bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific IgE and IgG4 Profiles of House Dust Mite Components in Allergen-Specific Immunotherapy
Authors: Yang Lin , Yang Yaqi , Xu Qingxiu , Zhang Wei , Jiang Qing , Li Wenjing , Wang Yin , Ma Dongxia , Lin Xiaomin , Sun Baoqing , Zhu Rongfei
Published: February 2022

Background

Allergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production. However, the longitudinal data of sIgE and sIgG4 to allergen components during AIT are limited.

Objective

We sought to investigate the persistence and evolution of sIgE and sIgG4 against house dust mite (HDM) components during AIT and explore their correlation with clinical responses.

Methods

Sixty allergic rhinitis (AR) with/without asthma patients receiving AIT for HDM were enrolled in AIT group. Thirty AR patients without receiving AIT served as control group. Blood samples were collected for sIgE, sIgG4 to HDM components (Derp 1, Derf 1, Derp 2, Derf 2, Derp 7, Derp 10, Derp 21 and Derp 23) assay at baseline, Month 6 and Month 18 of AIT. Combined symptom and medication scores (CSMS) were obtained accordingly.

Results

In the AIT group, sIgG4 to the HDM components of Derp 1, Derf 1, Derp 2 and Derf 2, Derp 21 significantly increased at Month 18 compared to the baseline (36.2 UA/mL vs 158.8 UA/mL, 46.4 UA/mL vs 94.6 UA/mL, 80.5 UA/mL vs 152.3 UA/mL, 78.3 UA/mL vs 205.1 UA/mL, 42.3 UA/mL vs 59.3 UA/mL, all p<0.05), sIgE to HDM components didn’t see differences at baseline and at Month 18 (all p>0.05).The numbers of positive HDM component sIgE and sIgG4 increased from 4.5 to 5 and 0 to 1.5 respectively (both p<0.05). However, the changes of sIgE, sIgG4, sIgE/sIgG4 ratio and the numbers of positive HDM components had no correlations with the improvement of CSMS after AIT (all ρ<0.3). For the control group, the sIgE and sIgG4 did not change significantly during the observational period (all p>0.05).

Conclusion

AIT can induce the production of sIgG4 to HDM components. However, the increased sIgG4 levels of HDM component do not correlate with the corresponding sIgE levels at baseline or with AIT response. sIgG4 to HDM components do not qualify as a biomarker to evaluate the efficacy of AIT.
The Emerging Roles of Pellino Family in Pattern Recognition Receptor Signaling
Authors: Zhang E , Li Xia
Published: February 2022

The Pellino family is a novel and well-conserved E3 ubiquitin ligase family and consists of Pellino1, Pellino2, and Pellino3. Each family member exhibits a highly conserved structure providing ubiquitin ligase activity without abrogating cell and structure-specific function. In this review, we mainly summarized the crucial roles of the Pellino family in pattern recognition receptor-related signaling pathways: IL-1R signaling, Toll-like signaling, NOD-like signaling, T-cell and B-cell signaling, and cell death-related TNFR signaling. We also summarized the current information of the Pellino family in tumorigenesis, microRNAs, and other phenotypes. Finally, we discussed the outstanding questions of the Pellino family in immunity.
Tofacitinib Suppresses Natural Killer Cells In Vitro and In Vivo: Implications for Amyotrophic Lateral Sclerosis
Authors: Figueroa-Romero Claudia , Monteagudo Alina , Murdock Benjamin J. , Famie Joshua P. , Webber-Davis Ian F. , Piecuch Caroline E. , Teener Samuel J. , Pacut Crystal , Goutman Stephen A. , Feldman Eva L.
Published: February 2022

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease with few therapeutic options. However, the immune system, including natural killer (NK) cells, is linked to ALS progression and may constitute a viable therapeutic ALS target. Tofacitinib is an FDA-approved immunomodulating small molecule which suppresses immune cell function by blocking proinflammatory cytokine signaling. This includes the cytokine IL-15 which is the primary cytokine associated with NK cell function and proliferation. However, the impact of tofacitinib on NK activation and cytotoxicity has not been thoroughly investigated, particularly in ALS. We therefore tested the ability of tofacitinib to suppress cytotoxicity and cytokine production in an NK cell line and in primary NK cells derived from control and ALS participants. We also investigated whether tofacitinib protected ALS neurons from NK cell cytotoxicity. Finally, we conducted a comprehensive pharmacokinetic study of tofacitinib in mice and tested the feasibility of administration formulated in chow. Success was assessed through the impact of tofacitinib on peripheral NK cell levels in mice. We found tofacitinib suppressed IL-15-induced activation as measured by STAT1 phosphorylation, cytotoxicity, pro-inflammatory gene expression, and pro-inflammatory cytokine secretion in both an NK cell line and primary NK cells. Furthermore, tofacitinib protected ALS neurons from NK cell-mediated cytotoxicity. In mice, we found tofacitinib bioavailability was 37% in both male and female mice; using these data we formulated mouse containing low and high doses of tofacitinib and found that the drug suppressed peripheral NK cell levels in a dose-dependent manner. These results demonstrate that tofacitinib can suppress NK cell function and may be a viable therapeutic strategy for ALS.
Deep Immune Phenotyping and Single-Cell Transcriptomics Allow Identification of Circulating TRM-Like Cells Which Correlate With Liver-Stage Immunity and Vaccine-Induced Protection From Malaria
Authors: Noé Andrés , Datoo Mehreen S. , Flaxman Amy , Husainy Mohammad Ali , Jenkin Daniel , Bellamy Duncan , Makinson Rebecca A. , Morter Richard , Ramos Lopez Fernando , Sheridan Jonathan , Voukantsis Dimitrios , Prasad Naveen , Hill Adrian V. S. , Ewer Katie J. , Spencer Alexandra J.
Published: February 2022

Protection from liver-stage malaria requires high numbers of CD8+ T cells to find and killPlasmodium-infected cells. A new malaria vaccine strategy, prime-target vaccination, involves sequential viral-vectored vaccination by intramuscular and intravenous routes to target cellular immunity to the liver. Liver tissue-resident memory (TRM) CD8+ T cells have been shown to be necessary and sufficient for protection against rodent malaria by this vaccine regimen. Ultimately, to most faithfully assess immunotherapeutic responses by these local, specialised, hepatic T cells, periodic liver sampling is necessary, however this is not feasible at large scales in human trials. Here, as part of a phase I/IIP. falciparumchallenge study of prime-target vaccination, we performed deep immune phenotyping, single-cell RNA-sequencing and kinetics of hepatic fine needle aspirates and peripheral blood samples to study liver CD8+ TRM cells and circulating counterparts. We found that while these peripheral ‘TRM-like’ cells differed to TRM cells in terms of previously described characteristics, they are similar phenotypically and indistinguishable in terms of key T cell residency transcriptional signatures. By exploring the heterogeneity among liver CD8+ TRM cells at single cell resolution we found two main subpopulations that each share expression profiles with blood T cells. Lastly, our work points towards the potential for using TRM−like cells as a correlate of protection by liver-stage malaria vaccines and, in particular, those adopting a prime-target approach. A simple and reproducible correlate of protection would be particularly valuable in trials of liver-stage malaria vaccines as they progress to phase III, large-scale testing in African infants. We provide a blueprint for understanding and monitoring liver TRM cells induced by a prime-target malaria vaccine approach.
Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm
Authors: Chen Siteng , Zhang Encheng , Jiang Liren , Wang Tao , Guo Tuanjie , Gao Feng , Zhang Ning , Wang Xiang , Zheng Junhua
Published: February 2022

It is of great urgency to explore useful prognostic markers and develop a robust prognostic model for patients with clear-cell renal cell carcinoma (ccRCC). Three independent patient cohorts were included in this study. We applied a high-level neural network based on TensorFlow to construct the robust model by using the deep learning algorithm. The deep learning-based model (FB-risk) could perform well in predicting the survival status in the 5-year follow-up, which could also significantly distinguish the patients with high overall survival risk in three independent patient cohorts of ccRCC and a pan-cancer cohort. High FB-risk was found to be partially associated with negative regulation of the immune system. In addition, the novel phenotyping of ccRCC based on the F-box gene family could robustly stratify patients with different survival risks. The different mutation landscapes and immune characteristics were also found among different clusters. Furthermore, the novel phenotyping of ccRCC based on the F-box gene family could perform well in the robust stratification of survival and immune response in ccRCC, which might have potential for application in clinical practices.
Mucosal Vaccination With Recombinant Tm-WAP49 Protein Induces Protective Humoral and Cellular Immunity Against Experimental Trichuriasis in AKR Mice
Authors: Wei Junfei , Hegde Venkatesh L. , Yanamandra Ananta V. , O’Hara Madison P. , Keegan Brian , Jones Kathryn M. , Strych Ulrich , Bottazzi Maria Elena , Zhan Bin , Sastry K. Jagannadha , Hotez Peter J.
Published: February 2022

Trichuriasis is one of the most common neglected tropical diseases of the world’s poorest people. A recombinant vaccine composed ofTm-WAP49, an immunodominant antigen secreted by adultTrichurisstichocytes into the mucosa of the cecum to which the parasite attaches, is under development. The prototype is being evaluated in a mouse model ofTrichuris murisinfection, with the ultimate goal of producing a mucosal vaccine through intranasal delivery. Intranasal immunization of mice withTm-WAP49 formulated with the adjuvant OCH, a truncated analog of alpha-GalCer with adjuvanticity to stimulate natural killer T cells (NKT) and mucosal immunity, induced significantly high levels of IgG and its subclasses (IgG1 and IgG2a) in immunized mice. This also resulted in a significant reduction of worm burden after challenge withT. muris-infective eggs. The addition of QS-21 adjuvant to this vaccine formulation further reduced worm counts. The improved protection from the dual-adjuvanted vaccine correlated with higher serum antibody responses (IgG, IgG1, IgG2a, IgA) as well as with the induction of antigen-specific IgA in the nasal mucosa. It was also associated with the robust cellular responses including functional subsets of CD4 T cells producing IL-4, and cytotoxic CD8 T cells expressing granzyme B. The worm reduction achieved by mucosal immunization was higher than that induced by subcutaneous immunization. Intranasal immunization also induced a significantly higher nasal mucosa-secreted antigen-specific IgA response, as well as higher functional cellular responses including CD4+IL4+(Th1) and CD8+GnzB+(Th2) T cells, and antigen-specific INFγ-producing T cells in both spleen and MLNs and antibody-producing B cells (CD19+B220+/B220+GL7+). Mucosal immunization further induced long-term T lymphocyte memory with increased central (CD62L+CD44+) and effector (CD62L-CD44+) memory subsets of both CD4 and CD8 T cells at 60 days after the last immunization. In summary, intranasal immunization with recombinantTm-WAP49 protein induced strong protection versus murine trichuriasis. It represents a promising vaccination approach against intestinal nematodes.
Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis
Authors: Han Juan-Juan , Wang Xue-Qiang , Zhang Xin-An
Published: February 2022

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that affect synovitis, bone, cartilage, and joint. RA leads to bone and cartilage damage and extra-articular disorders. However, the pathogenesis of RA is still unclear, and the lack of effective early diagnosis and treatment causes severe disability, and ultimately, early death. Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in RA. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, FLS, and PBMC, participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response. Thereby providing new strategies for its diagnosis and treatment. In this review, we comprehensively summarized the regulatory mechanisms of lncRNA/circRNA-miRNA-mRNA network and the potential roles of non-coding RNAs as biomarkers and therapeutic targets for the diagnosis and treatment of RA.
How Much Marsh Restoration Is Enough to Deliver Wave Attenuation Coastal Protection Benefits?
Authors: Castagno Katherine A. , Ganju Neil K. , Beck Michael W. , Bowden Alison A. , Scyphers Steven B.
Published: February 2022

As coastal communities grow more vulnerable to sea-level rise and increased storminess, communities have turned to nature-based solutions to bolster coastal resilience and protection. Marshes have significant wave attenuation properties and can play an important role in coastal protection for many communities. Many restoration projects seek to maximize this ecosystem service but how much marsh restoration is enough to deliver measurable coastal protection benefits is still unknown. This question is critical to guiding assessments of cost effectiveness and for funding, implementation, and optimizing of marsh restoration for risk reduction projects. This study uses SWAN model simulations to determine empirical relationships between wave attenuation and marsh vegetation. The model runs consider several different common marsh morphologies (including systems with channels, ponds, and fringing mudflats), vegetation placement, and simulated storm intensity. Up to a 95% reduction in wave energy is seen at as low as 50% vegetation cover. Although these empirical relationships between vegetative cover and wave attenuation provide essential insight for marsh restoration, it is also important to factor in lifespan estimates of restored marshes when making overall restoration decisions. The results of this study are important for coastal practitioners and managers seeking performance goals and metrics for marsh restoration, enhancement, and creation.
Application of Quick Response Code in Sea Turtle Conservation: Overcoming Limitations of Existing Individual Markers
Authors: Xia Zhongrong , Yu Haoqi , Yang Fan , Liu Xiaofeng , Yu Dongmei , Hu Huijian
Published: February 2022

Hatchery release has been used for the conservation of green turtles for many years. To improve the rescue management of released individuals and avoid their negative impact on wild populations, the application of individual markers is particularly important. Quick response (QR) code was used to tag the individual of released turtles in Huidong Sea Turtle National Nature Reserve, the unique spawning site and nature reserve for sea turtles in China. The viscosity differences of four safe and non-toxic glues (e.g., epoxy resin, acrylic glue, ABS glue, and nail gel 401) in different age groups were tested. The results revealed that epoxy resin glue has the best adhesion effect on 8-year-old turtles, and the intact rate after 50 days was 100%. It is suitable to be used for the rescue of stranded turtles within 50 days of release. Nail gel 401 has the best adhesion effect on the carapace of 1-year-old turtles, with an intact rate of 100% after 50 days, which can be used for short-time conservation of young turtles. The release experiments of 18 eight-year-old sea turtles with passive integrated transponder (PIT) tags, QR codes, and steel tags showed that QR codes are conducive to public participation and improve rescue efficiency. In fact, QR code is a powerful measure to overcome the limitations of the existing individual label. However, the QR code fused with turtle carapace can only be applied for turtle rescue and tracing in the short-term due to its limited persistence.
Modified Long-Axis In-plane Technique for Radial Artery Cannulation in Children: A Randomized Controlled Trial
Authors: Yu Liu , Zhong Heying , Jiang Yan , Zhang Wangping , Liu Zhiwei
Published: February 2022

Background

Radial artery catheterization is a challenge for anesthetists in the pediatric population. The purpose of this study was to determine whether the modified long-axis in-plane (MLAX-IP) technique increased the success rate of radial artery catheterization in children.

Methods

This study involved 80 children who required arterial catheterization and were randomly divided into the MLAX-IP group and dynamic needle tip positioning (DNTP) group (40 cases in each group). Radial artery catheterization was performed using either the MLAX-IP technique or the DNTP technique.

Results

The first-attempt cannulation success rate was higher in the MLAX-IP group than in the DNTP group (95 vs. 80%, P = 0.043). The imaging time of the artery in the MLAX-IP group was longer than in the DNTP group (19.1 ± 3.1 vs. 9.6 ± 2.4 s, P < 0.001). While the total catheterization time was similar between the 2 groups (88.1 ± 23 vs. 86.9 ± 46.1 s, P = 0.475).

Conclusion

The first-attempt cannulation success rate with the MLAX-IP technique is increased, while the total catheterization time is similar between the 2 groups and puncture-related complications are fewer.
The Application of Awake-Prone Positioning Among Non-intubated Patients With COVID-19-Related ARDS: A Narrative Review
Authors: Chen Lingli , Zhang Yan , Li Yi , Song Chao , Lin Fengyu , Pan Pinhua
Published: February 2022

The coronavirus disease (COVID-19) pandemic has significantly increased the number of patients with acute respiratory distress syndrome (ARDS), necessitating respiratory support. This strain on intensive care unit (ICU) resources forces clinicians to limit the use of mechanical ventilation by seeking novel therapeutic strategies. Awake-prone positioning appears to be a safe and tolerable intervention for non-intubated patients with hypoxemic respiratory failure. Meanwhile, several observational studies and meta-analyses have reported the early use of prone positioning in awake patients with COVID-19-related ARDS (C-ARDS) for improving oxygenation levels and preventing ICU transfers. Indeed, some international guidelines have recommended the early application of awake-prone positioning in patients with hypoxemic respiratory failure attributable to C-ARDS. However, its effectiveness in reducing intubation rate, mortality, applied timing, and optimal duration is unclear. High-quality evidence of awake-prone positioning for hypoxemic patients with COVID-19 is still lacking. Therefore, this article provides an update on the current state of published literature about the physiological rationale, effect, timing, duration, and populations that might benefit from awake proning. Moreover, the risks and adverse effects of awake-prone positioning were also investigated. This work will guide future studies and aid clinicians in deciding on better treatment plans.
Contribution of the Gut Microbiota to Intestinal Fibrosis in Crohn's Disease
Authors: Watanabe Daisuke , Kamada Nobuhiko
Published: February 2022

In Crohn's disease (CD), intestinal fibrosis is a critical determinant of a patient's prognosis. Although inflammation may be a prerequisite for the initiation of intestinal fibrosis, research shows that the progression or continuation of intestinal fibrosis can occur independently of inflammation. Thus, once initiated, intestinal fibrosis may persist even if medical treatment controls inflammation. Clearly, an understanding of the pathophysiological mechanisms of intestinal fibrosis is required to diminish its occurrence. Accumulating evidence suggests that the gut microbiota contributes to the pathogenesis of intestinal fibrosis. For example, the presence of antibodies against gut microbes can predict which CD patients will have intestinal complications. In addition, microbial ligands can activate intestinal fibroblasts, thereby inducing the production of extracellular matrix. Moreover, in various animal models, bacterial infection can lead to the development of intestinal fibrosis. In this review, we summarize the current knowledge of the link between intestinal fibrosis in CD and the gut microbiota. We highlight basic science and clinical evidence that the gut microbiota can be causative for intestinal fibrosis in CD and provide valuable information about the animal models used to investigate intestinal fibrosis.
Profiling the Bladder Microbiota in Patients With Bladder Cancer
Authors: Parra-Grande Mónica , Oré-Arce Martín , Martínez-Priego Llúcia , D’Auria Giuseppe , Rosselló-Mora Ramón , Lillo Marta , Sempere Andrea , Lumbreras Blanca , Sánchez-Hellín Victoria
Published: February 2022

Evidence suggests that microbiota may contribute to the pathogenesis of several diseases, including cancer. In the case of bladder cancer, preliminary studies have found alterations in the urinary microbiota of patients with urothelial carcinoma compared with healthy individuals. Conversely, the urinary microbiota differ between men and women, and it has been hypothesized that these differences are associated with the lower incidence of bladder cancers in women. The objective of this study was to characterize the bladder microbiota in paired samples of tumor and non-tumor mucosa of patients with malignant bladder neoplasia using next-generation sequencing. In addition, we aimed to study potential differences in microbial composition in tumor samples according to clinical and pathological variables, and to determine possible microbial profiles. We found significant differences in microbial richness at the genus level, with a higher richness observed in the non-tumor compared with the tumor mucosa. It was also shown that Actinobacteria were significantly more enriched in the non-tumor compared with the tumor mucosa (P = 0.014). In the multivariate analysis, we found significant differences in microbial composition according to tumor grade (P = 0.03 and 0.04 at the phylum and genus levels, respectively). Moreover, we detected a higher microbial richness in non-tumor vs. tumor tissues which agrees with the global assumption that microbial richness is an indicator of health. The greater abundance of members of the Actinobacteria phylum in the non-neoplastic bladder mucosa samples supports the hypothesis that a higher abundance of Actinomycetes is associated with a lower rate of bladder cancer in women and suggests a protective role for these microbiota. We detected a microbial profile that was enriched for Enterococcus in low-grade tumors. Finally, we identified the presence of two clusters in the microbial composition of the tumor mucosa samples, significantly enriched for the genera Barnesiella, Parabacteroides, Prevotella, Alistipes, and Lachnospiracea_incertae_sedis (Cluster 1), or Staphylococcus (Cluster 2). Further longitudinal studies are needed to assess the role of the bladder microbiota in carcinogenesis.
Inhibition of AdeB, AceI, and AmvA Efflux Pumps Restores Chlorhexidine and Benzalkonium Susceptibility in Acinetobacter baumannii ATCC 19606
Authors: Migliaccio Antonella , Esposito Eliana Pia , Bagattini Maria , Berisio Rita , Triassi Maria , De Gregorio Eliana , Zarrilli Raffaele
Published: February 2022

The management of infections caused by Acinetobacter baumannii is hindered by its intrinsic tolerance to a wide variety of biocides. The aim of the study was to analyze the role of different A. baumannii efflux pumps (EPs) in tolerance to chlorhexidine (CHX) and benzalkonium (BZK) and identify non-toxic compounds, which can restore susceptibility to CHX and BZK in A. baumannii. A. baumannii ATCC 19606 strain was tolerant to both CHX and BZK with MIC and MBC value of 32 mg/L. CHX subMIC concentrations increased the expression of adeB and adeJ (RND superfamily), aceI (PACE family) and amvA (MFS superfamily) EP genes. The values of CHX MIC and MBC decreased by eightfold in ΔadeB and twofold in ΔamvA or ΔaceI mutants, respectively, while not affected in ΔadeJ mutant; EPs double and triple deletion mutants showed an additive effect on CHX MIC. CHX susceptibility was restored in double and triple deletion mutants with inactivation of adeB gene. BZK MIC was decreased by fourfold in ΔadeB mutant, and twofold in ΔamvA and ΔaceI mutants, respectively; EPs double and triple deletion mutants showed an additive effect on BZK MIC. BZK susceptibility was recovered in ΔadeB ΔaceI ΔadeJ and ΔamvA ΔadeB ΔadeJ triple mutants. The structural comparison of AdeB and AdeJ protomers showed a more negatively charged entrance binding site and F-loop in AdeB, which may favor the transport of CHX. The carbonyl cyanide m-chlorophenylhydrazine protonophore (CCCP) EP inhibitor reduced dose-dependently CHX MIC in A. baumannii ATCC 19606 and in ΔadeJ, ΔaceI, or ΔamvA mutants, but not in ΔadeB mutant. Either piperine (PIP) or resveratrol (RV) at non-toxic concentrations inhibited CHX MIC in A. baumannii ATCC 19606 parental strain and EPs gene deletion mutants, and CHX-induced EP gene expression. Also, RV inhibited BZK MIC and EP genes expression in A. baumannii ATCC 19606 parental strain and EPs mutants. These results demonstrate that tolerance to CHX and BZK in A. baumannii is mediated by the activation of AdeB, AceI and AmvA EPs, AdeB playing a major role. Importantly, inhibition of EP genes expression by RV restores CHX and BZK susceptibility in A. baumannii.
Bacterial Genes Encoding Resistance Against Antibiotics and Metals in Well-Maintained Drinking Water Distribution Systems in Finland
Authors: Tiwari Ananda , Gomez-Alvarez Vicente , Siponen Sallamaari , Sarekoski Anniina , Hokajärvi Anna-Maria , Kauppinen Ari , Torvinen Eila , Miettinen Ilkka T. , Pitkänen Tarja
Published: February 2022

Information on the co-occurrence of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) among bacterial communities in drinking water distribution systems (DWDSs) is scarce. This study characterized ARGs and MRGs in five well-maintained DWDSs in Finland. The studied DWDSs had different raw water sources and treatment methods. Two of the waterworks employed artificially recharged groundwater (ARGW) and used no disinfection in the treatment process. The other three waterworks (two surface and one groundwater source) used UV light and chlorine during the treatment process. Ten bulk water samples (two from each DWDS) were collected, and environmental DNA was extracted and then sequenced using the Illumina HiSeq platform for high-throughput shotgun metagenome sequencing. A total of 430 ARGs were characterized among all samples with the highest diversity of ARGs identified from samples collected from non-disinfected DWDSs. Furthermore, non-disinfected DWDSs contained the highest diversity of bacterial communities. However, samples from DWDSs using disinfectants contained over double the ratio of ARG reads to 16S rRNA gene reads and most of the MRG (namely mercury and arsenic resistance genes). The total reads and types of ARGs conferring genes associated with antibiotic groups namely multidrug resistance, and bacitracin, beta-lactam, and aminoglycoside and mercury resistance genes increased in waterworks treating surface water with disinfection. The findings of this study contribute toward a comprehensive understanding of ARGs and MRGs in DWDSs. The occurrence of bacteria carrying antibiotic or metal resistance genes in drinking water causes direct exposure to people, and thus, more systematic investigation is needed to decipher the potential effect of these resistomes on human health.
Hypoxia Improves Endurance Performance by Enhancing Short Chain Fatty Acids Production via Gut Microbiota Remodeling
Authors: Huang Li , Li Tianyou , Zhou Min , Deng Mengyan , Zhang Lidong , Yi Long , Zhu Jundong , Zhu Xiaohui , Mi Mantian
Published: February 2022

Hypoxia environment has been widely used to promote exercise capacity. However, the underlying mechanisms still need to be further elucidated. In this study, mice were exposed to the normoxia environment (21% O2) or hypoxia environment (16.4% O2) for 4 weeks. Hypoxia-induced gut microbiota remodeling characterized by the increased abundance of Akkermansia and Bacteroidetes genera, and their related short-chain fatty acids (SCFAs) production. It was observed that hypoxia markedly improved endurance by significantly prolonging the exhaustive running time, promoting mitochondrial biogenesis, and ameliorating exercise fatigue biochemical parameters, including urea nitrogen, creatine kinase, and lactic acid, which were correlated with the concentrations of SCFAs. Additionally, the antibiotics experiment partially inhibited hypoxia-induced mitochondrial synthesis. The microbiota transplantation experiment demonstrated that the enhancement of endurance capacity induced by hypoxia was transferable, indicating that the beneficial effects of hypoxia on exercise performance were partly dependent on the gut microbiota. We further identified that acetate and butyrate, but not propionate, stimulated mitochondrial biogenesis and promoted endurance performance. Our results suggested that hypoxia exposure promoted endurance capacity partially by the increased production of SCFAs derived from gut microbiota remodeling.
Patterns of Relative Bacterial Richness and Community Composition in Seawater and Marine Sediment Are Robust for Both Operational Taxonomic Units and Amplicon Sequence Variants
Authors: Kerrigan Zak , D’Hondt Steven
Published: February 2022

To understand the relative influences of operational taxonomic units (OTUs) and amplicon sequence variants (ASVs) on patterns of marine microbial diversity and community composition, we examined bacterial diversity and community composition of seawater from 12 sites in the North Atlantic Ocean and Canadian Arctic and sediment from two sites in the North Atlantic. For the seawater analyses, we included samples from three to six zones in the water column of each site. For the sediment analyses, we included over 20 sediment horizons at each of two sites. For all samples, we amplified the V4–V5 hypervariable region of the 16S ribosomal RNA (rRNA) gene. We analyzed each sample in two different ways: (i) by clustering its reads into 97%-similar OTUs and (ii) by assigning sequences to unique ASVs. OTU richness is much higher than ASV richness for every sample, but both OTUs and ASVs exhibit similar vertical patterns of relative diversity in both the water column and the sediment. Bacterial richness is highest just below the photic zone in the water column and at the seafloor in the sediment. For both OTUs and ASVs, richness estimates depend on the number of sequences analyzed. Both methods yield broadly similar community compositions for each sample at the taxonomic levels of phyla to families. While the two methods yield different richness values, broad-scale patterns of relative richness and community composition are similar with both methods.
High Dynamics of Ciliate Community Revealed via Short-Term, High-Frequency Sampling in a Subtropical Estuarine Ecosystem
Authors: Gu Bowei , Huang Hungchia , Zhang Yizhe , Li Ran , Wang Lei , Wang Ying , Sun Jia , Wang Jianning , Zhang Rui , Jiao Nianzhi , Xu Dapeng
Published: February 2022

Ciliates are pivotal components of the marine microbial food web, exerting profound impacts on oceanic biogeochemical cycling. However, the temporal dynamics of ciliate assemblages on a short time scale in the highly fluctuating estuarine ecosystem remain largely unexplored. We studied changes in the ciliate community during a short time frame in the high salinity waters (>26) of a subtropical estuary. Ciliate abundance, biomass, size and oral diameter structure, and community composition fluctuated considerably and irregularly over a few days or even a few hours. Spearman correlations and the generalized linear model revealed that heterotrophic prokaryotes (HPs) and viral abundances drove the dynamics of ciliate abundance and biomass. The structural equation model further identified a major path from the high-fluorescence content virus (HFV) to HPs and then ciliates. Given the substantial correlation between salinity and HPs/HFV, we proposed that the response of HPs and HFV to salinity drives the dynamics of ciliate biomass. Additionally, the Mantel test showed that phytoplankton pigments such as Lutein and Neoxanthin, phosphate, and pigmented picoeukaryotes were key covariates of the ciliate community composition. This study demonstrated the highly changing patterns of ciliate assemblages and identified potential processes regulating ciliate biomass and community composition on short timescales in a subtropical, hydrographically complex estuary.
Molecular Epidemiological Characteristics and Risk Factors for Acquiring HBV Among Li Ethnic in Baisha County, Hainan Island-Subgenotype D3 Was First Discovered in China
Authors: Xu Ru , Song Dandan , Wang Min , Huang Jieting , Liao Qiao , Shan Zhengang , Rong Xia , Fu Yongshui
Published: February 2022

The residents of Baisha, a county of Hainan Island, mainly composed of Li ethnic population and relatively closed living environment with its unique geographical location. Our previous study showed that Li ethnic population of Baisha is an endemic center for hepatitis C virus, with significantly higher rates than in other parts of China. However, the epidemiology of HBV in this region remains unclear. Therefore, we conducted a comprehensive epidemiological survey of HBV in Baisha County, including 1,682 Li ethnic residents. The total seropositive rate for HBsAg was 10.2% and was higher than other parts of China. HBV-positive status was associated with the 20–40-year-old group (OR = 1.27, 95%CI 1.04–1.39, P < 0.01) and alcohol consumption (OR = 2.17, 95%CI 1.58–2.99, P < 0.01). Phylogenetic analysis showed that HBV subgenotype D3 was predominant in Baisha County which was first discovered in China, followed by C5, C1, B2, and undetermined subgenotypes which were significantly different from other geographical distribution of main genotypes in China. The most recent common ancestor (tMRCA) of the HBV genotype C in the Li ethnic of Baisha County was 1846 (95%CI: 1739–1932), and Baisha-C5 was earlier than Baisha-C1 and Baisha-C2. Most Baisha-D3 sequences were concentrated in one bundle and unrelated to those D3 genome sequences elsewhere in the world. According to the phylogenetic tree, D3 was introduced into Baisha County in 1884 (95%CI: 1816–1993) and became a local endemic virus. In conclusion, HBV infection in the Li ethnic group is characterized by a high prevalence rate in 20–40-year-old individuals and a unique genotype distribution which were significantly different from other geographical distribution of main genotypes in China, and subgenotype D3 was first discovered in China.
Long-Read Sequencing Reveals Genetic Adaptation of Bartonella Adhesin A Among Different Bartonella henselae Isolates
Authors: Thibau Arno , Hipp Katharina , Vaca Diana J. , Chowdhury Sounak , Malmström Johan , Saragliadis Athanasios , Ballhorn Wibke , Linke Dirk , Kempf Volkhard A. J.
Published: February 2022

Bartonella henselae is the causative agent of cat scratch disease and other clinical entities such as endocarditis and bacillary angiomatosis. The life cycle of this pathogen, with alternating host conditions, drives evolutionary and host-specific adaptations. Human, feline, and laboratory adapted B. henselae isolates often display genomic and phenotypic differences that are related to the expression of outer membrane proteins, for example the Bartonella adhesin A (BadA). This modularly-structured trimeric autotransporter adhesin is a major virulence factor of B. henselae and is crucial for the initial binding to the host via the extracellular matrix proteins fibronectin and collagen. By using next-generation long-read sequencing we demonstrate a conserved genome among eight B. henselae isolates and identify a variable genomic badA island with a diversified and highly repetitive badA gene flanked by badA pseudogenes. Two of the eight tested B. henselae strains lack BadA expression because of frameshift mutations. We suggest that active recombination mechanisms, possibly via phase variation (i.e., slipped-strand mispairing and site-specific recombination) within the repetitive badA island facilitate reshuffling of homologous domain arrays. The resulting variations among the different BadA proteins might contribute to host immune evasion and enhance long-term and efficient colonisation in the differing host environments. Considering the role of BadA as a key virulence factor, it remains important to check consistently and regularly for BadA surface expression during experimental infection procedures.
RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC
Authors: Shang Haitao , Chen Yichi , Wang Chunyue , Zhang Shentao , Wu Bolin , Liang Xitian , Liu Zhao , Wang Qiucheng , Cheng Wen
Published: February 2022

Sonodynamic therapy is widely used in the treatment and research of hepatocellular carcinoma. A novel targeted nanobubble complex mediated with Hematoporphyrin monomethyl ether and Lonidamine was structured as a sensitizer, characterized the properties, and studied the therapeutic effect on hepatocellular carcinoma. The complexes can promote the apoptosis of hepatocellular carcinoma cells and work better in combination with sonodynamic therapy. The differential expression of multiple types of RNA in hepatocellular carcinoma with sonodynamic therapy can be identified accurately with high-throughput RNA sequencing. The differential expressions of mRNA, lncRNA, and circRNA were analyzed by RNA-Seq. The enrichment analyses (Gene Ontology and KEGG) prompted the meaningful genes and pathways in the process of sonodynamic therapy in hepatocellular carcinoma cells. HMME-LND@C3F8-NBs conjugated with ultrasound is confirmed efficiently for inhibiting the development of hepatocellular carcinoma cells, and it is a combination of multiple genes and mechanisms.
Neuromeric Distribution of Nicotinamide Adenine Dinucleotide Phosphate-Diaphorase Activity in the Adult Lamprey Brain
Authors: Pombal Manuel A. , Megías Manuel , Lozano Daniel , López Jesús M.
Published: February 2022

This study reports for the first time the distribution and morphological characterization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d; a reliable marker of nitric oxide synthase activity) positive elements in the central nervous system of the adult river lamprey (Lampetra fluviatilis) on the framework of the neuromeric model and compares their cytoarchitectonic organization with that of gnathostomes. Both NADPH-d exhibiting cells and fibers were observed in all major divisions of the lamprey brain as well as in the spinal cord. In the secondary prosencephalon, NADPH-d positive cells were observed in the mitral cell layer of the olfactory bulb, evaginated pallium, amygdala, dorsal striatum, septum, lateral preoptic nucleus, caudal paraventricular area, posterior entopeduncular nucleus, nucleus of the stria medullaris, hypothalamic periventricular organ and mamillary regionsensu lato. In the lamprey diencephalon, NADPH-d labeled cells were observed in several nuclei of the prethalamus, epithalamus, pretectum, and the basal plate. Especially remarkable was the staining observed in the right habenula and several pretectal nuclei. NADPH-d positive cells were also observed in the following mesencephalic areas: optic tectum (two populations), torus semicircularis, nucleus M5 of Schöber, and a ventral tegmental periventricular nucleus. Five different cell populations were observed in the isthmic region, whereas the large sensory dorsal cells, some cells located in the interpeduncular nucleus, the motor nuclei of most cranial nerves, the solitary tract nucleus, some cells of the reticular nuclei, and small cerebrospinal fluid-contacting (CSF-c) cells were the most evident stained cells of the rhombencephalon proper. Finally, several NADPH-d positive cells were observed in the rostral part of the spinal cord, including the large sensory dorsal cells, numerous CSF-c cells, and some dorsal and lateral interneurons. NADPH-d positive fibers were observed in the olfactory pathways (primary olfactory fibers and stria medullaris), the fasciculus retroflexus, and the dorsal column tract. Our results on the distribution of NADPH-d positive elements in the brain of the adult lampreyL. fluviatilisare significantly different from those previously reported in larval lampreys and demonstrated that these animals possess a complex nitrergic system readily comparable to those of other vertebrates, although important specific differences also exist.
Alzheimer’s Disease: From Pathogenesis to Mesenchymal Stem Cell Therapy – Bridging the Missing Link
Authors: Hu Jingqiong , Wang Xiaochuan
Published: February 2022

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide. With the increasing trend of population aging, the estimated number of AD continues to climb, causing enormous medical, social and economic burden to the society. Currently, no drug is available to cure the disease or slow down its progression. There is an urgent need to improve our understanding on the pathogenesis of AD and develop novel therapy to combat it. Despite the two well-known pathological hallmarks (extracellular amyloid plaques and intracellular Neurofibrillary Tangles), the exact mechanisms for selective degeneration and loss of neurons and synapses in AD remain to be elucidated. Cumulative studies have shown neuroinflammation plays a central role in pathogenesis of AD. Neuroinflammation is actively involved both in the onset and the subsequent progression of AD. Microglia are the central player in AD neuroinflammation. In this review, we first introduced the different theories proposed for the pathogenesis of AD, focusing on neuroinflammation, especially on microglia, systemic inflammation, and peripheral and central immune system crosstalk. We explored the possible mechanisms of action of stem cell therapy, which is the only treatment modality so far that has pleiotropic effects and can target multiple mechanisms in AD. Mesenchymal stem cells are currently the most widely used stem cell type in AD clinical trials. We summarized the ongoing major mesenchymal stem cell clinical trials in AD and showed how translational stem cell therapy is bridging the gap between basic science and clinical intervention in this devastating disorder.
Case Report: Neurodegenerative Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Infection, a Report of Three Cases: Creutzfeldt–Jakob Disease, Rapidly Progressive Alzheimer's Disease, and Frontotemporal Dementia
Authors: Pimentel Gabriela Almeida , Guimarães Thiago Gonçalves , Silva Guilherme Diogo , Scaff Milberto
Published: February 2022

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurodegenerative diseases is yet to be fully clarified. Rapid worsening and even new-onset cases of those disorders have been reported in association with coronavirus disease 2019 (COVID-19). We describe three cases of neurodegenerative diseases in patients with SARS-CoV-2: a case of Creutzfeldt–Jakob disease during the COVID-19 acute phase, to our knowledge, is the second one described in the literature; a rapidly progressive Alzheimer's Disease; and a patient with frontotemporal dementia, and a quick decline of both cognitive and behavioral domains. This report suggests an association between SARS-CoV-2 infection and a higher probability of developing or accelerating neurodegenerative chronic neurologic conditions. We reinforce the need for a close cognitive follow-up in the aftermath of Sars-Cov2 infection.
Phenotype of VCP Mutations in Chinese Amyotrophic Lateral Sclerosis Patients
Authors: Feng Shu-Yan , Lin Han , Che Chun-Hui , Huang Hua-Pin , Liu Chang-Yun , Zou Zhang-Yu
Published: February 2022

Mutations in the valosin-containing protein (VCP) gene have been linked to amyotrophic lateral sclerosis (ALS) in the Caucasian populations. However, the phenotype of VCP mutations in Chinese patients with (ALS) remains unclear. Targeted next-generation sequencing covered 28 ALS-related genes including the VCP gene was undertaken to screen in a Chinese cohort of 275 sporadic ALS cases and 15 familial ALS pedigrees. An extensive literature review was performed to identify all patients with ALS carrying VCP mutations previously reported. The clinical characteristics and genetic features of ALS patients with VCP mutations were reviewed. One known p.R155C mutation in the VCP gene was detected in two siblings from a familial ALS pedigree and two sporadic individuals. In addition, the same VCP p.R155C mutation was detected in an additional patient with ALS referred in 2021. Three patients with VCP p.R155C mutation presented with muscular weakness starting from proximal extremities to distal extremities. The other patient developed a phenotype of Paget's disease of bone in addition to the progressive muscular atrophy. We reported the first VCP mutation carrier manifesting ALS with Paget's disease of bone in the Chinese population. Our findings expand the phenotypic spectrum of the VCP mutations in Chinese patients with ALS and suggest that ALS patients with VCP p.R155C mutations tend to present with relatively young onset, symmetrical involvement of proximal muscles weakness of arms or legs, and then progressed to distal muscles of limbs.
Mechanical Thrombectomy for M1 Subocclusive Thrombus With Lateral Lenticulostriate Artery Occlusion: A Case Report and Literature Review
Authors: Yajima Hirohisa , Koizumi Satoshi , Miyawaki Satoru , Saito Nobuhito
Published: February 2022

The treatment for middle cerebral artery subocclusive thrombi is not standardized. Here, we report a case of M1 subocclusive thrombus with lateral lenticulostriate artery occlusion that was successfully treated with mechanical thrombectomy. This article describes a treatment strategy for M1 subocclusive thrombus, focusing on the indications for mechanical thrombectomy. A 58-year-old male on admission for pneumonia had a sudden onset of dysarthria and motor deficits. He has a history of dilated cardiomyopathy and underwent left ventricular assist device implantation 3 years ago. At onset, his National Institutes of Health Stroke Scale (NIHSS) score was nine. Computed tomography angiography demonstrated a filling defect in the distal right M1 segment of the middle cerebral artery. Angiography confirmed the presence of a subocclusive thrombus within the distal right M1 segment, although peripheral blood flow was maintained. Mechanical thrombectomy was performed for the M1 subocclusive thrombus using a direct aspiration first-pass technique, resulting in successful aspiration of the thrombus on the first pass. After the procedure, recanalization of the lateral lenticulostriate artery was detected, and the patient demonstrated full recovery (NIHSS score 0). Mechanical thrombectomy can be considered as a treatment option in cases of acute ischemic stroke caused by M1 subocclusive thrombus with lateral lenticulostriate artery occlusion, which presents with a high NIHSS score or neurological deterioration.