kuang Hao , Mao Zhenxing , Zhuo Xiaojing , Li Mengkang , Liu Chao
Published: June 2022

The carbonate successions from the Chihsia Formation play an important role for hydrocarbon exploration in the South China. However, the dolomites occurring in the upper section of the Chihsia Formation have been enigmatic, which confined further understanding of the depositional and/or diagenetic fluids and hydrocarbon prediction. In this study, the Pingdingshan section was investigated as a typical outcrop of Chihsian carbonates. On the basis of lithofacies/mineralogic observation of hand specimens and thin-sections, three types of dolomites were classified according to their crystal sizes, that is, micritic dolomite, sucrosic dolomite, and saddle dolomite. Comprehensive, micro-area geochemical proxies, including homogenization temperatures of fluid-inclusions, carbon and oxygen isotopes, and trace and rare-earth elements, were analyzed on different types of dolomites and matrix calcites. The results revealed that the selected samples were representative of temporal seawater and were not contaminated by terrestrial input. The temperatures and salinities of fluid-inclusions, combined with carbon and oxygen isotopic values, revealed that sucrosic dolomites originated from penecontemporaneous micritic dolomites, which had been crystallized and altered into fine- to medium-sized dolomite clusters during the later-stage burying process. In contrast, the saddle dolomites occurring in carbonate matrix or fractures were formed in a hydrothermal environment with a dolomitizing fluid temperature higher than 170°C. This inference is consistent with evidence from rare-earth elements and carbon and oxygen isotopes. Our findings provide new clues for the origin elucidation of dolomitizing fluids in the Chihsia Formation, South China.
Rock Physical Modeling of Tight Sandstones Based on Digital Rocks and Reservoir Porosity Prediction From Seismic Data
Authors: Guo Wei , Dong Chunmei , Lin Chengyan , Wu Yuqi , Zhang Xianguo , Liu Jinshuai
Published: June 2022

Digital rock physics (DRP) has become an important tool to analyze the characteristics of pore structures and minerals and reveal the relationships between microscopic structures and the physical properties of reservoirs. However, it is greatly difficult to upscale the rock physical parameters, such as P-wave velocity, S-wave velocity, and elastic moduli, from DRP to large-scale boreholes and reservoirs. On the other hand, theoretical rock physical modeling can establish the internal relationship between the elastic properties and physical parameters of tight sandstones, which provides a theoretical basis for seismic inversion and seismic forward modeling. Therefore, the combination of digital rock physics and rock physical modeling can guide the identification and evaluation of the gas reservoir’s “sweet spot.” In this study, the CT images are used to analyze the mineral and pore characteristics. After that, the V-R-H model is used to calculate the equivalent elastic moduli of rocks containing only the mineral matrix, and then, the differential equivalent medium (DEM) model is used to obtain the elastic moduli of dry rocks containing minerals and pores. Subsequently, the homogeneous saturation model is used to fill the fluids in the pores and the Gassmann equation is used to calculate the equivalent elastic moduli of the saturated rock of tight sandstones. Rock physical modeling is calibrated, and the reliability of the rock physical model is verified by comparing those with the logging data. Afterward, the empirical relationship of rock porosity established from CT images and rock elastic moduli is obtained, and then, the elastic parameters obtained by seismic data inversion are converted into porosity parameters by using this empirical relationship. Finally, the porosity prediction of large-scale reservoirs in the study area is realized to figure out the distribution of gas reservoirs with high porosity. The results show that the H3b and H3c sections of the study area exhibit higher porosity than H3a. For the H3b reservoir, the northeast and middle areas of the gas field are potential targets since their porosity is larger than that of others, from 10% to 20%. Because of the effects of the provenance from the east direction, the southeast region of the H3c reservoir exhibits higher porosity than others.
Hypovitaminosis D Is Prevalent in Patients With Renal AL Amyloidosis and Associated With Renal Outcome
Authors: Muchtar Eli , Drake Matthew T. , Leung Nelson , Dispenzieri Angela , Lacy Martha Q. , Buadi Francis K. , Dingli David , Hayman Suzanne R. , Kapoor Prashant , Hwa Yi Lisa , Fonder Amie , Hobbs Miriam , Gonsalves Wilson , Kourelis Taxiarchis V. , Warsame Rahma , Russell Stephen , Go Ronald S. , Binder Moritz , Kyle Robert A. , Rajkumar S. Vincent , Kumar Shaji K. , Gertz Morie A.
Published: June 2022

Introduction

Vitamin D deficiency is common, but no data have been reported on vitamin D levels in light chain (AL) amyloidosis.

Patients and Methods

In this exploratory study, stored serum samples from 173 patients with newly diagnosed AL amyloidosis were analyzed for vitamin studies which included 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin D binding protein (DBP). Measurements were made by liquid chromatography-tandem mass spectrometry. Kidney survival and overall survival (OS) were assessed in association to vitamin D status.

Results

Cardiac and kidney involvement occurred in 69% and 63% of patients, respectively. 25(OH)D deficiency (<20 ng/mL) was seen in 56.6% of the patients and was notably found among patients with heavy proteinuria (96%), hypoalbuminemia (84.3%) and morbidly obese patients (68.3%). Heavy proteinuria (>5 gr/24-h) and vitamin D supplementation were independent predictors of 25(OH)D level on nominal multivariate regression analysis. 1,25(0H)2D deficiency was noted in 37.6% of patients and was independently associated with low eGFR and hypoalbuminemia. Progression to ESRD occurred in 23.7% of evaluable patients. Patients who progressed to ESRD had lower serum 25(OH)D and 1,25(OH)2D levels compared to those who did not progress to ESRD. On a multivariate analysis, severe 25(OH)D deficiency was an independent predictor of progression to ESRD as was renal stage, while 1,25(OH)2D deficiency was not.

Conclusions

Hypovitaminosis D is common in AL amyloidosis, particularly among patients with heavy proteinuria. Severe 25(OH)D deficiency at time of diagnosis predicts progression to ESRD.
Comparative Study of Impacts of Typical Bio-Inspired Optimization Algorithms on Source Inversion Performance
Authors: Mao Shushuai , Hu Feng , Lang Jianlei , Chen Tian , Cheng Shuiyuan
Published: June 2022

Accurate identification of source information (i.e., source strength and location) is crucial for the air pollution control or effective accidental response. Optimization inversion based on bio-inspired algorithms (BIOs) is an effective method for estimating source information. However, the impacts of different BIOs and the shared parameter of population size in BIOs on source inversion performance have not been revealed. Here the source inversion performance (i.e., accuracy and robustness) of six typical BIOs [i.e., bacterial foraging optimization algorithm (BFO), chicken swarm optimization algorithm (CSO), differential evolution algorithm (DE), genetic algorithm (GA), particle swarm optimization (PSO), and seeker optimization algorithm (SOA)], and their population sizes are evaluated based on the Prairie Grass dataset which covering different atmospheric conditions (i.e., Pasquill stability classes A, B, C, D, E, and F). Results indicated the population size has substantial influence on source inversion. The accuracy of all BIOs in source strength fluctuated greatly when the population size was small, whereas, tended to be stable as the population size increased. Overall, the BFO had the best accuracy with lowest deviations (74.5% for source strength and 29.7 m for location parameter x0), whereas SOA had the best robustness for all source parameters. Atmospheric conditions indicated an obvious influence on the inversion performance of the BIOs. The BFO and CSO performed the best with the lowest deviations [137.5 and 26.7% for unstable conditions (A, B, and C) and stable condition (E), respectively], all algorithms are comparable (67.4 ± 2.1%) in neutral condition (D), and BFO and CSO had the comparable performances (23.2 and 24.3%) and performed better under extremely stable condition (F). This study enhances the understanding of the factors inﬂuencing source inversion and provides a reference for the selection of appropriate bio-inspired algorithms and the reasonable setting of population size parameter for source inversion in practical environmental management.
How Multi-Dimensional Local Government Competition Impacts Green Economic Growth? A Case Study of 272 Chinese Cities
Authors: Su Xufeng , Liu Guangliang , Xu Yang , Ge Wenfeng , Shen Bing , Ran Qiying , Zhou Hui
Published: June 2022

Green economic growth is an unavoidable choice for China’s development model, while the government-led Chinese economic development system determines that local government competition may have an essential impact on green economic growth. For this purpose, this study employs data on Chinese 272 prefecture-level cities and the system generalized method of moments (SYS-GMM) model to investigate the impact of multi-dimensional local government competition (ecological competition, service competition, economic competition, and comprehensive competition) on green economic growth. The empirical results reveal that local government competition significantly influences green economic growth, in which economic competition significantly inhibits green economic growth, and ecological competition, service competition, and comprehensive competition positively influences green economic growth. The influence mechanism indicates that economic competition, ecological competition, service competition, and comprehensive competition significantly affect green economic growth through economic agglomeration and industrial structure upgrading, respectively. Moreover, the impact of multi-dimensional local government competition on green economic growth shows significant temporal and regional heterogeneity. Therefore, policymakers should further develop a multi-dimensional local government competition target system for local government officials and moderately enhance both ecological competition and service competition that is oriented to green economic growth.
Revealing the Satellite DNA History in Psalidodon and Astyanax Characid Fish by Comparative Satellitomics
Authors: Goes Caio Augusto Gomes , dos Santos Rodrigo Zeni , Aguiar Weidy Rozendo Clemente , Alves Dálete Cássia Vieira , Silva Duílio Mazzoni Zerbinato de Andrade , Foresti Fausto , Oliveira Claudio , Utsunomia Ricardo , Porto-Foresti Fabio
Published: June 2022

Eukaryotic genomes are usually enriched in repetitive DNA sequences, which can be classified as dispersed or tandemly repeated elements. Satellite DNAs are noncoding monomeric sequences organized in a head-to-tail fashion that are generally located on the subtelomeric and/or pericentromeric heterochromatin. In general, a single species incorporates a diverse group of satellite DNA families, which collection is called satellitome. Here, we characterized three new satellitomes from distinct characid fish (Psalidodon fasciatus, P. bockmanni, and Astyanax lacustris) using a combination of genomic, cytogenetic, and bioinformatic protocols. We also compared our data with the available satellitome of P. paranae. We described 57 satellite DNA (satDNA) families of P. fasciatus (80 variants), 50 of P. bockmanni (77 variants), and 33 of A. lacustris (54 variants). Our analyses demonstrated that several sequences were shared among the analyzed species, while some were restricted to two or three species. In total, we isolated 104 distinctive satDNA families present in the four species, of which 10 were shared among all four. Chromosome mapping revealed that the clustered satDNA was mainly located in the subtelomeric and pericentromeric areas. Although all Psalidodon species demonstrated the same pattern of clusterization of satDNA, the number of clusters per genome was variable, indicating a high dynamism of these sequences. In addition, our results expand the knowledge of the As51 satellite DNA family, revealing that P. bockmanni and P. paranae exhibited an abundant variant of 39 bp, while P. fasciatus showed a variant of 43 bp. The majority of satDNAs in the satellitomes analyzed here presented a common library repetitive sequence in Psalidodon and Astyanax, with abundance variations in each species, as expected for closely related groups. In addition, we concluded that the most abundant satDNA in Psalidodon (As51) passed through a diversification process in this group, resulting in new variants exclusive of Psalidodon.
Nanomaterials in Animal Husbandry: Research and Prospects
Authors: Wang Kun , Lu Xubin , Lu Yi , Wang Jiacheng , Lu Qinyue , Cao Xiang , Yang Yi , Yang Zhangping
Published: June 2022

Anti-inflammatory, antiviral, and anti-cancer treatments are potential applications of nanomaterials in biology. To explore the latest discoveries in nanotechnology, we reviewed the published literature, focusing on co-assembled nanoparticles for anti-inflammatory and anti-tumor properties, and their applications in animal husbandry. The results show that nanoparticles have significant anti-inflammation and anti-tumor effects, demonstrating broad application prospects in animal breeding. Furthermore, pooled evidence suggests that the mechanism is to have a positive impact on inflammation and tumors through the specific drug loading by indirectly or directly targeting the disease sites. Because the precise regulatory mechanism remains unclear, most studies have focused on regulating particular sites or even specific genes in the nucleus by targeting functional co-assembled nanoparticles. Hence, despite the intriguing scenarios for nanotechnology in farmed animals, most results cannot yet be translated into field applications. Overall, nanomaterials outperformed similar materials in terms of anti-inflammatory and anti-tumor. Nanotechnology also has promising applications in animal husbandry and veterinary care, and its application and development in animal husbandry remain an exciting area of research.
Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia
Authors: Yang Yang , Su Yi , Wei Guiming , Kang Zhewei , Lu Zhe , Liao Yundan , Lu Tianlan , Yan Hao , Yue Weihua , Qin Ying , Zhang Yuyanan
Published: June 2022

BACKGROUND: Schizophrenia is a severe mental disorder with high heritability, and cognitive dysfunction is one of the core features. Growing evidence suggests the genetic risk of schizophrenia may contribute to cognitive impairments. The variant rs1635 (nucleotide sequence: c.455C>A; amino acid sequence: T152N) located on the (NFKB activating protein like) NKAPL gene confers risk for schizophrenia and might play a role in the neurodevelopmental process, which is particularly relevant to cognitive function. However, the relationship between rs1635 and cognitive function remains unclear.

METHODS: A total of 130 patients with early-onset schizophrenia (EOS) and 300 patients with adult-onset schizophrenia (AOS) of Han Chinese were recruited and underwent neurocognitive tests by using the MATRICS Consensus Cognitive Battery (MCCB). The NKAPL rs1635 was genotyped by using DNA sequencing. The peripheral blood NKAPL mRNA expression level was examined in 152T or 152N carriers (n = 20) in EOS patients, by using the qRT-PCR. The phosphorylation level of NAKPL T152N polymorphism was detected by cell experiments. In utero electroporation of mouse embryos was examined to explore the effect of Nkapl on neuronal migration.

RESULTS: Compared with rs1635 AA and AC carriers, CC (the CC genotype encodes the protein NKAPL-152T) carriers of EOS patients performed better in cognitive domain of speed of processing (t = 2.644, p = 0.009), trail making test (t = 2.221, p = 0.028) and category fluency (t = 2.578, p = 0.011). However, patients with AOS exhibited no significant differences in seven domains among the three genotype groups. There were no significant differences in cognitive performance between EOS and AOS. In EOS patients, NKAPL mRNA level in NKAPL-152N carriers is significantly lower than that of NKAPL-152T carriers. The phosphorylation level of NKAPL-152N is significantly decreased compared to NKAPL-152T. In utero electroporation showed that Nkapl deletion impairs the embryonic radial migration process.

CONCLUSION: The present study found that NKAPL rs1635 was associated with cognitive impairments and peripheral blood mRNA expression level in EOS patients. The NKAPL full-length protein is required for embryonic cortical neuronal migration. The phosphorylation level of NKAPL-152N is significantly decreased. The NKAPL T152N may affect the NAKPL mRNA expression level and embryonic cortical neuronal migration by regulating the NAKPL protein phosphorylation. These data suggest that NKAPL rs1635 affects cognitive function by regulating early brain development in early-onset schizophrenia.
Milk Fat Globule Membrane Attenuates Acute Colitis and Secondary Liver Injury by Improving the Mucus Barrier and Regulating the Gut Microbiota
Authors: Wu Zhenhua , Liu Xiaoyi , Huang Shimeng , Li Tiantian , Zhang Xiangyu , Pang Jiaman , Zhao Junying , Chen Lijun , Zhang Bing , Wang Junjun , Han Dandan
Published: June 2022

Objective

Inflammatory bowel disease (IBD) often occurs along with extraintestinal manifestations, including hepatic injury. Milk fat globule membrane (MFGM) is an active substance with a potential anti-inflammation activity. However, its alleviated effect and mechanisms in IBD as well as the IBD-induced secondary liver injury are still unclear.

Methods

C57BL/6J mice were administered with a 21-day oral gavage of MFGM, followed by 7 days of drinking water with 4% dextran sulfate sodium (DSS). Disease activity index (DAI), histological features, and cytokines of the colon and liver were evaluated. Then, RNA-seq of the colon and liver was conducted. The gut microbiota was assessed by analyzing 16S rRNA gene sequences, and finally the integrity and the function of the mucus barrier were evaluated by Alcian blue staining, real-time quantitative PCR, and ELISA.

Results

Prophylactic MFGM treatment was effective against colitis to include effects in body weight loss, DAI score, colonic length, intestinal pathology, and histological score. Additionally, prophylactic MFGM decreased the levels of interleukin (IL)-1β, IL-6, and myeloperoxidase in colonic tissue, while it increased the IL-10 level. Moreover, the gene expressions of MUC2, MUC4, Reg3b, and Reg3g associated with the production of the molecular mediator of immune response, membrane invagination, and response to protozoan were strikingly upregulated when administered with MFGM. On the other hand, the beneficial effects of MFGM were related to the enriched abundance of genera such as Faccalibacumum and Roseburia in feces samples. Consistently, the administration of MFGM was also found to alleviate DSS-induced hepatic injury. Furthermore, the glutathione transferase activity pathway was enriched in the liver of MFGM-treated mice after DSS administration. Mechanistically, prophylactic MFGM enhanced the mucosal barrier by increasing the gene levels of Reg3b and Reg3g. Meanwhile, the alleviation of MFGM on liver injury was dependent on the reduced hepatic oxidative stress.

Conclusions

MFGM attenuated colitis and hepatic injury by maintaining the mucosal barrier and bacterial community while inhibiting oxidative stress, which might be an effective therapy of hepatic injury secondary to IBD.
Case Report: Successful Treatment With Monoclonal Antibodies in One APDS Patient With Prolonged SARS-CoV-2 Infection Not Responsive to Previous Lines of Treatment
Authors: Rivalta Beatrice , Amodio Donato , Giancotta Carmela , Santilli Veronica , Pacillo Lucia , Zangari Paola , Cotugno Nicola , Manno Emma Concetta , Finocchi Andrea , Bernardi Stefania , Colagrossi Luna , Gentile Leonarda , Russo Cristina , Perno Carlo Federico , Rossi Paolo , Cancrini Caterina , Palma Paolo
Published: June 2022

We described the case of a patient affected by activated PI3K-kinase delta syndrome (APDS) and a long-lasting and pauci-symptomatic SARS-CoV-2 infection, treated with multiple therapeutic agents including remdesivir and SARS-CoV-2-neutralizing monoclonal antibodies. We detected the clearance of the virus 105 days from the first positive swab and 7 days after monoclonal antibody administration. At genotyping, the SARS-CoV-2 virus resulted as wild type on all samples tested. This case shows the monoclonal antibodies’ good tolerability and efficacy in reducing viral shedding in long-lasting infections refractory to other treatments.
Candidate Drugs Screening for Behcet’s Disease Based on Bioinformatics Analysis and Mouse Experiments
Authors: Xia Qinyun , Lyu Chujun , Li Fang , Pang Binbin , Guo Xiaoyu , Ren He , Xing Yiqiao , Chen Zhen
Published: June 2022

Background

Behcet’s disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used bioinformatics to identify potential drugs and validated them in mouse models.

Methods

Behcet’s disease-related target genes and proteins were screened in the PubMed and UVEOGENE databases. The biological functions and pathways of the target genes were analyzed in detail by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed by the STRING database, and hub genes were identified by the Cytoscape plug-in CytoHubba. Gene-drug interactions were identified from the DGIdb database. Experimental autoimmune uveitis (EAU) mice were used as an animal model for drug validation.

Results

A total of 249 target genes and proteins with significant differences in BD were screened, and the results of functional enrichment analysis suggested that these genes and proteins were more located on the cell membrane, involved in regulating the production of cytokines and affecting the activity of cytokines. They mainly regulated “Cytokine- Cytokine receptor interaction”, “Inflammatory bowel disease (IBD)” and “IL-17 signaling Pathway”. In addition, 10 hub genes were obtained through PPI network construction and CytoHubba analysis, among which the top 3 hub genes were closely related to BD. The DGIdb analysis enriched seven drugs acting together on the top 3 hub genes, four of which were confirmed for the treatment of BD or its complications. There is no evidence in the research to support the results in omeprazole, rabeprazole, and celastrol. However, animal experiments showed that rabeprazole and celastrol reduced anterior chamber inflammation and retinal inflammation in EAU mice.

Conclusions

The functional analysis of genes and proteins related to BD, identification of hub genes, and validation of potential drugs provide new insights into the disease mechanism and potential for the treatment of BD.
Multi-Modal Single-Cell Sequencing Identifies Cellular Immunophenotypes Associated With Juvenile Dermatomyositis Disease Activity
Authors: Neely Jessica , Hartoularos George , Bunis Daniel , Sun Yang , Lee David , Kim Susan , Ye Chun Jimmie , Sirota Marina
Published: June 2022

Juvenile dermatomyositis (JDM) is a rare autoimmune condition with insufficient biomarkers and treatments, in part, due to incomplete knowledge of the cell types mediating disease. We investigated immunophenotypes and cell-specific genes associated with disease activity using multiplexed RNA and protein single-cell sequencing applied to PBMCs from 4 treatment-naïve JDM (TN-JDM) subjects at baseline, 2, 4, and 6 months post-treatment and 4 subjects with inactive disease on treatment. Analysis of 55,564 cells revealed separate clustering of TN-JDM cells within monocyte, NK, CD8+ effector T and naïve B populations. The proportion of CD16+ monocytes was reduced in TN-JDM, and naïve B cells and CD4+ Tregs were expanded. Cell-type differential gene expression analysis and hierarchical clustering identified a pan-cell-type IFN gene signature over-expressed in TN-JDM in all cell types and correlated with disease activity most strongly in cytotoxic cell types. TN-JDM CD16+ monocytes expressed the highest IFN gene score and were highly skewed toward an inflammatory and antigen-presenting phenotype at both the transcriptomic and proteomic levels. A transitional B cell population with a distinct transcriptomic signature was expanded in TN-JDM and characterized by higher CD24 and CD5 proteins and less CD39, an immunoregulatory protein. This data provides new insights into JDM immune dysregulation at cellular resolution and serves as a novel resource for myositis investigators.
Nuclear Coregulatory Complexes in Tregs as Targets to Promote Anticancer Immune Responses
Authors: Christensen Lanette M. , Hancock Wayne W.
Published: June 2022

T-regulatory (Treg) cells display considerable heterogeneity in their responses to various cancers. The functional differences among this cell type are heavily influenced by multiprotein nuclear complexes that control their gene expression. Many such complexes act mechanistically by altering epigenetic profiles of genes important to Treg function, including the forkhead P3 (Foxp3) transcription factor. Complexes that form with certain members of the histone/protein deacetylase (HDAC) class of enzymes, like HDACs 1, 2, and 3, along with histone methyltransferase complexes, are important in the induction and stabilization of Foxp3 and Treg identity. The functional behavior of both circulating and intratumoral Tregs greatly impacts the antitumor immune response and can be predictive of patient outcome. Thus, targeting these regulatory complexes within Tregs may have therapeutic potential, especially in personalized immunotherapies.
A Novel Drug Combination of Mangiferin and Cinnamic Acid Alleviates Rheumatoid Arthritis by Inhibiting TLR4/NFκB/NLRP3 Activation-Induced Pyroptosis
Authors: Li Weijie , Wang Kexin , Liu Yudong , Wu Hao , He Yan , Li Congchong , Wang Qian , Su Xiaohui , Yan Shikai , Su Weiwei , Zhang Yanqiong , Lin Na
Published: June 2022

Growing evidence shows that Baihu-Guizhi decoction (BHGZD), a traditional Chinese medicine (TCM)-originated disease-modifying anti-rheumatic prescription, may exert a satisfying clinical efficacy for rheumatoid arthritis (RA) therapy. In our previous studies, we verified its immunomodulatory and anti-inflammatory activities. However, bioactive compounds (BACs) of BHGZD and the underlying mechanisms remain unclear. Herein, an integrative research strategy combining UFLC-Q-TOF-MS/MS, gene expression profiling, network calculation, pharmacokinetic profiling, surface plasmon resonance, microscale thermophoresis, and pharmacological experiments was carried out to identify the putative targets of BHGZD and underlying BACs. After that, both in vitro and in vivo experiments were performed to determine the drug effects and pharmacological mechanisms. As a result, the calculation and functional modularization based on the interaction network of the “RA-related gene–BHGZD effective gene” screened the TLR4/PI3K/AKT/NFκB/NLRP3 signaling-mediated pyroptosis to be one of the candidate effective targets of BHGZD for reversing the imbalance network of “immune-inflammation” during RA progression. In addition, both mangiferin (MG) and cinnamic acid (CA) were identified as representative BACs acting on that target, for the strong binding affinities between compounds and target proteins, good pharmacokinetic features, and similar pharmacological effects to BHGZD. Notably, both BHGZD and the two-BAC combination of MG and CA effectively alleviated the disease severity of the adjuvant-induced arthritis-modified rat model, including elevating pain thresholds, relieving joint inflammation and bone erosion via inhibiting NF-κB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream caspase-1, the reduced release of IL-1β and IL-18, and the modulation of GSDMD-mediated pyroptosis. Consistent data were obtained based on the in vitro pyroptosis cellular models of RAW264.7 and MH7A cells induced by LPS/ATP. In conclusion, these findings offer an evidence that the MG and CA combination identified from BHGZD may interact with TLR4/PI3K/AKT/NFκB signaling to inhibit NLRP3 inflammasome activation and modulate pyroptosis, which provides the novel representative BACs and pharmacological mechanisms of BHGZD against active RA. Our data may shed new light on the mechanisms of the TCM formulas and promote the modernization development of TCM and drug discovery.
In Silico Docking of Nematode β-Tubulins With Benzimidazoles Points to Gene Expression and Orthologue Variation as Factors in Anthelmintic Resistance
Authors: Jones Ben P. , van Vliet Arnoud H. M. , LaCourse E. James , Betson Martha
Published: June 2022

The efficacy of benzimidazole anthelmintics can vary depending on the target parasite, with Ascaris nematodes being highly responsive, and whipworms being less responsive. Anthelmintic resistance has become widespread, particularly in strongyle nematodes such as Haemonchus contortus in ruminants, and resistance has recently been detected in hookworms of humans and dogs. Past work has shown that there are multiple β-tubulin isotypes in helminths, yet only a few of these contribute to benzimidazole interactions and resistance. The β-tubulin isotypes of ascarids and soil-transmitted helminths were identified by mining available genome data, and phylogenetic analysis showed that the ascarids share a similar repertoire of seven β-tubulin isotypes. Strongyles also have a consistent pattern of four β-tubulin isotypes. In contrast, the whipworms only have two isotypes, with one of these clustering more basally and distinct from any other group. Key β-tubulin isotypes selected based on previous studies were the focus of in silico molecular docking simulations to look at the interactions with benzimidazoles. These showed that all β-tubulins had similar interactions with benzimidazoles and maintained the key bond with residue E198 in all species, indicating similar mechanisms of action. However, the interaction was stronger and more consistent in the strongyles and whipworms than it was in the ascarids. Alteration of β-tubulin isotypes with the common resistance-associated mutations originally identified in H. contortus resulted in similar interaction modeling for all species. In conclusion, ascarids, strongyles, and whipworms all have their own unique repertoire of β-tubulins, which could explain why benzimidazole resistance and susceptibility varies between these groups of parasites. These data complement recent work that has highlighted the roles of essential residues in benzimidazole drug binding and shows that there is a separation between strongyle parasites that frequently develop resistance and ascarid parasites, which have been much less prone to developing resistance.
Model Simulation of Storm Surge in the Northwestern South China Sea Under the Impact of Sea Level Rise: A Case Study of Super Typhoon Rammasun (2014)
Authors: Zhou Yongdong , Ni Zekai , Vetter Philip Adam , Xu Hongzhou , Hong Bo , Wang Hui , Li Wenshan , Liu Sumin
Published: June 2022

Because of global warming, the sea level is expected to continue to rise, possibly having a significant impact on the intensities and spatial distribution characteristics of coastal storm surges. In this study, we took super typhoon Rammasun (2014) as a case study and applied the SCHISM (Semi-implicit Cross-scale Hydroscience Integrated System Model) to simulate storm surge in the northwestern South China Sea under future sea level rise (SLR) scenarios. To improve the accuracy of storm surge hindcast, we used reconstructed wind field to drive the model in which ERA5 reanalysis data were superposed on the wind field calculated from the Holland parametric cyclone model. The results show that the storm surge hindcast was significantly improved by using this reconstructed wind forcing. 2-D and 3-D model hindcast capabilities were compared; the 3-D model reproduced the storm surge better. The regional sea level projections in 2050, 2100, 2200, and 2300 for RCP 4.5 scenarios (provided by the IPCC AR6 dataset) were superposed on the original water depth as the predicted sea levels, then those depths were used in models of storm surge in the study area under a typhoon identical to Rammasun. Model results demonstrate that storm surge peaks in most sea areas decrease nearly linearly with SLR, especially in regions of high surges.
mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study
Authors: Pinchera Biagio , Spirito Lorenzo , Buonomo Antonio Riccardo , Foggia Maria , Carrano Rosa , Salemi Fabrizio , Schettino Elisa , Papa Fortuna , La Rocca Roberto , Crocetto Felice , Napolitano Luigi , Villari Riccardo , Gentile Ivan
Published: June 2022

Introduction

In solid organ transplant recipients, COVID-19 is associated with a poor prognosis because of immunosuppression. Some studies suggest a potential therapeutic role of mammalian Target of Rapamycin (mTOR) inhibitors in SARS-CoV-2 infection. This study aimed to assess the impact of mTOR employment on the evolution and outcome of SARS-CoV-2 infection in solid organ transplant recipients.

Methods

We enrolled kidney transplant patients attending the Azienda Ospedaliera Universitaria Federico II in Naples and followed up on these patients from March 2020 to June 2021. We evaluated the risk of acquiring the SARS-CoV-2 infection, the clinical presentation of the disease, and its outcome together with the type of immunosuppressive therapy. Finally, we assessed the impact of mTOR inhibitors on relevant clinical metrics of SARS-CoV-2 infection.

Results

We enrolled 371 patients, of whom 56 (15.1%) contracted SARS-CoV-2 infection during the period of the study. There were no differences observed among the different immunosuppressive therapies concerning the risk of acquiring SARS-CoV-2 infection. In contrast, the type of immunosuppressive therapy had a significant impact on the outcome of the disease. In detail, patients who received mTOR inhibitors, as part of their immunosuppressive therapy, compared to other regimens had a lower chance of developing a moderate or severe form of the disease (OR = 0.8, 95, CI: (0.21–0.92), P = 0.041).

Conclusion

In kidney transplant patients, the use of mTOR inhibitors as part of an immunosuppressive regimen is associated with a better prognosis in the case of COVID-19.
Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma
Authors: Zhou Bo , Li Manxiang , Chen Tianjun , She Jianqing
Published: June 2022

Background

Durvalumab, as a PD-L1 inhibitor, is commonly used for the treatment of various cancers. Adverse events associated with the therapy include hepatitis, nephritis, dermatitis, and myocarditis. Especially, myocarditis as an adverse event after PD-L1 inhibitor therapy is characterized for its low incidence and high mortality.

Case Summary

Here we present a rare case of a 67-year-old male with lung squamous cell carcinoma complicated with empyema who experienced myocarditis after only PD-L1 inhibitor durvalumab monotherapy. He presented with markedly decrease left ventricular ejection fraction, elevated Natriuretic peptide BNP, Troponin T, Troponin I, ESR, CRP and interleukin-6. The electrocardiogram showed sinus tachycardia, low voltage of limb leads, T wave inversion in anterior waves and V1-V3 QS type. Myocardial injury occurred in a short period and quickly returned to normal after glucocorticoids therapy.

Conclusion

This case report is of clinical value for the treatment of PD-L1 related myocarditis.
Static Balance and Chair-Rise Performance in Neurogeriatric Patients: Promising Short Physical Performance Battery-Derived Predictors of Fear of Falling
Authors: Scholz Katharina , Geritz Johanna , Kudelka Jennifer , Rogalski Marten , Niemann Katharina , Maetzler Corina , Welzel Julius , Drey Michael , Prell Tino , Maetzler Walter
Published: June 2022

Background:

Fear of falling (FOF) negatively affects health-related quality of life and is common in neurogeriatric patients, however, related parameters are not well understood. This study investigated the relationship between FOF, physical performance (as assessed with the Short Physical Performance Battery and its subscores) and other aspects of sarcopenia in a sample of hospitalized neurogeriatric patients.

Methods

In 124 neurogeriatric patients, FOF was assessed with the Falls Efficacy Scale International (FES-I). Physical performance was measured using the Short Physical Performance Battery (SPPB) including walking duration, balance and five times sit-to-stand task (5xSST) subscores. Appendicular skeletal muscle mass (ASMM) was estimated with the cross-validated Sergi equation using Bioelectrical impedance analysis measures. The Depression im Alter-Skala (DIA-S) was used to assess depressive symptoms. Multiple regression models with FES-I score as outcome variable were computed using backward selection with AICc as selection criterion, including: (i) SPPB total score, ASMM/height2, grip strength, age, gender, positive fall history, number of medications, use of a walking aid, DIA-S score and Montreal Cognitive Assessment (MoCA) score; and (ii) SPPB subscores, ASMM/height2, grip strength, age, gender, positive fall history, number of medications, DIA-S score and MoCA score, once with and once without including use of a walking aid as independent variable.

Results

Lower SPPB total score, as well as lower SPPB balance and 5xSST subscores were associated with higher FES-I scores, but SPPB walking duration subscore was not. Moreover, DIA-S, number of medications and use of a walking aid were significantly associated with FOF.

Conclusion

Our preliminary results suggest that -if confirmed by subsequent studies- it may be worthwhile to screen patients with low SPPB balance and 5xSST subscores for FOF, and to treat especially these mobility deficits in neurogeriatric patients with FOF. Moreover, training neurogeriatric patients to use their walking aids correctly, critical evaluation of medication and treating depressive symptoms may further help reduce FOF in this highly vulnerable cohort.
Trends, Advantages and Disadvantages in Combined Extracorporeal Lung and Kidney Support From a Technical Point of View
Authors: Martins Costa Ana , Halfwerk Frank , Wiegmann Bettina , Neidlin Michael , Arens Jutta
Published: June 2022

Extracorporeal membrane oxygenation (ECMO) provides pulmonary and/or cardiac support for critically ill patients. Due to their diseases, they are at high risk of developing acute kidney injury. In that case, continuous renal replacement therapy (CRRT) is applied to provide renal support and fluid management. The ECMO and CRRT circuits can be combined by an integrated or parallel approach. So far, all methods used for combined extracorporeal lung and kidney support present serious drawbacks. This includes not only high risks of circuit related complications such as bleeding, thrombus formation, and hemolysis, but also increase in technical workload and health care costs. In this sense, the development of a novel optimized artificial lung device with integrated renal support could offer important treatment benefits. Therefore, we conducted a review to provide technical background on existing techniques for extracorporeal lung and kidney support and give insight on important aspects to be addressed in the development of this novel highly integrated artificial lung device.
First 1000 Days and Beyond After Birth: Gut Microbiota and Necrotizing Enterocolitis in Preterm Infants
Authors: Zeng Shuqin , Ying Junjie , Li Shiping , Qu Yi , Mu Dezhi , Wang Shaopu
Published: June 2022

Preterm birth remains a major maternal and infant health issue worldwide particularly with an increase in the global preterm birth rate, which requires more interventions to manage the consequences of preterm birth. In addition to traditional complications, recent studies have shown that the succession of gut microbiota of preterm infants is disordered due to the systemic physiological immaturity, which confers negative influences on the growth, development, and health of infants. In the present study, we briefly discussed the prevalence of preterm birth worldwide and then highlighted the signatures of gut microbiota in preterm infants within the first 1000 days of life after the birth categorized into birth, infancy, and childhood. Afterward, we focused on the potential association of clinical phenotypes typically associated with preterm birth (i.e., necrotizing enterocolitis) with gut microbiota, and the potential directions for future studies in this field are finally discussed.
High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
Authors: Jee Hyunseok , Park Eunmi , Hur Kyunghoon , Kang Minjeong , Kim Yoosik
Published: June 2022

High-intensity aerobic exercise (90% of the maximal heart rate) can effectively suppress cancer cell proliferation in vivo. However, the molecular effects of exercise and its relevance to cancer prevention remain uninvestigated. In this study, mice with colorectal cancer were subjected to high-intensity aerobic exercise, and mRNA-seq analysis was performed on the heart, lungs, and skeletal muscle tissues to analyze the genome-wide molecular effects of exercise. The skeletal muscle-derived genes with exercise-dependent differential expression were further evaluated for their effects on colorectal cancer cell viability. Compared to the results obtained for the control groups (healthy and cancer with no exercise), the regular and high-intensity aerobic physical activity in the mice produced positive results in comprehensive parameters (i.e., food intake, weight gain, and survival rate). A heatmap of differentially expressed genes revealed markedly different gene expression patterns among the groups. RNA-seq analysis of 23,282 genes expressed in the skeletal muscle yielded several anticancer effector genes (e.g., Trim63, Fos, Col1a1, and Six2). Knockdown and overexpression of selected anticancer genes repressed CT26 murine colorectal carcinoma cell proliferation by 20% (p < 0.05). Our findings, based on the aerobic exercise cancer mouse model, suggest that high-intensity aerobic exercise results in a comprehensive change in the expression patterns of genes, particularly those that can affect cancer cell viability. Such an approach may identify key exercise-regulated genes that can help the body combat cancer.
The Mechanism and Clinical Application of Constraint-Induced Movement Therapy in Stroke Rehabilitation
Authors: Wang Dong , Xiang Junlu , He Ying , Yuan Min , Dong Li , Ye Zhenli , Mao Wei
Published: June 2022

Constraint-induced movement therapy (CIMT) has been widely applied in stroke rehabilitation, and most relevant studies have shown that CIMT helps improve patients’ motor function. In practice, however, principal issues include inconsistent immobilization durations and methods, while incidental issues include a narrow application scope and an emotional impact. Although many studies have explored the possible internal mechanisms of CIMT, a mainstream understanding has not been established.
Extra-Cranial Carotid Artery Stenosis: An Objective Analysis of the Available Evidence
Authors: Abbott Anne L.
Published: June 2022

Background and Purpose

Carotid stenosis is arterial disease narrowing of the origin of the internal carotid artery (main brain artery). Knowing how to best manage this is imperative because it is common in older people and an important cause of stroke. Inappropriately high expectations have grown regarding the value of carotid artery procedures, such as surgery (endarterectomy) and stenting, for lowering the stroke risk associated with carotid stenosis. Meanwhile, the improving and predominant value of medical intervention (lifestyle coaching and medication) continues to be underappreciated.

Methods and Results

This article aims to be an objective presentation and discussion of the scientific literature critical for decision making when the primary goal is to optimize patient outcome. This compilation follows from many years of author scrutiny to separate fact from fiction. Common sense conclusions are drawn from factual statements backed by original citations. Detailed research methodology is given in cited papers. This article has been written in plain language given the importance of the general public understanding this topic. Issues covered include key terminology and the economic impact of carotid stenosis. There is a summary of the evidence-base regarding the efficacy and safety of procedural and medical (non-invasive) interventions for both asymptomatic and symptomatic patients. Conclusions are drawn with respect to current best management and research priorities. Several “furphies” (misconceptions) are exposed that are commonly used to make carotid stenting and endarterectomy outcomes appear similar. Ongoing randomized trials are mentioned and why they are unlikely to identify a routine practice indication for carotid artery procedures. There is a discussion of relevant worldwide guidelines regarding carotid artery procedures, including how they should be improved. There is an outline of systematic changes that are resulting in better application of the evidence-base.

Conclusion

The cornerstone of stroke prevention is medical intervention given it is non-invasive and protects against all arterial disease complications in all at risk. The “big” question is, does a carotid artery procedure add patient benefit in the modern era and, if so, for whom?