bluuebunny/crossref_metadata_2025 huggingface dataset:
Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis
Authors: Giannini Margherita , Ellezam Benjamin , Leclair Valérie , Lefebvre Frédéric , Troyanov Yves , Hudson Marie , Senécal Jean-Luc , Geny Bernard , Landon-Cardinal Océane , Meyer Alain
Published: January 2023

Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma. Autoimmune myositis is also a heterogeneous group of myopathies that classically encompass necrotizing myopathy, antisynthetase syndrome, dermatomyositis and inclusion body myositis. Recent data revealed that an additional disease subset, denominated “scleromyositis”, should be recognized within both the systemic sclerosis and the autoimmune myositis spectrum. We performed an in-depth review of the literature with the aim of better delineating scleromyositis. Our review highlights that this concept is supported by recent clinical, serological and histopathological findings that have important implications for patient management and understanding of the disease pathophysiology. As compared with other subsets of systemic sclerosis and autoimmune myositis, scleromyositis patients can present with a characteristic pattern of muscle involvement (i.e. distribution of muscle weakness) along with multisystemic involvement, and some of these extra-muscular complications are associated with poor prognosis. Several autoantibodies have been specifically associated with scleromyositis, but they are not currently integrated in diagnostic and classification criteria for systemic sclerosis and autoimmune myositis. Finally, striking vasculopathic lesions at muscle biopsy have been shown to be hallmarks of scleromyositis, providing a strong anatomopathological substratum for the concept of scleromyositis. These findings bring new insights into the pathogenesis of scleromyositis and help to diagnose this condition, in patients with subtle SSc features and/or no autoantibodies (i.e. “seronegative” scleromyositis). No guidelines are available for the management of these patients, but recent data are showing the way towards a new therapeutic approach dedicated to these patients.
RAGE contributes to allergen driven severe neutrophilic airway inflammation via NLRP3 inflammasome activation in mice
Authors: Killian Katherine N. , Kosanovich Jessica L. , Lipp Madeline A. , Empey Kerry M. , Oury Tim D. , Perkins Timothy N.
Published: January 2023

Background

Asthma is a major public healthcare burden, affecting over 300 million people worldwide. While there has been great progress in the treatment of asthma, subsets of patients who present with airway neutrophilia, often have more severe disease, and tend to be resistant to conventional corticosteroid treatments. The receptor for advanced glycation endproducts (RAGE) plays a central role in the pathogenesis of eosinophilic asthma, however, it’s role in neutrophilic asthma remains largely uninvestigated.

Methods

A mouse model of severe steroid resistant neutrophilic airway disease (SSRNAD) using the common fungal allergen Alternaria alternata (AA) was employed to evaluate the effects of genetic ablation of RAGE and pharmacological inhibition of the NLRP3 inflammasome on neutrophilic airway inflammation.

Results

AA exposure induced robust neutrophil-dominant airway inflammation and increased BALF levels of Th1/Th17 cytokines in wild-type mice, which was significantly reduced in RAGE-/- mice. Serum levels of IgE and IgG1 were increased similarly in both wild-type and RAGE-/- mice. Pharmacological inhibition of NLRP3 blocked the effects of AA exposure and NLRP3 inflammasome activation was RAGE-dependent. Neutrophil extracellular traps were elevated in the BALF of wild-type but not RAGE-/- mice and an atypical population of SiglecF+ neutrophils were identified in the BALF. Lastly, time-course studies found that RAGE expression promoted sustained neutrophil accumulation in the BALF of mice in response to AA.
TLQP-21 is a low potency partial C3aR activator on human primary macrophages
Authors: Li Xaria X. , Lee John D. , Lee Han S. , Clark Richard J. , Woodruff Trent M.
Published: January 2023

TLQP-21 is a 21-amino acid neuropeptide derived from the VGF precursor protein. TLQP-21 is expressed in the nervous system and neuroendocrine glands, and demonstrates pleiotropic roles including regulating metabolism, nociception and microglial functions. Several possible receptors for TLQP-21 have been identified, with complement C3a receptor (C3aR) being the most commonly reported. However, few studies have characterised the activity of TLQP-21 in immune cells, which represent the major cell type expressing C3aR. In this study, we therefore aimed to define the activity of both human and mouse TLQP-21 on cell signalling in primary human and mouse macrophages. We first confirmed that TLQP-21 induced ERK signalling in CHO cells overexpressing human C3aR, and did not activate human C5aR1 or C5aR2. TLQP-21 mediated ERK signalling was also observed in primary human macrophages. However, the potency for human TLQP-21 was 135,000-fold lower relative to C3a, and only reached 45% at the highest dose tested (10 μM). Unlike in humans, mouse TLQP-21 potently triggered ERK signalling in murine macrophages, reaching near full activation, but at ~10-fold reduced potency compared to C3a. We further confirmed the C3aR dependency of the TLQP-21 activities. Our results reveal significant discrepancy in TLQP-21 C3aR activity between human and murine receptors, with mouse TLQP-21 being consistently more potent than the human counterpart in both systems. Considering the supraphysiological concentrations of hTLQP-21 needed to only partially activate macrophages, it is likely that the actions of TLQP-21, at least in these immune cells, may not be mediated by C3aR in humans.
Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer
Authors: Zheng Liang , Xiong Anning , Wang Shuyuan , Xu Jianlin , Shen Yinchen , Zhong Runbo , Lu Jun , Chu Tianqing , Zhang Wei , Li Ying , Zheng Xiaoxuan , Han Baohui , Zhong Hua , Nie Wei , Zhang Xueyan
Published: January 2023

Objectives

Immune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy.

Methods

The present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLR/NLR/PLR and increased MLR/NLR/PLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed.

Results

A total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P<0.001) and multivariate (P<0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P=0.007) and multivariate (P=0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P=0.001) and prolonged PFS in univariate analysis (P=0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P<0.001) and multivariate (P=0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions.

Conclusion

Decreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.
gC1qR: A New Target for Cancer Immunotherapy
Authors: Lei Yanna , Li Xiaoyu , Qin Diyuan , Zhang Yugu , Wang Yongsheng
Published: January 2023

Although breakthroughs in cancer treatment have been achieved, immunotherapy yields only modest benefits in most patients. There is still a gap in clarifying the immune evasiveness and immune-resistance mechanisms. Identifying other candidate targets for cancer immunotherapy is therefore a clear unmet clinical need. The complement system, a pillar of innate immunity, has recently entered the limelight due to its immunoregulatory functions in the tumor microenvironment (TME). In particular, gC1qR, a receptor for globular heads of C1q, serves as a promising new target and has attracted more attention. gC1qR, also named P32/C1qBP/HABP1, is a multifunctional protein that is overexpressed in various cancers and holds prognostic value. It regulates the tumorigenic, progression and metastatic properties of tumor cells through several downstream signaling pathways, including the Wnt/β-catenin, PKC–NF-κB and Akt/PKB pathways. A few preclinical experiments conducted through gC1qR interventions, such as monoclonal antibody, chimeric antigen receptor T‐cell (CAR‐T) therapy, and tumor vaccination, have shown encouraging results in anticancer activity. The efficacy may rely on the regulatory role on the TME, induction of tumor cells apoptosis and antiangiogenic activity. Nevertheless, the current understanding of the relationship between cancer immunotherapy and gC1qR remains elusive and often contradictory, posing both opportunities and challenges for therapeutic translation in the clinic. In this review, we focus on the current understanding of gC1qR function in cancer immunology and highlight the vital roles in regulating the TME. We also examines the rationale behind targeting gC1qR and discusses the potential for translating into clinical practice.
IgD shapes the pre-immune naïve B cell compartment in humans
Authors: Dirks Johannes , Andres Oliver , Paul Luisa , Manukjan Georgi , Schulze Harald , Morbach Henner
Published: January 2023

B cell maturation and immunoglobulin (Ig) repertoire selection are governed by expression of a functional B cell receptor (BCR). Naïve B cells co-express their BCR as IgM and IgD isotype. However, the role of the additionally expressed IgD on naïve B cells is not known. Here we assessed the impact of IgD on naïve B cell maturation and Ig repertoire selection in 8 individuals from 3 different families with heterozygous loss-of-function or loss-of expression mutations in IGHD. Although naïve B cells from these individuals expressed IgM on their surface, the IGHD variant in heterozygous state entailed a chimeric situation by allelic exclusion with almost half of the naïve B cell population lacking surface IgD expression. Flow cytometric analyses revealed a distinct phenotype of IgD-negative naïve B cells with decreased expression of CD19, CD20 and CD21 as well as lower BAFF-R and integrin-β7 expression. IgD-negative B cells were less responsive in vitro after engaging the IgM-BCR, TLR7/9 or CD40 pathway. Additionally, a selective disadvantage of IgD-negative B cells within the T2 transitional and mature naïve B cell compartment as well as reduced frequencies of IgMlo/- B cells within the mature naïve B cell compartment lacking IgD were evident. RNA-Ig-seq of bulk sorted B cell populations showed an altered selection of distinct VH segments in the IgD-negative mature naïve B cell population. We conclude that IgD expression on human naïve B cells is redundant for generation of naïve B cells in general, but further shapes the naive B cell compartment starting from T2 transitional B cells. Our observations suggest an unexpected role of IgD expression to be critical for selection of distinct Ig VH segments into the pre-immune Ig repertoire and for the survival of IgMlo/- naïve B cells known to be enriched in poly-/autoreactive B cell clones.
Characterization of myeloperoxidase and its contribution to antimicrobial effect on extracellular traps in flounder (Paralichthys olivaceus)
Authors: Gan Qiujie , Chi Heng , Dalmo Roy Ambli , Meng Xianghu , Tang Xiaoqian , Xing Jing , Sheng Xiuzhen , Zhan Wenbin
Published: January 2023

Myeloperoxidase (MPO) is a cationic leukocyte haloperoxidase and together with other proteins, they possess activities against various microorganisms and are involved in extracellular trap (ET) formation. The present work describes the gene and deduced protein sequences, and functions of MPO in flounder (PoMPO). The PoMPO possesses a 2313 bp open reading frame (ORF) that encodes a protein of 770 amino acids. The highest PoMPO mRNA expression levels were found in the head kidney, followed by peritoneal cells, gill, spleen, skin, muscle, and liver. PoMPO was expressed in MHCII+ and GCSFR+ cells which indicated that PoMPO mainly is expressed in flounder macrophages and granulocytes. Bacterial lipopolysaccharide-stimulated peritoneal leukocytes showed an increased protein level of PoMPO while it seemed that LPS also promoted the migration of MPO+ cells from the head kidney into the peripheral blood and peritoneal cavity. After phorbol 12-myristate 13-acetate (PMA) or bacterial stimulation, flounder leukocytes produced typical ET structures containing DNA with decoration by MPO. The ETs containing DNA and PoMPO effectively inhibited the proliferation of ET-trapped bacteria. Blocking PoMPO with antibodies decreased the enzymatic activity, which attenuated the antibacterial activity of ETs. This study pinpoints the involvement of ETs in flounder innate responses to pathogens.
Inflammation balance in skeletal muscle damage and repair
Authors: Tu Huiyin , Li Yu-Long
Published: January 2023

Responding to tissue injury, skeletal muscles undergo the tissue destruction and reconstruction accompanied with inflammation. The immune system recognizes the molecules released from or exposed on the damaged tissue. In the local minor tissue damage, tissue-resident macrophages sequester pro-inflammatory debris to prevent initiation of inflammation. In most cases of the skeletal muscle injury, however, a cascade of inflammation will be initiated through activation of local macrophages and mast cells and recruitment of immune cells from blood circulation to the injured site by recongnization of damage-associated molecular patterns (DAMPs) and activated complement system. During the inflammation, macrophages and neutrophils scavenge the tissue debris to release inflammatory cytokines and the latter stimulates myoblast fusion and vascularization to promote injured muscle repair. On the other hand, an abundance of released inflammatory cytokines and chemokines causes the profound hyper-inflammation and mobilization of immune cells to trigger a vicious cycle and lead to the cytokine storm. The cytokine storm results in the elevation of cytolytic and cytotoxic molecules and reactive oxygen species (ROS) in the damaged muscle to aggravates the tissue injury, including the healthy bystander tissue. Severe inflammation in the skeletal muscle can lead to rhabdomyolysis and cause sepsis-like systemic inflammation response syndrome (SIRS) and remote organ damage. Therefore, understanding more details on the involvement of inflammatory factors and immune cells in the skeletal muscle damage and repair can provide the new precise therapeutic strategies, including attenuation of the muscle damage and promotion of the muscle repair.
Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis
Authors: Lai Zhen-Zhen , Zhang Jie , Zhou Wen-Jie , Shi Jia-Wei , Yang Hui-Li , Yang Shao-Liang , Wu Jiang-Nan , Xie Feng , Zhang Tao , Li Ming-Qing
Published: January 2023

Introduction

Recurrent implantation failure (RIF) is a frustrating challenge because the cause is unknown. The current study aims to identify differentially expressed genes (DEGs) in the endometrium on the basis of immune cell infiltration characteristics between RIF patients and healthy controls, as well as to investigate potential prognostic markers in RIF.

Methods

GSE103465, and GSE111974 datasets from the Gene Expression Omnibus database were obtained to screen DEGs between RIF and control groups. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, Gene Set Enrichment Analysis, and Protein-protein interactions analysis were performed to investigate potential biological functions and signaling pathways. CIBERSORT was used to describe the level of immune infiltration in RIF, and flow cytometry was used to confirm the top two most abundant immune cells detected.

Results

122 downregulated and 66 upregulated DEGs were obtained between RIF and control groups. Six immune-related hub genes were discovered, which were involved in Wnt/-catenin signaling and Notch signaling as a result of our research. The ROC curves revealed that three of the six identified genes (AKT1, PSMB8, and PSMD10) had potential diagnostic values for RIF. Finally, we used cMap analysis to identify potential therapeutic or induced compounds for RIF, among which fulvestrant (estrogen receptor antagonist), bisindolylmaleimide-ix (CDK and PKC inhibitor), and JNK-9L (JNK inhibitor) were thought to influence the pathogenic process of RIF. Furthermore, our findings revealed the level of immune infiltration in RIF by highlighting three signaling pathways (Wnt/-catenin signaling, Notch signaling, and immune response) and three potential diagnostic DEGs (AKT1, PSMB8, and PSMD10).

Conclusion

Importantly, our findings may contribute to the scientific basis for several potential therapeutic agents to improve endometrial receptivity.
A non-inferiority and GLP-compliant study of broflanilide IRS (VECTRON™ T500), a novel meta-diamide insecticide against Anopheles arabiensis
Authors: Mbewe Njelembo J. , Kirby Matthew J. , Snetselaar Janneke , Kaaya Robert D. , Small Graham , Azizi Salum , Ezekia Kisengwa , Manunda Baltazari , Shirima Boniface , Mosha Franklin W. , Rowland Mark W.
Published: January 2023

Management of insecticide resistance in vector control requires development and evaluation of active ingredients (AIs) with new modes of action. VECTRON™ T500 is a wettable powder formulation used for Indoor Residual Spraying (IRS) containing 50% of broflanilide as an AI. This study evaluated the efficacy of VECTRON™ T500 sprayed on blocks of different substrates (concrete, mud and plywood) against pyrethroid susceptible and resistant Anopheles gambiae sensu stricto (s.s.) strains, and wild An. arabiensis. It also assessed the efficacy of VECTRON™ T500 in experimental huts plastered with mud and concrete against wild free-flying An. arabiensis; and non-inferiority to a World Health Organization listed indoor residual spraying product Actellic® 300CS in terms of mortality in Moshi, Tanzania.Monthly cone bioassays on blocks and in experimental huts (against pyrethroid susceptible and resistant An. gambiae s.s.) were conducted over a 12-month period after spraying of VECTRON™ T500 and Actellic® CS300. Collections of wild free-flying An. arabiensis were also done in the sprayed huts. The main outcome for cone bioassays was mortality while for the wild hut trial collections, it was mortality and blood feeding inhibition. Grouped logistic regressions with random effects were used to analyse all dichotomous outcome variables from wild collections.The results showed residual efficacy of VECTRON™ T500 of at least 80% mortality was longest on concrete, followed by plywood and then mud substrates for all mosquito strains. Furthermore, VECTRON™ T500 significantly increased the likelihood of mortality (OR:> 1.37, P<0.001) in wild collections of An. arabiensis compared to Actellic® 300CS. Blood feeding was not significantly different in the wild collection of An. arabiensis between VECTRON™ T500 and Actellic® 300CS arms.These results show that VECTRON™ T500 is efficacious against pyrethroid-resistant An. gambiae s.s. and non-inferior to Actellic® 300CS. Therefore, it should be an important addition to the current arsenal of insecticides used for insecticide resistance management and vector control.
Effects of season and diel cycle on hydroacoustic estimates of density, Target Strength, and vertical distribution of fish in Yudong Reservoir, a plateau deep water reservoir in southwest China in a plateau deep
Authors: Mei Feng , Zhang Chaoshuo , Luo Bin , Zhang Dongxu , Hu Shaoqiu , Bao Jianghui , Lian Yuxi , Zhao Daxian , Duan Ming
Published: January 2023

Hydroacoustics is a non-invasive fish stock assessment sampling technique that plays an important role in fishery science and management. However, non-standard hydroacoustic surveys could lead to biased results, and the factor of the sampling period (e.g., season and diel cycle) is extremely critical as it can greatly affect hydroacoustic results. Efforts to improve the accuracy and credibility of the hydroacoustic survey results are getting more and more attention. Thus, we conducted two diel hydroacoustic surveysin situin summer and winter to detect whether there were diel and seasonal differences in density, Target Strength (TS) and vertical distribution of fish. The results indicated that nighttime had significantly higher fish mean density than daytime in summer and winter. No significant difference between summer and winter daytime, however, significant difference between summer and winter nighttime, but this bias could be accepted from the fisheries management perspective; The meanTSof the summer daytime was significantly higher than that of summer nighttime, winter daytime and winter nighttime, but there were no significant differences among summer nighttime, winter daytime, and winter nighttime, mainly due to meanTSmay be overestimated from fish schooling behavior during summer daytime; The fish vertical distribution had significant seasonal correlations and was more dispersed in different water layers during the nighttime, proving that the assessment was better at nighttime than during the daytime. Consequently, the hydroacoustic surveys in Yudong Reservoir and other similar plateau deep water reservoirs should be performed at nighttime, which will yield relatively accurate density andTS, and dispersed vertical distribution of fish.
Spatial link between Adélie penguin foraging effort and krill swarm abundance and distribution
Authors: Riaz Javed , Bestley Sophie , Wotherspoon Simon , Cox Martin J. , Emmerson Louise
Published: January 2023

Understanding how predator foraging behaviour is influenced by the distribution and abundance of prey is a fundamental challenge in marine foraging ecology. This is particularly relevant in Southern Ocean ecosystems where the relationships between select predator species and Antarctic krill (Euphausia superba) can inform ecosystem conservation and precautionary fisheries management. In this study, we examine the spatial associations between krill swarm characteristics and Adélie penguin (Pygoscelis adeliae) foraging effort at Béchervaise Island, a long-term monitoring site in East Antarctica. Spatially integrating two years of regional-scale krill acoustic data with contemporaneous horizontal and vertical movement information from chick-rearing adult Adélie penguins, we assessed how penguin foraging effort changed in relation to krill swarm abundance and distribution across the survey area. Our findings show that penguin diving effort was focused in areas with a high number of krill swarms, yet they did not focus their effort in areas with high krill biomass. These results suggest the spatial organisation of Adélie penguin foraging effort can provide an indication of krill presence (and/or availability) but may not reflect krill abundance. We discuss our results in the context of penguin foraging strategies, capturing single krill within the water column rather than the engulfment feeding strategy of larger marine mammals such as whales. Our work substantially improves understanding of penguin-krill dynamics in East Antarctica and provides a greater level of nuance regarding the utility of Adélie penguins as indicator species under CCAMLR’s Ecosystem Monitoring Programme (CEMP). Understanding these predator-prey linkages will become increasingly important for managing any expanding krill fisheries in the region or changes in the prey field under future climate change scenarios. Thus, our results can be interpreted alongside other ecological indicators to support management of the East Antarctic sector of the Southern Ocean ecosystem.
Phytoplankton community structure in the Western Subarctic Gyre of the Pacific Ocean during summer determined by a combined approach of HPLC-pigment CHEMTAX and metabarcoding sequencing
Authors: Xin Quandong , Qin Xiaohan , Wu Guannan , Ding Xiaokun , Wang Xinliang , Hu Qingjing , Mu Changkao , Wei Yuqiu , Chen Jufa , Jiang Tao
Published: January 2023

The Western Subarctic Gyre (WSG) is a cyclonic upwelling gyre in the northwest subarctic Pacific, which is a region with a high concentration of nutrients but low chlorophyll. We investigated the community structure and spatial distribution of phytoplankton in this area by using HPLC-pigment CHEMTAX (a chemotaxonomy program) and metabarcoding sequencing during the summer of 2021. The phytoplankton community showed significant differences between the two methods. The CHEMTAX analyses identified eight major marine phytoplankton assemblages. Cryptophytes were the major contributors (24.96%) to the total Chl a, followed by pelagophytes, prymnesiophytes, diatoms, and chlorophytes. The eukaryotic phytoplankton OTUs obtained by metabarcoding were categorized into 149 species in 96 genera of 6 major groups (diatoms, prymnesiophytes, pelagophytes, chlorophytes, cryptophytes, and dinoflagellates). Dinoflagellates were the most abundant group, accounting for 44.74% of the total OTUs obtained, followed by cryptophytes and pelagophytes. Sixteen out of the 97 identified species were annotated as harmful algal species, and Heterocapsa rotundata, Karlodinium veneficum, and Aureococcus anophagefferens were assigned to the abundant group (i.e., at least 0.1% of the total reads). Nutrients were more important in shaping the phytoplankton community than temperature and salinity. The 24 stations were divided into southern and northern regions along 44°N according to the k-means method, with the former being dominated by high Chl a and low nutrients. Although different phytoplankton assemblages analyzed by the two methods showed various relationships with environmental factors, a common feature was that the dinoflagellate proportion showed a significantly negative correlation with low nutrients and a positive correlation with Chl a.
PathNarratives: Data annotation for pathological human-AI collaborative diagnosis
Authors: Zhang Heyu , He Yan , Wu Xiaomin , Huang Peixiang , Qin Wenkang , Wang Fan , Ye Juxiang , Huang Xirui , Liao Yanfang , Chen Hang , Guo Limei , Shi Xueying , Luo Lin
Published: January 2023

Pathology is the gold standard of clinical diagnosis. Artificial intelligence (AI) in pathology becomes a new trend, but it is still not widely used due to the lack of necessary explanations for pathologists to understand the rationale. Clinic-compliant explanations besides the diagnostic decision of pathological images are essential for AI model training to provide diagnostic suggestions assisting pathologists practice. In this study, we propose a new annotation form, PathNarratives, that includes a hierarchical decision-to-reason data structure, a narrative annotation process, and a multimodal interactive annotation tool. Following PathNarratives, we recruited 8 pathologist annotators to build a colorectal pathological dataset, CR-PathNarratives, containing 174 whole-slide images (WSIs). We further experiment on the dataset with classification and captioning tasks to explore the clinical scenarios of human-AI-collaborative pathological diagnosis. The classification tasks show that fine-grain prediction enhances the overall classification accuracy from 79.56 to 85.26%. In Human-AI collaboration experience, the trust and confidence scores from 8 pathologists raised from 3.88 to 4.63 with providing more details. Results show that the classification and captioning tasks achieve better results with reason labels, provide explainable clues for doctors to understand and make the final decision and thus can support a better experience of human-AI collaboration in pathological diagnosis. In the future, we plan to optimize the tools for the annotation process, and expand the datasets with more WSIs and covering more pathological domains.
Bitter-RF: A random forest machine model for recognizing bitter peptides
Authors: Zhang Yu-Fei , Wang Yu-Hao , Gu Zhi-Feng , Pan Xian-Run , Li Jian , Ding Hui , Zhang Yang , Deng Ke-Jun
Published: January 2023

Introduction

Bitter peptides are short peptides with potential medical applications. The huge potential behind its bitter taste remains to be tapped. To better explore the value of bitter peptides in practice, we need a more effective classification method for identifying bitter peptides.

Methods

In this study, we developed a Random forest (RF)-based model, called Bitter-RF, using sequence information of the bitter peptide. Bitter-RF covers more comprehensive and extensive information by integrating 10 features extracted from the bitter peptides and achieves better results than the latest generation model on independent validation set.

Results

The proposed model can improve the accurate classification of bitter peptides (AUROC = 0.98 on independent set test) and enrich the practical application of RF method in protein classification tasks which has not been used to build a prediction model for bitter peptides.

Discussion

We hope the Bitter-RF could provide more conveniences to scholars for bitter peptide research.
Lacticaseibacillus rhamnosus C1 effectively inhibits Penicillium roqueforti: Effects of antimycotic culture supernatant on toxin synthesis and corresponding gene expression
Authors: An Peipei , Li Li , Huang Pei , Zheng Yin , Jin Zekun , Korma Sameh A. , Ren Namei , Zhang Nan
Published: January 2023

Recently, consumers are increasingly concerned about the contamination of food by molds and the addition of chemical preservatives. As natural and beneficial bacteria, probiotics are a prospective alternative in food conservation because of their antimycotic activities, although the mechanism has not been explained fully at the level of metabolites. This study aimed at investigating the antifungal activities and their mechanisms of five potential probiotic strains (Lacticaseibacillus rhamnosus C1, Lacticaseibacillus casei M8, Lactobacillus amylolyticus L6, Schleiferilactobacillus harbinensis M1, and Limosilactobacillus fermentum M4) against Penicillium roqueforti, the common type of mold growth on the bread. Results showed that C1 emerged the strongest effectiveness at blocking mycelium growth, damaging the morphology of hyphae and microconidia, decreasing DNA content and interfering in the synthesis of the fungal toxins patulin, roquefortine C and PR-toxin, as well as downregulating the expression of key genes associated with the toxin biosynthesis pathways. Further metabonomic investigation revealed that protocatechuic acid with the minimum inhibitory concentration of 0.40 mg/mL, may be most likely responsible for positively correlated with the antimycotic effects of C1. Thus, C1 is expected to be both a potentially greatly efficient and environmental antimycotic for controlling P. roqueforti contamination in foods.
Biotin pathway in novel Fodinibius salsisoli sp. nov., isolated from hypersaline soils and reclassification of the genus Aliifodinibius as Fodinibius
Authors: Galisteo Cristina , de la Haba Rafael R. , Sánchez-Porro Cristina , Ventosa Antonio
Published: January 2023

Hypersaline soils are extreme environments that have received little attention until the last few years. Their halophilic prokaryotic population seems to be more diverse than those of well-known aquatic systems. Among those inhabitants, representatives of the family Balneolaceae (phylum Balneolota) have been described to be abundant, but very few members have been isolated and characterized to date. This family comprises the genera Aliifodinibius and Fodinibius along with four others. A novel strain, designated 1BSP15-2V2T, has been isolated from hypersaline soils located in the Odiel Saltmarshes Natural Area (Southwest Spain), which appears to represent a new species related to the genus Aliifodinibius. However, comparative genomic analyses of members of the family Balneolaceae have revealed that the genera Aliifodinibius and Fodinibius belong to a single genus, hence we propose the reclassification of the species of the genus Aliifodinibius into the genus Fodinibius, which was first described. The novel strain is thus described as Fodinibius salsisoli sp. nov., with 1BSP15-2V2T (=CCM 9117T = CECT 30246T) as the designated type strain. This species and other closely related ones show abundant genomic recruitment within 80–90% identity range when searched against several hypersaline soil metagenomic databases investigated. This might suggest that there are still uncultured, yet abundant closely related representatives to this family present in these environments. In-depth in-silico analysis of the metabolism of Fodinibius showed that the biotin biosynthesis pathway was present in the genomes of strain 1BSP15-2V2T and other species of the family Balneolaceae, which could entail major implications in their community role providing this vitamin to other organisms that depend on an exogenous source of this nutrient.
Group A streptococci induce stronger M protein-fibronectin interaction when specific human antibodies are bound
Authors: Wrighton Sebastian , Ahnlide Vibha Kumra , André Oscar , Bahnan Wael , Nordenfelt Pontus
Published: January 2023

Group A streptococcus (GAS) is a highly adapted, human-specific pathogen that is known to manipulate the immune system through various mechanisms. GAS’ M protein constitutes a primary target of the immune system due to its spatial configuration and dominance on the bacterial surface. Antibody responses targeting the M protein have been shown to favor the conserved C region. Such antibodies (Abs) circumvent antigenic escape and efficiently bind to various M types. The ability of GAS to bind to fibronectin (Fn), a high molecular weight glycoprotein of the extracellular matrix, has long been known to be essential for the pathogen’s evolutionary success and fitness. However, some strains lack the ability to efficiently bind Fn. Instead, they have been found to additionally bind Fn via the A-B domains of their M proteins. Here, we show that human Abs can induce increased Fn-binding affinity in M proteins, likely by enhancing the weak A-B domain binding. We found that this enhanced Fn binding leads to a reduction in Ab-mediated phagocytosis, indicating that this constitutes a GAS immune escape mechanism. We could show that the Fc domain of Abs is necessary to trigger this phenomenon and that Ab flexibility may also play a key role. We, moreover, saw that our Abs could enhance Fn binding in 3 out of 5 emm type strains tested, belonging to different clades, making it likely that this is a more generalizable phenomenon. Together our results suggest a novel synergistic interplay of GAS and host proteins which ultimately benefits the bacterium.
An exploration of alginate oligosaccharides modulating intestinal inflammatory networks via gut microbiota
Authors: Zhang Zhikai , Wang Xuejiang , Li Feng
Published: January 2023

Alginate oligosaccharides (AOS) can be obtained by acidolysis and enzymatic hydrolysis. The products obtained by different methods have different structures and physiological functions. AOS have received increasing interest because of their many health-promoting properties. AOS have been reported to exert protective roles for intestinal homeostasis by modulating gut microbiota, which is closely associated with intestinal inflammation, gut barrier strength, bacterial infection, tissue injury, and biological activities. However, the roles of AOS in intestinal inflammation network remain not well understood. A review of published reports may help us to establish the linkage that AOS may improve intestinal inflammation network by affecting T helper type 1 (Th1) Th2, Th9, Th17, Th22 and regulatory T (Treg) cells, and their secreted cytokines [the hub genes of protein–protein interaction networks include interleukin-1 beta (IL-1β), IL-2, IL-4, IL-6, IL-10 and tumor necrosis factor alpha (TNF-α)] via the regulation of probiotics. The potential functional roles of molecular mechanisms are explored in this study. However, the exact mechanism for the direct interaction between AOS and probiotics or pathogenic bacteria is not yet fully understood. AOS receptors may be located on the plasma membrane of gut microbiota and will be a key solution to address such an important issue. The present paper provides a better understanding of the protecting functions of AOS on intestinal inflammation and immunity.
Distinct response patterns of plants and soil microorganisms to agronomic practices and seasonal variation in a floodplain ecosystem
Authors: Yu Yanyan , Liu Hao , Zhang Lanlan , Sun Zhongjie , Lei Binghai , Miao Yuan , Chu Haiyan , Han Shijie , Shi Yu , Zheng Junqiang
Published: January 2023

Introduction

Climate change and anthropogenic activities are the greatest threats to floodplain ecosystems. A growing body of literature shows that floodplain ecosystems have experienced increased chemical fertilizer and pesticide loads, which will disturb the above and belowground ecosystems. However, we lack knowledge regarding the effects of such human activities on the vegetation and soil microbiomes in these ecosystems.

Methods

In the present study, plant functional traits and Illumina Mi-Seq sequencing were to assess the impact of nitrogen fertilizer and glyphosate addition on the structure and function of the vegetation and soil microbiomes (bacteria, fungi, and protists) in a floodplain ecosystem, and to assess the influence of seasonal variation.

Results

We identified distinct response mechanisms of plant and microbial communities to the addition of nitrogen fertilizer and glyphosate, and seasonal variation. Nitrogen fertilizer and glyphosate significantly affected plant diversity, aboveground and underground biomass, and C and N content and significantly changed the leaf area and plant stature of dominant plants. However, the addition of nitrogen fertilizer and glyphosate did not significantly affect the diversity and structure of bacterial, fungal, and protist communities. The application of nitrogen fertilizer could improve the negative effects of glyphosate on the functional traits of plant communities. The seasonal variation of floodplain has significantly changed the soil’s physical, chemical, and biological properties. Our results showed that compared with that in summer, the soil ecosystem multifunctionality of the floodplain ecosystem in autumn was significantly lower. Seasonal variation had a significant effect on plant diversity and functional traits. Moreover, seasonal variation significantly affected the community compositions, diversity, and structure of bacteria, fungi, and protists. Seasonal variation had a stronger impact on fungal community assembly than on that of bacteria and protists. In summer, the assembly of the fungal community was dominated by a deterministic process, while in autumn, it is dominated by a stochastic process. In addition, the negative association among bacteria, fungi, and protists has been strengthened in autumn and formed a more robust network to cope with external changes.

Discussion

These results extended our understanding of the ecological patterns of soil microbiomes in floodplain ecosystems and provided support for enhancing the ecological barrier function and the service potential of floodplain ecosystems.
The hidden microbial ecosystem in the perennial ice from a Pyrenean ice cave
Authors: Ruiz-Blas Fátima , Muñoz-Hisado Víctor , Garcia-Lopez Eva , Moreno Ana , Bartolomé Miguel , Leunda Maria , Martinez-Alonso Emma , Alcázar Alberto , Cid Cristina
Published: January 2023

Over the last years, perennial ice deposits located within caves have awakened interest as places to study microbial communities since they represent unique cryospheric archives of climate change. Since the beginning of the twentieth century, the temperature has gradually increased, and it is estimated that by the end of this century the increase in average temperature could be around 4.0°C. In this context of global warming the ice deposits of the Pyrenean caves are undergoing a significant regression. Among this type of caves, that on the Cotiella Massif in the Southern Pyrenees is one of the southernmost studied in Europe. These types of caves house microbial communities which have so far been barely explored, and therefore their study is necessary. In this work, the microbial communities of the Pyrenean ice cave A294 were identified using metabarcoding techniques. In addition, research work was carried out to analyze how the age and composition of the ice affect the composition of the bacterial and microeukaryotic populations. Finally, the in vivo effect of climate change on the cellular machinery that allow microorganisms to live with increasing temperatures has been studied using proteomic techniques.
Infection and innate immune mechanism of goose astrovirus
Authors: Xu Linhua , Jiang Bowen , Cheng Yao , He Yu , Wu Zhen , Wang Mingshu , Jia Renyong , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Mao Sai , Ou Xumin , Gao Qun , Sun Di , Cheng Anchun , Chen Shun
Published: January 2023

Goose astrovirus (GAstV, genus Avian Astrovirus, family Astrovirus) was first discovered in 2005, but was not considered as a pathogen of gosling gout until 2016. Since then, goose astrovirus has erupted in Chinese goslings, causing at most 50% of gosling deaths. By December 2022, the disease had become epidemic and prevailed in goose farms in Jiangsu, Shandong, Anhui, Henan, Guangdong, Liaoning, Sichuan and other places in China. The disease mainly affects goslings within 3 weeks old. The typical symptoms of goose astrovirus are large deposits of urate in the viscera, joint cavity and ureter surface of infected goslings. Goose astrovirus infection can trigger high levels of iNOS, limiting goose astrovirus replication. The ORF2 domain P2 of the goose astrovirus activates the OASL protein, limiting its replication. Goose astrovirus can also activate pattern recognition receptors (RIG-I, MDA-5, TLR-3), causing an increase in MHC-Ia, MHC-Ib and CD81 mRNA, activating humoral and cellular immunity, thereby hindering virus invasion. Goose astrovirus also regulates the activation of IFNs and other antiviral proteins (Mx1, IFITM3, and PKR) in the spleens and kidneys to inhibit viral replication. The innate immune response process in goslings also activates TGF-β, which may be closely related to the immune escape of goose astrovirus. Gaining insight into the infection and innate immune mechanism of goose astrovirus can help researchers study and prevent the severe disease in goslings better.
Advanced bioactive nanomaterials for diagnosis and treatment of major chronic diseases
Authors: Liu Yongfei , Yi Yi , Zhong Chengqian , Ma Zecong , Wang Haifeng , Dong Xingmo , Yu Feng , Li Jing , Chen Qinqi , Lin Chaolu , Li Xiaohong
Published: January 2023

With the rapid innovation of nanoscience and technology, nanomaterials have also been deeply applied in the medical and health industry and become one of the innovative methods to treat many diseases. In recent years, bioactive nanomaterials have attracted extensive attention and have made some progress in the treatment of some major chronic diseases, such as nervous system diseases and various malignant tumors. Bioactive nanomaterials depend on their physical and chemical properties (crystal structure, surface charge, surface functional groups, morphology, and size, etc.) and direct produce biological activity and play to the role of the treatment of diseases, compared with the traditional nanometer pharmaceutical preparations, biological active nano materials don’t exert effects through drug release, way more directly, also is expected to be more effective for the treatment of diseases. However, further studies are needed in the evaluation of biological effects, fatein vivo, structure-activity relationship and clinical transformation of bionanomaterials. Based on the latest research reports, this paper reviews the application of bioactive nanomaterials in the diagnosis and treatment of major chronic diseases and analyzes the technical challenges and key scientific issues faced by bioactive nanomaterials in the diagnosis and treatment of diseases, to provide suggestions for the future development of this field.
Is DNA methylation in the brain a mechanism of alcohol use disorder?
Authors: Jarczak Justyna , Miszczak Michalina , Radwanska Kasia
Published: January 2023

Alcohol use disorder (AUD) is a worldwide problem. Unfortunately, the molecular mechanisms of alcohol misuse are still poorly understood, therefore successful therapeutic approaches are limited. Accumulating data indicate that the tendency for compulsive alcohol use is inherited, suggesting a genetic background as an important factor. However, the probability to develop AUD is also affected by life experience and environmental factors. Therefore, the epigenetic modifications that are altered over lifetime likely contribute to increased risk of alcohol misuse. Here, we review the literature looking for the link between DNA methylation in the brain, a common epigenetic modification, and AUD-related behaviors in humans, mice and rats. We sum up the main findings, identify the existing gaps in our knowledge and indicate future directions of the research.