bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Regulation of Damage-Associated Molecular Pattern Release in a Mouse Model of Skeletal Muscle Ischemia/Reperfusion Injury
Authors: Furubeppu Hiroaki , Ito Takashi , Kakuuchi Midori , Yasuda Tomotsugu , Kamikokuryo Chinatsu , Yamada Shingo , Maruyama Ikuro , Kakihana Yasuyuki
Published: July 2021

Background

Skeletal muscle ischemia/reperfusion (I/R) injury is an important clinical issue that can cause remote organ injury. Although its pathogenesis has not been fully elucidated, recent studies have suggested that damage-associated molecular patterns (DAMPs) are mediators of remote organ injury in sterile inflammation. The purpose of this study was to investigate the possible involvement of DAMPs, including the nuclear proteins high-mobility group box 1 (HMGB1) and histone H3, in the pathogenesis of skeletal muscle I/R injury in mice.

Methods

Hindlimb ischemia was induced in mice through bilateral ligation of inguinal regions using rubber grommets. Reperfusion was induced by cutting the rubber grommets after 2–12 h of ischemic period. Survival rates, localization of HMGB1 and histone H3 in the gastrocnemius muscle, and circulating HMGB1 and histone H3 levels were analyzed. The effect of anti-HMGB1 and anti-histone H3 antibodies on survival was analyzed in mice with I/R injury.

Results

All mice with hindlimb ischemia survived for at least 36 h, while all mice died within 24 h if the hindlimbs were reperfused after ischemia for 4–12 h. Immunohistochemical analysis revealed that HMGB1 translocated from the nucleus to the cytoplasm in the ischemic gastrocnemius muscle, while histone H3 was confined to the nucleus. Accordingly, serum HMGB1 levels were significantly elevated in mice with hindlimb I/R compared with normal mice or mice with hindlimb ischemia (P < 0.05). Serum histone H3 levels were not elevated after I/R. Treatment with anti-HMGB1 antibodies significantly improved survival of mice with hindlimb I/R injury compared with control antibodies (P < 0.05).

Conclusions

HMGB1, but not histone H3, translocated to the cytoplasm during skeletal muscle ischemia, and was released into the systemic circulation after reperfusion in mice with I/R injury. Treatment with anti-HMGB1 antibodies partially improved survival.
The Roles of Kidney-Resident ILC2 in Renal Inflammation and Fibrosis
Authors: Nagashima Ryuichi , Iyoda Masayuki
Published: July 2021

Innate lymphoid cells (ILCs) are a recently discovered lymphocyte population with high cytokine productive capacity. Type-2 ILCs (ILC2s) are the most studied, and they exert a rapid type-2 immune response to eliminate helminth infections. Massive and sustainable ILC2 activation induces allergic tissue inflammation, so it is important to maintain correct ILC2 activity for immune homeostasis. The ILC2-activating cytokine IL-33 is released from epithelial cells upon tissue damage, and it is upregulated in various kidney disease mouse models and in kidney disease patients. Various kidney diseases eventually lead to renal fibrosis, which is a common pathway leading to end-stage renal disease and is a chronic kidney disease symptom. The progression of renal fibrosis is affected by the innate immune system, including renal-resident ILC2s; however, the roles of ILC2s in renal fibrosis are not well understood. In this review, we summarize renal ILC2 function and characterization in various kidney diseases and highlight the known and potential contributions of ILC2s to kidney fibrosis.
The Ability of Porcine Reproductive and Respiratory Syndrome Virus Isolates to Induce Broadly Reactive Neutralizing Antibodies Correlates With In Vivo Protection
Authors: Martínez-Lobo Francisco Javier , Díez-Fuertes Francisco , Simarro Isabel , Castro José M. , Prieto Cinta
Published: July 2021

Porcine reproductive and respiratory syndrome (PRRS) is considered one of the most relevant diseases of swine. The condition is caused by PRRS virus (PRRSV), an extremely variable virus of the Arteriviridae family. Its heterogeneity can be responsible, at least partially, of the poor cross-protection observed between PRRSV isolates. Neutralizing antibodies (NAs), known to play a role in protection, usually poorly recognize heterologous PRRSV isolates, indicating that most NAs are strain-specific. However, some pigs develop broadly reactive NAs able to recognize a wide range of heterologous isolates. The aim of this study was to determine whether PRRSV isolates that induce broadly reactive NAs as determined in vitro are able to confer a better protection in vivo. For this purpose two in vivo experiments were performed. Initially, 40 pigs were immunized with a PRRSV-1 isolate known to induce broadly reactive NAs and 24 additional pigs were used as controls. On day 70 after immunization, the pigs were divided into eight groups composed by five immunized and three control pigs and exposed to one of the eight different heterologous PRRSV isolates used for the challenge. In the second experiment, the same experimental design was followed but the pigs were immunized with a PRRSV-1 isolate, which is known to generate mostly strain-specific NAs. Virological parameters, specifically viremia and the presence of challenge virus in tonsils, were used to determine protection. In the first experiment, sterilizing immunity was obtained in three groups, prevention of viremia was observed in two additional groups, although the challenge virus was detected occasionally in the tonsils of immunized pigs, and partial protection, understood as a reduction in the frequency of viremia compared with controls, was recorded in the remaining three groups. On the contrary, only partial protection was observed in all groups in the second experiment. The results obtained in this study confirm that PRRSV-1 isolates differ in their ability to induce cross-reactive NAs and, although other components of the immune response might have contributed to protection, pigs with cross-reactive NAs at the time of challenge exhibited better protection, indicating that broadly reactive NAs might play a role in protection against heterologous reinfections.
Activation of NLRP3 Inflammasome and Onset of Alzheimer’s Disease
Authors: Bai Hua , Zhang Qifang
Published: July 2021

The nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor protein 3 (NLRP3) is an important pattern recognition receptor in human innate immunity. Activation of the NLRP3 inflammasome play a key role in the pathogenesis of Alzheimer’s disease (AD). Theories explaining activation of the NLRP3 inflammasome include the reactive oxygen species theory, the lysosomal damage theory and the mitochondrial DNA theory. The NLRP3 activation promotes occurrence of AD by producing IL-1β, IL-18 and other cytokines, and then by affecting the deposition of Aβ and tau proteins. Over-activated NLRP3 inflammasome often impair cell function and induces immune-related diseases. Some mechanisms have been found to negatively regulate activation of the NLRP3 inflammasome, which may be through receptor binding blocking mechanism, autophagy related mechanism, abnormal cytokine secretion mechanism, or interference related gene expression regulation mechanism. In this review, we summarize the possible mechanisms by which the activation of NLRP3 inflammasomes affects the pathogenesis of AD, and the recent advances in the prevention and treatment of AD by controlling the activation of NLRP3 inflammasomes. By researching the activation or inactivation of NLRP3 inflammasome, it is possible to reveal the pathogenesis of AD from a new perspective and provide a new idea for the prevention and treatment of AD.
Spatial Variability of Abyssal Nitrifying Microbes in the North-Eastern Clarion-Clipperton Zone
Authors: Hollingsworth Anita L. , Jones Daniel O. B. , Young C. Robert
Published: July 2021

Abyssal microbes drive biogeochemical cycles, regulate fluxes of energy and contribute to organic carbon production and remineralization. Therefore, characterizing the spatial variability of benthic microbes is important for understanding their roles in benthic environments and for conducting baseline assessments of areas of the seabed that might be targeted by commercial mining activities. Yet, detailed assessments of the spatial distributions of benthic microbial communities in these regions are still incomplete, and these efforts have not yet considered the influence of seafloor topography and heterogeneity on microbial distributions across a range of scales. In this study, we investigated the composition and spatial variability of benthic microbial assemblages found in sediments and polymetallic nodules collected from the Clarion Clipperton Zone (CCZ) in the equatorial Pacific (4000–4300 m water depth). We used 16S rRNA gene sequences to characterize these communities. The upper 20 cm of abyssal sediments harbored diverse and distinctive microbial communities in both sediments and their associated polymetallic nodules, with high similarity across topographical areas of the seabed. Assemblage composition differed vertically through the sediment, by habitat and across small to mesoscales. Potential carbon-fixing microbes formed more than 25% relative abundance of sediment assemblages, which were dominated by ammonia-oxidizing ArchaeaNitrosopumilus. Non-photosynthetic Cyanobacteria were more frequent in the deeper sediment layers and nodules. Sediment communities had a higher abundance of taxa involved in nitrogen cycling, such asNitrosopumilus,Nitrospina,Nitrospira,AqS1(Nitrosococcaceae), and methanogenswb1-A12(NC10 phylum). In contrast, nodules were more enriched in Alphaproteobacteria, Gammaproteobacteria, Planctomycetes, Acidobacteria, Bacteroidetes, Nanoarchaeaeota, andCalditrichaeota. Microbes related to potential metal-cycling (Magnetospiraceae andKiloniellaceae), organic carbon remineralization (Woeseia), and sulfur-oxidizing Thiohalorhabdaceae were also more enriched in nodules. Our results indicate that benthic microbial community composition is driven by sediment profile depth and seafloor heterogeneity at small and mesoscales. The most abundant microbial taxa within the sediments were nitrifying and putative carbon-fixing microbes, and may have key ecological roles in mediating biogeochemical cycles in this habitat.
Slower Ship Speed in the Bahamas Due to COVID-19 Produces a Dramatic Reduction in Ocean Sound Levels
Authors: Dunn Charlotte , Theriault James , Hickmott Leigh , Claridge Diane
Published: July 2021

As underwater noise from ship traffic increases, profound effects on the marine environment highlight the need for improved mitigation measures. One measure, reduction in ship speed, has been shown to be one of the key drivers in reducing sound source levels of vessels. In 2017, a study began to assess the impacts of increasing commercial shipping traffic on sperm whales in Northwest Providence Channel, northern Bahamas, an international trade route that primarily serves the southeast US. Ship data were collected from an Automatic Identification System (AIS) station combined with recordings from an acoustic recorder to measure underwater sound levels and to detect the presence of sperm whales. Here we analyze a subset of these data to opportunistically investigate potential changes in ship traffic before and during the COVID-19 pandemic. These data span one calendar year from October 2019 to October 2020. A pre-COVID-19 dataset of 121 days, from a recorder approximately 2 km from the shipping route was compared to a 134-day dataset collected during COVID-19 from the same site, comprising 2900 and 3181 ten-minute recordings, respectively. A dramatic decrease in ocean noise levels concurrent with changes in shipping activity occurred during the pandemic. The mean pre-COVID-19 power density level in the 111–140 Hz 1/3-octave band was 88.81 dB re 1 μPa (range 81.38–100.90) and decreased to 84.27 dB re 1 μPa (range 78.60–99.51) during COVID-19, equating to a 41% reduction in sound pressure levels (SPL). After differences in seasonal changes in wind speed were accounted for, SPL decreased during the pandemic by 3.98 dB (37%). The most notable changes in ship activity were significantly reduced vessel speeds for all ship types and fewer ships using the area during the pandemic. Vessel speed was highly correlated to SPL and the only ship-based variable that predicted SPLs. Despite the opportunistic nature [i.e., not a standard before-after-control-impact (BACI) study], this study provides a unique opportunity to assess the effectiveness of ship traffic management strategies, such as slowing ships down, to mitigate impacts on marine life in the study area, including local sperm whale populations.
Effect of Iron Tailings and Slag Powders on Workability and Mechanical Properties of Concrete
Authors: Ruidong Wu , Yu Shen , Juanhong Liu , Linian Cheng , Guangtian Zhang , Yueyue Zhang
Published: July 2021

Tailings are one of the largest solid wastes in stock at present. In order to improve the comprehensive utilization rate of tailings, especially to solve the problems of fine-grained tailings treatment, the concrete composite admixture was prepared by using iron tailings powder and slag powder. In order to study the influence of iron tailings powder on the workability and long-term mechanical properties of concrete, C30 and C50 concrete with different iron tailings powder dosages were prepared, and the slump, expansion, flexural strength, splitting tensile strength, and compressive strength of concrete at different ages were tested. The results showed that the proper addition of iron tailing powder is beneficial to the working performance of concrete and can effectively reduce the time-loss of concrete fluidity. When the content of iron tailings powder in the composite admixture is 50%, the 1080d long age strength of C30 and C50 concrete can reach 50.3 and 80.7 MPa. Based on the 28d compressive strength, the relative strength-age prediction model of iron tailings powder concrete was established. The calculation and experimental results show that the model can accurately predict the compressive strength of micro-powder concrete of iron tailings at long age, and the error rate is less than 1%. The results lay a theoretical foundation for the utilization of iron tailings in concrete.
Distribution of Pathogens in Elderly Chinese Patients With Pneumonia: A Systematic Review and Meta-Analysis
Authors: Chen Luming , Huang Hongqiang , Chen Xiaolin
Published: July 2021

Background: To summarize the distribution of pathogenic bacteria in elderly Chinese patients with pneumonia and provide guidance for the clinical application of antibiotics.

Methods: The electronic databases of PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure were searched. The primary outcomes included the prevalence of gram-positive cocci, gram-negative bacilli, and fungus. The summary prevalence and 95% confidence interval (CI) were calculated using the random-effects model.

Results: A total of 17 retrospective studies reporting a total of 5,729 elderly patients with pneumonia were selected for final analysis. The summary prevalence of gram-positive cocci was 25% (95% CI: 20–30%; p < 0.001), whereas the prevalence of gram-negative bacilli was 56% (95% CI: 46–67%; p < 0.001). Moreover, the pooled prevalence of fungus in elderly patients with pneumonia was 11% (95% CI: 8–14%; p < 0.001). The most common gram-positive cocci were Staphylococcus aureus (ES: 8%; 95% CI: 6–11%; p <0.001), Streptococcus hemolyticus (ES: 7%; 95% CI: 6–8%; p < 0.001), and Streptococcus pneumoniae (ES: 5%; 95% CI: 3–7%; p < 0.001). Pseudomonas aeruginosa (ES: 18%; 95% CI: 14–22%; p <0.001) and Klebsiella pneumoniae (ES: 14%; 95% CI: 11–18%; p <0.001) were most common gram-negative bacilli. Furthermore, the pooled prevalence of Candida albicans in elderly patients with pneumonia was 6% (95% CI: 5–8%; p < 0.001).

Conclusions: The findings demonstrated the comprehensive distribution of pathogenic bacteria in elderly Chinese patients with pneumonia, which could guide further antibiotic therapies.
The Role of Glucocorticoids in the Treatment of ARDS: A Multicenter Retrospective Study Based on the eICU Collaborative Research Database
Authors: Zhang Luming , Wang Zichen , Xu Fengshuo , Ren Yinlong , Wang Hao , Han Didi , Lyu Jun , Yin Haiyan
Published: July 2021

Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in patients in intensive care unit (ICU). The therapeutic value of glucocorticoids (GCs) in the prognosis of ARDS remains controversial. The aim of this research is studying the impacts of GCs treatment on ARDS patients in ICU.

Methods: We retrospectively studied 2,167 ARDS patients whose data were collected from the public eICU Collaborative Research Database, among which 254 patients who received glucocorticoid (GCs) treatment were 1:1 matched by propensity matching analysis (PSM). The primary outcome was ICU mortality. Every oxygenation index (PaO2/FiO2) measurement before death or ICU discharge was recorded. A joint model (JM) which combined longitudinal sub-model (mixed-effect model) and time-to-event sub-model (Cox regression model) by trajectory functions of PaO2/FiO2 was conducted to determine the effects of GCs treatment on both ICU mortality and PaO2/FiO2 level and further PaO2/FiO2's effect on event status. The marginal structural cox model (MSCM) adjusted the overall PaO2/FiO2 of patients to further validate the results.

Results: The result of the survival sub-model showed that GCs treatment was significantly associated with reduced ICU mortality in ARDS patients [HR (95% CI) = 0.642 (0.453, 0.912)], demonstrating that GCs treatment was a protective factor of ICU mortality. In the longitudinal sub-model, GCs treatment was not correlated to the PaO2/FiO2. After adjusted by the JM, the HR of GCs treatment was 0.602 while GCs was still not significantly related to PaO2/FiO2 level. The JM-induced association showed that higher PaO2/FiO2 was a significant protective factor of mortality in ARDS patients and the HR was 0.991 which demonstrated that one level increase of PaO2/FiO2 level decreased 0.9% risk of ICU mortality. MSCM results also show that GCs can improve the prognosis of patients.

Conclusion: Rational use of GCs can reduce the ICU mortality of ARDS patients in ICU. In addition to the use of GCs treatment, clinicians should also focus on the shifting trend of PaO2/FiO2 level to provide better conditions for patients' survival.
Metagenomic Next-Generation Sequencing Can Clinch Diagnosis of Non-Tuberculous Mycobacterial Infections: A Case Report
Authors: Zhu He , Zhu Min , Lei Jia-Hui , Xiao Ya-Li , Zhao Li-Min
Published: July 2021

Non-tuberculou Mycobacteria (NTM) is ubiquitous in the environment and is conditional pathogen. Due to NTM and Mycobacterium tuberculosis belong to the genus Mycobacterium, their pathogenic mechanisms and clinical manifestations are similar. Therefore, NTM can cause tuberculosis-like lesions and lead to misdiagnosis. Early diagnosis and treatment greatly improve prognosis. However, traditional pathogenic microorganism detection has limitations, and it is difficult to accurately identify strains in clinical practice. Here, we report a 65-year-old man with NTM who presented with recurrent fever and cough. Computed tomography of the chest revealed a lung infection. The previous improper diagnosis and treatment did not improve his condition. With the aid of metagenomic next-generation sequencing, the pathogen was identified as Mycobacterium avium complex. Subsequently, he received accurate treatment and made significant improvements in clinical and radiology.
Acupuncture as an Add-On Treatment for Functional Dyspepsia: A Systematic Review and Meta-Analysis
Authors: Kwon Chan-Young , Ko Seok-Jae , Lee Boram , Cha Jae Myung , Yoon Jin Young , Park Jae-Woo
Published: July 2021

Background: We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of evidence (QoE) of these findings.

Methods: A total of 12 English, Korean, and Chinese databases were searched on December 18, 2020. Randomized controlled trials (RCTs) assessing the effectiveness of acupuncture as an add-on therapy to conventional WM for functional dyspepsia (FD) were included. The primary outcome was the symptom score of FD. The risk of bias of the included studies and QoE were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation method, respectively.

Results: A total of 22 RCTs were included. The total and individual FD symptom scores were significantly improved in the acupuncture combined with WM groups compared with the WM alone groups, except for in one study. The Nepean dyspepsia index score and total effective rate mostly improved significantly in the acupuncture group, regardless of the WM used and acupuncture type. FD-related biomarkers, such as ghrelin and gastrin levels, showed mixed results. The acupuncture group showed a significantly lower recurrence rate after 3–6 months of follow-up than the WM alone group. There were no differences in the incidence of adverse events between the two groups. The included studies generally had low methodological quality. The QoE for the main findings was generally very low to moderate.

Conclusion: Limited evidence suggests that acupuncture has the potential to improve FD treatment in combination with conventional WM. Furthermore, the methodological quality of the included studies and QoE of the main findings were generally low. Therefore, RCTs with a rigorous methodology, including sham acupuncture and multiethnic subjects, should be performed.

Systematic Review Registration: OSF registries [https://osf.io/mxren], PROSPERO [CRD42021226608].
Neutrophil-to-Lymphocyte Ratio and Treatment Failure in Peritoneal Dialysis-Associated Peritonitis
Authors: He Peng , He Li-jie , Huang Chen , Hu Jin-ping , Sun Shi-ren
Published: July 2021

Objective: We sought to explore if there is an association between neutrophil-to-lymphocyte ratio (NLR) and treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP).

Methods: Our cohort involved 337 episodes of PDAP experienced by 202 patients who were undergoing continuous ambulatory peritoneal dialysis at a single center from 1 July 2013 to 30 June 2018. The exposures were log-transformed NLR and a categorical variable grouped by the tertiles of NLR levels (T1, <3.75; T2, 3.75–6.53; and T3, >6.53) at baseline. Generalized estimating equation (GEE) and restricted cubic spline (RCS) analyses were done to determine the association between NLR and treatment failure, defined as catheter removal or all-cause mortality during therapy.

Results: After adjusting for other potential predictors, the log-transformed NLR exhibited an incremental relationship with the risk of treatment failure (odds ratio, 1.82; 95% confidence interval, 1.05–3.15). RCS analyses showed that the relationship was positively and linearly correlated (P for nonlinearity = 0.104). As a three-level categorical variable, in reference to T1, the T3 of NLR showed a 3.41-fold increased venture of treatment failure in fully adjusted model. Subgroup analyses suggested that the prognostic relevance of NLR in PDAP was particularly significant in gram-negative peritonitis.

Conclusions: A greater level of NLR at baseline was remarkably associated with a higher incidence of treatment failure among PDAP episodes regardless of other potential risk factors.
Microbiome in Blood Samples From the General Population Recruited in the MARK-AGE Project: A Pilot Study
Authors: D’Aquila Patrizia , Giacconi Robertina , Malavolta Marco , Piacenza Francesco , Bürkle Alexander , Villanueva María Moreno , Dollé Martijn E. T. , Jansen Eugène , Grune Tilman , Gonos Efstathios S. , Franceschi Claudio , Capri Miriam , Grubeck-Loebenstein Beatrix , Sikora Ewa , Toussaint Olivier , Debacq-Chainiaux Florence , Hervonen Antti , Hurme Mikko , Slagboom P. Eline , Schön Christiane , Bernhardt Jürgen , Breusing Nicolle , Passarino Giuseppe , Provinciali Mauro , Bellizzi Dina
Published: July 2021

The presence of circulating microbiome in blood has been reported in both physiological and pathological conditions, although its origins, identities and function remain to be elucidated. This study aimed to investigate the presence of blood microbiome by quantitative real-time PCRs targeting the 16S rRNA gene. To our knowledge, this is the first study in which the circulating microbiome has been analyzed in such a large sample of individuals since the study was carried out on 1285 Randomly recruited Age-Stratified Individuals from the General population (RASIG). The samples came from several different European countries recruited within the EU Project MARK-AGE in which a series of clinical biochemical parameters were determined. The results obtained reveal an association between microbial DNA copy number and geographic origin. By contrast, no gender and age-related difference emerged, thus demonstrating the role of the environment in influencing the above levels independent of age and gender at least until the age of 75. In addition, a significant positive association was found with Free Fatty Acids (FFA) levels, leukocyte count, insulin, and glucose levels. Since these factors play an essential role in both health and disease conditions, their association with the extent of the blood microbiome leads us to consider the blood microbiome as a potential biomarker of human health.
Malate-Aspartate Shuttle Plays an Important Role in LPS-Induced Neuroinflammation of Mice Due to its Effect on STAT3 Phosphorylation
Authors: Zhou Cuiyan , Shang Wangsong , Yin Shan-Kai , Shi Haibo , Ying Weihai
Published: July 2021

Neuroinflammation is a key pathological factor in numerous neurological disorders. Cumulating evidence has indicated critical roles of NAD+/NADH metabolism in multiple major diseases, while the role of malate-aspartate shuttle (MAS) - a major NADH shuttle - in inflammation has remained unclear. In this study we investigated the roles of MAS in LPS-induced neuroinflammation both in vivo and in vitro. Immunofluorescence staining, Western blot assay and Real-time PCR assays were conducted to determine the activation of Iba-1, the protein levels of iNOS and COX2 and the mRNA levels of IL-1β, IL-6, and TNF-α in vivo, showing that both pre-treatment and post-treatment of aminooxyacetic acid (AOAA) - an MAS inhibitor - profoundly decreased the LPS-induced neuroinflammation in mice. BV2 microglia was also used as a cellular model to investigate the mechanisms of this finding, in which such assays as Western blot assay and nitrite assay. Our study further indicated that AOAA produced its effects on LPS-induced microglial activation by its effects on MAS: Pyruvate treatment reversed the effects of AOAA on the cytosolic NAD+/NADH ratio, which also restored the LPS-induced activation of the AOAA-treated microglia. Moreover, the lactate dehydrogenase (LDH) inhibitor GSK2837808A blocked the effects of pyruvate on the AOAA-produced decreases in both the cytosolic NAD+/NADH ratio and LPS-induced microglial activation. Our study has further suggested that AOAA produced inhibition of LPS-induced microglial activation at least partially by decreasing STAT3 phosphorylation. Collectively, our findings have indicated AOAA as a new and effective drug for inhibiting LPS-induced neuroinflammation. Our study has also indicated that MAS is a novel mediator of LPS-induced neuroinflammation due to its capacity to modulate LPS-induced STAT3 phosphorylation, which has further highlighted a critical role of NAD+/NADH metabolism in inflammation.
Chaperonin Abundance Enhances Bacterial Fitness
Authors: Kumar C. M. Santosh , Chugh Kritika , Dutta Anirban , Mahamkali Vishnuvardhan , Bose Tungadri , Mande Sharmila S. , Mande Shekhar C. , Lund Peter A.
Published: July 2021

The ability of chaperonins to buffer mutations that affect protein folding pathways suggests that their abundance should be evolutionarily advantageous. Here, we investigate the effect of chaperonin overproduction on cellular fitness inEscherichia coli. We demonstrate that chaperonin abundance confers 1) an ability to tolerate higher temperatures, 2) improved cellular fitness, and 3) enhanced folding of metabolic enzymes, which is expected to lead to enhanced energy harvesting potential.
MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body
Authors: Xu Xiaoyang , Hong Pengyu , Wang Zhefu , Tang Zhangui , Li Kun
Published: July 2021

Fibrosis, a major cause of morbidity and mortality, is a histopathological manifestation of many chronic inflammatory diseases affecting different systems of the human body. Two types of transforming growth factor beta (TGF-β) signaling pathways regulate fibrosis: the canonical TGF-β signaling pathway, represented by SMAD-2 and SMAD-3, and the noncanonical pathway, which functions without SMAD-2/3 participation and currently includes TGF-β/mitogen-activated protein kinases, TGF-β/SMAD-1/5, TGF-β/phosphatidylinositol-3-kinase/Akt, TGF-β/Janus kinase/signal transducer and activator of transcription protein-3, and TGF-β/rho-associated coiled-coil containing kinase signaling pathways. MicroRNA (miRNA), a type of non-coding single-stranded small RNA, comprises approximately 22 nucleotides encoded by endogenous genes, which can regulate physiological and pathological processes in fibrotic diseases, particularly affecting organs such as the liver, the kidney, the lungs, and the heart. The aim of this review is to introduce the characteristics of the canonical and non-canonical TGF-β signaling pathways and to classify miRNAs with regulatory effects on these two pathways based on the influenced organ. Further, we aim to summarize the limitations of the current research of the mechanisms of fibrosis, provide insights into possible future research directions, and propose therapeutic options for fibrosis.
Host - Bacterial Pathogen Communication: The Wily Role of the Multidrug Efflux Pumps of the MFS Family
Authors: Pasqua Martina , Bonaccorsi di Patti Maria Carmela , Fanelli Giulia , Utsumi Ryutaro , Eguchi Yoko , Trirocco Rita , Prosseda Gianni , Grossi Milena , Colonna Bianca
Published: July 2021

Bacterial pathogens are able to survive within diverse habitats. The dynamic adaptation to the surroundings depends on their ability to sense environmental variations and to respond in an appropriate manner. This involves, among others, the activation of various cell-to-cell communication strategies. The capability of the bacterial cells to rapidly and co-ordinately set up an interplay with the host cells and/or with other bacteria facilitates their survival in the new niche. Efflux pumps are ubiquitous transmembrane transporters, able to extrude a large set of different molecules. They are strongly implicated in antibiotic resistance since they are able to efficiently expel most of the clinically relevant antibiotics from the bacterial cytoplasm. Besides antibiotic resistance, multidrug efflux pumps take part in several important processes of bacterial cell physiology, including cell to cell communication, and contribute to increase the virulence potential of several bacterial pathogens. Here, we focus on the structural and functional role of multidrug efflux pumps belonging to the Major Facilitator Superfamily (MFS), the largest family of transporters, highlighting their involvement in the colonization of host cells, in virulence and in biofilm formation. We will offer an overview on how MFS multidrug transporters contribute to bacterial survival, adaptation and pathogenicity through the export of diverse molecules. This will be done by presenting the functions of several relevant MFS multidrug efflux pumps in human life-threatening bacterial pathogens as Staphylococcus aureus, Listeria monocytogenes, Klebsiella pneumoniae, Shigella/E. coli, Acinetobacter baumannii.
Functional MRI-Specific Alterations in Salience Network in Mild Cognitive Impairment: An ALE Meta-Analysis
Authors: Song Yu , Xu Wenwen , Chen Shanshan , Hu Guanjie , Ge Honglin , Xue Chen , Qi Wenzhang , Lin Xingjian , Chen Jiu
Published: July 2021

Background Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Amnestic MCI (aMCI) and non-amnestic MCI are the two subtypes of MCI with the former having a higher risk for progressing to Alzheimer's disease (AD). Compared with healthy elderly adults, individuals with MCI have specific functional alterations in the salience network (SN). However, no consistent results are documenting these changes. This meta-analysis aimed to investigate the specific functional alterations in the SN in MCI and aMCI.

Methods: We systematically searched PubMed, Embase, and Web of Science for scientific neuroimaging literature based on three research methods, namely, functional connectivity (FC), regional homogeneity (ReHo), and the amplitude of low-frequency fluctuation or fractional amplitude of low-frequency fluctuation (ALFF/fALFF). Then, we conducted the coordinate-based meta-analysis by using the activation likelihood estimation algorithm.

Results: In total, 30 functional neuroimaging studies were included. After extracting the data and analyzing it, we obtained specific changes in some brain regions in the SN including decreased ALFF/fALFF in the left superior temporal gyrus, the insula, the precentral gyrus, and the precuneus in MCI and aMCI; increased FC in the thalamus, the caudate, the superior temporal gyrus, the insula, and the cingulate gyrus in MCI; and decreased ReHo in the anterior cingulate gyrus in aMCI. In addition, as to FC, interactions of the SN with other networks including the default mode network and the executive control network were also observed mainly in the middle frontal gyrus and superior frontal gyrus in MCI and inferior frontal gyrus in aMCI.

Conclusions: Specific functional alternations in the SN and interactions of the SN with other networks in MCI could be useful as potential imaging biomarkers for MCI or aMCI. Meanwhile, it provided a new insight in predicting the progression of health to MCI or aMCI and novel targets for proper intervention to delay the progression.

Systematic Review Registration: [PROSPERO], identifier [No. CRD42020216259].
tDCS-Induced Memory Reconsolidation Effects and Its Associations With Structural and Functional MRI Substrates in Subjective Cognitive Decline
Authors: Vaqué-Alcázar Lídia , Mulet-Pons Lídia , Abellaneda-Pérez Kilian , Solé-Padullés Cristina , Cabello-Toscano María , Macià Dídac , Sala-Llonch Roser , Bargalló Nuria , Solana Javier , Cattaneo Gabriele , Tormos José M. , Pascual-Leone Alvaro , Bartrés-Faz David
Published: July 2021

Previous evidence suggests that transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (l-DLPFC) can enhance episodic memory in subjects with subjective cognitive decline (SCD), known to be at risk of dementia. Our main goal was to replicate such findings in an independent sample and elucidate if baseline magnetic resonance imaging (MRI) characteristics predicted putative memory improvement. Thirty-eight participants with SCD (aged: 60–65 years) were randomly assigned to receive active (N = 19) or sham (N = 19) tDCS in a double-blind design. They underwent a verbal learning task with 15 words (DAY-1), and 24 h later (DAY-2) stimulation was applied for 15 min at 1.5 mA targeting the l-DLPFC after offering a contextual reminder. Delayed recall and recognition were measured 1 day after the stimulation session (DAY-3), and at 1-month follow-up (DAY-30). Before the experimental session, structural and functional MRI were acquired. We identified a group∗time interaction in recognition memory, being the active tDCS group able to maintain stable memory performance between DAY-3 and DAY-30. MRI results revealed that individuals with superior tDCS-induced effects on memory reconsolidation exhibited higher left temporal lobe thickness and greater intrinsic FC within the default-mode network. Present findings confirm that tDCS, through the modulation of memory reconsolidation, is capable of enhancing performance in people with self-perceived cognitive complaints. Results suggest that SCD subjects with more preserved structural and functional integrity might benefit from these interventions, promoting maintenance of cognitive function in a population at risk to develop dementia.
Neuropsychobiological Fingerprints of Chronic Fatigue in Sarcoidosis
Authors: Kettenbach Sarah , Radke Sina , Müller Tobias , Habel Ute , Dreher Michael
Published: July 2021

Background

Chronic fatigue is a prominent symptom in many sarcoidosis patients, affecting quality of life and interfering with treatment. This study investigated neuropsychobiological mechanisms and markers of chronic fatigue in sarcoidosis.

Methods

Thirty patients with a histological diagnosis of sarcoidosis were included. The Multidimensional Fatigue Inventory was used to define patients with and without chronic fatigue. All patients were then characterised using several depression, quality of life questionnaires, and executive functioning. Cognitive functioning and underlying neural correlates were assessed using an n-back task measuring working memory and (sustained) attention during functional magnetic resonance imaging. Sarcoidosis disease activity was determined using lung function, laboratory parameters, and exercise capacity.

Results

Nineteen patients had chronic fatigue and 11 did not; both groups had similar demographic and disease activity characteristics. Chronic fatigue patients showed more symptoms of depression and anxiety, and lower quality of life. During the n-back task, chronic fatigue was associated with a smaller increase in brain activation with increasing task difficulty versus the group without fatigue, especially in the angular gyrus.

Conclusion

Inadequate adjustment of brain activation with increasing demands appears to be a potential neurobiological marker of chronic fatigue in sarcoidosis patients. The angular gyrus, which plays an important role in the working memory system, was the major area in which fatigue patients showed smaller increase of brain activation compared to those without fatigue. These findings might be relevant for a deeper understanding of chronic fatigue mechanisms in sarcoidosis and future clinical treatment of this disabling syndrome.

Trial Registration

ClinicalTrials.gov, Trial registration number: NCT04178239

Date of registration: November 26, 2019, retrospectively registered

URL: https://clinicaltrials.gov/ct2/show/NCT04178239.
Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
Authors: Moulson Aaron J. , Squair Jordan W. , Franklin Robin J. M. , Tetzlaff Wolfram , Assinck Peggy
Published: July 2021

Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.
Oculomotor Deficits and Symptom Severity Are Associated With Poorer Dynamic Mobility in Chronic Mild Traumatic Brain Injury
Authors: D'Silva Linda J. , Chalise Prabhakar , Obaidat Sakher , Rippee Michael , Devos Hannes
Published: July 2021

Oculomotor deficits, vestibular impairments, and persistent symptoms are common after a mild traumatic brain injury (mTBI); however, the relationship between visual-vestibular deficits, symptom severity, and dynamic mobility tasks is unclear. Twenty-three individuals (mean age 55.7 ± 9.3 years) with persistent symptoms after mTBI, who were between 3 months to 2 years post-injury were compared with 23 age and sex-matched controls. Oculomotor deficits [depth perception, near-point convergence, baseline visual acuity (BLVA), perception time], vestibular deficits (dynamic visual acuity in the pitch and yaw planes), dynamic mobility measured by the Functional Gait Assessment (FGA), and symptoms measured by the Post-Concussion Symptom Scale (PCSS) and Dizziness Handicap Inventory (DHI) were compared between groups. Participants with mTBI had poorer performance on the FGA (p< 0.001), higher symptom severity on the PCSS (p< 0.001), and higher DHI scores (p< 0.001) compared to controls. Significant differences were seen on specific items of the FGA between individuals with mTBI and controls during walking with horizontal head turns (p= 0.002), walking with vertical head tilts (p< 0.001), walking with eyes closed (p= 0.003), and stair climbing (p= 0.001). FGA performance was correlated with weeks since concussion (r= −0.67,p< 0.001), depth perception (r= −0.5348,p< 0.001), near point convergence (r= −0.4717,p= 0.001), baseline visual acuity (r= −0.4435,p= 0.002); as well as with symptoms on the PCSS (r= −0.668,p< 0.001), and DHI (r= −0.811,p< 0.001). Dynamic balance deficits persist in chronic mTBI and may be addressed using multifaceted rehabilitation strategies to address oculomotor dysfunction, post-concussion symptoms, and perception of handicap due to dizziness.
Electrophysiological and Transcriptomic Features Reveal a Circular Taxonomy of Cortical Neurons
Authors: Rodríguez-Collado Alejandro , Rueda Cristina
Published: July 2021

The complete understanding of the mammalian brain requires exact knowledge of the function of each neuron subpopulation composing its parts. To achieve this goal, an exhaustive, precise, reproducible, and robust neuronal taxonomy should be defined. In this paper, a new circular taxonomy based on transcriptomic features and novel electrophysiological features is proposed. The approach is validated by analysing more than 1850 electrophysiological signals of different mouse visual cortex neurons proceeding from the Allen Cell Types database. The study is conducted on two different levels: neurons and their cell-type aggregation into Cre lines. At the neuronal level, electrophysiological features have been extracted with a promising model that has already proved its worth in neuronal dynamics. At the Cre line level, electrophysiological and transcriptomic features are joined on cell types with available genetic information. A taxonomy with a circular order is revealed by a simple transformation of the first two principal components that allow the characterization of the different Cre lines. Moreover, the proposed methodology locates other Cre lines in the taxonomy that do not have transcriptomic features available. Finally, the taxonomy is validated by Machine Learning methods which are able to discriminate the different neuron types with the proposed electrophysiological features.
A Sham-Controlled Study of Neurofeedback for Pain Management
Authors: Ide-Walters Charlotte , Thompson Trevor
Published: July 2021

Background

Neurofeedback (NFB) attempts to alter the brain’s electrophysiological activity and has shown potential as a pain management technique. Existing studies, however, often lack appropriate control groups or fail to assess whether electrophysiological activity has been successfully regulated. The current study is a randomized controlled trial comparing changes in brain activity and pain during NFB with those of a sham-control group.

Methods

An experimental pain paradigm in healthy participants was used to provide optimal control of pain sensation. Twenty four healthy participants were blind randomized to receive either 10 × NFB (with real EEG feedback) or 10 × sham (with false EEG feedback) sessions during noxious cold stimulation. Prior to actual NFB training, training protocols were individually determined for each participant based on a comparison of an initial 32-channel qEEG assessment administered at both baseline and during an experimental pain task. Each individual protocol was based on the electrode site and frequency band that showed the greatest change in amplitude during pain, with alpha or theta up-regulation at various electrode sites (especially Pz) the most common protocols chosen. During the NFB sessions themselves, pain was assessed at multiple times during each session on a 0–10 rating scale, and ANOVA was used to examine changes in pain ratings and EEG amplitude both across and during sessions for both NFB and sham groups.

Results

For pain, ANOVA trend analysis found a significant general linear decrease in pain across the 10 sessions (p = 0.015). However, no significant main or interaction effects of group were observed suggesting decreases in pain occurred independently of NFB. For EEG, there was a significant During Session X Group interaction (p = 0.004), which indicated that EEG amplitude at the training site was significantly closer to the target amplitude for the NFB compared to the sham group during painful stimulation, but this was only the case at the beginning of the cold task.

Conclusion

While these results must be interpreted within the context of an experimental pain model, they underline the importance of including an appropriate comparison group to avoid attributing naturally occurring changes to therapeutic effects.
Effects of Different Treatment Methods of Dried Citrus Peel (Chenpi) on Intestinal Microflora and Short-Chain Fatty Acids in Healthy Mice
Authors: Qian Yujiao , Gao Zhipeng , Wang Chen , Ma Jie , Li Gaoyang , Fu Fuhua , Guo Jiajing , Shan Yang
Published: July 2021

Chenpi is a kind of dried citrus peel from Citrus reticulata, and it is often used as traditional Chinese medicine to treat dyspepsia and respiratory tract inflammation. In this study, to determine which way of chenpi treatment plays a better effect on the prevention of obesity in healthy mice, we conducted 16S ribosomal RNA (rRNA) gene sequencing for intestinal microbiota and gas chromatography-mass spectrometry detector (GC/MSD) analysis for short-chain fatty acids (SCFAs) of female rats fed with either chenpi decoction or chenpi powder-based diet (n = 10 per group) for 3 weeks. Chenpi powder (CP) group significantly reduced abdominal adipose tissues, subcutaneous adipose tissue, and the serum level of total triacylglycerol (TG). At a deeper level, chenpi powder has a better tendency to increase the ratio of Bacteroidetes to Firmicutes. It alters the Muribaculaceae and Muribaculum in intestinal microbiota, though it is not significant. The concentrations of acetic acid, valeric acid, and butyric acid increased slightly but not significantly in the CP group. Chenpi decoction just reduced perirenal adipose tissues, but it shows better antioxidant activity. It has little effect on intestinal microbiota. No differences were found for SCFAs in the chenpi decoction (CD) group. The results indicated that chenpi powder has a better effect in preventing obesity in mice. It can provide a basis for the development of functional products related to chenpi powder.