bluuebunny/crossref_metadata_2025 huggingface dataset:
Status of Earthquake Early Warning in Switzerland
Authors: Massin Frédérick , Clinton John , Böse Maren
Published: September 2021

The Swiss Seismological Service (SED) at ETH has been developing methods and open-source software for Earthquake Early Warning (EEW) for more than a decade and has been using SeisComP for earthquake monitoring since 2012. The SED has built a comprehensive set of SeisComP modules that can provide EEW solutions in a quick and transparent manner by any seismic service operating SeisComP. To date, implementations of the Virtual Seismologist (VS) and Finite-Fault Rupture Detector (FinDer) EEW algorithms are available. VS provides rapid EEW magnitudes building on existing SeisComP detection and location modules for point-source origins. FinDer matches growing patterns of observed high-frequency seismic acceleration amplitudes with modeled templates to identify rupture extent, and hence can infer on-going finite-fault rupture in real-time. Together these methods can provide EEW for all event dimensions from moderate to great, if a high quality, EEW-ready, seismic network is available. In this paper, we benchmark the performance of this SeisComP-based EEW system using recent seismicity in Switzerland. Both algorithms are observed to be similarly fast and can often produce first EEW alerts within 4–6 s of origin time. In real time performance, the median delay for the first VS alert is 8.7 s after origin time (56 earthquakes since 2014, from M2.7 to M4.6), and 7 s for FinDer (10 earthquakes since 2017, from M2.7 to M4.3). The median value for the travel time of the P waves from event origin to the fourth station accounts for 3.5 s of delay; with an additional 1.4 s for real-time data sample delays. We demonstrate that operating two independent algorithms provides redundancy and tolerance to failures of a single algorithm. This is documented with the case of a moderate M3.9 event that occured seconds after a quarry blast, where picks from both events produced a 4 s delay in the pick-based VS, while FinDer performed as expected. Operating on the Swiss Seismic Network, that is being continuously optimised for EEW, the SED-ETHZ SeisComP EEW system is achieving performance that is comparable to operational EEW systems around the world.
Teacher Stress: A Psychobiological Approach to Stressful Interactions in the Classroom
Authors: Wettstein Alexander , Schneider Sandra , grosse Holtforth Martin , La Marca Roberto
Published: September 2021

Teachers report elevated levels of stress and psychosomatic illnesses compared to other professions. Teacher stress has far-reaching consequences on their health outcomes, the student's motivation, and the economy. However, research on teacher stress relies mainly on self-reports, hence, assesses stress on purely subjective perception. Personal or subjective aspects can strongly influence these measures, and biological stress may even be unnoticed. It is, therefore, necessary to include both subjective and objective measures to investigate stress, preferably in real-life situations. This review aims to demonstrate the importance of a psychobiological ambulatory assessment (AA) approach to investigate teacher stress, in contrast to purely subjective measures. We discuss classroom disruptions as the primary stress factor within the classroom and how a multimethod AA approach using psychological measures while simultaneously recording classroom disruptions and biological stress reactions of teachers would enable a much deeper understanding of stressful transactional processes taking place in the classroom that has not been achieved before.
Screening and Identification of Key Genes for Activation of Islet Stellate Cell
Authors: Wang Xiaohang , Carvalho Vladmir , Wang Qianqian , Wang Jinbang , Li Tingting , Chen Yang , Ni Chengming , Liu Lili , Yuan Yang , Qiu Shanhu , Sun Zilin
Published: September 2021

Background

It has been demonstrated that activated islet stellate cells (ISCs) play a critical role in islet fibrogenesis and significantly contribute to the progression of type 2 diabetes mellitus. However, the key molecules responsible for ISCs activation have not yet been determined. This study aimed to identify the potential key genes involved in diabetes-induced activation of ISCs.

Method

Stellate cells were isolated from three 10-week-old healthy male Wistar rats and three Goto-Kakizaki (GK) rats. Cells from each rat were primary cultured under the same condition. A Genome-wide transcriptional sequence of stellate cells was generated using the Hiseq3000 platform. The identified differentially expressed genes were validated using quantitative real-time PCR and western blotting in GK rats, high fat diet (HFD) rats, and their controls.

Results

A total of 204 differentially expressed genes (DEGs) between GK. ISCs and Wistar ISCs (W.ISCs) were identified, accounting for 0.58% of all the 35,362 genes detected. After the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the mRNA levels of these genes were further confirmed by real-time PCR in cultured ISCs. We then selected Fos, Pdpn, Bad as the potential key genes for diabetes-induced activation of ISCs. Finally, we confirmed the protein expression levels of FOS, podoplanin, and Bad by western blotting and immunofluorescence in GK rats, HFD rats, and their controls. The results showed that the expression level of FOS was significantly decreased, while podoplanin and Bad were significantly increased in GK.ISCs and HFD rats compared with controls, which were consistent with the expression of α-smooth muscle actin.

Conclusions

A total of 204 DEGs were found between the GK.ISCs and W.ISCs. After validating the expression of potential key genes from GK rats and HFD rats, Fos, Pdpn, and Bad might be potential key genes involved in diabetes-induced activation of ISCs.
Construction of a Prognostic Risk Prediction Model for Obesity Combined With Breast Cancer
Authors: Sun Na , Ma Dandan , Gao Pingping , Li Yanling , Yan Zexuan , Peng Zaihui , Han Fei , Zhang Yi , Qi Xiaowei
Published: September 2021

The improvement in the quality of life is accompanied by an accelerated pace of living and increased work-related pressures. Recent decades has seen an increase in the proportion of obese patients, as well as an increase in the prevalence of breast cancer. More and more evidences prove that obesity may be one of a prognostic impact factor in patients with breast cancer. Obesity presents unique diagnostic and therapeutic challenges in the population of breast cancer patients. Therefore, it is essential to have a better understanding of the relationship between obesity and breast cancer. This study aims to construct a prognostic risk prediction model combining obesity and breast cancer. In this study, we obtained a breast cancer sample dataset from the GEO database containing obesity data [determined by the body mass index (BMI)]. A total of 1174 genes that were differentially expressed between breast cancer samples of patients with and without obesity were screened by the rank-sum test. After weighted gene co-expression network analysis (WGCNA), 791 related genes were further screened. Relying on single-factor COX regression analysis to screen the candidate genes to 30, these 30 genes and another set of TCGA data were intersected to obtain 24 common genes. Finally, lasso regression analysis was performed on 24 genes, and a breast cancer prognostic risk prediction model containing 6 related genes was obtained. The model was also found to be related to the infiltration of immune cells. This study provides a new and accurate prognostic model for predicting the survival of breast cancer patients with obesity.
Lowered Serum Testosterone Concentration Is Associated With Enhanced Inflammation and Worsened Lipid Profile in Men
Authors: Grandys Marcin , Majerczak Joanna , Zapart-Bukowska Justyna , Duda Krzysztof , Kulpa Jan K. , Zoladz Jerzy A.
Published: September 2021

The negative relationship between testosterone and inflammatory cytokines has been reported for decades, although the exact mechanisms of their interactions are still not clear. At the same time, little is known about the relation between androgens and acute phase proteins. Therefore, in this investigation, we aimed to study the relationship between androgen status and inflammatory acute phase reactants in a group of men using multi-linear regression analysis. Venous blood samples were taken from 149 men ranging in age from 18 to 77 years. Gonadal androgens [testosterone (T) and free testosterone (fT)], acute phase reactants [C-reactive protein (CRP), ferritin (FER), alpha-1-acid glycoprotein (AAG), and interleukin-6 (IL-6)], cortisol (C), and lipid profile concentrations were determined. It was demonstrated that the markers of T and fT were negatively correlated with all acute phase proteins (CRP, FER, and AAG; p < 0.02) and the blood lipid profile [total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG); p < 0.03]. Multivariate analysis showed that T, fT, and the fT/C ratio were inversely correlated with the CRP, AAG, and FER concentrations independently of age and blood lipids. When adjustment for BMI was made, T, fT, and the fT/C ratio were negatively correlated with the AAG concentrations only. In addition, it was demonstrated that gonadal androgens were positively correlated with physical activity level (p < 0.01). We have concluded that a lowered serum T concentration may promote inflammatory processes independently of adipose tissue and age through a reduced inhibition of inflammatory cytokine synthesis, which leads to enhanced acute phase protein production. Therefore, a low serum T concentration appears to be an independent risk factor in the development of atherosclerosis and cardiovascular diseases. Moreover, the positive correlation between testosterone and physical activity level suggests that exercise training attenuates the age-related decrease in gonadal androgens and, in this way, may reduce the enhancement of systemic low-grade inflammation in aging men.
Maternal Circulating Exosomal miRNAs as Non-invasive Biomarkers for the Prediction of Fetal Ventricular Septal Defect
Authors: Jin Yuxia , Ai Ling , Chai Xiaojun , Tang Ping , Zhang Weihua , Yang Li , Hu Yue , Xu Ying , Li Suping
Published: September 2021

Objective: This study aimed to identify maternal circulating exosomal miRNAs as potential non-invasive biomarkers for the early detection of fetal ventricular septal defects (VSDs).

Methods: In total, 182 pregnant women, comprising 91 VSD cases and 91 matched controls, were included in this study. Exosomes were isolated; dysregulated exosomal miRNAs were profiled using next-generation sequencing. Differential abundance of miRNAs was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was evaluated by constructing receiver operating characteristic (ROC) curves.

Results: In total, 77 serum exosomal miRNAs were found to be differentially expressed in the VSD group compared to their expression in the control group. Among these, five downregulated exosomal miRNAs were validated using qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSD cases from controls (area under the ROC curve [AUC]: 0.997; p < 1.00E-05).

Conclusion: Circulating exosomal miRNAs, particularly hsa-miR-146a-5p, may be predictive biomarkers for the non-invasive prenatal diagnosis of fetal VSDs.
Localization of RNA Pol II CTD (S5) and Transcriptome Analysis of Testis in Diploid and Tetraploid Hybrids of Red Crucian Carp (♀) × Common Carp (♂)
Authors: Zhou Yi , Zhu La , Sun Yu , Zhang Hui , Wang Jiaojiao , Qin Weilin , He Wangchao , Zhou Luojing , Li Qi , Zhao Rurong , Luo Kaikun , Tang Chenchen , Zhang Chun , Liu Shaojun
Published: September 2021

Polyploidy occurs naturally in fish; however, the appearance of these species is an occasional and gradual process, which makes it difficult to trace the changes in phenotypes, genotypes, and regulation of gene expression. The allotetraploid hybrids (4nAT) of red crucian carp (RCC; ♀) × common carp (CC; ♂) generated from interspecies crossing are a good model to investigate the initial changes after allopolyploidization. In the present study, we focused on the changes in the active sites of the testicular transcriptome of the allotetraploid by localization of RNA Pol II CTD YSPTSPS (phospho S5) using immunofluorescence and RNA-seq data via bioinformatic analysis. The results showed that there was no significant difference in signal counts of the RNA Pol II CTD (S5) between the different types of fish at the same stages, including RCC, CC, 2nF1, and 4nAT, which means that the number of transcriptionally active sites on germ cell chromosomes was not affected by the increase in chromosome number. Similarly, RNA-seq analysis indicated that in the levels of chromosomes and 10-kb regions in the genome, there were no significant changes in the highly active sites in RCC, 2nF1, and 4nAT. These findings suggest that at the beginning of tetraploid origin, the active transcriptome site of 4nAT in the testis was conserved in the regions of the genome compared to that in RCC and 2nF1. In conclusion, 4nAT shared a similar gene expression model in the regions of the genome with RCC and 2nF1 with significantly different expression levels.
Integrated Analysis of the Expression Characteristics, Prognostic Value, and Immune Characteristics of PPARG in Breast Cancer
Authors: Wu Jianbin , Luo Mingmin , Chen Zhuangwei , Li Lei , Huang Xiaoxi
Published: September 2021

Background: Breast cancer (BRCA) is the most frequent malignancy. Identification of potential biomarkers could help to better understand and combat the disease at early stages.

Methods: We selected the overlapping genes of differential expressed genes and genes in BRCA-highly correlated modules by Weighted Gene Co-Expression Network Analysis (WGCNA) in TCGA and GEO data and performed KEGG and GO enrichment. PPARG was achieved from Protein-Protein Interaction (PPI) network analysis and prognostic analysis. TIMER, UALCAN, GEO, TCGA, and western blot analysis were used to validate the expression of PPARG in BRCA. PPARG was further analyzed by DNA methylation, immune parameters, and tumor mutation burden.

Results: Among 381 overlapping genes, the lipid metabolic process was identified as highly enriched pathways in BRCA by TCGA and GEO data. When the prognostic analysis of 10 core genes by PPI network was performed, results revealed that high expression of PPARG was significantly correlated to a better prognosis. PPARG was lesser expression in BRCA according to TIMER, UALCAN, GEO, TCGA, and western blot in both mRNA level and protein level. PPARG had several high DNA methylation level sites and the methylation level is negatively correlated to expression. PPARG is also correlated to TNM stages, tumor microenvironment, and tumor burden.

Conclusions: Findings of our study identified the PPARG as a potential biomarker by confirming its low expression in BRCA and its correlation to prognosis. Moreover, its correlation to DNA methylation and tumor microenvironment may guide new therapeutic strategies for BRCA patients.
The CSF1R-Microglia Axis Has Protective Host-Specific Roles During Neurotropic Picornavirus Infection
Authors: Sanchez John Michael S. , DePaula-Silva Ana Beatriz , Doty Daniel J. , Hanak Tyler J. , Truong Amanda , Libbey Jane E. , Fujinami Robert S.
Published: September 2021

Viral encephalitis is a major cause of morbidity and mortality, but the manifestation of disease varies greatly between individuals even in response to the same virus. Microglia are professional antigen presenting cells that reside in the central nervous system (CNS) parenchyma that are poised to respond to viral insults. However, the role of microglia in initiating and coordinating the antiviral response is not completely understood. Utilizing Theiler’s murine encephalomyelitis virus (TMEV), a neurotropic picornavirus, and PLX5622, a small molecule inhibitor of colony-stimulating factor 1 receptor (CSF1R) signaling that can deplete microglia in the CNS; we investigated the role of the CSF1R-microglia axis in neurotropic picornavirus infection of C57BL/6J and SJL/J mice. These mouse strains differ in their ability to clear TMEV and exhibit different neurological disease in response to TMEV infection. CSF1R antagonism in C57BL/6J mice, which normally clear TMEV in the CNS, led to acute fatal encephalitis. In contrast, CSF1R antagonism in SJL/J mice, which normally develop a chronic CNS TMEV infection, did not result in acute encephalitis, but exacerbated TMEV-induced demyelination. Immunologically, inhibition of CSF1R in C57BL/6J mice reduced major histocompatibility complex II expression in microglia, decreased the proportion of regulatory T cells in the CNS, and upregulated proinflammatory pathways in CNS T cells. Acute CSF1R inhibition in SJL/J mice had no effect on microglial MHC-II expression and upregulated anti-inflammatory pathways in CNS T cells, however chronic CSF1R inhibition resulted in broad immunosuppression. Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.
Metabolic Reprogramming and Immune Evasion in Nasopharyngeal Carcinoma
Authors: Huang Huimei , Li Shisheng , Tang Qinglai , Zhu Gangcai
Published: September 2021

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharynx mainly characterized by geographic distribution and EBV infection. Metabolic reprogramming, one of the cancer hallmarks, has been frequently reported in NPCs to adapt to internal energy demands and external environmental pressures. Inevitably, the metabolic reprogramming within the tumor cell will lead to a decreased pH value and diverse nutritional supplements in the tumor-infiltrating micro-environment incorporating immune cells, fibroblasts, and endothelial cells. Accumulated evidence indicates that metabolic reprogramming derived from NPC cells may facilitate cancer progression and immunosuppression by cell-cell communications with their surrounding immune cells. This review presents the dysregulated metabolism processes, including glucose, fatty acid, amino acid, nucleotide metabolism, and their mutual interactions in NPC. Moreover, the potential connections between reprogrammed metabolism, tumor immunity, and associated therapy would be discussed in this review. Accordingly, the development of targets on the interactions between metabolic reprogramming and immune cells may provide assistances to overcome the current treatment resistance in NPC patients.
The Interplay Among HIV, LINE-1, and the Interferon Signaling System
Authors: Zhao Xu , Zhao Yifei , Du Juan , Gao Pujun , Zhao Ke
Published: September 2021

Human immunodeficiency viruses (HIVs) are retroviruses that replicate effectively in human CD4+ cells and cause the development of acquired immune deficiency syndrome (AIDS). On the other hand, type 1 long interspersed elements (LINE-1s or L1s) are the only active retroelements that can replicate autonomously in human cells. They, along with other active yet nonautonomous retroelements, have been associated with autoimmune diseases. There are many similarities between HIV and LINE-1. Being derived (or evolved) from ancient retroviruses, both HIV and LINE-1 replicate through a process termed reverse transcription, activate endogenous DNA and RNA sensors, trigger innate immune activation to promote interferon (IFN) expression, and are suppressed by protein products of interferon-stimulated genes (ISGs). However, these similarities make it difficult to decipher or even speculate the relationship between HIV and LINE-1, especially regarding the involvement of the IFN signaling system. In this review, we summarize previous findings on the relationships between HIV and innate immune activation as well as between LINE-1 and IFN upregulation. We also attempt to elucidate the interplay among HIV, LINE-1, and the IFN signaling system in hopes of guiding future research directions for viral suppression and immune regulation.
Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19
Authors: Du Juan , Wei Lirong , Li Guoli , Hua Mingxi , Sun Yao , Wang Di , Han Kai , Yan Yonghong , Song Chuan , Song Rui , Zhang Henghui , Han Junyan , Liu Jingyuan , Kong Yaxian
Published: September 2021

Background

The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection.

Methods

A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.

Results

We revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.

Conclusions

Our findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.
Individual and Interactive Effects of Ocean Warming and Acidification on Adult Favites colemani
Authors: Tañedo Mikhael Clotilde S. , Villanueva Ronald D. , Torres Andrew F. , Ravago-Gotanco Rachel , San Diego-McGlone Maria Lourdes
Published: September 2021

Tropical coral reefs are threatened by local-scale stressors that are exacerbated by global ocean warming and acidification from the post-industrial increase of atmospheric CO2 levels. Despite their observed decline in the past four decades, little is known on how Philippine coral reefs will respond to ocean warming and acidification. This study explored individual and synergistic effects of present-day (pH 8.0, 28°C) and near-future (pH 7.7, 32°C) scenarios of ocean temperature and pH on the adult Favites colemani, a common massive reef-building coral in Bolinao-Anda, Philippines. Changes in seawater temperature drive the physiological responses of F. colemani, whereas changes in pH create an additive effect on survival, growth, and photosynthetic efficiency. Under near-future scenarios, F. colemani showed sustained photosynthetic competency despite the decline in growth rate and zooxanthellae density. F. colemani exhibited specificity with the Cladocopium clade C3u. This coral experienced lower growth rates but survived projected near-future ocean warming and acidification scenarios. Its pH-thermal stress threshold is possibly a consequence of acclimation and adaptation to local environmental conditions and past bleaching events. This research highlights the importance of examining the susceptibility and resilience of Philippine corals to climate-driven stressors for future conservation and restoration efforts in the changing ocean.
Its What’s on the Inside That Counts: An Effective, Efficient, and Streamlined Method for Quantification of Octocoral Symbiodiniaceae and Chlorophyll
Authors: Steinberg Rosemary Kate , Johnston Emma L. , Bednarek Teresa , Dafforn Katherine A. , Ainsworth Tracy D.
Published: September 2021

Ocean warming driven bleaching is one of the greatest threats to zooxanthellate cnidarians in the Anthropocene. Bleaching is the loss of Symbiodiniaceae, chlorophyll, or both from zooxanthellate animals. To quantify bleaching and recovery, standardised methods for quantification of Symbiodiniaceae and chlorophyll concentrations have been developed for reef-building scleractinian corals, but no such standard method has been developed for octocorals. For stony corals, quantification of Symbiodiniaceae and chlorophyll concentrations often relies on normalisation to skeletal surface area or unit of biomass [i.e., protein, ash-free dry weight (AFDW)]. Stiff octocorals do not change their volume, as such studies have used volume and surface area to standardise densities, but soft-bodied octocorals can alter their size using water movement within the animal; therefore, Symbiodiniaceae and chlorophyll cannot accurately be measured per unit of surface area and are instead measured in units of Symbiodiniaceae and chlorophyll per μg of host protein or AFDW. Though AFDW is more representative of the full biomass composition than host protein, AFDW is more time and resource intensive. Here, we provide a streamlined methodology to quantify Symbiodiniaceae density, chlorophyll concentration, and protein content in soft-bodied octocorals. This technique uses minimal equipment, does not require freeze-drying or burning samples to obtain ash weight, and is effective for down to 0.2 g wet tissue. Bulk samples can be centrifuged, the Symbiodiniaceae pellet washed, and the supernatant saved for protein analysis. This efficient technique allows for clean, easy to count samples of Symbiodiniaceae with minimal animal protein contamination. Chlorophyll a and c2 extractions occurs at different rates, with chlorophyll a taking 24 h to extract completely at 4°C and chlorophyll c2 taking 48 h. Finally, we found that where necessary, wet weight may be used as a proxy for protein content, but the correlation of protein and wet weight varies by species and protein should be used when possible. Overall, we have created a rapid and accurate method for quantification of bleaching markers in octocorals.
Harmful Algae and Oceanographic Conditions in the Strait of Georgia, Canada Based on Citizen Science Monitoring
Authors: Esenkulova Svetlana , Suchy Karyn D. , Pawlowicz Rich , Costa Maycira , Pearsall Isobel A.
Published: September 2021

In British Columbia (BC), harmful algal blooms (HABs) regularly cause severe economic losses through finfish mortalities and shellfish harvest closures due to toxin accumulation, gill damage, or hypoxia. As there is no routine governmental monitoring of HAB phenomena in BC, HAB variability, and its potential links to environmental drivers are not well understood. Here we present results from a well-managed citizen science program which collected an unprecedented 4 year, high-resolution (∼bi-monthly, ∼80 stations) dataset of harmful algae (HA) concentrations and corresponding physical and chemical properties of seawater throughout the Strait of Georgia (SoG), BC. Analysis of this dataset revealed statistically significant interannual and seasonal relationships between environmental drivers and the most common HA taxa: Rhizosolenia setigera, Dictyocha spp., Alexandrium spp., Heterosigma akashiwo, Chaetoceros convolutus, and C. concavicornis. HABs exhibited significant interannual variations; specifically, no HABs were found during the summer of 2015, blooms of Dictyocha occurred in 2016 and 2017, and dense blooms of Heterosigma and Noctiluca occurred in 2018. In addition, HA prevalence corresponded with negative effects observed in local aquaculture facilities where higher toxins concentrations (causing Paralytic and Diarrhetic Shellfish Poisonings) in shellfish flesh were detected during years with greater abundance of Alexandrium and Dinophysis. Furthermore, salmon mass mortality at fish farms corresponded to years with high concentrations of Heterosigma and Dictyocha. As such, these results highlight the need for long-term data to evaluate the potential role of HA as a stressor on the SoG ecosystem.
Dynamic Triaxial Test and Microscopic Study of Solidified Muddy Soil With Different Mixing Ratios and Curing Ages
Authors: Chen Zhou , Xu Haocheng , Cheng Mayao , Lu Hanwen , Wang Zhijian , Feng Peiyu
Published: September 2021

Aiming to explore the optimal mixture ratio and curing age of solidified muddy soil under dynamic load, the paper intends to investigate whether the solidified muddy soil can be used as filling of high-speed railway subgrade. Based on the dynamic triaxial test, the investigation measured the dynamic strain and dynamic elastic modulus of solidified muddy soil under different mix ratios and curing ages, and also observed the microscopic morphology of solidified muddy soil samples by using scanning electron microscope. The results show that the addition of cement and curing agent significantly increases the dynamic strength and elastic modulus of muddy soil, which effectively improve the dynamic characteristics of muddy soil. The curing effect of the curing agent is more obvious with the increase of the dosage of cement and curing agent under different mix ratio. The content of curing agent plays a leading role in the hydration reaction between cement, curing agent and soil particles. Additionally, in case of the same test conditions, when the ratio of cement mass to dry silt mass is 1:20, the ratio of diluent volume to dry silt mass is 1:20, with 28 days of curing age, its curing effect will reach the best.
Influence of CYP2D6 and CYP3A5 Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients
Authors: Chan Sze Wa , Chu Tanya T. W. , Ho Chung Shun , Kong Alice P. S. , Tomlinson Brian , Zeng Weiwei
Published: September 2021

Purpose: This study was performed to investigate the effects of common polymorphisms in CYP2D6 and CYP3A5 on the plasma concentrations and antihypertensive effects of bisoprolol in hypertensive Chinese patients.

Methods: One hundred patients with essential hypertension were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Clinic blood pressure (BP) and ambulatory BP (ABP) were measured after the placebo run-in and after 6 weeks treatment. Peak plasma concentrations of bisoprolol were measured at 3 h after the first dose and 3 h after the dose after 6 weeks treatment. Trough levels were measured before the dose after 6 weeks treatment. Bisoprolol plasma concentrations were measured with a validated liquid chromatography tandem mass spectrometry method. Six common polymorphisms in CYP2D6 and the CYP3A5*3 polymorphism were genotyped by TaqMan® assay.

Results: After 6 weeks of treatment, clinic BP and heart rate were significantly reduced by 14.3 ± 10.9/8.4 ± 6.2 mmHg (P < 0.01) and 6.3 ± 7.6 BPM (P < 0.01), respectively. Similar reductions were seen in ABP values. Bisoprolol plasma concentration at 3 h after the first dose and 3 h post-dose after 6 weeks of treatment were significantly associated with baseline body weight (P < 0.001) but there was no significant effect of the CYP2D6 and CYP3A5 polymorphisms on these or the trough plasma concentrations. There was no significant association of the CYP2D6 and CYP3A5 polymorphisms or plasma bisoprolol concentrations with the clinic BP or ABP responses to bisoprolol.

Conclusion: Bisoprolol 2.5 mg daily effectively reduced BP and HR. The common polymorphisms in CYP2D6 that were examined and the CYP3A5*3 polymorphism appear to have no benefit in predicting the hemodynamic response to bisoprolol in these patients.
Network Meta-Analysis of Different Clinical Commonly Used Drugs for the Treatment of Hypertrophic Scar and Keloid
Authors: Yang Sha , Luo Yujia J. , Luo Cong
Published: September 2021

Background: There is no uniform treatment for pathological scars, including keloids and hypertrophic scars, in clinic currently. Previously, multiple randomized controlled trials have examined the clinical efficacy of different treatments. Nonetheless, the results are inconsistent, and many treatments have not been directly compared. This makes it difficult to conclude which approach is more favorable, in terms of efficacy and safety, for the treatment of pathological scarring. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid.

Methods: Relevant literature from PubMed, Medline, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CCRCT), and WHO International Clinical Trials Registry Platform (WHO-ICTRP) were searched, from database inception through November 2020. Randomized clinical trials evaluating different treatment strategies of pathological scars, including triamcinolone acetonide (TAC), verapamil (VER), 5-fluorouracil (5-FU), botulinum toxin A (BTA), bleomycin (BLM), and silicone gels were included in the study.

Results: The network meta-analysis included a total of 2,009 patients from 29 studies. A network meta-analysis of injection and topical treatment strategies showed that the efficacy of TAC combined with BTA was best in the treatment of pathological scars. Combination therapies of TAC with 5-FU and TAC with BTA significantly improved the clinical efficiency. However, there was no statistically significant difference between other treatment strategies. The order of efficacy predicted by the surface under the cumulative ranking (SUCRA) curve was as follows: TAC+BTA (82.2%) > TAC+5-FU (69.8%) > BTA (67.3%) > 5-FU+silicone (59.4%) > TAC+silicone (58.3%) > 5-FU (49.8%) > BLM (42.0%) > TAC (26.7%) > VER (26.2%) > silicone (18.3%). There was no publication bias revealed based on the funnel diagram.

Conclusion: This study recommends intralesional injection of TAC-BTA and TAC-5-FU combined therapies. But for patients who cannot tolerate the side effects, the use of silicone gels in combination with TAC is recommended. However, these conclusions need to be further confirmed by more randomized controlled trials.
Smart and Active Food Packaging: Insights in Novel Food Packaging
Authors: Ahari Hamed , Soufiani Solmaz P.
Published: September 2021

Graphical Abstract

Novel food packaging comprises several technologies.
Functional Mapping of Phenotypic Plasticity of Staphylococcus aureus Under Vancomycin Pressure
Authors: Yang Dengcheng , Zheng Xuyang , Jiang Libo , Ye Meixia , He Xiaoqing , Jin Yi , Wu Rongling
Published: September 2021

Phenotypic plasticity is the exhibition of various phenotypic traits produced by a single genotype in response to environmental changes, enabling organisms to adapt to environmental changes by maintaining growth and reproduction. Despite its significance in evolutionary studies, we still know little about the genetic control of phenotypic plasticity. In this study, we designed and conducted a genome-wide association study (GWAS) to reveal genetic architecture of how Staphylococcus aureus strains respond to increasing concentrations of vancomycin (0, 2, 4, and 6 μg/mL) in a time course. We implemented functional mapping, a dynamic model for genetic mapping using longitudinal data, to map specific loci that mediate the growth trajectories of abundance of vancomycin-exposed S. aureus strains. 78 significant single nucleotide polymorphisms were identified following analysis of the whole growth and development process, and seven genes might play a pivotal role in governing phenotypic plasticity to the pressure of vancomycin. These seven genes, SAOUHSC_00020 (walR), SAOUHSC_00176, SAOUHSC_00544 (sdrC), SAOUHSC_02998, SAOUHSC_00025, SAOUHSC_00169, and SAOUHSC_02023, were found to help S. aureus regulate antibiotic pressure. Our dynamic gene mapping technique provides a tool for dissecting the phenotypic plasticity mechanisms of S. aureus under vancomycin pressure, emphasizing the feasibility and potential of functional mapping in the study of bacterial phenotypic plasticity.
Prudent Use of Tylosin for Treatment of Mycoplasma gallisepticum Based on Its Clinical Breakpoint and Lung Microbiota Shift
Authors: Huang Anxiong , Wang Shuge , Guo Jinli , Gu Yufeng , Li Jun , Huang Lingli , Wang Xu , Tao Yanfei , Liu Zhenli , Yuan Zonghui , Hao Haihong
Published: September 2021

The aim of this study was to explore the prudent use of tylosin for the treatment of chronic respiratory infectious diseases in chickens caused by Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and its effect on lung microbiota. The CBP was established based on the wild-type/epidemiological cutoff value (COWT/ECV), pharmacokinetics-pharmacodynamics (PK-PD) cutoff value (COPD), and clinical cutoff value (COCL) of tylosin against MG. The minimum inhibitory concentration (MIC) of tylosin against 111 MG isolates was analyzed and the COWT was 2 μg/ml. M17 with MIC of 2 μg/ml was selected as a representative strain for the PK-PD study. The COPD of tylosin against MG was 1 μg/ml. The dosage regimen formulated by the PK-PD study was 3 days administration of tylosin at a dose of 45.88 mg/kg b.w. with a 24-h interval. Five different MIC MGs were selected for clinical trial, and the COCL of tylosin against MG was 0.5 μg/ml. According to the CLSI decision tree, the CBP of tylosin against MG was set up as 2 μg/ml. The effect of tylosin on lung microbiota of MG-infected chickens was analyzed by 16S rRNA gene sequencing. Significant change of the lung microbiota was observed in the infection group and treatment group based on the principal coordinate analysis and the Venn diagrams of the core and unique OTU. The phyla Firmicutes and Proteobacteria showed difference after MG infection and treatment. This study established the CBP of tylosin against MG. It also provided scientific data for the prudent use of tylosin based on the evaluation of MG infection and tylosin treatment on the lung microbiota.
Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes
Authors: Zhang Kai-Lu , Zhou Jian-Li , Yang Jing-Fang , Zhao Yu-Zhen , Das Debatosh , Hao Ge-Fei , Wu Caie , Zhang Jianhua , Zhu Fu-Yuan , Chen Mo-Xian , Zhou Shao-Ming
Published: September 2021

As a pivotal regulator of 5’ splice site recognition, U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of the U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to a variety of diseases, including cancer. However, the phylogenetic relationships and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared them to homologues from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved and is found in multiple copies in a few members of the U1C gene family. Furthermore, the expression patterns reveal that U1Cs have potential roles in cancer progression and human development. In summary, our study presents a comprehensive overview of the animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.
PIEZO1 Ion Channel Mediates Ionizing Radiation-Induced Pulmonary Endothelial Cell Ferroptosis via Ca2+/Calpain/VE-Cadherin Signaling
Authors: Guo Xue-Wei , Zhang Hao , Huang Jia-Qi , Wang Si-Nian , Lu Yan , Cheng Bo , Dong Su-He , Wang Ying-Ying , Li Feng-Sheng , Li Yong-Wang
Published: September 2021

Pulmonary endothelial cell dysfunction plays an important role in ionizing radiation (IR)-induced lung injury. Whether pulmonary endothelial cell ferroptosis occurs after IR and what are the underlying mechanisms remain elusive. Here, we demonstrate that 15-Gy IR induced ferroptosis characterized by lethal accumulation of reactive oxygen species (ROS), lipid peroxidation, mitochondria shrinkage, and decreased glutathione peroxidase 4 (GPX4) and SLC7A11 expression in pulmonary endothelial cells. The phenomena could be mimicked by Yoda1, a specific activator of mechanosensitive calcium channel PIEZO1. PIEZO1 protein expression was upregulated by IR in vivo and in vitro. The increased PIEZO1 expression after IR was accompanied with increased calcium influx and increased calpain activity. The effects of radiation on lung endothelial cell ferroptosis was partly reversed by inhibition of PIEZO1 activity using the selective inhibitor GsMTx4 or inhibition of downstreaming Ca2+/calpain signaling using PD151746. Both IR and activation of PIEZO1 led to increased degradation of VE-cadherin, while PD151746 blocked these effects. VE-cadherin knockdown by specific siRNA causes ferroptosis-like phenomena with increased ROS and lipid peroxidation in the lung endothelial cells. Overexpression of VE-cadherin partly recused the ferroptosis caused by IR or PIEZO1 activation as supported by decreased ROS production, lipid peroxidation and mitochondria shrinkage compared to IR or PIEZO1 activation alone. In summary, our study reveals a previously unrecognized role of PIEZO1 in modulating ferroptosis, providing a new target for future mitigation of radiation-induced lung injury.
Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review
Authors: Ilangumaran Ponmalar Ilanila , Sarangi Nirod K. , Basu Jaydeep K. , Ayappa K. Ganapathy
Published: September 2021

Pore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane. Bacterial pore forming toxins (PFTs) belong to a subclass of pore forming proteins widely implicated in bacterial infections. Although the action of PFTs on target cells have been widely investigated, the underlying membrane response of lipids during membrane binding and pore formation has received less attention. With the advent of superresolution microscopy as well as the ability to carry out molecular dynamics (MD) simulations of the large protein membrane assemblies, novel microscopic insights on the pore forming mechanism have emerged over the last decade. In this review, we focus primarily on results collated in our laboratory which probe dynamic lipid reorganization induced in the plasma membrane during various stages of pore formation by two archetypal bacterial PFTs, cytolysin A (ClyA), an α-toxin and listeriolysin O (LLO), a β-toxin. The extent of lipid perturbation is dependent on both the secondary structure of the membrane inserted motifs of pore complex as well as the topological variations of the pore complex. Using confocal and superresolution stimulated emission depletion (STED) fluorescence correlation spectroscopy (FCS) and MD simulations, lipid diffusion, cholesterol reorganization and deviations from Brownian diffusion are correlated with the oligomeric state of the membrane bound protein as well as the underlying membrane composition. Deviations from free diffusion are typically observed at length scales below ∼130 nm to reveal the presence of local dynamical heterogeneities that emerge at the nanoscale—driven in part by preferential protein binding to cholesterol and domains present in the lipid membrane. Interrogating the lipid dynamics at the nanoscale allows us further differentiate between binding and pore formation of β- and α-PFTs to specific domains in the membrane. The molecular insights gained from the intricate coupling that occurs between proteins and membrane lipids and receptors during pore formation are expected to improve our understanding of the virulent action of PFTs.
Collective Emotional Contagion in Zebrafish
Authors: Burbano Lombana Daniel Alberto , Macrì Simone , Porfiri Maurizio
Published: September 2021

Seeking to match our emotional state with one of those around us is known as emotional contagion-a fundamental biological process that underlies social behavior across several species and taxa. While emotional contagion has been traditionally considered to be a prerogative of mammals and birds, recent findings are demonstrating otherwise. Here, we investigate emotional contagion in groups of zebrafish, a freshwater model species which is gaining momentum in preclinical studies. Zebrafish have high genetic homology to humans, and they exhibit a complex behavioral repertoire amenable to study social behavior. To investigate whether individual emotional states can be transmitted to group members, we pharmacologically modulated anxiety-related behaviors of a single fish through Citalopram administration and we assessed whether the altered emotional state spread to a group of four untreated conspecifics. By capitalizing upon our in-house developed tracking algorithm, we successfully preserved the identity of all the subjects and thoroughly described their individual and social behavioral phenotypes. In accordance with our predictions, we observed that Citalopram administration consistently reduced behavioral anxiety of the treated individual, in the form of reduced geotaxis, and that such a behavioral pattern readily generalized to the untreated subjects. A transfer entropy analysis of causal interactions within the group revealed that emotional contagion was directional, whereby the treated individual influenced untreated subjects, but not vice-versa. This study offers additional evidence that emotional contagion is biologically preserved in simpler living organisms amenable to preclinical investigations.
P300 as a Potential Indicator in the Evaluation of Neurocognitive Disorders After Traumatic Brain Injury
Authors: Li Haozhe , Li Ningning , Xing Yan , Zhang Shengyu , Liu Chao , Cai Weixiong , Hong Wu , Zhang Qinting
Published: September 2021

Few objective indices can be used when evaluating neurocognitive disorders after a traumatic brain injury (TBI). P300 has been widely studied in mental disorders, cognitive dysfunction, and brain injury. Daily life ability and social function are key indices in the assessment of neurocognitive disorders after a TBI. The present study focused on the correlation between P300 and impairment of daily living activity and social function. We enrolled 234 patients with neurocognitive disorders after a TBI according to ICD-10 and 277 age- and gender-matched healthy volunteers. The daily living activity and social function were assessed by the social disability screening schedule (SDSS) scale, activity of daily living (ADL) scale, and scale of personality change following a TBI. P300 was evoked by a visual oddball paradigm. The results showed that the scores of the ADL scale, SDSS scale, and scale of personality change in the patient group were significantly higher than those in the control group. The amplitudes of Fz, Cz, and Pz in the patient group were significantly lower than those in the control group and were negatively correlated with the scores of the ADL and SDSS scales. In conclusion, a lower P300 amplitude means a greater impairment of daily life ability and social function, which suggested more severity of neurocognitive disorders after a TBI. P300 could be a potential indicator in evaluating the severity of neurocognitive disorders after a TBI.