bluuebunny/crossref_metadata_2025 huggingface dataset:
Microencapsulated Neural Stem Cells Inhibit Sciatic Nerve Injury-Induced Pain by Reducing P2 × 4 Receptor Expression
Authors: Zhang Wen-jun , Luo Chen , Huang Chao , Liu Si-cheng , Luo Hong-liang
Published: September 2021

Objectives: The purpose of this study is to investigate the effects of transplantation of microencapsulated neural stem cells (MC-NSCs), which downregulate the P2 × 4 receptor (P2 × 4R) overexpression and relieve neuropathic pain (NPP).

Methods: Neural stem cells (NSCs) and MC-NSCs were transplanted to the injured sciatic nerve. Transmission electron microscope and immunofluorescence were used to observe the changes of injured sciatic nerve. Behavioral methods were used to detect mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats. Expression levels of P2 × 4Rs and p-p65 in the spinal cord segment of rats were measured by using molecular biology methods. The concentrations of IL-1β and TNF-α were detected in serum of rats by ELISA.

Results: After sciatic nerve injury, the sciatic nerve fibers had the myelinated lamina separated, and disintegrated fragments could be seen. The fluorescence intensity of myelin MBP was weakened. The MWT and TWL were significantly decreased, the expression of P2 × 4Rs and p-p65 were significantly increased, and the concentrations of IL-1β and TNF-α were increased. After NSC and MC-NSC transplantation, the myelin sheath of the sciatic nerve was relatively intact, some demyelination changes could be seen, and the injured sciatic nerve has been improved. The fluorescence intensity of myelin MBP was increased. The MWT and TWL were increased, expression levels of P2 × 4Rs and p-p65 were decreased, and the concentrations of IL-1β and TNF-α were significantly decreased. Compared with NSC transplantation, transplantation of MC-NSCs could better repair the damaged sciatic nerve, decrease the expression of P2 × 4Rs and p-p65, decrease the level of IL-1β and TNF-α, and relieve pain (all p-values < 0.05).

Conclusion: NSCs and MC-NSCs transplantation may alleviate pain by reducing the expression of P2 × 4Rs and inhibiting the activation of NF-KB signaling, while MC-NSCs transplantation has a better effect of suppressing pain. Our experimental results provide new data support for the treatment of NPP.
Human Three-Finger Protein Lypd6 Is a Negative Modulator of the Cholinergic System in the Brain
Authors: Kulbatskii Dmitrii , Shenkarev Zakhar , Bychkov Maxim , Loktyushov Eugene , Shulepko Mikhail , Koshelev Sergey , Povarov Igor , Popov Alexander , Peigneur Steve , Chugunov Anton , Kozlov Sergey , Sharonova Irina , Efremov Roman , Skrebitsky Vladimir , Tytgat Jan , Kirpichnikov Mikhail , Lyukmanova Ekaterina
Published: September 2021

Lypd6 is a GPI-tethered protein from the Ly-6/uPAR family expressed in the brain. Lypd6 enhances the Wnt/β-catenin signaling, although its action on nicotinic acetylcholine receptors (nAChRs) have been also proposed. To investigate a cholinergic activity of Lypd6, we studied a recombinant water-soluble variant of the human protein (ws-Lypd6) containing isolated “three-finger” LU-domain. Experiments at different nAChR subtypes expressed in Xenopus oocytes revealed the negative allosteric modulatory activity of ws-Lypd6. Ws-Lypd6 inhibited ACh-evoked currents at α3β4- and α7-nAChRs with IC50 of ∼35 and 10 μM, respectively, and the maximal amplitude of inhibition of 30–50%. EC50 of ACh at α3β4-nAChRs (∼30 μM) was not changed in the presence of 35 μM ws-Lypd6, while the maximal amplitude of ACh-evoked current was reduced by ∼20%. Ws-Lypd6 did not elicit currents through nAChRs in the absence of ACh. Application of 1 μM ws-Lypd6 significantly inhibited (up to ∼28%) choline-evoked current at α7-nAChRs in rat hippocampal slices. Similar to snake neurotoxin α-bungarotoxin, ws-Lypd6 suppressed the long-term potentiation (LTP) in mouse hippocampal slices. Colocalization of endogenous GPI-tethered Lypd6 with α3β4- and α7-nAChRs was detected in primary cortical and hippocampal neurons. Ws-Lypd6 interaction with the extracellular domain of α7-nAChR was modeled using the ensemble protein-protein docking protocol. The interaction of all three Lypd6 loops (“fingers”) with the entrance to the orthosteric ligand-binding site and the loop C of the primary receptor subunit was predicted. The results obtained allow us to consider Lypd6 as the endogenous negative modulator involved in the regulation of the cholinergic system in the brain.
Tau and Membranes: Interactions That Promote Folding and Condensation
Authors: Sallaberry Chad A. , Voss Barbie J. , Majewski Jaroslaw , Biernat Jacek , Mandelkow Eckhard , Chi Eva Y. , Vander Zanden Crystal M.
Published: September 2021

Tau misfolding and assembly is linked to a number of neurodegenerative diseases collectively described as tauopathies, including Alzheimer’s disease (AD) and Parkinson’s disease. Anionic cellular membranes, such as the cytosolic leaflet of the plasma membrane, are sites that concentrate and neutralize tau, primarily due to electrostatic interactions with tau’s microtubule binding repeat domain (RD). In addition to electrostatic interactions with lipids, tau also has interactions with membrane proteins, which are important for tau’s cellular functions. Tau also interacts with lipid tails to facilitate direct translocation across the membrane and can form stable protein-lipid complexes involved in cell-to-cell transport. Concentrated tau monomers at the membrane surface can form reversible condensates, change secondary structures, and induce oligomers, which may eventually undergo irreversible crosslinking and fibril formation. These β-sheet rich tau structures are capable of disrupting membrane organization and are toxic in cell-based assays. Given the evidence for relevant membrane-based tau assembly, we review the emerging hypothesis that polyanionic membranes may serve as a site for phase-separated tau condensation. Membrane-mediated phase separation may have important implications for regulating tau folding/misfolding, and may be a powerful mechanism to spatially direct tau for native membrane-mediated functions.
The Expression and Prognostic Value of SUMO1-Activating Enzyme Subunit 1 and Its Potential Mechanism in Triple-Negative Breast Cancer
Authors: Wang Qingshui , Zhong Wenting , Deng Lin , Lin Qili , Lin Youyu , Liu Hongxia , Xu Luyun , Lu Lingfang , Chen Yajuan , Huang Jianping , Jiang Meichen , Xiao Han , Zhang Jie , Li He , Lin Yuxiang , Song Chuangui , Lin Yao
Published: September 2021

Background: Triple-negative breast cancer (TNBC) is the most invasive and metastatic subtype of breast cancer. SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme, is indispensable for protein SUMOylation. SAE1 has been found to be a relevant biomarker for progression and prognosis in several tumor types. However, the role of SAE1 in TNBC remains to be elucidated.

Methods: In the research, the mRNA expression of SAE1 was analyzed via the cancer genome atlas (TCGA) and gene expression omnibus (GEO) database. Cistrome DB Toolkit was used to predict which transcription factors (TFs) are most likely to increase SAE1 expression in TNBC. The correlation between the expression of SAE1 and the methylation of SAE1 or quantity of tumor-infiltrating immune cells was further invested. Single-cell analysis, using CancerSEA, was performed to query which functional states are associated with SAE1 in different cancers in breast cancer at the single-cell level. Next, weighted gene coexpression network (WGCNA) was applied to reveal the highly correlated genes and coexpression networks of SAE1 in TNBC patients, and a prognostic model containing SAE1 and correlated genes was constructed. Finally, we also examined SAE1 protein expression of 207 TNBC tissues using immunohistochemical (IHC) staining.

Results: The mRNA and protein expression of SAE1 were increased in TNBC tissues compared with adjacent normal tissues, and the protein expression of SAE1 was significantly associated with overall survival (OS) and disease-free survival (DFS). Correlation analyses revealed that SAE1 expression was positively correlated with forkhead box M1 (FOXM1) TFs and negatively correlated with SAE1 methylation site (cg14042711) level. WGCNA indicated that the genes coexpressed with SAE1 belonged to the green module containing 1,176 genes. Through pathway enrichment analysis of the module, 1,176 genes were found enriched in cell cycle and DNA repair. Single-cell analysis indicated that SAE1 and its coexpression genes were associated with cell cycle, DNA damage, DNA repair, and cell proliferation. Using the LASSO COX regression, a prognostic model including SAE1 and polo-like kinase 1 (PLK1) was built to accurately predict the likelihood of DFS in TNBC patients.

Conclusion: In conclusion, we comprehensively analyzed the mRNA and protein expression, prognosis, and interaction genes of SAE1 in TNBC and constructed a prognostic model including SAE1 and PLK1. These results might be important for better understanding of the role of SAE1 in TNBC. In addition, DNA methyltransferase and TFs inhibitor treatments targeting SAE1 might improve the survival of TNBC patients.
Rheological and Printability Assessments on Biomaterial Inks of Nanocellulose/Photo-Crosslinkable Biopolymer in Light-Aided 3D Printing
Authors: Wang Qingbo , Backman Oskar , Nuopponen Markus , Xu Chunlin , Wang Xiaoju
Published: September 2021

Biomaterial inks based on cellulose nanofibers (CNFs) and photo-crosslinkable biopolymers have great potential as a high-performance ink system in light-aided, hydrogel extrusion-based 3D bioprinting. However, the colloidal stability of surface charged nanofibrils is susceptible to mono-cations in physiological buffers, which complexes the application scenarios of these systems in formulating cell-laden bioinks. In this study, biomaterial inks formulated by neutral and negatively surface charged CNFs (GrowInk-N and GrowInk-T) and photo-crosslinkable biopolymers (gelatin methacryloyl (GelMA) and methacrylated galactoglucomannan (GGMMA)) were prepared with Milli-Q water or PBS buffer. Quantitative rheological measurements were performed on the ink formulations to characterize their shear flow recovery behavior and to understand the intermolecular interactions between the CNFs of different kinds with GGMMA or GelMA. Meanwhile, printability assessments, including filament extrudability and shape fidelity of the printed scaffold under varying printing conditions, were carried out to optimize the printing process. Our study provides extensive supporting information for further developing these nanocellulose-based systems into photo-crosslinkable bioinks in the service of cell-laden 3D bioprinting.
Synthesis, Characterization, and Photocatalytic Activities of Graphene Oxide/metal Oxides Nanocomposites: A Review
Authors: Jamjoum Hayfa Alajilani Abraheem , Umar Khalid , Adnan Rohana , Razali Mohd. R. , Mohamad Ibrahim Mohamad Nasir
Published: September 2021

Sustainable water processing techniques have been extensively investigated and are capable of improving water quality. Among the techniques, photocatalytic technology has shown great potential in recent years as a low cost, environmentally friendly and sustainable technology. However, the major challenge in the industrial development of photocatalyst technology is to develop an ideal photocatalyst which must have high photocatalytic activity, a large specific surface area, harvest sunlight and shows recyclability. Keeping these views, the present review highlighted the synthesis approaches of graphene/metal oxide nanocomposite, characterization techniques and their prominent applications in photocatalysis. Various parameters such as photocatalyst loading, structure of photocatalyst, temperature, pH, effect of oxidizing species and wavelength of light were addressed which could affect the rate of degradation. Moreover, the formation of intermediates during photo-oxidation of organic pollutants using these photocatalysts is also discussed. The analysis concluded with a synopsis of the importance of graphene-based materials in pollutant removal. Finally, a brief overview of the problems and future approaches in the field is also presented.
Microbiota Emergencies in the Diagnosis of Lung Diseases: A Meta-Analysis
Authors: Ruan Renyu , Deng Xiangmin , Dong Xiaoyan , Wang Qi , Lv Xiaoling , Si Caijuan
Published: September 2021

Although many studies have reported that microbiota emergencies are deeply involved in the occurrence and subsequent progression of lung diseases, the present diagnosis of lung disease depends on microbiota markers, which is still poorly understood. Therefore, a meta-analysis was performed to confirm lung microbiota markers for the diagnosis of lung diseases. Literature databases were searched following the inclusion and exclusion criteria. There are 6 studies including 1347 patients and 26 comparisons to be enrolled, and then the diagnostic effect was evaluated using Stata 14.0 and Meta-disc 1.4 software. The pooled sensitivity (SEN), specificity (SPE), diagnostic likelihood ratio positive (DLR+), diagnostic likelihood ratio negative (DLR−), and diagnostic OR (DOR), as well as area under the curve (AUC) of microbiota markers in the diagnosis of lung diseases were 0.90 (95% CI: 0.83-0.94), 0.89 (95% CI: 0.76-0.95), 7.86 (95% CI: 3.39-18.21), 0.12 (95% CI: 0.06-0.21), 22.254 (95% CI: 12.83-39.59.14), and 0.95 (95% CI: 0.93-0.97), respectively. Subgroup analysis revealed that research based on Caucasian, adult, BAL fluid, PCR, pneumonia obtained higher AUC values. The microbiota markers have shown potential diagnosis value for lung diseases. But further large-scale clinical studies are still needed to verify and replicate the diagnostic value of lung microbiota markers.
Biofilm Formation by Pseudomonas aeruginosa in a Novel Septic Arthritis Model
Authors: Li Dingbin , Zhang Li , Liang Jinhua , Deng Wusheng , Wei Qingjun , Wang Ke
Published: September 2021

Background

Bacterial biofilms generally contribute to chronic infections and complicate effective treatment outcomes. To date, there have been no reports describing biofilm formation in animal models of septic arthritis caused by Pseudomonas aeruginosa (P. aeruginosa). P. aeruginosa is an opportunistic pathogenic bacterium which can lead to septic arthritis. The purpose of this study was to establish a rabbit model of septic arthritis caused by P. aeruginosa to determine whether it leads to biofilm formation in the knee joint cavity. In addition, we explored the role of cyclic di-GMP (c-di-GMP) concentrations in biofilm formation in rabbit models.

Methods

Twenty rabbits were randomly assigned to five groups: PAO1 (n = 4), PAO1ΔwspF (n = 4), PAO1/plac-yhjH (n = 4) infection group, Luria–Bertani (LB) broth (n = 4), and magnesium tetrasilicate (talc) (n = 4) control groups. Inoculation in the rabbit knee of P. aeruginosa or with the same volume of sterile LB or talc in suspension (control group) was used to induce septic arthritis in the animal model. In the infection groups, septic arthritis was caused by PAO1, PAO1ΔwspF, and PAO1/plac-yhjH strains, respectively. Rabbits were euthanized after 7 days, and pathological examination of synovial membrane was performed. The biofilms on the surface of the synovial membrane were observed by scanning electron microscopy, while the biofilms’ fiber deposition was discriminated using peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH).

Results

A rabbit model for knee septic arthritis induced by P. aeruginosa was successfully established. Scanning electron microscopy revealed that PAO1 strains were surrounded in a self-produced extracellular matrix on the surface of synovial membrane and showed biofilm structures. The biofilms in the fibrous deposition were also observed by PNA-FISH. The PNA-FISH assay revealed that the red fluorescence size in the PAO1ΔwspF group was greater than in PAO1 and PAO1/plac-yhjH groups.

Conclusions

This is the first study to provide evidence that P. aeruginosa forms biofilms in a rabbit model for septic knee arthritis. The rabbit model can be used to investigate new approaches to treatment of biofilms in septic arthritis. Furthermore, c-di-GMP is a key signaling molecule which impacts on biofilm formation in rabbit models of knee septic arthritis.
A Comprehensive Analysis of the Genetic Diversity of Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2) in the Brazilian Amazon
Authors: Costa Gabriel Luíz , Mascarenhas Maria Eduarda Pereira , Martin Thamires Oliveira Gasquez , Fortini Laura Guimarães , Louzada Jaime , Pereira Dhélio Batista , Aguiar Anna Caroline Campos , Carvalho Luzia Helena , de Brito Cristiana Ferreira Alves , Fontes Cor Jesus Fernandes , de Sousa Tais Nóbrega
Published: September 2021

Early diagnosis and treatment are fundamental to the control and elimination of malaria. In many endemic areas, routine diagnosis is primarily performed microscopically, although rapid diagnostic tests (RDTs) provide a useful point-of-care tool. Most of the commercially available RDTs detect histidine-rich protein 2 (HRP2) of Plasmodium falciparum in the blood of infected individuals. Nonetheless, parasite isolates lacking the pfhrp2 gene are relatively frequent in some endemic regions, thereby hampering the diagnosis of malaria using HRP2-based RDTs. To track the efficacy of RDTs in areas of the Brazilian Amazon, we assessed pfhrp2 deletions in 132 P. falciparum samples collected from four malaria-endemic states in Brazil. Our findings show low to moderate levels of pfhrp2 deletion in different regions of the Brazilian Amazon. Overall, during the period covered by this study (2002-2020), we found that 10% of the P. falciparum isolates were characterized by a pfhrp2 deletion. Notably, however, the presence of pfhrp2-negative isolates has not been translated into a reduction in RDT efficacy, which in part may be explained by the presence of polyclonal infections. A further important finding was the discrepancy in the proportion of pfhrp2 deletions detected using two assessed protocols (conventional PCR versus nested PCR), which reinforces the need to perform a carefully planned laboratory workflow to assess gene deletion. This is the first study to perform a comprehensive analysis of PfHRP2 sequence diversity in Brazilian isolates of P. falciparum. We identified 10 PfHRP2 sequence patterns, which were found to be exclusive of each of the assessed regions. Despite the small number of PfHRP2 sequences available from South America, we found that the PfHRP2 sequences identified in Brazil and neighboring French Guiana show similar sequence patterns. Our findings highlight the importance of continuously monitoring the occurrence and spread of parasites with pfrhp2 deletions, while also taking into account the limitations of PCR-based testing methods associated with accuracy and the complexity of infections.
Study on Optimal Parameter and Target for Pulsed-Field Ablation of Atrial Fibrillation
Authors: Ye Xuying , Liu Shangzhong , Yin Huijuan , He Qiang , Xue Zhixiao , Lu Chengzhi , Su Siying
Published: September 2021

Pulsed-field ablation (PFA) had potential advantages in atrial fibrillation ablation, and we aim to confirm the optimal parameter and target of PFA for atrial fibrillation. Two ablation modes in vitro of single-cell system (ablation in electrode cup) and monolayer cell system (ablation in inserts with electrode tips) were established to perform PFA for myocardial cell H9C2 and smooth muscle cell A7r5. Ablation effect, calcium ion influx, the expression of Cx45, and surface morphological change were observed. Three Bama minipigs were used to verify the in vivo ablation effect of PFA. In monolayer cell system, H9C2 was significantly sensitive to PFA compared with A7r5, with shrinking of the whole monolayer. The ablation effect of bidirectional pulse was weaker than that of the two mono-polar pulses. Expressed Cx45 proteins were increased in H9C2 but decreased in A7r5 cells. Bidirectional PFA performed on Bama minipigs was able to effectively block electrical activity from the pulmonary vein to the atrium with week muscle contraction, not generating pulmonary vein stenosis. Bidirectional PFA was able to significantly ablate myocardial cells, maintain cell–cell connection, and reduce muscle contraction, which was a kind of optimized PFA strategy for atrial fibrillation.
Inotrope Use and Intensive Care Unit Mortality in Patients With Cardiogenic Shock: An Analysis of a Large Electronic Intensive Care Unit Database
Authors: Gao Fei , Zhang Yun
Published: September 2021

Purpose: To determine whether inotrope administration is associated with increased all-cause mortality in cardiogenic shock (CS) patients and to identify inotropes superior for improving mortality.

Methods: This retrospective cohort study analyzed data retrieved from the Philips Electronic ICU (eICU) database, a clinical database of 200,859 patients from over 208 hospitals located throughout the United States. The database was searched for patients admitted with CS to the intensive care unit (ICU) between 2014 and 2015. We evaluated 34,381 CS patients. They were classified into the inotrope and non-inotrope groups based on whether inotropes were administered during hospitalization. The primary endpoint was all-cause hospital mortality.

Findings: In total, 15,021 (43.69%) patients received inotropes during hospitalization. The in-hospital mortality rate was significantly higher in the inotrope group than in the non-inotrope group (2,999 [24.03%] vs. 1,547 [12.40%], adjusted hazard ratio: 2.24; 95% confidence interval [CI]: 2.09–2.39; p < 0.0001). After propensity score matching according to the cardiac index, 359 patients were included in each group. The risk of ICU (OR 5.65, 95% CI, 3.17–10.08, p < 0.001) and hospital (OR 2.63, 95% CI: 1.75–3.95, p < 0.001) mortality in the inotrope group was significantly higher. In the inotrope group, the administration of norepinephrine ≤0.1 μg/kg/min and dopamine ≤15 μg/kg/min did not increase the risk of hospital mortality, and milrinone administration was associated with a lower mortality risk (odds ratio: 0.559, 95% CI: 0.430–0.727, p < 0.001). Meanwhile, the administration of >0.1 μg/kg/min dobutamine, epinephrine, and norepinephrine and dopamine >15 μg/kg/min was associated with a higher risk of hospital mortality.

Conclusions: Inotropes should be used cautiously because they may be associated with a higher risk of mortality in CS patients. Low-dose norepinephrine and milrinone may associated with lower risk of hospital mortality in these patients, and supportive therapies should be considered when high-dose inotropes are administered.
Research Progress of Imaging Methods for Detection of Microvascular Angina Pectoris in Diabetic Patients
Authors: Qi Yiming , Li Lihua , Feng Guoquan , Shao Chen , Cai Yue , Wang Zhongqun
Published: September 2021

Diabetes is a complex metabolic disease characterized by hyperglycemia. Its complications are various, often involving the heart, brain, kidney, and other essential organs. At present, the number of diabetic patients in the world is growing day by day. The cardiovascular disease caused by diabetes has dramatically affected the quality of life of diabetic patients. It is the leading cause of death of diabetic patients. Diabetic patients often suffer from microvascular angina pectoris without obstructive coronary artery disease. Still, there are typical ECG ischemia and angina pectoris, that is, chest pain and dyspnea under exercise. Unlike obstructive coronary diseases, nitrate does not affect chest pain caused by coronary microvascular angina in most cases. With the increasing emphasis on diabetic microvascular angina, the need for accurate diagnosis of the disease is also increasing. We can use SPECT, PET, CMR, MCE, and other methods to evaluate coronary microvascular function. SPECT is commonly used in clinical practice, and PET is considered the gold standard for non-invasive detection of myocardial blood flow. This article mainly introduces the research progress of these imaging methods in detecting microvascular angina in diabetic patients.
Clinical Features in Children With Kawasaki Disease Shock Syndrome: A Systematic Review and Meta-Analysis
Authors: Zheng Zhimin , Huang Yanzhi , Wang Zhiyi , Tang Jia , Chen Xiaoqian , Li Ying , Li Meng , Zang Chengye , Wang Yibo , Wang Liwu , Ma Yingwei , Sun Liwei
Published: September 2021

Objective: This study aimed to identify the clinical features of Kawasaki disease shock syndrome (KDSS) in children.

Methods: The case-control studies of KDSS and KD children up until April 30, 2021 were searched in multiple databases. The qualified research were retrieved by manually reviewing the references. Review Manager 5.3 software was used for statistical analysis.

Results: The results showed that there was no significant difference in the incidence of male and female in children with KDSS. Children with KDSS compared with non-shocked KD, there were significant difference in age, duration of fever, white blood cell (WBC) count, percentage of neutrophils (NEUT%), platelet count (PLT), c-reactive protein level (CRP), alanine transaminase concentration (ALT), aspartate transaminase concentration (AST), albumin concentration (ALB), sodium concentration (Na), ejection fraction, and length of hospitalization as well as the incidence of coronary artery dilation, coronary artery aneurysm, left ventricular dysfunction, mitral regurgitation, pericardial effusion, initial diagnosis of KD, intravenous immunoglobulin (IVIG) resistance and receiving second dose of IVIG, vasoactive drugs, hormones, and albumin. In contrast, there was no difference in the hemoglobin concentration, erythrocyte sedimentation rate, and the incidence of conjunctival injection, oropharyngeal change, polymorphous rash, extremity change, and incomplete KD.

Conclusion: Current evidence suggested that the children with KDSS had more severe indicators of inflammation and more cardiac abnormalities. These patients were resistant to immunoglobulin treatment and required extra anti-inflammatory treatment.

Systematic Review Registration: PROSPERO registration number CRD42021241207.
A Framework to Foster Oral Health Literacy and Oral/General Health Integration
Authors: Kleinman Dushanka V. , Horowitz Alice M. , Atchison Kathryn A.
Published: September 2021

Science and technology advances have led to remarkable progress in understanding, managing, and preventing disease and promoting human health. This phenomenon has created new challenges for health literacy and the integration of oral and general health. We adapted the 2004 Institute of Medicine health literacy framework to highlight the intimate connection between oral health literacy and the successful integration of oral and general health. In doing so we acknowledge the roles of culture and society, educational systems and health systems as overlapping intervention points for effecting change. We believe personal and organizational health literacy not only have the power to meet the challenges of an ever- evolving society and environment, but are essential to achieving oral and general health integration. The new “Oral Health Literacy and Health Integration Framework” recognizes the complexity of efforts needed to achieve an equitable health system that includes oral health, while acknowledging that the partnership of health literacy with integration is critical. The Framework was designed to stimulate systems-thinking and systems-oriented approaches. Its interconnected structure is intended to inspire discussion, drive policy and practice actions and guide research and intervention development.
Peripheral Nerve Conduction And Sympathetic Skin Response Are Reliable Methods to Detect Diabetic Cardiac Autonomic Neuropathy
Authors: Lin Xiaopu , Chen Chuna , Liu Yingshan , Peng Yu , Chen Zhenguo , Huang Haishan , Xu Lingling
Published: September 2021

Aim

This study aimed to investigate the role of nerve conduction studies (NCS) and sympathetic skin response (SSR) in evaluating diabetic cardiac autonomic neuropathy (DCAN).

Methods

DCAN was diagnosed using the Ewing test combined with heart rate variability analysis. NCS and SSR were assessed by electrophysiological methods. The association between NCS/SSR and DCAN was assessed via multivariate regression and receiver-operating characteristic analyses.

Results

The amplitude and conduction velocity of the motor/sensory nerve were found to be significantly lower in the DCAN+ group (all P < 0.05). A lower amplitude of peroneal nerve motor fiber was found to be associated with increased odds for DCAN (OR 2.77, P < 0.05). The SSR amplitude was lower while the SSR latency was longer in the DCAN+ group than in the DCAN– group. The receiver-operating characteristic analysis revealed that the optimal cutoff points of upper/lower limb amplitude of SSR to indicate DCAN were 1.40 mV (sensitivity, 61.9%; specificity, 66.3%, P < 0.001) and 0.85 mV (sensitivity, 66.7%; specificity, 68.5%, P < 0.001), respectively. The optimal cutoff points of upper/lower limb latency to indicate DCAN were 1.40 s (sensitivity, 61.9%; specificity, 62%, P < 0.05) and 1.81 s (sensitivity, 69.0%; specificity, 52.2%, P < 0.05), respectively.

Conclusions

NCS and SSR are reliable methods to detect DCAN. Abnormality in the peroneal nerve (motor nerve) is crucial in predicting DCAN. SSR may help predict DCAN.
Heterogeneous miRNA-mRNA Regulatory Networks of Visceral and Subcutaneous Adipose Tissue in the Relationship Between Obesity and Renal Clear Cell Carcinoma
Authors: Liu Yuyan , Liu Yang , Hu Jiajin , He Zhenwei , Liu Lei , Ma Yanan , Wen Deliang
Published: September 2021

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urologic cancer. Associations of both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with ccRCC have been reported, and underlying mechanisms of VAT perhaps distinguished from SAT, considering their different structures and functions. We performed this study to disclose different miRNA-mRNA networks of obesity-related ccRCC in VAT and SAT using datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA); and find out different RNAs correlated with the prognosis of ccRCC in VAT and SAT.

Methods

We screened out different expressed (DE) mRNAs and miRNAs of obesity, in both VAT and SAT from GEO datasets, and constructed miRNA-mRNA networks of obesity-related ccRCC. To evaluate the sensitivity and specificity of RNAs in networks of obesity-related ccRCC in both VAT and SAT, Receiver Operating Characteristic (ROC) analyses were conducted using TCGA datasets. Spearman correlation analyses were then performed to find out RNA pairs with inverse correlations. We also performed Cox regression analyses to estimate the association of all DE RNAs of obesity with the overall survival.

Results

136 and 185 DE mRNAs of obesity in VAT and SAT were found out. Combined with selected DE miRNAs, miRNA-mRNA networks of obesity-related ccRCC were constructed. By performing ROC analyses, RNAs with same trend as shown in networks and statistically significant ORs were selected to be paired. Three pairs were finally remained in Spearman correlation analyses, including hsa-miR-182&ATP2B2, hsa-miR-532&CDH2 in VAT, and hsa-miR-425&TFAP2B in SAT. Multivariable Cox regression analyses showed that several RNAs with statistically significant adjusted HRs remained consistent trends as shown in DE analyses of obesity. Risk score analyses using selected RNAs showed that the overall survival time of patients in the low‐risk group was significantly longer than that in the high‐risk group regardless of risk score models.

Conclusions

We found out different miRNA-mRNA regulatory networks of obesity-related ccRCC for both VAT and SAT; and several DE RNAs of obesity-related ccRCC were found to remain consistent performance in terms of ccRCC prognosis. Our findings could provide valuable evidence on the targeted therapy of obesity-related ccRCC.
Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review
Authors: Querat Bruno
Published: September 2021

The glycoprotein hormones (GPH) are heterodimers composed of a common α subunit and a specific β subunit. They act by activating specific leucine-rich repeat G protein-coupled receptors. However, individual subunits have been shown to elicit responses in cells devoid of the receptor for the dimeric hormones. The α subunit is involved in prolactin production from different tissues. The human chorionic gonadotropin β subunit (βhCG) plays determinant roles in placentation and in cancer development and metastasis. A truncated form of the thyrotropin (TSH) β subunit is also reported to have biological effects. The GPH α- and β subunits are derived from precursor genes (gpa and gpb, respectively), which are expressed in most invertebrate species and are still represented in vertebrates as GPH subunit paralogs (gpa2 and gpb5, respectively). No specific receptor has been found for the vertebrate GPA2 and GPB5 even if their heterodimeric form is able to activate the TSH receptor in mammals. Interestingly, GPA and GPB are phylogenetically and structurally related to cysteine-knot growth factors (CKGF) and particularly to a group of antagonists that act independently on any receptor. This review article summarizes the observed actions of individual GPH subunits and presents the current hypotheses of how these actions might be induced. New approaches are also proposed in light of the evolutionary relatedness with antagonists of the CKGF family of proteins.
An Adaptive Sliding Mode Control Based on Disturbance Observer for LFC
Authors: Wei Mofan , Lin Sheng , Zhao Yan , Wang Hao , Liu Qian
Published: September 2021

In the power system, the loads and nonlinearity parameters cause the system frequency deviation, which complicates the load frequency control (LFC). To deal with the above problem, an adaptive sliding mode control (SMC) based on disturbance observer is proposed to eliminate frequency deviation for interconnected power system in this paper. Firstly, the mathematical model of the power system is established, where the power exchange between the tie line is considered as the variable of the designed sliding surface. Secondly, the nonlinear disturbance observer is constructed to estimate the parameter uncertainty and load of power system. Thirdly, combined with the estimated value of the disturbance observer and integral sliding mode surface, the SMC is designed. Moreover, considering the inherent shortcoming of SMC—the chattering problem, an adaptive strategy is applied to the SMC to ensure the stability of controller. Next, the stability of the designed SMC is proved by Lyapunov stability theory. Finally, to verify the effectiveness of the proposed controller, several simulations are presented.
Environmental Fate and Behavior of the Herbicide Glyphosate in Sandy Soils of Florida Under Citrus Production
Authors: Gairhe Biwek , Liu Wenwen , Batuman Ozgur , Dittmar Peter , Kadyampakeni Davie , Kanissery Ramdas
Published: September 2021

Chemical weed control using herbicide glyphosate to manage emerged weeds is an important production practice in Florida citrus. Despite the extensive use of glyphosate in citrus orchards, very limited information is available on its environmental fate and behavior in Florida soils that are predominantly sandy in nature. Hence, the study’s objective was to understand the adsorption-desorption, dissipation dynamics, and vertical movement or leaching of glyphosate in sandy soils in citrus orchards. Laboratory, field, and greenhouse experiments were conducted at Southwest Florida Research and Education Center in Immokalee, Florida. The adsorption-desorption behavior of glyphosate in the soils from three major citrus production areas in Florida was studied utilizing a batch equilibrium method. The dissipation of glyphosate was tracked in the field following its application at the rate of 4.20 kg ae ha−1. Soil leaching columns in greenhouse conditions were used to study the vertical movement of glyphosate. The results suggest that glyphosate has a relatively lower range of adsorption or binding (Kads = 14.28–30.88) in the tested soil types. The field dissipation half-life (DT50) of glyphosate from surface soil was found to be ∼26 days. Glyphosate moved vertically or leached into the soil profile, up to 40 cm in the soil column, when analyzed 40 days after herbicide application. The primary degradation product of glyphosate, i.e., aminomethyl phosphonic acid (AMPA), was also detected up to the depth of 30 cm below the soil surface, indicating the presence of microbial metabolism of glyphosate in the soil.
Biogeography Meets Niche Modeling: Inferring the Role of Deep Time Climate Change When Data Is Limited
Authors: Culshaw Victoria , Mairal Mario , Sanmartín Isabel
Published: September 2021

Geographic range shifts are one major organism response to climate change, especially if the rate of climate change is higher than that of species adaptation. Ecological niche models (ENM) and biogeographic inferences are often used in estimating the effects of climatic oscillations on species range dynamics. ENMs can be used to track climatic suitable areas over time, but have often been limited to shallow timescales; biogeographic inference can reach greater evolutionary depth, but often lacks spatial resolution. Here, we present a simple approach that treats them as independent and complementary sources of evidence, which, when used in partnership, can be employed to reconstruct geographic range shifts over deep evolutionary timescales. For testing this, we chose two extreme African disjunctions:Camptoloma(Scrophulariaceae) andCanarina(Campanulaceae), each comprising of three species disjunctly distributed in Macaronesia and eastern/southern Africa. Using inferred ancestral ranges in tandem with preindustrial and paleoclimate ENM hindcastings, we show that the disjunct pattern was the result of fragmentation and extinction events linked to Neogene aridification cycles. Our results highlight the importance of considering temporal resolution when building ENMs for rare endemics with small population sizes and restricted climatic tolerances such asCamptoloma, for which models built on averaged monthly variables were more informative than those based on annual bioclimatic variables. Additionally, we show that biogeographic information can be used as truncation threshold criteria for building ENMs in the distant past. Our approach is suitable when there is sparse sampling on species occurrences and associated patterns of genetic variation, such as in the case of ancient endemics with widely disjunct distributions as a result of climate change.
Prevalence and Characteristics of STRC Gene Mutations (DFNB16): A Systematic Review and Meta-Analysis
Authors: Han Shuang , Zhang Dejun , Guo Yingyuan , Fu Zeming , Guan Guofang
Published: September 2021

Background: Mutations in the STRC (MIM 606440) gene, inducing DFNB16, are considered a major cause of mild–moderate autosomal recessive non-syndromic hearing loss (ARNSHL). We conducted a systematic review and meta-analysis to determine the global prevalence and characteristics of STRC variations, important information required for genetic counseling.

Methods: PubMed, Google Scholar, Medline, Embase, and Web of Science were searched for relevant articles published before January 2021.

Results: The pooled prevalence of DFNB16 in GJB2-negative patients with hearing loss was 4.08% (95% CI: 0.0289–0.0573), and the proportion of STRC variants in the mild–moderate hearing loss group was 14.36%. Monoallelic mutations of STRC were 4.84% (95% CI: 0.0343–0.0680) in patients with deafness (non-GJB2) and 1.36% (95% CI: 0.0025–0.0696) in people with normal hearing. The DFNB16 prevalence in genetically confirmed patients (non-GJB2) was 11.10% (95% CI: 0.0716–0.1682). Overall pooled prevalence of deafness–infertility syndrome (DIS) was 36.75% (95% CI: 0.2122–0.5563) in DFNB16. The prevalence of biallelic deletions in STRC gene mutations was 70.85% (95% CI: 0.5824–0.8213).

Conclusion: Variants in the STRC gene significantly contribute to mild–moderate hearing impairment. Moreover, biallelic deletions are a main feature of STRC mutations. Copy number variations associated with infertility should be seriously considered when investigating DFNB16.
Chromosomal Differentiation of Deschampsia (Poaceae) Based on Four Satellite DNA Families
Authors: González María Laura , Chiapella Jorge Oscar , Urdampilleta Juan Domingo
Published: September 2021

Diverse families of satellite DNA (satDNA) were detected in heterochromatin regions of Deschampsia. This kind of repetitive DNA consists of tandem repeat sequences forming big arrays in genomes, and can contribute to lineages differentiation. The differentiation between types of satDNA is related to their sequence identity, the size and number of monomers forming the array, and their chromosomal location. In this work, four families of satDNA (D2, D3, D12, D13), previously isolated by genomic analysis, were studied on chromosomal preparations of 12 species of Deschampsia (D. airiformis, D. antarctica, D. cespitosa, D. cordillerarum, D. elongata, D. kingii, D. laxa, D. mendocina, D. parvula, D. patula, D. venustula, and Deschampsia sp) and one of Deyeuxia (D. eminens). Despite the number of satDNA loci showing interspecific variation, the general distribution pattern of each satDNA family is maintained. The four satDNA families are AT-rich and associated with DAPI + heterochromatin regions. D2, D3, and D12 have mainly subterminal distribution, while D13 is distributed in intercalary regions. Such conservation of satDNA patterns suggests a not random distribution in genomes, where the variation between species is mainly associated with the array size and the loci number. The presence of satDNA in all species studied suggests a low genetic differentiation of sequences. On the other hand, the variation of the distribution pattern of satDNA has no clear association with phylogeny. This may be related to high differential amplification and contraction of sequences between lineages, as explained by the library model.
Epitope Profiling Reveals the Critical Antigenic Determinants in SARS-CoV-2 RBD-Based Antigen
Authors: Jiang Min , Zhang Gaiping , Liu Hongliang , Ding Peiyang , Liu Yunchao , Tian Yuanyuan , Wang Yanwei , Wang Aiping
Published: September 2021

The ongoing COVID-19 pandemic caused by SARS-CoV-2 is a huge public health crisis for the globe. The receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein plays a vital role in viral infection and serves as a major target for developing neutralizing antibodies. In this study, the antibody response to the RBD of SARS-CoV-2 S protein was analyzed by a panel of sera from animals immunized with RBD-based antigens and four linear B-cell epitope peptides (R345, R405, R450 and R465) were revealed. The immunogenicity of three immunodominant peptides (R345, R405, R465) was further accessed by peptide immunization in mice, and all of them could induced potent antibody response to SARS-CoV-2 S protein, indicating that the three determinants in the RBD were immunogenic. We further generated and characterized monoclonal antibodies (15G9, 12C10 and 10D2) binding to these epitope peptides, and finely mapped the three immunodominant epitopes using the corresponding antibodies. Neutralization assays showed that all three monoclonal antibodies had neutralization activity. Results from IFA and western blotting showed that 12C10 was a cross-reactive antibody against both of SARS-CoV-2 and SARS-CoV. Results from conservative and structural analysis showed that 350VYAWN354 was a highly conserved epitope and exposed on the surface of SARS-CoV-2 S trimer, whereas 473YQAGSTP479 located in the receptor binding motif (RBM) was variable among different SARS-CoV-2 strains. 407VRQIAP412 was a highly conserved, but cryptic epitope shared between SARS-CoV-2 and SARS-CoV. These findings provide important information for understanding the humoral antibody response to the RBD of SARS-CoV-2 S protein and may facilitate further efforts to design SARS-CoV-2 vaccines and the target of COVID-19 diagnostic.
The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?
Authors: Parodi Benedetta , Kerlero de Rosbo Nicole
Published: September 2021

A large and expending body of evidence indicates that the gut-brain axis likely plays a crucial role in neurological diseases, including multiple sclerosis (MS). As a whole, the gut-brain axis can be considered as a bi-directional multi-crosstalk pathway that governs the interaction between the gut microbiota and the organism. Perturbation in the commensal microbial population, referred to as dysbiosis, is frequently associated with an increased intestinal permeability, or “leaky gut”, which allows the entrance of exogeneous molecules, in particular bacterial products and metabolites, that can disrupt tissue homeostasis and induce inflammation, promoting both local and systemic immune responses. An altered gut microbiota could therefore have significant repercussions not only on immune responses in the gut but also in distal effector immune sites such as the CNS. Indeed, the dysregulation of this bi-directional communication as a consequence of dysbiosis has been implicated as playing a possible role in the pathogenesis of neurological diseases. In multiple sclerosis (MS), the gut-brain axis is increasingly being considered as playing a crucial role in its pathogenesis, with a major focus on specific gut microbiota alterations associated with the disease. In both MS and its purported murine model, experimental autoimmune encephalomyelitis (EAE), gastrointestinal symptoms and/or an altered gut microbiota have been reported together with increased intestinal permeability. In both EAE and MS, specific components of the microbiota have been shown to modulate both effector and regulatory T-cell responses and therefore disease progression, and EAE experiments with germ-free and specific pathogen-free mice transferred with microbiota associated or not with disease have clearly demonstrated the possible role of the microbiota in disease pathogenesis and/or progression. Here, we review the evidence that can point to two possible consequences of the gut-brain axis dysfunction in MS and EAE: 1. A pro-inflammatory intestinal environment and “leaky” gut induced by dysbiosis could lead to an altered communication with the CNS through the cholinergic afferent fibers, thereby contributing to CNS inflammation and disease pathogenesis; and 2. Neuroinflammation affecting efferent cholinergic transmission could result in intestinal inflammation as disease progresses.