bluuebunny/crossref_metadata_2025 huggingface dataset:
Kidney Normothermic Machine Perfusion Can Be Used as a Preservation Technique and a Model of Reperfusion to Deliver Novel Therapies and Assess Inflammation and Immune Activation
Authors: Mellati Azita , Lo Faro Letizia , Dumbill Richard , Meertens Pommelien , Rozenberg Kaithlyn , Shaheed Sadr , Snashall Corinna , McGivern Hannah , Ploeg Rutger , Hunter James
Published: June 2022

Ischaemia–reperfusion injury (IRI) is an inevitable process in transplantation and results in inflammation and immune system activation. Alpha-1 antitrypsin (AAT) has anti-inflammatory properties. Normothermic machine perfusion (NMP) can be used to deliver therapies and may help in assessing the effects of IRI and immunity. This study investigated the effects of AAT on IRI and inflammation in pig kidneys when administered during preservation, followed by normothermic reperfusion (NR) with autologous whole blood, as a surrogate for transplant. Two different models were used to deliver AAT or placebo to paired slaughterhouse pig kidneys: Model 1: 7-h static cold storage (SCS) + 3-h NR (n = 5 pairs), where either AAT (10 mg/ml) or placebo was delivered in the flush following retrieval; Model 2: 4-h SCS + 3-h NMP + 3-h NR (n = 5 pairs), where either AAT or placebo was delivered during NMP. Injury markers and cytokines levels were analysed in the perfusate, and heat shock protein 70 KDa (HSP-70) was analysed in biopsies. AAT delivered to kidneys showed no adverse effects on perfusion parameters. HSP-70 fold changes were significantly lower in the AAT group during NMP (P < 0.01, paired t-test) but not during NR. Interleukin-1 receptor antagonist (IL-1ra) fold changes were significantly higher in the AAT group during NR model 1 (p < 0.05, two-way ANOVA). In contrast to the AAT group, significant upregulation of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) between t = 90 min and t = 180 min and interleukin-8 (IL-8) between baseline and t = 90 min was observed in the control group in NR model 2 (p < 0.05, Tukey’s multiple comparison test). However, overall inflammatory cytokines and injury markers showed similar levels between groups. Delivery of AAT to pig kidneys was safe without any detrimental effects. NMP and NR provided excellent methods for comparison of inflammation and immune activation in the delivery of a novel therapy.
Induction Strategies in Lung Transplantation: Alemtuzumab vs. Basiliximab a Single-Center Experience
Authors: Furukawa Masashi , Chan Ernest G. , Ryan John P. , Hyzny Eric J. , Sacha Lauren M. , Coster Jenalee N. , Pilewski Joseph M. , Lendermon Elizabeth A. , Kilaru Silpa D. , McDyer John F. , Sanchez Pablo G.
Published: June 2022

Background

Induction therapy is used in about 80% of lung transplant centers and is increasing globally. Currently, there are no standards or guidelines for the use of induction therapy. At our institution, we have two induction strategies, basiliximab, and alemtuzumab. The goal of this manuscript is to share our experience and practice since this is an area of controversy.

Methods

We retrospectively reviewed 807 lung transplants performed at our institution between 2011 and 2020. Indications for the use of the basiliximab protocol were as follows: patients over the age of 70 years, history of cancer, hepatitis C virus or human immunodeficiency virus infection history, and cytomegalovirus or Epstein-Barr virus (donor positive/ recipient negative). In the absence of these clinical factors, the alemtuzumab protocol was used.

Results

453 patients underwent alemtuzumab induction and 354 patients underwent basiliximab. There were significant differences in delayed chest closure (24.7% alemtuzumab vs 31.4% basiliximab, p = 0.037), grade 3 primary graft dysfunction observed within 72 hours (19.9% alemtuzumab vs 29.9% basiliximab, p = 0.002), postoperative hepatic dysfunction (8.8% alemtuzumab vs 14.7% basiliximab, p = 0.009), acute cellular rejection in first year (39.1% alemtuzumab vs 53.4% basiliximab, p < 0.001). The overall survival rate of the patients with alemtuzumab induction was significantly higher than those of the patients with basiliximab induction (5 years survival rate: 64.1% alemtuzumab vs 52.3%, basiliximab, p < 0.001). Multivariate Cox regression analysis confirmed lower 5-year survival for basiliximab induction (HR = 1.41, p = 0.02), recipient cytomegalovirus positive (HR = 1.49, p = 0.01), postoperative hepatic dysfunction (HR = 2.20, p < 0.001), and acute kidney injury requiring renal replacement therapy (HR = 2.27, p < 0.001).

Conclusions

In this single center retrospective review, there was a significant difference in survival rates between induction strategies. This outcome may be attributable to differences in recipient characteristics between the groups. However, the Alemtuzumab group experienced less episodes of acute cellular rejection within the first year.
The Extended N-Terminal Domain Confers Atypical Chemokine Receptor Properties to CXCR3-B
Authors: D’Uonnolo Giulia , Reynders Nathan , Meyrath Max , Abboud Dayana , Uchański Tomasz , Laeremans Toon , Volkman Brian F. , Janji Bassam , Hanson Julien , Szpakowska Martyna , Chevigné Andy
Published: June 2022

The chemokine receptor CXCR3 plays a critical role in immune cell recruitment and activation. CXCR3 exists as two main isoforms, CXCR3-A and CXCR3-B, resulting from alternative splicing. Although the two isoforms differ only by the presence of an N-terminal extension in CXCR3-B, they have been attributed divergent functional effects on cell migration and proliferation. CXCR3-B is the more enigmatic isoform and the mechanisms underlying its function and signaling remain elusive. We therefore undertook an in-depth cellular and molecular comparative study of CXCR3-A and CXCR3-B, investigating their activation at different levels of the signaling cascades, including G protein coupling, β-arrestin recruitment and modulation of secondary messengers as well as their downstream gene response elements. We also compared the subcellular localization of the two isoforms and their trafficking under resting and stimulated conditions along with their ability to internalize CXCR3-related chemokines. Here, we show that the N-terminal extension of CXCR3-B drastically affects receptor features, modifying its cellular localization and preventing G protein coupling, while preserving β-arrestin recruitment and chemokine uptake capacities. Moreover, we demonstrate that gradual truncation of the N terminus leads to progressive recovery of surface expression and G protein coupling. Our study clarifies the molecular basis underlying the divergent effects of CXCR3 isoforms, and emphasizes the β-arrestin-bias and the atypical nature of CXCR3-B.
Untangling the Knots of Regulatory T Cell Therapy in Solid Organ Transplantation
Authors: Orozco Gabriel , Gupta Meera , Gedaly Roberto , Marti Francesc
Published: June 2022

Numerous preclinical studies have provided solid evidence supporting adoptive transfer of regulatory T cells (Tregs) to induce organ tolerance. As a result, there are 7 currently active Treg cell-based clinical trials in solid organ transplantation worldwide, all of which are early phase I or phase I/II trials. Although the results of these trials are optimistic and support both safety and feasibility, many experimental and clinical unanswered questions are slowing the progression of this new therapeutic alternative. In this review, we bring to the forefront the major challenges that Treg cell transplant investigators are currently facing, including the phenotypic and functional diversity of Treg cells, lineage stability, non-standardizedex vivoTreg cell manufacturing process, adequacy of administration route, inability of monitoring and tracking infused cells, and lack of biomarkers or validated surrogate endpoints of efficacy in clinical trials. With this plethora of interrogation marks, we are at a challenging and exciting crossroad where properly addressing these questions will determine the successful implementation of Treg cell-based immunotherapy in clinical transplantation.
Case Report: Immune Checkpoint Blockade Plus Interferon-Γ Add-On Antifungal Therapy in the Treatment of Refractory Covid-Associated Pulmonary Aspergillosis and Cerebral Mucormycosis
Authors: Serris Alexandra , Ouedrani Amani , Uhel Fabrice , Gazzano Marianne , Bedarida Vincent , Rouzaud Claire , Bougnoux Marie-Elisabeth , Raphalen Jean-Herlé , Poirée Sylvain , Lambotte Olivier , Martin-Blondel Guillaume , Lanternier Fanny
Published: June 2022

Invasive fungal diseases (IFD) still cause substantial morbidity and mortality, and new therapeutic approaches are urgently needed. Recent data suggest a benefit of checkpoint inhibitors (ICI). We report the case of a diabetic patient with refractory IFD following a SARSCoV-2 infection treated by ICI and interferon-gamma associated with antifungal treatment.
Plankton Metabolism in Coastal Waters of the Guangdong-Hong Kong-Macao Greater Bay: Regional Variance and Driving Factors
Authors: Zhang Liangkui , Li Gang , Xiang Chenhui , Huang Yadong , Fu Xiaoming , Zheng Chuanyang , Wang Zheng , Ouyang Zhiyuan , Song Xingyu
Published: June 2022

Metabolisms of field plankton community, including gross primary production (GPP), community respiration (CR), and net community production (NCP), usually indicate the status of the health, resource production, and carbon budget of marine ecosystems. In this study, we explored the regional variance and driving forces of plankton metabolism in coastal waters of the Guangdong-Hong Kong-Macao Greater Bay Area (GGBA), a fast-developed area with complex hydrological and environmental states. The results showed that the maximum GPP and CR occurred in the estuarine plume of the GGBA in summer, while in winter the more active metabolisms of plankton community occurred in the Daya Bay, with the GPP and CR being respectively mediated by the nutrient level and temperature. Moreover, four regional zones were divided on the base of the environments and biological factors in surface water of the GGBA i.e., the river-runoff zone, river-plume zone, nearshore and far-offshore zones. The metabolic states in these zones varied significantly due to the regional and seasonal variations of, for example, the nutrient level, temperature, and turbidity driven by multiple factors including land-derived runoffs, anthropogenic activities, the Yuedong Coastal Current, and offshore seawater-intrusions. On the whole, the GGBA areas exhibited the weak heterotrophic processes in both summer (NCP = -24.9 ± 26.7 mg C m-3 d-1) and winter (NCP = -51.2 ± 8.51 mg C m -3 d-1). In addition, we found that the higher CR occurred to the bottom layers of the river plume and nearshore zones wherein hypoxia happened, indicating a possible attribution of plankton community respiration to the hypoxia in the GGBA.
The Contents of Some Trace Elements (As, Br, Cu, Hg, Se, and Zn) in Mytilus galloprovincialis Mussels From Agigea Port, Romania
Authors: Bucşe Andra , Pârvulescu Oana Cristina , Vasiliu Dan , Mureșan Mihaela
Published: June 2022

This study aimed at assessing the accumulation of some trace elements (arsenic, bromine, copper, mercury, selenium, and zinc) in the soft tissue of Mediterranean mussels (Mytilus galloprovincialis) from the Black Sea, near Agigea Port. The mussel samples were collected on a monthly basis between February and June 2019 from two stations located in front of the Danube–Black Sea Canal lock, along the two artificial dikes. The mussels (260 samples) were divided into three classes according to their length: A (3−5.9 cm), B (6−8.9 cm), and C (9−12 cm). The concentrations (dry basis) of As (12.5 ± 3.0 mg/kg), Br (173.6 ± 53.9 mg/kg), Cu (11.2 ± 2.5 mg/kg), Hg (0.02 ± 0.02 mg/kg), Se (2.9 ± 1.1 mg/kg), and Zn (179.5 ± 2.5 mg/kg) were determined using spectrometric techniques. The mean daily values of the physicochemical parameters of seawater (temperature, salinity, pH, chlorophyll a content, and dissolved oxygen content) within the study area were reported. Higher element concentrations were generally found for mussels from size classes A and B compared with those of the larger and older mussels from class C. Principal component analysis (PCA) suggested that the phytoplankton represented an important source of As and Br for the smaller mussels collected in February (when the levels of seawater temperature were lower and those of pH and salinity higher) compared to the larger mussels collected in June. Moreover, the multivariate analysis suggested that Cu, Se, Zn, and Br originated from similar anthropogenic sources and their higher concentrations reported in February and June were obtained at lower levels of seawater salinity. The contents of Cu, Zn, Se, As, and Hg in the mussel soft tissue were lower than the maximum permissible levels.
Community Interaction Co-limitation: Nutrient Limitation in a Marine Microbial Community Context
Authors: Bannon Catherine , Rapp Insa , Bertrand Erin M.
Published: June 2022

The simultaneous limitation of productivity by two or more nutrients, commonly referred to as nutrient co-limitation, affects microbial communities throughout the marine environment and is of profound importance because of its impacts on various biogeochemical cycles. Multiple types of co-limitation have been described, enabling distinctions based on the hypothesized mechanisms of co-limitation at a biochemical level. These definitions usually pertain to individuals and do not explicitly, or even implicitly, consider complex ecological dynamics found within a microbial community. However, limiting and co-limiting nutrients can be produced in situ by a subset of microbial community members, suggesting that interactions within communities can underpin co-limitation. To address this, we propose a new category of nutrient co-limitation, community interaction co-limitation (CIC). During CIC, one part of the community is limited by one nutrient, which results in the insufficient production or transformation of a biologically produced nutrient that is required by another part of the community, often primary producers. Using cobalamin (vitamin B12) and nitrogen fixation as our models, we outline three different ways CIC can arise based on current literature and discuss CIC’s role in biogeochemical cycles. Accounting for the inherent and complex roles microbial community interactions play in generating this type of co-limitation requires an expanded toolset – beyond the traditional approaches used to identify and study other types of co-limitation. We propose incorporating processes and theories well-known in microbial ecology and evolution to provide meaningful insight into the controls of community-based feedback loops and mechanisms that give rise to CIC in the environment. Finally, we highlight the data gaps that limit our understanding of CIC mechanisms and suggest methods to overcome these and further identify causes and consequences of CIC. By providing this framework for understanding and identifying CIC, we enable systematic examination of the impacts this co-limitation can have on current and future marine biogeochemical processes.
Metagenomic Analysis Revealed Differences in Composition and Function Between Liquid-Associated and Solid-Associated Microorganisms of Sheep Rumen
Authors: Su Manchun , Hao Ziyun , Shi Huibin , Li Taotao , Wang Huihui , Li Qiao , Zhang Yong , Ma Youji
Published: June 2022

The rumen microbiota plays a key role in the utilization of plant materials by ruminants, yet little is known about the key taxa and their genetic functions of the rumen sub-environment involved in the ruminal degradation process. Understanding the differences in the composition and function of ruminal microbiota in the liquid-associated (LA) and solid-associated (SA) systems is needed to further study and regulate rumen function and health. In this study, rumen contents of nine sheep were collected to separate LA and SA systems with elution and centrifugal precipitation. Metagenome sequencing was used to investigate the differences in microbial composition and genetic functions of LA and SA systems, with special emphasis on their degradational potential toward carbohydrates. Results showed that the dominant species composition was similar between the two systems, but SA microorganisms had a higher relative abundance than LA microorganisms in all taxa. The concentration of fiber-degrading bacteria, such as Ruminococcus, Treponema, and Fibrobacter, was higher and Prevotella was lower in the SA vs. LA system. Additionally, SA microorganisms dominated in cellulose degradation, while LA microorganisms were more important in starch utilization based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO)'s functional categories and Carbohydrate-Active Enzymes (CAZymes). In general, SA microorganisms are more abundant and important in metabolic functions than LA, such as carbohydrate and amino acid metabolisms. In summary, the key differential biomarkers between LA and SA systems were Prevotella, Ruminococcus, Treponema, and Fibrobacter. Ruminal microbes degraded carbohydrates synergistically with SA, thus, more focusing on cellulose and hemicellulose, while LA is more important to starch.
Electrochemical and Microbial Dissection of Electrified Biotrickling Filters
Authors: Korth Benjamin , Pous Narcís , Hönig Richard , Haus Philip , Corrêa Felipe Borim , Nunes da Rocha Ulisses , Puig Sebastià , Harnisch Falk
Published: June 2022

Electrified biotrickling filters represent sustainable microbial electrochemical technology for treating organic carbon-deficient ammonium-contaminated waters. However, information on the microbiome of the conductive granule bed cathode remains inexistent. For uncovering this black box and for identifying key process parameters, minimally invasive sampling units were introduced, allowing for the extraction of granules from different reactor layers during reactor operation. Sampled granules were analyzed using cyclic voltammetry and molecular biological tools. Two main redox sites [−288 ± 18 mV and −206 ± 21 mV vs. standard hydrogen electrode (SHE)] related to bioelectrochemical denitrification were identified, exhibiting high activity in a broad pH range (pH 6–10). A genome-centric analysis revealed a complex nitrogen food web and the presence of typical denitrifiers like Pseudomonas nitroreducens and Paracoccus versutus with none of these species being identified as electroactive microorganism so far. These are the first results to provide insights into microbial structure-function relationships within electrified biotrickling filters and underline the robustness and application potential of bioelectrochemical denitrification for environmental remediation.
A Phage Receptor-Binding Protein as a Promising Tool for the Detection of Escherichia coli in Human Specimens
Authors: Costa Susana P. , Cunha Alexandra P. , Freitas Paulo P. , Carvalho Carla M.
Published: June 2022

Escherichia coli is a problematic pathogen that causes life-threatening diseases, being a frequent causative agent of several nosocomial infections such as urinary tract and bloodstream infections. Proper and rapid bacterial identification is critical for allowing prompt and targeted antimicrobial therapy. (Bacterio)phage receptor-binding proteins (RBPs) display high specificity for bacterial surface epitopes and, therefore, are particularly attractive as biorecognition elements, potentially conferring high sensitivity and specificity in bacterial detection. In this study, we elucidated, for the first time, the potential of a recombinant RBP (Gp17) to recognize E. coli at different viability states, such as viable but not culturable cells, which are not detected by conventional techniques. Moreover, by using a diagnostic method in which we combined magnetic and spectrofluorimetric approaches, we demonstrated the ability of Gp17 to specifically detect E. coli in various human specimens (e.g., whole blood, feces, urine, and saliva) in about 1.5 h, without requiring complex sample processing.
Effects of Probiotics at the Interface of Metabolism and Immunity to Prevent Colorectal Cancer-Associated Gut Inflammation: A Systematic Network and Meta-Analysis With Molecular Docking Studies
Authors: Patra Sinjini , Sahu Nilanjan , Saxena Shivam , Pradhan Biswaranjan , Nayak Saroj Kumar , Roychowdhury Anasuya
Published: June 2022

Background

Dysbiosis/imbalance in the gut microbial composition triggers chronic inflammation and promotes colorectal cancer (CRC). Modulation of the gut microbiome by the administration of probiotics is a promising strategy to reduce carcinogenic inflammation. However, the mechanism remains unclear.

Methods

In this study, we presented a systematic network, meta-analysis, and molecular docking studies to determine the plausible mechanism of probiotic intervention in diminishing CRC-causing inflammations.

Results

We selected 77 clinical, preclinical, in vitro, and in vivo articles (PRISMA guidelines) and identified 36 probiotics and 135 training genes connected to patients with CRC with probiotic application. The meta-analysis rationalizes the application of probiotics in the prevention and treatment of CRC. An association network is generated with 540 nodes and 1,423 edges. MCODE cluster analysis identifies 43 densely interconnected modules from the network. Gene ontology (GO) and pathway enrichment analysis of the top scoring and functionally significant modules reveal stress-induced metabolic pathways (JNK, MAPK), immunomodulatory pathways, intrinsic apoptotic pathways, and autophagy as contributors for CRC where probiotics could offer major benefits. Based on the enrichment analyses, 23 CRC-associated proteins and 7 probiotic-derived bacteriocins were selected for molecular docking studies. Results indicate that the key CRC-associated proteins (e.g., COX-2, CASP9, PI3K, and IL18R) significantly interact with the probiotic-derived bacteriocins (e.g., plantaricin JLA-9, lactococcin A, and lactococcin mmfii). Finally, a model for probiotic intervention to reduce CRC-associated inflammation has been proposed.

Conclusion

Probiotics and/or probiotic-derived bacteriocins could directly interact with CRC-promoting COX2. They could modulate inflammatory NLRP3 and NFkB pathways to reduce CRC-associated inflammation. Probiotics could also activate autophagy and apoptosis by regulating PI3K/AKT and caspase pathways in CRC. In summary, the potential mechanisms of probiotic-mediated CRC prevention include multiple signaling cascades, yet pathways related to metabolism and immunity are the crucial ones.
Plant Interaction Patterns Shape the Soil Microbial Community and Nutrient Cycling in Different Intercropping Scenarios of Aromatic Plant Species
Authors: Sun Yue , Chen Li , Zhang Shiyi , Miao Yantao , Zhang Yan , Li Zhenglin , Zhao Jingya , Yu Lu , Zhang Jie , Qin Xiaoxiao , Yao Yuncong
Published: June 2022

Intercropping systems improve the soil nutrient cycle through microbial community activity and then land productivity. However, their interactions mechanism underlying that the mixed aromatic plant species intercropping regulate the soil microbiome and nutrient cycling on the perennial woody orchard is still uncovered. We designed treatments with 0, 1, and 3 aromatic plant species intercropped in two scenarios of clean tillage (T model, T1, T2, and T4) and natural grass (G model, G1, G2, and G4) in apple orchards, and investigated intercrops effects at the branch growing stage (BGS) and fruit development stage (FDS), respectively. Compared with T model, G model in FDS increased alpha diversity of bacterial community and Shannon index fungal community, the relative abundance of dominant taxa, such as Acidobacteria and Actinobacteria, and also the numbers of up and down-regulated OTUs, the most of indices of co-occurrence network in both bacterial and fungal community, and then improved invertase activity and available nitrogen content. Relative to G1, G2 and G4 reduced diversity bacterial community in FDS, the relative abundance of dominant taxa, the most of indices of co-occurrence network, and then improved soil invertase activity and total phosphorus content in soil. Moreover, Shannon index of fungal community, the altered number of OTUs and the most indices of co-occurrence network were higher in G4 than those in G2 in FDS. These changes above in FDS were more markedly than those in BGS, suggesting that chemical diversity of litter from mixed species of aromatic plants in natural grass scenario led to diversity, complexity, and stability of soil microbial community and then nutrient cycling. It provided a novel highlight and method to modulate biocenosis and then improve the soil nutrient cycling.
Cronobacter spp. in Commercial Powdered Infant Formula Collected From Nine Provinces in China: Prevalence, Genotype, Biofilm Formation, and Antibiotic Susceptibility
Authors: Fei Peng , Jing He , Ma Yan , Dong Gege , Chang Yunhe , Meng Zhaoxu , Jiang Shilong , Xie Qinggang , Li Shuzhen , Chen Xi , Yang Weiwei
Published: June 2022

The purpose of this study was to investigate the prevalence of Cronobacter spp. in commercial powdered infant formula (PIF) from nine provinces in China from March 2018 to September 2020, and to reveal the genotype, biofilm-forming ability, and antibiotic susceptibility of these isolates. A total of 27 Cronobacter strains, consisting of 22 Cronobacter sakazakii strains, 3 Cronobacter malonaticus strains, 1 Cronobacter turicensis strain, and 1 Cronobacter dublinensis strain, were isolated from 3,600 commercial PIF samples with a prevalence rate of 0.75%. Compared with the other 8 provinces, PIF from Shaanxi province had a higher prevalence rate (1.25%) of Cronobacter spp. These isolates were divided into 14 sequence types (STs), and 6 Cronobacter serotypes. The main Cronobacter STs were ST4, ST1, and ST64, and the dominant Cronobacter serotype was C. sakazakii serotype O2. Approximately 88.89% of Cronobacter isolates had a strong ability (OD595 > 1) to form biofilms on tinplate, among which the strains with ST4 were more dominant. All isolates were susceptible to ampicillin-sulbactam, ceftriaxone, cefotaxime, sulfadiazine, sulfadoxine, trimethoprim-sulfamethoxazole, gentamicin, tetracycline, ciprofloxacin, and colistin, while 55.56 and 96.30% isolates were resistant to cephalothin and vancomycin, respectively. Taken together, our findings highlighted the contamination status and characterization of Cronobacter spp. in commercial PIF from nine provinces of China, and provided guidance for the effective prevention and control of this pathogen in the production of PIF.
Application Potential of Baijiu Non-Saccharomyces Yeast in Winemaking Through Sequential Fermentation With Saccharomyces cerevisiae
Authors: Li Rui-Rui , Xu Meng , Zheng Jia , Liu Yan-Jun , Sun Chun-Hong , Wang Huan , Guo Xue-Wu , Xiao Dong-Guang , Wu Xiao-Le , Chen Ye-Fu
Published: June 2022

To explore the potential application of non-Saccharomyces yeasts screened from Baijiu fermentation environment in winemaking, the effect of four Baijiu non-Saccharomyces yeasts (two Zygosaccharomyces bailii and two Pichia kudriavzevii) sequentially fermented with Saccharomyces cerevisiae on the physicochemical parameters and volatile compounds of wine was analyzed. The results indicated that there was no obvious antagonism between S. cerevisiae and Z. bailli or P. kudriavzevii in sequential fermentations, and all strains could be detected at the end of alcoholic fermentation. Compare with S. cerevisiae pure fermentation, Z. bailii/S. cerevisiae sequential fermentations significantly reduced higher alcohols, fatty acids, and ethyl esters and increased acetate esters; P. kudriavzevii/S. cerevisiae sequential fermentations reduced the contents of C6 alcohols, total higher alcohols, fatty acids, and ethyl esters and significantly increased the contents of acetate esters (especially ethyl acetate and 3-methylbutyl acetate). Sequential fermentation of Baijiu non-Saccharomyces yeast and S. cerevisiae improved the flavor and quality of wine due to the higher ester content and lower concentration of higher alcohols and fatty acids, non-Saccharomyces yeasts selected from Baijiu fermentation environment have potential applications in winemaking, which could provide a new strategy to improve wine flavor and quality.
Trends on Microalgae-Fungi Consortia Research: An Alternative for Biofuel Production?
Authors: Lobo-Moreira Ana Beatriz , Xavier-Santos Solange , Damacena-Silva Luciana , Caramori Samantha Salomão
Published: June 2022

The utilization of microalgae and fungi on an industrial scale is a challenge for researchers. Based on the question “how fungi have contributed to microalgae research?,” we verified the scientific trends on microalgae-fungi consortia focused on biofuels production by searching for articles on the Web of Science and Scopus databases through the terms “microalgae*” or phytoplankton and “fung*.” We found 1,452 articles published between 1950 and 2020; since 2006, the publication numbers have increased rapidly. The articles were published in 12 languages, but most were written in English (96.3%). Among 72 countries, China (360 articles), USA (344), and Germany (155) led the publication rank. Among the 10 most-prolific authors, 8 were Chinese, like 5 of the most-productive institutions, whereas the National Cheng Kung University was on the top of the list. The sources that published the most on the subject were: Bioresource Technology (96), PLoS ONE (28), and Science of the Total Environment (26). The keyword analysis emphasized the magnitude of applications in microalgae-fungi consortia research. Confirming this research question, biofuels appeared as a research trend, especially biodiesel, biogas, and related terms like lipid, lipid accumulation, anaerobic digestion, and biogas upgrading. For 70 years, articles have been published, where China and the United States seem to dominate the research scenario, and biodiesel is the main biofuel derived from this consortium. However, microalgae-based biofuel biorefinery is still a bottleneck on an industrial scale. Recent environmental challenges, such as greenhouse gas mitigation, can be a promising field for that microalgae-fungi application.
Antimicrobial Peptide Analogs From Scorpions: Modifications and Structure-Activity
Authors: Amorim-Carmo Bruno , Parente Adriana M. S. , Souza Eden S. , Silva-Junior Arnóbio A. , Araújo Renata M. , Fernandes-Pedrosa Matheus F.
Published: June 2022

The rapid development of multidrug-resistant pathogens against conventional antibiotics is a global public health problem. The irrational use of antibiotics has promoted therapeutic limitations against different infections, making research of new molecules that can be applied to treat infections necessary. Antimicrobial peptides (AMPs) are a class of promising antibiotic molecules as they present broad action spectrum, potent activity, and do not easily induce resistance. Several AMPs from scorpion venoms have been described as a potential source for the development of new drugs; however, some limitations to their application are also observed. Here, we describe strategies used in several approaches to optimize scorpion AMPs, addressing their primary sequence, biotechnological potential, and characteristics that should be considered when developing an AMP derived from scorpion venoms. In addition, this review may contribute towards improving the understanding of rationally designing new molecules, targeting functional AMPs that may have a therapeutic application.
Decreased Cerebral Blood Flow and Delayed Arterial Transit Are Independently Associated With White Matter Hyperintensity
Authors: Zhang Ruiting , Huang Peiyu , Wang Shuyue , Jiaerken Yeerfan , Hong Hui , Zhang Yao , Yu Xinfeng , Lou Min , Zhang Minming
Published: June 2022

Aim

White matter hyperintensities (WMH) and lacunes were important features of cerebral small vessel disease (CSVD), which contributes to 25% of ischemic strokes and 45% of dementias. Currently, the underlying mechanisms of WMH and lacunes are not clear, and the role of hemodynamic changes is not fully investigated. In this study, we aimed to measure the cerebral blood flow (CBF) and arterial transit in CSVD patients and to investigate their association with WMH and lacunes.

Methods

We retrospectively analyzed the prospectively collected database of CSVD patients. Ninety-two CSVD patients with complete imaging data were included. We used arterial spin labeling (ASL) with post-labeling delay time (PLD) of 1,525 ms and 2,025 ms to measure CBF respectively, and the difference between CBFPLD1.5 and CBFPLD2.0 was recorded as δCBF. We performed regression analysis to understand the contribution of CBF, δCBF to CSVD imaging markers.

Results

We found that CBF derived from both PLDs was associated with WMH volume and the presence of lacune. CBFPLD1.5 was significantly lower than CBFPLD2.0 in CSVD patients, and δCBF was correlated with WMH volume but not the presence of lacune. Furthermore, CBFPLD2.0 and δCBF were both associated with WMH in multiple regression analyses, suggesting an independent effect of delayed arterial transit. On an exploratory basis, we also investigated the relationship between venous disruption on δCBF, and we found that δCBF correlated with deep medullary veins score.

Conclusion

Both CBF and arterial transit were associated with WMH. ASL with multiple PLDs could provide additional hemodynamic information to CSVD-related studies.
Association Between Physical Activity Intensity and the Risk for Depression Among Adults From the National Health and Nutrition Examination Survey 2007–2018
Authors: Yang Donghui , Yang Ming , Bai Jianjun , Ma Yudiyang , Yu Chuanhua
Published: June 2022

Objective

Whether vigorous physical activities (VPA) bring additional benefits to depression prevention in comparison with moderate physical activity (MPA) remains unclear. The aim of this study was to find the correlation between the proportion of VPA to moderate-to-VPA (MVPA) (a combination of VPA and MPA) and the risk for depression, as well as to explore whether correlations differ among subgroups separated by age and sex.

Methods

The data originating from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 were applied. The total amount of PA per week was obtained by multiplying frequency and duration. The proportion of VPA to MVPA was obtained among the participants who performed any MVPA. Depression was set for those who scored 10 and above in the Patient Health Questionnaire-9 (PHQ-9). The odds ratios (ORs) and 95% confidence intervals (95% CIs) for depression were evaluated using logistic regression.

Results

Among 26,849 participants of this study, only 12,939 adults were found with any MVPA, in which 748 participants with depression were detected. Logistic regression was conducted among 12,939 participants. The participants with higher than 66.7–100% of MVPA as VPA were inversely correlated with a 30% (OR = 0.70, 95% CI = 0.50, 0.99) lower risk for depression. The subgroup analyses revealed that significant correlations were only found in men and those aged 45 years and above.

Conclusion

This study suggested that a higher proportion of VPA to MVPA might be correlated with a lower risk for depression in men and those aged 45 years and above. Besides the recommendation, adults should perform 150 min MVPA per week, more time should be spent in performing VPA in MVPA among men and older adults.
Physical Exercise-Induced Astrocytic Neuroprotection and Cognitive Improvement Through Primary Cilia and Mitogen-Activated Protein Kinases Pathway in Rats With Chronic Cerebral Hypoperfusion
Authors: Cao Wenyue , Lin Junbin , Xiang Wei , Liu Jingying , Wang Biru , Liao Weijing , Jiang Ting
Published: June 2022

Chronic cerebral hypoperfusion (CCH) is closely related to vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). The neuroinflammation involving astrocytes is an important pathogenic mechanism. Along with the advancement of the concept and technology of astrocytic biology, the astrocytes have been increasingly regarded as the key contributors to neurological diseases. It is well known that physical exercise can improve cognitive function. As a safe and effective non-drug treatment, physical exercise has attracted continuous interests in neurological research. In this study, we explored the effects of physical exercise on the response of reactive astrocytes, and its role and mechanism in CCH-induced cognitive impairment. A rat CCH model was established by 2 vessel occlusion (2VO) and the wheel running exercise was used as the intervention. The cognitive function of rats was evaluated by morris water maze and novel object recognition test. The phenotypic polarization and the primary cilia expression of astrocytes were detected by immunofluorescence staining. The activation of MAPKs cascades, including ERK, JNK, and P38 signaling pathways, were detected by western blot. The results showed that physical exercise improved cognitive function of rats 2 months after 2VO, reduced the number of C3/GFAP-positive neurotoxic astrocytes, promoted the expression of S100A10/GFAP-positive neuroprotective astrocytes, and enhanced primary ciliogenesis. Additionally, physical exercise also alleviated the phosphorylation of ERK and JNK proteins induced by CCH. These results indicate that physical exercise can improve the cognitive function of rats with CCH possible by promoting primary ciliogenesis and neuroprotective function of astrocytes. The MAPKs signaling cascade, especially ERK and JNK signaling pathways may be involved in this process.
Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction
Authors: Fan Xing , Xia Liye , Zhou Zheng , Qiu Yanyan , Zhao Chenhao , Yin Xiaomin , Qian Wei
Published: June 2022

Alzheimer's disease (AD) is characterized by two pathological features: neurofibrillary tangles (NFTs), formed by microtubule-associated protein tau, and abnormal accumulation of amyloid-β (Aβ). Multiple evidence placed synaptic tau as the vital fact of AD pathology, especially at the very early stage of AD. In the present review, we discuss tau phosphorylation, which is critical for the dendritic localization of tau and synaptic plasticity. We review the related kinases and phosphatases implicated in the synaptic function of tau. We also review the synergistic effects of these kinases and phosphatases on tau-associated synaptic deficits. We aim to open a new perspective on the treatment of AD.
Sepsis-Associated Encephalopathy: A Mini-Review of Inflammation in the Brain and Body
Authors: Ito Hiroshi , Hosomi Sanae , Koyama Yoshihisa , Matsumoto Hisatake , Imamura Yukio , Ogura Hiroshi , Oda Jun
Published: June 2022

Sepsis is defined as a life-threatening multi-organ dysfunction triggered by an uncontrolled host response to infectious disease. Systemic inflammation elicited by sepsis can cause acute cerebral dysfunction, characterized by delirium, coma, and cognitive dysfunction, known as septic encephalopathy. Recent evidence has reported the underlying mechanisms of sepsis. However, the reasons for the development of inflammation and degeneration in some brain regions and the persistence of neuroinflammation remain unclear. This mini-review describes the pathophysiology of region-specific inflammation after sepsis-associated encephalopathy (SAE), clinical features, and future prospects for SAE treatment. The hippocampus is highly susceptible to inflammation, and studies that perform treatments with antibodies to cytokine receptors, such as interleukin-1β, are in progress. Future development of clinically applicable therapies is expected.
The Detection of Invisible Abnormal Metabolism in the FDG-PET Images of Patients With Anti-LGI1 Encephalitis by Machine Learning
Authors: Pan Jian , Lv Ruijuan , Zhou Guifei , Si Run , Wang Qun , Zhao Xiaobin , Liu Jiangang , Ai Lin
Published: June 2022

Objective

This study aims to detect the invisible metabolic abnormality in PET images of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis using a multivariate cross-classification method.

Methods

Participants were divided into two groups, namely, the training cohort and the testing cohort. The training cohort included 17 healthy participants and 17 patients with anti-LGI1 encephalitis whose metabolic abnormality was able to be visibly detected in both the medial temporal lobe and the basal ganglia in their PET images [completely detectable (CD) patients]. The testing cohort included another 16 healthy participants and 16 patients with anti-LGI1 encephalitis whose metabolic abnormality was not able to be visibly detected in the medial temporal lobe and the basal ganglia in their PET images [non-completely detectable (non-CD) patients]. Independent component analysis (ICA) was used to extract features and reduce dimensions. A logistic regression model was constructed to identify the non-CD patients.

Results

For the testing cohort, the accuracy of classification was 90.63% with 13 out of 16 non-CD patients identified and all healthy participants distinguished from non-CD patients. The patterns of PET signal changes resulting from metabolic abnormalities related to anti-LGI1 encephalitis were similar for CD patients and non-CD patients.

Conclusion

This study demonstrated that multivariate cross-classification combined with ICA could improve, to some degree, the detection of invisible abnormal metabolism in the PET images of patients with anti-LGI1 encephalitis. More importantly, the invisible metabolic abnormality in the PET images of non-CD patients showed patterns that were similar to those seen in CD patients.
Longitudinal Progression of Essential Tremor: Do Tremor Severity Scores Increase at a Uniform Rate?
Authors: McGurn Margaret M. , Berry Diane S. , Dworkin Jordan D. , Louis Elan D.
Published: June 2022

Background

Few longitudinal studies assess the progression of essential tremor (ET). One unexplored issue is whether tremor severity increases across time at a uniform rate. That is, does the observed rate of change in tremor severity within a particular patient remain constant or vary across time? This question of intra-individual differences is particularly important since it reflects a primary patient concern–will the nature of change I have seen to date be what I can expect in the future?

Methods

ET cases were enrolled in a prospective, longitudinal study. We selected 35 cases and assessed tremor severity via Bain and Findley ratings of Archimedes spirals assigned by a senior movement disorders neurologist. After reviewing both the change in spiral scores and the rate of change in scores, we identified five mutually exclusive patterns of severity change. We calculated the prevalence of each category using two complementary sets of classification criteria.

Results

Length of follow-up was 4.5 to 16.0 years, mean=10.2 years. Mean baseline tremor severity score was 4.6, SD=1.6. Depending upon the classification criteria used, the tremor scores of one-third to one-half of cases did not increase in a uniform fashion but were better described as demonstrating jumps and/or reversals in scores across time.

Conclusions

We document the nature of changes in ET tremor severity scores across a ten-year period via expert ratings of Archimedes spiral drawings. Such natural history data are valuable to patients and clinicians who hope to better understand and predict the likely course of ET symptoms.
Modified Interpretations of the Supine Roll Test in Horizontal Canal BPPV Based on Simulations: How the Initial Position of the Debris in the Canal and the Sequence of Testing Affects the Direction of the Nystagmus and the Diagnosis
Authors: Bhandari Anita , Bhandari Rajneesh , Kingma Herman , Strupp Michael
Published: June 2022

Background and Objectives

The aim of this study was to show with three-dimensional simulations how the diagnostic supine roll test (SRT) is affected by the initial position of the debris within the horizontal canal (hc) and study the nystagmus patterns on changing the sequence of testing and its impact on the diagnosis of the side of involvement in hc-BPPV.

Methods

A 3D dynamic simulation model was developed and applied based on reconstructed MRI images and fluid dynamics. Each semicircular canal was linked to the respective extraocular muscles to visualize nystagmus generated on stimulation of the canal.

Results

The simulations of hc-canalithiasis showed that the nystagmus pattern seen with the SRT is changed by the initial position of the otolith debris within the canal and the sequence of testing. The debris changes position during SRT so that sequential steps do not start at the initial position as previously assumed. The sequence of performing the SRT steps from the right or left side influences the nystagmus pattern generated: bilateral direction-changing, bilateral direction-fixed, and unilateral nystagmus can be seen in different test conditions. The SRT itself may even reposition the debris out of the canal.

Conclusions and Clinical Implications

Simulations provide a dynamic tool to study the diagnostic SRT in hc-canalithiasis. Starting the SRT from right or left has a major impact on the test outcome (unlike the Dix-Hallpike maneuver). The findings provide a new interpretation for the results of the SRT. The simulations explain the phenomenon of direction-fixed nystagmus as a logical consequence of starting the SRT with the head turned toward the non-affected side in hc-canalithiasis with debris in the ampullary arm. They also show that unilateral nystagmus seen on SRT indicates canalithiasis of the non-ampullary arm of the side opposite to the side of nystagmus. The generation of bilateral direction-changing, bilateral direction-fixed, and unilateral nystagmus can be the cause of misdiagnoses in terms of the affected side and underlying mechanisms. Finally, a recommendation for a standardized protocol for the sequence of positional tests should be established to ensure uniform interpretation of test results.
ALS/FTD: Evolution, Aging, and Cellular Metabolic Exhaustion
Authors: Henderson Robert David , Kepp Kasper Planeta , Eisen Andrew
Published: June 2022

Amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) are neurodegenerations with evolutionary underpinnings, expansive clinical presentations, and multiple genetic risk factors involving a complex network of pathways. This perspective considers the complex cellular pathology of aging motoneuronal and frontal/prefrontal cortical networks in the context of evolutionary, clinical, and biochemical features of the disease. We emphasize the importance of evolution in the development of the higher cortical function, within the influence of increasing lifespan. Particularly, the role of aging on the metabolic competence of delicately optimized neurons, age-related increased proteostatic costs, and specific genetic risk factors that gradually reduce the energy available for neuronal function leading to neuronal failure and disease.
Improving Technology to Diagnose Tuberculous Meningitis: Are We There Yet?
Authors: Ssebambulidde Kenneth , Gakuru Jane , Ellis Jayne , Cresswell Fiona V. , Bahr Nathan C.
Published: June 2022

Diagnosis of tuberculous meningitis (TBM) remains challenging due to a paucity of high-performance diagnostics. Even those that have reasonable sensitivity are not adequate to ‘rule out' TBM. Therefore, a combination of clinical factors alongside microbiological, molecular, and radiological investigations are utilized, depending on availability. A low threshold for starting empiric therapy in the appropriate clinical scenario remains crucial for good outcomes in many cases. Herein, we review the current TBM diagnostics landscape with a focus on limitations frequently encountered, such as diagnostic test performance, cost, laboratory infrastructure, and clinical expertise. Though molecular technologies, particularly GeneXpert MTB/Rif Ultra, have been a step forward, diagnosis of TBM remains difficult. We also provide an overview of promising technologies, such as cerebrospinal fluid (CSF) lactate, a new lipoarabinomannan test (FujiLAM), metagenomic next-generation sequencing, and transcriptomics that may further improve our TBM diagnostic capacity and lead to better outcomes.