bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast cancer detection: Shallow convolutional neural network against deep convolutional neural networks based approach
Authors: Das Himanish Shekhar , Das Akalpita , Neog Anupal , Mallik Saurav , Bora Kangkana , Zhao Zhongming
Published: January 2023

Introduction: Of all the cancers that afflict women, breast cancer (BC) has the second-highest mortality rate, and it is also believed to be the primary cause of the high death rate. Breast cancer is the most common cancer that affects women globally. There are two types of breast tumors: benign (less harmful and unlikely to become breast cancer) and malignant (which are very dangerous and might result in aberrant cells that could result in cancer).

Methods: To find breast abnormalities like masses and micro-calcifications, competent and educated radiologists often examine mammographic images. This study focuses on computer-aided diagnosis to help radiologists make more precise diagnoses of breast cancer. This study aims to compare and examine the performance of the proposed shallow convolutional neural network architecture having different specifications against pre-trained deep convolutional neural network architectures trained on mammography images. Mammogram images are pre-processed in this study's initial attempt to carry out the automatic identification of BC. Thereafter, three different types of shallow convolutional neural networks with representational differences are then fed with the resulting data. In the second method, transfer learning via fine-tuning is used to feed the same collection of images into pre-trained convolutional neural networks VGG19, ResNet50, MobileNet-v2, Inception-v3, Xception, and Inception-ResNet-v2.

Results: In our experiment with two datasets, the accuracy for the CBIS-DDSM and INbreast datasets are 80.4%, 89.2%, and 87.8%, 95.1% respectively.

Discussion: It can be concluded from the experimental findings that the deep network-based approach with precise tuning outperforms all other state-of-the-art techniques in experiments on both datasets.
Identification of oncogenes and tumor-suppressor genes with hepatocellular carcinoma: A comprehensive analysis based on TCGA and GEO datasets
Authors: Zhu Yue , Wang Yanfei , Hu Mengyao , Lu Xiaoting , Sun Guoping
Published: January 2023

Aim: Existing targeted therapies for hepatocellular carcinoma (HCC) are resistant and have limitations. It is crucial to find new HCC-related target genes.

Methods: RNA-sequencing data of HCC were gathered from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Initially, differentially expressed genes between normal and tumor tissues were identified from four Gene Expression Omnibus datasets, GSE36376, GSE102079, GSE54236, and GSE45267. GO terms and KEGG pathway enrichment analyses were performed to explore the potential biological functions of differentially expressed genes. A PPI network was constructed by using the STRING database, and up-regulated and down-regulated hub genes were defined through 12 topological approaches. Subsequently, the correlation bounded by up-regulated genes and down-regulated genes in the diagnosis, prognosis, and clinicopathological features of HCC was analyzed. Beyond a shadow of doubt, the key oncogene PBK and tumor suppressor gene F9 were screened out, and the specific mechanism was investigated through GSEA enrichment analysis and immune correlation analysis. The role of PBK in HCC was further verified by western blot, CCK8, transwell, and tube formation experiments.

Results:CDCA5, CDC20, PBK, PRC1, TOP2A, and NCAPG are good indicators of HCC diagnosis and prognosis. The low expressions of F9, AFM, and C8B indicate malignant progression and poor prognosis of HCC. PBK was found to be closely related to VEGF, VEGFR, and PDGFR pathways. Experiments showed that PBK promotes HCC cell proliferation, migration, invasion, and tube formation in HUVEC cells. F9 was negatively correlated with the degree of immune infiltration, and low expression of F9 suggested a poor response to immunotherapy.

Conclusion: The role of HCC-related oncogenes and tumor-suppressor genes in diagnosis and prognosis was identified. In addition, we have found that PBK may promote tumor proliferation through angiogenesis and F9 may be a predictor of tumor immunotherapy response.
Identification of an unrecognized circRNA associated with development of renal fibrosis
Authors: Zhu Yun , Yan Weimin , Xu Shuangyan , Yu Xiaochao , Sun Shuo , Zhang Shaoxiong , Zhao Ran , Tao Jiayue , Li Yunwei , Li Cuie
Published: January 2023

Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive.

Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly.

Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis.

Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.
Genomic diversity and relationship analyses of endangered German Black Pied cattle (DSN) to 68 other taurine breeds based on whole-genome sequencing
Authors: Neumann Guilherme B. , Korkuć Paula , Arends Danny , Wolf Manuel J. , May Katharina , König Sven , Brockmann Gudrun A.
Published: January 2023

German Black Pied cattle (Deutsches Schwarzbuntes Niederungsrind, DSN) are an endangered dual-purpose cattle breed originating from the North Sea region. The population comprises about 2,500 cattle and is considered one of the ancestral populations of the modern Holstein breed. The current study aimed at defining the breeds closest related to DSN cattle, characterizing their genomic diversity and inbreeding. In addition, the detection of selection signatures between DSN and Holstein was a goal. Relationship analyses using fixation index (FST), phylogenetic, and admixture analyses were performed between DSN and 68 other breeds from the 1000 Bull Genomes Project. Nucleotide diversity, observed heterozygosity, and expected heterozygosity were calculated as metrics for genomic diversity. Inbreeding was measured as excess of homozygosity (FHom) and genomic inbreeding (FRoH) through runs of homozygosity (RoHs). Region-wide FST and cross-population-extended haplotype homozygosity (XP-EHH) between DSN and Holstein were used to detect selection signatures between the two breeds, and RoH islands were used to detect selection signatures within DSN and Holstein. DSN showed a close genetic relationship with breeds from the Netherlands, Belgium, Northern Germany, and Scandinavia, such as Dutch Friesian Red, Dutch Improved Red, Belgian Red White Campine, Red White Dual Purpose, Modern Angler, Modern Danish Red, and Holstein. The nucleotide diversity in DSN (0.151%) was higher than in Holstein (0.147%) and other breeds, e.g., Norwegian Red (0.149%), Red White Dual Purpose (0.149%), Swedish Red (0.149%), Hereford (0.145%), Angus (0.143%), and Jersey (0.136%). The FHom and FRoH values in DSN were among the lowest. Regions with high FST between DSN and Holstein, significant XP-EHH regions, and RoH islands detected in both breeds harbor candidate genes that were previously reported for milk, meat, fertility, production, and health traits, including one QTL detected in DSN for endoparasite infection resistance. The selection signatures between DSN and Holstein provide evidence of regions responsible for the dual-purpose properties of DSN and the milk type of Holstein. Despite the small population size, DSN has a high level of diversity and low inbreeding. FST supports its relatedness to breeds from the same geographic origin and provides information on potential gene pools that could be used to maintain diversity in DSN.
The altered metabolites contributed by dysbiosis of gut microbiota are associated with microbial translocation and immune activation during HIV infection
Authors: Zhang Yu , Xie Zhiman , Zhou Jie , Li Yanjun , Ning Chuanyi , Su Qisi , Ye Li , Ai Sufang , Lai Jingzhen , Pan Peijiang , Liu Ningmei , Liao Yanyan , Su Qijian , Li Zhuoxin , Liang Hao , Cui Ping , Huang Jiegang
Published: January 2023

Background

The immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported.

Methods

We conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples.

Results

The pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation.

Conclusions

Metabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.
The relevance between hypoxia-dependent spatial transcriptomics and the prognosis and efficacy of immunotherapy in claudin-low breast cancer
Authors: Sun Huizhi , Li Yanlei , Zhang Yanhui , Zhao Xiulan , Dong Xueyi , Guo Yuhong , Mo Jing , Che Na , Ban Xinchao , Li Fan , Bai Xiaoyu , Li Yue , Hao Jihui , Zhang Danfang
Published: January 2023

Introduction

Hypoxia is an important characteristic of solid tumors. However, spatial transcriptomics (ST) of hypoxia-associated heterogeneity is not clear.

Methods

This study integrated Spatial Transcriptomics (ST) with immunofluorescence to demonstrate their spatial distribution in human claudin-low breast cancer MDA-MB-231 engraft. ST spots were clustered with differentially expression genes. The data were combined with hypoxia-specific marker and angiogenesis marker-labeled serial sections to indicate the spatial distribution of hypoxia and hypoxia-inducted transcriptional profile. Moreover, marker genes, cluster-specific hypoxia genes, and their co-essential relationship were identified and mapped in every clusters. The clinicopathological association of marker genes of hypoxia-dependent spatial clusters was explored in 1904 breast cancers from METABRIC database.

Results

The tumor from center to periphery were enriched into five hypoxia-dependent subgroups with differentially expressed genes, which were matched to necrosis, necrosis periphery, hypoxic tumor, adaptive survival tumor, and invasive tumor, respectively. Different subgroups demonstrated distinct hypoxia condition and spatial heterogeneity in biological behavior and signaling pathways. Cox regression analysis showed that the invasive tumor (cluster 0) and hypoxic tumor (cluster 6) score could be served as independent prognostic factors in claudin-low patients. KM analysis indicated that high invasive tumor (cluster 0) and hypoxic tumor (cluster 6) score was associated with poor prognoses of claudin-low patients. Further analysis showed that hypoxia-induced immune checkpoints, such as CD276 and NRP1, upregulation in invasive tumor to block infiltration and activation of B cells and CD8+ T cells to change tumor immune microenvironment.

Discussion

This study reveals hypoxia-dependent spatial heterogeneity in claudin-low breast cancer and highlights its potential value as a predictive biomarker of clinical outcomes and immunotherapy response. The molecules found in this study also provided potential molecular mechanisms and therapeutic targets for subsequent studies.
Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis
Authors: Zhu Youwen , Liu Kun , Qin Qun , Zhu Hong
Published: January 2023

Introduction

The ASTRUM-005 trial (NCT04063163) revealed that combination serplulimab plus chemotherapy (etoposide and carboplatin [EC]) treatment was associated with survival advantages relative to chemotherapy alone in patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC). As these immuno-chemotherapeutic regimens are extremely expensive, however, it is critical that the relative cost-effectiveness of combination serplulimab and chemotherapy treatment as a first-line treatment for ES-SCLC patients be examined in detail.

Methods

The cost-effectiveness of combined serplulimab plus chemotherapeutic treatment was examined using a comprehensive Markov model with a 10-year boundary, enabling the calculation of overall cost, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model instability was interrogated through one-way and probabilistic sensitivity analyses.

Results

Serplulimab plus chemotherapy or chemotherapy alone respectively yielded 1.217 QALYs (2.243 LYs) and 0.885 QALYs (1.661 LYs) with corresponding total costs of $11,202 and $7,194, with an ICER of $12,077 per QALY ($6,883 per LY). This model was most strongly influenced by the utility of progression-free survival. Probabilistic sensitivity analysis showed that serplulimab plus chemotherapy had a 91.6% probability of being cost-effective at a willingness-to-pay (WTP) of $37,653 per QALY (3 × capita gross domestic product of China in 2021). In subgroup analyses, this combination treatment regimen was found to be most cost-effective in patients who were former smokers, had an ECOG performance status of 0, and were diagnosed with brain metastases.

Conclusion

From a payer perspective in China, combination serplulimab plus chemotherapy treatment represents a cost-effective first-line intervention for ES-SCLC patients.
Drastic transformation of visceral adipose tissue and peripheral CD4 T cells in obesity
Authors: Shirakawa Kohsuke , Sano Motoaki
Published: January 2023

Obesity has a pronounced effect on the immune response in systemic organs that results in not only insulin resistance but also altered immune responses to infectious diseases and malignant tumors. Obesity-associated microenvironmental changes alter transcriptional expression and metabolism in T cells, leading to alterations in T-cell differentiation, proliferation, function, and survival. Adipokines, cytokines, and lipids derived from obese visceral adipose tissue (VAT) may also contribute to the systemic T-cell phenotype, resulting in obesity-specific pathogenesis. VAT T cells, which have multiple roles in regulating homeostasis and energy utilization and defending against pathogens, are most susceptible to obesity. In particular, many studies have shown that CD4 T cells are deeply involved in the homeostasis of VAT endocrine and metabolic functions and in obesity-related chronic inflammation. In obesity, macrophages and adipocytes in VAT function as antigen-presenting cells and contribute to the obesity-specific CD4 T-cell response by inducing CD4 T-cell proliferation and differentiation into inflammatory effectors via interactions between major histocompatibility complex class II and T-cell receptors. When obesity persists, prolonged stimulation by leptin and circulating free fatty acids, repetitive antigen stimulation, activating stress responses, and hypoxia induce exhaustion of CD4 T cells in VAT. T-cell exhaustion is characterized by restricted effector function, persistent expression of inhibitory receptors, and a transcriptional state distinct from functional effector and memory T cells. Moreover, obesity causes thymic regression, which may result in homeostatic proliferation of obesity-specific T-cell subsets due to changes in T-cell metabolism and gene expression in VAT. In addition to causing T-cell exhaustion, obesity also accelerates cellular senescence of CD4 T cells. Senescent CD4 T cells secrete osteopontin, which causes further VAT inflammation. The obesity-associated transformation of CD4 T cells remains a negative legacy even after weight loss, causing treatment resistance of obesity-related conditions. This review discusses the marked transformation of CD4 T cells in VAT and systemic organs as a consequence of obesity-related microenvironmental changes.
Modulating the tumor immune microenvironment with locoregional image-guided interventions
Authors: Jain Samagra , Sheth Rahul A.
Published: January 2023

Cancer immunotherapy has gained significant attention in recent years and has revolutionized the modern approach to cancer therapy. However, cancer immunotherapy is still limited in its full potential due to various tumor immune-avoidance behaviors and delivery barriers, and this is seen in the low objective response rates of most cancers to immunotherapy. A novel approach to immunotherapy utilizes image-guided administration of immunotherapeutic agents directly into a tumor site; this technique offers several advantages, including avoidance of potent toxicity, bypassing the tumor immunosuppressive microenvironment, and higher therapeutic bioavailability relative to systemic drug administration. This review presents the biological rationale for locoregional image-guided immunotherapy administration, summarizes the existing interventional oncology approaches to immunotherapy, and discusses emerging technological advances in biomaterials and drug delivery that could further advance the field of interventional oncology.
Mannose-modified erythrocyte membrane-encapsulated chitovanic nanoparticles as a DNA vaccine carrier against reticuloendothelial tissue hyperplasia virus
Authors: Feng Yangyang , Tang Feng , Li Sheng , Wu Daiyan , Liu Qianqian , Li Hangyu , Zhang Xinnan , Liu Ziwei , Zhang Linzi , Feng Haibo
Published: January 2023

Introduction

The erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs).

Methods

In this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo.

Results

CS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge.

Conclusion

Overall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects.
The potential role of cfDNA-related innate immune responses in postoperative bone loss after alveolar bone grafting
Authors: Huang Hanyao , Yang Renjie , Shi Bing
Published: January 2023

The purpose of treating alveolar bone cleft is to restore a normal maxilla structure. Multiple factors have been identified that can affect the success of alveolar bone grafting. However, with consistent treatment modifications, the surgical outcomes have been improved, but alveolar bone loss still exists. Thus, a new aspect should be found to solve this problem. As alveolar bone belongs to the periodontal tissues, the mechanism of the alveolar bone loss after bone grafting in patients with alveolar bone cleft may be similar to the development of alveolar bone loss in periodontitis. Cell-free DNA (cfDNA) has been demonstrated as a key promoter of alveolar bone loss during periodontal inflammation. We hypothesized that cfDNA-related innate immune responses could be a major inducement for postoperative bone loss after alveolar bone grafting. In this perspective, we preliminarily proved the potential association between cfDNA, TLR9 pathway, and alveolar bone grafting operation, and it might verify that surgical trauma could accumulate cfDNA, which can further activate cellular TLR9 signaling.
A case report of steroid-refractory bullous pemphigoid induced by immune checkpoint inhibitor therapy
Authors: Guan Shasha , Zhang Linlin , Zhang Junyan , Song Wenjing , Zhong Diansheng
Published: January 2023

The widespread use of immune checkpoint inhibitors in several malignancies has revealed new immune-related adverse events. Bullous pemphigoid (BP) is an antibody-driven autoimmune disease characterized by skin inflammation and fluid-filled bullae. Herein, a 69-year-old man with lung squamous cell carcinoma developed multiple vesicles and tense bullae 3 weeks after the initiation of a programmed death-1 (PD-1) inhibitor, pembrolizumab, and chemotherapy. Biopsy revealed a subepidermal bulla with lymphocytic and eosinophil infiltration, and immunohistochemical studies predominantly showed CD4+ cells, a few CD8+ cells, and the occasional CD20+ lymphocyte. The serum anti-BP180 antibody level, as well as the interleukin-6 and interleukin-10 levels, were elevated compared to the lower levels of tumor necrosis factor-α. Eosinophil levels were high and consistent with the development of blisters. A diagnosis of BP associated with PD-1 inhibitor therapy was made, and the Common Terminology Criteria for Adverse Events classification was grade 3. Immunotherapy was permanently discontinued, and the patient’s bullous lesions failed to react to high-dose systemic corticosteroids combined with minocycline and niacinamide. Intermittent blister recurrence occurred in 2 months, eventually improving with the administration of two courses of intravenous immunoglobulin. At 5 weeks of follow-up, the patient’s tumor was reduced on a computed tomographic scan. Despite stable BP treatment, however, he repeatedly developed complications due to the complexity of his underlying disease and could not be treated with anti-tumor therapy. Early recognition and management of serious immune-related bullous dermatologic toxicity are essential for patient safety.
Functional changes in cytotoxic CD8+ T-cell cross-reactivity against the SARS-CoV-2 Omicron variant after mRNA vaccination
Authors: Nogimori Takuto , Suzuki Koichiro , Masuta Yuji , Washizaki Ayaka , Yagoto Mika , Ikeda Mami , Katayama Yuki , Kanda Hidenori , Takada Minoru , Minami Shohei , Kobayashi Takeshi , Takahama Shokichi , Yoshioka Yasuo , Yamamoto Takuya
Published: January 2023

Understanding the T-cell responses involved in inhibiting COVID-19 severity is crucial for developing new therapeutic and vaccine strategies. Here, we characterized SARS-CoV-2 spike-specific CD8+ T cells in vaccinees longitudinally. The BNT162b2 mRNA vaccine can induce spike-specific CD8+ T cells cross-reacting to BA.1, whereas the T-cell receptor (TCR) repertoire usages decreased with time. Furthermore the mRNA vaccine induced spike-specific CD8+ T cells subpopulation expressing Granzyme A (GZMA), Granzyme B (GZMB) and Perforin simultaneously in healthy donors at 4 weeks after the second vaccination. The induced subpopulation was not maintained at 12 weeks after the second vaccination. Incorporating factors that efficiently induce CD8+ T cells with highly cytotoxic activity could improve future vaccine efficacy against such variants.
Comparison of first-line treatments for elderly patients with diffuse large B-cell lymphoma: A systematic review and network meta-analysis
Authors: Wang Yangyang , Ren Xiyang , Huang Keke , Liang Xue , Pu Lianfang , Hu Linhui , Zhai Zhimin
Published: January 2023

Background

The incidence of DLBCL in elderly patients has been gradually increased. Considering their comorbidities and performance status, the first-line standard treatment hasn’t been determined for the elderly.

Methods

We performed a systemic review and network meta-analysis to compare the efficacy and safety of all eligible regimens as first line treatment for elderly patients with DLBCL. We searched PubMed, Cochrane Library, and Embase Library proceedings up to March 2022.

Results

Our search yielded thirteen trials including 1839 patients. R2CHOP21 showed the best PFS with a statistical difference and the most favorable OS without a statistical difference. RCOMP showed the most clinical benefits in EFS, CR and OR with no significant difference. The point estimate was in favored improved DFS with RCHOP14 than RCHOP21, although this was not statistically significant. In a subgroup analysis concerning 3-4 grade AEs revealed R-COMP was associated with a decrease in grade III/IV neutropenia and cardiac toxic events; RminiCEOP was associated with the lower rates of 3-4 grade anemia, thrombocytopenia and infection; RCHOP21 had the lowest rate of 3-4 grade AE of neurotoxicity.

Conclusion

The findings of our meta-analysis indicated that R2CHOP21 provided the best disease control in PFS and represented an optimal first-line treatment option in the elderly with DLBCL. Furthermore, RCOMP, RminiCEOP and RCHOP21 exhibited lower rates in different 3-4 grade AEs and might be reasonable treatment options in the elderly with poor general conditions.
Maternal Lactobacillus rhamnosus administration impacts neonatal CD4 T-cell activation and prevents murine T helper 2-type allergic airways disease
Authors: Smout Justine , Valentin Clara , Delbauve Sandrine , Pauwels Jeanne , Köhler Arnaud , Flamand Véronique
Published: January 2023

Gut microbiota plays a role in the neonatal immune education and could influence susceptibility to Th2-type immune disorders, such as allergies, the most prevalent chronic diseases in early childhood. We studied the impact of oral Lactobacillus rhamnosus (L.rhamnosus) supplementation to pregnant/breastfeeding C57BL/6 mice on the development of allergic airways disease in their offspring. We observed that mice, from L.rhamnosus-treated mothers, inoculated with ovalbumin (OVA)-Aluminium hydroxide (ALUM) at 3 days of life and challenged intranasally 4 weeks later showed decreased Th2-associated cytokines, IgE and IgG1, lung eosinophilia and airway hyper-reactivity compared to OVA-sensitized mice from untreated mothers. In that setting, the L.rhamnosus treatment increased the number and maturation of splenic neonatal type 1 conventional dendritic cells (cDC1) that remained largely dominant over the cDC2 and favored their OVA-specific Th1 differentiation. In response to inhaled house dust mite (HDM) allergen, the maternal L.rhamnosus supplementation increased the number of neonatal pulmonary cDC1 expressing lower amount of costimulatory molecules compared with no supplementation and decreased the number of cDC2 without affecting their costimulatory molecules expression. An HDM-specific Foxp3+RORγt+ Treg polarization was monitored in the lung draining lymph nodes. Finally, we confirmed the inhibitory effect of maternal L.rhamnosus treatment on all the measured features of the HDM allergic airways reaction in their offspring. We conclude that maternal L.rhamnosus administration prevents Th2-type allergic airways disease in their neonates by favoring splenic cDC1/Th1 responses against ALUM-adjuvanted OVA or by promoting a pulmonary Foxp3+RORγt+ Treg activation against inhaled HDM.
Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19
Authors: Hopkins Francis R. , Govender Melissa , Svanberg Cecilia , Nordgren Johan , Waller Hjalmar , Nilsdotter-Augustinsson Åsa , Henningsson Anna J. , Hagbom Marie , Sjöwall Johanna , Nyström Sofia , Larsson Marie
Published: January 2023

Introduction

After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.

Methods

Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.

Results

We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.

Conclusion

By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.
Narciclasine inhibits phospholipase A2 and regulates phospholipid metabolism to ameliorate psoriasis-like dermatitis
Authors: Kong Yi , Jiang Jian , Huang Yuqiong , Liu Xin , Jin Zilin , Li Li , Wei Fen , Liu Xinxin , Yin Jie , Zhang Yonghui , Tong Qingyi , Chen Hongxiang
Published: January 2023

Introduction

Psoriasis is a common inflammatory skin disease recognized by the World Health Organization as "an incurable chronic, noninfectious, painful, disfiguring and disabling disease." The fact that metabolic syndrome (MetS) is the most common and important comorbidities of psoriasis suggests an important role of lipid metabolism in the pathogenesis of psoriasis. Narciclasine (Ncs) is an alkaloid isolated from the Amaryllidaceae plants. Its biological activities include antitumor, antibacterial, antiinflammatory, anti-angiogenic and promoting energy expenditure to improve dietinduced obesity. Here, we report that Ncs may be a potential candidate for psoriasis, acting at both the organismal and cellular levels.

Methods

The therapeutic effect of Ncs was assessed in IMQ-induced psoriasis-like mouse model. Then, through in vitro experiments, we explored the inhibitory effect of Ncs on HaCaT cell proliferation and Th17 cell polarization; Transcriptomics and lipidomics were used to analyze the major targets of Ncs; Single-cell sequencing data was used to identify the target cells of Ncs action.

Results

Ncs can inhibit keratinocyte proliferation and reduce the recruitment of immune cells in the skin by inhibiting psoriasis-associated inflammatory mediators. In addition, it showed a direct repression effect on Th17 cell polarization. Transcriptomic and lipidomic data further revealed that Ncs extensively regulated lipid metabolismrelated genes, especially the Phospholipase A2 (PLA2) family, and increased antiinflammatory lipid molecules. Combined with single-cell data analysis, we confirmed that keratinocytes are the main cells in which Ncs functions.

Discussion

Taken together, our findings indicate that Ncs alleviates psoriasiform skin inflammation in mice, which is associated with inhibition of PLA2 in keratinocytes and improved phospholipid metabolism. Ncs has the potential for further development as a novel anti-psoriasis drug.
m6A eraser FTO modulates autophagy by targeting SQSTM1/P62 in the prevention of canagliflozin against renal fibrosis
Authors: Yang Youjing , Li Qianmin , Ling Yi , Leng Linxin , Ma Yu , Xue Lian , Lu Guoyuan , Ding Yue , Li Jianzhong , Tao Shasha
Published: January 2023

The dysregulation of autophagy contributes to renal fibrosis. N6-Methyladenosine (m6A) RNA modification is a critical mediator of autophagy. Our previous studies have reported that the disorder of the PPARα/fatty acid oxidation (FAO) axis in renal tubular cells is suppressed by STAT6, which is involved in the regulation of renal fibrotic processes. Here, we found that canagliflozin significantly upregulates SQSTM1/P62, promoting PPARα-mediated FAO by inducing autophagy-dependent STAT6 degradation both in TGF-β1-treated HK2 cells and in unilateral ureteral occlusion (UUO) and ischemia–reperfusion (I/R) renal fibrosis mouse models. Knockdown of P62/SQSTM1 led to the impairment autophagic flux and the dysregulation of the STAT6/PPARα axis, which was confirmed by SQSTM1/P62cKO mice with UUO treatment along with bioinformatics analysis. Furthermore, SQSTM1/P62 deficiency in renal tubular cells inhibited canagliflozin’s effects that prevent FAO disorder in renal tubular cells and renal fibrosis. Mechanistically, the level of m6A eraser FTO, which interacted with SQSTM1 mRNA, decreased in the renal tubular cells both in vitro and in vivo after canagliflozin administration. Decrease in FTO stabilized SQSTM1 mRNA, which induced autophagosome formation. Collectively, this study uncovered a previously unrecognized function of canagliflozin in FTO in the autophagy modulation through the regulation of SQSTM1 mRNA stability in the renal tubular STAT6/PPARα/FAO axis and renal fibrosis.
Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis
Authors: Liu Peng , Qian Yerong , Liu Xin , Zhu Xulong , Zhang Xufeng , Lv Yi , Xiang Junxi
Published: January 2023

Liver fibrosis is a fibrogenic and inflammatory process that results from hepatocyte injury and is characterized by hepatic architectural distortion and resultant loss of liver function. There is no effective treatment for advanced fibrosis other than liver transplantation, but it is limited by expensive costs, immune rejection, and postoperative complications. With the development of regenerative medicine in recent years, mesenchymal stem cell (MSCs) transplantation has become the most promising treatment for liver fibrosis. The underlying mechanisms of MSC anti-fibrotic effects include hepatocyte differentiation, paracrine, and immunomodulation, with immunomodulation playing a central role. This review discusses the immune cells involved in liver fibrosis, the immunomodulatory properties of MSCs, and the immunomodulation mechanisms of MSC-based strategies to attenuate liver fibrosis. Meanwhile, we discuss the current challenges and future directions as well.
Granulocytic myeloid-derived suppressor cells increase infection risk via the IDO/IL-10 pathway in patients with hepatitis B virus-related liver failure
Authors: Yu Xueping , Sun Jian , Yang Feifei , Mao Richeng , Shen Zhiqing , Ren Lan , Yuan Songhua , He Qian , Zhang Linxia , Yang Yu , Ding Xiangqing , He Yongquan , Zhu Haoxiang , Shen Zhongliang , Zhu Mengqi , Qiu Chao , Su Zhijun , Zhang Jiming
Published: January 2023

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) results in high susceptibility to infection. Although granulocytic myeloid-derived suppressor cells (gMDSC) are elevated in patients with HBV-ACLF, their role in HBV-ACLF pathogenesis is unknown. To elucidate the mechanism of gMDSC expansion and susceptibility to infection in HBV-ACLF patients, we analyzed the proportion of gMDSC in the peripheral blood and organ tissues of patients with HBV-ACLF and an ACLF mouse model established by continuous injection (eight times) of Concanavalin by flow cytometry and immunohistochemistry. We found that the proportion of gMDSC increased significantly in the blood and liver of patients with HBV-ACLF. This increase was positively correlated with disease severity, prognosis, and infection. gMDSC percentages were higher in peripheral blood, liver, spleen, and bone marrow than control levels in the ACLF mouse model. Immunofluorescence revealed that the gMDSC count increased in the liver of patients with HBV-ACLF as well as in the liver and spleen of ACLF mice. We further exposed peripheral blood monocyte cells from healthy donors to plasma from HBV-ACLF patients, recombinant cytokines, or their inhibitor, and found that TNF-α led to gMDSC expansion and significant upregulation of indoleamine 2, 3-dioxygenase (IDO), while blocking TNF-α signaling decreased gMDSC. Moreover, we detected proliferation and cytokine secretion of T lymphocytes when purified gMDSC was co-cultured with Pan T cells or IDO inhibitor and found that TNF-α-induced gMDSC inhibited T cell proliferation and interferon-γ production through the IDO signaling pathway. Lastly, the ability of gMDSC to phagocytose bacteria was low in patients with HBV-ACLF. Our findings elucidate HBV-ACLF pathogenesis and provide potential therapeutic targets.
Impact of ashes from the 2022 Tonga volcanic eruption on satellite ocean color signatures
Authors: Whiteside Andra , Dupouy Cécile , Singh Awnesh , Bani Philipson , Tan Jing , Frouin Robert
Published: January 2023

A powerful eruption within the Hunga Tonga-Hunga Ha’apai (HTHH) volcano (20.64°S, 175.19°W) in the Kingdom of Tonga, occurred on 15 January 2022. The volcanic blast was enormous, leading many scientists to investigate the full impact and magnitude of this event via satellite observations. In this study, we describe a new ocean color signature from a discolored water patch created by the HTHH eruption using NASA and CMEMS products of satellite-derived biological and optical properties. Elevated surface chlorophyll-a concentration (Chl-a) between 0.15 to 2.7 mg.m-3 was not associated with phytoplankton growth, but to basalt-andesitic ash material expelled by the volcano and into the ocean, which resulted in erroneous Chl-a estimates. Distribution of the patch over time was aligned with CMEMS ocean currents for 19 days. The gradual decrease of light attenuation or diffuse attenuation coefficient for downward irradiance at 490 nm, Kd(490), was interpreted as due to the sinking of ash particles with time. It is suggested that due to high porosity of 30-40%, a density close to that of seawater, ash particles stay suspended in the water column for more than 10 days with sustained high values of satellite-derived Chl-a, Kd(490), and particulate backscattering coefficient at 443 nm. The high attenuation of light due to ash, reducing the penetration depth to less than 10 meters during the first period after the eruption may have had implications on ecological processes and biogeochemical cycles in Tongan waters.
Cascade effects of seafloor litter on benthic ecosystems in the northern Yellow Sea
Authors: Teng Guangliang , Shan Xiujuan , Jin Xianshi
Published: January 2023

The accumulation of seafloor litter changes the habitats of benthic organisms and thus affects their spatial distribution. Previous studies suggested that the accumulation of seafloor litter might contribute to the bloom of Metridium senile fimbriatum, given that seafloor litter could serve as “vectors” for M. senile dispersal and provide with “natural habitat” for their settlement. As a common fouler and invader, M. senile bloom will inevitably affect the benthic ecosystems. The cascading effects of seafloor litter on benthic ecosystems can be explored by studying the interactions between this litter-associated anemone and other co-occurred species. Therefore, this study uses stable isotope analysis to study the food composition of M. senile attached to the seafloor litter and the niche relationship with co-occurred species. First, by comparing the stable isotope ratios of the pedal disc and tentacle of M. senile, it was found that the δ15N of the foot disc is more stable than that of the tentacle, so the pedal disc was chosen as the sampling tissue. The mean δ13C value of M. senile was -19.34 ± 0.86‰, which ranged from -22.30‰ to -18.17‰. For δ15N, the mean value was 12.02 ± 0.95‰, which ranged from 9.22‰ to 13.31‰. Then, we quantified the contribution of the potential food resources of M. senile using the SIMMR model. M. senile has the highest feeding proportion to crustaceans, followed by juvenile fish, zooplankton and other macrobenthos. Meanwhile, M. senile has high uncertainty in the feeding proportion of crustaceans and juvenile fish. In addition, the trophic niche overlap between different functional groups was calculated by the SIBER model, and the results showed that the isotopic niche of M. senile was overlapped with different functional groups, ranging from 34.29 to 35.25%. Therefore, this study suggests that M. senile, as litter-associated carnivorous anemone, interacts with other components in the ecosystems through predation and competition, which also reveals the cascade effect of seafloor litter on the benthic ecosystems of the northern Yellow Sea.
Spatial and seasonal variability of horizontal temperature fronts in the Mozambique Channel for both epipelagic and mesopelagic realms
Authors: Sudre Floriane , Dewitte Boris , Mazoyer Camille , Garçon Véronique , Sudre Joel , Penven Pierrick , Rossi Vincent
Published: January 2023

Introduction

Ocean fronts are moving ephemeral biological hotspots forming at the interface of cooler and warmer waters. In the open ocean, this is where marine organisms, ranging from plankton to mesopelagic fish up to megafauna, gather and where most fishing activities concentrate. Fronts are critical ecosystems so that understanding their spatio-temporal variability is essential not only for conservation goals but also to ensure sustainable fisheries. The Mozambique Channel (MC) is an ideal laboratory to study ocean front variability due to its energetic flow at sub-to-mesoscales, its high biodiversity and the currently debated conservation initiatives. Meanwhile, fronts detection relying solely on remotely-sensed Sea Surface Temperature (SST) cannot access aspects of the subsurface frontal activity that may be relevant for understanding ecosystem dynamics.

Method

In this study, we used the Belkin and O’Reilly Algorithm on remotely-sensed SST and hindcasts of a high-resolution nested ocean model to investigate the spatial and seasonal variability of temperature fronts at different depths in the MC.

Results

We find that the seasonally varying spatial patterns of frontal activity can be interpreted as resulting from main features of the mean circulation in the MC region. In particular, horizontally, temperature fronts are intense and frequent along continental shelves, in islands’ wakes, at the edge of eddies, and in the pathways of both North-East Madagascar Current (NEMC) and South-East Madagascar Current (SEMC). In austral summer, thermal fronts in the MC are mainly associated with the Angoche upwelling and seasonal variability of the Mozambique current. In austral winter, thermal fronts in the MC are more intense when the NEMC and the Seychelles-Chagos and South Madagascar upwelling cells intensify. Vertically, the intensity of temperature fronts peaks in the vicinity of the mean thermocline.

Discussion

Considering the marked seasonality of frontal activity evidenced here and the dynamical connections of the MC circulation with equatorial variability, our study calls for addressing longer timescales of variability to investigate how ocean ecosystem/front interactions will evolve with climate change.
Stock assessment using length–based Bayesian evaluation method for Trichiurus lepturus in the East China Sea
Authors: Zhu Kai , Zhu Wenbin , Shi Yongchuang
Published: January 2023

Fishery resources assessment is the basis of scientific management and sustainable development of fisheries.Trichiurus lepturus, one of the major commercial fishes in the East China Sea, is of great significance to study its stocks status. Based on length frequency data ofT. lepturuscollected in the East China Sea from 2016 to 2020, we estimated asymptotic length, optimal length at first capture, relative mortality, and relative biomass of the stock using length–based Bayesian biomass estimation (LBB). The analysis shows a high exploitation rate and low biomass suggesting that the stock ofT. lepturushas been overfished and is currently under heavy fishing pressure. Although the number of fishing vessels decreased by 29% from 2016 to 2020, the fishing horsepower decreased by only 9%, indicating that the fishing pressure on fishery resources is still high. To recover the stock, we consider the reduction of fishing intensity and enforcing of size–at–first–capture regulations to be imperative. In addition to reducing fishing boats and horsepower, it is essential to increase the escape proportion of juvenile fish by increasing the mesh size, and reduce the proportion of juvenile fish in the catch. The result in this study can provide informative reference for fishery stock assessmentT. lepturusin the East China Sea under the data–limited conditions.