bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance
Authors: Zhang Wensheng , Wang Yong , Zhong Fushun , Wang Xinghuan , Sucher Robert , Lin Cheng-Hung , Brandacher Gerald , Solari Mario G. , Gorantla Vijay S. , Zheng Xin Xiao
Published: February 2023

Compelling experimental evidence confirms that the robustness and longevity of mixed chimerism (MC) relies on the persistence and availability of donor-derived hematopoietic stem cell (HSC) niches in recipients. Based on our prior work in rodent vascularized composite allotransplantation (VCA) models, we hypothesize that the vascularized bone components in VCA bearing donor HSC niches, thus may provide a unique biologic opportunity to facilitate stable MC and transplant tolerance. In this study, by utilizing a series of rodent VCA models we demonstrated that donor HSC niches in the vascularized bone facilitate persistent multilineage hematopoietic chimerism in transplant recipients and promote donor-specific tolerance without harsh myeloablation. In addition, the transplanted donor HSC niches in VCA facilitated the donor HSC niches seeding to the recipient bone marrow compartment and contributed to the maintenance and homeostasis of stable MC. Moreover, this study provided evidences that chimeric thymus plays a role in MC-mediated transplant tolerance through a mechanism of thymic central deletion. Mechanistic insights from our study could lead to the use of vascularized donor bone with pre-engrafted HSC niches as a safe, complementary strategy to induce robust and stable MC-mediated tolerance in VCA or solid organ transplantation recipients.
Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients
Authors: Bulnes-Ramos Ángel , Pozo-Balado María Mar , Olivas-Martínez Israel , Garrido-Rodríguez Vanesa , Bernal-Blanco Gabriel , Suárez-Benjumea Alejandro , Álvarez-Ríos Ana Isabel , Lozano Carmen , González-Corvillo Carmen , Suñer-Poblet Marta , González-Roncero Francisco Manuel , Sánchez Berta , Maldonado-Calzado Isabel , Lara-Ruiz José Manuel , Gonzalez-Escribano María Francisca , Pacheco Yolanda María
Published: February 2023

Introduction

Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients.

Methods

To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response.

Results

Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses.

Discussion

In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.
Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study
Authors: Wang Kang , Xiang Yan-Jun , Yu Hong-Ming , Cheng Yu-Qiang , Liu Zong-Han , Zhong Jing-Ya , Feng Shuang , Ni Qian-Zhi , Zhu Hong-Fei , Pan Wei-Wei , Li Jing-Jing , Liang Chao , Zhou Hong-Kun , Meng Yan , Lau Wan Yee , Cheng Shu-Qun
Published: February 2023

Background and aims

The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients.

Methods

This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety.

Results

Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths.

Conclusions

IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study.

Clinical trial registration

http://www.chictr.org.cn, Identifier ChiCTR2200061793.
Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?
Authors: Lechuga Susana , Braga-Neto Manuel B. , Naydenov Nayden G. , Rieder Florian , Ivanov Andrei I.
Published: February 2023

Disruption of the intestinal epithelial barrier is a hallmark of mucosal inflammation. It increases exposure of the immune system to luminal microbes, triggering a perpetuating inflammatory response. For several decades, the inflammatory stimuli-induced breakdown of the human gut barrier was studied in vitro by using colon cancer derived epithelial cell lines. While providing a wealth of important data, these cell lines do not completely mimic the morphology and function of normal human intestinal epithelial cells (IEC) due to cancer-related chromosomal abnormalities and oncogenic mutations. The development of human intestinal organoids provided a physiologically-relevant experimental platform to study homeostatic regulation and disease-dependent dysfunctions of the intestinal epithelial barrier. There is need to align and integrate the emerging data obtained with intestinal organoids and classical studies that utilized colon cancer cell lines. This review discusses the utilization of human intestinal organoids to dissect the roles and mechanisms of gut barrier disruption during mucosal inflammation. We summarize available data generated with two major types of organoids derived from either intestinal crypts or induced pluripotent stem cells and compare them to the results of earlier studies with conventional cell lines. We identify research areas where the complementary use of colon cancer-derived cell lines and organoids advance our understanding of epithelial barrier dysfunctions in the inflamed gut and identify unique questions that could be addressed only by using the intestinal organoid platforms.
The intestine: A highly dynamic microenvironment for IgA plasma cells
Authors: Pracht Katharina , Wittner Jens , Kagerer Fritz , Jäck Hans-Martin , Schuh Wolfgang
Published: February 2023

To achieve longevity, IgA plasma cells require a sophisticated anatomical microenvironment that provides cytokines, cell-cell contacts, and nutrients as well as metabolites. The intestinal epithelium harbors cells with distinct functions and represents an important defense line. Anti-microbial peptide-producing paneth cells, mucus-secreting goblet cells and antigen-transporting microfold (M) cells cooperate to build a protective barrier against pathogens. In addition, intestinal epithelial cells are instrumental in the transcytosis of IgA to the gut lumen, and support plasma cell survival by producing the cytokines APRIL and BAFF. Moreover, nutrients are sensed through specialized receptors such as the aryl hydrocarbon receptor (AhR) by both, intestinal epithelial cells and immune cells. However, the intestinal epithelium is highly dynamic with a high cellular turn-over rate and exposure to changing microbiota and nutritional factors. In this review, we discuss the spatial interplay of the intestinal epithelium with plasma cells and its potential contribution to IgA plasma cell generation, homing, and longevity. Moreover, we describe the impact of nutritional AhR ligands on intestinal epithelial cell-IgA plasma cell interaction. Finally, we introduce spatial transcriptomics as a new technology to address open questions in intestinal IgA plasma cell biology.
Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy
Authors: Zhang Luyao , Chen Zihua , Wang Lanting , Luo Xiaoqun
Published: February 2023

Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP is mainly based on the systemic use of corticosteroids, but long-term use of corticosteroids results in a series of side effects. Type 2 inflammation is an immune response largely mediated by group 2 innate lymphoid cells, type 2 T helper cells, eosinophils, and inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13. Among patients with BP, the levels of immunoglobulin E and eosinophils are significantly increased in the peripheral blood and skin lesions, suggesting that the pathogenesis is tightly related to type 2 inflammation. To date, various targeted drugs have been developed to treat type 2 inflammatory diseases. In this review, we summarize the general process of type 2 inflammation, its role in the pathogenesis of BP and potential therapeutic targets and medications related to type 2 inflammation. The content of this review may contribute to the development of more effective drugs with fewer side effects for the treatment of BP.
Brief report: Assessment of mucosal barrier integrity using serological biomarkers in preclinical stages of rheumatoid arthritis
Authors: Gilbert Benoît Thomas P. , Lamacchia Céline , Amend Lena , Strowig Till , Rodriguez Emiliana , Palmer Gaby , Finckh Axel
Published: February 2023

Background

The pathogenesis of rheumatoid arthritis (RA) is believed to initiate at mucosal sites. The so-called ‘mucosal origin hypothesis of RA’ postulates an increased intestinal permeability before disease onset. Several biomarkers, including lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP), have been proposed to reflect gut mucosa permeability and integrity, while serum calprotectin is a new inflammation marker proposed in RA.

Methods

We analyzed serum samples of individuals genetically at increased risk of RA in a nested-case-control study. Participants from a longitudinal cohort of first-degree relatives of RA patients (SCREEN-RA cohort) were divided into three pre-clinical stages of RA, based on the presence of risk factors for subsequent RA onset: 1) low-risk healthy asymptomatic controls; 2) intermediate-risk individuals without symptoms, but with RA-associated auto-immunity; 3) high-risk individuals with clinically suspect arthralgias. Five patients with newly diagnosed RA were also sampled. Serum LBP, I-FABP and calprotectin were measured using commercially available ELISA kits.

Results

We included 180 individuals genetically at increased risk for RA: 84 asymptomatic controls, 53 individuals with RA-associated autoimmunity and 38 high risk individuals. Serum LBP, I-FAPB or calprotectin concentrations did not differ between individuals in different pre-clinical stages of RA.

Conclusion

Based on the serum biomarkers LBP, I-FABP and calprotectin, we could not detect any evidence for intestinal injury in pre-clinical stages of RA.
LIS1, a glyco-humanized swine polyclonal anti-lymphocyte globulin, as a novel induction treatment in solid organ transplantation
Authors: Rousse Juliette , Royer Pierre-Joseph , Evanno Gwénaëlle , Lheriteau Elsa , Ciron Carine , Salama Apolline , Shneiker Françoise , Duchi Roberto , Perota Andrea , Galli Cesare , Cozzi Emmanuele , Blancho Gilles , Duvaux Odile , Brouard Sophie , Soulillou Jean-Paul , Bach Jean-Marie , Vanhove Bernard
Published: February 2023

Anti-thymocyte or anti-lymphocyte globulins (ATGs/ALGs) are immunosuppressive drugs used in induction therapies to prevent acute rejection in solid organ transplantation. Because animal-derived, ATGs/ALGs contain highly immunogenic carbohydrate xenoantigens eliciting antibodies that are associated with subclinical inflammatory events, possibly impacting long-term graft survival. Their strong and long-lasting lymphodepleting activity also increases the risk for infections. We investigated here the in vitro and in vivo activity of LIS1, a glyco-humanized ALG (GH-ALG) produced in pigs knocked out for the two major xeno-antigens αGal and Neu5Gc. It differs from other ATGs/ALGs by its mechanism of action excluding antibody-dependent cell-mediated cytotoxicity and being restricted to complement-mediated cytotoxicity, phagocyte-mediated cytotoxicity, apoptosis and antigen masking, resulting in profound inhibition of T-cell alloreactivity in mixed leucocyte reactions. Preclinical evaluation in non-human primates showed that GH-ALG dramatically reduced CD4+ (p=0.0005,***), CD8+ effector T cells (p=0.0002,***) or myeloid cells (p=0.0007,***) but not T-reg (p=0.65, ns) or B cells (p=0.65, ns). Compared with rabbit ATG, GH-ALG induced transient depletion (less than one week) of target T cells in the peripheral blood (<100 lymphocytes/L) but was equivalent in preventing allograft rejection in a skin allograft model. The novel therapeutic modality of GH-ALG might present advantages in induction treatment during organ transplantation by shortening the T-cell depletion period while maintaining adequate immunosuppression and reducing immunogenicity.
The roles of COX-2 in protozoan infection
Authors: Wang Xinlei , Chen Jie , Zheng Jingtong
Published: February 2023

Protozoan diseases cause great harm in animal husbandry and require human-provided medical treatment. Protozoan infection can induce changes in cyclooxygenase-2 (COX-2) expression. The role played by COX-2 in the response to protozoan infection is complex. COX-2 induces and regulates inflammation by promoting the synthesis of different prostaglandins (PGs), which exhibit a variety of biological activities and participate in pathophysiological processes in the body in a variety of ways. This review explains the roles played by COX-2 in protozoan infection and analyzes the effects of COX-2-related drugs in protozoan diseases.
Challenges and strategies for the uptake of mass drug administration among pastoralist communities in South Sudan
Authors: Muchiri Geoffrey , Okwii Moses , Bukuluki Paul , Willems Johan , Amanyi-Enegela Juliana A. , Yibi Makoy , Sankar Girija
Published: February 2023

Preventive chemotherapy through mass drug administration (MDA) to control and eliminate neglected tropical diseases (NTDs) requires the active participation of communities living with NTDs, or at risk of NTD infections. Despite considerable progress by national control and elimination programs, achieving consistent and sustainable treatment campaigns that reach pastoralist communities remains challenging, which in turn delays the achievement of global disease elimination goals. The challenges of accessing pastoralist communities for treatment also hinder the achievement of the UN’s Sustainable Development Goals’ (SDGs) pledge to “leave no one behind“. Elimination targets cannot be achieved if significant proportions of endemic populations, such as pastoralists, are missed out during treatment campaigns. In South Sudan, close to 70% of the population is categorized as pastoralist, with previous data on MDA showing low access to and acceptance of MDA among the pastoralist community, as well as inconsistent treatment coverage. To address this challenge, a cross-sectional study design was conducted in five counties, with 239 pastoralist community respondents participating in in-depth interviews (IDIs), key informant interviews (KIIs), and focus group discussions (FGDs). Our findings show that, in the pastoralist community, high mobility, lay perceptions about the causes of NTDs and methods of treating them, limited awareness of MDA, and suboptimal health-seeking behaviors are the major factors that limit accessibility and participation. Our results suggest that improved uptake of MDA in these communities may be achieved by timing treatment campaigns to take account of pastoralists’ seasonal migration patterns, by involving pastoralist leaders in planning and social mobilization activities, by engaging community members as community drug distributors (CDDs), by using participatory behavior change approaches to design NTD interventions, and by addressing negative perceptions around the medicines involved, including those related to drug expiry and drugs causing impotence or other side effects. The results from this study could enable national programs to address the challenges of implementing treatment campaigns through the enhanced involvement and representation of pastoralist communities.
Comparative investigation of fractional bioconvection and magnetohydrodynamic flow induced by hybrid nanofluids through a channel
Authors: Raza Ali , Nigar Niat , Khan Umair , Elattar Samia , Eldin Sayed M. , Abed Ahmed M.
Published: February 2023

The functional effects of medications, such as those that slow down and calm the body, have been investigated for the polarized diffusion coefficient based on the subsequent increase through magnetism. This study examines generalized Mittag–Lefer kernel-based fractional derivatives in MHD Brinkman-type fluids under bioconvection that contain hybrid titanium dioxide (TiO2) and silver (Ag) nanoparticles with water (H2O) and sodium alginate (NaC6H7O6) as the base fluids. Atangana–Baleanu (AB) and Caputo–Fabrizio (CF) fractional derivatives, which are two contemporary definitions of fractional-order derivatives with a memory effect, were used to explore the modified fractional model utilizing the Laplace transformation and certain numerical algorithms. The impacts of restrictions on various nanoparticles were investigated and graphically displayed. We observed that the volumetric fraction improvement controls the fluid velocity by slowing it down. The water-based hybrid nanofluid has a greater influence on the temperature and momentum fields than the sodium alginate-based hybrid nanofluid due to the physical characteristics of the explored nanoparticles and base fluids. Additionally, the memory effect causes a higher substantial value for the AB-fractional derivative of the velocity profile than the CF-fractional derivative.
Developing a novel tool to assess the ability to self-administer medication – A systematic evaluation of patients’ video recordings in the ABLYMED study
Authors: Luegering Anneke , Langner Robert , Wilm Stefan , Doeppner Thorsten R. , Hermann Dirk M. , Frohnhofen Helmut , Gronewold Janine
Published: February 2023

Background

Older people often experience medication management problems due to multimorbidity, polypharmacy and medication complexity. There is often a large gap between patients’ self-reported and actual abilities to handle the self-administration of their medication. Here we report on the development and evaluation of a new tool to assess the ability of non-demented hospitalized patients to self-administer medication in different dosage forms. To this end, we video-recorded the patients’ medication management performance and implemented a novel assessment scheme, which was applied by several independent raters.

Methods

Sixty-seven in-patients ≥70 years of age and regularly taking ≥5 different drugs autonomously of the ABLYMED study agreed to the video recording of their medication management performance with five different dosage forms. All raters underwent a training and applied a standardized assessment form and written guide with rating rules for evaluation. In a pilot phase, video recordings of three patients were rated by 19 raters (15 medical students, two expert raters to determine a reference standard, and two main raters who later rated the total sample). In the rating phase, based on the ratings obtained from the two main raters, we determined interrater (assessed every section of 20 patients as agreement between the raters at one point of time) and intrarater (assessed as consistency within each rater across three points of time) agreement by intraclass correlation analysis.

Results

In the pilot phase we obtained an overall sufficient agreement pattern, with an adjustment of the rating rules for patches. In the rating phase we achieved satisfactory agreement between the two raters (interrater reliability) and across different points of time (intrarater reliability). For two dosage forms (eye-drops and pen), rater training needed to be repeated to reach satisfactory levels.

Discussion

Our novel rating procedure was found to be objective, valid and reproducible, given appropriate training of the raters. Our findings are an important part of a larger research project to implement a novel assessment for the ability to self-administer medication in different dosage forms. Further, they can support the development of patient trainings to improve medication management and secure independent living.
Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis
Authors: Jaeger Zachary J. , Raval Neel S. , Maverakis Natalia K. A. , Chen David Y. , Ansstas George , Hardi Angela , Cornelius Lynn A.
Published: February 2023

Introduction

NRAS mutations are common in melanoma and confer a worse prognosis. Although most patients with metastatic melanoma receive immune checkpoint inhibitors (ICIs), the impact of NRAS mutational status on their efficacy remains under debate.

Methods

We performed a comprehensive literature search across several large databases. Inclusion criteria were trials, cohorts, and large case series that analyzed the primary outcome of objective response rate by NRAS mutational status in patients with melanoma treated with any line of ICI. At least two reviewers independently screened studies using Covidence software, extracted data, and assessed risk of bias. Standard meta-analysis was performed in R with sensitivity analysis and tests for bias.

Results

Data on 1770 patients from ten articles were pooled for meta-analysis, and the objective response rate to ICIs was calculated to compare NRAS-mutant and NRAS-wildtype melanoma. The objective response rate was 1.28 (95% confidence interval: 1.01–1.64). Sensitivity analysis identified the study by Dupuis et al. with influential impact on the pooled effect size and heterogeneity, favoring NRAS-mutant melanoma.

Discussion

In this meta-analysis evaluating the impact of NRAS mutational status on objective response to ICIs in metastatic melanoma, NRAS-mutant cutaneous melanoma demonstrated an increased likelihood of partial or complete tumor response, relative to NRAS-wildtype cutaneous melanoma. Genomic screening for NRAS mutations in patients with metastatic melanoma may improve predictive ability when initiating ICIs.
Function-driven design of Bacillus kochii and Filobasidium magnum co-culture to improve quality of flue-cured tobacco
Authors: Wu Xinying , Cai Wen , Zhu Pengcheng , Peng Zheng , Zheng Tianfei , Li Dongliang , Li Jianghua , Zhou Guanyu , Zhang Juan , Du Guocheng
Published: February 2023

Flue-cured tobacco (FCT) is an economical raw material whose quality affects the quality and cost of the derived product. However, the time-consuming and inefficient spontaneous aging is the primary process for improving the FCT quality in the industry. In this study, a function-driven co-culture with functional microorganisms was built in response to the quality-driven need for less irritation and more aroma in FCT. The previous study has found that Bacillus kochii SC could degrade starch and protein to reduce tobacco irritation and off-flavors. The Filobasidium magnum F7 with high lipoxygenase activity was screened out for degrading higher fatty acid esters and terpenoids to promote the aroma and flavor of FCT. Co-cultivation with strain SC and F7 obtained better quality improvement than mono-culture at an initial inoculation ratio of 1:3 for 2 days, representing a significant breakthrough in efficiency and a reduction in production costs compared to the more than 2 years required for the spontaneous aging process. Through the analysis of microbial diversity, predicted flora functions, enzyme activities and volatile compositions within the mono- and co-cultivation, our study showed the formation of a function-driven co-culture between two strains through functional division of labor and nutritional feeding. Herein, the function-driven co-culture via bioaugmentation will become an increasingly implemented approach for the tobacco industry.
Three new yeast species from flowers of Camellia sinensis var. assamica collected in Northern Thailand and their tannin tolerance characterization
Authors: Kanpiengjai Apinun , Kodchasee Pratthana , Unban Kridsada , Kumla Jaturong , Lumyong Saisamorn , Khunnamwong Pannida , Sarkar Dipayan , Shetty Kalidas , Khanongnuch Chartchai
Published: February 2023

Our recent research study focused on Miang fermentation revealed that tannin-tolerant yeasts and bacteria play vital roles in the Miang production process. A high proportion of yeast species are associated with plants, insects, or both, and nectar is one of the unexplored sources of yeast biodiversity. Therefore, this study aimed to isolate and identify yeasts of tea flowers of Camellia sinensis var. assamica and to investigate their tannin tolerance, which is a property essential to Miang production processes. A total of 82 yeasts were recovered from a total of 53 flower samples in Northern Thailand. It was found that two and eight yeast strains were distinct from all other known species within the genera Metschnikowia and Wickerhamiella, respectively. These yeast strains were described as three new species, namely, Metschnikowia lannaensis, Wickerhamiella camelliae, and W. thailandensis. The identification of these species was based on phenotypic (morphological, biochemical, and physiological characteristics) and phylogenetic analyses of a combination of the internal transcribed spacer (ITS) regions and the D1/D2 domains of the large subunit (LSU) ribosomal RNA gene. The yeast diversity in tea flowers acquired from Chiang Mai, Lampang, and Nan provinces had a positive correlation with those acquired from Phayao, Chiang Rai, and Phrae, respectively. Wickerhamiella azyma, Candida leandrae, and W. thailandensis were the species uniquely found in tea flowers collected from Nan and Phrae, Chiang Mai, and Lampang provinces, respectively. Some of the tannin-tolerant and/or tannase-producing yeasts were associated with yeasts in the commercial Miang process and those found during Miang production, i.e., C. tropicalis, Hyphopichia burtonii, Meyerozyma caribbica, Pichia manshurica, C. orthopsilosis, Cyberlindnera fabianii, Hanseniaspora uvarum, and Wickerhamomyces anomalus. In conclusion, these studies suggest that floral nectar could support the formation of yeast communities that are beneficial for Miang production.
Genome analysis and genomic comparison of a fungal cultivar of the nonsocial weevil Euops chinensis reveals its plant decomposition and protective roles in fungus-farming mutualism
Authors: Guo Wenfeng , Wang Wei , Tang Jun , Li Tianyu , Li Xiaoqiong
Published: February 2023

Fungus-farming mutualisms are models for studying co-evolutionary among species. Compared to well-documented fungus-farming in social insects, the molecular aspects of fungus-farming mutualisms in nonsocial insects have been poorly explored.Euops chinensisis a solitary leaf-rolling weevil feeding on Japanese knotweed (Fallopia japonica). This pest has evolved a special proto-farming bipartite mutualism with the fungusPenicillium herquei, which provide nutrition and defensive protection for theE. chinensislarvae. Here, the genome ofP. herqueiwas sequenced, and the structure and specific gene categories in theP. herqueigenome were then comprehensively compared with the other two well-studiedPenicilliumspecies (P. decumbensandP. chrysogenum). The assembledP. herqueigenome had a 40.25  Mb genome size with 46.7% GC content. A diverse set of genes associating with carbohydrate-active enzymes, cellulose and hemicellulose degradation, transporter, and terpenoid biosynthesis were detected in theP. herqueigenome. Comparative genomics demonstrate that the threePenicilliumspecies show similar metabolic and enzymatic potential, however,P. herqueihas more genes associated with plant biomass degradation and defense but less genes associating with virulence pathogenicity. Our results provide molecular evidence for plant substrate breakdown and protective roles ofP. herqueiinE. chinensismutualistic system. Large metabolic potential shared byPenicilliumspecies at the genus level may explain why somePenicilliumspecies are recruited by theEuopsweevils as crop fungi.
Projected 21st-century changes in marine heterotrophic bacteria under climate change
Authors: Kim Heather H. , Laufkötter Charlotte , Lovato Tomas , Doney Scott C. , Ducklow Hugh W.
Published: February 2023

Marine heterotrophic Bacteria (or referred to as bacteria) play an important role in the ocean carbon cycle by utilizing, respiring, and remineralizing organic matter exported from the surface to deep ocean. Here, we investigate the responses of bacteria to climate change using a three-dimensional coupled ocean biogeochemical model with explicit bacterial dynamics as part of the Coupled Model Intercomparison Project Phase 6. First, we assess the credibility of the century-scale projections (2015–2099) of bacterial carbon stock and rates in the upper 100 m layer using skill scores and compilations of the measurements for the contemporary period (1988–2011). Second, we demonstrate that across different climate scenarios, the simulated bacterial biomass trends (2076–2099) are sensitive to the regional trends in temperature and organic carbon stocks. Bacterial carbon biomass declines by 5–10% globally, while it increases by 3–5% in the Southern Ocean where semi-labile dissolved organic carbon (DOC) stocks are relatively low and particle-attached bacteria dominate. While a full analysis of drivers underpinning the simulated changes in all bacterial stock and rates is not possible due to data constraints, we investigate the mechanisms of the changes in DOC uptake rates of free-living bacteria using the first-order Taylor decomposition. The results demonstrate that the increase in semi-labile DOC stocks drives the increase in DOC uptake rates in the Southern Ocean, while the increase in temperature drives the increase in DOC uptake rates in the northern high and low latitudes. Our study provides a systematic analysis of bacteria at global scale and a critical step toward a better understanding of how bacteria affect the functioning of the biological carbon pump and partitioning of organic carbon pools between surface and deep layers.
The effects of cultivation patterns and nitrogen levels on fertility and bacterial community characteristics of surface and subsurface soil
Authors: Xu Chengyu , Chen Yuanjie , Zang Qian , Li Yulin , Zhao Jinbiao , Lu Xuanrui , Jiang Min , Zhuang Hengyang , Huang Lifen
Published: February 2023

The cropping system affects the physicochemical property and microbial community of paddy soil. Previous research mostly focused on the study of soil 0–20 cm underground. However, there may be difference in the laws of nutrient and microorganism distribution at different depths of arable soil. In surface (0–10 cm) and subsurface (10–20 cm) soil, a comparative analysis including soil nutrients, enzymes, and bacterial diversity was carried out between the organic and conventional cultivation patterns, low and high nitrogen levels. Analysis results suggested that under the organic farming pattern, the contents of total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP), and soil organic matter (SOM) as well as alkaline phosphatase and sucrose activity increased in surface soil, but the SOM concentration and urease activity decreased in subsurface soil. A moderate reduction of nitrogen applied to soil could enhance soil enzyme activity. It was demonstrated by α diversity indices that high nitrogen levels remarkably undermined soil bacterial richness and diversity. Venn diagrams and NMDS analysis manifested great difference in bacterial communities and an apparent clustering tendency under different treatment conditions. Species composition analysis indicated that the total relative abundance of Proteobacteria, Acidobacteria, and Chloroflexi retained stable in paddy soil. LEfSe results revealed that a low nitrogen organic treatment could elevate the relative abundance of Acidobacteria in surface soil and Nitrosomonadaceae in subsurface soil, thereby tremendously optimizing the community structure. Moreover, Spearman’s correlation analysis was also performed, which proved the significant correlation of diversity with enzyme activity and AN concentration. Additionally, redundancy analysis disclosed that the Acidobacteria abundance in surface soil and Proteobacteria abundance in subsurface soil exerted conspicuous influence on environmental factors and the microbial community structure. According to the findings of this study, it was believed that reasonable nitrogen application together with an organic agriculture cultivation system could effectively improve soil fertility in Gaoyou City, Jiangsu Province, China.
Diaporthe species associated with the maritime grass Festuca rubra subsp. pruinosa
Authors: Toghueo Rufin Marie Kouipou , Vázquez de Aldana Beatriz R. , Zabalgogeazcoa Iñigo
Published: February 2023

Festuca rubra subsp. pruinosa is a perennial grass growing in sea cliffs where plants are highly exposed to salinity and marine winds, and often grow in rock fissures where soil is absent. Diaporthe species are one of the most abundant components of the root microbiome of this grass and several Diaporthe isolates have been found to produce beneficial effects in their host and other plant species of agronomic importance. In this study, 22 strains of Diaporthe isolated as endophytes from roots of Festuca rubra subsp. pruinosa were characterized by molecular, morphological, and biochemical analyses. Sequences of the nuclear ribosomal internal transcribed spacers (ITS), translation elongation factor 1-α (TEF1), beta-tubulin (TUB), histone-3 (HIS), and calmodulin (CAL) genes were analyzed to identify the isolates. A multi-locus phylogenetic analysis of the combined five gene regions led to the identification of two new species named Diaporthe atlantica and Diaporthe iberica. Diaporthe atlantica is the most abundant Diaporthe species in its host plant, and Diaporthe iberica was also isolated from Celtica gigantea, another grass species growing in semiarid inland habitats. An in vitro biochemical characterization showed that all cultures of D. atlantica produced indole-3-acetic acid and ammonium, and the strains of D. iberica produced indole 3-acetic acid, ammonium, siderophores, and cellulase. Diaporthe atlantica is closely related to D. sclerotioides, a pathogen of cucurbits, and caused a growth reduction when inoculated in cucumber, melon, and watermelon.
Benzyl isothiocyanate improves the prognosis of Aspergillus fumigatus keratitis by reducing fungal load and inhibiting Mincle signal pathway
Authors: Yi Wendan , Gu Lingwen , Wang Yuwei , Lin Jing , Zhang Lina , Wang Qian , Diao Weilin , Qi Yinghe , Chi Menghui , Yin Min , Li Cui , Zhao Guiqiu
Published: February 2023

Aspergillus fumigatus keratitis is a potential blinding disease associated with A. fumigatus invasion and excessive inflammatory response. Benzyl isothiocyanate (BITC) is a secondary metabolite with broad antibacterial and anti-inflammatory activity extracted from cruciferous species. However, the role of BITC in A. fumigatus keratitis has not been discovered yet. This study aims to explore the antifungal and anti-inflammatory effects and mechanisms of BITC in A. fumigatus keratitis. Our results provided evidences that BITC exerted antifungal effects against A. fumigatus by damaging cell membranes, mitochondria, adhesion, and biofilms in a concentration-dependent manner. In vivo, fungal load and inflammatory response including inflammatory cell infiltration and pro-inflammatory cytokine expression were reduced in BITC-treated A. fumigatus keratitis. Additionally, BITC significantly decreased Mincle, IL-1β, TNF-α, and IL-6 expression in RAW264.7 cells that stimulated by A. fumigatus or Mincle ligand trehalose-6,6-dibehenate. In summary, BITC possessed fungicidal activities and could improve the prognosis of A. fumigatus keratitis by reducing fungal load and inhibiting the inflammatory response mediated by Mincle.
Predicting Plasmodium knowlesi transmission risk across Peninsular Malaysia using machine learning-based ecological niche modeling approaches
Authors: Phang Wei Kit , Hamid Mohd Hafizi bin Abdul , Jelip Jenarun , Mudin Rose Nani binti , Chuang Ting-Wu , Lau Yee Ling , Fong Mun Yik
Published: February 2023

The emergence of potentially life-threatening zoonotic malaria caused by Plasmodium knowlesi nearly two decades ago has continued to challenge Malaysia healthcare. With a total of 376 P. knowlesi infections notified in 2008, the number increased to 2,609 cases in 2020 nationwide. Numerous studies have been conducted in Malaysian Borneo to determine the association between environmental factors and knowlesi malaria transmission. However, there is still a lack of understanding of the environmental influence on knowlesi malaria transmission in Peninsular Malaysia. Therefore, our study aimed to investigate the ecological distribution of human P. knowlesi malaria in relation to environmental factors in Peninsular Malaysia. A total of 2,873 records of human P. knowlesi infections in Peninsular Malaysia from 1st January 2011 to 31st December 2019 were collated from the Ministry of Health Malaysia and geolocated. Three machine learning-based models, maximum entropy (MaxEnt), extreme gradient boosting (XGBoost), and ensemble modeling approach, were applied to predict the spatial variation of P. knowlesi disease risk. Multiple environmental parameters including climate factors, landscape characteristics, and anthropogenic factors were included as predictors in both predictive models. Subsequently, an ensemble model was developed based on the output of both MaxEnt and XGBoost. Comparison between models indicated that the XGBoost has higher performance as compared to MaxEnt and ensemble model, with AUCROC values of 0.933 ± 0.002 and 0.854 ± 0.007 for train and test datasets, respectively. Key environmental covariates affecting human P. knowlesi occurrence were distance to the coastline, elevation, tree cover, annual precipitation, tree loss, and distance to the forest. Our models indicated that the disease risk areas were mainly distributed in low elevation (75–345 m above mean sea level) areas along the Titiwangsa mountain range and inland central-northern region of Peninsular Malaysia. The high-resolution risk map of human knowlesi malaria constructed in this study can be further utilized for multi-pronged interventions targeting community at-risk, macaque populations, and mosquito vectors.
The Fault in Our Astrocytes - cause or casualties of proteinopathies of ALS/FTD and other neurodegenerative diseases?
Authors: Bustos Lynette M. , Sattler Rita
Published: February 2023

Many neurodegenerative diseases fall under the class of diseases known as proteinopathies, whereby the structure and localization of specific proteins become abnormal. These aberrant proteins often aggregate within cells which disrupts vital homeostatic and physiological cellular functions, ultimately contributing to cell death. Although neurodegenerative disease research is typically neurocentric, there is evidence supporting the role of non-neuronal cells in the pathogenesis of these diseases. Specifically, the role of astrocytes in neurodegenerative diseases has been an ever-growing area of research. Astrocytes are one of the most abundant cell types in the central nervous system (CNS) and provide an array of essential homeostatic functions that are disrupted in neurodegenerative diseases. Astrocytes can exhibit a reactive phenotype that is characterized by molecular changes, as well as changes in morphology and function. In neurodegenerative diseases, there is potential for reactive astrocytes to assume a loss-of-function phenotype in homeostatic operations such as synapse maintenance, neuronal metabolic support, and facilitating cell-cell communication between glia and neurons. They are also able to concurrently exhibit gain-of-function phenotypes that can be destructive to neural networks and the astrocytes themselves. Additionally, astrocytes have been shown to internalize disease related proteins and reflect similar or exacerbated pathology that has been observed in neurons. Here, we review several major neurodegenerative disease-specific proteinopathies and what is known about their presence in astrocytes and the potential consequences regarding cell and non-cell autonomous neurodegeneration.
lncRNA-associated ceRNA network revealing the potential regulatory roles of ferroptosis and immune infiltration in Alzheimer’s disease
Authors: Tan Yejun , Tang Wang , Xiao Wenbiao , Huang Roujie , Li Xin , Peng Weijun , Yan Kuipo , Cao Yuan , Zeng Yi , Kang Jin
Published: February 2023

Background

Alzheimer’s disease (AD) is the most common form of dementia characterized by a prominent cognitive deterioration of sufficient magnitude to impair daily living. Increasing studies indicate that non-coding RNAs (ncRNAs) are involved in ferroptosis and AD progression. However, the role of ferroptosis-related ncRNAs in AD remains unexplored.

Methods

We obtained the intersection of differentially expressed genes in GSE5281 (brain tissue expression profile of patients with AD) from the GEO database and ferroptosis-related genes (FRGs) from the ferrDb database. Least absolute shrinkage and selection operator model along with weighted gene co-expression network analysis screened for FRGs highly associated with AD.

Results

A total of five FRGs were identified and further validated in GSE29378 (area under the curve = 0.877, 95% confidence interval = 0.794–0.960). A competing endogenous RNA (ceRNA) network of ferroptosis-related hub genes (EPT1, KLHL24, LRRFIP1, CXCL2 and CD44) was subsequently constructed to explore the regulatory mechanism between hub genes, lncRNAs and miRNAs. Finally, CIBERSORT algorithms were used to unravel the immune cell infiltration landscape in AD and normal samples. M1 macrophages and mast cells were more infiltrated whereas memory B cells were less infiltrated in AD samples than in normal samples. Spearman’s correlation analysis revealed that LRRFIP1 was positively correlated with M1 macrophages (r = -0.340, P < 0.001) whereas ferroptosis-related lncRNAs were negatively correlated with immune cells, wherein miR7-3HG correlated with M1 macrophages and NIFK-AS1, EMX2OS and VAC14-AS1 correlated with memory B cells (|r| > 0.3, P < 0.001).

Conclusion

We constructed a novel ferroptosis-related signature model including mRNAs, miRNAs and lncRNAs, and characterized its association with immune infiltration in AD. The model provides novel ideas for the pathologic mechanism elucidation and targeted therapy development of AD.
Bifurcation analysis of motoneuronal excitability mechanisms under normal and ALS conditions
Authors: Moustafa Muhammad , Mousa Mohamed H. , Saad Mohamed S. , Basha Tamer , Elbasiouny Sherif M.
Published: February 2023

Introduction

Bifurcation analysis allows the examination of steady-state, non-linear dynamics of neurons and their effects on cell firing, yet its usage in neuroscience is limited to single-compartment models of highly reduced states. This is primarily due to the difficulty in developing high-fidelity neuronal models with 3D anatomy and multiple ion channels in XPPAUT, the primary bifurcation analysis software in neuroscience.

Methods

To facilitate bifurcation analysis of high-fidelity neuronal models under normal and disease conditions, we developed a multi-compartment model of a spinal motoneuron (MN) in XPPAUT and verified its firing accuracy against its original experimental data and against an anatomically detailed cell model that incorporates known MN non-linear firing mechanisms. We used the new model in XPPAUT to study the effects of somatic and dendritic ion channels on the MN bifurcation diagram under normal conditions and after amyotrophic lateral sclerosis (ALS) cellular changes.

Results

Our results show that somatic small-conductance Ca2+-activated K (SK) channels and dendritic L-type Ca2+ channels have the strongest effects on the bifurcation diagram of MNs under normal conditions. Specifically, somatic SK channels extend the limit cycles and generate a subcritical Hopf bifurcation node in the V-I bifurcation diagram of the MN to replace a supercritical node Hopf node, whereas L-type Ca2+ channels shift the limit cycles to negative currents. In ALS, our results show that dendritic enlargement has opposing effects on MN excitability, has a greater overall impact than somatic enlargement, and dendritic overbranching offsets the dendritic enlargement hyperexcitability effects.

Discussion

Together, the new multi-compartment model developed in XPPAUT facilitates studying neuronal excitability in health and disease using bifurcation analysis.