bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Fidelity MC-DEM Modeling and Uncertainty Analysis of HTR-PM First Criticality
Authors: Li Ruihan , Liu Zhaoyuan , Feng Zhiyuan , Liang Jingang , Zhang Liguo
Published: January 2022

A high-fidelity model for the first criticality of pebble-bed reactor HTR-PM is built using Monte Carlo (MC) code RMC and discrete element method (DEM) code LAMMPS. Randomly packed TRi-structural ISOtropic (TRISO) particles and fuel pebbles are modeled explicitly. A cone structure on the top of the pebble bed is also taken into account. Criticality calculation result agrees well with the experiment. Uncertainty analysis is carried out considering three inherent aspects: the randomness of MC code, the randomness of TRISO particle and pebble position, and the randomness of mixed pebbles. Results show that these factors have a significant impact on the uncertainty of effective multiplication factor (keff). And the most influential factor is expected to be the randomness of mixed pebbles. The influence of several configuration factors is studied as well. It is observed that the effects of cross-section library, the heterogeneity of TRISO particles, and the angle of pebble bed cone are nonnegligible contributors. However, the results between randomly and regularly placed TRISO particles are not noticeably different.
Dynamics of Restored and Natural Oyster Reefs After a Hurricane
Authors: Martinez Meghan J. , Palmer Terence A. , Breaux Natasha J. , Beseres Pollack Jennifer
Published: January 2022

Restoration of shellfish reefs has increased exponentially over the past two decades, due in part to increased awareness of widespread oyster habitat loss. Large-scale, acute disturbances such as hurricanes have the potential to influence restoration outcomes, but because storm occurrence is unpredictable with respect to restoration timelines, the responses of restored habitats are not well understood. We quantified the ecological dynamics of a newly constructed Crassostrea virginica oyster reef and nearby reference reef in a Texas estuary immediately after Hurricane Harvey, a major category 4 storm. Biophysical structure (e.g., oyster density, shell height, sediment grain size), and community composition (abundance of reef-associated epifauna, and nearby infauna) were measured for 18 months. A sharp decrease in salinity and temporary deposition of fine sediments within the first 3 months corresponded with increases in oyster and epifaunal recruitment on the restored reef, although densities were generally below those measured on restored reefs without hurricanes. Criteria for oyster reef restoration success were met within 12–18 months post-storm. Infaunal densities decreased but returned to pre-storm densities within 2 months, but bivalves were delayed, returning to pre-storm levels after 9 months. A lack of historical baseline data on the newly restored reef limited our ability to assess the magnitude of reef recovery to pre-disturbance levels or separate the direct effects of the hurricane from the dynamics of early recruitment and growth. Results provide important information about restored and natural oyster reef dynamics after large-scale disturbance and can help inform effective management and conservation measures.
Identification and Validation of Ferroptosis-Related LncRNA Signatures as a Novel Prognostic Model for Colon Cancer
Authors: Wu Zhiwei , Lu Zhixing , Li Liang , Ma Min , Long Fei , Wu Runliu , Huang Lihua , Chou Jing , Yang Kaiyan , Zhang Yi , Li Xiaorong , Hu Gui , Zhang Yi , Lin Changwei
Published: January 2022

Background

Ferroptosis is a newly defined form of programmed cell death that plays an important role in many cancers. However, ferroptosis-related lncRNAs (FRLs) involved in the regulation of colon cancer are not thoroughly understood. This study aimed to identify a prognostic FRL signature in colon cancer and explore its potential molecular function.

Methods

RNA-seq data and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database, and a list of ferroptosis-related genes was extracted from the FerrDb website. Analysis of differentially expressed FRLs was performed using the ‘limma’ package in R software. By implementing coexpression analysis and univariate Cox analysis, we then identified prognostic FRLs. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 4 FRLs. We evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between the signature and immune landscape, somatic mutation and drug sensitivity were explored. Finally, in vitro experiments were conducted to validate the functions of AP003555.1 and AC000584.1.

Results

A 4-FRL signature was constructed. Two risk groups were classified based on the risk score calculated by this signature. The signature-based risk score exhibited a more powerful capacity for survival prediction than traditional clinicopathological features in colon patients. Additionally, we observed a significant difference in immune cells, such as CD4+ and CD8+ T cells and macrophages, between the two groups. Moreover, the high-risk group exhibited lower IC50 values for certain chemotherapy drugs, such as cisplatin, docetaxel, bleomycin or axitinib. Finally, the in vitro experiments showed that ferroptosis processes were suppressed after AP003555.1 and AC000584.1 knockdown.

Conclusion

The proposed 4-FRL signature is a promising biomarker to predict clinical outcomes and therapeutic responses in colon cancer patients.
An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation
Authors: Lu Can , Chen Huihui , Wang Chang , Yang Fei , Li Jun , Liu Hong , Chen Guochun
Published: January 2022

T cell immunoglobulin domain and mucin domain 3 (TIM3) was initially identified as an inhibitory molecule on IFNγ-producing T cells. Further research discovered the broad expression of TIM3 on different immune cells binding to multiple ligands. Apart from its suppressive effects on the Th1 cells, recent compelling experiments highlighted the indispensable role of TIM3 in the myeloid cell-mediated inflammatory response, supporting that TIM3 exerts pleiotropic effects on both adaptive and innate immune cells in a context-dependent manner. A large number of studies have been conducted on TIM3 biology in the disease settings of infection, cancer, and autoimmunity. However, there is a lack of clinical evidence to closely evaluate the role of T cell-expressing TIM3 in the pathogenesis of chronic kidney disease (CKD). Here, we reported an intriguing case of Mycobacterium tuberculosis (Mtb) infection that was characterized by persistent overexpression of TIM3 on circulating T cells and ongoing kidney tubulointerstitial inflammation for a period of 12 months. In this case, multiple histopathological biopsies revealed a massive accumulation of recruited T cells and macrophages in the enlarged kidney and liver. After standard anti-Mtb treatment, repeated renal biopsy identified a dramatic remission of the infiltrated immune cells in the tubulointerstitial compartment. This is the first clinical report to reveal a time-course expression of TIM3 on the T cells, which is pathologically associated with the progression of severe kidney inflammation in a non-autoimmunity setting. Based on this case, we summarize the recent findings on TIM3 biology and propose a novel model of CKD progression due to the aberrant crosstalk among immune cells.
Identification of a Novel Mutation in TNFAIP3 in a Family With Poly-Autoimmunity
Authors: Rossi Marianna Nicoletta , Federici Silvia , Uva Andrea , Passarelli Chiara , Celani Camilla , Caiello Ivan , Matteo Valentina , Petrocchi Stefano , Mortari Eva Piano , De Benedetti Fabrizio , Prencipe Giusi , Insalaco Antonella
Published: January 2022

Haploinsufficiency of A20 (HA20) is an inflammatory disease caused by mutations in the TNFAIP3 gene classically presenting with Behcet’s-like disease. A20 acts as an inhibitor of inflammation through its effect on NF-kB pathway. Here we describe four consanguineous patients (three sisters and their mother) with a predominantly autoimmune phenotype, including thyroiditis, type I diabetes, hemolytic anemia and chronic polyarthritis. All patients had recurrent oral ulcers, with only 1 patient presenting also recurrent fever episodes, as a classical autoinflammatory feature. Next generation sequencing identified a novel heterozygous frameshift mutation (p.His577Alafs*95) that causes a premature stop codon in the zinc finger domain of A20, leading to a putative haploinsufficiency of the protein. Functional analyses confirmed the pathogenicity of the mutation. The variant was associated with decreased levels of A20 in blood cells. Accordingly, ex-vivo lipopolysaccharide (LPS)-stimulated patients’ peripheral blood mononuclear cells (PBMCs) showed higher levels of p65 NF-kB phosphorylation, as well as increased production of the proinflammatory cytokines IL-1β, IL-6 and TNF-α. Moreover, in agreement with recent observations, demonstrating a role for A20 in inhibiting STAT1 and IFNγ pathways, markedly higher circulating levels of the two IFNγ-inducible chemokines CXCL9 and CXCL10 were detected in all patients. Supporting the findings of a hyperactivation of IFNγ signaling pathway in HA20 patients, patients’ monocytes showed higher levels of STAT1 without stimulation, as well as higher phosphorylated (active) STAT1 levels following IFNγ stimulation. In conclusion, our study show that in the clinical spectrum of HA20 autoimmune features may predominate over autoinflammatory features and demonstrate, from a molecular point of view, the involvement of A20 in modulating not only the NF-kB, but also the IFNγ pathway.
Aerosolized Intratracheal Inoculation of Recombinant Protective Antigen (rPA) Vaccine Provides Protection Against Inhalational Anthrax in B10.D2-Hc0 Mice
Authors: Song Xiaolin , Zhang Wei , Zhai Lina , Guo Jianshu , Zhao Yue , Zhang Lili , Hu Lingfei , Xiong Xiaolu , Zhou Dongsheng , Lv Meng , Yang Wenhui
Published: January 2022

Anthrax caused by Bacillus anthracis is a fatal zoonotic disease with a high lethality and poor prognosis. Inhalational anthrax is the most severe of the three forms of anthrax. The currently licensed commercial human anthrax vaccines require a complex immunization procedure for efficacy and have side effects that limit its use in emergent situations. Thus, development of a better anthrax vaccine is necessary. In this study, we evaluate the potency and efficacy of aerosolized intratracheal (i.t.) inoculation with recombinant protective antigen (rPA) subunit vaccines against aerosolized B. anthracis Pasteur II spores (an attenuated strain) challenge in a B10.D2-Hc0 mouse (deficient in complement component C5) model. Immunization of rPA in liquid, powder or powder reconstituted formulations via i.t. route conferred 100% protection against a 20× LD50 aerosolized Pasteur II spore challenge in mice, compared with only 50% of subcutaneous (s.c.) injection with liquid rPA. Consistently, i.t. inoculation of rPA vaccines induced a higher lethal toxin (LeTx) neutralizing antibody titer, a stronger lung mucosal immune response and a greater cellular immune response than s.c. injection. Our results demonstrate that immunization with rPA dry powder vaccine via i.t. route may provide a stable and effective strategy to improve currently available anthrax vaccines and B10.D2-Hc0 mice challenged with B. anthracis attenuated strains might be an alternative model for anthrax vaccine candidate screening.
Lactic Acid Bacteria Mixture Isolated From Wild Pig Alleviated the Gut Inflammation of Mice Challenged by Escherichia coli
Authors: Zhong Yifan , Fu Dongyan , Deng Zhaoxi , Tang Wenjie , Mao Jiangdi , Zhu Tao , Zhang Yu , Liu Jianxin , Wang Haifeng
Published: January 2022

Wild pigs usually showed high tolerance and resistance to several diseases in the wild environment, suggesting that the gut bacteria of wild pigs could be a good source for discovering potential probiotic strains. In our study, wild pig feces were sequenced and showed a higher relative abundance of the genus Lactobacillus (43.61% vs. 2.01%) than that in the domestic pig. A total of 11 lactic acid bacteria (LAB) strains including two L. rhamnosus, six L. mucosae, one L. fermentum, one L. delbrueckii, and one Enterococcus faecalis species were isolated. To investigate the synergistic effects of mixed probiotics strains, the mixture of 11 LAB strains from an intestinal ecology system was orally administrated in mice for 3 weeks, then the mice were challenged with Escherichia coli ATCC 25922 (2 × 109 CFU) and euthanized after challenge. Mice administrated with LAB strains showed higher (p < 0.05) LAB counts in feces and ileum. Moreover, alterations of specific bacterial genera occurred, including the higher (p < 0.05) relative abundance of Butyricicoccus and Clostridium IV and the lower (p < 0.05) abundance of Enterorhabdus in mice fed with mixed LAB strains. Mice challenged with Escherichia coli showed vacuolization of the liver, lower GSH in serum, and lower villus to the crypt proportion and Claudin-3 level in the gut. In contrast, administration of mixed LAB strains attenuated inflammation of the liver and gut, especially the lowered IL-6 and IL-1β levels (p < 0.05) in the gut. Our study highlighted the importance of gut bacterial diversity and the immunomodulation effects of LAB strains mixture from wild pig in gut health.
Corrosion Experimental Research on Local Damage of Epoxy-Coated Steel Bars in Concrete Under Marine Environment
Authors: Cao Hongfei , Lyu Zhongda , Dong Wei , Zhao Zhuo , Gan Weizhong , Wang Yonggang
Published: January 2022

Epoxy coating has been proven to protect steel bars from corrosion. However, the damage of epoxy coating is inevitable, and this may lead to more serious corrosion of steel bar. In order to study the corrosion resistance of steel bars with damaged epoxy coating, two groups of coating-damaged bar and one group of coating-intact rebar were designed, and six specimens were made. The influence of electrolyte concentration on the corrosion rate of steel bars was studied by setting different concentrations. After 30 days of accelerated corrosion, electrochemical data were recorded by the electrochemical workstation. The experimental result shows that the steel bars with coating damage have obvious polarization curve characteristics of corrosion, and corrosion resistance decreases obviously. According to the corrosion current and potential, the larger the damaged area of the coating, the faster will be the corrosion rate. According to the polarization curve data, the polarization resistance is modified, and the result is closer to the real polarization resistance value. The calculated corrosion rate shows that the corrosion rate of reinforcement is affected by both electrolyte concentration and coating damage area, and electrolyte concentration has a greater influence on the corrosion rate.
The Role of Disease Severity and Demographics in the Clinical Course of COVID-19 Patients Treated With Convalescent Plasma
Authors: Ma Tengfei , Wiggins Chad C. , Kornatowski Breanna M. , Hailat Ra'ed S. , Clayburn Andrew J. , Guo Winston L. , Johnson Patrick W. , Senefeld Jonathon W. , Klassen Stephen A. , Baker Sarah E. , Bruno Katelyn A. , Fairweather DeLisa , Wright R. Scott , Carter Rickey E. , Li Chenxi , Joyner Michael J. , Paneth Nigel S.
Published: January 2022

Treatment of patients with COVID-19 using convalescent plasma from recently recovered patients has been shown to be safe, but the time course of change in clinical status following plasma transfusion in relation to baseline disease severity has not yet been described. We analyzed short, descriptive daily reports of patient status in 7,180 hospitalized recipients of COVID-19 convalescent plasma in the Mayo Clinic Expanded Access Program. We assessed, from the day following transfusion, whether the patient was categorized by his or her physician as better, worse or unchanged compared to the day before, and whether, on the reporting day, the patient received mechanical ventilation, was in the ICU, had died or had been discharged. Most patients improved following transfusion, but clinical improvement was most notable in mild to moderately ill patients. Patients classified as severely ill upon enrollment improved, but not as rapidly, while patients classified as critically ill/end-stage and patients on ventilators showed worsening of disease status even after treatment with convalescent plasma. Patients age 80 and over showed little or no clinical improvement following transfusion. Clinical status at the time of convalescent plasma treatment and age appear to be the primary factors in determining the therapeutic effectiveness of COVID-19 convalescent plasma among hospitalized patients.
Metabolomics-Based Frailty Biomarkers in Older Chinese Adults
Authors: Pan Yiming , Li Yun , Liu Pan , Zhang Yaxin , Li Bowen , Liu Zuyun , Shui Guanghou , Ma Lina
Published: January 2022

Background/Objectives

Owing to accelerated population aging, health in older adults is becoming increasingly important. Frailty can reflect the health status and disease risks of older adults; however, appropriate biomarkers for early screening of frailty have not been identified. Here, we applied metabolomics to identify frailty biomarkers and potential pathogenic mechanisms of frailty.

Methods

Serum metabolic profiles from 25 frail and 49 non-frail (control) older adults were systematically investigated by liquid chromatography-mass spectrometry-based metabolomics.

Results

We identified 349 metabolites of 46 classes, with four increased and seven decreased metabolites in frail older adults. Pearson correlation analysis identified 11 and 21 metabolites that were positively and negatively correlated with grip strength, and 7 and 76 metabolites that were positively and negatively correlated with gait speed, respectively. Pathway analysis identified 10 metabolite sets and 13 pathways significantly associated with one or more frailty phenotype criteria.

Conclusion

These results revealed the metabolite characteristics of serum in frail older adults. Intermediates of carbohydrate metabolism (e.g., isocitrate, malate, fumarate, cis-aconitate, glucuronate, and pyruvate), saturated fatty acids (e.g., palmitic acid), unsaturated fatty acids (e.g., arachidonate and linoleic acid), and certain essential amino acids (e.g., tryptophan) may be candidate biomarkers for the early diagnosis of frailty. Mitochondrial function disorders, saturated fatty acid-mediated lipotoxicity, aberrant unsaturated fatty acid metabolism, and increased tryptophan degradation could be potential mechanisms of frailty.
Significantly Increased Risk of All-Cause Mortality Among Type 2 Diabetes Patients Living Alone
Authors: Fu Liyao , Zhou Ying , Sun Jiaxing , Xing Zhenhua , Wang Yongjun , Tai Shi
Published: January 2022

Background

There is a lack of studies evaluating the association between living status and subsequent outcomes in patients with type 2 diabetes (T2DM).

Objectives

This study aimed to assess the association between living alone and the risk of all-cause mortality in T2DM patients.

Methods

We performed a secondary analysis in patients with long-lasting T2DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The primary outcome was all-cause mortality. Multivariable Cox proportional hazard models was used to analyze and compare the hazard ratios (HRs) in patients living alone and with one or more adults.

Results

This study included 10,249 patients with T2DM. Of these, 2,078 (20.28%) were living alone and 8,171 (79.72%) lived with one or more adults. Over a median total follow-up of 8.8 years, 1,958 patients developed the primary endpoint. The all-cause mortality rates in patients living alone or living with one or more adults were 23.24 and 18.05%, respectively. Cox proportional hazard analysis showed that T2DM patients living alone had significantly higher rate of all-cause mortality than those living with others (HR, 1.34; 95% confidence interval [CI], 1.20–1.48; p < 0.001). After multivariable adjustment, living alone was an independent risk factor for all-cause mortality in patients with T2DM (adjusted HR, 1.27; 95% CI, 1.14–1.41; p < 0.001). Furthermore, the risks of both congestive heart failure (CHF) and fatal coronary heart disease (CHD) among 4,050 propensity score-matched patients were higher for patients living alone (respectively HR, 1.37; 95% CI, 1.08–1.74; p = 0.010; and HR, 1.16; 95% CI, 1.00–1.34; p = 0.047).

Conclusions

The risk of all-cause mortality was significantly higher in T2DM patients living alone than in those living with one or more adults.
Saliva Sampling for Prospective SARS-CoV-2 Screening of Healthcare Professionals
Authors: Raimann Adalbert , Farr Alex , Huscsava Mercedes , Krois Wilfried , Strassl Robert , Schellnegger Julia , Eibensteiner Fabian , Göschl Bernadette , Schned Hannah , Steinbauer Philipp , Hetzmannseder Mathias , Stiegner Fabian , Greber-Platzer Susanne , Kiss Herbert , Plener Paul L. , Aufricht Christoph , Berger Angelika , Wagner Michael
Published: January 2022

Objective

The objective of this study was to analyze the feasibility and acceptance of a non-invasive, daily and proactive screening program for SARS-CoV-2 infection employing serial saliva testing, in combination with a digital questionnaire among healthcare providers (HCPs) in a multi-professional setting.

Design

This was a prospective cohort study involving HCPs from different units at a single tertiary care center, over a pilot phase of 4 weeks during the first wave of the COVID-19 pandemic from April 18th to June 6th, 2020.

Setting

Pediatric tertiary patient care units, Comprehensive Center for Pediatrics, Medical University of Vienna.

Subjects

HCPs from different units, including physicians, nurses, midwives, and administrative staff (with patient contact) were considered eligible for the study. Study participants were working in different settings in our center at varying levels of risk exposure.

Interventions

Saliva collection from mouth gargle and electronic symptom and exposure monitoring (eSEM) was performed by participants at the onset of each regular clinical shift (day or night shift), using an anonymous ID for matching the results.

Measurements

RT-PCR of all saliva samples, eSEM, as well as feasibility and acceptance thereof.

Results

Two hundred and seventy-five volunteers collected 1,865 saliva samples and responded 1,378 times in the eSEM during a 4-week period. 1,331 (96.7%) responses were that the testing was feasible and acceptable. The most common severe symptom during the 4-week period mentioned by HCPs was headache, reported 54 times (3.9%). Two SARS-CoV-2 positive samples—one of them being associated with symptoms—were identified. The acceptance rate among HCPs was 96.6%.

Conclusion

Serial saliva screening was a well-accepted and feasible method for monitoring SARS-CoV-2 infectious state in health care professionals. Combination of regular SARS-CoV-2 tests with sequential saliva collection and storage could potentially represent a highly efficient strategy to identify and trace virus positive staff for employee and patient safety.
Clinical Aspects and Detection of Emerging Rickettsial Pathogens: A “One Health” Approach Study in Serbia, 2020
Authors: Banović Pavle , Díaz-Sánchez Adrian A. , Simin Verica , Foucault-Simonin Angélique , Galon Clemence , Wu-Chuang Alejandra , Mijatović Dragana , Obregón Dasiel , Moutailler Sara , Cabezas-Cruz Alejandro
Published: January 2022

Ticks carry numerous pathogens that, if transmitted, can cause disease in susceptible humans and animals. The present study describes our approach on how to investigate clinical presentations following tick bites in humans. To this aim, the occurrence of major tick-borne pathogens (TBPs) in human blood samples (n = 85) and the ticks collected (n = 93) from the same individuals were tested using an unbiased high-throughput pathogen detection microfluidic system. The clinical symptoms were characterized in enrolled patients. In patients with suspected TBP infection, serological assays were conducted to test for the presence of antibodies against specific TBPs. A field study based on One Health tenets was further designed to identify components of a potential chain of infection resulting in Rickettsia felis infection in one of the patients. Ticks species infesting humans were identified as Ixodes ricinus, Rhipicephalus sanguineus sensu lato (s.l.), Dermacentor reticulatus, and Haemaphysalis punctata. Five patients developed local skin lesions at the site of the tick bite including erythema migrans, local non-specific reactions, and cutaneous hypersensitivity reaction. Although Borrelia burgdorferi s.l., Babesia microti, Anaplasma phagocytophilum, and Candidatus Cryptoplasma sp. DNAs were detected in tick samples, different Rickettsia species were the most common TBPs identified in the ticks. The presence of TBPs such as Rickettsia helvetica, Rickettsia monacensis, Borrelia lusitaniae, Borrelia burgdorferi, Borrelia afzelii, A. phagocytophilum, and B. microti in ticks was further confirmed by DNA sequencing. Two of the patients with local skin lesions had IgG reactive against spotted fever group rickettsiae, while IgM specific to B. afzelii, Borrelia garinii, and Borrelia spielmanii were detected in the patient with erythema migrans. Although R. felis infection was detected in one human blood sample, none of the components of the potential chain of infection considered in this study tested positive to this pathogen either using direct pathogen detection in domestic dogs or xenodiagnosis in ticks collected from domestic cats. The combination of high-throughput screening of TBPs and One Health approaches might help characterize chains of infection leading to human infection by TBPs, as well as prevalence of emerging rickettsial pathogens in the Balkan region.
Assessment of Bacterial Inoculant Delivery Methods for Cereal Crops
Authors: Chai Yen Ning , Futrell Stephanie , Schachtman Daniel P.
Published: January 2022

Despite growing evidence that plant growth-promoting bacteria can be used to improve crop vigor, a comparison of the different methods of delivery to determine which is optimal has not been published. An optimal inoculation method ensures that the inoculant colonizes the host plant so that its potential for plant growth-promotion is fully evaluated. The objective of this study was to compare the efficacy of three seed coating methods, seedling priming, and soil drench for delivering three bacterial inoculants to the sorghum rhizosphere and root endosphere. The methods were compared across multiple time points under axenic conditions and colonization efficiency was determined by quantitative polymerase chain reaction (qPCR). Two seed coating methods were also assessed in the field to test the reproducibility of the greenhouse results under non-sterile conditions. In the greenhouse seed coating methods were more successful in delivering the Gram-positive inoculant (Terrabacter sp.) while better colonization from the Gram-negative bacteria (Chitinophaga pinensis and Caulobacter rhizosphaerae) was observed with seedling priming and soil drench. This suggested that Gram-positive bacteria may be more suitable for the seed coating methods possibly because of their thick peptidoglycan cell wall. We also demonstrated that prolonged seed coating for 12 h could effectively enhance the colonization of C. pinensis, an endophytic bacterium, but not the rhizosphere colonizing C. rhizosphaerae. In the field only a small amount of inoculant was detected in the rhizosphere. This comparison demonstrates the importance of using the appropriate inoculation method for testing different types of bacteria for their plant growth-promotion potential.
Ranolazine Inhibits Pyroptosis via Regulation of miR-135b in the Treatment of Diabetic Cardiac Fibrosis
Authors: Ren Long , Chen Xi , Nie Binyang , Qu Huan , Ju Jiaming , Bai Yunlong
Published: January 2022

Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus (DM), and cardiac fibrosis is a characteristic pathological manifestation of DCM. DCM can be exacerbated by pyroptosis, and pyroptosis is a potential target of microRNAs (miRNAs). miR-135b is involved in delaying the progression of numerous cardiovascular diseases, Nonetheless, the role of miR-135b in diabetic cardiac fibrosis is unclear. Ranolazine is a piperazine derivative and is effective for the treatment of cardiovascular disease. The purpose of the study was to elucidate the mechanism of action of ranolazine against diabetic cardiac fibrosis and to investigate the role of miR-135b in this process. Functional and structural changes in the rat heart were examined by echocardiography, hematoxylin-eosin (H&E) and Masson staining. Immunohistochemistry was used to assess the expression of caspase-1, interleukin-1β (IL-1β), gasdermin D (GSDMD), transforming growth factor-β1 (TGF-β1), collagen I and collagen III in the rat left ventricle. Western blot and immunofluorescence were used to detect the protein expression of caspase-1, IL-1β, GSDMD, TGF-β1, collagen I and collagen III proteins, and the mRNA levels were determined using fluorescent quantitative PCR. Ranolazine reduced pyroptosis and inhibited collagen deposition, improving cardiac function in rats. Ranolazine increased miR-135b expression in high glucose-treated cardiac fibroblasts, and miR-135b directly bound to caspase-1. Interference with miR-135b reduced the effects of ranolazine on pyroptosis and collagen deposition. Ranolazine treatment of diabetic cardiac fibrosis inhibited pyroptosis and collagen deposition by upregulating miR-135b. Our study provides a solid theoretical basis for understanding the pathogenesis of diabetic cardiac fibrosis and the clinical use of ranolazine in the treatment of DCM.
Gut Microbiota Alteration Is Associated With Cognitive Deficits in Genetically Diabetic (Db/db) Mice During Aging
Authors: Zhang Jiawei , Zhang Yaxuan , Yuan Yuan , Liu Lan , Zhao Yuwu , Wang Xiuzhe
Published: January 2022

Recent studies have revealed that the microbiota may be implicated in diabetes-related cognitive dysfunction. However, the relationship between gut microbiota and cognitive dysfunction during the progression of type 2 diabetes remains elusive. We used 16S rRNA sequencing combined with conventional behavioral tests to explore the longitudinal changes of gut microbiota and cognition in diabetic db/db mice (leptin receptor knockout mice) and their wild-type littermates at different ages. Prussian blue staining was performed to detect the microhemorrhage in the brain, and immunofluorescent study was applied to analyze microglia activation. Moreover, a Meso Scale Discovery kit was used to determine the cytokine levels in the brain. Db/db mice exhibited age dependent pathological characteristics, including cognitive deficits, neuron damage, spontaneous hemorrhages and neuroinflammation. Furthermore, we observed that the diversity and composition of gut microbiota significantly differed between the wild-type and db/db mice during aging. We found that compared to age-matched wild-type mice, genus Helicobacter was significant higher in db/db mice at 18 and 26 weeks. Correlation analysis revealed that Helicobacter is positively associated with Iba-1 positive cells and TNF-α expression. Collectively, our longitudinal study suggests that diabetic cognitive impairment during aging is associated with abnormal gut microbiota composition, which may play a role in the regulation of neuroinflammation.
Single Cell Transcriptomic and Chromatin Profiles Suggest Layer Vb Is the Only Layer With Shared Excitatory Cell Types in the Medial and Lateral Entorhinal Cortex
Authors: Blankvoort Stefan , Olsen Lene Christin , Kentros Clifford G.
Published: January 2022

All brain functionality arises from the activity in neural circuits in different anatomical regions. These regions contain different circuits comprising unique cell types. An integral part to understanding neural circuits is a full census of the constituent parts, i.e., the neural cell types. This census can be based on different characteristics. Previously combinations of morphology and physiology, gene expression, and chromatin accessibility have been used in various cortical and subcortical regions. This has given an extensive yet incomplete overview of neural cell types. However, these techniques have not been applied to all brain regions. Here we apply single cell analysis of accessible chromatin on two similar but different cortical regions, the medial and the lateral entorhinal cortices. Even though these two regions are anatomically similar, their intrinsic and extrinsic connectivity are different. In 4,136 cells we identify 20 different clusters representing different cell types. As expected, excitatory cells show regionally specific clusters, whereas inhibitory neurons are shared between regions. We find that several deep layer excitatory neuronal cell types as defined by chromatin profile are also shared between the two different regions. Integration with a larger scRNA-seq dataset maintains this shared characteristic for cells in Layer Vb. Interestingly, this layer contains three clusters, two specific to either subregion and one shared between the two. These clusters can be putatively associated with particular functional and anatomical cell types found in this layer. This information is a step forwards into elucidating the cell types within the entorhinal circuit and by extension its functional underpinnings.
Sex Differences in Cerebral Blood Flow and Serum Inflammatory Cytokines and Their Relationships in Mild Traumatic Brain Injury
Authors: Zhao Pinghui , Zhu Pingyi , Zhang Danbin , Yin Bo , Wang Yu , Hussein Nimo Mohamed , Yan Zhihan , Liu Xiaozheng , Bai Guanghui
Published: January 2022

This study aimed to investigate sex differences in cerebral blood flow (CBF) and serum inflammatory cytokines, as well as their correlations in patients with acute-stage mild traumatic brain injury (mTBI). Forty-one patients with mTBI and 23 matched healthy controls underwent 3D-pseudo-continuous arterial spin labeling imaging on 3T magnetic resonance imaging. The patients underwent cognitive evaluations and measurement of a panel of ten serum cytokines: interleukin (IL)-1I, IL-4, IL-6, IL-8, IL-10, IL-12, C–C motif chemokine ligand 2, interferon-gamma, nerve growth factor-beta (β-NGF), and tumor necrosis factor-alpha (TNF-α). Spearman rank correlation analysis was performed to evaluate the relationship between inflammation levels and CBF. We found that both male and female patients showed increased IL-1L and IL-6 levels. Female patients also demonstrated overexpression of IL-8 and low expression of IL-4. As for CBF levels, three brain regions [the right superior frontal gyrus (SFG_R), left putamen, and right precuneus] increased in male patients while three brain regions [the right superior temporal gyrus (STG_R), left middle occipital gyrus, and right postcentral (PoCG_R)] decreased in female patients. Furthermore, the STG_R in female controls was positively correlated with β-NGF while the right PoCG_R in female patients was negatively correlated with IL-8. In addition, compared with male patients, female patients showed decreased CBF in the right pallidum, which was negatively correlated with IL-8. These findings revealed abnormal expression of serum inflammatory cytokines and CBF levels post-mTBI. Females may be more sensitive to inflammatory and CBF changes and thus more likely to get cognitive impairment. This may suggest the need to pay closer attention to the female mTBI group.
Cortical Visual Impairment in CDKL5 Deficiency Disorder
Authors: Quintiliani Michela , Ricci Daniela , Petrianni Maria , Leone Simona , Orazi Lorenzo , Amore Filippo , Gambardella Maria Luigia , Contaldo Ilaria , Veredice Chiara , Perulli Marco , Musto Elisa , Mercuri Eugenio Maria , Battaglia Domenica Immacolata
Published: January 2022

Background

CDKL5 deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene cyclin-dependent kinase-like 5. Cerebral visual impairment (CVI) is frequent in patients with CDD. In addition to being recognized as a specific feature of the pathology, it has been suggested that visual impairment may correlate with neurodevelopmental outcome and epilepsy severity, but no systematic behavioral visual assessment has been performed. The aim of our study was to evaluate clinical and electrophysiological profile of CVI in patients with CDD, to correlate various aspects of visual function to neurodevelopmental and epileptic features.

Methods

The study included all patients with CDD from the National Pathology Registry. All patients underwent neurological examination, a disease-specific functional assessment, structured clinical evaluation of visual functions, including pattern reversal visual evoked potential (VEP), and a detailed monitoring of epileptic features, including video-EEG.

Results

All the 11 patients recorded in the CDKL5 national registry, 10 females and one male, age range of 1.5 to 24 years (mean 9, SD 7.7, median 6.5), were enrolled. Visual function is impaired in all patients; in particular, visual fields, visual acuity, contrast sensitivity, and stereopsis were consistently abnormal whereas other aspects, such as fixing and tracking, were relatively preserved. Pattern reversal VEP was abnormal in nearly 80% of our patients. No correlation was found among CVI severity, age, level of psychomotor development, EEG abnormalities, and pathology stages even if an overall less abnormal EEG pattern was more often associated with better visual results.

Conclusion

In conclusion, CVI can be considered as a major feature of CDD with a diffuse involvement in several behavioral and electrophysiological aspects. Larger cohorts will help to better clarify the possible prognostic role of EEG severity in predicting both visual and developmental abnormalities.
Avenir® vs. AxiumTM Coils for the Treatment of Intracranial Aneurysms: Results of a Multicenter Randomized Controlled Trial With Short-Term Follow-Up
Authors: Li Wei , Ye Ming , Cimpoca Alexandru , Henkes Hans , Wang Honglei , Xu Xiang , Gu Yuxiang , Shi Huaizhang , Ji Hongming , Wang Feng , Zhao Yuanli , Guo Geng , Zhang Hongqi , Li Youxiang
Published: January 2022

Purpose

Endovascular coil occlusion is a successful and rapidly evolving strategy used to treat patients who present with intracranial aneurysms. This study aimed to compare the safety and efficacy of the Avenir® and AxiumTM passive mechanically detachable coil systems.

Methods

A prospective, multicenter, randomized controlled study was carried out at ten medical centers from March 2018 to December 2019. A series of consecutive patients diagnosed with intracranial aneurysms were randomly assigned to undergo endovascular treatment with either the Avenir® or the AxiumTM mechanically detachable coil systems. The short-term outcomes from the two groups were compared with a focus on treatment efficacy and safety.

Results

A total of 162 and 161 patients were enrolled in the Avenir and Axium groups, respectively. The rate of successful coil detachment was 100% for the Avenir group and 99.38% for the Axium group. At the six-month follow-up visit, the overall aneurysm occlusion rate was 94.66% for the Avenir group and 96.95% for the Axium group (p > 0.05). We observed no statistically significant differences in clinical condition (as per the modified Rankin Scale) or the degree of aneurysm occlusion (as determined by digital subtraction angiography [DSA] and Raymond-Roy Occlusion Classification). Surgical complications were reported in 27 subjects in the Avenir group and 22 in the Axium group (p > 0.05). DSA performed at 6 months revealed complete aneurysm occlusion in 84 and 86% of patients in the Avenir and Axium groups, respectively.

Conclusion

We observed no significant short-term differences with respect to efficacy or safety when using either Avenir® or AxiumTM coils for the treatment of intracranial aneurysms.
People With Parkinson’s Disease and Freezing of Gait Show Abnormal Low Frequency Activity of Antagonistic Leg Muscles
Authors: Breu Maria-Sophie , Schneider Marlieke , Klemt Johannes , Cebi Idil , Gharabaghi Alireza , Weiss Daniel
Published: January 2022

Objective

Freezing of gait is detrimental to patients with idiopathic Parkinson’s disease (PD). Its pathophysiology represents a multilevel failure of motor processing in the cortical, subcortical, and brainstem circuits, ultimately resulting in ineffective motor output of the spinal pattern generator. Electrophysiological studies pointed to abnormalities of oscillatory activity in freezers that covered a broad frequency range including the theta, alpha, and beta bands. We explored muscular frequency domain activity with respect to freezing, and used deep brain stimulation to modulate these rhythms thereby evaluating the supraspinal contributions to spinal motor neuron activity.

Methods

We analyzed 9 PD freezers and 16 healthy controls (HC). We studied the patients after overnight withdrawal of dopaminergic medication with stimulation off, stimulation of the subthalamic nucleus (STN-DBSonly) or the substantia nigra pars reticulate (SNr-DBSonly), respectively. Patients performed a walking paradigm passing a narrow obstacle. We analyzed the frequency-domain spectra of the tibialis anterior (TA) and gastrocnemius (GA) muscles in ‘regular gait’ and during the ‘freezing’ episodes.

Results

In stimulation off, PD freezers showed increased muscle activity of the alpha and low-beta band compared to HC in both TA and GA. This activity increase was present during straight walking and during the freezes to similar extent. STN- but not SNr-DBS decreased this activity and paralleled the clinical improvement of freezing.

Conclusion

We found increased muscle activation of the alpha and lower beta band in PD freezers compared to HC, and this was attenuated with STN-DBS. Future studies may use combined recordings of local field potentials, electroencephalography (EEG), and electromyography (EMG) to interrogate the supraspinal circuit mechanisms of the pathological activation pattern of the spinal pattern generator.
Effects of Hydrostatic Pressure on Electrical Retinal Activity in a Multielectrode Array-Based ex vivo Glaucoma Acute Model
Authors: Ingensiep Claudia , Schaffrath Kim , Walter Peter , Johnen Sandra
Published: January 2022

Glaucoma is a heterogeneous eye disease causing atrophy of the optic nerve head (ONH). The optic nerve is formed by the axons of the retinal ganglion cells (RGCs) that transmit visual input to the brain. The progressive RGC loss during glaucoma leads to irreversible vision loss. An elevated intraocular pressure (IOP) is described as main risk factor in glaucoma. In this study, a multielectrode array (MEA)-based ex vivo glaucoma acute model was established and the effects of hydrostatic pressure (10, 30, 60, and 90 mmHg) on the functionality and survival of adult male and female wild-type mouse (C57BL/6) retinae were investigated. Spontaneous activity, response rate to electrical and light stimulation, and bursting behavior of RGCs was analyzed prior, during, and after pressure stress. No pressure related effects on spontaneous firing and on the response rate of the RGCs were observed. Even a high pressure level (90 mmHg for 2 h) did not disturb the RGC functionality. However, the cells’ bursting behavior significantly changed under 90 mmHg. The number of spikes in bursts doubled during pressure application and stayed on a high level after pressure stress. Addition of the amino sulfonic acid taurine (1 mM) showed a counteracting effect. OFF ganglion cells did not reveal an increase in bursts under pressure stress. Live/dead staining after pressure application showed no significant changes in RGC survival. The findings of our ex vivo model suggest that RGCs are tolerant toward high, short-time pressure stress.
Perspectives of Circadian-Based Music Therapy for the Pathogenesis and Symptomatic Treatment of Neurodegenerative Disorders
Authors: Sharma Arastu , Moon Eric , Kim Geunhoo , Kang Sung-Ung
Published: January 2022

Music therapy (MT) and other rhythmic-based interventions for the treatment of neurodegeneration (ND) have been successful in improving the quality of life of affected individuals. Music therapy and rhythm-based stimuli affect patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) respectively not only through cognitive channels and subjective qualifications but also through altered brain structures and neural systems. Often implicated in the pathogenesis and resulting symptoms of these diseases is the role of aberrant circadian rhythmicity (CR), namely disrupted sleep. Recent literature suggests that proper maintenance of this timekeeping framework may be beneficial for patients with neurodegenerative disorders and serve a neuroprotective role. While music therapy can improve the quality of life for neurodegenerative patients, longitudinal studies analyzing sleep patterns of affected individuals and possible mechanisms of intervention remain sparse. Furthermore, the role of music therapy in the context of circadian rhythmicity has not been adequately explored. By analyzing the links between circadian rhythmicity, neurodegeneration, and music therapy, a more comprehensive picture emerges, suggesting that possible uses of non-pharmacological circadian-based music therapy to target mechanisms involved in the pathogenesis of Alzheimer’s disease and Parkinson’s disease may enhance clinical treatment and potentially indicate neuroprotection as a preventative measure.