bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Systemic and Intestinal Inflammatory Response Are Associated With Gut Microbiome Disorder After Cardiovascular Surgery
Authors: Xia Xiong , Ni Jiangjin , Yin Shengnan , Yang Zhipeng , Jiang Haini , Wang Chao , Peng Jian , Wei Hongkui , Wang Xingyu
Published: August 2021

Systemic inflammatory response after cardiovascular surgery is associated with poor prognosis, to which gut barrier impairment is related. To investigate whether perioperative changes of the gut microbiome are associated with systemic and intestinal inflammatory response, we examined changes of the gut microbiome, intestinal homeostasis, and systemic inflammatory response in cardiovascular patients before (Pre) surgery and on the first defecation day [postoperative time 1 (Po1)] or a week [postoperative time 2 (Po2)] postsurgery. Markedly, the enhanced systemic inflammatory response was observed in Po1 and Po2 compared with that in Pre. In line with inflammatory response, impaired gut barrier and elevated gut local inflammation were observed in Po1 and Po2. Microbiome analysis showed a remarkable and steady decline of alpha diversity perioperatively. In addition, microbial composition in the postoperation period was characterized by significant expansion of Enterococcus along with a decrease in anaerobes (Blautia, Faecalibacterium, Bifidobacterium, Roseburia, Gemmiger, [Ruminococcus], and Coprococcus), which were typically health-associated bacteria. Spearman correlation analysis showed microbiome disorder was associated with enhanced systemic inflammatory response and intestinal dysbiosis. These results suggest that microbiome disorder was related to disturbed gut homeostatic and subsequently elevates plasma endotoxin and systemic inflammatory response after cardiovascular surgery. This study not only highlights gut microbiome would be considered in future clinical practice but also proposes a promising perspective of potential diagnostic and therapeutic options for perioperative management of cardiovascular surgery patients.
Enhanced Biocontrol of Cucumber Fusarium Wilt by Combined Application of New Antagonistic Bacteria Bacillus amyloliquefaciens B2 and Phenolic Acid-Degrading Fungus Pleurotus ostreatus P5
Authors: Wang Hongwei , Cai Xiao-Yu , Xu Man , Tian Feng
Published: August 2021

Continuous monoculture of cucumber (Cucumis sativus L.) typically leads to the frequent incidence of Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum (FOC). As potent allelochemicals, phenolic acids are believed to be associated with soilborne diseases. This study aimed to investigate the effect of single or co-inoculation of antagonistic bacteria Bacillus amyloliquefaciens B2 and phenolic acid-degrading fungus Pleurotus ostreatus P5 on the suppression of cucumber Fusarium wilt. The strain B2 was identified as B. amyloliquefaciens based on biochemical, physiological, and 16S rDNA and gyrB gene sequence analyses. Strain B2 showed indole-3-acetic acid (IAA) and siderophore production and phosphate solubilization in in vitro assays. Scanning electron microscope (SEM) imaging showed the ability of strain B2 to adhere to the root surface of cucumber. P. ostreatus P5 could effectively degrade mixed phenolic acids as its sole source of carbon and energy for growth in liquid medium. In a pot experiment, four treatments were established as follows: (1) CK, uninoculated control; (2) B2, inoculation of strain B2; (3) P5, inoculation of strain P5; and (4) B2 + P5, co-inoculation of strain B2 and strain P5. At the end of the 60-day pot experiment, the B2, P5, and B2 + P5 treatments significantly reduced disease incidence by 48.1, 22.2, and 63.0%, respectively, compared to the CK treatment (p < 0.05). All three inoculation treatments significantly increased the growth of cucumber seedlings and suppressed the FOC population compared to the control (p < 0.05). High-performance liquid chromatography (HPLC) analysis showed that total phenolic acids were decreased by 18.9, 35.9, and 63.2% in the B2, P5, and B2 + P5 treatments, respectively. The results from this study suggest that combined application of B. amyloliquefaciens B2 and P. ostreatus P5 could be a promising strategy for suppressing Fusarium wilt and improving plant growth of cucumber seedlings under continuous cropping conditions.
The Red Harmful Plague in Times of Climate Change: Blooms of the Cyanobacterium Planktothrix rubescens Triggered by Stratification Dynamics and Irradiance
Authors: Knapp Deborah , Fernández Castro Bieito , Marty Daniel , Loher Eugen , Köster Oliver , Wüest Alfred , Posch Thomas
Published: August 2021

Planktothrix rubescensis a harmful planktonic cyanobacterium, forming concentrated metalimnetic populations in deep oligo- and mesotrophic lakes, even after successful restoration. In Lake Zurich (Switzerland),P. rubescensemerged as a keystone species with annual mass developments since the 1970s. Its success was partly attributed to effects of lake warming, such as changes in thermal stratification and seasonal deep mixing. However, recent observations based on a biweekly monitoring campaign (2009–2020) revealed two massive breakdowns and striking seasonal oscillations of the population. Here, we disentangle positive from negative consequences of secular lake warming and annual variations in weather conditions onP. rubescensdynamics: (i) despite the high survival rates of overwintering populations (up to 25%) during three consecutive winters (2014–2016) of incomplete deep convective mixing, cyanobacterial regrowth during the following stratified season was moderate and not overshooting a distinct standing stock threshold. Moreover, we recorded a negative trend for annual population maxima and total population size, pointing to a potential nutrient limitation after a series of incomplete winter mixing. Thus, the predication of steadily increasing blooms ofP. rubescenscould not be confirmed for the last decade. (ii) The seasonal reestablishment ofP. rubescenswas strongly coupled with a timely formation of a stable metalimnion structure, where the first positive net growth in the following productive summer season was observed. The trigger for the vertical positioning of filaments within the metalimnion was irradiance and not maximal water column stability. Repetitive disruptions of the vernal metalimnion owing to unstable weather conditions, as in spring 2019, went in parallel with a massive breakdown of the standing stock and marginal regrowth during thermal stratification. (iii) Driven by light intensity,P. rubescenswas entrained into the turbulent epilimnion in autumn, followed by a second peak in population growth. Thus, the typical bimodal growth pattern was still intact during the last decade. Our long-term study highlights the finely tuned interplay between climate-induced changes and variability of thermal stratification dynamics and physiological traits ofP. rubescens, determining its survival in a mesotrophic temperate lake.
Autophagy Induced by the N-Terminus of the Classic Swine Fever Virus Nonstructural Protein 5A Protein Promotes Viral Replication
Authors: Zhang Chengcheng , Wang Xiuling , Sun Jiahao , Guo Mengjiao , Zhang Xiaorong , Wu Yantao
Published: August 2021

Although classic swine fever virus (CSFV) infection has been reported to induce autophagy, the specific induced mechanism remains unrevealed. Nonstructural protein 5A (NS5A) of CSFV is a multiphosphorylated protein with multiple functions to regulate viral replication and the host cell immune responses. Herein, we demonstrated that CSFV NS5A could induce cellular autophagy and promote viral replication. In the current study, we showed that NS5A expression significantly increased the levels of autophagy-related genes (ATGs), including light chain 3 (LC3), ATG5, and Beclin 1; conversely, degradation of P62/sequestosome 1 (SQSTM1) was observed by Western blotting. The number of autophagy-like vesicles was also obviously increased in NS5A-expressing cells, as analyzed by transmission electron microscopy (TEM). Furthermore, we observed the co-localization of the NS5A and LC3 proteins by confocal immunofluorescence analysis. Direct binding of NS5A to the autophagy-related LC3 protein was confirmed by coimmunoprecipitation in vivo and by a GST pulldown assay in vitro. Through segmentation and point mutation research on the NS5A protein, we found that the N-terminal region and the phosphorylation of amino acids 81 and 92 of the NS5A protein were essential for inducing autophagy. Finally, we demonstrated that the LC3 protein had a positive effect on CSFV replication. These findings emphasize a previously unascertained interaction relationship between NS5A and LC3 in the autophagy process. Furthermore, our research revealed a new role of CSFV NS5A, particularly its N-terminal amino acids serine 81 and serine 92, as a critical regulator of CSFV-induced autophagy and have significance for extending our understanding of the CSFV-autophagy interplay.
Computational and NMR Conformational Analysis of Galactofuranoside Cycles Presented in Bacterial and Fungal Polysaccharide Antigens
Authors: Gerbst Alexey G. , Krylov Vadim B. , Nifantiev Nikolay E.
Published: August 2021

Unlike pyranoside cycles which are generally characterized by strictly defined conformational preferences, furanosides are flexible and may adopt a wide range of available conformations. During our previous studies, conformational changes of galactofuranoside cycles upon total sulfation were described computationally, using a simple Hartree–Fock (HF) method, and principal conformers of the 5-membered galactose ring were revealed. However, in the case of more complex disaccharide structures, it was found that this method and the widely applied DFT-B3LYP produced results that deviated from experimental evidence. In this study, other DFT functionals (PBE0 and double hybrid B2PLYP) along with RI-MP2 are employed to study the conformational behavior of the galactofuranoside ring. Reinvestigation of galactofuranosides with a lactic acid substituent at O-3 revealed that changes in the orientation of lactic acid residue at O-3 might induce conformational changes of the furanoside cycle. Such findings are important for further modeling of carbohydrate–protein interaction.
The Effect of MicroRNA-126 Mimic Administration on Vascular Perfusion Recovery in an Animal Model of Hind Limb Ischemia
Authors: Theofilis Panagiotis , Vogiatzi Georgia , Oikonomou Evangelos , Gazouli Maria , Siasos Gerasimos , Katifelis Hector , Perrea Despoina , Vavuranakis Manolis , Iliopoulos Dimitrios C , Tsioufis Costas , Tousoulis Dimitris
Published: August 2021

Background: MicroRNAs have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases.

Methods: Ten-week-old male C57Bl/6 mice were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5 mg/kg (Group A, n = 10) or 5 mg/kg microRNA mimic negative control (Group B, n = 10) on days 1, 3, and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR.

Results: Following microRNA-126 mimic administration in Group A subjects, we noted a stepwise increase in I/N hind limb perfusion ratio (Day 0: 0.364 ± 0.032 vs. Day 8: 0.788 ± 0.049 vs. Day 28: 0.750 ± 0.039, p = 0.001). In Group B a stepwise increase in I/N hind limb perfusion ratio was observed (Day 0: 0.272 ± 0.057 vs. Day 8: 0.382 ± 0.020 vs. Day 28: 0.542 ± 0.028, p = 0.074). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p < 0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (p < 0.001). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population.

Conclusion: MicroRNA-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.
Magnetic Resonance Image of Neonatal Acute Bilirubin Encephalopathy: A Diffusion Kurtosis Imaging Study
Authors: Zheng Hongyi , Lin Jiefen , Lin Qihuan , Zheng Wenbin
Published: August 2021

Background and Objective: The abnormal T1-weighted imaging of MRI can be used to characterize neonatal acute bilirubin encephalopathy (ABE) in newborns, but has limited use in evaluating the severity and prognosis of ABE. This study aims to assess the value of diffusion kurtosis imaging (DKI) in detecting ABE and understanding its pathogenesis.

Method: Seventy-six newborns with hyperbilirubinemia were grouped into three groups (mild group, moderate group, and severe group) based on serum bilirubin levels. All the patients underwent conventional MRI and DKI serial, as well as 40 healthy full-term infants (control group). The regions of interest (ROIs) were the bilateral globus pallidus, dorsal thalamus, frontal lobe, auditory radiation, superior temporal gyrus, substantia nigra, hippocampus, putamen, and inferior olivary nucleus. The values of mean diffusivity (MD), axial kurtosis (AK), radial kurtosis (RK), and mean kurtosis (MK), and fractional anisotropy (FA), radial diffusivity (RD), and axis diffusivity (AD) of the ROIs were evaluated. All newborns were followed up and evaluated using the Denver Development Screening Test (DDST). According to the follow-up results, the patients were divided into the normal group, the suspicious abnormal group, and the abnormal group.

Result: Compared with the control group, significant differences were observed with the increased MK of dorsal thalamus, AD of globus pallidus in the moderate group, and increased RD, MK, AK, and RK value of globus pallidus, dorsal thalamus, auditory radiation, superior temporal gyrus, and hippocampus in the severe group. The peak value of total serum bilirubin was moderately correlated with the MK of globus pallidus, dorsal thalamus, and auditory radiation and was positively correlated with the other kurtosis value. Out of 76 patients, 40 finished the DDST, and only 9 patients showed an abnormality. Compared with the normal group, the AK value of inferior olivary nucleus showed significant differences (p < 0.05) in the suspicious abnormal group, and the MK of globus pallidus, temporal gyrus, and auditory radiation; RK of globus pallidus, dorsal thalamus, and auditory radiation; and MD of globus pallidus showed significant differences (p < 0.05) in the abnormal group.

Conclusion: DKI can reflect the subtle structural changes of neonatal ABE, and MK is a sensitive indicator to indicate the severity of brain damage.
Individual-, Family-, and School-Level Ecological Correlates With Physical Fitness Among Chinese School-Aged Children and Adolescents: A National Cross-Sectional Survey in 2014
Authors: Dong Yanhui , Chen Manman , Chen Li , Wen Bo , Yang Yide , Wang Zhenghe , Ma Yinghua , Song Yi , Ma Jun , Lau Patrick W. C.
Published: August 2021

Introduction: Few studies have examined the association between the individual-, family-, and school-level ecological correlates and physical fitness among Chinese children and adolescents, which is the purpose of the present study.

Methods: A total of 157,168 children and adolescents, 10-18 years of age, with physical fitness data in 2014, participated in the study. Physical fitness was assessed, using six tests: forced vital capacity, standing long jump, sit and reach, body muscle strength, 50-m dash, and endurance running. Scores were aggregated to form a summary physical fitness indicator (PFI), which was then classified into five levels: low, low-middle, middle, middle-high, and high. Each option of individual-, family-, and school-level measures were constructed into a positive or negative correlate of physical fitness and then accumulated as a composite ecological score.

Results: Among the 20 individual-, family-, and school-level correlates, 18 were found to be significantly associated with PFI, with high PFI levels being correlated with the positive group of correlates and low PFI levels correlated with the negative group of correlates (p < 0.05). High scores of ecological correlates were associated with a high level of PFI [adjusted odds ratio (OR) = 1.06, 95% CI: 1.06, 1.07)] whereas low scores were associated with a low level of PFI (OR = 0.95, 95% CI:0.95, 0.95). The ecological correlates at the individual, school- and family-levels were shown to be significantly related to high PFI among Chinese children and adolescents aged 10-18 years with different ORs of 5.97 (95% CI: 5.51, 6.47), 3.94 (3.66, 4.24), and 1.25 (1.19, 1.31). The PAR% of 20 cumulative factors effects due to the negative and positive responses for low PFI levels were 35.9 and 16.1%, and, for high PFI levels, were 15.3 and 24.1%, among Chinese children and adolescents, respectively. Compared with the correlates at family and school levels, the correlates at individual levels had the largest PAR%.

Conclusion: Individual-, family-, and school-multilevel factors had a significant cumulative association with either improving or worsening aspects of physical fitness. Individual level factors remain at the core of physical fitness improvement. Comprehensive policies and measures are urgently needed to enhance the physical fitness of Chinese children and adolescents through involving further individual and environmental factors.
Diagnostic Value of Endotracheal Tube-Aspirate Soluble Triggering Receptor Expressed on Myeloid Cells-1 Concentration for Neonatal Ventilator-Associated Pneumonia
Authors: Zhou Jian , Zhou Jingqian , Hong Yan , Wang Youcheng , Lin Hailong , Huang Leting
Published: August 2021

Background: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is regarded as a biological marker of infection. We aimed to evaluate the diagnostic value of endotracheal tube (ETT)-sTREM-1 concentration in neonatal ventilator-associated pneumonia (NVAP), to explore the difference of (ETT)-sTREM-1 between preterm and full-term, and to investigate the influence of extrapulmonary infection on (ETT)-sTREM-1 concentration.

Methods: In this multicenter, controlled clinical trial of 60 preterm and 33 full-term neonates on mechanical ventilators, we measured concentrations of ETT-aspirate and serum sTREM-1, serum C-reactive protein, and serum procalcitonin, as well as white blood cell count. We initially divided cases into eight groups, based on three categories: preterm of full-term; NVAP or non-NVAP; and extrapulmonary infection present or absent. Groups were compared, and logistic regression analysis and receiver operating characteristic (ROC) analysis was performed to determine diagnostic value.

Results: The mean gestational age (± standard deviation) of preterm and full-term neonates was 28.9 ± 2.2 weeks and 39.5 ± 1.7 weeks, respectively, and 32/60 were male. The ETT-aspirate sTREM-1 concentration was higher in NVAP cases than in non-NVAP cases, irrespective of extrapulmonary infection. ROC analysis revealed that ETT-aspirate sTREM-1 concentration had an area under the curve (AUC) of 0.986 and a cutoff value of 228.0 pg/ml (sensitivity, 94.3%; specificity, 96%) in preterm neonates; the same values in full-term neonates were 0.938 and 245.5 pg/ml (sensitivity, 100%; specificity, 93.7%), respectively. The optimal combination of indicators was ETT-aspirate sTREM-1 and serum C-reactive protein concentration. All indicators were present at lower levels on days 8 and 10 of ventilation in neonates who ultimately recovered than in those who did not.

Conclusions: ETT-aspirate sTREM-1 and serum C-reactive protein concentrations may be useful for the diagnosis of NVAP.
Allogeneic Hematopoietic Stem Cell Transplantation for PEX1-Related Zellweger Spectrum Disorder: A Case Report and Literature Review
Authors: Chen Kai , Zhang Na , Shao Jing-Bo , Li Hong , Li Jie , Xi Jia-Ming , Xu Wu-Hen , Jiang Hui
Published: August 2021

Zellweger spectrum disorder (ZSD) is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation and attributable to mutations in the PEX gene family. Patients with ZSD have profound neurologic impairments, including seizures, severe retardation, and dysmorphic features, and poor prognosis. Currently, there is no specific, effective treatment. Here, we investigated the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on PEX1-related ZSD. The suspected clinical proband was first diagnosed at the Department of Neurology of our hospital. The proband died soon after diagnosis, and his family was studied. We found that a brother had the same genetic alterations, and he was diagnosed with Infantile Refsum disease (IRD) as the mildest form of ZSD. We implemented treatment with allo-HSCT, at the request of the child's parents. After transplantation, we observed significant improvements in the clinical manifestations, very-long-chain fatty acids, and brain MRI. The patient has recovered well and not showed any abnormal clinical manifestations after 2 years of follow-up. We have achieved satisfactory short-term results in the treatment of ZSD-IRD with allo-HSCT. Long-term follow-up and observation will be performed to determine the long-term prognosis.
Case Report: Paradoxical Inflammatory Response Syndrome in a Previously Healthy, HIV-Negative, Pediatric Patient With Cryptococcus gatii Meningitis
Authors: Cheng Jessica H. , Cheema Ritu , Williamson Peter R. , Dimitriades Victoria R.
Published: August 2021

The immunological response of patients with cryptococcal meningitis (CM), particularly those not known to be immunocompromised, has generated an increased interest recently. Although CM is an infection with significant rates of morbidity and mortality, its sequelae may also include a post-infectious inflammatory response syndrome (PIIRS) in patients who have already achieved microbiological control. PIIRS can cause substantial immune-mediated damage to the central nervous system resulting in long-term neurological disability or even death. Steroids have been used successfully in the management of PIIRS in adults. In this report, we present the case of a previously healthy adolescent male with Cryptococcus gattii meningitis who experienced neurological deterioration due to PIIRS after the initiation of antifungal therapy. Immunological workup did not demonstrate any frank underlying immunodeficiencies, and genetic primary immunodeficiency screening was unremarkable. He was treated with steroids and recovered clinically; however, intermittent inflammatory episodes needed to be managed through several flares of symptoms. In the setting of the current literature, we discuss the management and monitoring of PIIRS in a pediatric patient, along with considerations of targeted future therapies.
Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
Authors: Yang Runan , Li Zijing , Zou Yuting , Yang Jingjian , Li Lin , Xu Xiumei , Schmalzing Günther , Nie Hong , Li Guilin , Liu Shuangmei , Liang Shangdong , Xu Changshui
Published: August 2021

Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway.
β-Patchoulene Ameliorates Water Transport and the Mucus Barrier in 5-Fluorouracil-Induced Intestinal Mucositis Rats via the cAMP/PKA/CREB Signaling Pathway
Authors: Wu Jiazhen , Gan Yuxuan , Luo Huijuan , Xu Nan , Chen Liping , Li Mengyao , Guan Fengkun , Su Ziren , Lin Zhixiu , Xie Jianhui , Liu Yuhong
Published: August 2021

Intestinal mucositis (IM) is the main side effect observed in patients who receive cancer chemotherapy. The characteristics of ulceration, vomiting, and severe diarrhea cause patients to delay or abandon further treatment, thereby aggravating their progress. Hence, IM cannot be overlooked. β-patchoulene (β-PAE) is an active ingredient isolated from Pogostemon cablin (Blanco) Benth (Labiatae) and has shown a marked protective effect against gastrointestinal diseases in previous studies. However, whether β-PAE plays a positive role in IM is still unknown. Herein, we explore the effects and the underlying mechanism of β-PAE against 5-fluorouracil (5-FU)-induced IM in IEC-6 cells and rats. β-PAE significantly recovered cell viability, upregulated the IM-induced rat body weight and food intake and improved the pathological diarrhea symptoms. Aquaporin is critical for regulating water fluid homeostasis, and its abnormal expression was associated with pathological diarrhea in IM. β-PAE displayed an outstanding effect in inhibiting aquaporin 3 (AQP3) via the cAMP/protein kinase A (PKA)/cAMP-response element-binding protein (CREB) signaling pathway. Besides, inflammation-induced mucus barrier injury deteriorated water transport and aggravated diarrhea in IM-induced rats. β-PAE’s effect on suppressing inflammation and recovering the mucus barrier strengthened its regulation of water transport and thus alleviated diarrhea in IM-induced rats. In sum, β-PAE improved IM in rats mainly by improving water transport and the mucus barrier, and these effects were correlated with its function on inhibiting the cAMP/PKA/CREB signaling pathway.
Glycogen Metabolism Predicts the Efficacy of Immunotherapy for Urothelial Carcinoma
Authors: Zhang Yueming , Li Xuechun , Zhou Rui , Lin Anqi , Cao Manming , Lyu Qingwen , Luo Peng , Zhang Jian
Published: August 2021

Urothelial cancer (UC) is one of the common refractory tumors and chemotherapy is the primary treatment for it. The advent of immune checkpoint inhibitors (ICI) has facilitated the development of treatment strategies for UC patients. To screen out UC patients sensitive to ICI, researchers have proposed that PD-L1, tumor mutation burden and TCGA molecular subtypes can be used as predictors of ICI efficacy. However, the performance of these predictors needs further validation. We need to identify novel biomarkers to screen out UC patients sensitive to ICI. In our study, we collected the data of two clinical cohorts: the ICI cohort and the TCGA cohort. The result of the multivariate Cox regression analysis showed that glycogen metabolism score (GMS) (HR = 1.26, p = 0.017) was the negative predictor of prognosis for UC patients receiving ICI treatment. Low-GMS patients had a higher proportion of patients achieving complete response or partial response to ICI. After the comparison of gene mutation status between high-GMS and low-GMS patients, we identified six genes with significant differences in mutation frequencies, which may provide new directions for potential drug targets. Moreover, we analyzed the immune infiltration status and immune-related genes expression between high-GMS and low-GMS patients. A reduced proportion of tumor-associated fibroblasts and elevated proportion of CD8+ T cells can be observed in low-GMS patients while several immunosuppressive molecules were elevated in the high-GMS patients. Using the sequencing data of the GSE164042 dataset, we also found that myeloid-derived suppressor cell and neutrophil related signature scores were lower in α-glucosidase knockout bladder carcinoma cells when compared to the control group. In addition, angiogenesis, classic carcinogenic pathways, immunosuppressive cells related pathways and immunosuppressive cytokine secretion were mainly enriched in high-GMS patients and cell samples from the control group. Finally, we suspected that the combination treatment of ICI and histone deacetylase inhibitors may achieve better clinical responses in UC patients based on the analysis of drug sensitivity data. In conclusion, our study revealed the predictive value of GMS for ICI efficacy of UC patients, providing a novel perspective for the exploration of new drug targets and potential treatment strategies.
MicroRNA as an Important Target for Anticancer Drug Development
Authors: Fu Zhiwen , Wang Liu , Li Shijun , Chen Fen , Au-Yeung Kathy Ka-Wai , Shi Chen
Published: August 2021

Cancer has become the second greatest cause of death worldwide. Although there are several different classes of anticancer drugs that are available in clinic, some tough issues like side-effects and low efficacy still need to dissolve. Therefore, there remains an urgent need to discover and develop more effective anticancer drugs. MicroRNAs (miRNAs) are a class of small endogenous non-coding RNAs that regulate gene expression by inhibiting mRNA translation or reducing the stability of mRNA. An abnormal miRNA expression profile was found to exist widely in cancer cell, which induces limitless replicative potential and evading apoptosis. MiRNAs function as oncogenes (oncomiRs) or tumor suppressors during tumor development and progression. It was shown that regulation of specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways, and reverse the phenotypes in cancer cells. The miRNA hence provides an attractive target for anticancer drug development. In this review, we will summarize the latest publications on the role of miRNA in anticancer therapeutics and briefly describe the relationship between abnormal miRNAs and tumorigenesis. The potential of miRNA-based therapeutics for anticancer treatment has been critically discussed. And the current strategies in designing miRNA targeting therapeutics are described in detail. Finally, the current challenges and future perspectives of miRNA-based therapy are conferred.
Transverse and Quantum Localization of Light: A Review on Theory and Experiments
Authors: Giordani Taira , Schirmacher Walter , Ruocco Giancarlo , Leonetti Marco
Published: August 2021

Anderson localization is an interference effect yielding a drastic reduction of diffusion—including complete hindrance—of wave packets such as sound, electromagnetic waves, and particle wave functions in the presence of strong disorder. In optics, this effect has been observed and demonstrated unquestionably only in dimensionally reduced systems. In particular, transverse localization (TL) occurs in optical fibers, which are disordered orthogonal to and translationally invariant along the propagation direction. The resonant and tube-shaped localized states act as micro-fiber-like single-mode transmission channels. Since the proposal of the first TL models in the early eighties, the fabrication technology and experimental probing techniques took giant steps forwards: TL has been observed in photo-refractive crystals, in plastic optical fibers, and also in glassy platforms, while employing direct laser writing is now possible to tailor and “design” disorder. This review covers all these aspects that are today making TL closer to applications such as quantum communication or image transport. We first discuss nonlinear optical phenomena in the TL regime, enabling steering of optical communication channels. We further report on an experiment testing the traditional, approximate way of introducing disorder into Maxwell’s equations for the description of TL. We find that it does not agree with our findings for the average localization length. We present a new theory, which does not involve an approximation and which agrees with our findings. Finally, we report on some quantum aspects, showing how a single-photon state can be localized in some of its inner degrees of freedom and how quantum phenomena can be employed to secure a quantum communication channel.
Is Oxidative Stress the Link Between Cerebral Small Vessel Disease, Sleep Disruption, and Oligodendrocyte Dysfunction in the Onset of Alzheimer’s Disease?
Authors: Lloret Ana , Esteve Daniel , Lloret Maria Angeles , Monllor Paloma , López Begoña , León José Luis , Cervera-Ferri Ana
Published: August 2021

Oxidative stress is an early occurrence in the development of Alzheimer’s disease (AD) and one of its proposed etiologic hypotheses. There is sufficient experimental evidence supporting the theory that impaired antioxidant enzymatic activity and increased formation of reactive oxygen species (ROS) take place in this disease. However, the antioxidant treatments fail to stop its advancement. Its multifactorial condition and the diverse toxicological cascades that can be initiated by ROS could possibly explain this failure. Recently, it has been suggested that cerebral small vessel disease (CSVD) contributes to the onset of AD. Oxidative stress is a central hallmark of CSVD and is depicted as an early causative factor. Moreover, data from various epidemiological and clinicopathological studies have indicated a relationship between CSVD and AD where endothelial cells are a source of oxidative stress. These cells are also closely related to oligodendrocytes, which are, in particular, sensitive to oxidation and lead to myelination being compromised. The sleep/wake cycle is another important control in the proliferation, migration, and differentiation of oligodendrocytes, and sleep loss reduces myelin thickness. Moreover, sleep plays a crucial role in resistance against CSVD, and poor sleep quality increases the silent markers of this vascular disease. Sleep disruption is another early occurrence in AD and is related to an increase in oxidative stress. In this study, the relationship between CSVD, oligodendrocyte dysfunction, and sleep disorders is discussed while focusing on oxidative stress as a common occurrence and its possible role in the onset of AD.
Localized Pulmonary Vein Scar Promotes Atrial Fibrillation in High Left Atrial Pressure
Authors: Gottlieb Lisa A. , Vaillant Fanny , Abell Emma , Belterman Charly , Loyer Virginie , El Hamrani Dounia , Naulin Jérôme , Constantin Marion , Quesson Bruno , Boukens Bastiaan J. , Coronel Ruben , Dekker Lukas R. C.
Published: August 2021

Background

Pulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure.

Methods

Radiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode’s solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes).

Results

In high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011).

Conclusion

Localized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.
Data Mining Identifies Differentially Expressed Circular RNAs in Skeletal Muscle of Thermally Challenged Turkey Poults
Authors: Reed Kent M. , Mendoza Kristelle M. , Abrahante Juan E. , Velleman Sandra G. , Strasburg Gale M.
Published: August 2021

Precise regulation of gene expression is critical for normal muscle growth and development. Changes in gene expression patterns caused by external stressors such as temperature can have dramatic effects including altered cellular structure and function. Understanding the cellular mechanisms that underlie muscle growth and development and how these are altered by external stressors are crucial in maintaining and improving meat quality. This study investigated circular RNAs (circRNAs) as an emerging aspect of gene regulation. We used data mining to identify circRNAs and characterize their expression profiles within RNAseq data collected from thermally challenged turkey poults of the RBC2 and F-lines. From sequences of 28 paired-end libraries, 8924 unique circRNAs were predicted of which 1629 were common to all treatment groups. Expression analysis identified significant differentially expressed circRNAs (DECs) in comparisons between thermal treatments (41 DECs) and between genetic lines (117 DECs). No intersection was observed between the DECs and differentially expressed gene transcripts indicating that the DECs are not simply the result of expression changes in the parental genes. Comparative analyses based on the chicken microRNA (miRNA) database suggest potential interactions between turkey circRNAs and miRNAs. Additional studies are needed to reveal the functional significance of the predicted circRNAs and their role in muscle development in response to thermal challenge. The DECs identified in this study provide an important framework for future investigation.
Reinforcement Learning to Improve Image-Guidance of Ablation Therapy for Atrial Fibrillation
Authors: Muizniece Laila , Bertagnoli Adrian , Qureshi Ahmed , Zeidan Aya , Roy Aditi , Muffoletto Marica , Aslanidi Oleg
Published: August 2021

Atrial fibrillation (AF) is the most common cardiac arrhythmia and currently affects more than 650,000 people in the United Kingdom alone. Catheter ablation (CA) is the only AF treatment with a long-term curative effect as it involves destroying arrhythmogenic tissue in the atria. However, its success rate is suboptimal, approximately 50% after a 2-year follow-up, and this high AF recurrence rate warrants significant improvements. Image-guidance of CA procedures have shown clinical promise, enabling the identification of key patient anatomical and pathological (such as fibrosis) features of atrial tissue, which require ablation. However, the latter approach still suffers from a lack of functional information and the need to interpret structures in the images by a clinician. Deep learning plays an increasingly important role in biomedicine, facilitating efficient diagnosis and treatment of clinical problems. This study applies deep reinforcement learning in combination with patient imaging (to provide structural information of the atria) and image-based modelling (to provide functional information) to design patient-specific CA strategies to guide clinicians and improve treatment success rates. To achieve this, patient-specific 2D left atrial (LA) models were derived from late-gadolinium enhancement (LGE) MRI scans of AF patients and were used to simulate patient-specific AF scenarios. Then a reinforcement Q-learning algorithm was created, where an ablating agent moved around the 2D LA, applying CA lesions to terminate AF and learning through feedback imposed by a reward policy. The agent achieved 84% success rate in terminating AF during training and 72% success rate in testing. Finally, AF recurrence rate was measured by attempting to re-initiate AF in the 2D atrial models after CA with 11% recurrence showing a great improvement on the existing therapies. Thus, reinforcement Q-learning algorithms can predict successful CA strategies from patient MRI data and help to improve the patient-specific guidance of CA therapy.
Overexpression of a Banana Aquaporin Gene MaPIP1;1 Enhances Tolerance to Multiple Abiotic Stresses in Transgenic Banana and Analysis of Its Interacting Transcription Factors
Authors: Xu Yi , Liu Juhua , Jia Caihong , Hu Wei , Song Shun , Xu Biyu , Jin Zhiqiang
Published: August 2021

Aquaporins can improve the ability of plants to resist abiotic stresses, but the mechanism is still not completely clear. In this research, overexpression ofMaPIP1;1in banana improved tolerance to multiple stresses. The transgenic plants resulted in lower ion leakage and malondialdehyde content, while the proline, chlorophyll, soluble sugar, and abscisic acid (ABA) contents were higher. In addition, under high salt and recovery conditions, the content of Na+and K+is higher, also under recovery conditions, the ratio of K+/Na+is higher. Finally, under stress conditions, the expression levels of ABA biosynthesis and response genes in the transgenic lines are higher than those of the wild type. In previous studies, we proved that the MaMADS3 could bind to the promoter region ofMaPIP1;1, thereby regulating the expression ofMaPIP1;1and affecting the drought tolerance of banana plants. However, the mechanism ofMaPIP1;1gene response to stress under different adversity conditions might be regulated differently. In this study, we proved that some transcription factor genes, including MaERF14, MaDREB1G, MaMYB1R1, MaERF1/39, MabZIP53, and MaMYB22, showed similar expression patterns withMaPIP1;1under salt or cold stresses, and their encoded proteins could bind to the promoter region ofMaPIP1;1. Here we proposed a novelMaPIP1;1-mediated mechanism that enhanced salt and cold tolerance in bananas. The results of this study have enriched the stress-resistant regulatory network of aquaporins genes and are of great significance for the development of molecular breeding strategies for stress-resistant fruit crops.
First Report of CRISPR/Cas9 Gene Editing in Castanea sativa Mill
Authors: Pavese Vera , Moglia Andrea , Corredoira Elena , Martínez Mª Teresa , Torello Marinoni Daniela , Botta Roberto
Published: August 2021

CRISPR/Cas9 has emerged as the most important tool for genome engineering due to its simplicity, design flexibility, and high efficiency. This technology makes it possible to induce point mutations in one or some target sequences simultaneously, as well as to introduce new genetic variants by homology-directed recombination. However, this approach remains largely unexplored in forest species. In this study, we reported the first example of CRISPR/Cas9-mediated gene editing in Castanea genus. As a proof of concept, we targeted the gene encoding phytoene desaturase (pds), whose mutation disrupts chlorophyll biosynthesis allowing for the visual assessment of knockout efficiency. Globular and early torpedo-stage somatic embryos of Castanea sativa (European chestnut) were cocultured for 5 days with a CRISPR/Cas9 construct targeting two conserved gene regions of pds and subsequently cultured on a selection medium with kanamycin. After 8 weeks of subculture on selection medium, four kanamycin-resistant embryogenetic lines were isolated. Genotyping of these lines through target Sanger sequencing of amplicons revealed successful gene editing. Cotyledonary somatic embryos were maturated on maltose 3% and cold-stored at 4°C for 2 months. Subsequently, embryos were subjected to the germination process to produce albino plants. This study opens the way to the use of the CRISPR/Cas9 system in European chestnut for biotechnological applications
Well-Being of Adolescents in De-Escalation Situation: Physical, Emotional, Social, and Academic Impact
Authors: Berasategi Santxo Naiara , Idoiaga Mondragon Nahia , Ozamiz-Etxebarria Naiara , Dosil-Santamaria Maria
Published: August 2021

The Covid-19 pandemic has changed the world we knew in recent months. In the interest of maintaining social distance, lockdown periods have been established and schools in many countries have closed their doors. In this context, the objective of this research was to analyze the well-being of adolescents in Spain after lock-down and during the de-escalation process in a holistic way; taking into account their indicators on physical, emotional, social, and academic levels. The “Well-being of Children in Lockdown” (WCL) scale was used to measure the well-being of adolescents using these same parameters. The results point out that the general well-being of adolescents in the pandemic situation was situated at an intermediate level. Taking into account the different aspects measured within the general well-being, the domains that obtained the lowest scores were the domains of addictions and playful and creative activities. Intermediate scores were also obtained in the physical activity, emotional and academic domains, with the routine and academic domains having the highest scores. Boys and younger adolescents are those who show higher scores in the general well-being. Moreover, correlations appear between academic task stress and emotions, playful and creative activities, addictions, physical activity, routine, academic and overall well-being.
Modeling Bilingual Lexical Processing Through Code-Switching Speech: A Network Science Approach
Authors: Xu Qihui , Markowska Magdalena , Chodorow Martin , Li Ping
Published: August 2021

The study of code-switching (CS) speech has produced a wealth of knowledge in the understanding of bilingual language processing and representation. Here, we approach this issue by using a novel network science approach to map bilingual spontaneous CS speech. In Study 1, we constructed semantic networks on CS speech corpora and conducted community detections to depict the semantic organizations of the bilingual lexicon. The results suggest that the semantic organizations of the two lexicons in CS speech are largely distinct, with a small portion of overlap such that the semantic network community dominated by each language still contains words from the other language. In Study 2, we explored the effect of clustering coefficients on language choice during CS speech, by comparing clustering coefficients of words that were code-switched with their translation equivalents (TEs) in the other language. The results indicate that words where the language is switched have lower clustering coefficients than their TEs in the other language. Taken together, we show that network science is a valuable tool for understanding the overall map of bilingual lexicons as well as the detailed interconnections and organizations between the two languages.