bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Assessment of Typhoon Disaster Chains in the Guangdong–Hong Kong–Macau Greater Bay Area, China
Authors: Wang Yujie , Yin Yizhou , Song Lianchun
Published: March 2022

The typhoon disaster chain is one of the leading climate risks in constructing the Guangdong–Hong Kong–Macau Greater Bay Area (GBA). In this study, the risks of the typhoon disaster chains including typhoon-induced gales, rainstorms, and storm surges in the GBA, as well as the comprehensive risk of typhoon disaster, are investigated at county level by comprehensively analyzing the hazard, exposure, and vulnerability. The results show that the high- and very-high-risk areas of typhoon–gale disaster chain are located in Zhuhai, Zhongshan, Foshan, Dongguan, central-southern Jiangmen, southern Shenzhen, and parts of Huizhou. The high- and very high-risk areas of typhoon–rainstorm disaster chain include Zhuhai, Zhongshan, Shenzhen, central-southern Foshan, northern Dongguan, central Jiangmen, and central Huizhou. Regarding the typhoon–storm surge disaster chain, the areas at high and very high risk are located in Zhuhai, eastern Zhongshan, and the coastal areas of the Pearl River Estuary. In addition, the comprehensive risk of typhoon disaster is very high in Zhuhai and high in Zhongshan, Jiangmen, Dongguan, and Shenzhen. By verifying the spatial correlation between typhoon disaster risk indexes and actual losses, it is found that the comprehensive risk index of typhoon disaster constructed in this study can better reflect the actual losses. Overall, the findings of this study can provide a scientific basis for typhoon disaster prevention and mitigation in the GBA, and it can also serve as a reference for typhoon disaster risk research in other areas.
Effects of Desk-Bike Cycling on Phonological Working Memory Performance in Adolescents With Attention Deficit Hyperactivity Disorder
Authors: Ruiter Margina , Görlich Emma , Loyens Sofie , Wong Jacqueline , Paas Fred
Published: March 2022

We investigated the effects of active workstations on cognitive control functions in individuals diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). In a fully counterbalanced randomized control design, we examined the effects of cycling on a desk bike on phonological working memory (WM) in 18 adolescents with ADHD. Adolescents performed a phonological WM test across two separate sessions during which they either cycled or not. It was hypothesized that participants would perform better on the WM task while cycling as compared to seated-rest. Results showed that total WM performance was not affected by desk-bike cycling. Exploratory analyses suggested that cycling during more difficult trials (i.e., high WM demands) is beneficial for WM performance. More research is needed to shed light on how task difficulty moderates the potential compensatory effect of desk-bike cycling on WM performance in adolescent ADHD participants.
Shipborne Observations of Chemical Characterization and Light Extinction of Aerosol Along the Yangtze River, China
Authors: Chen Dong , Zhao Qiuyue , Li Li , Xia Sijia , Chen Feng , Wei Mengqi , Li Huipeng , Zhang Lei , Guan Miao
Published: March 2022

The study of air quality over the Yangtze River is important for the pollution of urban agglomeration along the longest river in China. A comprehensive 15-day shipborne observation was conducted in the Yangtze River of the Jiangsu section in the summer of 2019. Through online observation and offline chemistry analysis of aerosol and gaseous pollutants, the result showed that the air pollution over the Yangtze River was more severe than that in surrounding cities. Sulfate, nitrate, and ammonium (SNA) dominated the water-soluble inorganic species and accounted for 35.0% ± 7.3% of the fine particle concentration (PM2.5) along the Yangtze River. The high concentration of sulfate in the droplet mode (0.56–1.0 μm) was due to the formation of sulfate through in-cloud processes under high sulfur dioxide (SO2) concentration by ship emission and high relative humidity along the river. The strong correlation between the measured mass absorption efficiency value by carbon analyzer and that simulated based on the assumption of core–shell suggested that the core–shell mode was the main composition form of aerosol in the Yangtze River. The scattering effect was the main part of the aerosol light extinction, and the scattering coefficient of 0.4- to 1.1-μm particles accounted for 85.0% of the total extinction coefficient. Positive matrix factorization model was applied for the source apportionment of particle size segment of main extinction contribution (0.4–2.1 μm), and the result showed that secondary nitrate, ship emission, coal combustion, fugitive dust, and biomass burning were the main sources of aerosols in the Yangtze River. After source reanalysis, the result indicated that the contribution of secondary nitrate from nitrogen oxide (NOx) by ship emission and coal combustion should not be ignored.
Resequencing and Signatures of Selective Scans Point to Candidate Genetic Variants for Hair Length Traits in Long-Haired and Normal-Haired Tianzhu White Yak
Authors: Bao Qi , Ma Xiaoming , Jia Congjun , Wu Xiaoyun , Wu Yi , Meng Guangyao , Bao Pengjia , Chu Min , Guo Xian , Liang Chunnian , Yan Ping
Published: March 2022

Tianzhu white yak is a rare local yak breed with a pure white coat in China. In recent years, breeders have discovered long-haired individuals characterized by long hair on the forehead in the Tianzhu white yak, and the length and density of the hair on these two parts of the body are higher than that of the normal Tianzhu white yak. To elucidate the genetic mechanism of hair length in Tianzhu white yak, we re-sequence the whole genome of long-haired Tianzhu White yak (LTWY) (n = 10) and normal Tianzhu White yak (NTWY) (n = 10). Then, fixation index (FST), θπ ratio, cross-population composite likelihood ratio (XP-CLR), integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and one composite method, the de-correlated composite of multiple signals (DCMS) were performed to discover the loci and genes related to long-haired traits. Based on five single methods, we found two hotspots of 0.2 and 1.1 MB in length on chromosome 6, annotating two (FGF5, CFAP299) and four genes (ATP8A1, SLC30A9, SHISA3, TMEM33), respectively. Function enrichment analysis of genes in two hotspots revealed Ras signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway were involved in the process of hair length differences. Besides, the DCMS method further found that four genes (ACOXL, PDPK1, MAGEL2, CDH1) were associated with hair follicle development. Henceforth, our work provides novel genetic insights into the mechanisms of hair growth in the LTWY.
Management of BMI Is a Potential New Approach for the Prevention of Idiopathic Pulmonary Fibrosis
Authors: Ma Yuchao , Feng Chang , Tang Haibo , Deng Peizhi , Li Yalan , Wang Jie , Zhu Shaihong , Zhu Liyong
Published: March 2022

Aims: Current idiopathic pulmonary fibrosis (IPF) therapies usually show a poor outcome or treatment efficacy. The search for new risk factors has significant implications in preventing, delaying, and treating IPF. The association between obesity and the risk of IPF is not clear. This study aimed to investigate the role of different obesity types in IPF risk, which provides the possibility of weight loss as a new approach for IPF prevention.

Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect of obesity on IPF risk. We collected summary data of genetically determined obesity-related traits, including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) from large-scale consortia (the sample size ranging from 232,101 to 681,275), and genetic association with IPF from one of the largest meta-analyses including 2,668 cases. A total of 35–469 single nucleotide polymorphisms were selected as instrumental variables for obesity-related traits. We further performed multivariable MR to estimate the independent effect of BMI and WC on the risk of IPF.

Results: Increased BMI and WC were associated with higher risk of IPF [odds ratio (OR) = 1.51, 95% confidence interval (CI) (1.22–1.87), p = 1.27 × 10–4, and OR = 1.71, 95% CI (1.08–2.72), p = 2.33 × 10–2, respectively]. Similar results for the BMI and WC were obtained in the replicated analysis. Subsequently, only the result for BMI survived following the multiple testing correction and showed good consistency with the weighted median estimator. Sensitivity analyses indicated that there was no heterogeneity or horizontal pleiotropy for MR estimations. Further multivariable MR suggested that the BMI showed the same direction and similar magnitude with that in the univariable MR analysis. There was little evidence to support the causal role of WHR on the risk of IPF in this study.

Conclusion: Genetically determined BMI demonstrates a causal risk for IPF, which offers a novel insight into probing potential mechanisms. Meanwhile, these results also suggest that weight loss may be beneficial to IPF prevention.
Investigating the Functional Role of Hypothetical Proteins From an Antarctic Bacterium Pseudomonas sp. Lz4W: Emphasis on Identifying Proteins Involved in Cold Adaptation
Authors: Ijaq Johny , Chandra Deepika , Ray Malay Kumar , Jagannadham M. V.
Published: March 2022

Exploring the molecular mechanisms behind bacterial adaptation to extreme temperatures has potential biotechnological applications. In the present study, Pseudomonas sp. Lz4W, a Gram-negative psychrophilic bacterium adapted to survive in Antarctica, was selected to decipher the molecular mechanism underlying the cold adaptation. Proteome analysis of the isolates grown at 4°C was performed to identify the proteins and pathways that are responsible for the adaptation. However, many proteins from the expressed proteome were found to be hypothetical proteins (HPs), whose function is unknown. Investigating the functional roles of these proteins may provide additional information in the biological understanding of the bacterial cold adaptation. Thus, our study aimed to assign functions to these HPs and understand their role at the molecular level. We used a structured insilico workflow combining different bioinformatics tools and databases for functional annotation. Pseudomonas sp. Lz4W genome (CP017432, version 1) contains 4493 genes and 4412 coding sequences (CDS), of which 743 CDS were annotated as HPs. Of these, from the proteome analysis, 61 HPs were found to be expressed consistently at the protein level. The amino acid sequences of these 61 HPs were submitted to our workflow and we could successfully assign a function to 18 HPs. Most of these proteins were predicted to be involved in biological mechanisms of cold adaptations such as peptidoglycan metabolism, cell wall organization, ATP hydrolysis, outer membrane fluidity, catalysis, and others. This study provided a better understanding of the functional significance of HPs in cold adaptation of Pseudomonas sp. Lz4W. Our approach emphasizes the importance of addressing the “hypothetical protein problem” for a thorough understanding of mechanisms at the cellular level, as well as, provided the assessment of integrating proteomics methods with various annotation and curation approaches to characterize hypothetical or uncharacterized protein data. The MS proteomics data generated from this study has been deposited to the ProteomeXchange through PRIDE with the dataset identifier–PXD029741.
The Potential Role of Epigenetic Mechanisms in the Development of Retinitis Pigmentosa and Related Photoreceptor Dystrophies
Authors: Dvoriantchikova Galina , Lypka Karin Rose , Ivanov Dmitry
Published: March 2022

Retinitis pigmentosa and related photoreceptor dystrophies (RPRPD) are rare retinal diseases caused by hereditary gene mutations resulting in photoreceptor death, followed by vision loss. While numerous genes involved in these diseases have been identified, many cases have still not been associated with any gene, indicating that new mechanisms may be involved in the pathogenesis of these photoreceptor dystrophies. Many genes associated with RPRPD regulate photoreceptor specification and maturation in the developing retina. Since retinal development begins with a population of equivalent, proliferating retinal progenitor cells (RPCs) having a specific “competence” in generating all types of retinal neurons, including cone and rod photoreceptors, we tested the epigenetic changes in promoters of genes required for photoreceptor development and genes associated with RPRPD during RPC differentiation into cone and rod photoreceptors. We found that promoters of many of these genes are epigenetically repressed in RPCs but have no epigenetic restrictions in photoreceptors. Our findings also suggest that DNA methylation as an epigenetic mark, and DNA demethylation as a process, are more important than other epigenetic marks or mechanisms in the pathogenesis of these diseases. Most notably, irregularities in the DNA demethylation process during the RPC-to-photoreceptor transition may significantly contribute to retinitis pigmentosa (RP) pathogenesis since genes with hypermethylated promoters in RPCs account for at least 40% of autosomal recessive RP cases and at least 30% of autosomal dominant RP cases. Thus, we proposed an epigenetic model according to which unsuccessful demethylation of regulatory sequences (e.g., promoters, enhancers) of genes required for photoreceptor development, maturation, and function during the RPC-to-photoreceptor transition may reduce or even eliminate their activity, leading to RPRPD without any inheritable mutations in these genes.
First Comprehensive Characterization of Phayre’s Leaf-Monkey (Trachypithecus phayrei) Karyotype
Authors: Fan Xiaobo , Pinthong Krit , de Oliveira Edivaldo H. C. , Tanomtong Alongklod , Chen Hongwei , Weise Anja , Liehr Thomas
Published: March 2022

The chromosomal homologies of human (Homo sapiens—HSA) and Trachypithecus phayrei (TPH—Phayre’s leaf-monkey, family Cercopithecidae) have previously been studied by using classical chromosome staining/banding and fluorescence in situ hybridization (FISH) from the 1970s to 1990s. In this study, we carried out molecular cytogenetics applying human multicolor banding (MCB), locus-specific, and human heterochromatin-specific probes to establish the first detailed chromosomal map of TPH, which was not available until now. Accordingly, it was possible to precisely determine evolutionary-conserved breakpoints (ECBs) and the orientation of evolutionary-conserved segments compared to HSA. It could be shown that five chromosomes remained completely unchanged between these two species, and 16 chromosomes underwent only intrachromosomal changes. In addition, 50 ECBs that failed to be resolved in previous reports were exactly identified and characterized in this study. It could also be shown that 43.5% of TPH centromere positions were conserved and 56.5% were altered compared to HSA. Interestingly, 82% ECBs in TPH corresponded to human fragile sites. Overall, this study is an essential contribution to future studies and reviews on chromosomal evolution in Cercopithecidae.
Case Report: Be Aware of “New” Features of Niemann–Pick Disease: Insights From Two Pediatric Cases
Authors: Chen Fan , Guo Shan , Li Xuesong , Liu Shengxuan , Wang Li , Zhang Victor Wei , Xu Hui , Huang Zhihua , Ying Yanqin , Shu Sainan
Published: March 2022

Niemann–Pick disease is a relatively common lysosomal storage disease. Cholestatic liver disease is a typical clinical phenotype of Niemann–Pick disease in infancy. The diagnosis is traditionally based on Niemann–Pick cells in bone marrow smears or liver biopsies. Treatment for cholestatic liver disease mainly includes ursodeoxycholic acid and liver protection drugs. Here, we reported two cases of Niemann–Pick disease type C, diagnosed by genetic analysis during early infancy. Besides cholestatic jaundice, the two patients also exhibited signs of immune system hyperactivity, such as elevated immunoglobulins or multiple autoantibodies, which might require the application of glucocorticoids. In addition, three novel missense variants of the NPC1 gene were identified. The findings suggest that immune activation should be considered as a “new” clinical phenotype of lysosomal storage diseases.
A Multi-Omics Pan-Cancer Analysis of 4EBP1 in Cancer Prognosis and Cancer-Associated Fibroblasts Infiltration
Authors: Du Kunpeng , Zou Jingwen , Liu Chunshan , Khan Muhammad , Xie Tao , Huang Xiaoting , Zhang Ke , Yuan Yawei , Wang Baiyao
Published: March 2022

Background: Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (4EBP1) involved in inhibition of protein translation and synthesis. However, the phosphoprotein of 4EBP1 (p-4EBP1) promotes the translation and synthesis of several proteins, including multiple classic oncogenic proteins. The prognostic significance of 4EBP1 mRNA, 4EBP1 protein, and p-4EBP1 in Pan-cancer are still unclear.

Methods: In this study, we provided a multi-Omics investigation for the prognostic value of 4EBP1 mRNA, 4EBP1 protein, and different 4EBP1 phosphoproteins in a Pan-cancer manner based on the TCGA projects. We explored the correlation between 4EBP1 expression and the cancer-associated fibroblast (CAFs) infiltration, respectively using the EPIC, MCPCOUNTER, and TIDE algorithms. The functional states of 4EBP1 were explored using single-cell sequencing analysis in Pan-Cancer. Immunohistochemistry staining was used to detect and verify the expression of 4EBP1 in several cancers.

Results: 4EBP1 mRNA was aberrantly overexpressed in most cancers, and was associated with the poor prognosis in ten cancers. Notably, increased 4EBP1 mRNA expression significantly correlated with tumor staging and worse prognosis in BRCA, KIRC, and KIRP, while having the opposite effect in STAD. 4EBP1 expression was associated with the CAFs infiltration level in ten cancer types. Interestingly, the correlation between 4EBP1 and CAFs infiltration had pronounced heterogeneity in digestive system tumors and urinary system tumors. In BLCA, KIRC, and ACC as well as BRCA, 4EBP1 was significantly positively correlated with CAFs infiltration and was associated with a poor prognosis. In STAD and COAD, 4EBP1 is negatively correlated with CAFs infiltration and was associated with a better prognosis. Lastly, the expression and prognostic significance of 4EBP1 protein and different p-4EBP1 varied enormously among cancers.

Conclusion: Our multi-omics study indicates that 4EBP1-driven CAFs infiltration is associated with cancer prognosis and 4EBP1 mRNA, 4EBP1 protein, and p-4EBP1 proteins may serve as potential prognostic biomarkers and therapeutic targets in diverse cancer.
CPIELA: Computational Prediction of Plant Protein–Protein Interactions by Ensemble Learning Approach From Protein Sequences and Evolutionary Information
Authors: Li Li-Ping , Zhang Bo , Cheng Li
Published: March 2022

Identification and characterization of plant protein–protein interactions (PPIs) are critical in elucidating the functions of proteins and molecular mechanisms in a plant cell. Although experimentally validated plant PPIs data have become increasingly available in diverse plant species, the high-throughput techniques are usually expensive and labor-intensive. With the incredibly valuable plant PPIs data accumulating in public databases, it is progressively important to propose computational approaches to facilitate the identification of possible PPIs. In this article, we propose an effective framework for predicting plant PPIs by combining the position-specific scoring matrix (PSSM), local optimal-oriented pattern (LOOP), and ensemble rotation forest (ROF) model. Specifically, the plant protein sequence is firstly transformed into the PSSM, in which the protein evolutionary information is perfectly preserved. Then, the local textural descriptor LOOP is employed to extract texture variation features from PSSM. Finally, the ROF classifier is adopted to infer the potential plant PPIs. The performance of CPIELA is evaluated via cross-validation on three plant PPIs datasets: Arabidopsis thaliana, Zea mays, and Oryza sativa. The experimental results demonstrate that the CPIELA method achieved the high average prediction accuracies of 98.63%, 98.09%, and 94.02%, respectively. To further verify the high performance of CPIELA, we also compared it with the other state-of-the-art methods on three gold standard datasets. The experimental results illustrate that CPIELA is efficient and reliable for predicting plant PPIs. It is anticipated that the CPIELA approach could become a useful tool for facilitating the identification of possible plant PPIs.
New Insights Into the Lineage-Specific Expansion and Functional Diversification of Lamprey AID/APOBEC Family
Authors: Chen Yan , Luo Lingjie , Deng Lisi , Tian Xiaoxue , Chen Shangwu , Xu Anlong , Yuan Shaochun
Published: March 2022

The AID/APOBEC family which converts cytidine to uridine on RNA or DNA experienced dynamic expansion in primates in order to resist exogenous viruses and endogenous retrotransposons. Recently, expansion of AID/APOBEC-like homologs has also been observed in the extant jawless vertebrate lamprey. To reveal what causes such expansion and leads to the functional diversification of lamprey cytosine deaminases (CDAs), we reassessed the CDA genes in Lethenteron japonicum (Lj). We first confirmed the expansion of LjCDA1L1 (CDA1-like 1) genes and found the expression correlation of LjCDA2 and LjCDA1L2 with LjVLRs (variable lymphocyte receptors). Among up to 14 LjCDA1L1 proteins, LjCDA1L1_4a has an extremely high deamination activity on ssDNA and buDNA and, unexpectedly, on dsDNA. LjCDA1L1s can also restrict the infection of HSV-1 particles. Thus, the arms race between the host and pathogens along with the recruitment by VLR assembly may participate together to form a driving force in the expansion and diversification of the lamprey AID/APOBEC family.
Ischemic Preconditioning Modulates the Peripheral Innate Immune System to Promote Anti-Inflammatory and Protective Responses in Mice Subjected to Focal Cerebral Ischemia
Authors: Amantea Diana , La Russa Daniele , Frisina Marialaura , Giordano Francesca , Di Santo Chiara , Panno Maria Luisa , Pignataro Giuseppe , Bagetta Giacinto
Published: March 2022

The development of tolerance triggered by a sublethal ischemic episode (preconditioning, PC) involves a complex crosstalk between neurons, astrocytes and microglia, although the role of the peripheral immune system in this context is largely unexplored. Here, we report that severe cerebral ischemia caused by transient middle cerebral artery occlusion (MCAo) in adult male mice elevates blood counts of inflammatory neutrophils and monocytes, and plasma levels of miRNA-329-5p. These inflammatory responses are prevented by ischemic PC induced by 15 min MCAo, 72h before the severe insult (1h MCAo). As compared with sham-operated animals, mice subjected to either ischemic PC, MCAo or a combination of both (PC+MCAo) display spleen contraction. However, protein levels of Ym1 (a marker of polarization of myeloid cells towards M2/N2 protective phenotypes) are elevated only in spleen from the experimental groups PC and PC+MCAo, but not MCAo. Conversely, Ym1 protein levels only increase in circulating leukocytes from mice subjected to 1h MCAo, but not in preconditioned animals, which is coincident with a dramatic elevation of Ym1 expression in the ipsilateral cortex. By immunofluorescence analysis, we observe that expression of Ym1 occurs in amoeboid-shaped myeloid cells, mainly representing inflammatory monocytes/macrophages and neutrophils. As a result of its immune-regulatory functions, ischemic PC prevents elevation of mRNA levels of the pro-inflammatory cytokine interleukin (IL)-1β in the ipsilateral cortex, while not affecting IL-10 mRNA increase induced by MCAo. Overall, the elevated anti-inflammatory/pro-inflammatory ratio observed in the brain of mice pre-exposed to PC is associated with reduced brain infarct volume and ischemic edema, and with amelioration of functional outcome. These findings reaffirm the crucial and dualistic role of the innate immune system in ischemic stroke pathobiology, extending these concepts to the context of ischemic tolerance and underscoring their relevance for the identification of novel therapeutic targets for effective stroke treatment.
Perioperative Outcomes of Minimally Invasive Esophagectomy After Neoadjuvant Immunotherapy for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma
Authors: Cheng Jiahan , Guo Minzhang , Yang Yushang , Liu Yilin , Hu Weipeng , Shang Qixin , Li Chuan , Xia Liang , Wang Yun , Wang Wenping , Tian Dong , Yuan Yong , Hu Yang , Chen Longqi
Published: March 2022

Background

Immunotherapy has become a pillar of advanced solid tumors treatment. Patients are more likely to benefit from neoadjuvant immunotherapy compared with traditional neoadjuvant therapy. However, the safety and efficacy of neoadjuvant immunotherapy for the treatment of locally advanced, surgically resectable Esophageal squamous cell carcinoma (ESCC) remain unknown.

Method

ESCC patients who received neoadjuvant treatment following minimally invasive esophagogastrostomy were enrolled from June 2020 to September 2021. The characteristics of neoadjuvant treatment and surgery were investigated to determine the safety and efficacy of the neoadjuvant combination of chemotherapy and immunotherapy (NCI).

Results

A total of 149 patients were included in the study. Patient ratio was 40:109 between NCI and neoadjuvant chemotherapy plus radiotherapy (NCR) groups. No significant difference was found in terms of pathological characteristics, including ypN stage, ypTNM stage, differentiation, lymphovascular invasion, perineural invasion, pathological complete regression and tumor regression score, and these parameters were not correlated with NCI or NCR (all p>0.05). Regarding to the operation, the NCI group had less blood loss (49.25 ± 13.47 vs. 57.02 ± 47.26, p<0.001), and shorter operation time (247.75 ± 28.28 vs. 285.83 ± 52.43, p<0.001) than the NCR group. Additionally, the NCI group demonstrated a lower rate of overall perioperative complications (p=0.003) and grade >2 perioperative complications (p=0.042) than the NCR group.

Conclusion

Overall, the findings reported here indicate NCI could result in better outcome and less complications to locally advanced ESCC patients compared with NCR therapy. As a novel therapeutic option, the efficacy and safety of NCI appears to be feasible and safe, while long-term survival data is still needed.
The Roles of Monocytes and Macrophages in Behçet’s Disease With Focus on M1 and M2 Polarization
Authors: Hirahara Lisa , Takase-Minegishi Kaoru , Kirino Yohei , Iizuka-Iribe Yuki , Soejima Yutaro , Yoshimi Ryusuke , Nakajima Hideaki
Published: March 2022

Behçet’s disease (BD) is a systemic inflammatory disease characterized by recurrent oral ulcers, genital ulcers, cutaneous inflammation, and uveitis. In addition, other potentially life-threatening lesions may occur in the intestinal tract, blood vessels, and central nervous system. This heterogeneity of the BD phenotype hampers development of a targeted treatment strategy. The pathogenesis of BD is not fully elucidated, but it is likely that genetically susceptible people develop BD in response to environmental factors, such as microbiome factors. Genetic analyses have identified various BD susceptibility loci that function in HLA-antigen presentation pathways, Th1 and Th17 cells, and autoinflammation related to monocytes/macrophages, or that increase levels of pro-inflammatory cytokines, reduce levels of anti-inflammatory cytokines, or act in dysfunctional mucous barriers. Our functional analyses have revealed that impairment of M2 monocyte/macrophage-mediated anti-inflammatory function through IL-10 is crucial to BD pathogenesis. We, therefore, propose that BD is an M1-dominant disease. In this review, we describe the roles of monocytes and macrophages in BD and consider the potential of these cells as therapeutic targets.
Tissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease
Authors: Lee Juyeun , Kim Dongkyun , Min Booki
Published: March 2022

Foxp3+ regulatory T (Treg) cells are a CD4 T cell subset with unique immune regulatory function that are indispensable in immunity and tolerance. Their indisputable importance has been investigated in numerous disease settings and experimental models. Despite the extensive efforts in determining the cellular and molecular mechanisms operating their functions, our understanding their biology especially in vivo remains limited. There is emerging evidence that Treg cells resident in the non-lymphoid tissues play a central role in regulating tissue homeostasis, inflammation, and repair. Furthermore, tissue-specific properties of those Treg cells that allow them to express tissue specific functions have been explored. In this review, we will discuss the potential mechanisms and key cellular/molecular factors responsible for the homeostasis and functions of tissue resident Treg cells under steady-state and inflammatory conditions.
Dynamic Analysis of Monopile-Type Offshore Wind Turbine Under Sea Ice Coupling With Fluid-Structure Interaction
Authors: Liu Yingzhou , Shi Wei , Wang Wenhua , Li Xin , Qi Shengwenjun , Wang Bin
Published: March 2022

The interaction between vertical offshore wind turbine (OWT) and sea ice with fluid is a complex process including local and global crushing of ice fragments and vibration of OWT. It is crucial to study the ice resistance of OWT structures considering the fluid-structure interaction (FSI). This article investigates a complete process of dynamic sea ice-monopile OWT interaction considering soil-structure interaction (SSI) and FSI effects. A fully coupled dynamic collision model of sea ice and OWT incorporating with the explicit non-linear collision tool ANSYS/LS-DYNA is proposed. The simulated ice loads in this study is verified by different simulation methods and international static ice force standards closely related to ice dynamic characteristic parameters. Then, the dynamic response and damage of the OWT structure during ice-structure interaction are studied using the fully interaction model with FSI coupling. The simulated ice force can produce a significant vibration response in the structure coupling with FSI due to occurrence of ice-induced resonance in the ice velocity range of 2.5–3.5 cm/s. Finally, the effect of fluid on the sea ice-OWT interaction in the initial velocity collision of sea ice is analyzed. FSI coupling can cause a certain level of collision hysteresis, accelerate the failure of sea ice breaking and reasonably reduce the energy of the structure.
On the Scope of GaN-Based Avalanche Photodiodes for Various Ultraviolet-Based Applications
Authors: Ji Dong , Chowdhury Srabanti
Published: March 2022

We present a review of GaN avalanche photodiodes. GaN-based avalanche photodiodes are of emerging interest to the device community. The review covers various important aspects of the device such as the design space, substrate choice, edge termination efficacy, and last, but not least, the physics behind the avalanche breakdown in GaN. The study comprehends the reported impact ionization coefficients and how they may affect the device performances. Finally various reported GaN APDs are summarized and compared. We conclude that hole-initiated GaN APDs on free-standing GaN substrates can offer unprecedented advantages as ultraviolet light detectors, due to their ultra-high responsivity and low dark current.
Magnetorheological Fluid Filled Spring for Variable Stiffness and Damping: Current and Potential Performance
Authors: Sikulskyi Stanislav , Malik Aryslan , Kim Daewon
Published: March 2022

Magnetorheological (MR) fluid is a smart material utilized for semi-active damping devices thanks to its ability to become viscoelastic solid under a magnetic field and provide variable damping. While most of these devices primarily utilize the fluid’s drastic increase in viscosity, its variable stiffness is rarely utilized. A MR fluid filled spring is a novel device with variable stiffness and damping and is the subject of the present study. First, the derived analytical model and the device’s controllable stiffness capability were experimentally validated by performing tensile tests with a fabricated hollow polymer spring filled with MRF-132DG. The analytical model was proved to describe the MR fluid static effect of increased spring stiffness accurately. Secondly, dynamic testing demonstrated the device’s controllable damping and capability to shift natural frequencies. In addition, the testing unveiled an enhanced dynamic performance of the spring due to the cumulative effect of MR fluid activation and specifically aligned uniform magnetic field. Finally, the hollow spring design was optimized through analytical and non-linear finite element buckling analysis to maximize MR fluid stiffness effect. The resulting critical parameters of the optimized design were used to estimate the effects of hollow spring material and operating conditions on the variable stiffness of the device.
SARS-CoV-2 Spike Glycoprotein and ACE2 Interaction Reveals Modulation of Viral Entry in Wild and Domestic Animals
Authors: Praharaj Manas Ranjan , Garg Priyanka , Kesarwani Veerbhan , Topno Neelam A. , Khan Raja Ishaq Nabi , Sharma Shailesh , Panigrahi Manjit , Mishra B. P. , Mishra Bina , Kumar G. Sai , Gandham Ravi Kumar , Singh Raj Kumar , Majumdar Subeer , Mohapatra Trilochan
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral pathogen causing life-threatening diseases in humans. Interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) is a potential factor in the infectivity of a host. In this study, the interaction of SARS-CoV-2 spike protein with its receptor, ACE2, in different hosts was evaluated to predict the probability of viral entry. Phylogeny and alignment comparison of the ACE2 sequences did not lead to any meaningful conclusion on viral entry in different hosts. The binding ability between ACE2 and the spike protein was assessed to delineate several spike binding parameters of ACE2. A significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders into infected or uninfected. Finally, a logistic regression model constructed using spike binding parameters of ACE2, revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had a high probability of viral entry. However, among the Proboscidea, African elephants had a low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. The findings prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.
Pre-Clinical Proof of Concept: Intra-Carotid Injection of Autologous CD34-Positive Cells for Chronic Ischemic Stroke
Authors: Ogawa Yuko , Okinaka Yuka , Kikuchi-Taura Akie , Saino Orie , Tani-Yokoyama Ayumi , Masuda Satoru , Komatsu-Horii Miki , Ikemoto Yoshihiko , Kawamoto Atsuhiko , Fukushima Masanori , Taguchi Akihiko
Published: March 2022

This study was conducted to evaluate the safety and efficacy of human peripheral blood CD34 positive (CD34+) cells transplanted into a murine chronic stroke model to obtain pre-clinical proof of concept, prior to clinical testing. Granulocyte colony stimulating factor (G-CSF) mobilized human CD34+ cells [1 × 104 cells in 50 μl phosphate-buffered saline (PBS)] were intravenously (iv) or intra-carotid arterially (ia) transplanted 4 weeks after the induction of stroke (chronic stage), and neurological function was evaluated. In this study, severe combined immune deficiency (SCID) mice were used to prevent excessive immune response after cell therapy. Two weeks post cell therapy, the ia CD34+ cells group demonstrated a significant improvement in neurological functions compared to the PBS control. The therapeutic effect was maintained 8 weeks after the treatment. Even after a single administration, ia transplantation of CD34+ cells had a significant therapeutic effect on chronic stroke. Based on the result of this pre-clinical proof of concept study, a future clinical trial of autologous peripheral blood CD34+ cells administration in the intra-carotid artery for chronic stroke patients is planned.
An Online Pre-procedural Nomogram for the Prediction of Contrast-Associated Acute Kidney Injury in Patients Undergoing Coronary Angiography
Authors: Li Duanbin , Jiang Hangpan , Yang Xinrui , Lin Maoning , Gao Menghan , Chen Zhezhe , Fu Guosheng , Lai Dongwu , Zhang Wenbin
Published: March 2022

Background

Identifying high-risk patients for contrast-associated acute kidney injury (CA-AKI) helps to take early preventive interventions. The current study aimed to establish and validate an online pre-procedural nomogram for CA-AKI in patients undergoing coronary angiography (CAG).

Methods

In this retrospective dataset, 4,295 patients undergoing CAG were enrolled and randomized into the training or testing dataset with a split ratio of 8:2. Optimal predictors for CA-AKI were determined by Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) algorithm. Nomogram was developed and deployed online. The discrimination and accuracy of the nomogram were evaluated by receiver operating characteristic (ROC) and calibration analysis, respectively. Clinical usefulness was estimated by decision curve analysis (DCA) and clinical impact curve (CIC).

Results

A total of 755 patients (17.1%) was diagnosed with CA-AKI. 7 pre-procedural predictors were identified and integrated into the nomogram, including age, gender, hemoglobin, N-terminal of the prohormone brain natriuretic peptide, neutrophil-to-lymphocyte ratio, cardiac troponin I, and loop diuretics use. The ROC analyses showed that the nomogram had a good discrimination performance for CA-AKI in the training dataset (area under the curve, AUC = 0.766, 95%CI [0.737 to 0.794]) and testing dataset (AUC = 0.737, 95%CI [0.693 to 0.780]). The nomogram was also well-calibrated in both the training dataset (P = 0.965) and the testing dataset (P = 0.789). Good clinical usefulness was identified by DCA and CIC. Finally, this model was deployed in a web server for public use (https://duanbin-li.shinyapps.io/DynNomapp/).

Conclusion

An easy-to-use pre-procedural nomogram for predicting CA-AKI was established and validated in patients undergoing CAG, which was also deployed online.
Secular Trends of Acute Viral Hepatitis Incidence and Mortality in China, 1990 to 2019 and Its Prediction to 2030: The Global Burden of Disease Study 2019
Authors: Su Xing , Zheng Lin , Zhang Huami , Shen Ting , Liu Yingna , Hu Xiaowei
Published: March 2022

Background

Understanding the patterns and trends in the context of both incidence and mortality and anticipating future trends is important for viral hepatitis prevention, treatment, and guiding resource allocation in China. The objective of this study is to provide a comprehensive temporal analysis of acute viral hepatitis and its type using the most updated data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2019) to estimate the incidence and mortality of hepatitis from 1990 to 2019 and make predictions to 2030.

Methods

The age-standardized incidence (ASIR) and mortality rate (ASMR) of viral hepatitis in China were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2019). Trends of ASIR and ASMR for viral hepatitis were plotted using locally weighted regression (LOESS). We used joinpoint regression analysis to detect temporal changes and estimate the annual percent of change (APC) of each trend segment and the corresponding 95% confidence interval (CI). A Bayesian age-period-cohort analysis was employed to describe ASIR and ASMR trends between 1990 and 2019 and projections to 2030.

Results

In 1990, there were 67 million incident cases of acute viral hepatitis, which then decreased to 47 million incidence cases in 2019. Hepatitis A and hepatitis B account for the majority of acute viral hepatitis, and the most pronounced declines in hepatitis B (−48.7%) and hepatitis C (−39.0%) were observed between 1990 and 2019. The ASIR of overall acute viral hepatitis shows a persistent decline, with an average annual percent of change (AAPC) of −1.9% (95% CI: −1.9, −1.8) between 1990 and 2019. The trend of ASMR demonstrated a rapid decline between 1990 and 2005, followed by a slow decline until 2030.

Conclusion

Our study reveals favorable declining trends of incidence and mortality for acute viral hepatitis in China from 1990 and 2019, and these favorable trends are predicted to continue up to 2030. Despite the favorable trends observed, the absolute number of viral hepatitis, especially hepatitis A and B, is still substantial in China. A scaled-up vaccine campaign is still needed to tackle the large number of vaccine preventable hepatitis infections.
Milk Transmission of HTLV-1 and the Need for Innovative Prevention Strategies
Authors: Millen Sebastian , Thoma-Kress Andrea K.
Published: March 2022

Breastfeeding is recommended by the World Health Organization for at least 6 months up to 2 years of age, and breast milk protects against several diseases and infections. Intriguingly, few viruses are transmitted via breastfeeding including Human T-cell leukemia virus Type 1 (HTLV-1). HTLV-1 is a highly oncogenic yet neglected retrovirus, which primarily infects CD4+ T-cells in vivo and causes incurable diseases like HTLV-1-associated inflammatory conditions or Adult T-cell leukemia/lymphoma (ATLL) after lifelong viral persistence. Worldwide, at least 5–10 million people are HTLV-1-infected and most of them are unaware of their infection posing the risk of silent transmissions. HTLV-1 is transmitted via cell-containing body fluids such as blood products, semen, and breast milk, which constitutes the major route of mother-to-child transmission (MTCT). Risk of transmission increases with the duration of breastfeeding, however, abstinence from breastfeeding as it is recommended in some endemic countries is not an option in resource-limited settings or underrepresented areas and populations. Despite significant progress in understanding details of HTLV-1 cell-to-cell transmission, it is still not fully understood, which cells in which organs get infected via the oral route, how these cells get infected, how breast milk affects this route of infection and how to inhibit oral transmission despite breastfeeding, which is an urgent need especially in underrepresented areas of the world. Here, we review these questions and provide an outlook how future research could help to uncover prevention strategies that might ultimately allow infants to benefit from breastfeeding while reducing the risk of HTLV-1 transmission.
Different Regulatory Strategies of Arsenite Oxidation by Two Isolated Thermus tengchongensis Strains From Hot Springs
Authors: Yuan Changguo , Li Ping , Qing Chun , Kou Zhu , Wang Helin
Published: March 2022

Arsenic is a ubiquitous constituent in geothermal fluids. Thermophiles represented by Thermus play vital roles in its transformation in geothermal fluids. In this study, two Thermus tengchongensis strains, named as 15Y and 15W, were isolated from arsenic-rich geothermal springs and found different arsenite oxidation behaviors with different oxidation strategies. Arsenite oxidation of both strains occurred at different growth stages, and two enzyme-catalyzed reaction kinetic models were observed. The arsenite oxidase of Thermus strain 15W performed better oxidation activity, exhibiting typical Michaelis–Menten kinetics. The kinetic parameter of arsenite oxidation in whole cell showed a Vmax of 18.48 μM min–1 and KM of 343 μM. Both of them possessed the arsenite oxidase-coding genes aioB and aioA. However, the expression of gene aioBA was constitutive in strain 15W, whereas it was induced by arsenite in strain 15Y. Furthermore, strain 15Y harbored an intact aio operon including the regulatory gene of the ArsR family, whereas a genetic inversion of an around 128-kbp fragment produced the inactivation of this regulator in strain 15W, leading to the constitutive expression of aioBA genes. This study provides a valuable insight into the adaption of thermophiles to extreme environments.
Epidemiological Consequences of Viral Interference: A Mathematical Modeling Study of Two Interacting Viruses
Authors: Pinky Lubna , Dobrovolny Hana M.
Published: March 2022

Some viruses have the ability to block or suppress growth of other viruses when simultaneously present in the same host. This type of viral interference or viral block has been suggested as a potential interaction between some respiratory viruses including SARS-CoV-2 and other co-circulating respiratory viruses. We explore how one virus' ability to block infection with another within a single host affects spread of the viruses within a susceptible population using a compartmental epidemiological model. We find that population-level effect of viral block is a decrease in the number of people infected with the suppressed virus. This effect is most pronounced when the viruses have similar epidemiological parameters. We use the model to simulate co-circulating epidemics of SARS-CoV-2 and influenza, respiratory syncytial virus (RSV), and rhinovirus, finding that co-circulation of SARS-CoV-2 and RSV causes the most suppression of SARS-CoV-2. Paradoxically, co-circulation of SARS-CoV-2 and influenza or rhinovirus results in almost no change in the SARS-CoV-2 epidemic, but causes a shift in the timing of the influenza and rhinovirus epidemics.
Transient Antibiotic Tolerance Triggered by Nutrient Shifts From Gluconeogenic Carbon Sources to Fatty Acid
Authors: Hartline Christopher J. , Zhang Ruixue , Zhang Fuzhong
Published: March 2022

Nutrient shifts from glycolytic-to-gluconeogenic carbon sources can create large sub-populations of extremely antibiotic tolerant bacteria, called persisters. Positive feedback in Escherichia coli central metabolism was believed to play a key role in the formation of persister cells. To examine whether positive feedback in nutrient transport can also support high persistence to β-lactams, we performed nutrient shifts for E. coli from gluconeogenic carbon sources to fatty acid (FA). We observed tri-phasic antibiotic killing kinetics characterized by a transient period of high antibiotic tolerance, followed by rapid killing then a slower persister-killing phase. The duration of transient tolerance (3–44 h) varies with pre-shift carbon source and correlates strongly with the time needed to accumulate the FA degradation enzyme FadD after the shift. Additionally, FadD accumulation time and thus transient tolerance time can be reduced by induction of the glyoxylate bypass prior to switching, highlighting that two interacting feedback loops simultaneously control the length of transient tolerance. Our results demonstrate that nutrient switches along with positive feedback are not sufficient to trigger persistence in a majority of the population but instead triggers only a temporary tolerance. Additionally, our results demonstrate that the pre-shift metabolic state determines the duration of transient tolerance and that supplying glyoxylate can facilitate antibiotic killing of bacteria.