bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a Prediction Model for Survival in Diabetic Patients With Acute Kidney Injury
Authors: Mo Manqiu , Pan Ling , Huang Zichun , Liang Yuzhen , Liao Yunhua , Xia Ning
Published: December 2021

Objective

We aimed to analyze the risk factors affecting all-cause mortality in diabetic patients with acute kidney injury (AKI) and to develop and validate a nomogram for predicting the 90-day survival rate of patients.

Methods

Clinical data of diabetic patients with AKI who were diagnosed at The First Affiliated Hospital of Guangxi Medical University from April 30, 2011, to April 30, 2021, were collected. A total of 1,042 patients were randomly divided into a development cohort and a validation cohort at a ratio of 7:3. The primary study endpoint was all-cause death within 90 days of AKI diagnosis. Clinical parameters and demographic characteristics were analyzed using Cox regression to develop a prediction model for survival in diabetic patients with AKI, and a nomogram was then constructed. The concordance index (C-index), receiver operating characteristic curve, and calibration plot were used to evaluate the prediction model.

Results

The development cohort enrolled 730 patients with a median follow-up time of 87 (40–98) days, and 86 patients (11.8%) died during follow-up. The 90-day survival rate was 88.2% (644/730), and the recovery rate for renal function in survivors was 32.9% (212/644). Multivariate analysis showed that advanced age (HR = 1.064, 95% CI = 1.043–1.085), lower pulse pressure (HR = 0.964, 95% CI = 0.951–0.977), stage 3 AKI (HR = 4.803, 95% CI = 1.678–13.750), lower 25-hydroxyvitamin D3 (HR = 0.944, 95% CI = 0.930–0.960), and multiple organ dysfunction syndrome (HR = 2.056, 95% CI = 1.287–3.286) were independent risk factors affecting the all-cause death of diabetic patients with AKI (all p < 0.01). The C-indices of the prediction cohort and the validation cohort were 0.880 (95% CI = 0.839–0.921) and 0.798 (95% CI = 0.720–0.876), respectively. The calibration plot of the model showed excellent consistency between the prediction probability and the actual probability.

Conclusion

We developed a new prediction model that has been internally verified to have good discrimination, calibration, and clinical value for predicting the 90-day survival rate of diabetic patients with AKI.
A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19
Authors: Abuhasira Ran , Ayalon-Dangur Irit , Zaslavsky Neta , Koren Ronit , Keller Mally , Dicker Dror , Grossman Alon
Published: December 2021

Objective

To assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19).

Materials and Methods

We did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death).

Results

The mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5–28) in the standard of care group (hazard ratio, 1.22; 95% CI, 0.70–2.15; p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56; 95% CI, 0.16–1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel.

Conclusions

In this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT04371978.
Antibiotics Contaminated Irrigation Water: An Overview on Its Impact on Edible Crops and Visible Light Active Titania as Potential Photocatalysts for Irrigation Water Treatment
Authors: Jalloul Ghadeer , Keniar Imad , Tehrani Ali , Boyadjian Cassia
Published: December 2021

Sub-therapeutic levels of antibiotics (ABs) are given to animals and poultry to promote growth and reduce disease. In agricultural environments, ABs reach croplands via animal manure used as fertilizer and/or ABs-contaminated water used for irrigation. The continuous discharge of ABs into the ecosystem raises growing concerns on the ABs contamination of edible crops. Tetracyclines (TCs) are among the most widely used ABs around the world. In this review, we discuss the contamination of irrigation water with TCs, its impact on edible crops, and the potential risks of crop contamination with TCs on human health. We propose solar-mediated photocatalytic degradation using Titania (TiO2) photocatalyst as a promising method to remove TCs from irrigation water. The photocatalytic activity of TiO2 can be enhanced by chemical modification to expand its activity under visible light irradiation. Herein, we aim for providing literature-based guidance on developing a visible light–active TiO2-based system to degrade TCs and other ABs in water streams. We include a summary of recent advances on this topic based on three main modification methods of Titania: metal/non-metal/mixed doping, composite formation, and heterojunction construction. Among the investigated photocatalysts, Fe2O3-TiO2/Fe-zeolite and the N-doped TiO2/rGO immobilized composite catalysts were found to be very efficient in the degradation of TCs under visible light irradiation (i.e., 98% degradation within 60 min). Most immobilized TiO2 based composite systems exhibited improved performances and hence we highlight these as efficient, cost effective and ecofriendly photocatalysts for the degradation of TCs in irrigation water.
Fire Occurrence Mediates Small-Mammal Seed Removal of Native Tree Species in a Neotropical Savanna
Authors: Cazetta Thayse Cavicchioli , Vieira Emerson M.
Published: December 2021

Seed dispersal and predation are critical processes for plant recruitment which can be affected by fire events. We investigated community composition of small mammals in gallery forests with distinct burning histories (burned or not burned ∼3 years before) in the Cerrado (neotropical savanna). We evaluated the role of these animals as seed removers of six native tree species, potentially mediated by the occurrence of fire. We sampled four previously burned sites and four unburned ones. Seed removal was assessed using two exclusion treatments: exclusive access of small rodents and access of all seed-removing vertebrates. The previous burning changed the structural characteristics of the forests, increasing the density of the understory vegetation and herbaceous cover, which determined differences in species composition, richness, and abundance of small rodents (abundance in the burned forests was 1/6 of the abundance in the unburnt ones). Seed removal rates across the six species were reduced in burnt forests in both treatments and were higher for the “all vertebrates” treatment. Other vertebrates, larger than small rodents, played a significant role as seed removers for five of the six species. The effects of fire were consistent across species, but for the two species with the largest seeds (Hymenaea courbaril and Mauritia flexuosa) removal rates for both treatments were extremely low in the burned forests (≦5%). The observed decline in small rodent seed predation in the burned forests may have medium to long-term consequences on plant communities in gallery forests, potentially affecting community composition and species coexistence in these forests. Moreover, fire caused a sharp decline in seed removal by large mammals, indicating that the maintenance of dispersal services provided by these mammals (mainly the agouti Dasyprota azarae) for the large-seeded species may be jeopardized by the burning of gallery forests. This burning would also affect several small mammal species that occur in the surrounding typical savanna habitats but also use these forests. Fire events have been increasing in frequency and intensity because of human activities and climate changing. This current scenario poses a serious threat considering that these forests are fire-sensitive ecosystems within the Cerrado.
COVID-19 Transcriptomic Atlas: A Comprehensive Analysis of COVID-19 Related Transcriptomics Datasets
Authors: Alqutami Fatma , Senok Abiola , Hachim Mahmood
Published: December 2021

Background: To develop anti-viral drugs and vaccines, it is crucial to understand the molecular basis and pathology of COVID-19. An increase in research output is required to generate data and results at a faster rate, therefore bioinformatics plays a crucial role in COVID-19 research. There is an abundance of transcriptomic data from studies carried out on COVID-19, however, their use is limited by the confounding factors pertaining to each study. The reanalysis of all these datasets in a unified approach should help in understanding the molecular basis of COVID-19. This should allow for the identification of COVID-19 biomarkers expressed in patients and the presence of markers specific to disease severity and condition.

Aim: In this study, we aim to use the multiple publicly available transcriptomic datasets retrieved from the Gene Expression Omnibus (GEO) database to identify consistently differential expressed genes in different tissues and clinical settings.

Materials and Methods: A list of datasets was generated from NCBI’s GEO using the GEOmetadb package through R software. Search keywords included SARS-COV-2 and COVID-19. Datasets in human tissues containing more than ten samples were selected for this study. Differentially expressed genes (DEGs) in each dataset were identified. Then the common DEGs between different datasets, conditions, tissues and clinical settings were shortlisted.

Results: Using a unified approach, we were able to identify common DEGs based on the disease conditions, samples source and clinical settings. For each indication, a different set of genes have been identified, revealing that a multitude of factors play a role in the level of gene expression.

Conclusion: Unified reanalysis of publically available transcriptomic data showed promising potential in identifying core targets that can explain the molecular pathology and be used as biomarkers for COVID-19.
Blastocyst Morphology Based on Uniform Time-Point Assessments is Correlated With Mosaic Levels in Embryos
Authors: Chen Chien-Hong , Lee Chun-I , Huang Chun-Chia , Chen Hsiu-Hui , Ho Shu-Ting , Cheng En-Hui , Lin Pin‐Yao , Chen Chung-I , Lee Tsung-Hsien , Lee Maw-Sheng
Published: December 2021

Avoiding aneuploid embryo transfers has been shown to improve pregnancy outcomes in patients with implantation failure and pregnancy loss. This retrospective cohort study aims to analyze the correlation of time-lapse (TL)-based variables and numeric blastocyst morphological scores (TLBMSs) with different mosaic levels. In total, 918 biopsied blastocysts with time-lapse assessments at a uniform time-point were subjected to next-generation sequencing–based preimplantation genetic testing for aneuploidy. In consideration of patient- and cycle-related confounding factors, all redefined blastocyst morphology components of low-grade blastocysts, that is, expansion levels (odds ratio [OR] = 0.388, 95% confidence interval [CI] = 0.217–0.695; OR = 0.328, 95% CI = 0.181–0.596; OR = 0.343, 95% CI = 0.179–0.657), inner cell mass grades (OR = 0.563, 95% CI = 0.333–0.962; OR = 0.35, 95% CI = 0.211–0.58; OR = 0.497, 95% CI = 0.274–0.9), and trophectoderm grades (OR = 0.29, 95% CI = 0.178–0.473; OR = 0.242, 95% CI = 0.143–0.411; OR = 0.3, 95% CI = 0.162–0.554), were less correlated with mosaic levels ≤20%, <50%, and ≤80% as compared with those of top-grade blastocysts (p < 0.05). After converting blastocyst morphology grades into scores, high TLBMSs were associated with greater probabilities of mosaic levels ≤20% (OR = 1.326, 95% CI = 1.187–1.481), <50% (OR = 1.425, 95% CI = 1.262–1.608), and ≤80% (OR = 1.351, 95% CI = 1.186–1.539) (p < 0.001). The prediction abilities of TLBMSs were similar for mosaic levels ≤20% (AUC = 0.604, 95% CI = 0.565–0.642), <50% (AUC = 0.634, 95% CI = 0.598–0.671), and ≤80% (AUC = 0.617, 95% CI = 0.576–0.658). In conclusion, detailed evaluation with TL monitoring at the specific time window reveals that redefined blastocyst morphology components and converted numeric TLBMSs are significantly correlated with all of the threshold levels of mosaicism. However, the performance of TLBMSs to differentiate blastocysts with aberrant ploidy risk remains perfectible.
Colorectal Cancer-Associated Microbiome Patterns and Signatures
Authors: Zhao Lan , Cho William C. , Nicolls Mark R.
Published: December 2021

The gut microbiome is dynamic and shaped by diet, age, geography, and environment. The disruption of normal gut microbiota (dysbiosis) is closely related to colorectal cancer (CRC) risk and progression. To better identify and characterize CRC-associated dysbiosis, we collected six independent cohorts with matched normal pairs (when available) for comparison and exploration of the microbiota and their interactions with the host. Comparing the microbial community compositions between cancerous and adjacent noncancerous tissues, we found that more microbes were depleted than enriched in tumors. Despite taxonomic variations among cohorts, consistent depletion of normal microbiota (members of Clostridia and Bacteroidia) and significant enrichment of oral-originated pathogens (such as Fusobacterium nucleatum and Parvimonas micra) were observed in CRC compared to normal tissues. Sets of hub and hub-connecting microbes were subsequently identified to infer microbe-microbe interaction networks in CRC. Furthermore, biclustering was used for identifying coherent patterns between patients and microbes. Two patient-microbe interaction patterns, named P0 and P1, can be consistently identified among the investigated six CRC cohorts. Characterization of the microbial community composition of the two patterns revealed that patients in P0 and P1 differed significantly in microbial alpha and beta diversity, and CRC‐associated microbiota changes consist of continuous populations of widespread taxa rather than discrete enterotypes. In contrast to the P0, the patients in P1 have reduced microbial alpha diversity compared to the adjacent normal tissues, and P1 possesses more oral-related pathogens than P0 and controls. Collectively, our study investigated the CRC-associated microbiome changes, and identified reproducible microbial signatures across multiple independent cohorts. More importantly, we revealed that the CRC heterogeneity can be partially attributed to the variety and compositional differences of microbes and their interactions to humans.
An Improved Deep Learning Model: S-TextBLCNN for Traditional Chinese Medicine Formula Classification
Authors: Cheng Ning , Chen Yue , Gao Wanqing , Liu Jiajun , Huang Qunfu , Yan Cheng , Huang Xindi , Ding Changsong
Published: December 2021

Purpose: This study proposes an S-TextBLCNN model for the efficacy of traditional Chinese medicine (TCM) formula classification. This model uses deep learning to analyze the relationship between herb efficacy and formula efficacy, which is helpful in further exploring the internal rules of formula combination.

Methods: First, for the TCM herbs extracted from Chinese Pharmacopoeia, natural language processing (NLP) is used to learn and realize the quantitative expression of different TCM herbs. Three features of herb name, herb properties, and herb efficacy are selected to encode herbs and to construct formula-vector and herb-vector. Then, based on 2,664 formulae for stroke collected in TCM literature and 19 formula efficacy categories extracted from Yifang Jijie, an improved deep learning model TextBLCNN consists of a bidirectional long short-term memory (Bi-LSTM) neural network and a convolutional neural network (CNN) is proposed. Based on 19 formula efficacy categories, binary classifiers are established to classify the TCM formulae. Finally, aiming at the imbalance problem of formula data, the over-sampling method SMOTE is used to solve it and the S-TextBLCNN model is proposed.

Results: The formula-vector composed of herb efficacy has the best effect on the classification model, so it can be inferred that there is a strong relationship between herb efficacy and formula efficacy. The TextBLCNN model has an accuracy of 0.858 and an F1-score of 0.762, both higher than the logistic regression (acc = 0.561, F1-score = 0.567), SVM (acc = 0.703, F1-score = 0.591), LSTM (acc = 0.723, F1-score = 0.621), and TextCNN (acc = 0.745, F1-score = 0.644) models. In addition, the over-sampling method SMOTE is used in our model to tackle data imbalance, and the F1-score is greatly improved by an average of 47.1% in 19 models.

Conclusion: The combination of formula feature representation and the S-TextBLCNN model improve the accuracy in formula efficacy classification. It provides a new research idea for the study of TCM formula compatibility.
Characterization and Analysis of the Temporal and Spatial Dynamic of Several Enteritis Modeling Methodologies
Authors: Xu Huangru , Cai Fangfang , Li Ping , Wang Xiaoyang , Yao Yingying , Chang Xiaoyao , Bi Zhiqian , Sun Huisong , Zhuang Hongqin , Hua Zi-Chun
Published: December 2021

Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, is a complex disease involving genetic, immune, and microbiological factors. A variety of animal models of IBD have been developed to study the pathogenesis of human IBD, but there is no model that can fully represent the complexity of IBD. In this study, we established two acute enteritis models by oral 3% DSS or intraperitoneal injection of anti-CD3 antibody, and two chronic enteritis models by feeding 3 cycles of 1.5% DSS or 3 months of the high-fat diet, respectively, and then examined the clinical parameters, histological changes, and cytokine expression profiles after the successful establishment of the models. Our results indicated that in 3% DSS-induced acute enteritis, the colorectal injury was significantly higher than that of the small intestine, while in anti-CD3 antibody-induced acute enteritis, the small intestine injury was significantly higher than that of colorectal damage. Besides, in the 1.5% DSS-induced chronic enteritis, the damage was mainly concentrated in the colorectal, while the damage caused by long-term HFD-induced chronic enteritis was more focused on the small intestine. Therefore, our work provides a reference for selecting appropriate models when conducting research on factors related to the pathogenesis of IBD or evaluating the potential diagnosis and treatment possibilities of pharmaceuticals.
Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy
Authors: Li Xueyan , Zhong Jiahui , Deng Xue , Guo Xuan , Lu Yantong , Lin Juze , Huang Xuhui , Wang Changjun
Published: December 2021

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are activated under pathological conditions, such as cancer, or mature myeloid cells that are converted immune-suppressive cells via tumor-derived exosomes, and potently support the tumor processes at different levels. Currently, multiple studies have demonstrated that MDSCs induce immune checkpoint blockade (ICB) therapy resistance through their contribution to the immunosuppressive network in the tumor microenvironment. In addition, non-immunosuppressive mechanisms of MDSCs such as promotion of angiogenesis and induction of cancer stem cells also exert a powerful role in tumor progression. Thus, MDSCs are potential therapeutic targets to enhance the antitumor efficacy of ICB therapy in cases of multiple cancers. This review focuses on the tumor-promoting mechanism of MDSCs and provides an overview of current strategies that target MDSCs with the objective of enhancing the antitumor efficacy of ICB therapy.
Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic
Authors: Supriya Rashmi , Gao Yang , Gu Yaodong , Baker Julien S.
Published: December 2021

The COVID-19 pandemic has led to several pioneering scientific discoveries resulting in no effective solutions with the exception of vaccination. Moderate exercise is a significant non-pharmacological strategy, to reduce the infection-related burden of COVID-19, especially in patients who are obese, elderly, and with additional comorbidities. The imbalance of T helper type 1 (Th1) or T helper type 2 (Th2) cells has been well documented among populations who have suffered as a result of the COVID-19 pandemic, and who are at maximum risk of infection and mortality. Moderate and low intensity exercise can benefit persons at risk from the disease and survivors by favorable modulation in Th1/Th2 ratios. Moreover, in COVID-19 patients, mild to moderate intensity aerobic exercise also increases immune system function but high intensity aerobic exercise may have adverse effects on immune responses. In addition, sustained hypoxia in COVID-19 patients has been reported to cause organ failure and cell death. Hypoxic conditions have also been highlighted to be triggered in COVID-19-susceptible individuals and COVID-19 survivors. This suggests that hypoxia inducible factor (HIF 1α) might be an important focus for researchers investigating effective strategies to minimize the effects of the pandemic. Intermittent hypoxic preconditioning (IHP) is a method of exposing subjects to short bouts of moderate hypoxia interspersed with brief periods of normal oxygen concentrations (recovery). This methodology inhibits the production of pro-inflammatory factors, activates HIF-1α to activate target genes, and subsequently leads to a higher production of red blood cells and hemoglobin. This increases angiogenesis and increases oxygen transport capacity. These factors can help alleviate virus induced cardiopulmonary hemodynamic disorders and endothelial dysfunction. Therefore, during the COVID-19 pandemic we propose that populations should engage in low to moderate exercise individually designed, prescribed and specific, that utilizes IHP including pranayama (yoga), swimming and high-altitude hiking exercise. This would be beneficial in affecting HIF-1α to combat the disease and its severity. Therefore, the promotion of certain exercises should be considered by all sections of the population. However, exercise recommendations and prescription for COVID-19 patients should be structured to match individual levels of capability and adaptability.
Intrinsic Strand-Incision Activity of Human UNG: Implications for Nick Generation in Immunoglobulin Gene Diversification
Authors: Alexeeva Marina , Moen Marivi Nabong , Xu Xiang Ming , Rasmussen Anette , Leiros Ingar , Kirpekar Finn , Klungland Arne , Alsøe Lene , Nilsen Hilde , Bjelland Svein
Published: December 2021

Uracil arises in cellular DNA by cytosine (C) deamination and erroneous replicative incorporation of deoxyuridine monophosphate opposite adenine. The former generates C → thymine transition mutations if uracil is not removed by uracil-DNA glycosylase (UDG) and replaced by C by the base excision repair (BER) pathway. The primary human UDG is hUNG. During immunoglobulin gene diversification in activated B cells, targeted cytosine deamination by activation-induced cytidine deaminase followed by uracil excision by hUNG is important for class switch recombination (CSR) and somatic hypermutation by providing the substrate for DNA double-strand breaks and mutagenesis, respectively. However, considerable uncertainty remains regarding the mechanisms leading to DNA incision following uracil excision: based on the general BER scheme, apurinic/apyrimidinic (AP) endonuclease (APE1 and/or APE2) is believed to generate the strand break by incising the AP site generated by hUNG. We report here that hUNG may incise the DNA backbone subsequent to uracil excision resulting in a 3´-α,β-unsaturated aldehyde designated uracil-DNA incision product (UIP), and a 5´-phosphate. The formation of UIP accords with an elimination (E2) reaction where deprotonation of C2´ occurs via the formation of a C1´ enolate intermediate. UIP is removed from the 3´-end by hAPE1. This shows that the first two steps in uracil BER can be performed by hUNG, which might explain the significant residual CSR activity in cells deficient in APE1 and APE2.
Distinct Oncogenic Transcriptomes in Human Mammary Epithelial Cells Infected With Cytomegalovirus
Authors: Haidar Ahmad Sandy , Pasquereau Sébastien , El Baba Ranim , Nehme Zeina , Lewandowski Clara , Herbein Georges
Published: December 2021

Human cytomegalovirus is being recognized as a potential oncovirus beside its oncomodulation role. We previously isolated two clinical isolates, HCMV-DB (KT959235) and HCMV-BL (MW980585), which in primary human mammary epithelial cells promoted oncogenic molecular pathways, established anchorage-independent growth in vitro, and produced tumorigenicity in mice models, therefore named high-risk oncogenic strains. In contrast, other clinical HCMV strains such as HCMV-FS, KM, and SC did not trigger such traits, therefore named low-risk oncogenic strains. In this study, we compared high-risk oncogenic HCMV-DB and BL strains (high-risk) with low-risk oncogenic strains HCMV-FS, KM, and SC (low-risk) additionally to the prototypic HCMV-TB40/E, knowing that all strains infect HMECs in vitro. Numerous pro-oncogenic features including enhanced expression of oncogenes, cell survival, proliferation, and epithelial-mesenchymal transition genes were observed with HCMV-BL. In vitro, mammosphere formation was observed only in high-risk strains. HCMV-TB40/E showed an intermediate transcriptome landscape with limited mammosphere formation. Since we observed that Ki67 gene expression allows us to discriminate between high and low-risk HCMV strains in vitro, we further tested its expression in vivo. Among HCMV-positive breast cancer biopsies, we only detected high expression of the Ki67 gene in basal tumors which may correspond to the presence of high-risk HCMV strains within tumors. Altogether, the transcriptome of HMECs infected with HCMV clinical isolates displays an “oncogenic gradient” where high-risk strains specifically induce a prooncogenic environment which might participate in breast cancer development.
Gateway Reflex and Mechanotransduction
Authors: Matsuyama Shiina , Tanaka Yuki , Hasebe Rie , Hojyo Shintaro , Murakami Masaaki
Published: December 2021

The gateway reflex explains how autoreactive CD4+ T cells cause inflammation in tissues that have blood-barriers, such as the central nervous system and retina. It depends on neural activations in response to specific external stimuli, such as gravity, pain, stress, and light, which lead to the secretion of noradrenaline at specific vessels in the tissues. Noradrenaline activates NFkB at these vessels, followed by an increase of chemokine expression as well as a reduction of tight junction molecules to accumulate autoreactive CD4+ T cells, which breach blood-barriers. Transient receptor potential vanilloid 1 (TRPV1) molecules on sensory neurons are critical for the gateway reflex, indicating the importance of mechano-sensing. In this review, we overview the gateway reflex with a special interest in mechanosensory transduction (mechanotransduction).
Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases Identified That TNC Is a Novel Biomarker for Keloid
Authors: Xie Jiaheng , Chen Liang , Cao Yuan , Wu Dan , Xiong Wenwen , Zhang Kai , Shi Jingping , Wang Ming
Published: December 2021

Background

The pathophysiology of keloid formation is not yet understood, so the identification of biomarkers for kelod can be one step towards designing new targeting therapies which will improve outcomes for patients with keloids or at risk of developing keloids.

Methods

In this study, we performed single-cell RNA sequencing analysis, weighted co-expression network analysis, and differential expression analysis of keloids based on public databases. And 3 RNA sequencing data from keloid patients in our center were used for validation. Besides, we performed QRT-PCR on keloid tissue and adjacent normal tissues from 16 patients for further verification.

Results

We identified the sensitive biomarker of keloid: Tenascin-C (TNC). Then, Pseudotime analysis found that the expression level of TNC decreased first, then stabilized and finally increased with fibroblast differentiation, suggesting that TNC may play an potential role in fibroblast differentiation. In addition, there were differences in the infiltration level of macrophages M0 between the TNC-high group and the TNC-low group. Macrophages M0 had a higher infiltration level in low TNC- group (P<0.05).

Conclusion

Our results can provide a new idea for the diagnosis and treatment of keloid.
Examining the Role of Marine Mammals and Seabirds in Southeast Alaska’s Marine Ecosystem Dynamics
Authors: Rhodes-Reese Melissa , Clay David , Cunningham Curry , Moriles-Miller Janet , Reese Cheryl , Roman Joe , Warren Joseph D. , Pearson Heidi C.
Published: December 2021

Primary producers are the foundation of marine food webs and require reliable nutrient sources to maintain their important role with ecosystems. While marine mammals and seabirds can play critical roles in marine nutrient cycling, their contributions are often overlooked. Southeast Alaska’s marine environment supports abundant marine mammal and seabird populations in addition to valuable fisheries. Nonetheless, there is still relatively little known about nutrient sources and fluxes in this region which is a critical component of fisheries management. The goal of our study was to advance knowledge of the role of mammals and seabirds in marine nutrient cycling and to understand how changing marine mammal and seabird populations may alter ecosystem dynamics. We utilized qualitative network models (QNMs) to examine how a simulated Southeast Alaska ecosystem would respond to an increase in marine mammals, seabirds, and nutrients. Researchers are increasingly utilizing QNMs as a first step in the development of ecosystem-based fisheries management plans as their adaptable nature is well suited to address rapidly changing climatic conditions. Our results indicate that marine mammals and seabirds make important contributions to marine nutrient concentrations in the region and that these valuable ecosystem services should not be overlooked.
The Potential of Calcium Phosphate Nanoparticles as Adjuvants and Vaccine Delivery Vehicles
Authors: Sun Zhe , Li Wenyi , Lenzo Jason C. , Holden James A. , McCullough Michael J. , O’Connor Andrea J. , O’Brien-Simpson Neil M.
Published: December 2021

Vaccination is one of the most efficacious and cost-effective ways to protect people from infectious diseases and potentially cancer. The shift in vaccine design from disrupted whole pathogens to subunit antigens has brought attention on to vaccine delivery materials. For the last two decades, nanotechnology-based vaccines have attracted considerable attention as delivery vehicles and adjuvants to enhance immunogenicity, exemplified with the current COVID vaccines. The nanoparticle vaccines display unique features in protecting antigens from degradation, controlled antigen release and longer persisting immune response. Due to their size, shape and surface charge, they can be outstanding adjuvants to achieve various immunological effects. With the safety and biodegradable benefit of calcium phosphate nanoparticles (CaP NPs), they are an efficient carrier for vaccine design and adjuvants. Several research groups have studied CaP NPs in the field of vaccination with great advances. Although there are several reports on the overview of CaP NPs, they are limited to the application in biomedicine, drug delivery, bone regeneration and the methodologies of CaP NPs synthesis. Hence, we summarised the basic properties of CaP NPs and the recent vaccine development of CaP NPs in this review.
Exploitation of the Host Ubiquitin System: Means by Legionella pneumophila
Authors: Luo Jingjing , Wang Lidong , Song Lei , Luo Zhao-Qing
Published: December 2021

Ubiquitination is a commonly used post-translational modification (PTM) in eukaryotic cells, which regulates a wide variety of cellular processes, such as differentiation, apoptosis, cell cycle, and immunity. Because of its essential role in immunity, the ubiquitin network is a common target of infectious agents, which have evolved various effective strategies to hijack and co-opt ubiquitin signaling for their benefit. The intracellular pathogen Legionella pneumophila represents one such example; it utilizes a large cohort of virulence factors called effectors to modulate diverse cellular processes, resulting in the formation a compartment called the Legionella-containing vacuole (LCV) that supports its replication. Many of these effectors function to re-orchestrate ubiquitin signaling with distinct biochemical activities. In this review, we highlight recent progress in the mechanism of action of L. pneumophila effectors involved in ubiquitination and discuss their roles in bacterial virulence and host cell biology.
Identification of Diagnostic Markers Correlated With HIV+ Immune Non-response Based on Bioinformatics Analysis
Authors: Bai Ruojing , Li Zhen , Hou Yuying , Lv Shiyun , Wang Ran , Hua Wei , Wu Hao , Dai Lili
Published: December 2021

Background: HIV-infected immunological non-responders (INRs) are characterized by their inability to reconstitute CD4+ T cell pools after antiretroviral therapy. The risk of non-AIDS-related diseases in INRs is increased, and the outcome and prognosis of INRs are inferior to that of immunological responders (IRs). However, few markers can be used to define INRs precisely. In this study, we aim to identify further potential diagnostic markers associated with INRs through bioinformatic analyses of public datasets.

Methods: This study retrieved the microarray data sets of GSE106792 and GSE77939 from the Gene Expression Omnibus (GEO) database. After merging two microarray data and adjusting the batch effect, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) resource and Kyoto Encyclopedia of Genes and Genomes (KEGG) resource were conducted to analyze the biological process and functional enrichment. We performed receiver operating characteristic (ROC) curves to filtrate potential diagnostic markers for INRs. Gene Set Enrichment Analysis (GSEA) was conducted to perform the pathway enrichment analysis of individual genes. Single sample GSEA (ssGSEA) was performed to assess scores of immune cells within INRs and IRs. The correlations between the diagnostic markers and differential immune cells were examined by conducting Spearman’s rank correlation analysis. Subsequently, miRNA-mRNA-TF interaction networks in accordance with the potential diagnostic markers were built with Cytoscape. We finally verified the mRNA expression of the diagnostic markers in clinical samples of INRs and IRs by performing RT-qPCR.

Results: We identified 52 DEGs in the samples of peripheral blood mononuclear cells (PBMC) between INRs and IRs. A few inflammatory and immune-related pathways, including chronic inflammatory response, T cell receptor signaling pathway, were enriched. FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1 were considered as potential diagnostic markers. ssGSEA results showed that the IRs had significantly higher enrichment scores of seven immune cells compared with IRs. The miRNA-mRNA-TF network was constructed with 97 miRNAs, 6 diagnostic markers, and 26 TFs, which implied a possible regulatory relationship.

Conclusion: The six potential crucial genes, FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1, may be associated with clinical diagnosis in INRs. Our study provided new insights into diagnostic and therapeutic targets.
Membrane-Mediated Interactions Between Protein Inclusions
Authors: Gao Jie , Hou Ruihan , Li Long , Hu Jinglei
Published: December 2021

Integral or peripheral membrane proteins, or protein oligomers often get close to each other on cell membranes and carry out biological tasks in a collective manner. In addition to electrostatic and van der Waals interactions, those proteins also experience membrane-mediated interactions, which may be necessary for their functionality. The membrane-mediated interactions originate from perturbation of lipid membranes by the presence of protein inclusions, and have been the subject of intensive research in membrane biophysics. Here we review both theoretical and numerical studies of such interactions for membrane proteins and for nanoparticles bound to lipid membranes.
Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease
Authors: Yang Changwei , Wang Wuqiong , Deng Pengxi , Li Chen , Zhao Liangcai , Gao Hongchang
Published: December 2021

Microglial polarization and the subsequent neuroinflammatory response were identified as key contributors to the progress of Parkinson's disease (PD). Researchers have shown that fibroblast growth factor 21 (FGF21) plays multiple biological functions, including anti-inflammation and neuroprotection. However, the knowledge of FGF21 on microglial polarization in PD in vivo is far from completion. In this study, both in vivo and in vitro models were used to investigate whether FGF21 enhances the brain function by modulating microglial polarization in PD. The protective effects of FGF21 in vivo were conducted using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice model alongside intraperitoneally received FGF21. A behavioral test battery and tyrosine hydroxylase (TH) immunohistochemistry were conducted to evaluate the neuronal function and nigrostriatal tract integrity. Immunofluorescence assay and Western blot were used to examine M1/M2 microglial polarization. Then, a microglia-neuron co-culture system was adopted in vitro to identify the underlying molecular mechanisms of FGF21. The results showed that FGF21 significantly alleviated motor and cognitive impairment in mice with PD. FGF21 also protected TH-positive neuron cells in the striatum and midbrain. Mechanistically, FGF21 suppressed M1 microglial polarization and the subsequent mRNA expression of pro-inflammatory factors while promoting M2 microglial polarization with increasing anti-inflammatory factors in mice with PD. Furthermore, sirtuin 1 (SIRT1) and the nuclear factor-kappa B (NF-κB) pathway were involved in the FGF21-induced M2 microglial polarization. Conversely, SIRT1 inhibitor EX527 significantly prevented both the FGF21-induced SIRT1 expression and M2 microglial polarization. Moreover, FGF21 pretreatment of microglia significantly prevented neuronal cell apoptosis in a microglia-neuron co-culture system. In conclusion, our data demonstrate that FGF21 exerted its protective effects in the pathology of PD through SIRT1/NF-κB pathway-mediated microglial polarization. Given the safety record of human clinical trials, FGF21 could be a promising therapy for clinical trials to ameliorate motor and nonmotor deficits in patients with PD.
Repetitive Blast Exposure Increases Appetitive Motivation and Behavioral Inflexibility in Male Mice
Authors: Baskin Britahny , Lee Suhjung Janet , Skillen Emma , Wong Katrina , Rau Holly , Hendrickson Rebecca C. , Pagulayan Kathleen , Raskind Murray A. , Peskind Elaine R. , Phillips Paul E. M. , Cook David G. , Schindler Abigail G.
Published: December 2021

Blast exposure (via detonation of high explosives) represents a major potential trauma source for Servicemembers and Veterans, often resulting in mild traumatic brain injury (mTBI). Executive dysfunction (e.g., alterations in memory, deficits in mental flexibility, difficulty with adaptability) is commonly reported by Veterans with a history of blast-related mTBI, leading to impaired daily functioning and decreased quality of life, but underlying mechanisms are not fully understood and have not been well studied in animal models of blast. To investigate potential underlying behavioral mechanisms contributing to deficits in executive functioning post-blast mTBI, here we examined how a history of repetitive blast exposure in male mice affects anxiety/compulsivity-like outcomes and appetitive goal-directed behavior using an established mouse model of blast mTBI. We hypothesized that repetitive blast exposure in male mice would result in anxiety/compulsivity-like outcomes and corresponding performance deficits in operant-based reward learning and behavioral flexibility paradigms. Instead, results demonstrate an increase in reward-seeking and goal-directed behavior and a congruent decrease in behavioral flexibility. We also report chronic adverse behavioral changes related to anxiety, compulsivity, and hyperarousal. In combination, these data suggest that potential deficits in executive function following blast mTBI are at least in part related to enhanced compulsivity/hyperreactivity and behavioral inflexibility and not simply due to a lack of motivation or inability to acquire task parameters, with important implications for subsequent diagnosis and treatment management.
Multi-Parameter Physiological State Monitoring in Target Detection Under Real-World Settings
Authors: Chang Yang , He Congying , Tsai Bo-Yu , Ko Li-Wei
Published: December 2021

Mental state changes induced by stimuli under experimental settings or by daily events in real life affect task performance and are entwined with physical and mental health. In this study, we developed a physiological state indicator with five parameters that reflect the subject’s real-time physiological states based on online EEG signal processing. These five parameters are attention, fatigue, stress, and the brain activity shifts of the left and right hemispheres. We designed a target detection experiment modified by a cognitive attention network test for validating the effectiveness of the proposed indicator, as such conditions would better approximate a real chaotic environment. Results demonstrated that attention levels while performing the target detection task were significantly higher than during rest periods, but also exhibited a decay over time. In contrast, the fatigue level increased gradually and plateaued by the third rest period. Similar to attention levels, the stress level decreased as the experiment proceeded. These parameters are therefore shown to be highly correlated to different stages of the experiment, suggesting their usage as primary factors in passive brain-computer interfaces (BCI). In addition, the left and right brain activity indexes reveal the EEG neural modulations of the corresponding hemispheres, which set a feasible reference of activation for an active BCI control system, such as one executing motor imagery tasks. The proposed indicator is applicable to potential passive and active BCI applications for monitoring the subject’s physiological state change in real-time, along with providing a means of evaluating the associated signal quality to enhance the BCI performance.
Nano-Organization at the Synapse: Segregation of Distinct Forms of Neurotransmission
Authors: Guzikowski Natalie J. , Kavalali Ege T.
Published: December 2021

Synapses maintain synchronous, asynchronous, and spontaneous modes of neurotransmission through distinct molecular and biochemical pathways. Traditionally a single synapse was assumed to have a homogeneous organization of molecular components both at the active zone and post-synaptically. However, recent advancements in experimental tools and the further elucidation of the physiological significance of distinct forms of release have challenged this notion. In comparison to rapid evoked release, the physiological significance of both spontaneous and asynchronous neurotransmission has only recently been considered in parallel with synaptic structural organization. Active zone nanostructure aligns with postsynaptic nanostructure creating a precise trans-synaptic alignment of release sites and receptors shaping synaptic efficacy, determining neurotransmission reliability, and tuning plasticity. This review will discuss how studies delineating synaptic nanostructure create a picture of a molecularly heterogeneous active zone tuned to distinct forms of release that may dictate diverse synaptic functional outputs.
A Systematic Review and Recommendations Around Frameworks for Evaluating Scientific Validity in Nutritional Genomics
Authors: Keathley Justine , Garneau Véronique , Zavala-Mora Daniela , Heister Robyn R. , Gauthier Ellie , Morin-Bernier Josiane , Green Robert , Vohl Marie-Claude
Published: December 2021

Background: There is a significant lack of consistency used to determine the scientific validity of nutrigenetic research. The aims of this study were to examine existing frameworks used for determining scientific validity in nutrition and/or genetics and to determine which framework would be most appropriate to evaluate scientific validity in nutrigenetics in the future.

Methods: A systematic review (PROSPERO registration: CRD42021261948) was conducted up until July 2021 using Medline, Embase, and Web of Science, with articles screened in duplicate. Gray literature searches were also conducted (June-July 2021), and reference lists of two relevant review articles were screened. Included articles provided the complete methods for a framework that has been used to evaluate scientific validity in nutrition and/or genetics. Articles were excluded if they provided a framework for evaluating health services/systems more broadly. Citing articles of the included articles were then screened in Google Scholar to determine if the framework had been used in nutrition or genetics, or both; frameworks that had not were excluded. Summary tables were piloted in duplicate and revised accordingly prior to synthesizing all included articles. Frameworks were critically appraised for their applicability to nutrigenetic scientific validity assessment using a predetermined categorization matrix, which included key factors deemed important by an expert panel for assessing scientific validity in nutrigenetics.

Results: Upon screening 3,931 articles, a total of 49 articles representing 41 total frameworks, were included in the final analysis (19 used in genetics, 9 used in nutrition, and 13 used in both). Factors deemed important for evaluating nutrigenetic evidence related to study design and quality, generalizability, directness, consistency, precision, confounding, effect size, biological plausibility, publication/funding bias, allele and nutrient dose-response, and summary levels of evidence. Frameworks varied in the components of their scientific validity assessment, with most assessing study quality. Consideration of biological plausibility was more common in frameworks used in genetics. Dose-response effects were rarely considered. Two included frameworks incorporated all but one predetermined key factor important for nutrigenetic scientific validity assessment.

Discussion/Conclusions: A single existing framework was highlighted as optimal for the rigorous evaluation of scientific validity in nutritional genomics, and minor modifications are proposed to strengthen it further.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261948, PROSPERO [CRD42021261948].