bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis
Authors: Sun Xiaolin , Ding Tiantian , Wang Baoyue , Chang Zhifang , Fei Hongchang , Geng Lixia , Wang Yongfu
Published: February 2023

Objective

This study aimed to analyze potential biomarkers for systemic sclerosis (SSc) by constructing lncRNA–miRNA–mRNA networks in circulating exosomes (cirexos).

Materials and methods

Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in SSc cirexos were screened using high-throughput sequencing and detected with real-time quantitative PCR (RT-qPCR). Differentially expressed genes (DEGs) were analyzed using the DisGeNET, GeneCards, GSEA4.2.3, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Receiver operating characteristic (ROC) curves, correlation analyses, and a double-luciferase reporter gene detection assay were used to analyze competing endogenous RNA (ceRNA) networks and clinical data.

Results

In this study, 286 DEmRNAs and 192 DElncRNAs were screened, of which 18 DEGs were the same as the SSc-related genes. The main SSc-related pathways included extracellular matrix (ECM) receptor interaction, local adhesion, platelet activation, and IgA production by the intestinal immune network. A hub gene, COL1A1, was obtained by a protein–protein interaction (PPI) network. Four ceRNA networks were predicted through Cytoscape. The relative expression levels of COL1A1, ENST0000313807, and NON-HSAT194388.1 were significantly higher in SSc, while the relative expression levels of hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p were significantly lower in SSc (P < 0.05). The ROC curve showed that the ENST00000313807-hsa-miR-29a-3p-COL1A1 network as a combined biomarker of SSc is more valuable than independent diagnosis, and that it is correlated with high-resolution CT (HRCT), Scl-70, C-reactive protein (CRP), Ro-52, IL-10, IgM, lymphocyte percentage, neutrophil percentage, albumin divided by globulin, urea, and RDW-SD (P < 0.05). Double-luciferase reporter gene detection showed that ENST00000313807 interacts with hsa-miR-29a-3p, which interacts with COL1A1.

Conclusion

The ENST00000313807-hsa-miR-29a-3p-COL1A1 network in plasma cirexos represents a potential combined biomarker for the clinical diagnosis and treatment of SSc.
New perspective: Symbiotic pattern and assembly mechanism of Cantharellus cibarius-associated bacteria
Authors: Ge Wei , Ren Yulian , Dong Chunbo , Shao Qiuyu , Bai Yanmin , He Zhaoying , Yao Ting , Zhang Yanwei , Zhu Guosheng , Deshmukh Sunil Kumar , Han Yanfeng
Published: February 2023

Cantharellus cibarius, an ectomycorrhizal fungus belonging to the Basidiomycetes, has significant medicinal and edible value, economic importance, and ecological benefits. However, C. cibarius remains incapable of artificial cultivation, which is thought to be due to the presence of bacteria. Therefore, much research has focused on the relationship between C. cibarius and bacteria, but rare bacteria are frequently overlooked, and symbiotic pattern and assembly mechanism of the bacterial community associated with C. cibarius remain unknown. In this study, the assembly mechanism and driving factors of both abundant and rare bacterial communities of C. cibarius were revealed by the null model. The symbiotic pattern of the bacterial community was examined using a co-occurrence network. Metabolic functions and phenotypes of the abundant and rare bacteria were compared using METAGENassist2, and the impacts of abiotic variables on the diversity of abundant and rare bacteria were examined using partial least squares path modeling. In the fruiting body and mycosphere of C. cibarius, there was a higher proportion of specialist bacteria compared with generalist bacteria. Dispersal limitation dominated the assembly of abundant and rare bacterial communities in the fruiting body and mycosphere. However, pH, 1-octen-3-ol, and total phosphorus of the fruiting body were the main driving factors of bacterial community assembly in the fruiting body, while available nitrogen and total phosphorus of the soil affected the assembly process of the bacterial community in the mycosphere. Furthermore, bacterial co-occurrence patterns in the mycosphere may be more complex compared with those in the fruiting body. Unlike the specific potential functions of abundant bacteria, rare bacteria may provide supplementary or unique metabolic pathways (such as sulfite oxidizer and sulfur reducer) to enhance the ecological function of C. cibarius. Notably, while volatile organic compounds can reduce mycosphere bacterial diversity, they can increase fruiting body bacterial diversity. Findings from this study further, our understanding of C. cibarius-associated microbial ecology.
Soil temperature, microbial biomass and enzyme activity are the critical factors affecting soil respiration in different soil layers in Ziwuling Mountains, China
Authors: Qu Ruosong , Liu Guanzhen , Yue Ming , Wang Gangsheng , Peng Changhui , Wang Kefeng , Gao Xiaoping
Published: February 2023

Soil microorganisms are critical biological indicators for evaluating soil health and play a vital role in carbon (C)-climate feedback. In recent years, the accuracy of models in terms of predicting soil C pools has been improved by considering the involvement of microbes in the decomposition process in ecosystem models, but the parameter values of these models have been assumed by researchers without combining observed data with the models and without calibrating the microbial decomposition models. Here, we conducted an observational experiment from April 2021 to July 2022 in the Ziwuling Mountains, Loess Plateau, China, to explore the main influencing factors of soil respiration (RS) and determine which parameters can be incorporated into microbial decomposition models. The results showed that the RS rate is significantly correlated with soil temperature (TS) and moisture (MS), indicating that TS increases soil C loss. We attributed the non-significant correlation between RS and soil microbial biomass carbon (MBC) to variations in microbial use efficiency, which mitigated ecosystem C loss by reducing the ability of microorganisms to decompose organic resources at high temperatures. The structural equation modeling (SEM) results demonstrated that TS, microbial biomass, and enzyme activity are crucial factors affecting soil microbial activity. Our study revealed the relations between TS, microbial biomass, enzyme activity, and RS, which had important scientific implications for constructing microbial decomposition models that predict soil microbial activity under climate change in the future. To better understand the relationship between soil dynamics and C emissions, it will be necessary to incorporate climate data as well as RS and microbial parameters into microbial decomposition models, which will be important for soil conservation and reducing soil C loss in the Loess Plateau.
Production and characterization of bioemulsifier by Parapedobacter indicus
Authors: Devale Anushka , Sawant Rupali , Pardesi Karishma , Perveen Kahkashan , Khanam Mehrun NIsha , Shouche Yogesh , Mujumdar Shilpa
Published: February 2023

The current study evaluated Parapedobacter indicus MCC 2546 for its potential to produce a bioemulsifier (BE). Screening methods performed for BE production by P. indicus MCC 2546 showed good lipase activity, positive drop collapse test, and oil-spreading activity. Furthermore, it showed maximum emulsification activity (225 EU/ml) and emulsification index (E24 50%) at 37°C in Luria Bertani broth at 72 h with olive oil as a substrate. The optimal pH and NaCl concentration for maximum emulsification activity were 7 and 1%, respectively. P. indicus MCC 2546 lowered the surface tension of the culture medium from 59.65 to 50.42 ± 0.78 mN/m. BE produced was composed of 70% protein and 30% carbohydrate, which showed the protein–polysaccharide nature of the BE. Furthermore, Fourier transform infrared spectroscopy analysis confirmed the same. P. indicus MCC 2546 showed a catecholate type of siderophore production. This is the first report on BE and siderophore production by the genus Parapedobacter.
Regulation of pSYSA defense plasmid copy number in Synechocystis through RNase E and a highly transcribed asRNA
Authors: Kaltenbrunner Alena , Reimann Viktoria , Hoffmann Ute A. , Aoyagi Tomohiro , Sakata Minori , Nimura-Matsune Kaori , Watanabe Satoru , Steglich Claudia , Wilde Annegret , Hess Wolfgang R.
Published: February 2023

Synthetic biology approaches toward the development of cyanobacterial producer strains require the availability of appropriate sets of plasmid vectors. A factor for the industrial usefulness of such strains is their robustness against pathogens, such as bacteriophages infecting cyanobacteria. Therefore, it is of great interest to understand the native plasmid replication systems and the CRISPR-Cas based defense mechanisms already present in cyanobacteria. In the model cyanobacterium Synechocystis sp. PCC 6803, four large and three smaller plasmids exist. The ~100 kb plasmid pSYSA is specialized in defense functions by encoding all three CRISPR-Cas systems and several toxin-antitoxin systems. The expression of genes located on pSYSA depends on the plasmid copy number in the cell. The pSYSA copy number is positively correlated with the expression level of the endoribonuclease E. As molecular basis for this correlation we identified the RNase E-mediated cleavage within the pSYSA-encoded ssr7036 transcript. Together with a cis-encoded abundant antisense RNA (asRNA1), this mechanism resembles the control of ColE1-type plasmid replication by two overlapping RNAs, RNA I and II. In the ColE1 mechanism, two non-coding RNAs interact, supported by the small protein Rop, which is encoded separately. In contrast, in pSYSA the similar-sized protein Ssr7036 is encoded within one of the interacting RNAs and it is this mRNA that likely primes pSYSA replication. Essential for plasmid replication is furthermore the downstream encoded protein Slr7037 featuring primase and helicase domains. Deletion of slr7037 led to the integration of pSYSA into the chromosome or the other large plasmid pSYSX. Moreover, the presence of slr7037 was required for successful replication of a pSYSA-derived vector in another model cyanobacterium, Synechococcus elongatus PCC 7942. Therefore, we annotated the protein encoded by slr7037 as Cyanobacterial Rep protein A1 (CyRepA1). Our findings open new perspectives on the development of shuttle vectors for genetic engineering of cyanobacteria and of modulating the activity of the entire CRISPR-Cas apparatus in Synechocystis sp. PCC 6803.
Monthly dynamics of microbial communities and variation of nitrogen-cycling genes in an industrial-scale expanded granular sludge bed reactor
Authors: Zhang Kun , Zhang Yanling , Deng Maocheng , Wang Pengcheng , Yue Xiu , Wang Pandeng , Li Wenjun
Published: February 2023

Introduction

The expanded granular sludge bed (EGSB) is a major form of anaerobic digestion system during wastewater treatment. Yet, the dynamics of microbial and viral communities and members functioning in nitrogen cycling along with monthly changing physicochemical properties have not been well elucidated.

Methods

Here, by collecting the anaerobic activated sludge samples from a continuously operating industrial-scale EGSB reactor, we conducted 16S rRNA gene amplicon sequencing and metagenome sequencing to reveal the microbial community structure and variation with the ever-changing physicochemical properties along within a year.

Results

We observed a clear monthly variation of microbial community structures, while COD, the ratio of volatile suspended solids (VSS) to total suspended solids (TSS) (VSS/TSS ratio), and temperature were predominant factors in shaping community dissimilarities examined by generalized boosted regression modeling (GBM) analysis. Meanwhile, a significant correlation was found between the changing physicochemical properties and microbial communities (p <0.05). The alpha diversity (Chao1 and Shannon) was significantly higher (p <0.05) in both winter (December, January, and February) and autumn (September, October, and November) with higher organic loading rate (OLR), higher VSS/TSS ratio, and lower temperature, resulting higher biogas production and nutrition removal efficiency. Further, 18 key genes covering nitrate reduction, denitrification, nitrification, and nitrogen fixation pathways were discovered, the total abundance of which was significantly associated with the changing environmental factors (p <0.05). Among these pathways, the dissimilatory nitrate reduction to ammonia (DNRA) and denitrification had the higher abundance contributed by the top highly abundant genes narGH, nrfABCDH, and hcp. The COD, OLR, and temperature were primary factors in affecting DNRA and denitrification by GBM evaluation. Moreover, by metagenome binning, we found the DNRA populations mainly belonged to Proteobacteria, Planctomycetota, and Nitrospirae, while the denitrifying bacteria with complete denitrification performance were all Proteobacteria. Besides, we detected 3,360 non-redundant viral sequences with great novelty, in which Siphoviridae, Podoviridae, and Myoviridae were dominant viral families. Interestingly, viral communities likewise depicted clear monthly variation and had significant associations with the recovered populations (p <0.05).

Discussion

Our work highlights the monthly variation of microbial and viral communities during the continuous operation of EGSB affected by the predominant changing COD, OLR, and temperature, while DNRA and denitrification pathways dominated in this anaerobic system. The results also provide a theoretical basis for the optimization of the engineered system.
Reconsidering the role of blood-brain barrier in Alzheimer’s disease: From delivery to target
Authors: Sousa João André , Bernardes Catarina , Bernardo-Castro Sara , Lino Miguel , Albino Inês , Ferreira Lino , Brás José , Guerreiro Rita , Tábuas-Pereira Miguel , Baldeiras Inês , Santana Isabel , Sargento-Freitas João
Published: February 2023

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor–related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-β. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research.
Transcranial cortico-cortical paired associative stimulation (ccPAS) over ventral premotor-motor pathways enhances action performance and corticomotor excitability in young adults more than in elderly adults
Authors: Turrini Sonia , Bevacqua Naomi , Cataneo Antonio , Chiappini Emilio , Fiori Francesca , Candidi Matteo , Avenanti Alessio
Published: February 2023

Transcranial magnetic stimulation (TMS) methods such as cortico-cortical paired associative stimulation (ccPAS) can increase the strength of functional connectivity between ventral premotor cortex (PMv) and primary motor cortex (M1) via spike timing-dependent plasticity (STDP), leading to enhanced motor functions in young adults. However, whether this STDP-inducing protocol is effective in the aging brain remains unclear. In two groups of young and elderly healthy adults, we evaluated manual dexterity with the 9-hole peg task before and after ccPAS of the left PMv-M1 circuit. We observed that ccPAS enhanced dexterity in young adults, and this effect was anticipated by a progressive increase in motor-evoked potentials (MEPs) during ccPAS administration. No similar effects were observed in elderly individuals or in a control task. Across age groups, we observed that the magnitude of MEP changes predicted larger behavioral improvements. These findings demonstrate that left PMv-to-M1 ccPAS induces functionally specific improvements in young adults’ manual dexterity and an increase in corticomotor excitability, but altered plasticity prevents the effectiveness of ccPAS in the elderly.
Enriched environment promotes post-stroke angiogenesis through astrocytic interleukin-17A
Authors: Chen Xiuping , Liu Lingling , Zhong Yingjun , Liu Yang
Published: February 2023

Objective

Our previous studies have revealed that the protective effect of an enriched environment (EE) may be linked with astrocyte proliferation and angiogenesis. However, the relationship between astrocytes and angiogenesis under EE conditions still requires further study. The current research examined the neuroprotective effects of EE on angiogenesis in an astrocytic interleukin-17A (IL-17A)-dependent manner following cerebral ischemia/reperfusion (I/R) injury.

Methods

A rat model of ischemic stroke based on middle cerebral artery occlusion (MCAO) for 120 min followed by reperfusion was established, after which rats were housed in either EE or standard conditions. A set of behavior tests were conducted, including the modified neurological severity scores (mNSS) and the rotarod test. The infarct volume was evaluated by means of 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. To evaluate the levels of angiogenesis, the protein levels of CD34 were examined by means of immunofluorescence and western blotting, while the protein and mRNA levels of IL-17A, vascular endothelial growth factor (VEGF), and the angiogenesis-associated factors interleukin-6 (IL-6), JAK2, and STAT3 were detected by western blotting and real-time quantitative PCR (RT-qPCR).

Results

We found that EE promoted functional recovery, reduced infarct volume, and enhanced angiogenesis compared to rats in standard conditions. IL-17A expression in astrocytes was also increased in EE rats. EE treatment increased the levels of microvascular density (MVD) and promoted the expression of CD34, VEGF, IL-6, JAK2, and STAT3 in the penumbra, while the intracerebroventricular injection of the IL-17A-neutralizing antibody in EE rats attenuated EE-mediated functional recovery and angiogenesis.

Conclusion

Our findings revealed a possible neuroprotective mechanism of astrocytic IL-17A in EE-mediated angiogenesis and functional recovery after I/R injury, which might provide the theoretical basis for EE in clinical practise for stroke patients and open up new ideas for the research on the neural repair mechanism mediated by IL-17A in the recovery phase of stroke.
Selective intraarterial hypothermia combined with mechanical thrombectomy for acute cerebral infarction based on microcatheter technology: A single-center, randomized, single-blind controlled study
Authors: Wan Yue , Tian Hao , Wang Hui , Wang DaPeng , Jiang HaiWei , Fang Qi
Published: February 2023

Objective

To investigate the safety and efficacy of selective intraarterial hypothermia combined with mechanical thrombectomy in the treatment of acute cerebral infarction based on microcatheter technology.

Methods

A total of 142 patients with anterior circulation large vessel occlusion were randomly assigned to the hypothermic treatment group (test group) and the conventional treatment group (control group). National Institutes of Health Stroke Scale (NIHSS) scores, postoperative infarct volume, the 90-day good prognosis rate (modified Rankin Scale (mRS) score ≤ 2 points), and the mortality rate of the two groups were compared and analyzed. Blood specimens were collected from patients before and after treatment. Serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6), IL-10, and RNA-binding motif protein 3 (RBM3) were measured.

Results

The 7-day postoperative cerebral infarct volume [(63.7 ± 22.1) ml vs. (88.5 ± 20.8) ml] and NIHSS scores at postoperative Days 1, 7, and 14 [(6.8 ± 3.8) points vs. (8.2 ± 3.5) points; (2.6 ± 1.6) points vs. (4.0 ± 1.8) points; (2.0 ± 1.2) points vs. (3.5 ± 2.1) points] in the test group were significantly lower than those in the control group. The good prognosis rate at 90 days postoperatively (54.9 vs. 35.2%, P = 0.018) was significantly higher in the test group than in the control group. The 90-day mortality rate was not statistically significant (7.0 vs. 8.5%, P = 0.754). Immediately after surgery and 1 day after surgery, SOD, IL-10, and RBM3 levels in the test group were relatively higher than those in the control group, and the differences were statistically significant. Immediately after surgery and 1 day after surgery, MDA and IL-6 levels in the test group were relatively reduced compared with those in the control group, and the differences were statistically significant (P < 0.05). In the test group, RBM3 was positively correlated with SOD and IL-10.

Conclusion

Mechanical thrombectomy combined with intraarterial cold saline perfusion is a safe and effective measure for the treatment of acute cerebral infarction. Postoperative NIHSS scores and infarct volumes were significantly improved with this strategy compared with simple mechanical thrombectomy, and the 90-day good prognosis rate was improved. The mechanism by which this treatment exerts its cerebral protective effect may be by inhibiting the transformation of the ischaemic penumbra of the infarct core area, scavenging some oxygen free radicals, reducing inflammatory injury to cells after acute infarction and ischaemia–reperfusion, and promoting RBM3 production in cells.
Correlation of blood–brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer's disease
Authors: Cheng Zhaozhao , Dai Linbin , Wu Yan , Cao Yuqin , Chai Xianliang , Wang Peng , Liu Chang , Ni Ming , Gao Feng , Wang Qiong , Lv Xinyi
Published: February 2023

Background

Blood–brain barrier (BBB) damage is considered an important part of Alzheimer's disease (AD) progression, and cerebral small-vessel disease (CSVD) is commonly associated with AD. However, the relationship between BBB damage, small cerebrovascular lesions, especially cerebral microbleeds (CMBs), and amyloid and tau biomarkers remains controversial. Therefore, our study aimed to further investigate their association in our cohort of patients with AD.

Methods

A total of 139 individuals were divided into probable AD (18F-florbetapir PET positive, n = 101) and control group (cognitively normal, n = 38). The levels of cerebrospinal fluid (CSF) and plasma t-tau, p-tau181, Aβ40, Aβ42, and albumin were measured using corresponding commercial assay kits, and the CSF/plasma albumin ratio (Qalb), an indicator of BBB dysfunction, was calculated. CSVD burden and the number of CMBs were defined using magnetic resonance imaging.

Results

Patients with AD had higher Qalb (p = 0.0024), higher numbers of CMBs (p = 0.03), and greater CSVD burden (p < 0.0001). In the AD group, CMBs and CSVD correlated with a higher Qalb (p = 0.03), and the numbers of CMBs negatively correlated with CSF Aβ42 (p = 0.02).

Conclusion

Blood–brain barrier damage was accompanied by a more severe burden of CSVD, including CMB, in patients with AD.
A novel simulator-based checklist for evaluating residents' competence in cerebral angiography in China
Authors: Yi Xuxia , Wang Gang , Zhang Nai , Si Weixin , Lv Jianping
Published: February 2023

Background

Nowadays, with the fast-increasing demand for neuro-endovascular therapy, surgeons in this field are in urgent need. Unfortunately, there is still no formal skill assessment in neuro-endovascular therapy in China.

Methods

We used a Delphi method to design a newly objective checklist for standards of cerebrovascular angiography in China and evaluated its validity and reliability. A total of 19 neuro-residents with no interventional experience and 19 neuro-endovascular surgeons from two centers (Guangzhou and Tianjin) were recruited; they were divided into two groups: residents and surgeons. Residents completed a simulation-based cerebrovascular angiography operation training before assessment. Assessments were under live and video record forms with two tools: the existing global rating scale (GRS) of endovascular performance and the new checklist.

Results

The average scores of residents were significantly increased after training in two centers (p < 0.05). There is good consistency between GRS and the checklist (p = 0.856). Intra-rater reliability (Spearman's rho) of the checklist was >0.9, and the same result was also observed in raters between different centers and different assessment forms (p < 0.001, rho > 0.9). The reliability of the checklist was higher than that of the GRS (Kendall's harmonious coefficient is 0.849, while GRS is 0.684).

Conclusion

The newly developed checklist appears reliable and valid for evaluating the technical performance of cerebral angiography and differentiating between trained and untrained trainees' performance well. For its efficiency, our method has been proven to be a feasible tool for resident angiography examination in certification nationwide.
Interconnected sub-networks of the macaque monkey gustatory connectome
Authors: Hartig Renée , Karimi Ali , Evrard Henry C.
Published: February 2023

Macroscopic taste processing connectivity was investigated using functional magnetic resonance imaging during the presentation of sour, salty, and sweet tastants in anesthetized macaque monkeys. This examination of taste processing affords the opportunity to study the interactions between sensory regions, central integrators, and effector areas. Here, 58 brain regions associated with gustatory processing in primates were aggregated, collectively forming the gustatory connectome. Regional regression coefficients (or β-series) obtained during taste stimulation were correlated to infer functional connectivity. This connectivity was then evaluated by assessing its laterality, modularity and centrality. Our results indicate significant correlations between same region pairs across hemispheres in a bilaterally interconnected scheme for taste processing throughout the gustatory connectome. Using unbiased community detection, three bilateral sub-networks were detected within the graph of the connectome. This analysis revealed clustering of 16 medial cortical structures, 24 lateral structures, and 18 subcortical structures. Across the three sub-networks, a similar pattern was observed in the differential processing of taste qualities. In all cases, the amplitude of the response was greatest for sweet, but the network connectivity was strongest for sour and salty tastants. The importance of each region in taste processing was computed using node centrality measures within the connectome graph, showing centrality to be correlated across hemispheres and, to a smaller extent, region volume. Connectome hubs exhibited varying degrees of centrality with a prominent leftward increase in insular cortex centrality. Taken together, these criteria illustrate quantifiable characteristics of the macaque monkey gustatory connectome and its organization as a tri-modular network, which may reflect the general medial-lateral-subcortical organization of salience and interoception processing networks.
The emerging role of circular RNAs in Parkinson’s disease
Authors: Liao Jiajia , Zhang Qinxin , Huang Jinjun , He Honghu , Lei Jiang , Shen Yuefei , Wang Jin , Xiao Yousheng
Published: February 2023

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. It involves a gradual loss of dopaminergic neurons in the substantia nigra. Although many studies have been conducted, the underlying molecular pathways of PD remain largely unknown. Circular RNAs (circRNAs), a novel class of non-coding RNAs with a covalently closed loop structure, are common in the brain. They are stable, conserved molecules that are widely expressed in eukaryotes in tissue-, cell-, and development-specific patterns. Many circRNAs have recently been identified in nervous system diseases, and some circRNA expression profiles have been linked to PD. Given that recent research has indicated the essential roles of various circRNAs in the development and progression of neurodegenerative diseases, the identification of individual circRNAs may be a promising strategy for finding new treatment targets for PD. Moreover, the search for circRNAs with high specificity and sensitivity will open up new avenues for the early diagnosis and treatment of PD. Herein, we address the biogenesis, properties, and roles of circRNAs and review their potential utility as biomarkers and therapeutic targets in PD.
Oxygen switches: Refueling for cancer radiotherapy
Authors: Li Xianghui , Wang Haoran , Li Zhiyan , Tao Feng , Wu Jinhui , Guan Wenxian , Liu Song
Published: February 2023

Radiotherapy remains the major therapeutic intervention for tumor patients. However, the hypoxic tumor microenvironment leads to treatment resistance. Recently, a burgeoning number of nano-radiosensitizers designed to increase the oxygen concentration in tumors were reported. These nano radiosensitizers served as oxygen carriers, oxygen generators, and even sustained oxygen pumps, attracting increased research interest. In this review, we focus on the novel oxygen-enrich nano radiosensitizers, which we call oxygen switches, and highlight their influence in radiotherapy through different strategies. Physical strategies-based oxygen switches carried O2 into the tumor via their high oxygen capacity. The chemical reactions to generate O2in situ were triggered by chemical strategies-based oxygen switches. Biological strategies-based oxygen switches regulated tumor metabolism, remodeled tumor vasculature, and even introduced microorganisms-mediated photosynthesis for long-lasting hypoxia alleviating. Moreover, the challenges and perspectives of oxygen switches-mediated oxygen-enrich radiotherapy were discussed.
Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing’s sarcoma
Authors: Qu Guoxin , Xu Yuanchun , Qu Ye , Qiu Jinchao , Chen Guosheng , Zhao Nannan , Deng Jin
Published: February 2023

Background

Ewing’s sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods.

Methods

The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein–protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression.

Results

A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES.

Conlusion

UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.
The effect of perioperative blood transfusion on survival after renal cell carcinoma nephrectomy: A systematic review and meta-analysis
Authors: Liu Yang , Deng Xianzhong , Wen Zhi , Huang Jing , Wang Chongjian , Chen Caixia , Yang Xuesong
Published: February 2023

Background

The effect of perioperative blood transfusion (PBT) on postoperative survival in RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) remains controversial. Two meta-analyses in 2018 and 2019 reported the postoperative mortality of PBT patients with RCC, but they did not investigate the effect on the survival of patients. We performed a systematic review and meta-analysis of relevant literature to demonstrate whether PBT affected postoperative survival in RCC patients who received nephrectomy.

Methods

Pubmed, Web of Science, Cochrane, and Embase databases were searched. Studies comparing RCC patients with or without PBT following either RN or PN were included in this analysis. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included literature, and hazard ratios (HRs) of overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), as well as 95% confidence intervals, were considered as effect sizes. All data were processed using Stata 15.1.

Results

Ten retrospective studies involving 19,240 patients were included in this analysis, with the publication dates ranging from 2014 to 2022. Evidence revealed that PBT was significantly associated with the decline of OS (HR, 2.62; 95%CI: 1,98-3.46), RFS (HR, 2.55; 95%CI: 1.74-3.75), and CSS (HR, 3.15; 95%CI: 2.3-4.31) values. There was high heterogeneity among the study results due to the retrospective nature and the low quality of the included studies. Subgroup analysis findings suggested that the heterogeneity of this study might be caused by different tumor stages in the included articles. Evidence implied that PBT had no significant influence on RFS and CSS with or without robotic assistance, but it was still linked to worse OS (combined HR; 2.54 95% CI: 1.18, 5.47). Furthermore, the subgroup analysis with intraoperative blood loss lower than 800 ML revealed that PBT had no substantial impact on OS and CSS of postoperative RCC patients, whereas it was correlated with poor RFS (1.42, 95% CI: 1.02-1.97).

Conclusions

RCC patients undergoing PBT after nephrectomy had poorer survival.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363106.
Clinical and non-clinical determinants of cervical cancer mortality: A retrospective cohort study in Lagos, Nigeria
Authors: Ola Idris Olasunmbo , Okunowo Adeyemi Adebola , Habeebu Muhammad Yaqub , Miao Jonasson Junmei
Published: February 2023

Introduction

Cervical cancer (CCa) is the fourth most frequent and a common cause of cancer mortality in women, the majority of whom live in low- and middle-income countries. Data on CCa mortality and its determinants have been poorly studied in Nigeria, resulting in a paucity of information that can assist patient management and cancer control policy.

Aim

The purpose of this study was to assess the mortality rate among CCa patients in Nigeria as well as the major factors influencing CCa mortality.

Study design

Data from the medical records of 343 CCa patients seen at the Lagos University Teaching Hospital and NSIA-LUTH Cancer Center from 2015 to 2021 were used in a retrospective cohort analysis. The hazard ratios (HR) and confidence intervals (CI) associated with the exposure variables and CCa mortality were calculated using Cox proportional hazard regression.

Results

The CCa mortality rate was 30.5 per 100 women-years after 2.2 years of median follow-up. Clinical factors such as HIV/AIDS (adjusted HR [aHR]: 11.9; 95% CI: 4.6, 30.4), advanced clinical stage (aHR: 2.7; 95% CI: 1.5, 4.7), and anemia at presentation (aHR: 1.8; 95% CI: 1.1, 3.0) were associated with a higher mortality risk, as were non-clinical factors such as age at diagnosis >50 years (aHR: 1.4; 95% CI: 1.0, 1.9) and family history of CCa (aHR: 3.5; 95%CI: 1.1, 11.1)

Conclusion

CCa has a high mortality rate in Nigeria. Incorporating these clinical and non-clinical factors into CCa management and control policies may improve women’s outcomes.
Characteristics of recurrence, predictors for relapse and prognosis of rapid relapse triple-negative breast cancer
Authors: Cai Shuang-Long , Liu Jing-Jing , Liu Ying-Xue , Yu Shao-Hong , Liu Xu , Lin Xiu-Quan , Chen Hong-Dan , Fang Xuan , Ma Tao , Li Ya-Qing , Li Ying , Li Chun-Yan , Zhang Sheng , Chen Xiao-Geng , Guo Xiao-Jing , Zhang Jin
Published: February 2023

Background

Triple-negative breast cancer (TNBC) patients who recur at different times are associated with distinct biological characteristics and prognoses. Research on rapid-relapse TNBC (RR-TNBC) is sparse. In this study, we aimed to describe the characteristics of recurrence, predictors for relapse, and prognosis in rrTNBC patients.

Methods

Clinicopathological data of 1584 TNBC patients from 2014 to 2016 were retrospectively reviewed. The characteristics of recurrence were compared between patients with RR-TNBC and slow relapse TNBC(SR-TNBC). All TNBC patients were randomly divided into a training set and a validation set to find predictors for rapid relapse. The multivariate logistic regression model was used to analyze the data of the training set. C-index and brier score analysis for predicting rapid relapse in the validation set was used to evaluate the discrimination and accuracy of the multivariate logistic model. Prognostic measurements were analyzed in all TNBC patients.

Results

Compared with SR-TNBC patients, RR-TNBC patients tended to have a higher T staging, N staging, TNM staging, and low expression of stromal tumor-infiltrating lymphocytes (sTILs). The recurring characteristics were prone to appear as distant metastasis at the first relapse. The first metastatic site was apt to visceral metastasis and less likely to have chest wall or regional lymph node metastasis. Six predictors (postmenopausal status, metaplastic breast cancer,≥pT3 staging,≥pN1 staging, sTIL intermediate/high expression, and Her2 [1+]) were used to construct the predictive model of rapid relapse in TNBC patients. The C-index and brier score in the validation set was 0.861 and 0.095, respectively. This suggested that the predictive model had high discrimination and accuracy. The prognostic data for all TNBC patients showed that RR-TNBC patients had the worst prognosis, followed by SR-TNBC patients.

Conclusion

RR-TNBC patients were associated with unique biological characteristics and worse outcomes compared to non-RR-TNBC patients.
How to use participatory design to develop an eHealth intervention to reduce preprocedural stress and anxiety among children visiting the hospital: The Hospital Hero app multi-study and pilot report
Authors: Poot Charlotte C. , Meijer Eline , Bruil Annet , Venema Melanie , Vegt Niko J. H. , Donkel Nicole , van Noort Veronique , Chavannes Niels H. , Roest Arno A. W.
Published: February 2023

Background

Medical procedures can cause considerable stress and anxiety among children. Current interventions mainly diminish stress and anxiety during procedures, while stress and anxiety often build up at home. Moreover, interventions often focus on either distraction or preparation. eHealth can combine multiple strategies and provide a low-cost solution that can be used outside the hospital.

Objective

To develop an eHealth solution to diminish preprocedural stress and anxiety, and to evaluate the app on use, usability and user experience in practice. We also aimed to gain in-depth insights in children's and caregivers' opinions and experiences to inform future improvements.

Methods

This is a multi-study report on the development (Study 1) and evaluation (Study 2) of a first version of the developed app. In study 1 we adopted a participatory design approach in which children's experiences were central to the design process. We performed an experience journey session with stakeholders (n = 13) to map the child's outpatient journey, identify pains and gains, and formulate the desired experience journey. Iterative development and testing with children (n = 8) and caregivers (n = 6) resulted in a working prototype. The prototype was tested with children, resulting in a first version of the Hospital Hero app. The app was evaluated on use, user-experience and usability during an eight-week pilot study in practice (Study 2). We triangulated data from online interviews with children and caregivers (n = 21) and online questionnaires (n = 46).

Results

Multiple stress and anxiety experience touchpoints were identified. The Hospital Hero app supports children in their hospital journey by facilitating preparation at home and providing distraction at the hospital. The pilot study showed that the app was evaluated positively on usability and user-experience and is considered feasible. Qualitative data showed five themes: (1) user-friendliness, (2) coherence and power of storytelling, (3) motivation and reward, (4) fit with real hospital journey, (5) procedural comfort.

Discussion

Using participatory design, we developed a child-centered solution that supports children in the entire hospital journey and may diminish preprocedural stress and anxiety. Future efforts should create a more tailored journey, define an optimal engagement window and formulate implementation strategies.
Rearing behaviour in the mouse behavioural pattern monitor distinguishes the effects of psychedelics from those of lisuride and TBG
Authors: Chen Yahong , Liu Junhong , Yao Yishan , Yan Haitao , Su Ruibin
Published: February 2023

Psychedelics alter consciousness and may have potential for drug development. As psychedelics are likely therapeutically active, it is important to study their effects and mechanisms using preclinical models. Here, we examined the effects of phenylalkylamine and indoleamine psychedelics on locomotor activity and exploratory behaviour using the mouse Behavioural Pattern Monitor (BPM). DOM, mescaline, and psilocin reduced locomotor activity at high doses and influenced rearings, an exploratory behaviour, in a characteristic inverted U-shaped dose-response function. Pretreatment with the selective 5-HT2A antagonist M100907 reversed the drug-induced alterations in locomotor activity, rearings, and jumps after systemic administration of DOM at low doses. However, holepoking at the full range of doses tested was not blocked by M100907. Administration of the hallucinogenic 5-HT2A agonist 25CN-NBOH induced striking similarities in response to that to psychedelics; these alterations were significantly diminished by M100907, whereas the putatively non-hallucinogenic 5-HT2A agonist TBG did not affect locomotor activity, rearings, or jumps at the most effective doses. The nonhallucinogenic 5-HT2A agonist lisuride failed to increase rearing. The results of these experiments provide strong evidence that DOM-elicited increases in rearing are due to mediation by the 5-HT2A receptor. Finally, discriminant analysis was able to distinguish all four psychedelics from lisuride and TBG based on behavioural performance alone. Thus, increased rearing in mice could provide additional evidence of behavioural differences between hallucinogenic and nonhallucinogenic 5-HT2A agonists.
Lie symmetry analysis and exact solutions of the (3+1)-dimensional generalized Shallow Water-like equation
Authors: Yang Ben , Song Yunjia , Wang Zenggui
Published: February 2023

In this article, (3+1)-dimensional generalized Shallow Water-like (gSWl) equation is discussed. The infinitesimal generators of the equation are derived by using the Lie symmetry analysis method. The optimal system is obtained based on the adjoint table of the generators of the equation. Exact solutions of the equation are constructed by applying symmetry reduction, Exp−ϕ(ξ) expansion method, Exp-function expansion method, Riccati equation method, and G′/G expansion method. For analyzing the dynamical behavior of the solutions, we derive the physical structures of dark soliton, kink wave, and periodic solutions via numerical simulations.
A credible and adjustable load resource trading system based on blockchain networks
Authors: Jiang Wenqian , Lin Xiaoming , Yang Zhou , Xiao Yong , Zhang Kun , Zhou Mi , Qian Bin
Published: February 2023

In recent years, the residents’ demands for power supply is increasing. The load resource trading system responds to the demands through intelligent scheduling, which can effectively relieve the severe power load pressure. The load resource trading system is a type of nonlinear system because the trading price is adjustable with user’s credit, instead of being linear to the power trading volume. The adjustable load resource trading is faced with the challenges of large demands, strong user autonomy, and secure and tamper-proof transaction data. The blockchain technology has been widely concerned by industrial and academic domains due to its decentralization, strong encryption of account information, and traceability of transaction behaviour. In this paper, we propose a credible and adjustable load resource trading framework based on blockchain, which uses blockchain to achieve credible grid load resource trading. Firstly, we propose a two-layer blockchain architecture based on the alliance chain. The main chain maintains all the data of the system, and the station-area nodes constitute the alliance chain. We design a distributed trading processing mechanism based on hybrid consensus and sharding technologies, which promotes the speed of cross-station transaction consensus. Next, we propose a two-level bidding model, which determines the trading price of load resources based on the maximum benefit of users and the lowest cost of grid companies. The results of extensive experiments shows that our proposed framework can achieve the promising result.
Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges—The Hamburg perspective
Authors: Ismaili Djemail , Schulz Carl , Horváth András , Koivumäki Jussi T. , Mika Delphine , Hansen Arne , Eschenhagen Thomas , Christ Torsten
Published: February 2023

Models based on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are proposed in almost any field of physiology and pharmacology. The development of human induced pluripotent stem cell-derived cardiomyocytes is expected to become a step forward to increase the translational power of cardiovascular research. Importantly they should allow to study genetic effects on an electrophysiological background close to the human situation. However, biological and methodological issues revealed when human induced pluripotent stem cell-derived cardiomyocytes were used in experimental electrophysiology. We will discuss some of the challenges that should be considered when human induced pluripotent stem cell-derived cardiomyocytes will be used as a physiological model.