bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Porphyromonas gingivalis on Atherosclerosis-Related Cells
Authors: Zhang Jiaqi , Xie Mengru , Huang Xiaofei , Chen Guangjin , Yin Ying , Lu Xiaofeng , Feng Guangxia , Yu Ran , Chen Lili
Published: December 2021

Atherosclerosis (AS), one of the most common types of cardiovascular disease, has initially been attributed to the accumulation of fats and fibrous materials. However, more and more researchers regarded it as a chronic inflammatory disease nowadays. Infective disease, such as periodontitis, is related to the risk of atherosclerosis. Porphyromonas gingivalis (P. gingivalis), one of the most common bacteria in stomatology, is usually discovered in atherosclerotic plaque in patients. Furthermore, it was reported that P. gingivalis can promote the progression of atherosclerosis. Elucidating the underlying mechanisms of P. gingivalis in atherosclerosis attracted attention, which is thought to be crucial to the therapy of atherosclerosis. Nevertheless, the pathogenesis of atherosclerosis is much complicated, and many kinds of cells participate in it. By summarizing existing studies, we find that P. gingivalis can influence the function of many cells in atherosclerosis. It can induce the dysfunction of endothelium, promote the formation of foam cells as well as the proliferation and calcification of vascular smooth muscle cells, and lead to the imbalance of regulatory T cells (Tregs) and T helper (Th) cells, ultimately promoting the occurrence and development of atherosclerosis. This article summarizes the specific mechanism of atherosclerosis caused by P. gingivalis. It sorts out the interaction between P. gingivalis and AS-related cells, which provides a new perspective for us to prevent or slow down the occurrence and development of AS by inhibiting periodontal pathogens.
Identification of Molecular Subtypes and a Prognostic Signature Based on Inflammation-Related Genes in Colon Adenocarcinoma
Authors: Qiu Chenjie , Shi Wenxiang , Wu Huili , Zou Shenshan , Li Jianchao , Wang Dong , Liu Guangli , Song Zhenbiao , Xu Xintao , Hu Jiandong , Geng Hui
Published: December 2021

Both tumour-infiltrating immune cells and inflammation-related genes that can mediate immune infiltration contribute to the initiation and prognosis of patients with colon cancer. In this study, we developed a method to predict the survival outcomes among colon cancer patients and direct immunotherapy and chemotherapy. We obtained patient data from The Cancer Genome Atlas (TCGA) and captured inflammation-related genes from the GeneCards database. The package “ConsensusClusterPlus” was used to generate molecular subtypes based on inflammation-related genes obtained by differential expression analysis and univariate Cox analysis. A prognostic signature including four genes (PLCG2, TIMP1, BDNF and IL13) was also constructed and was an independent prognostic factor. Cluster 2 and higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints. Immune cell infiltration calculated by the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumour immune dysfunction and exclusion (TIDE), and tumour stemness indices (TSIs) were also compared on the basis of inflammation-related molecular subtypes and the risk signature. In addition, analyses of stratification, somatic mutation, nomogram construction, chemotherapeutic response prediction and small-molecule drug prediction were performed based on the risk signature. We finally used qRT–PCR to detect the expression levels of four genes in colon cancer cell lines and obtained results consistent with the prediction. Our findings demonstrated a four-gene prognostic signature that could be useful for prognostication in colon cancer patients and designing personalized treatments, which could provide new versions of personalized management for these patients.
Gut Microbiota as Regulators of Th17/Treg Balance in Patients With Myasthenia Gravis
Authors: Chen Pan , Tang Xiangqi
Published: December 2021

Myasthenia gravis (MG) is an acquired neurological autoimmune disorder characterized by dysfunctional transmission at the neuromuscular junction, with its etiology associated with genetic and environmental factors. Anti-inflammatory regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) cells functionally antagonize each other, and the immune imbalance between them contributes to the pathogenesis of MG. Among the numerous factors influencing the balance of Th17/Treg cells, the gut microbiota have received attention from scholars. Gut microbial dysbiosis and altered microbial metabolites have been seen in patients with MG. Therefore, correcting Th17/Treg imbalances may be a novel therapeutic approach to MG by modifying the gut microbiota. In this review, we initially review the association between Treg/Th17 and the occurrence of MG and subsequently focus on recent findings on alterations of gut microbiota and microbial metabolites in patients with MG. We also explore the effects of gut microbiota on Th17/Treg balance in patients with MG, which may provide a new direction for the prevention and treatment of this disease.
Heterogeneity of Transparent Exopolymer Particles in a Coastal Marine Environment (Sagami Bay, Japan): Seasonal Variation and Its Possible Bacterial Causes
Authors: Sugimoto Kugako , Fukuda Hideki , Koike Isao , Nagata Toshi
Published: December 2021

Transparent exopolymer particles (TEPs) play important roles in the regulation of carbon and pollutant (microplastics and spilled oils) transport in marine environments; however, the factors controlling TEP dynamics in coastal systems have yet to be fully clarified. A widely used colorimetric method quantifies TEPs as a homogeneous pool, which hampers the examination of internal TEP dynamics. Here, we used the microscopy to elucidate the seasonal dynamics of TEP subgroups and their controlling factors in Sagami Bay, Japan. TEPs were classified into three types: those not associated with other types of particles (Type I), those colonized by multiple types of particles (bacteria, algal cells, and detritus) (Type II), and those densely colonized by only bacterial clusters (Type III). Type II was generally the most dominant TEP component in terms of area, except in February, when Type I contributed substantially to the total TEP area. Type III was less abundant in terms of area but contributed substantially (up to 34%) to the total number of TEPs. The mean diameters were 14.0 ± 2.8 μm, 17.0 ± 5.8 μm, and 7.5 ± 0.9 μm for Type I, Type II, and Type III TEPs, respectively. Type I and Type III TEPs likely represent a transient phase of TEP development toward the formation of Type II, characterized by a high turnover and relatively low abundance in terms of area. The power-law slopes of the distributions of each TEP size, which reflected geometric features of the TEPs at steady state, changed dynamically over the seasons. The abundance of each type of TEP was significantly positively correlated with bacterial abundance, suggesting that bacteria are intimately involved in the regulation of internal TEP dynamics in Sagami Bay. Our results highlight the importance of investigating the internal dynamics of TEPs to improve current understanding of their roles in the regulation of carbon and pollutant transfer in marine environments.
From Validation Statistics to Uncertainty Estimates: Application to VIIRS Ocean Color Radiometric Products at European Coastal Locations
Authors: Mélin Frédéric
Published: December 2021

Uncertainty estimates are needed to assess ocean color products and qualify the agreement between missions. Comparison between field observations and satellite data, a process defined as validation, has been the traditional way to assess satellite products. However validation statistics can provide only an approximation for satellite data uncertainties as field measurements have their own uncertainties and as the validation process is imperfect, comparing data potentially differing in temporal, spatial or spectral characteristics. This study describes a method to interpret in terms of uncertainties the validation statistics obtained for ocean color remote sensing reflectance RRS knowing the uncertainties associated with field data. This approach is applied to observations collected at sites part of the Ocean Color component of the Aerosol Robotic Network (AERONET-OC) located in coastal regions of the European seas, and to RRS data from the VIIRS sensors on-board the SNPP and JPSS1 platforms. Similar estimates of uncertainties σVRS (term accounting for non-systematic contributions to the uncertainty budget) are obtained for both missions, decreasing with wavelength from the interval 0.8–1.4 10−3 sr−1 in the blue to a maximum of 0.24 10−3 sr−1 in the red, values that are at least twice (but up to 8 times) the uncertainties reported for the field data. These uncertainty estimates are then used to qualify the agreement between the VIIRS products, defining the extent to which they agree within their stated uncertainty. Despite significant biases between the two missions, their RRS products appear fairly compatible.
Submarine Groundwater and River Discharges Affect Carbon Cycle in a Highly Urbanized and River-Dominated Coastal Area
Authors: Wang Xuejing , Zhang Yan , Zheng Chunmiao , Luo Manhua , Yu Shengchao , Lu Meiqing , Li Hailong
Published: December 2021

Riverine carbon flux to the ocean has been considered in estimating coastal carbon budgets, but submarine groundwater discharge (SGD) has long been ignored. In this paper, the effects of both SGD and river discharges on the carbon cycle were investigated in the Guangdong-HongKong-Macao Greater Bay Area (GBA), a highly urbanized and river-dominated coastal area in China. SGD-derived nitrate (NO3–), dissolved organic carbon (DOC), and dissolved inorganic carbon (DIC) fluxes were estimated using a radium model to be (0.73–16.4) × 108 g/d, (0.60–9.94) × 109 g/d, and (0.77–3.29) × 1010 g/d, respectively. SGD-derived DOC and DIC fluxes are ∼2 times as great as riverine inputs, but SGD-derived NO3– flux is one-fourth of the riverine input. The additional nitrate and carbon inputs can stimulate new primary production, enhance biological pump efficiency, and affect the balance of the carbonate system in marine water. We found that SGD in the studied system is a potential net source of atmospheric CO2 with a flux of 1.46 × 109 g C/d, and river, however, is a potential net sink of atmospheric CO2 with a flux of 3.75 × 109 g C/d during the dry winter season. Two conceptual models were proposed illustrating the major potential processes of the carbon cycle induced by SGD and river discharges. These findings from this study suggested that SGD, as important as rivers, plays a significant role in the carbon cycle and should be considered in carbon budget estimations at regional and global scales future.
Comprehensive Analysis of N6-methyladenosine Modification Patterns Associated With Multiomic Characteristics of Bladder Cancer
Authors: Liu Jingchao , Wang Jianlong , Wu Meng , Zhang Wei , Meng Lingfeng , Wang Jiawen , Lv Zhengtong , Xia Haoran , Zhang Yaoguang , Wang Jianye
Published: December 2021

Purpose: To comprehensively analyze N6-methyladenosine modification patterns in bladder tumors and to further systematically explore the inherent relationships between these modification patterns and multiomic tumor characteristics.

Materials and Methods: A total of 901 bladder tumor samples, including 405 samples from TCGA database, 188 samples from GSE13507 and 308 samples from GSE32894, were included in this systematic analysis. The N6-methyladenosine modification patterns were identified utilizing unsupervised clustering analysis. To quantify N6-methyladenosine modification patterns, the m6Ascore of individual sample was developed using principal component analysis algorithms. Relationships among immune infiltration, tumor mutation burden, various clinical characteristics, molecular subtypes, and the m6Ascore were systematically analyzed. The guiding value of m6Ascore in immunotherapy was further validated in an external trial cohort. Genomics of Drug Sensitivity in Cancer expression references were also utilized to perform drug sensitivity analysis for patients with distinct m6A modification patterns.

Results: We determined three different N6-methyladenosine modification patterns for 901 bladder tumors. The quantitative m6Ascore of individual sample derived from N6-methyladenosine modification patterns could play a significant role in predicting overall survival, immune cell infiltration, and classic oncogene mutations. A low m6Ascore combined with high tumor mutation burden indicated better survival outcomes (p < 0.001). A higher m6Ascore also indicated a higher grade, higher T and N stage, elder ages, higher death rate, and higher PD1/PDL1/CTLA4 expressions (p < 0.01). The Basal type tended to exhibit significantly higher m6Ascores than the Luminal and Neuronal subtypes. External immunotherapy cohorts demonstrated that no difference in therapeutic effects was noted between the high and low m6Ascore groups when anti-PD1 immunotherapy was exclusively administered. When anti-PD1 and anti-CTLA4 immunotherapy were simultaneously administered, the high m6Ascore group had a significantly better prognosis than the low m6Ascore group (p < 0.001). High m6A groups were potentially sensitive to various medical treatments including Bleomycin, Bortezomib, Cisplatin, Cyclopamine, Dasatinib, Docetaxe, Rapamycin, and Vinblastine in this study.

Conclusions: This study systematically revealed the important roles of m6A methylation modification patterns in bladder tumors. Detailed quantification of m6A modification patterns could improve our understanding of the bladder tumor microenvironments and could provide guidance for future immunotherapy strategies.
Molecular Mechanisms of Proteinuria in Minimal Change Disease
Authors: Purohit Shrey , Piani Federica , Ordoñez Flor A. , de Lucas-Collantes Carmen , Bauer Colin , Cara-Fuentes Gabriel
Published: December 2021

Minimal change disease (MCD) is the most common type of idiopathic nephrotic syndrome in childhood and represents about 15% cases in adults. It is characterized by massive proteinuria, edema, hypoalbuminemia, and podocyte foot process effacement on electron microscopy. Clinical and experimental studies have shown an association between MCD and immune dysregulation. Given the lack of inflammatory changes or immunocomplex deposits in the kidney tissue, MCD has been traditionally thought to be mediated by an unknown circulating factor(s), probably released by T cells that directly target podocytes leading to podocyte ultrastructural changes and proteinuria. Not surprisingly, research efforts have focused on the role of T cells and podocytes in the disease process. Nevertheless, the pathogenesis of the disease remains a mystery. More recently, B cells have been postulated as an important player in the disease either by activating T cells or by releasing circulating autoantibodies against podocyte targets. There are also few reports of endothelial injury in MCD, but whether glomerular endothelial cells play a role in the disease remains unexplored. Genome-wide association studies are providing insights into the genetic susceptibility to develop the disease and found a link between MCD and certain human haplotype antigen variants. Altogether, these findings emphasize the complex interplay between the immune system, glomerular cells, and the genome, raising the possibility of distinct underlying triggers and/or mechanisms of proteinuria among patients with MCD. The heterogeneity of the disease and the lack of good animal models of MCD remain major obstacles in the understanding of MCD. In this study, we will review the most relevant candidate mediators and mechanisms of proteinuria involved in MCD and the current models of MCD-like injury.
Axl Is Essential for in-vitro Angiogenesis Induced by Vitreous From Patients With Proliferative Diabetic Retinopathy
Authors: Wu Wenyi , Xu Huizuo , Meng Zhishang , Zhu Jianxi , Xiong Siqi , Xia Xiaobo , Lei Hetian
Published: December 2021

Proliferative diabetic retinopathy (PDR), characterized mainly with abnormal epiretinal angiogenesis forming fibrovascular membranes (FVMs), threatens vision of people with diabetes; FVMs consist of extracellular matrix and a variety of cell types including vascular endothelial cells. Axl, one of receptor tyrosine kinases, can be activated indirectly by vascular endothelial growth factor-A (VEGF-A) via an intracellular route for promoting angiogenesis. In this study, we revealed that growth arrest-specific protein 6 (Gas6), a specific ligand of Axl, was elevated in vitreous from patients with PDR and that Axl was activated in FVMs from patients with PDR. In addition, we demonstrated that in cultured human retinal microvascular endothelial cells (HRECs), Axl inhibition via suppression of Axl expression with Clustered Regularly Interspaced Short Palindromic Repeats/ CRISPR-associated protein 9 or through inactivation with its specific inhibitor R428 blocked PDR vitreous-induced Akt activation and proliferation of HRECs. Furthermore, PDR vitreous-heightened migration and tube formation of HRECs were also blunted by restraining Axl. These results indicate that in the pathogenesis of PDR, Axl can be activated by Gas6 binding directly and by VEGF-A via an intracellular route indirectly, suggesting that Axl plays a pivotal role in the development of PDR and that Axl inhibition shows a bright promise for PDR therapy.
The Evolution of Device-Assisted Enteroscopy: From Sonde Enteroscopy to Motorized Spiral Enteroscopy
Authors: Nehme Fredy , Goyal Hemant , Perisetti Abhilash , Tharian Benjamin , Sharma Neil , Tham Tony C. , Chhabra Rajiv
Published: December 2021

The introduction of capsule endoscopy in 2001 opened the last “black box” of the gastrointestinal tract enabling complete visualization of the small bowel. Since then, numerous new developments in the field of deep enteroscopy have emerged expanding the diagnostic and therapeutic armamentarium against small bowel diseases. The ability to achieve total enteroscopy and visualize the entire small bowel remains the holy grail in enteroscopy. Our journey in the small bowel started historically with sonde type enteroscopy and ropeway enteroscopy. Currently, double-balloon enteroscopy, single-balloon enteroscopy, and spiral enteroscopy are available in clinical practice. Recently, a novel motorized enteroscope has been described with the potential to shorten procedure time and allow for total enteroscopy in one session. In this review, we will present an overview of the currently available techniques, indications, diagnostic yield, and complications of device-assisted enteroscopy.
The Performance of Two Rapid Antigen Tests During Population-Level Screening for SARS-CoV-2 Infection
Authors: Alghounaim Mohammad , Bastaki Hamad , Bin Essa Farah , Motlagh Hoda , Al-Sabah Salman
Published: December 2021

Background: SARS-CoV-2 antigen assays offer a rapid mean to diagnose and isolate infected individuals. However, their utility in population-level screening is unknown.

Objectives: The performance of two antigen tests in detecting SARS-CoV-2 was assessed among individuals randomly selected in the community.

Study Design: A prospective study that performed head-to-head comparison of two SARS-CoV-2 antigen assays. Individuals were recruited during community SARS-CoV-2 screening over 10 working days. Demographic and clinical data were collected. Standard Q COVID-19 Ag test, a point-of-care chromatographic assay, was conducted immediately, and then the sample was transported to the virology laboratory to perform PCR and the LIAISON SARS-CoV-2 Ag chemiluminesence immunoassay.

Results: respiratory samples from 991 individuals were collected, and 62 were positive by PCR. Inconclusive PCR results were observed in 19 samples and were excluded. The median age of participants was 40.2 years (IQR 32.3–47.8), and 932 (94%) were males. Most (77.4%) of infections were asymptomatic. The sensitivity and the specificity of the LIAISON assay were 43.3% (95%CI 30.6–56.8) and 99.9% (95%CI 99.3–100). The Standard Q assay had lower sensitivity (30.6%, 95%CI 19.6–43.7) but similar specificity (98.8%, 95%CI, 97.8–99.4). Similarly, the LIAISON assay had higher positive predictive value (96.3%, 95%CI 81–99.9% vs. 63.3%, 95%CI, 43.9–80.1%). Both assays performed better in symptomatic patients and among samples with a low-cycle threshold (Ct < 25).

Conclusion: In our setting of random community surveillance, rapid antigen testing of nasopharyngeal swabs by either LIAISON SARS-CoV-2 Ag (DiaSorin) or Standard Q COVID-19 Ag (SD Biosensor) was less sensitive to detecting SARS-CoV-2 than the TaqPath COVID-19 RT-PCR.
The Role of Internal Limiting Membrane Flap for Highly Myopic Macular Hole Retinal Detachment: Improving the Closure Rate but Leading to Excessive Gliosis
Authors: Chen Yiqi , Wang Jun , Ye Xin , Yu Jiafeng , Tao Jiwei , Lin Li , Wu Sulan , Qu Jia , Shen Lijun
Published: December 2021

Purpose: To investigate the surgical outcomes of the inverted internal limiting membrane (ILM) flap technique for macular hole retinal detachment (MHRD) in high myopia.

Methods: This was a retrospective interventional study on 45 highly myopic eyes with MHRD after ILM peeling (n = 24, peeling group) or the inverted ILM flap technique (n = 21, inverted group). The inverted group was consisted of autologous blood (AB) subgroup (n = 10) and perfluorocarbon liquid (PFCL) subgroup (n = 11). MH closure, best-corrected visual acuity (BCVA), foveal microstructures, and excessive gliosis were analyzed during a follow-up of over 12 months.

Results: The inverted group achieved a higher MH closure rate (95.24%) than the peeling group (41.67%; p < 0.001). No significant difference was found in postoperative BCVA between the two groups (p = 0.98) or between the closed MH with or without excessive gliosis (p = 0.60). Excessive gliosis was identified in 9 eyes in the inverted group, and there was no difference in the incidence of excessive gliosis between the AB subgroup (4 in 10 eyes, 40%) and the PFCL subgroup (5 in 11 eyes, 45.45%) (p > 0.999).

Conclusion: The inverted ILM flap technique was effective in MH closure but had no advantage in postoperative BCVA and microstructural restoration. Excessive gliosis was only detected in the inverted group but did not affect the postoperative BCVA. Additionally, the incidence of excessive gliosis was not affected by adjuvants.
Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis
Authors: Broderick David T. J. , Waite David W. , Marsh Robyn L. , Camargo Carlos A. , Cardenas Paul , Chang Anne B. , Cookson William O. C. , Cuthbertson Leah , Dai Wenkui , Everard Mark L. , Gervaix Alain , Harris J. Kirk , Hasegawa Kohei , Hoffman Lucas R. , Hong Soo-Jong , Josset Laurence , Kelly Matthew S. , Kim Bong-Soo , Kong Yong , Li Shuai C. , Mansbach Jonathan M. , Mejias Asuncion , O’Toole George A. , Paalanen Laura , Pérez-Losada Marcos , Pettigrew Melinda M. , Pichon Maxime , Ramilo Octavio , Ruokolainen Lasse , Sakwinska Olga , Seed Patrick C. , van der Gast Christopher J. , Wagner Brandie D. , Yi Hana , Zemanick Edith T. , Zheng Yuejie , Pillarisetti Naveen , Taylor Michael W.
Published: December 2021

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.

Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (<18 years) microbiota in acute and chronic respiratory conditions, with >10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.

Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.

Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.
Algal Cells-Derived Extracellular Vesicles: A Review With Special Emphasis on Their Antimicrobial Effects
Authors: Bayat Fereshteh , Afshar Alireza , Baghban Neda
Published: December 2021

Extracellular vesicles (EVs) originated from different cells of approximately all kinds of organisms, recently got more attention because of their potential in the treatment of diseases and reconstructive medicine. To date, lots of studies have been performed on mammalian-derived vesicles, but little attention has been paid to algae and marine cells as valuable sources of EVs. Proving the promising role of EVs in medicine requires sufficient resources to produce qualified microvesicles. Algae, same as its other sister groups, such as plants, have stem cells and stem cell niches. Previous studies showed the EVs in plants and marine cells. So, this study was set out to talk about algal extracellular vesicles. EVs play a major role in cell-to-cell communication to convey molecules, such as RNA/DNA, metabolites, proteins, and lipids within. The components of EVs depends on the origin of the primitive cells or tissues and the isolation method. Sufficient resources are needed to produce high-quality, stable, and compatible EVs as a drug or drug delivery system. Plant stem cells have great potential as a new controllable resource for the production of EVs. The EVs secreted from stem cells can easily be extracted from the cell culture medium and evaluated for medicinal uses. In this review, the aim is to introduce algae stem cells as well as EVs derived from algal cells. In the following, the production of the EVs¸ the properties of EVs extracted from these sources and their antimicrobial effects will be discussed.
Elucidating the Mechanisms Underlying Enhanced Drought Tolerance in Plants Mediated by Arbuscular Mycorrhizal Fungi
Authors: Cheng Shen , Zou Ying-Ning , Kuča Kamil , Hashem Abeer , Abd_Allah Elsayed Fathi , Wu Qiang-Sheng
Published: December 2021

Plants are often subjected to various environmental stresses during their life cycle, among which drought stress is perhaps the most significant abiotic stress limiting plant growth and development. Arbuscular mycorrhizal (AM) fungi, a group of beneficial soil fungi, can enhance the adaptability and tolerance of their host plants to drought stress after infecting plant roots and establishing a symbiotic association with their host plant. Therefore, AM fungi represent an eco-friendly strategy in sustainable agricultural systems. There is still a need, however, to better understand the complex mechanisms underlying AM fungi-mediated enhancement of plant drought tolerance to ensure their effective use. AM fungi establish well-developed, extraradical hyphae on root surfaces, and function in water absorption and the uptake and transfer of nutrients into host cells. Thus, they participate in the physiology of host plants through the function of specific genes encoded in their genome. AM fungi also modulate morphological adaptations and various physiological processes in host plants, that help to mitigate drought-induced injury and enhance drought tolerance. Several AM-specific host genes have been identified and reported to be responsible for conferring enhanced drought tolerance. This review provides an overview of the effect of drought stress on the diversity and activity of AM fungi, the symbiotic relationship that exists between AM fungi and host plants under drought stress conditions, elucidates the morphological, physiological, and molecular mechanisms underlying AM fungi-mediated enhanced drought tolerance in plants, and provides an outlook for future research.
Genomic Characterization of Streptococcus suis Serotype 24 Clonal Complex 221/234 From Human Patients
Authors: Kerdsin Anusak , Hatrongjit Rujirat , Wongsurawat Thidathip , Jenjaroenpun Piroon , Chopjitt Peechanika , Boueroy Parichart , Fittipaldi Nahuel , Zheng Han , Gottschalk Marcelo
Published: December 2021

Streptococcus suis is a zoonotic pathogen that causes invasive infections in humans and pigs. Although S. suis serotype 2 is prevalent among patient and swine infections, other serotypes are occasionally detected in humans. Of these, serotype 24 clonal complex (CC) 221/234 are recognized as emerging clones of human infection. Genomic exploration of three S. suis serotype 24 CC221/234 strains revealed antimicrobial resistance genes, pathotyping, virulence-associated gene (VAG) profiles, minimum core genome (MCG) typing, and comparison of the genomes. Based on these analyzes, all three serotype 24 strains were MCG7-3 and should be classified in the intermediate/weakly virulent (I/WV) group. All selected serotype 24 strains were susceptible to several antibiotics including β-lactam, fluoroquinolone, and chloramphenicol. Resistance to tetracycline, macrolide, and clindamycin was observed and attributed to the genes tet(O) and erm(B). Genomic comparison revealed the strains S12X, LSS66, LS0L, LS0E, 92–4,172, and IMT40201 that had phylogenetic affinity with serotype 24 CC221/234. Analysis of 80 virulence-associated genes (VAG) showed that all three serotype 24 strains lacked 24 genes consisting of adhesin P, epf, hyl, ihk, irr, mrp, nadR, neuB, NisK/R, ofs, permease (SSU0835), rgg, revS, salK/R, sao, sly, spyM3_0908, srtBCD, srtF, srtG, SSU05_0473, virA, virB4, and virD4. Eleven specific sequences were identified in the 3 serotype 24 genomes that differed from the genomes of the representative strains of epidemic (E; SC84), highly virulent (HV; P1/7), I/WV (89–1,591), and avirulent (T15 and 05HAS68).
An Unfolded Protein Response Related Signature Could Robustly Predict Survival Outcomes and Closely Correlate With Response to Immunotherapy and Chemotherapy in Bladder Cancer
Authors: Zhang Facai , Feng Dechao , Wang Xiaoming , Gu Yiwei , Shen Zhiyong , Yang Yubo , Wang Jiahao , Zhong Quliang , Li Dengxiong , Hu Huan , Han Ping
Published: December 2021

Background: The unfolded protein response (UPR) plays a significant role in maintaining protein hemostasis in tumor cells, which are crucial for tumor growth, invasion, and resistance to therapy. This study aimed to develop a UPR-related signature and explore its correlation with immunotherapy and chemotherapy in bladder cancer.

Methods: The differentially expressed UPR-related genes were put into Lasso regression to screen out prognostic genes, which constituted the UPR signature, and were incorporated into multivariate Cox regression to generate risk scores. Subsequently, the predictive performance of this signature was estimated by receiver operating characteristic (ROC) curves. The CIBERSORTx, the maftool, and Gene set enrichment analysis (GSEA) were applied to explore infiltrated immune cells, tumor mutational burden (TMB), and enriched signaling pathways in both risk groups, respectively. Moreover, The Cancer Immunome Atlas (TCIA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases were used to predict responses to chemotherapy and immunotherapy.

Results: Twelve genes constituted the UPR-related signature. Patients with higher risk scores had worse overall survival (OS) in training and three validation sets. The UPR-related signature was closely correlated with clinicopathologic parameters and could serve as an independent prognostic factor. M0 macrophages showed a significantly infiltrated difference in both risk groups. TMB analysis showed that the risk score in the wild type and mutation type of FGFR3 was significantly different. GSEA indicated that the immune-, extracellular matrix-, replication and repair associated pathways belonged to the high risk group and metabolism-related signal pathways were enriched in the low risk group. Prediction of immunotherapy and chemotherapy revealed that patients in the high risk group might benefit from chemotherapy, but had a worse response to immunotherapy. Finally, we constructed a predictive model with age, stage, and UPR-related risk score, which had a robustly predictive performance and was validated in GEO datasets.

Conclusion: We successfully constructed and validated a novel UPR-related signature in bladder cancer, which could robustly predict survival outcomes and closely correlate with the response to immunotherapy and chemotherapy in bladder cancer.
Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury
Authors: Kikuta Shu , Kuboki Akihito , Yamasoba Tatsuya
Published: December 2021

Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.
Mapping an Extended Metabolic Profile of Gliomas Using High-Resolution 31P MRSI at 7T
Authors: Korzowski Andreas , Weckesser Nina , Franke Vanessa L. , Breitling Johannes , Goerke Steffen , Schlemmer Heinz-Peter , Ladd Mark E. , Bachert Peter , Paech Daniel
Published: December 2021

Phosphorus magnetic resonance spectroscopic imaging (31P MRSI) is of particular interest for investigations of patients with brain tumors as it enables to non-invasively assess altered energy and phospholipid metabolism in vivo. However, the limited sensitivity of 31P MRSI hampers its broader application at clinical field strengths. This study aimed to identify the additional value of 31P MRSI in patients with glioma at ultra-high B0 = 7T, where the increase in signal-to-noise ratio may foster its applicability for clinical research. High-quality, 3D 31P MRSI datasets with an effective voxel size of 5.7 ml were acquired from the brains of seven patients with newly diagnosed glioma. An optimized quantification model was implemented to reliably extract an extended metabolic profile, including low-concentrated metabolites such as extracellular inorganic phosphate, nicotinamide adenine dinucleotide [NAD(H)], and uridine diphosphoglucose (UDPG), which may act as novel tumor markers; a background signal was extracted as well, which affected measures of phosphomonoesters beneficially. Application of this model to the MRSI datasets yielded high-resolution maps of 12 different 31P metabolites, showing clear metabolic differences between white matter (WM) and gray matter, and between healthy and tumor tissues. Moreover, differences between tumor compartments in patients with high-grade glioma (HGG), i.e., gadolinium contrast-enhancing/necrotic regions (C+N) and peritumoral edema, could also be suggested from these maps. In the group of patients with HGG, the most significant changes in metabolite intensities were observed in C+N compared to WM, i.e., for phosphocholine +340%, UDPG +54%, glycerophosphoethanolamine −45%, and adenosine-5′-triphosphate −29%. Furthermore, a prominent signal from mobile phospholipids appeared in C+N. In the group of patients with low-grade glioma, only the NAD(H) intensity changed significantly by −28% in the tumor compared to WM. Besides the potential of 31P MRSI at 7T to provide novel insights into the biochemistry of gliomas in vivo, the attainable spatial resolutions improve the interpretability of 31P metabolite intensities obtained from malignant tissues, particularly when only subtle differences compared to healthy tissues are expected. In conclusion, this pilot study demonstrates that 31P MRSI at 7T has potential value for the clinical research of glioma.
TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human
Authors: Delalande Jean Marie , Nagy Nandor , McCann Conor J. , Natarajan Dipa , Cooper Julie E. , Carreno Gabriela , Dora David , Campbell Alison , Laurent Nicole , Kemos Polychronis , Thomas Sophie , Alby Caroline , Attié-Bitach Tania , Lyonnet Stanislas , Logan Malcolm P. , Goldstein Allan M. , Davey Megan G. , Hofstra Robert M. W. , Thapar Nikhil , Burns Alan J.
Published: December 2021

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non-cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning.
Recent Advances in the Application Peptide and Peptoid in Diagnosis Biomarkers of Alzheimer’s Disease in Blood
Authors: Guo Yuxin , Hu Zhiyuan , Wang Zihua
Published: December 2021

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases with irreversible damage of the brain and a continuous pathophysiological process. Early detection and accurate diagnosis are essential for the early intervention of AD. Precise detection of blood biomarkers related to AD could provide a shortcut to identifying early-stage patients before symptoms. In recent years, targeting peptides or peptoids have been chosen as recognition elements in nano-sensors or fluorescence detection to increase the targeting specificity, while peptide-based probes were also developed considering their specific advantages. Peptide-based sensors and probes have been developed according to different strategies, such as natural receptors, high-throughput screening, or artificial design for AD detection. This review will briefly summarize the recent developments and trends of AD diagnosis platforms based on peptide and peptoid as recognition elements and provide insights into the application of peptide and peptoid with different sources and characteristics in the diagnosis of AD biomarkers.
The Origins of Passive, Active, and Sleep-Related Fatigue
Authors: Chong Steven D. , Baldwin Carryl L.
Published: December 2021

Driving is a safety-critical task that requires an alert and vigilant driver. Most research on the topic of vigilance has focused on its proximate causes, namely low arousal and resource expenditure. The present article aims to build upon previous work by discussing the ultimate causes, or the processes that tend to precede low arousal and resource expenditure. The authors review different aspects of fatigue that contribute to a loss of vigilance and how they tend to occur; specifically, the neurochemistry of passive fatigue, the electrophysiology of active fatigue, and the chronobiology of sleep-related fatigue.
Distinct Nutrient Intake Style in Inhabitants of Ultra-High-Altitude Areas in North of Tibet, China: A Cross-Sectional Study Based on Newly Developed Tibetan Food Frequency Questionnaires
Authors: Xiao Zhen , Sun Xianzhi , Zhaxi Duoji , Zhang Fan , Ji Yuchen , Cheng Tingting , Li Xiaofeng , Xu Xiaoguang
Published: December 2021

Dietary pattern is quite distinct among the inhabitants of high-altitude areas because of environmental and geographical uniqueness; hence, it is important to investigate this data as accurately as possible. However, very few data are related to these populations up to now. Based on the food frequency questionnaire (FFQ) used in the Chinese population, a revised Tibetan edition was developed with respect to the lifestyle in high-altitude areas. After assessment of validity and reproducibility, a nutrition intake survey was conducted among 1,071 randomly sampled Tibetan people. In addition, the Bland–Altman approach was used to compare the agreement between the two dietary tools. For the reproducibility analysis, intraclass correlation coefficients (ICC) were calculated to examine the agreement of food groups and nutrients from the two FFQs (FFQ1 and FFQ2). Nutrient intake was calculated using food composition tables. For the validity analysis, Pearson's correlation of food groups intakes varied from 0.22 to 0.91 (unadjusted). The correlations of nutrients ranged from 0.24 to 0.76 (unadjusted). In the analysis of reliability, the ICC of food groups varied from 0.27 to 0.70 (unadjusted). The ICC of nutrient intakes ranged from 0.22 to 0.87 (unadjusted). The results of nutritional analysis showed that ~25% of foods consumed frequently were traditional Tibetan foods. However, traditional Han foods were frequently consumed. In addition, the energy, iron, and protein intakes for male or female subjects were close to the Chinese Dietary Nutrient Reference Intake (Chinese DRIs); however, fat and sodium intakes were significantly higher than the Chinese DRIs. Interestingly, lower intakes of other types of nutrition, such as vitamin C were detected in people living in high-altitude areas. Our data indicated that excess consumption of fat and sodium and insufficient intake of vitamin C were common among Tibetan people, as compared with the most Chinese people living in the plateau areas. More investigations are needed to reveal the association between the food intake style and high-altitude endemic diseases.
Ketone Supplementation: Meeting the Needs of the Brain in an Energy Crisis
Authors: Poff Angela M. , Moss Sara , Soliven Maricel , D'Agostino Dominic P.
Published: December 2021

Diverse neurological disorders are associated with a deficit in brain energy metabolism, often characterized by acute or chronic glucose hypometabolism. Ketones serve as the brain's only significant alternative fuel and can even become the primary fuel in conditions of limited glucose availability. Thus, dietary supplementation with exogenous ketones represents a promising novel therapeutic strategy to help meet the energetic needs of the brain in an energy crisis. Preliminary evidence suggests ketosis induced by exogenous ketones may attenuate damage or improve cognitive and motor performance in neurological conditions such as seizure disorders, mild cognitive impairment, Alzheimer's disease, and neurotrauma.
Alterations in Intestinal Microbiota Composition in Mice Treated With Vitamin D3 or Cathelicidin
Authors: Jiang Yu , Wan Yue , Li Jing , Zhao Yueshui , Ma Yongshun , Yu Jing , Yuan Donghong , Xiang Shixin , Du Fukuan , Wu Xu , Li Mingxing , Chen Yu , Xiao Zhangang , Wen Qinglian , Hu Wei , Shen Jing
Published: December 2021

Gut microbiota is a complex aggregation of microbial organisms, which offers diverse protective benefits to the host. Dysbiosis of intestinal microbiota is frequently associated with many diseases. Vitamin D3 (VD), which was originally associated with bone health, also possesses antimicrobial activities and can act through antimicrobial peptide. Cathelicidin is a type of antimicrobial peptide in host to maintain the balance of gut microbiome. Our current study sought to evaluate the protective effect of VD and cathelicidin in mice intestines by administration of VD or mCRAMP-encoding L. lactis. We herein provided a comprehensive profile of the impact of VD and mCRAMP on gut microbiota using 16S rRNA sequencing, followed by bioinformatics and statistical analysis. Our results revealed an increased richness of bacterial community in mice intestines due to VD administration. Moreover, we showed a beneficial effect of VD and mCRAMP by enhancing the colonization of bacterial taxa that are associated with protective effects to the host but repressing the propagation of bacterial taxa that are associated with harmful effects to the host. Various metabolic pathways related to amino acid and lipid metabolism were affected in this process. We further established a bacterial panel as a reliable biomarker to evaluate the efficacy of remodeling the mice gut microbiota by VD and mCRAMP administration. The uncovered effects will deepen the comprehension about the antibacterial mechanisms of VD and mCRAMP and provide new insights for therapeutic implication of them.