bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel neutrophil extracellular trap signature to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma
Authors: Li Qilin , Chen Weimin , Li Qiuhui , Mao Jing , Chen Xin
Published: September 2022

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and patients with HNSCC possess early metastases and poor prognosis. Systematic therapies (including chemotherapy, targeted therapy, and immunotherapy) are generally applied in the advanced/late stages of HNSCC, but primary and acquired resistance eventually occurs. At present, reliable biomarkers to predict the prognosis of HNSCC have not been completely identified. Recent studies have shown that neutrophil extracellular traps (NETs) are implicated in cancer progression, metastasis and cancer immune response, and NET-related gene signatures are associated with the prognosis of patients with several human cancers. To explore whether NET-related genes play crucial roles in HNSCC, we have performed systematic analysis and reported several findings in the current study. Firstly, we identified seven novel NET-related genes and developed a NET-score signature, which was highly associated with the clinicopathological and immune traits of the HNSCC patients. Then, we, for the first time, found that NIFK was significantly upregulated in HNSCC patient samples, and its levels were significantly linked to tumor malignancy and immune status. Moreover, functional experiments confirmed that NIFK was required for HNSCC cell proliferation and metastasis. Altogether, this study has identified a novel NET-score signature based on seven novel NET-related genes to predict the prognosis of HNSCC and NIFK has also explored a new method for personalized chemo-/immuno-therapy of HNSCC.
Serum hepatitis B virus large and medium surface proteins as novel tools for predicting HBsAg clearance
Authors: Lin Xiao , Zheng Yanhong , Li Hong , Lu Junfeng , Ren Shan , Liu Yisi , Wang Xiaoxiao , Zheng Sujun , Ma Lina , Cao Zhenhuan , Chen Xinyue
Published: September 2022

Background

There is still lack of reliable predictors for hepatitis B surface antigen (HBsAg) clearance. Recent studies have shown that the levels of large (LHBs) and medium hepatitis B surface proteins (MHBs) are closely related to antiviral efficacy. This study aimed to investigate the possibility of LHB and MHB levels to predict HBsAg clearance.

Methods

An inactive HBsAg carriers (IHCs) cohort that had received pegylated interferon (Peg-IFN) treatment was divided into the HBsAg-cleared group (R group) and the HBsAg non-cleared group (NR group) based on whether HBsAg was cleared at 96 weeks. We detected the levels of LHBs and MHBs to evaluate the possibility of predicting HBsAg clearance.

Results

There were 39 patients in the R group and 21 in the NR group. The total HBsAg, LHB, and MHB levels at baseline and at 12 weeks were significantly lower in the R group than in the NR group (all p< 0.05). Multivariate logistic regression indicated that LHB and MHB levels at baseline and 12 weeks were independent predictors of HBsAg clearance (OR = 0.435, p = 0.016; OR = 0.136, p = 0.003; OR = 0.137, p = 0.033; OR = 0.049, p = 0.043). The area under the curve (AUC) for the baseline and 12-week LHB and MHB levels was 0.827-0.896, which were greater than that of the total HBsAg level at baseline and 12-week (AUC: 0.654-0.755). Compared with the prediction results of a single indicator, the combination of LHB and MHB levels had better value in predicting HBsAg clearance. The AUCs of combination factor 1, constructed from baseline LHB and MHB, and combination factor 2, constructed from 12-week LHB and MHB, were 0.922 and 0.939, respectively, and the sensitivity (82.05%-100.00%) and specificity (85.71%-100.00%) were both high. The combined indicators based on baseline LHBs ≤ 13.99 ng/mL and MHBs ≤ 7.95 ng/mL predicted HBsAg clearance rate of more than 90%.

Conclusion

Baseline and 12-week LHB and MHB levels can predict HBsAg clearance obtained by Peg-IFN therapy in IHCs, and the predictive value is higher than that of the total HBsAg levels.
GSDMD contributes to myocardial reperfusion injury by regulating pyroptosis
Authors: Ye Xiaomiao , Zhang Peng , Zhang Yuting , Luan Jingyun , Xu Caili , Wu Zhengyu , Ju Dianwen , Hu Wei
Published: September 2022

Background

Gasdermin D (GSDMD) plays an essential role in the pathway of pyroptosis. However, whether GSDMD participates in myocardial ischaemia/reperfusion injury (MI/RI) remains poorly understood.

Methods

Serum levels of GSDMD and IL-18 in ST-segment elevation myocardial infarction (STEMI) patients were measured by ELISA. The expression of GSDMD and GSDMD N-terminal (GSDMD-NT) in vivo and in vitro was assessed by western blot and immunofluorescence staining. GSDMD-/- mice and wild type (WT) mice were induced MI/RI, followed by cardiac ultrasound and histological analysis.

Results

Clinically, patients suffering from STEMI after percutaneous coronary intervention (PCI) exhibited higher levels of GSDMD and IL-18 than that in the controls. In vitro, the cleavage of GSDMD was significantly upregulated in macrophages exposed to hypoxia/reoxygenation or H2O2. In vivo, the levels of GSDMD and GSDMD-NT increased notably after MI/RI, especially in macrophages infiltrating in the infarct area. Moreover, compared with WT mice, GSDMD-/- mice showed reduced infarct size (25.45 ± 3.07% versus 36.47 ± 3.72%), improved left ventricular ejection fraction (37.71 ± 1.81% versus 29.44 ± 2.28%) and left ventricular fractional shortening (18.01 ± 0.97% versus 13.62 ± 1.15%) as well as attenuated pathological damage after I/R injury, along with reduced levels of proinflammatory cytokines and decreased infiltration of neutrophils.

Conclusions

Our study revealed that GSDMD deficiency significantly alleviated the inflammatory response by regulating pyroptosis, reduced the infarct size and preserved cardiac function after MI/RI, thus providing a potential strategy for the treatment of myocardial reperfusion injury.
Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience
Authors: Miyamoto Takayuki , Honda Yoshitaka , Izawa Kazushi , Kanazawa Nobuo , Kadowaki Saori , Ohnishi Hidenori , Fujimoto Masakazu , Kambe Naotomo , Kase Naoya , Shiba Takeshi , Nakagishi Yasuo , Akizuki Shuji , Murakami Kosaku , Bamba Masahiro , Nishida Yutaka , Inui Ayano , Fujisawa Tomoo , Nishida Daisuke , Iwata Naomi , Otsubo Yoshikazu , Ishimori Shingo , Nishikori Momoko , Tanizawa Kiminobu , Nakamura Tomoyuki , Ueda Takeshi , Ohwada Yoko , Tsuyusaki Yu , Shimizu Masaki , Ebato Takasuke , Iwao Kousho , Kubo Akiharu , Kawai Toshinao , Matsubayashi Tadashi , Miyazaki Tatsuhiko , Kanayama Tomohiro , Nishitani-Isa Masahiko , Nihira Hiroshi , Abe Junya , Tanaka Takayuki , Hiejima Eitaro , Okada Satoshi , Ohara Osamu , Saito Megumu K. , Takita Junko , Nishikomori Ryuta , Yasumi Takahiro
Published: September 2022

Purpose

Upregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature.

Methods

The type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature.

Results

A total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling.

Conclusions

Half of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.
Modeling the effect of environmental cytokines, nutrient conditions and hypoxia on CD4+ T cell differentiation
Authors: Martínez-Méndez David , Huerta Leonor , Villarreal Carlos
Published: September 2022

Upon antigen stimulation and co-stimulation, CD4+ T lymphocytes produce soluble factors that promote the activity of other immune cells against pathogens or modified tissues; this task must be performed in presence of a variety of environmental cytokines, nutrient, and oxygen conditions, which necessarily impact T cell function. The complexity of the early intracellular processes taking place upon lymphocyte stimulation is addressed by means of a mathematical model based on a network that integrates variable microenvironmental conditions with intracellular activating, regulatory, and metabolic signals. Besides the phenotype subsets considered in previous works (Th1, Th2, Th17, and Treg) the model includes the main early events in differentiation to the TFH phenotype. The model describes how cytokines, nutrients and oxygen availability regulate the differentiation of naïve CD4+ T cells into distinct subsets. Particularly, it shows that elevated amounts of an all-type mixture of effector cytokines under optimal nutrient and oxygen availability conduces the system towards a highly-polarized Th1 or Th2 state, while reduced cytokine levels allow the expression of the Th17, Treg or TFH subsets, or even hybrid phenotypes. On the other hand, optimal levels of an all-type cytokine mixture in combination with glutamine or tryptophan restriction implies a shift from Th1 to Th2 expression, while decreased levels of the Th2-inducing cytokine IL-4 leads to the rupture of the Th1-Th2 axis, allowing the manifestation of different (or hybrid) subsets. Modeling proposes that, even under reduced levels of pro-inflammatory cytokines, the sole action of hypoxia boost Th17 expression.
Exploration of immune response mechanisms in cadmium and copper co-exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling
Authors: Bao Xiaokai , Wang Weijun , Chen Xipan , Feng Yanwei , Xu Xiaohui , Sun Guohua , Li Bin , Liu Xiumei , Li Zan , Yang Jianmin
Published: September 2022

Sepia esculenta is a popular economic cephalopod with high yield, delicious meat, and rich nutrition. With the rapid development of heavy industry and medical industry, a large amount of waste has been released into the ocean recklessly in recent years, inducing a significant increase in the content of heavy metals, especially cadmium (Cd) and copper (Cu), in the ocean. This phenomenon significantly affects the growth and development of S. esculenta, causing a serious blow to its artificial breeding. In this study, transcriptome analysis is used to initially explore immune response mechanisms of Cd and Cu co-exposed juvenile S. esculenta. The results show that 1,088 differentially expressed genes (DEGs) are identified. And DEGs functional enrichment analysis results suggests that co-exposure may promote inflammatory and innate immune responses in juvenile S. esculenta. Fifteen key genes that might regulate the immunity of S. esculenta are identified using protein-protein interaction (PPI) network and KEGG enrichment analyses, of which the three genes with the highest number of interactions or involve in more KEGG pathways are identified as hub genes that might significantly affect the immune response processes. Comprehensive analysis of PPI network and KEGG signaling pathway is used for the first time to explore co-exposed S. esculenta juvenile immune response processes. Our results preliminarily reveal immune response mechanisms of cephalopods exposed to heavy metals and provide a valuable resource for further understanding of mollusk immunity.
Kinetics of vaccine-induced neutralizing antibody titers and estimated protective immunity against wild-type SARS-CoV-2 and the Delta variant: A prospective nationwide cohort study comparing three COVID-19 vaccination protocols in South Korea
Authors: Nham Eliel , Ko Jae-Hoon , Song Kyoung-Ho , Choi Ju-Yeon , Kim Eu Suk , Kim Hye-Jin , Kim Byoungguk , Lim Hee-Young , Kim Kyung-Chang , Jang Hee-Chang , Lee Kyoung Hwa , Song Young Goo , Baek Yae Jee , Ahn Jin Young , Choi Jun Yong , Kim Yong Chan , Park Yoon Soo , Choi Won Suk , Bae Seongman , Kim Sung-Han , Kang Eun-Suk , Jeong Hye Won , Kim Shin-Woo , Kwon Ki Tae , Kim Sung Soon , Peck Kyong Ran
Published: September 2022

Introduction

Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy.

Methods

We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant.

Results

We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2–99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7–100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0–87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT).

Conclusion

Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.
Diagnosis and treatment for the early stage of cytomegalovirus infection during hematopoietic stem cell transplantation
Authors: Cui Jiaqi , Zhao Kui , Sun Yanling , Wen Ruijuan , Zhang Xiangzhong , Li Xudong , Long Bing
Published: September 2022

Cytomegalovirus (CMV) infection remains a frequent complication after hematopoietic stem cell transplantation (HSCT) and causes significant morbidity and mortality in transplantation recipients. In this review, we highlight the role of major risk factors that are associated with the incidence of CMV infection. Advances in immunosurveillance may predict CMV infection, allowing early interventions to prevent severe infection. Furthermore, numerous therapeutic strategies against CMV infection after HSCT are summarized. A comprehensive understanding of the current situation of CMV treatment may provide a hint for clinical practice and even promote the development of novel strategies for precision medicine.
Protective role of host complement system in Aspergillus fumigatus infection
Authors: Shende Rajashri , Wong Sarah Sze Wah , Meitei Heikrujam Thoihen , Lal Girdhari , Madan Taruna , Aimanianda Vishukumar , Pal Jayanta Kumar , Sahu Arvind
Published: September 2022

Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined thein vivorole of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection byAspergillus fumigatus, the main species responsible for IA. We show that C3 knockout (C3-/-) mice are highly susceptible to systemic infection ofA. fumigatus. Intriguingly, C4-/-and factor B (FB)-/-mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically byA. fumigatusprotease. Ourin vitrostudy substantiates the presence of C3 and C5 cleaving proteases inA. fumigatus. Examination of the importance of the terminal complement pathway employing C5-/-and C5aR1-/-mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection byA. fumigatus.
Applications of machine learning in tumor-associated macrophages
Authors: Li Zhen , Yu Qijun , Zhu Qingyuan , Yang Xiaojing , Li Zhaobin , Fu Jie
Published: September 2022

Evaluation of tumor-host interaction and intratumoral heterogeneity in the tumor microenvironment (TME) is gaining increasing attention in modern cancer therapies because it can reveal unique information about the tumor status. As tumor-associated macrophages (TAMs) are the major immune cells infiltrating in TME, a better understanding of TAMs could help us further elucidate the cellular and molecular mechanisms responsible for cancer development. However, the high-dimensional and heterogeneous data in biology limit the extensive integrative analysis of cancer research. Machine learning algorithms are particularly suitable for oncology data analysis due to their flexibility and scalability to analyze diverse data types and strong computation power to learn underlying patterns from massive data sets. With the application of machine learning in analyzing TME, especially TAM’s traceable status, we could better understand the role of TAMs in tumor biology. Furthermore, we envision that the promotion of machine learning in this field could revolutionize tumor diagnosis, treatment stratification, and survival predictions in cancer research. In this article, we described key terms and concepts of machine learning, reviewed the applications of common methods in TAMs, and highlighted the challenges and future direction for TAMs in machine learning.
Case Report: Paroxysmal hyperhidrosis as an initial symptom in a patient with anti-LGI1 encephalitis
Authors: Qiao Tingting , Chen Lanlan , Jiang Li , Wei Hua , Chen Xin , Li Xiaobo , Chen Yingzhu , Xu Yao
Published: September 2022

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common cause of autoimmune encephalitis and is characterized by cognitive impairment, psychiatric disorders, and faciobrachial dystonic seizures. In recent decades, literature reports have expanded the phenotypic spectrum associated with the LGI1 autoantibody. The present report describes the case of a 58-year-old man who presented with repetitive unilateral hyperhidrosis of the body and arm as an initial symptom and gradually developed psychiatric symptoms, involuntary movements of the face and arms, and progressive cognitive decline. Anti-LGI1 antibodies were positive in both the serum and cerebrospinal fluid at approximately 2 months after symptom onset, and the patient was, therefore, diagnosed with anti-LGI1 encephalitis. His symptoms, namely hyperhidrosis and involuntary movements, were not relieved by antiepileptic drug treatment, but responded favorably to high-dose steroid therapy and intravenous immunoglobulin. We interpreted the repetitive unilateral hyperhidrosis as possible epilepsy. Based on this case, unilateral hyperhidrosis of the body and arm as a rare neurological presentation can be added to the phenotypic spectrum of anti-LGI1 encephalitis, and early recognition of this manifestation might support timely diagnosis and treatment.
Investigation of the efficacy and safety of cryoablation and intra-arterial PD-1 inhibitor in patients with advanced disease not responding to checkpoint inhibitors: An exploratory study
Authors: Wei Fuqun , Guo Rui , Yan Yuan , Lin Ruixiang , Chen Jin , Lin Zhengyu
Published: September 2022

Objective

To explore the effectiveness of cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors in overcoming immune resistance in advanced solid cancers.

Methods

In this pilot retrospective study, nine patients with solid cancers were treated with tumour cryoablation and arterial perfusion with programmed cell death protein 1 inhibitors, which had previously proven ineffective. The CIBERSORT software was used to estimate the levels of tumour-infiltrating immune cells in the challenged tumour. Changes in the levels of circulating T cells were assessed using flow cytometry. The primary endpoints were disease control and objective response rates, and the secondary endpoint was safety.

Results

The nine patients with advanced solid tumours received cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors between June and December 2021. The median follow-up time was 5.8 months. We recorded an objective response rate in two patients (22.22%). The best overall responses were partial responses in two patients (22.22%) and one case (11.11%) of stable disease, while six patients (66.67%) presented progressive disease. However, the median overall survival time was not reached. The median progression-free survival was 2.4 months. Treatment-related severe adverse events included one case of abdominal infection and one case of upper gastrointestinal bleeding, which were cured after the intervention. The CIBERSORT software confirmed the importance of cryoablation in regulating tumour-infiltrating immune cells. Thus, macrophage polarisation from the M2 to the M1 phenotype in the challenged tumour and a gradual increase in the levels of circulating CD4+ T cells were observed after administration of the combination therapy.

Conclusion

Cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors has the potential efficacy and safety to overcome immune resistance in patients with advanced solid cancers. The combination therapy leads to macrophage polarisation from the M2 to the M1 phenotype in the challenged tumour to enhance antitumour immunity.
Therapeutic strategies for gastric cancer targeting immune cells: Future directions
Authors: Zhao Yan , Bai Yuansong , Shen Meili , Li Yapeng
Published: September 2022

Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte–associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell–based therapeutic methods will be developed and applied.
Discovery and characterization of SARS-CoV-2 reactive and neutralizing antibodies from humanized CAMouseHG mice through rapid hybridoma screening and high-throughput single-cell V(D)J sequencing
Authors: Yang Xi , Chi Hang , Wu Meng , Wang Zhenshan , Lang Qiaoli , Han Qiuxue , Wang Xinyue , Liu Xueqin , Li Yuanguo , Wang Xiwen , Huang Nan , Bi Jinhao , Liang Hao , Gao Yuwei , Zhao Yongkun , Feng Na , Yang Songtao , Wang Tiecheng , Xia Xianzhu , Ge Liangpeng
Published: September 2022

The coronavirus disease 2019 pandemic has caused more than 532 million infections and 6.3 million deaths to date. The reactive and neutralizing fully human antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective detection tools and therapeutic measures. During SARS-CoV-2 infection, a large number of SARS-CoV-2 reactive and neutralizing antibodies will be produced. Most SARS-CoV-2 reactive and neutralizing fully human antibodies are isolated from human and frequently encoded by convergent heavy-chain variable genes. However, SARS-CoV-2 viruses can mutate rapidly during replication and the resistant variants of neutralizing antibodies easily survive and evade the immune response, especially in the face of such focused antibody responses in humans. Therefore, additional tools are needed to develop different kinds of fully human antibodies to compensate for current deficiency. In this study, we utilized antibody humanized CAMouseHG mice to develop a rapid antibody discovery method and examine the antibody repertoire of SARS-CoV-2 RBD-reactive hybridoma cells derived from CAMouseHG mice by using high-throughput single-cell V(D)J sequencing analysis. CAMouseHG mice were immunized by 28-day rapid immunization method. After electrofusion and semi-solid medium screening on day 12 post-electrofusion, 171 hybridoma clones were generated based on the results of SARS-CoV-2 RBD binding activity assay. A rather obvious preferential usage of IGHV6-1 family was found in these hybridoma clones derived from CAMouseHG mice, which was significantly different from the antibodies found in patients with COVID-19. After further virus neutralization screening and antibody competition assays, we generated a noncompeting two-antibody cocktail, which showed a potent prophylactic protective efficacy against SARS-CoV-2 in cynomolgus macaques. These results indicate that humanized CAMouseHG mice not only provide a valuable platform to obtain fully human reactive and neutralizing antibodies but also have a different antibody repertoire from humans. Thus, humanized CAMouseHG mice can be used as a good complementary tool in discovery of fully human therapeutic and diagnostic antibodies.
Outcome of SARS-CoV-2 infection among patients with common variable immunodeficiency and a matched control group: A Danish nationwide cohort study
Authors: Katzenstein Terese L. , Rasmussen Line D. , Drabe Camilla Helberg , Larsen Carsten Schade , Hansen Ann-Brit Eg , Stærkind Mette , Knudsen Lene Surland , Hansen Christian Holm , Obel Niels
Published: September 2022

The risk of severe adult respiratory coronavirus-2 (SARS-CoV-2) infection and the course of the infection among individuals with common variable immunodeficiency (CVID) relative to the general population have been a matter of debate. We conducted a Danish nationwide study comparing the timing of SARS-CoV-2 vaccination, the risk of first confirmed SARS-CoV-2 infection, re-infection, and the outcome of infection among individuals with CVID relative to an age- and gender matched control group. Cox regression was used to calculate incidence rate ratios. The CVID patients received SARS-CoV-2 vaccinations earlier than those included in the population control group. Even so, the risks of both first infection and re-infection were increased among the individuals with CVID. The CVID group also had increased risk for hospital contacts due to SARS-CoV-2 infection relative to the general population. However, reassuringly, the risk of mechanical ventilation and death did not differ between the groups, but the numbers were low in both groups, making the estimates uncertain. Though this is the largest study to investigate the risk of SARS-CoV-2 infections and outcomes hereof among individuals with CVID relative to the general population, we cannot rule out minor differences in severity, which might only be detectable with an even larger sample size.
Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target
Authors: Liu Rongzeng , Du Shushu , Zhao Lili , Jain Sahil , Sahay Kritika , Rizvanov Albert , Lezhnyova Vera , Khaibullin Timur , Martynova Ekaterina , Khaiboullina Svetlana , Baranwal Manoj
Published: September 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron’s axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown. However, immune mechanisms, especially those linked to the aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 and Th17 populations of lymphocytes were primarily associated with MS pathogenesis. These lymphocytes are essential for differentiation of encephalitogenic CD8+ T cell and Th17 lymphocyte crossing the blood brain barrier and targeting myelin sheath in the CNS. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies. In later studies, aberrant function of Treg and Th9 cells was identified as contributing to MS. This review summarizes the aberrant function and count of lymphocyte, and the contributions of these cell to the mechanisms of MS. Additionally, we have outlined the novel MS therapeutics aimed to amend the aberrant function or counts of these lymphocytes.
Comprehensive characterisation of immunogenic cell death in melanoma revealing the association with prognosis and tumor immune microenvironment
Authors: Ren Jie , Yang Jiaqi , Na Song , Wang Yiqian , Zhang Linyun , Wang Jinkui , Liu Jiwei
Published: September 2022

Increasing evidence has highlighted the critical functions of immunogenic cell death (ICD) within many tumors. However, the therapeutic possibilities and mechanism of utilizing ICD in melanoma are still not well investigated. Melanoma samples involved in our study were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. First, pan-cancer analysis of ICD systematically revealed its expression characteristics, prognostic values, mutation information, methylation level, pathway regulation relationship in multiple human cancers. The non-negative matrix factorization clustering was utilized to separate the TCGA-melanoma samples into two subtypes (i.e. C1 and C2) with different prognosis and immune microenvironment based on the expression traits of ICD. Then, LASSO-Cox regression analysis was utilized to determine an ICD-dependent risk signature (ICDRS) based on the differentially expressed genes (DEGs) between the two subtypes. Principal component analysis and t-distributed stochastic neighbor embedding analysis of ICDRS showed that high- and low-risk subpopulations could be clearly distinguished. Survival analysis and ROC curves in the training, internal validation, and external validation cohorts highlighted the accurate prognosis evaluation of ICDRS. The obvious discrepancies of immune microenvironment between the different risk populations might be responsible for the different prognoses of patients with melanoma. These findings revealed the close association of ICD with prognosis and tumor immune microenvironment. More importantly, ICDRS-based immunotherapy response and targeted drug prediction might be beneficial to different risk subpopulations of patients with melanoma. The innotative ICDRS could function as a marker to determine the prognosis and tumor immune microenvironment in melanoma. This will aid in patient classification for individualized melanoma treatment.
Categorizing numeric nutrients criteria and implications for water quality assessment in the Pearl River Estuary, China
Authors: Zhang Peng , Ou Shujun , Zhang Junxiao , Zhao Lirong , Zhang Jibiao
Published: September 2022

Coastal eutrophication, the over-enrichment of water with nutrients, has become a global ecological problem. As coastal waters are subjected to great pressure due to anthropogenic influences and climate change, establishing numeric nutrient criteria for coastal waters has been exceedingly complex at present. To control and improve the water quality of the Pearl River Estuary (PRE), based on the data from 2015 to 2020, the nutrient criteria of the PRE and adjacent waters were established using frequency statistical analysis. Based on the spatiotemporal salinity patterns, the coastal waters of the PRE were divided in three subareas namely freshwater (Zone I), mixed (Zone II), and seawater (Zone III) using cluster analysis. The recommended criteria values of dissolved inorganic nitrogen (DIN) were 0.573, 0.312, and 0.134 mg·L-1in Zones I, II, and III, respectively. The total nitrogen (TN) criterion for Zone III (0.222 mg·L-1) was much lower than those for Zone I (0.902 mg·L-1) and Zone II (0.885 mg·L-1).The dissolved inorganic phosphorus (DIP) criteria were different for the three Zones, ranging from 0.004 to 0.009 mg·L-1, and the total phosphorus (TP) recommended criteria in Zones I, II, and III were 0.039, 0.028, and 0.020 mg·L-1, respectively. In the water quality assessment, the categorizing numeric nutrients criteria can be referred and applied into fresh, mixed, and seawater zones of PRE. The results of this study provide a new nutrient reference condition in the PRE, which could be helpful in establishing integrated land-ocean unified nutrient criteria and water quality assessment, and implementing effective coastal eutrophication control in the future.
Impact of ocean acidification on the physiology of digestive gland of razor clams Sinonovacula constricta
Authors: Liang Jian , Liu Yuhang , Zhu Feixia , Li Yongren , Liang Shuang , Guo Yongjun
Published: September 2022

Ocean acidification (OA) can have widespread implications for marine bivalves. While our current understanding of OA effects on the physiological performance is increasing, very little is known about the physiology of digestive gland of marine bivalves in response to OA. Here, we examined how the digestive system of razor clams (Sinonovacula constricta) responded to OA. Following 35-day exposure to CO2-driven seawater acidification, no significant decreases in phenotypic traits, such as dry body weight gain, specific growth rate, condition index and survival rate, as well physiological functions, such as activities of antioxidant and digestive enzymes, were observed, demonstrating the resistance of razor clams under acidified conditions. Histological results showed that some direct damages on the structure of digestive gland was observed, including degradation of digestive tubular, atrophy of epithelial cells, loose cell arrangement, even diffuse. This study provides insights into the digestive performance of marine bivalves in a rapidly acidifying ocean.
Characteristics of Desalination Brine and Its Impacts on Marine Chemistry and Health, With Emphasis on the Persian/Arabian Gulf: A Review
Authors: Omerspahic Mustafa , Al-Jabri Hareb , Siddiqui Simil Amir , Saadaoui Imen
Published: September 2022

At a time when worldwide water shortage is increasing, seawater is being viewed as an inexhaustible supply of freshwater via the process of seawater desalination. As a result, seawater desalination is becoming more popular, especially in areas where freshwater is scarce, such as the Middle East and North Africa (MENA), which accounts for half of all global saltwater desalination activities. To enhance the efficiency of saltwater desalination, thermal and membrane-based desalination technologies are continually being developed and hybridized systems established. Brine is an unavoidable product of seawater desalination and is commonly disposed of in oceans and seas, where it has negative effects on the surrounding marine environment and its biodiversity due to the resultant increased salinity and temperature, as well as the presence of chemicals. Furthermore, the quality and amount of brine are influenced by several parameters, including the input quality and quantity, the desalination process, and the discharge method. The intensity of brine’s influence on the marine biota is determined by a number of factors; nevertheless, marine species differ in their tolerance to brine’s effects. Desalination technology is improving to maximize water recovery and reduce the volume of brine produced, with the objective of eventually reaching zero liquid discharge and limiting harmful effects on the marine environment. Meanwhile, proper systems for analyzing the effects of seawater desalination facilities on the marine ecology must be implemented. This review study will look at all of the factors that determine the physicochemical features of desalination brine, with a focus on its impact on marine chemistry and biodiversity. More crucially, the most cutting-edge brine management methods will be investigated for long-term desalination and a healthy marine ecosystem.
Evaluating the impacts of mesoscale eddies on abundance and distribution of neon flying squid in the Northwest Pacific Ocean
Authors: Zhang Yuchen , Yu Wei , Chen Xinjun , Zhou Mo , Zhang Chunling
Published: September 2022

Mesoscale eddies are ubiquitous in global oceans yielding significant impacts on marine life. As a short-lived pelagic squid species, the population of neon flying squid (Ommastrephes bartramii) is extremely sensitive to changes in ambient oceanic variables. However, a comprehensive understanding of how mesoscale eddies affect the O. bartramii population in the Northwest Pacific Ocean is still lacking. In this study, a 10-year squid fisheries dataset with eddy tracking and high-resolution reanalysis ocean reanalysis data was used to evaluate the impact of mesoscale eddies and their induced changes in environmental conditions on the abundance and habitat distribution of O. bartramii in the Northwest Pacific Ocean. A weighted-based habitat suitability index (HSI) model was developed with three crucial environmental factors: sea surface temperature (SST), seawater temperature at 50-m depth (T50m), and chlorophyll-a concentration (Chl-a). During years with an unstable Kuroshio Extension (KE) state, the abundance of O. bartramii was significantly higher in anticyclonic eddies (AEs) than that in cyclonic eddies (CEs). This difference was well explained by the distribution pattern of suitable habitats in eddies derived from the HSI model. Enlarged ranges of the preferred SST, T50m, and Chl-a for O. bartramii within AEs were the main causes of more squids occurring inside the warm-core eddies, whereas highly productive CEs matching with unfavorable thermal conditions tended to form unsuitable habitats for O. bartramii. Our findings suggest that with an unstable KE background, suitable thermal conditions combined with favorable foraging conditions within AEs were the main drivers that yielded the high abundance of O. bartramii in the warm eddies.
Oil-degrading bacterial consortium from Gulf of Mexico designed by a factorial method, reveals stable population dynamics
Authors: Rojas-Vargas Jorge , Adaya Libertad , Silva-Jiménez Hortencia , Licea-Navarro Alexei Fedorovish , Sanchez-Flores Alejandro , Gracia Adolfo , Pardo-López Liliana
Published: September 2022

We describe an assembled marine bacterial consortium designed for bioremediation of oil-contaminated seawater, based on a statistical method using a Plackett-Burman (PB) experimental approach. The final consortium consists of four bacteria isolated from the Gulf of Mexico, from four genera: Pseudomonas, Halopseudomonas, Paenarthrobacter, and Alcanivorax. Individually, bacterial oil removal by these microorganisms was evaluated by gravimetry, reaching 39% at maximum after 75 days, whereas in consortium it was ~62%. We also measured biodegradation levels by Gas Chromatography/Mass Spectrometry (GC-MS) observing 12 polyaromatic hydrocarbons (PAHs) degradation analyzed and n-alkanes degradation with a preference for specific chain length. Consortium population analysis using the V3-V4 region of 16S rRNA showed a stable community, suggesting that the metabolic load was distributed among bacteria and that stable dynamic interactions were achieved. In this work, we show that the use of a factorial method for synthetic consortium design offers the possibility of improving oil degradation efficiency with stable bacterial populations.
Implications for functional diversity conservation of China’s marine fisheries
Authors: Zhao Kangshun , He Yuhan , Su Guohuan , Xu Congjun , Xu Xiaoqi , Zhang Min , Zhang Peiyu
Published: September 2022

Functional diversity is critical to ecosystem stability and resilience to disturbances as it supports the delivery of ecosystem services on which human societies rely. However, changes in functional diversity over space and time, as well as the importance of particular marine fish species to functional space are less known. Here, we reported a temporal change in the functional diversity of marine capture fisheries from all coastal provinces in China from 1989 to 2018. We suggested that both functional evenness (FEve) and functional divergence (FDiv) changed substantially over time, especially with considerable geographic variation in FEve in the detected patterns. Even within the same sea, the relative contributions of fishes with various water column positions and trophic levels in different waters have different patterns. Together these results underline the need of implementing specific climate-adaptive functional diversity conservation measures and sustainable fisheries management in different waters.
How a holobiome perspective could promote intensification, biosecurity and eco-efficiency in the shrimp aquaculture industry
Authors: Gutiérrez-Pérez Eric D. , Vázquez-Juárez Ricardo , Magallón-Barajas Francisco J. , Martínez-Mercado Miguel Á. , Escobar-Zepeda Alejandra , Magallón-Servín Paola
Published: September 2022

The aquaculture industry faces many challenges regarding the intensification of shrimp rearing systems. One of these challenges is the release of excessive amounts of nitrogen and phosphorus into coastal areas, causing disruption in nutrient cycling and microbial equilibrium, which are important for coastal productivity. Biosecurity within the shrimp rearing systems can also be compromised by disruption to the nutrient fluxes, and as consequence the microbiome of the system. In certain conditions, these changes could lead to the blooming of potentially pathogenic bacteria. These changes in the external microbiome of the system and the constant fluctuations of nutrients can affect the intestinal microbiome of shrimp, which is involved in the growth and development of the host, affecting nutrient absorption, regulating metabolic processes, synthesising vitamins, modulating the immune response and preventing growth of pathogenic bacteria. It has been suggested that specific changes in the intestinal microbiome of Litopenaeus vannamei may be an avenue through which to overcome some of the problems that this industry faces, in terms of health, growth and waste. Recent research, however, has focussed mainly on changes in the intestinal microbiome. Researchers have overlooked the relevance of other aspects of the system, such as the microbiome from the benthic biofilms; zooplankton, plankton and bacterioplankton; and other sources of microorganisms that can directly affect the microbial status of the intestinal and epiphytic communities, especially in rearing systems that are based on intensification and microbial maturation processes, such as a biofloc system. It is therefore necessary to place holobiome studies into context, including the ‘holobiome of the aquaculture system’ (microbiomes that make up the culture system and their interactions) and not only the intestinal microbiome. Thus, we describe factors that affect the shrimp microbiome, the methodology of study, from sampling to bioinformatic workflows, and introduce the concept of the ‘holobiome of the aquaculture system’ and how this enables us to promote the intensification, biosafety and eco-efficiency of shrimp farming. The holobiome perspective implies a greater investment of resources and time for research, but it will accelerate the development of technology that will benefit the development and sustainability of the aquaculture industry.
Responses of three nesting sea turtle species to hard-armoring structures
Authors: Hirsch Sarah E. , Toonder Madison , Reilly Jennifer D. , Hoover Shelby R. , Perrault Justin R.
Published: September 2022

In the face of modern challenges, analyzing sea turtle nesting trends is critical to better understand impacts to these vulnerable species. The introduction of hard-armoring structures (e.g., seawalls, rock revetments) on sea turtle nesting beaches poses a threat to nesting leatherback (Dermochelys coriacea), loggerhead (Caretta caretta), and green (Chelonia mydas) sea turtles due to habitat loss and turtle interactions with the physical structure. Despite much of Florida’s coastline being protected by some form of hard-armoring technology, research on the impacts of these structures to sea turtles is limited to loggerheads. Our objectives were to (1) examine nest density, nesting success, washout rates, and hatching and emergence success at hard-armoring sites in comparison to a control area and (2) characterize impacts of obstructions encountered by sea turtles nesting in northern Palm Beach County, Florida. Our results indicate that the hard-armoring site showed significantly lower nest density for green turtles and nesting success for loggerheads and green turtles in comparison to a control area. Additionally, nesting success for loggerheads and green turtles that encountered hard-armoring structures was significantly lower in comparison to those that encountered no obstructions or other obstructions (e.g., beach furniture, walkovers, escarpments, etc.). These results suggest that hard-armoring structures negatively impact sea turtle nesting behavior, which could result in loss of energy or other physiological derangements. Green turtles showed the most significant differences between the two sites, likely a result of their typical nest site selection favoring the upper portions of the beach, crawling further distances from the high-water line than loggerheads or leatherbacks. Before additional hard-armoring structures are permitted and installed, governing agencies should first consider more natural methods of protecting shorelines (e.g., dune restoration).