bluuebunny/crossref_metadata_2025 huggingface dataset:
Subclinical Thyrotoxicosis and Cardiovascular Risk: Assessment of Circulating Endothelial Progenitor Cells, Proangiogenic Cells, and Endothelial Function
Authors: Phowira Jason , Bakhashab Sherin , Doddaballapur Anuradha , Weaver Jolanta U.
Published: July 2022

Background

Subclinical thyrotoxicosis (SCT) is defined by low or undetectable thyroid-stimulating hormones and normal thyroid hormones. The treatment of SCT is uncertain despite being associated with increased cardiovascular risk (CVR) and mortality. Circulating endothelial progenitor cells (cEPCs) and circulating angiogenic cells (CACs) have been found to be reduced in conditions with CVR. We aimed to evaluate whether endothelial function and cEPC and CAC counts were reduced in SCT and to study the in vitro effect of triiodothyronine (T3) on proangiogenic cell (PAC) function from young healthy controls.

Methods

cEPCs (quantified by flow cytometry, 20 SCT/20 controls), CACs following in vitro cultures (15 SCT/14 controls), paracrine function of CACs, endothelial function by flow-mediated dilation (FMD, 9 SCT/9 controls), and the effect of T3 on apoptosis and endothelial nitric oxide synthase (eNOS) expression in PACs were studied.

Results

p < 0.001, CD133+/VEGFR-2+ 0.4 (0.0–0.7) vs. 0.6 (0.0–4.6), p = 0.009, CD34+/VEGFR-2+ 0.3 (0.0–1.0) vs. 0.7 (0.1–4.9), p = 0.002; while CAC count was similar. SCT predicted a lower cEPC count after adjustment for conventional CVR factors. FMD was lower in SCT subjects versus controls (% mean ± SD, 2.7 ± 2.3 vs. 6.1 ± 2.3, p = 0.005). In vitro studies showed T3 increased early apoptosis and reduced eNOS expression in PACs.

Conclusions

In conclusion, SCT is associated with reduced cEPC count and FMD, confirming increased CVR in SCT. Future outcome trials are required to examine if treatment of this subclinical hyperactive state improves cardiovascular outcome.

Clinical Trial Registration

http://www.controlled-trials.com/isrctn/, identifier ISRCTN70334066.
Data-Driven Reliability Evaluation of the Integrated Energy System Considering Optimal Service Restoration
Authors: Dai Pan , Yang Li , Zeng Yang , Niu Ming , Zhu Chao , Hu Zhesheng , Zhao Yuheng
Published: July 2022

The demand for environmental protection and energy utilization transformation has promoted the rapid development of integrated energy systems (IES). Reliability evaluation is a fundamental element in designing IES as it could instruct the planning and operation of IES. This study proposes a novel data-driven reliability improvement and evaluation method considering the three-state reliability model and an optimal service restoration model (OSR). First, a multi-energy flow model is introduced and linearized in order to reduce the computing complexity. Next, a three-state reliability model is developed, considering the transitional process and partial failure mode. Furthermore, an optimal service restoration model is established to determine the best repairment moment for minimizing the load curtailment, and a data-driven reliability evaluation method is developed that integrates OSR and models the stochastic state transition process using the historical measurement data of the smart meters. Finally, the proposed reliability evaluation method is tested on a test IES, and the numerical results validate its effectiveness in evaluating the reliability of IES and improving the overall reliability.
Appraisal-and-commendation policy and carbon emissions: Evidence from the national civilised city program in China
Authors: Huang Guobin , Zhao Guoqin , Huang Nan
Published: July 2022

Based on the theory of “Non-Economic Promotion Championship,” this paper takes Appraisal-And-Commendation (AAC) policy of National Civilised City (NCC) program in China as the research object, and analyses the influence and mechanism of the NCC on carbon emissions from the perspective of energy demand. We find that NCC reduces carbon emissions significantly, and this reduction effect continues to expand over time. Furthermore, the NCC reduces carbon emissions through two mechanisms: First, the NCC reduces carbon emissions by slowing urbanisation. This mechanism mainly functions in big cities, megacities, and super cities, and does not function in small and medium cities. Second, the NCC reduces carbon emissions by promoting industrial restructuring from secondary industry to tertiary industry. This carbon reduction effect is a pure structural adjustment effect, regardless of any effects on technological level and productivity. Moreover, there are regional differences in the reduction of carbon emissions by NCC through industrial restructuring in two dimensions: In the first dimension, compared with the western region and the northeast region, the eastern and central regions are more able and willing to reduce carbon emissions through industrial restructuring. In the second dimension, compared with the northern region, the southern region is more likely to reduce carbon emissions through industrial restructuring.
Impact of a water-sediment regulation scheme on nutrient variations at the Lijin station of the Yellow River
Authors: Li Chang , Wang Zhili , Liu Huaixiang , Zuo Liqin , Lu Yan , Wu Pan , Lu Yongjun
Published: July 2022

The water-sediment regulation scheme (WSRS) imposed on dams throughout the Yellow River not only alleviates siltation in the downstream section but also alters the nutrient characteristics, which indirectly affects the enrichment of nutrients in the estuary. Nevertheless, the long-term changes in the nutrient contents and their causes in the lower Yellow River (LYR) remain unclear, and the nutrients characteristics during the years with and without WSRS have yet to be compared. Therefore, the purpose of this study was to explore the variations in the nutrient contents and limitations at the Lijin station on the LYR over the past decade, especially during the annual WSRS period, and to compare the water quality characteristics at Lijin between the years with and without WSRS. The results reveal that WSRS significantly changed the seasonal nutrient concentrations (nitrogen, phosphorus and silicon) at the Lijin station. The fluxes of these nutrients during WSRS (excluding 2016 and 2017) accounted for 11.64–40.63% of the total annual fluxes. The N concentration in the LYR was higher than that in some global rivers, while the concentrations of dissolved inorganic phosphorus (DIP) and dissolved silica (DSi) were lower than the average levels in other rivers. In addition, higher values of dissolved inorganic nitrogen (DIN), DSi and the Redfield ratio indicated that the growth of phytoplankton at the Lijin station was strongly restricted by P. However, during the 2 years without WSRS (2016 and 2017), the proportions of the nutrient fluxes in June were less than 66% of those in the WSRS period in other years. Additionally, there was a potential Si limitation in June in these 2 years. Furthermore, due to the occurrence of floods upstream of the Yellow River and the low-level operation of the Xiaolangdi Reservoir, the fluxes of nutrients during WSRS in 2018 were approximately 0.90–4.20 times those during the same period in 2009–2015 and 6.30–35.76 times those in June 2016 and June 2017. This study shows that WSRS effectively changes the nutrient balance in the LYR and provides a reference for the multi-objective collaborative optimization of WSRS to improve siltation and control flood in the LYR.
Marine Ecological Governance Under New Media Environment: Tripartite Evolutionary Game and Simulation Analysis
Authors: Gao Lehua , Yan An , Yin Qiaorong
Published: July 2022

Based on the general reality that new media with massive information and strong interactivity play an increasingly prominent role in marine ecological governance, this study introduces the coastal public participation mechanism under the new media environment. Furthermore, based on the assumption of limited rationality, an evolutionary game model among local governments, marine enterprises, and the coastal public is constructed to explore the changes in game strategies among the three participating subjects over time. Then, we used MATLAB to simulate and analyze the evolutionary stabilization strategies under different parameters by combining our research data on governments at all levels, marine enterprises, and the coastal public in 14 cities in coastal areas of China. The study shows that: 1) an objective and a fair new media environment exert a positive guiding effect on marine ecological governance, whereas a false and distorted one will lead to chaos in marine ecological governance. 2) Considering the high accuracy of new media reports, the higher the sensitivity of the local governments and marine enterprises to media reports, the more inclined they are toward strong regulation and active governance. 3) The local governments can effectively restrain the marine hazard behavior of the marine enterprises by increasing penalties and environmental protection taxes, and it is equally important to guide marine enterprises to fully utilize high and new technology in the marine industry for improving economic benefits and reducing governance costs. 4) Coastal public participation can effectively compensate for the local governments’ regulatory loopholes and can reduce the cost of government regulation. Therefore, for ensuring objective reports of new media by establishing reward and punishment mechanisms and regularly selecting excellent new media, using new media to enhance the level of marine publicity and education to encourage the coastal public to widely and fully participate in marine ecological governance is an effective means.
Songbirds use scent cues to relocate to feeding sites after displacement: An experiment in great tits (Parus major)
Authors: Mahr Katharina , Nowack Linda , Knauer Felix , Hoi Herbert
Published: July 2022

Air-borne chemicals are highly abundant sensory cues and their use in navigation might be one of the major evolutionary mechanisms explaining the development of olfaction in animals. Despite solid evidence for the importance of olfaction in avian life (e.g., foraging or mating), the importance of chemical cues in avian orientation remains controversial. In particular, songbirds are sorely neglected models, despite their remarkable orientation skills. Here we show that great tits (Parus major) require olfactory cues to orientate toward winter-feeding sites within their home range after displacement. Birds that received an olfaction-depriving treatment were impaired in homing. However, the return rates between olfaction-deprived and control individuals did not differ. Birds with decreased perception of olfactory cues required more time to return to the winter feeding sites. This effect became apparent when the distance between the releasing and capture sites was greater. Our results indicate that even in a familiar environment with possible visual landmarks, scent cues might serve as an important source of information for orientation.
Integrated Bioinformatics Analysis of Serine Racemase as an Independent Prognostic Biomarker in Endometrial Cancer
Authors: Cui Zhiwei , Mo Jiantao , Wang Lijun , Wang Rongli , Cheng Feiyan , Wang Lihui , Yang Xinyuan , Wang Wei
Published: July 2022

Endometrial cancer (EC) kills about 76,000 women worldwide, with the highest incidence in industrialized countries. Because of the rise in disease mortality and new diagnoses, EC is now a top priority for women’s health. Serine racemase (SRR) is thought to play a role in the central nervous system, but its role in cancers, particularly in EC, is largely unknown. The current study starts with a pan-cancer examination of SRR’s expression and prognostic value before delving into SRR’s potential cancer-suppressing effect in patients with EC. SRR may affect the endometrial tumor immune microenvironment, according to subsequent immune-related analysis. SRR expression is also linked to several genes involved in specific pathways such as ferroptosis, N6-methyladenosine methylation, and DNA damage repair. Finally, we used the expression, correlation, and survival analyses to investigate the upstream potential regulatory non-coding RNAs of SRR. Overall, our findings highlight the prognostic significance of SRR in patients with EC, and we can formulate a reasonable hypothesis that SRR influences metabolism and obstructs key carcinogenic processes in EC.
Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID
Authors: Luo Yu-Si , Luo Lei , Li Wei , Chen Yan , Wu Guo-Feng , Chen Fang , Shen Hu-Yan , Li Hong-Man , Guo Ming-Yang , Yin Sha , Zhang Ke , Cheng Zhong-Shan
Published: July 2022

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as “brain fog”, which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.
Comprehensive Analysis Identifies and Validates the Tumor Microenvironment Subtypes to Predict Anti-Tumor Therapy Efficacy in Hepatocellular Carcinoma
Authors: Zhang Haohan , Yao Yi , Wu Jie , Zhou Jin , Zhao Chen , He Junju , Xu Bin
Published: July 2022

Objective

The objective of this study was to explore and verify the subtypes in hepatocellular carcinoma based on the immune (lymphocyte and myeloid cells), stem, and stromal cells in the tumor microenvironment and analyze the biological characteristics and potential relevance of each cluster.

Methods

We used the xCell algorithm to calculate cell scores and got subtypes by k-means clustering. In the external validation sets, we verified the conclusion stability by a neural network model. Simultaneously, we speculated the inner connection between clusters by pseudotime trajectory analysis and confirmed it by pathway enrichment, TMB, CNV, etc., analysis.

Result

According to the results of the consensus cluster, we chose k = 4 as the optimal value and got four different subtypes (C1, C2, C3, and C4) with different biological characteristics based on infiltrating levels of 48 cells in TME. In univariable Cox regression, the hazard ratio (HR) value of C3 versus C1 was 2.881 (95% CI: 1.572–5.279); in multivariable Cox regression, we corrected the age and TNM stage, and the HR value of C3 versus C1 was 2.510 (95% CI: 1.339–4.706). C1 and C2 belonged to the immune-active type, C3 and C4 related to the immune-insensitive type and the potential conversion relationships between clusters. We established a neural network model, and the area under the curves of the neural network model was 0.949 in the testing cohort; the same survival results were also observed in the external validation set. We compared the differences in cell infiltration, immune function, pathway enrichment, TMB, and CNV of four clusters and speculated that C1 and C2 were more likely to benefit from immunotherapy and C3 may benefit from FGF inhibitors.

Discussion

Our analysis provides a new approach for the identification of four tumor microenvironment clusters in patients with liver cancer and identifies the biological differences and predicts the immunotherapy efficacy between the four subtypes.
Cytokine Activation Reveals Tissue-Imprinted Gene Profiles of Mesenchymal Stromal Cells
Authors: Wiese Danielle M. , Wood Catherine A. , Ford Barry N. , Braid Lorena R.
Published: July 2022

Development of standardized metrics to support manufacturing and regulatory approval of mesenchymal stromal cell (MSC) products is confounded by heterogeneity of MSC populations. Many reports describe fundamental differences between MSCs from various tissues and compare unstimulated and activated counterparts. However, molecular information comparing biological profiles of activated MSCs across different origins and donors is limited. To better understand common and source-specific mechanisms of action, we compared the responses of 3 donor populations each of human umbilical cord (UC) and bone marrow (BM) MSCs to TNF-α, IL-1β or IFN-γ. Transcriptome profiles were analysed by microarray and select secretome profiles were assessed by multiplex immunoassay. Unstimulated (resting) UC and BM-MSCs differentially expressed (DE) 174 genes. Signatures of TNF-α-stimulated BM and UC-MSCs included 45 and 14 new DE genes, respectively, while all but 7 of the initial 174 DE genes were expressed at comparable levels after licensing. After IL-1β activation, only 5 of the 174 DE genes remained significantly different, while 6 new DE genes were identified. IFN-γ elicited a robust transcriptome response from both cell types, yet nearly all differences (171/174) between resting populations were attenuated. Nine DE genes predominantly corresponding to immunogenic cell surface proteins emerged as a BM-MSC signature of IFN-γ activation. Changes in protein synthesis of select analytes correlated modestly with transcript levels. The dynamic responses of licensed MSCs documented herein, which attenuated heterogeneity between unstimulated populations, provide new insight into common and source-imprinted responses to cytokine activation and can inform strategic development of meaningful, standardized assays.
Role of Vγ9vδ2 T lymphocytes in infectious diseases
Authors: Gay Laetitia , Mezouar Soraya , Cano Carla , Frohna Paul , Madakamutil Loui , Mège Jean-Louis , Olive Daniel
Published: July 2022

The T cell receptor Vγ9Vδ2 T cells bridge innate and adaptive antimicrobial immunity in primates. These Vγ9Vδ2 T cells respond to phosphoantigens (pAgs) present in microbial or eukaryotic cells in a butyrophilin 3A1 (BTN3) and butyrophilin 2A1 (BTN2A1) dependent manner. In humans, the rapid expansion of circulating Vγ9Vδ2 T lymphocytes during several infections as well as their localization at the site of active disease demonstrates their important role in the immune response to infection. However, Vγ9Vδ2 T cell deficiencies have been observed in some infectious diseases such as active tuberculosis and chronic viral infections. In this review, we are providing an overview of the mechanisms of Vγ9Vδ2 T cell-mediated antimicrobial immunity. These cells kill infected cells mainly by releasing lytic mediators and pro-inflammatory cytokines and inducing target cell apoptosis. In addition, the release of chemokines and cytokines allows the recruitment and activation of immune cells, promoting the initiation of the adaptive immune response. Finaly, we also describe potential new therapeutic tools of Vγ9Vδ2 T cell-based immunotherapy that could be applied to emerging infections.
Resident Memory B Cells in Barrier Tissues
Authors: Lee Choong Man , Oh Ji Eun
Published: July 2022

Epithelial barriers, which include the gastrointestinal, respiratory, and genitourinary mucosa, compose the body’s front line of defense. Since barrier tissues are persistently exposed to microbial challenges, a rapid response that can deal with diverse invading pathogens is crucial. Because B cells have been perceived as indirectly contributing to immune responses through antibody production, B cells functioning in the peripheral organs have been outside the scope of researchers. However, recent evidence supports the existence of tissue-resident memory B cells (BRMs) in the lungs. This population’s defensive response was stronger and faster than that of their circulating counterparts and could resist heterogeneous strains. With such traits, BRMs could be a promising target for vaccine design, but much about them remains to be revealed, including their locations, origin, specific markers, and the mechanisms of their establishment and maintenance. There is evidence for resident B cells in organs other than the lungs, suggesting that B cells are directly involved in the immune reactions of multiple non-lymphoid organs. This review summarizes the history of the discovery of BRMs and discusses important unresolved questions. Unique characteristics of humoral immunity that play an important role in the peripheral organs will be described briefly. Future research on B cells residing in non-lymphoid organs will provide new insights to help solve major problems regarding human health.
In Vivo and Clinical Studies of Sea Cucumber-Derived Bioactives for Human Health and Nutrition From 2012-2021
Authors: Liang Qi , Ahmed Faruq , Zhang Miansong , Sperou Niki , Franco Christopher M. M. , Feng Qianjin , Zhang Wei
Published: July 2022

Sea cucumbers are amongst the highest value seafoods available commercially, especially in the south-east Asian region, primarily due to their nutritional and health benefits as applied in Traditional Chinese Medicine. While the majority of studies for nutritional products derived from sea cucumber compounds have been conducted in vitro, the number of in vivo and evidence-based human clinical studies are limited. This review has critically assessed the advances in in vivo and clinical studies of sea cucumber-derived bioactives (both extracts and compounds) via a comprehensive literature research on papers published in the last ten years from 2012-2021. Sea cucumber-derived compounds were reported to have the following activities: anticancer, antihyperlipidemic, antihyperglycemic, anti-inflammatory, anticoagulant/antithrombotic, antioxidant, and antihypertension, immunomodulatory, wound healing and as treatments for Alzheimer’s and Parkinson’s diseases. These active compounds include triterpene glycosides (saponins), fucosylated chondroitin sulfate (FCS), cerebrosides, glycosaminoglycan, fucoidan, phospholipids, polysaccharides, peptides, long-chain bases, Frondanol A5, acid mucopolysaccharide, and phosphatidylcholines. Gaps, challenges and future directions have been identified and discussed separately to progress different areas of research and to further scientific validation, development and application of sea cucumbers for human health and nutritional products.
YciR, a Specific 3′-Phosphodiesterase, Plays a Role in the Pathogenesis of Uropathogenic Escherichia coli CFT073
Authors: Zhang Si , Wang Jingting , Fan Yu , Meng Wang , Qian Chengqian , Liu Peng , Wei Yi , Yuan Chao , Du Yuhui , Yin Zhiqiu
Published: July 2022

Urinary tract infections (UTIs), with the characteristics of recurrence and resistance to antibiotics due to misuse, remain a common health and economic issue for patients. Uropathogenic Escherichia coli (UPEC), which is capable of evading the immune response by forming intracellular bacterial communities (IBCs) in the cytoplasm of bladder epithelial cells (BECs) after invasion, has been shown to be the prevailing cause of UTIs. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a small molecule responsible for eliciting the innate immune response of the host only if it has not been degraded by some phosphodiesterases (PDEs), such as YciR. The relationship between YciR and c-di-GMP levels in UPEC is inconclusive. In this study, we investigated the gene expression profile of UPEC in BECs and identified yciR as an upregulated gene. Western blot revealed that YciR enhanced the virulence of UPEC by inhibiting the phosphorylation of NF-κB. The expression of yciR could be repressed by HupB in a directly binding manner. We identified YciR, a novel PDE, and defined its possible function in innate immune evasion. We also demonstrated that YciR is an HupB-dependent PDE that degrades c-di-GMP and that a low concentration of c-di-GMP might make NF-κB less phosphorylated, thereby reducing the host’s pro-inflammatory response. This is the first time that YciR has been identified as a virulence factor in the pathogenesis of UPEC. These findings further increase our understanding of the pathogenesis of UPEC and provide a theoretical basis for further studies.
Metagenomics: An Approach for Unraveling the Community Structure and Functional Potential of Activated Sludge of a Common Effluent Treatment Plant
Authors: Vasudeva Gunjan , Singh Harpreet , Paliwal Sakshi , Pinnaka Anil Kumar
Published: July 2022

The common effluent treatment plant (CETP) located at Baddi treats the industrial effluent from various industries, leading to the pooling of a diverse range of substrates and metabolites. The nutrient loading and its availability decide the balance of the microbial community and its diversity. The samples thus collected from the activated sludge (BS14) of CETP and Sirsa river (SR1) from the vicinity of CETP effluent discharge were processed for the whole metagenome analysis to reveal the microbial community and its functional potential. The taxonomic classification of the BS14 sample showed the dominance of the bacterial community with 96% of abundance, whereas the SR1 was populated by eukaryotes representing 50.4% of the community of SR1. The bacterial community of SR1 was constituted of 47.2%. The functional analysis of BS14 and SR1 with GhostKOALA against the KEGG database assigned 43.7% and 27.8% of the open reading frames (ORFs) with functions. It revealed the xenobiotic degradation modules with complete pathways along with resistance against the beta-lactams. The analysis with the comprehensive antibiotic resistance database (CARD) revealed 33 and 32 unique types of antimicrobial resistance in BS14 and SR1, respectively. Both the samples were dominated by the beta-lactam resistance genes. The carbohydrate-active enzyme (CAZy) database assigned a total of 6,611 and 2,941 active enzymes to BS14 and SR1, respectively. In contrast, the glycosyl hydrolases (GH) and glycosyltransferases (GT) class of enzymes were found to be abundant in both the samples as compared with polysaccharide lyases (PL), auxiliary activities (AA), carbohydrate esterases (CE), and carbohydrate-binding module (CBM).
The Gut Microbiota Determines the High-Altitude Adaptability of Tibetan Wild Asses (Equus kiang) in Qinghai-Tibet Plateau
Authors: Liu Hongjin , Han Xueping , Zhao Na , Hu Linyong , Wang Xungang , Luo Chongliang , Chen Yongwei , Zhao Xinquan , Xu Shixiao
Published: July 2022

It was acknowledged long ago that microorganisms have played critical roles in animal evolution. Tibetan wild asses (TWA,Equus kiang) are the only wild perissodactyls on the Qinghai-Tibet Plateau (QTP) and the first national protected animals; however, knowledge about the relationships between their gut microbiota and the host's adaptability remains poorly understood. Herein, 16S rRNA and meta-genomic sequencing approaches were employed to investigate the gut microbiota–host associations in TWA and were compared against those of the co-resident livestock of yak (Bos grunnies) and Tibetan sheep (Ovis aries). Results revealed that the gut microbiota of yak and Tibetan sheep underwent convergent evolution. By contrast, the intestinal microflora of TWA diverged in a direction enabling the host to subsist on sparse and low-quality forage. Meanwhile, high microbial diversity (Shannon and Chao1 indices), cellulolytic activity, and abundant indicator species such as Spirochaetes, Bacteroidetes,Prevotella_1, andTreponema_2supported forage digestion and short-chain fatty acid production in the gut of TWA. Meanwhile, the enterotype identification analysis showed that TWA shifted their enterotype in response to low-quality forage for a better utilization of forage nitrogen and short-chain fatty acid production. Metagenomic analysis revealed that plant biomass degrading microbial consortia, genes, and enzymes like the cellulolytic strains (Prevotella ruminicola, Ruminococcus flavefaciens, Ruminococcus albus, Butyrivibrio fibrisolvens, andRuminobacter amylophilus), as well as carbohydrate metabolism genes (GH43, GH3, GH31, GH5, and GH10) and enzymes (β-glucosidase, xylanase, and β-xylosidase, etc.) had a significantly higher enrichment in TWA. Our results indicate that gut microbiota can improve the adaptability of TWA through plant biomass degradation and energy maintenance by the functions of gut microbiota in the face of nutritional deficiencies and also provide a strong rationale for understanding the roles of gut microbiota in the adaptation of QTP wildlife when facing harsh feeding environments.
Characterization of novel small non-coding RNAs and their modifications in bladder cancer using an updated small RNA-seq workflow
Authors: Su Zhangli , Monshaugen Ida , Klungland Arne , Ougland Rune , Dutta Anindya
Published: July 2022

Background: Bladder cancer (BLCA) is one of the most common cancer types worldwide. The disease is responsible for about 200,000 deaths annually, thus improved diagnostics and therapy is needed. A large body of evidence reveal that small RNAs of less than 40 nucleotides may act as tumor suppressors, oncogenes, and disease biomarkers, with a major focus on microRNAs. However, the role of other families of small RNAs is not yet deciphered. Recent results suggest that small RNAs and their modification status, play a role in BLCA development and are promising biomarkers due to their high abundance in the exomes and body fluids (including urine). Moreover, free modified nucleosides have been detected at elevated levels from the urine of BLCA patients. A genome-wide view of small RNAs, and their modifications, will help pinpoint the molecules that could be used as biomarker or has important biology in BLCA development.

Methods: BLCA tumor tissue specimens were obtained from 12 patients undergoing transurethral resection of non-muscle invasive papillary urothelial carcinomas. Genome-wide profiling of small RNAs less than 40 bases long was performed by a modified protocol with TGIRT (thermostable group II reverse transcriptase) to identify novel small RNAs and their modification status.

Results: Comprehensive analysis identified not only microRNAs. Intriguingly, 57 ± 15% (mean ± S.D.) of sequencing reads mapped to non-microRNA-small RNAs including tRNA-derived fragments (tRFs), ribosomal RNA-derived fragments (rRFs) and YRNA-derived fragments (YRFs). Misincorporation (mismatch) sites identified potential base modification positions on the small RNAs, especially on tRFs, corresponding to m1A (N1-methyladenosine), m1G (N1-methylguanosine) and m22G (N2, N2-dimethylguanosine). We also detected mismatch sites on rRFs corresponding to known modifications on 28 and 18S rRNA.

Conclusion: We found abundant non-microRNA-small RNAs in BLCA tumor samples. Small RNAs, especially tRFs and rRFs, contain modifications that can be captured as mismatch by TGIRT sequencing. Both the modifications and the non-microRNA-small RNAs should be explored as a biomarker for BLCA detection or follow-up.
Meta-Analysis of qPCR for Bovine Respiratory Disease Based on MIQE Guidelines
Authors: Barnewall Rebecca J. , Marsh Ian B. , Quinn Jane C.
Published: July 2022

Qualitative and quantitative PCR-based tests are widely used in both diagnostics and research to assess the prevalence of disease-causing pathogens in veterinary medicine. The efficacy of these tests, usually measured in terms of sensitivity and specificity, is critical in confirming or excluding a clinical diagnosis. We undertook a meta-analysis to assess the inherent value of published PCR diagnostic approaches used to confirm and quantify bacteria and viruses associated with bovine respiratory disease (BRD) in cattle. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough search of nine electronic databases (Web of Science, EBSCOhost, Cambridge journals online, ProQuest, PubMed, Sage journals online, ScienceDirect, Wiley online library and MEDLINE) was undertaken to find studies that had reported on the use of PCR and/or qPCR for the detection and/or quantification of BRD associated organisms. All studies meeting the inclusion criteria for reporting quantitative PCR for identification of BRD associated microorganisms were included in the analysis. Studies were then assessed on the applications of the Minimum Information for Publication of Quantitative Real-Time PCR Experiment (MIQE) and PCR primer/probe sequences were extracted and tested for in silico specificity using a high level of stringency. Fourteen full-text articles were included in this study. Of these, 79% of the analysed articles did not report the application of the MIQE guidelines in their study. High stringency in silico testing of 144 previously published PCR primer/probe sequences found many to have questionable specificity. This review identified a high occurrence of primer/probe sequences with a variable in silico specificity such that this may have implications for the accuracy of reporting. Although this analysis was only applied to one specific disease state, identification of animals suspected to be suffering from bovine respiratory disease, there appears to be more broadly a need for veterinary diagnostic studies to adopt international best practice for reporting of quantitative PCR diagnostic data to be both accurate and comparable between studies and methodologies.
A Deep Spatiotemporal Attention Network for Mild Cognitive Impairment Identification
Authors: Feng Quan , Huang Yongjie , Long Yun , Gao Le , Gao Xin
Published: July 2022

Mild cognitive impairment (MCI) is a nervous system disease, and its clinical status can be used as an early warning of Alzheimer's disease (AD). Subtle and slow changes in brain structure between patients with MCI and normal controls (NCs) deprive them of effective diagnostic methods. Therefore, the identification of MCI is a challenging task. The current functional brain network (FBN) analysis to predict human brain tissue structure is a new method emerging in recent years, which provides sensitive and effective medical biomarkers for the diagnosis of neurological diseases. Therefore, to address this challenge, we propose a novel Deep Spatiotemporal Attention Network (DSTAN) framework for MCI recognition based on brain functional networks. Specifically, we first extract spatiotemporal features between brain functional signals and FBNs by designing a spatiotemporal convolution strategy (ST-CONV). Then, on this basis, we introduce a learned attention mechanism to further capture brain nodes strongly correlated with MCI. Finally, we fuse spatiotemporal features for MCI recognition. The entire network is trained in an end-to-end fashion. Extensive experiments show that our proposed method significantly outperforms current baselines and state-of-the-art methods, with a classification accuracy of 84.21%.
The Fate of Tau Aggregates Between Clearance and Transmission
Authors: Seitkazina Assel , Kim Kyu Hyeon , Fagan Erin , Sung Yoonsik , Kim Yun Kyung , Lim Sungsu
Published: July 2022

Neuronal accumulation of mis-folded tau is the pathological hallmark of multiple neurodegenerative disorders, including Alzheimer’s disease. Distinct from amyloid plaques, which appear simultaneously throughout the brain, tau pathology develops first in a specific brain region and then propagates to neuroanatomically connected brain regions, exacerbating the disease. Due to the implication in disease progression, prevention of tau transmission is recognized as an important therapeutic strategy that can halt disease progression in the brain. Recently, accumulating studies have demonstrated diverse cellular mechanisms associated with cell-to-cell transmission of tau. Once transmitted, mis-folded tau species act as a prion-like seed for native tau aggregation in the recipient neuron. In this review, we summarize the diverse cellular mechanisms associated with the secretion and uptake of tau, and highlight tau-trafficking receptors, which mediate tau clearance or cell-to-cell tau transmission.
Prevention and treatment of natural products from Traditional Chinese Medicine in depression: Potential targets and mechanisms of action
Authors: He Ming-Chao , Feng Rui , Wang Jing , Xia Shi-Hui , Wang Yong-Jun , Zhang Yan
Published: July 2022

The molecular pathology involved in the development of depression is complex. Many signaling pathways and transcription factors have been demonstrated to display crucial roles in the process of depression occurrence and development. The multi-components and multi-targets of Traditional Chinese Medicine (TCM) are uniquely advantageous in the prevention and treatment of chronic diseases. This review summarizes the pharmacological regulations of natural products from TCM in the prevention and treatment of depression from the aspects of transcription factors (CREB, NF-κB, Nrf2) and molecular signaling pathways (BDNF-TrkB, MAPK, GSK-3β, TLR-4).
An innovative therapeutic educational program to support older drivers with cognitive disorders: Description of a randomized controlled trial study protocol
Authors: Delphin-Combe Floriane , Coste Marie-Hélène , Bachelet Romain , Llorens Mélissa , Gentil Claire , Giroux Marion , Paire-Ficout Laurence , Ranchet Maud , Krolak-Salmon Pierre
Published: July 2022

Older drivers face the prospect of having to adjust their driving habits because of health problems, which can include neurocognitive disorders. Self-awareness of driving difficulties and the interaction between individual with neurocognitive disorders and natural caregiver seem to be important levers for the implementation of adaptation strategies and for the subsequent voluntary cessation of driving when the cognitive disorders become too severe. This study aims to evaluate an educational program for patient/natural caregiver dyads who wish to implement self-regulation strategies in driving activity, and to improve self-awareness of driving ability. The ACCOMPAGNE program is based on seven group workshops, which target the dyad. The workshops deal with the impact of cognitive, sensory and iatrogenic disorders on driving. They tackle questions about responsibility, and about autonomy and social life. They also provide alternative solutions aimed at maintaining outward-looking activities even if driving is reduced or stopped. A randomized controlled trial is planned to evaluate the effectiveness of the program 2 months and 6 months after inclusion, and to compare this to the effectiveness of conventional approaches. The main outcome of this trial (i.e., the implementation of self-regulated driving strategies), will be measured based on scores on the “Current Self-Regulatory Practices” subscale of the Driver Perception and Practices Questionnaire. The Driving Habits Questionnaire will be used to measure secondary outcomes (indicators of driving changes; indicators of changes in mood, quality of life and caregiver burden; and self-awareness of driving abilities). Indicators will be collected for both patients and natural caregivers. This cognitive, social and psychological program should allow older individuals with cognitive disorders to drive more safely, and help to maintain the quality of life and mood of both patient and natural caregiver despite driving limitations. The patient's care path would be optimized, as he/she would become an actor in the process of giving up driving, which will, most certainly, be needed at some point in the progress of neurocognitive disorders. This process ranges from becoming aware of driving difficulties, to implementing self-regulation strategies, through to complete cessation of driving when necessary.

Clinical trial registration number

NCT04493957.
Citicoline Treatment in Acute Ischemic Stroke: A Randomized, Single-Blind TMS Study
Authors: Premi Enrico , Cantoni Valentina , Benussi Alberto , Gilberti Nicola , Vergani Veronica , Delrio Ilenia , Gamba Massimo , Spezi Raffaella , Costa Angelo , Padovani Alessandro , Borroni Barbara , Magoni Mauro
Published: July 2022

Background

Recent research on animal models of ischemic stroke supports the idea that pharmacological treatment potentially enhancing intrinsic brain plasticity could modulate acute brain damage, with improved functional recovery. One of these new drugs is citicoline, which could provide neurovascular protection and repair effects.

Objectives

The objective of this randomized, single-blind experimental study was to evaluate whether the treatment with Rischiaril® Forte was able to restore intracortical excitability measures, evaluated through transcranial magnetic stimulation (TMS) protocols, in patients with acute ischemic stroke.

Methods

Patients with acute ischemic stroke were recruited and assigned to an eight-week therapy of standard treatment (control group - CG) or CDP-choline (Rischiaril® Forte, containing 1,000 mg of citicoline sodium salt) added to conventional treatment (treatment group - TG). Each subject underwent a clinical evaluation and neurophysiological assessment using TMS, pretretament and posttreatment.

Results

A total of thirty participants (mean [SD] age, 68.1 [9.6] years; 11 women [37%]) completed the study. We did not observe significant changes in clinical scores after CDP-choline treatment (all p > 0.05), but we observed a significant improvement in short-interval intracortical inhibition (SAI) (p = 0.003) in the TG group compared to the CG group.

Conclusions

The eight-week treatment with citicoline after acute ischemic stroke may restore intracortical excitability measures, which partially depends on cholinergic transmission. This study extends current knowledge of the application of citicoline in acute ischemic stroke.
Bidirectional Relationship Between Sleep Disturbances and Parkinson's Disease
Authors: Minakawa Eiko N.
Published: July 2022

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Both diseases share common clinical and pathological features: the gradual progression of neurological and psychiatric symptoms caused by neuronal dysfunction and neuronal cell death due to the accumulation of misfolded and neurotoxic proteins. Furthermore, both of them are multifactorial diseases in which both genetic and non-genetic factors contribute to the disease course. Non-genetic factors are of particular interest for the development of preventive and therapeutic approaches for these diseases because they are modifiable; of these, sleep is a particularly intriguing factor. Sleep disturbances are highly prevalent among both patients with AD and PD. To date, research has suggested that sleep disturbances are a consequence as well as a risk factor for the onset and progression of AD, which implies a bidirectional relationship between sleep and AD. Whether such a relationship exists in PD is less certain, albeit highly plausible given the shared pathomechanisms. This review examines the current evidence for the bidirectional relationship between sleep and PD. It includes research in both humans and animal models, followed by a discussion of the current understanding of the mechanisms underlying this relationship. Finally, potential avenues of research toward achieving disease modification to treat or prevent PD are proposed. Although further efforts are crucial for preventing the onset and slowing the progress of PD, it is evident that sleep is a valuable candidate target for future interventions to improve the outcomes of PD patients.
Incongruity of Geometric and Spectral Markers in the Assessment of Body Sway
Authors: Sozzi Stefania , Ghai Shashank , Schieppati Marco
Published: July 2022

Different measurements of body oscillations in the time or frequency domain are being employed as markers of gait and balance abnormalities. This study investigates basic relationships within and between geometric and spectral measures in a population of young adult subjects. Twenty healthy subjects stood with parallel feet on a force platform with and without a foam pad. Adaptation effects to prolonged stance were assessed by comparing the first and last of a series of eight successive trials. Centre of Foot Pressure (CoP) excursions were recorded with Eyes Closed (EC) and Open (EO) for 90s. Geometric measures (Sway Area, Path Length), standard deviation (SD) of the excursions, and spectral measure (mean power Spectrum Level and Median Frequency), along the medio-lateral (ML) and antero-posterior (AP) direction were computed. Sway Area was more strongly associated than Path Length with CoP SD and, consequently, with mean Spectrum Level for both ML and AP, and both visual and surface conditions. The squared-SD directly specified the mean power Spectrum Level of CoP excursions (ML and AP) in all conditions. Median Frequency was hardly related to Spectrum Level. Adaptation had a confounding effect, whereby equal values of Sway Area, Path Length, and Spectrum Level corresponded to different Median Frequency values. Mean Spectrum Level and SDs of the time series of CoP ML and AP excursions convey the same meaning and bear an acceptable correspondence with Sway Area values. Shifts in Median Frequency values represent important indications of neuromuscular control of stance and of the effects of vision, support conditions, and adaptation. The Romberg Quotient EC/EO for a given variable is contingent on the compliance of the base of support and adaptation, and different between Sway Area and Path Length, but similar between Sway Area and Spectrum Level (AP and ML). These measures must be taken with caution in clinical studies, and considered together in order to get a reliable indication of overall body sway, of modifications by sensory and standing condition, and of changes with ageing, medical conditions and rehabilitation treatment. However, distinct measures shed light on the discrete mechanisms and complex processes underpinning the maintenance of stance.
Biological current source imaging method based on acoustoelectric effect: A systematic review
Authors: Zhang Hao , Xu Minpeng , Liu Miao , Song Xizi , He Feng , Chen Shanguang , Ming Dong
Published: July 2022

Neuroimaging can help reveal the spatial and temporal diversity of neural activity, which is of utmost importance for understanding the brain. However, conventional non-invasive neuroimaging methods do not have the advantage of high temporal and spatial resolution, which greatly hinders clinical and basic research. The acoustoelectric (AE) effect is a fundamental physical phenomenon based on the change of dielectric conductivity that has recently received much attention in the field of biomedical imaging. Based on the AE effect, a new imaging method for the biological current source has been proposed, combining the advantages of high temporal resolution of electrical measurements and high spatial resolution of focused ultrasound. This paper first describes the mechanism of the AE effect and the principle of the current source imaging method based on the AE effect. The second part summarizes the research progress of this current source imaging method in brain neurons, guided brain therapy, and heart. Finally, we discuss the problems and future directions of this biological current source imaging method. This review explores the relevant research literature and provides an informative reference for this potential non-invasive neuroimaging method.