bluuebunny/crossref_metadata_2025 huggingface dataset:
A General Model for Biofilm-Driven Microbial Electrosynthesis of Carboxylates From CO2
Authors: Cabau-Peinado Oriol , Straathof Adrie J. J. , Jourdin Ludovic
Published: June 2021

Up to now, computational modeling of microbial electrosynthesis (MES) has been underexplored, but is necessary to achieve breakthrough understanding of the process-limiting steps. Here, a general framework for modeling microbial kinetics in a MES reactor is presented. A thermodynamic approach is used to link microbial metabolism to the electrochemical reduction of an intracellular mediator, allowing to predict cellular growth and current consumption. The model accounts for CO2 reduction to acetate, and further elongation to n-butyrate and n-caproate. Simulation results were compared with experimental data obtained from different sources and proved the model is able to successfully describe microbial kinetics (growth, chain elongation, and product inhibition) and reactor performance (current density, organics titer). The capacity of the model to simulate different system configurations is also shown. Model results suggest CO2 dissolved concentration might be limiting existing MES systems, and highlight the importance of the delivery method utilized to supply it. Simulation results also indicate that for biofilm-driven reactors, continuous mode significantly enhances microbial growth and might allow denser biofilms to be formed and higher current densities to be achieved.
Production of Sophorolipid Biosurfactant by Insect Derived Novel Yeast Metschnikowia churdharensis f.a., sp. nov., and Its Antifungal Activity Against Plant and Human Pathogens
Authors: Kumari Alka , Kumari Sumeeta , Prasad G. S. , Pinnaka Anil Kumar
Published: June 2021

Biosurfactants are potential biomolecules that have extensive utilization in cosmetics, medicines, bioremediation and processed foods. Yeast produced biosurfactants offer thermal resistance, antioxidant activity, and no risk of pathogenicity, illustrating their promising use in food formulations. The present study is aimed to assess potential of biosurfactant screened from a novel yeast and their inhibition against food spoilage fungi. A novel asexual ascomycetes yeast strain CIG-6AT producing biosurfactant, was isolated from the gut of stingless bee from Churdhar, HP, India. The phylogenetic analysis revealed that the strain CIG-6AT was closely related to Metschnikowia koreensis, showing 94.38% sequence similarity in the D1D2 region for which the name Metschnikowia churdharensis f.a., sp. nov., is proposed. The strain CIG-6AT was able to produce sophorolipid biosurfactant under optimum conditions. Sophorolipid biosurfactant from strain CIG-6AT effectively reduced the surface tension from 72.8 to 35 mN/m. Sophorolipid biosurfactant was characterized using TLC, FTIR, GC-MS and LC-MS techniques and was a mixture of both acidic and lactonic forms. Sophorolipid assessed promising activity against pathogenic fungi viz. Fusarium oxysporum (MTCC 9913), Fusarium solani (MTCC 350), and Colletotrichum gloeosporioides (MTCC 2190). The inhibitory effect of biosurfactant CIG-6AT against F. solani was studied and MIC was 49 μgm/ml, further confirmed through confocal laser scanning microscopy. We illustrated the antifungal activity of sophorolipid biosurfactant from Metschnikowia genus for the first time and suggested a novel antifungal compound against food spoilage and human fungal pathogen.
Programmed Deviations of Ribosomes From Standard Decoding in Archaea
Authors: De Lise Federica , Strazzulli Andrea , Iacono Roberta , Curci Nicola , Di Fenza Mauro , Maurelli Luisa , Moracci Marco , Cobucci-Ponzano Beatrice
Published: June 2021

Genetic code decoding, initially considered to be universal and immutable, is now known to be flexible. In fact, in specific genes, ribosomes deviate from the standard translational rules in a programmed way, a phenomenon globally termed recoding. Translational recoding, which has been found in all domains of life, includes a group of events occurring during gene translation, namely stop codon readthrough, programmed ± 1 frameshifting, and ribosome bypassing. These events regulate protein expression at translational level and their mechanisms are well known and characterized in viruses, bacteria and eukaryotes. In this review we summarize the current state-of-the-art of recoding in the third domain of life. In Archaea, it was demonstrated and extensively studied that translational recoding regulates the decoding of the 21st and the 22nd amino acids selenocysteine and pyrrolysine, respectively, and only one case of programmed –1 frameshifting has been reported so far in Saccharolobus solfataricus P2. However, further putative events of translational recoding have been hypothesized in other archaeal species, but not extensively studied and confirmed yet. Although this phenomenon could have some implication for the physiology and adaptation of life in extreme environments, this field is still underexplored and genes whose expression could be regulated by recoding are still poorly characterized. The study of these recoding episodes in Archaea is urgently needed.
Automatic Bayesian Weighting for SAXS Data
Authors: Spill Yannick G. , Karami Yasaman , Maisonneuve Pierre , Wolff Nicolas , Nilges Michael
Published: June 2021

Small-angle X-ray scattering (SAXS) experiments are important in structural biology because they are solution methods, and do not require crystallization of protein complexes. Structure determination from SAXS data, however, poses some difficulties. Computation of a SAXS profile from a protein model is expensive in CPU time. Hence, rather than directly refining against the data, most computational methods generate a large number of conformers and then filter the structures based on how well they satisfy the SAXS data. To address this issue in an efficient manner, we propose here a Bayesian model for SAXS data and use it to directly drive a Monte Carlo simulation. We show that the automatic weighting of SAXS data is the key to finding optimal structures efficiently. Another key problem with obtaining structures from SAXS data is that proteins are often flexible and the data represents an average over a structural ensemble. To address this issue, we first characterize the stability of the best model with extensive molecular dynamics simulations. We analyse the resulting trajectories further to characterize a dynamic structural ensemble satisfying the SAXS data. The combination of methods is applied to a tandem of domains from the protein PTPN4, which are connected by an unstructured linker. We show that the SAXS data contain information that supports and extends other experimental findings. We also show that the conformation obtained by the Bayesian analysis is stable, but that a minor conformation is present. We propose a mechanism in which the linker may maintain PTPN4 in an inhibited enzymatic state.
IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
Authors: Du Li , Nai Yaru , Shen Meiying , Li Tingting , Huang Jingjing , Han Xiaojian , Wang Wang , Pang Da , Jin Aishun
Published: June 2021

Adoptive immunotherapy using CAR-T cells is a promising curative treatment strategy for hematological malignancies. Current manufacture of clinical-grade CAR-T cells based on lentiviral/retrovirus transfection of T cells followed by anti-CD3/CD28 activation supplemented with IL-2 has been associated with low transfection efficiency and usually based on the use of terminally differentiated effector T cells. Thus, improving the quality and the quantity of CAR-T cells are essential for optimizing the CAR-T cell preparation. In our study, we focus on the role of IL-21 in the γc cytokine conditions for CAR-T cell preparation. We found for the first time that the addition of IL-21 in the CAR-T preparation improved T cell transfection efficiency through the reduction of IFN-γ expression 24–48 h after T cell activation. We also confirmed that IL-21 enhanced the enrichment and expansion of less differentiated CAR-T cells. Finally, we validated that IL-21 improved the CAR-T cell cytotoxicity, which was related to increased secretion of effector cytokines. Together, these findings can be used to optimize the CAR-T cell preparation.
Hyperbaric Oxygen Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice
Authors: Yuan Yuan , Li Yali , Qiao Guoqiang , Zhou Yilu , Xu Zijian , Hill Charlotte , Jiang Zhenglin , Wang Yihua
Published: June 2021

The prevalence of pulmonary fibrosis is increasing with an aging population and its burden is likely to increase following COVID-19, with large financial and medical implications. As approved therapies in pulmonary fibrosis only slow disease progression, there is a significant unmet medical need. Hyperbaric oxygen (HBO) is the inhaling of pure oxygen, under the pressure of greater than one atmosphere absolute, and it has been reported to improve pulmonary function in patients with pulmonary fibrosis. Our recent study suggested that repetitive HBO exposure may affect biological processes in mice lungs such as response to wounding and extracellular matrix. To extend these findings, a bleomycin-induced pulmonary fibrosis mouse model was used to evaluate the effect of repetitive HBO exposure on pulmonary fibrosis. Building on our previous findings, we provide evidence that HBO exposure attenuates bleomycin-induced pulmonary fibrosis in mice. In vitro, HBO exposure could reverse, at least partially, transforming growth factor (TGF)-β–induced fibroblast activation, and this effect may be mediated by downregulating TGF-β–induced expression of hypoxia inducible factor (HIF)-1α. These findings support HBO as a potentially life-changing therapy for patients with pulmonary fibrosis, although further research is needed to fully evaluate this.
Modulation of Septo-Hippocampal Neural Responses in Anesthetized and Behaving Rats by Septal AMPA Receptor Mechanisms
Authors: Ibrahim Khairunisa Mohamad , Ariffin Mohammed Zacky , Khanna Sanjay
Published: June 2021

This study explored the effects of septal glutamatergic transmission on septal-hippocampal theta activity via intraseptal microinjection of antagonist at AMPA receptors (AMPAR). The current results showed that microinjection of AMPAR antagonist, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione, 20 μg/μl, 0.5 μl), evoked a decrease in the frequency of theta activity evoked by various means in anesthetized and behaving rat. Theta wave activity was induced on: (a) intraseptal microinjection of carbachol, an agonist at cholinergic receptors, (b) reticular stimulation, (c) exploration in novel open field (OF), and (d) hind paw (HP) injection of the algogen, formalin. The effect on frequency in the formalin test was observed in an early period on injection of formalin, which was novel to the animal, but not in the later more sustained phase of the formalin test. The effect of NBQX, being seen in both anesthetized and behaving animals, suggests that the modulation of theta wave frequency, including in novelty, is a function of AMPAR in MS. The effect of the antagonist on theta power was less apparent, being observed only in anesthetized animals. In addition to theta power and frequency, intraseptal NBQX also attenuated suppression of CA1 population spike (PS) induced by intraseptal carbachol, thus suggesting that septal glutamate neurotransmission is involved in the spectrum of MS-mediated network responses. Indeed, in the context of behavior, formalin injection induced an increase in the level of septal glutamate, while NBQX attenuated nociceptive behaviors. Notably, MS is involved in the modulation of formalin nociception. These findings suggest that AMPA receptors are a key modulator of septal physiological function.
Retinal Axon Interplay for Binocular Mapping
Authors: Fassier Coralie , Nicol Xavier
Published: June 2021

In most mammals, retinal ganglion cell axons from each retina project to both sides of the brain. The segregation of ipsi and contralateral projections into eye-specific territories in their main brain targets—the dorsolateral geniculate nucleus and the superior colliculus—is critical for the processing of visual information. The investigation of the developmental mechanisms contributing to the wiring of this binocular map in mammals identified competitive mechanisms between axons from each retina while interactions between axons from the same eye were challenging to explore. Studies in vertebrates lacking ipsilateral retinal projections demonstrated that competitive mechanisms also exist between axons from the same eye. The development of a genetic approach enabling the differential manipulation and labeling of neighboring retinal ganglion cells in a single mouse retina revealed that binocular map development does not only rely on axon competition but also involves a cooperative interplay between axons to stabilize their terminal branches. These recent insights into the developmental mechanisms shaping retinal axon connectivity in the brain will be discussed here.
Translations of Steinhausen's Publications Provide Insight Into Their Contributions to Peripheral Vestibular Neuroscience
Authors: Straka Hans , Paulin Michael G. , Hoffman Larry F.
Published: June 2021

The quantitative relationship between angular head movement and semicircular canal function is most often referenced to the well-known torsion-pendulum model that predicts cupular displacement from input head acceleration. The foundation of this model can be traced back to Steinhausen's series of papers between 1927 and 1933 whereby he endeavored to document observations of cupular displacements that would directly infer movement of the endolymph resulting from angular rotation. He also was the first to establish the direct relationship between cupular displacement and compensatory eye movements. While the chronology of these findings, with their successes and pitfalls, are documented in Steinhausen's work, it reflects a fascinating journey that has been inaccessible to the non-German speaking community. Therefore, the present compilation of translations, with accompanying introduction and discussion, was undertaken to allow a larger component of the vestibular scientific community to gain insight into peripheral labyrinthine mechanics provided by this historical account.
Association Between Three-Dimensional Transrectal Ultrasound Findings and Tumor Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: An Observational Study
Authors: Zhang Xun , Fan Jin , Zhang Lijie , Wang Jingwen , Wang Minghe , Zhu Ji
Published: June 2021

Background

There is a significant demand for the development of non-surgical methods for the evaluation of complete response to tumor therapy. Predicting ability and image quality of routine imaging has not been satisfactory. To avoid the deficiencies, we assessed the capability of three-dimensional transrectal ultrasound in predicting the response to neoadjuvant chemoradiotherapy in rectal cancer patients.

Methods

The inclusion criteria were patients with locally advanced rectal adenocarcinoma, receiving capecitabine-based neoadjuvant chemoradiotherapy, distance from anal verge (≤6 cm), clinical stage T3-4 and/or N+ without evidence of distant metastasis, and restaging ycT0-3a (T3a <5 mm) after the end of neoadjuvant chemoradiotherapy. Three-dimensional transrectal ultrasound was performed 7 weeks after neoadjuvant chemoradiotherapy to discern the patients with complete response from the others. Eight main parameters were obtained from three-dimensional transrectal ultrasound: thickness of muscularis on the residual side, thickness of contralateral muscularis, angle of residual arc, regularity of the shape, integrity of the mucosal layer, blurring of the margin, internal echo, and posterior echo. The association between tumor response and three-dimensional transrectal ultrasound parameters was analyzed, and a model was developed by logistic regression.

Results

Between 2014 and 2019, 101 patients were recruited; 72 cases received total mesorectal excision, and 29 cases underwent watch-and-wait. Among the three-dimensional transrectal ultrasound parameters, the adjusted-thickness of the muscularis (P<0.01), angle of the residual arc (P<0.01), and regularity of the residual shape (P<0.01) were strongly associated with tumor response. In the dataset with total mesorectal excision cases (TME dataset), the residual adjusted-thickness (odds ratio [OR]=4.88, 95% confidence interval [CI]=1.44–16.6, P=0.01) and regularity of the residual shape (OR=5.00, 95% CI=1.13–22.2, P=0.03) were kept in the final logistic model. The area under the curve of the logistic model was 0.84. Among these parameters, residual adjusted-thickness correlated significantly with tumor response. Additionally, we observed similar results in the whole population of 101 cases (whole dataset) and in the cross-validation.

Conclusion

Three-dimensional transrectal ultrasound model is a valuable method for predicting tumor response in rectal cancer patients undergoing neoadjuvant chemoradiotherapy, which should be included as a factor for evaluating clinical complete response.

Trial Registration

This trial was registered with ClinicalTrials.gov, number NCT02605265. Registered 9 November 2015 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT02605265
FHL3 Contributes to EMT and Chemotherapy Resistance Through Up-Regulation of Slug and Activation of TGFβ/Smad-Independent Pathways in Gastric Cancer
Authors: Cao Guodong , Li Pengping , He Xiaobo , Jin Mengyao , Li Mengying , Chen Sihan , Xu Xin , Sun Qiang , Xiong Maoming , Chen Bo
Published: June 2021

Background

Gastric cancer presents high risk of metastasis and chemotherapy resistance. Hence, it is important to understand the mechanisms of gastric cancer distant metastasis and chemotherapeutic resistance. Our previous study has revealed Four and a Half LIM Domains 3 (FHL3) plays as a binding partner of Glycogen Synthase Kinase 3 Beta (GSK3β), promoted tumor metastasis in pancreatic cancer. However, the role of FHL3 in gastric cancer still remains unclear.

Methods

TCGA database and clinical samples are used for exploring the role of FHL3 in disease progression and prognosis. Oxaliplatin (OHP) resistance cell lines were established to study the role of FHL3 in chemotherapy resistance. The experiments about cell proliferation, apoptosis, and metastasis were performed to measure the chemotherapy effects of sh-FHL3 on gastric cancer cell lines and in vivo. That FHL3 changed the EMT phenotype was verified by western blot. Finally, we explored the mechanism of FHL3-mediated EMT and chemotherapy resistance.

Results

mRNA and protein level of FHL3 were significantly up-regulated in gastric cancer tissues when compared with adjacent tissue. FHL3 higher expression is always accompanied with higher TNM stage and worse overall survival. FHL3 over-expressed could lead to OHP resistance. Knockdown of FHL3 slightly inhibited the cell growth, while it obviously sensitized the chemotherapy in vivo and in vitro. In addition, down-regulation of FHL3 increased the mesenchymal markers, such as Slug, Snail, Twist Family BHLH Transcription Factor 1 (Twist1), and Vimentin, while it decreased the epithelial marker E-cadherin. Cell and animal experiments also proved that down-regulation of FHL3 can decrease cancer cell metastasis. For mechanism study, FHL3 knockdown down-regulated the expression level of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Regulated Protein Kinase (ERK) pathway and Transforming Growth Factor-β (TGFβ)/Phosphatidylinositol 3-Kinase (PI3K)/protein kinase B(Akt)/GSK3β-(Ring Finger Protein 146) RNF146/ubiquitin pathway. FHL3 competitively bonded the ubiquitin complex (Slug/GSK3β/RNF146) with Slug and inhibited ubiquitination of Slug. Mesenchymal phenotype cells hold higher level of Multidrug Resistance Gene1 (MDR1), and the FHL3 knockdown reverts the MDR1 in this type cell.

Conclusion

FHL3 high expression contributed to EMT and chemotherapy resistance via MAPK, and PI3K pathways were activated. FHL3 competitively bonded the ubiquitin complex with Slug, resulting in the up-regulation of Slug and leading to metastasis of gastric cancer.
The Novel Methylation Biomarker SCARA5 Sensitizes Cancer Cells to DNA Damage Chemotherapy Drugs in NSCLC
Authors: Peng Qi , Liu Yan , Kong Xuehua , Xian Jie , Ye Lin , Yang Li , Guo Shuliang , Zhang Yan , Zhou Lan , Xiang Tingxiu
Published: June 2021

Background

Scavenger Receptor Class A Member 5 (SCARA5), also known as TESR, is expressed in various tissues and organs and participates in host defense. Recent studies have found SCARA5 to produce an anti-tumor effect for multiple tumors, although the mechanistic basis for the effect is unknown.

Methods

Bioinformatics, methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR, and immunohistochemistry were used to assess promoter methylation and expression of SCARA5 in lung cancer tissues and cell lines. The biological effect of SCARA5 on lung cancer cells was confirmed by the CCK8 assay, colony formation assay, and flow cytometry. GSEA, Western blot, RNA sequencing, and luciferase-based gene reporter assay were used to explore the mechanistic basis for the anti-tumor effect of SCARA5. Chemosensitivity assays were used to evaluate the anti-tumor effect of SCARA5 in conjunction with chemotherapeutic drugs.

Results

We found SCARA5 to be downregulated in lung cancer cell lines and tissues with SCARA5 levels negatively related to promoter methylation. Ectopic expression of SCARA5 suppressed proliferation of lung cancer both in vitro and in vivo through upregulation of HSPA5 expression, which inhibited FOXM1 expression resulting in G2/M arrest of the A549 cell line. SCARA5 also improved susceptibility of A549 cells to chemotherapeutic drugs that damage DNA.

Conclusion

SCARA5 was silenced in NSCLC due to promoter methylation and could be a potential tumor marker in NSCLC.
LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1
Authors: Ji Weidan , Peng Zhangxiao , Sun Bin , Chen Lei , Zhang Qin , Guo Minggao , Su Changqing
Published: June 2021

Hepatocellular carcinoma (HCC) is a malignant cancer with rapid proliferation and high metastasis ability. To explore the crucial genes that maintain the aggressive behaviors of cancer cells is very important for clinical gene therapy of HCC. LpCat1 was reported to be highly expressed and exert pro-tumorigenic effect in a variety of cancers, including HCC. However, its detailed molecular mechanism remained unclear. In this study, we confirmed that LpCat1 was up-regulated in HCC tissues and cancer cell lines. The overexpressed LpCat1 promoted the proliferation, migration and invasion of HCC cells, and accelerated cell cycle progression, while knocking down LpCat1 significantly inhibited cell proliferation, migration and invasion in vitro and in vivo, and arrested HCC cells at G0/G1 phase. Moreover, we proved for the first time that LpCat1 directly interacted with STAT1 which was generally recognized as a tumor suppressor in HCC. High levels of LpCat1 in HCC could inhibit STAT1 expression, up-regulate CyclinD1, CyclinE, CDK4 and MMP-9, and decrease p27kip1 to promote cancer progression. Conversely, down-regulation of LpCat1 would cause the opposite changes to repress the viability and motility of HCC cells. Consequently, we concluded that LpCat1 was a contributor to progression and metastasis of HCC by interacting with STAT1.
Patient-Reported Outcomes Assessing the Impact of Palliative Radiotherapy on Quality of Life and Symptom Burden in Head and Neck Cancer Patients: A Systematic Review
Authors: Fabian Alexander , Domschikowski Justus , Hoffmann Markus , Weiner Oliver , Schmalz Claudia , Dunst Jürgen , Krug David
Published: June 2021

Incurable head and neck cancer has a poor prognosis and impairs a patient’s health-related quality of life. Palliative radiotherapy may improve or stabilize health-related quality of life and symptoms, best measured by patient-reported outcomes. There is no systematic analysis if palliative radiotherapy for head and neck cancer improves or stabilizes health-related quality of life or symptoms as validly measured by patient-reported outcomes. Therefore, the primary objective of this systematic review (PROSPERO-ID: CRD42020166434) was to assess the effect of palliative radiotherapy for head and neck cancer on patient-reported outcomes. The secondary objective was to assess the rate and quality of use of patient-reported outcomes in relevant studies claiming a “palliative effect” of radiotherapy. The databases MEDLINE/PubMed, EMBASE, Cochrane CENTRAL, “ClinicalTrials.gov” were searched. Concerning the primary objective, four studies were eligible to assess the effectiveness of palliative radiotherapy as measured by patient-reported outcomes. A narrative synthesis suggests a favorable impact of palliative radiotherapy on health-related quality of life and symptom burden. The risk of bias, however, is considerable and the overall quality of evidence low. Concerning the secondary objective, over 90% of studies claiming a “palliative effect” of palliative radiotherapy did either not use patient-reported outcomes or did so by limited quality. In conclusion, implementation of patient-reported outcomes in studies assessing palliative radiotherapy for head and neck cancer should be fostered. Palliative radiotherapy remains an option for head and neck cancer patients, although more studies focusing on patient-reported outcomes are needed.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42020166434
Anti-Tumor Effects of BDH1 in Acute Myeloid Leukemia
Authors: Han Fei , Zhao Huanhuan , Lu Jun , Yun Weina , Yang Lingling , Lou Yude , Su Dan , Chen Xin , Zhang Shixuan , Jin Hanwei , Li Xiang , Sun Jie , Huang He , Wang Qishan , Jiang Xi
Published: June 2021

Dysregulation of ketone metabolism has been reported in various types of cancer. In order to find out its role in acute myeloid leukemia (AML) pathogenesis, we first analyzed the expression levels of 10 key genes involved in ketone metabolism in AML blasts and CD34+ hematopoietic stem cells (HSCs) from healthy donors. We found that the expression level of BDH1 was significantly lower in AML than in normal HSCs. The downregulation of BDH1 gene expression in AML cell lines as compared with normal HSCs was further confirmed with real-time RT-PCR. Analysis of TCGA and other database revealed that the downregulation of BDH1 was associated with worse prognosis in AML patients. In addition, we showed that overexpression of BDH1 inhibited the viability and proliferation of AML cells. In contrast, BDH1 knock-down promoted AML cell growth. Collectively, our results suggest the previously unappreciated anti-tumor role of BDH1 in AML, and low BDH1 expression predicts poor survival.
Recurrent Wheezing and Asthma After Respiratory Syncytial Virus Bronchiolitis
Authors: Zhou Yunlian , Tong Lin , Li Mengyao , Wang Yingshuo , Li Lanxin , Yang Dehua , Zhang Yuanyuan , Chen Zhimin
Published: June 2021

Background: Respiratory syncytial virus (RSV) is the most common pathogen of acute bronchiolitis in children, which sometimes triggers the development of recurrent wheezing and increases the risk of childhood asthma.

Methods: We enrolled 425 children who were diagnosed with RSV-infected bronchiolitis at the department of pulmonology, Children's Hospital Zhejiang University School of Medicine in 2011. Long-term follow-up was performed to explore the consequence of bronchiolitis on subsequent recurrent wheezing and asthma.

Results: Of 425 patients, 266 cases completed the entire follow-up, the mean age of onset was 4.9 (3.3) months, and the male-to-female ratio was 2.5. The mean birth weight of all patients was 3.22 (0.63) kg, and the number of patients who had a history of cesarean section was 148. According to the outcome of follow-up, 36 were in the recurrent wheezing (RW) group, 65 were in the asthma (AS) group, and the remaining 165 were in the completely recovered (CR) group. The age of onset was older and the birth weights were higher in the AS group than those in the CR group (P < 0.05). And the higher proportion of cesarean sections was higher in the RW group than that in the CR group (P < 0.05). Furthermore, we found a remarkable increasing of serum IgE in the AS groups than that in the CR group (P < 0.01). Multiple logistic regression analysis showed that the cesarean section was the risk factor for the development of recurrent wheezing and the higher birth weight was the risk factor for the development of asthma.

Conclusion: RSV bronchiolitis might increase the incidence of recurrent wheezing and asthma. Allergic constitution was an important prerequisite for the occurrence of asthma, and related risk factor such as cesarean section can only increase recurrent wheezing to a certain extent within a certain period of time. And we also find higher birth weight and older onset age for those who develop asthma, which should be verified in the future.
The Role of Regional Anesthesia During the SARS-CoV2 Pandemic: Appraisal of Clinical, Pharmacological and Organizational Aspects
Authors: Cappelleri Gianluca , Fanelli Andrea , Ghisi Daniela , Russo Gianluca , Giorgi Antonio , Torrano Vito , Lo Bianco Giuliano , Salomone Salvatore , Fumagalli Roberto
Published: June 2021

The severe acute respiratory syndrome coronavirus SARS-CoV2 is spreading over millions of people worldwide, leading to thousands of deaths, even among the healthcare providers. Italy has registered the deaths of 337 physicians and more than 200 nurses as of March 14, 2021. Anesthesiologists are at higher risk as they are the care providers in both ICU and operating rooms.Although the vaccination of healthcare providers has been the prioirity, physicians are still continually exposed to the virus and potentially risk contagion and must thus protect themselves and their patients from the risks of infection while providing the best care to their surgical patients.Regional anesthesia allows for a reduction in airway manipulation, reducing environmental contamination as a result. Furthermore, regional anesthesia reduces the opioid requirements as well as the muscle paralysis due to muscle-relaxants and should be recommended whenever possible in COVID-19 patients. Our aim is to evaluate the advantages and criticisms of regional anesthesia in the management of surgical patients in the pandemic age.
Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease
Authors: Chu Junyi , Yan Ran , Wang Sai , Li Guoyang , Kang Xiaohui , Hu Yan , Lin Musen , Shan Wen , Zhao Yan , Wang Zhecheng , Sun Ruimin , Yao Jihong , Zhang Ning
Published: June 2021

Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process.
Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization
Authors: Noh Minyoung , Zhang Haiying , Kim Hyejeong , Park Songyi , Kim Young-Myeong , Kwon Young-Guen
Published: June 2021

Endothelial barrier integrity is important for vascular homeostasis, and hyperpermeability participates in the progression of many pathological states, such as diabetic retinopathy, ischemic stroke, chronic bowel disease, and inflammatory disease. Here, using drug repositioning, we discovered that primaquine diphosphate (PD), previously known as an antimalarial drug, was a potential blocker of vascular leakage. PD inhibited the linear pattern of vascular endothelial growth factors (VEGF)-induced disruption at the cell boundaries, blocked the formation of VEGF-induced actin stress fibers, and stabilized the cortactin actin rings in endothelial cells. PD significantly reduced leakage in the Miles assay and mouse model of streptozotocin (STZ)-induced diabetic retinopathy. Targeted prediction programs and deubiquitinating enzyme activity assays identified a potential mechanism of action for PD and demonstrated that this operates via ubiquitin specific protease 1 (USP1). USP1 inhibition demonstrated a conserved barrier function by inhibiting VEGF-induced leakage in endothelial permeability assays. Taken together, these findings suggest that PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity.
High Glucose Activates YAP Signaling to Promote Vascular Inflammation
Authors: Ortillon Jeremy , Le Bail Jean-Christophe , Villard Elise , Léger Bertrand , Poirier Bruno , Girardot Christine , Beeske Sandra , Ledein Laetitia , Blanchard Véronique , Brieu Patrice , Naimi Souâd , Janiak Philip , Guillot Etienne , Meloni Marco
Published: June 2021

Background and Aims

The YAP/TAZ signaling is known to regulate endothelial activation and vascular inflammation in response to shear stress. Moreover, YAP/TAZ signaling plays a role in the progression of cancers and renal damage associated with diabetes. However, whether YAP/TAZ signaling is also implicated in diabetes-associated vascular complications is not known.

Methods

The effect of high glucose on YAP/TAZ signaling was firstly evaluated in vitro on endothelial cells cultured under static conditions or subjected to shear stress (either laminar or oscillatory flow). The impact of diabetes on YAP/TAZ signaling was additionally assessed in vivo in db/db mice.

Results

In vitro, we found that YAP was dephosphorylated/activated by high glucose in endothelial cells, thus leading to increased endothelial inflammation and monocyte attachment. Moreover, YAP was further activated when high glucose was combined to laminar flow conditions. YAP was also activated by oscillatory flow conditions but, in contrast, high glucose did not exert any additional effect. Interestingly, inhibition of YAP reduced endothelial inflammation and monocyte attachment. Finally, we found that YAP is also activated in the vascular wall of diabetic mice, where inflammatory markers are also increased.

Conclusion

With the current study we demonstrated that YAP signaling is activated by high glucose in endothelial cells in vitro and in the vasculature of diabetic mice, and we pinpointed YAP as a regulator of high glucose-mediated endothelial inflammation and monocyte attachment. YAP inhibition may represent a potential therapeutic opportunity to improve diabetes-associated vascular complications.
AtSEC22 Regulates Cell Morphogenesis via Affecting Cytoskeleton Organization and Stabilities
Authors: Guan Li , Yang Shurui , Li Shenglin , Liu Yu , Liu Yuqi , Yang Yi , Qin Guochen , Wang Haihai , Wu Tao , Wang Zhigang , Feng Xianzhong , Wu Yongrui , Zhu Jian-Kang , Li Xugang , Li Lixin
Published: June 2021

The plant cytoskeleton forms a stereoscopic network that regulates cell morphogenesis. The cytoskeleton also provides tracks for trafficking of vesicles to the target membrane. Fusion of vesicles with the target membrane is promoted by SNARE proteins, etc. The vesicle-SNARE, Sec22, regulates membrane trafficking between the ER and Golgi in yeast and mammals. Arabidopsis AtSEC22 might also regulate early secretion and is essential for gametophyte development. However, the role of AtSEC22 in plant development is unclear. To clarify the role of AtSEC22 in the regulation of plant development, we isolated an AtSEC22 knock-down mutant, atsec22-4, and found that cell morphogenesis and development were seriously disturbed. atsec22-4 exhibited shorter primary roots (PRs), dwarf plants, and partial abortion. More interestingly, the atsec22-4 mutant had less trichomes with altered morphology, irregular stomata, and pavement cells, suggesting that cell morphogenesis was perturbed. Further analyses revealed that in atsec22-4, vesicle trafficking was blocked, resulting in the trapping of proteins in the ER and collapse of structures of the ER and Golgi apparatus. Furthermore, AtSEC22 defects resulted in impaired organization and stability of the cytoskeleton in atsec22-4. Our findings revealed essential roles of AtSEC22 in membrane trafficking and cytoskeleton dynamics during plant development.
Nitrogen Use Efficiency Definitions of Today and Tomorrow
Authors: Congreves Kate A. , Otchere Olivia , Ferland Daphnée , Farzadfar Soudeh , Williams Shanay , Arcand Melissa M.
Published: June 2021

Crop production has a large impact on the nitrogen (N) cycle, with consequences to climate, environment, and public health. Designing better N management will require indicators that accurately reflect the complexities of N cycling and provide biological meaning. Nitrogen use efficiency (NUE) is an established metric used to benchmark N management. There are numerous approaches to calculate NUE, but it is difficult to find an authoritative resource that collates the various NUE indices and systematically identifies their assets and shortcomings. Furthermore, there is reason to question the usefulness of many traditional NUE formulations, and to consider factors to improve the conceptualization of NUE for future use. As a resource for agricultural researchers and students, here we present a comprehensive list of NUE indices and discuss their functions, strengths, and limitations. We also suggest several factors—which are currently ignored in traditional NUE indices—that will improve the conceptualization of NUE, such as: accounting for a wider range of soil N forms, considering how plants mediate their response to the soil N status, including the below-ground/root N pools, capturing the synchrony between available N and plant N demand, blending agronomic performance with ecosystem functioning, and affirming the biological meaning of NUE.
New Players in the Interaction Between Beetle Polygalacturonases and Plant Polygalacturonase-Inhibiting Proteins: Insights From Proteomics and Gene Expression Analyses
Authors: Haeger Wiebke , Wielsch Natalie , Shin Na Ra , Gebauer-Jung Steffi , Pauchet Yannick , Kirsch Roy
Published: June 2021

Plants possess various defense strategies to counter attacks from microorganisms or herbivores. For example, plants reduce the cell-wall-macerating activity of pathogen- or insect-derived polygalacturonases (PGs) by expressing PG-inhibiting proteins (PGIPs). PGs and PGIPs belong to multi-gene families believed to have been shaped by an evolutionary arms race. The mustard leaf beetle Phaedon cochleariae expresses both active PGs and catalytically inactive PG pseudoenzymes. Previous studies demonstrated that (i) PGIPs target beetle PGs and (ii) the role of PG pseudoenzymes remains elusive, despite having been linked to the pectin degradation pathway. For further insight into the interaction between plant PGIPs and beetle PG family members, we combined affinity purification with proteomics and gene expression analyses, and identified novel inhibitors of beetle PGs from Chinese cabbage (Brassica rapa ssp. pekinensis). A beetle PG pseudoenzyme was not targeted by PGIPs, but instead interacted with PGIP-like proteins. Phylogenetic analysis revealed that PGIP-like proteins clustered apart from “classical” PGIPs but together with proteins, which have been involved in developmental processes. Our results indicate that PGIP-like proteins represent not only interesting novel PG inhibitor candidates in addition to “classical” PGIPs, but also fascinating new players in the arms race between herbivorous beetles and plant defenses.
Response Mechanisms of Plants Under Saline-Alkali Stress
Authors: Fang Shumei , Hou Xue , Liang Xilong
Published: June 2021

As two coexisting abiotic stresses, salt stress and alkali stress have severely restricted the development of global agriculture. Clarifying the plant resistance mechanism and determining how to improve plant tolerance to salt stress and alkali stress have been popular research topics. At present, most related studies have focused mainly on salt stress, and salt-alkali mixed stress studies are relatively scarce. However, in nature, high concentrations of salt and high pH often occur simultaneously, and their synergistic effects can be more harmful to plant growth and development than the effects of either stress alone. Therefore, it is of great practical importance for the sustainable development of agriculture to study plant resistance mechanisms under saline-alkali mixed stress, screen new saline-alkali stress tolerance genes, and explore new plant salt-alkali tolerance strategies. Herein, we summarized how plants actively respond to saline-alkali stress through morphological adaptation, physiological adaptation and molecular regulation.
Impact of Plant Growth-Promoting Rhizobacteria Inoculation and Grafting on Tolerance of Tomato to Combined Water and Nutrient Stress Assessed via Metabolomics Analysis
Authors: Kalozoumis Panagiotis , Savvas Dimitrios , Aliferis Konstantinos , Ntatsi Georgia , Marakis George , Simou Evridiki , Tampakaki Anastasia , Karapanos Ioannis
Published: June 2021

In the current study, inoculation with plant growth-promoting rhizobacteria (PGPR) and grafting were tested as possible cultural practices that may enhance resilience of tomato to stress induced by combined water and nutrient shortage. The roots of tomato grown on perlite were either inoculated or not with PGPR, applying four different treatments. These were PGPR-T1, a mix of two Enterobacter sp. strains (C1.2 and C1.5); PGPR-T2, Paenibacillus sp. strain DN1.2; PGPR-T3, Enterobacter mori strain C3.1; and PGPR-T4, Lelliottia sp. strain D2.4. PGPR-treated plants were either self-grafted or grafted onto Solanum lycopersicum cv. M82 and received either full or 50% of their standard water, nitrogen, and phosphorus needs. The vegetative biomass of plants subjected to PGPR-T1 was not reduced when plants were cultivated under combined stress, while it was reduced by stress to the rest of the PGPR treatments. However, PGPR-T3 increased considerably plant biomass of non-stressed tomato plants than did all other treatments. PGPR application had no impact on fruit biomass, while grafting onto ’M82’ increased fruit production than did self-grafting. Metabolomics analysis in tomato leaves revealed that combined stress affects several metabolites, most of them already described as stress-related, including trehalose, myo-inositol, and monopalmitin. PGPR inoculation with E. mori strain C3.1 affected metabolites, which are important for plant/microbe symbiosis (myo-inositol and monopalmitin). The rootstock M82 did not affect many metabolites in plant leaves, but it clearly decreased the levels of malate and D-fructose and imposed an accumulation of oleic acid. In conclusion, PGPR are capable of increasing tomato tolerance to combined stress. However, further research is required to evaluate more strains and refine protocols for their application. Metabolites that were discovered as biomarkers could be used to accelerate the screening process for traits such as stress tolerance to abiotic and/or abiotic stresses. Finally, ‘M82’ is a suitable rootstock for tomato, as it is capable of increasing fruit biomass production.
Genome-Wide Association Studies of Seed Performance Traits in Response to Heat Stress in Medicago truncatula Uncover MIEL1 as a Regulator of Seed Germination Plasticity
Authors: Chen Zhijuan , Ly Vu Joseph , Ly Vu Benoit , Buitink Julia , Leprince Olivier , Verdier Jerome
Published: June 2021

Legume seeds are an important source of proteins, minerals, and vitamins for human and animal diets and represent a keystone for food security. With climate change and global warming, the production of grain legumes faces new challenges concerning seed vigor traits that allow the fast and homogenous establishment of the crop in a wide range of environments. These seed performance traits are regulated during seed maturation and are under the strong influence of the maternal environment. In this study, we used 200 natural Medicago truncatula accessions, a model species of legumes grown in optimal conditions and under moderate heat stress (26°C) during seed development and maturation. This moderate stress applied at flowering onwards impacted seed weight and germination capacity. Genome-wide association studies (GWAS) were performed to identify putative loci or genes involved in regulating seed traits and their plasticity in response to heat stress. We identified numerous significant quantitative trait nucleotides and potential candidate genes involved in regulating these traits under heat stress by using post-GWAS analyses combined with transcriptomic data. Out of them, MtMIEL1, a RING-type zinc finger family gene, was shown to be highly associated with germination speed in heat-stressed seeds. In Medicago, we highlighted that MtMIEL1 was transcriptionally regulated in heat-stressed seed production and that its expression profile was associated with germination speed in different Medicago accessions. Finally, a loss-of-function analysis of the Arabidopsis MIEL1 ortholog revealed its role as a regulator of germination plasticity of seeds in response to heat stress.