bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher spring phenological sensitivity to forcing temperatures of Asian compared to European tree species under low and high pre-chilling conditions
Authors: Walde Manuel G. , Wu Zhaofei , Fox Tom , Baumgarten Frederik , Fu Yongshuo H. , Wang Shuxin , Vitasse Yann
Published: December 2022

Winter chilling, spring forcing temperature and photoperiod are the most important drivers explaining the spatial and temporal variability of spring phenology in temperate trees. However, how these factors interact with each other on dormancy release and spring budburst date remains unclear and varies greatly depending on species. Our knowledge is also limited as to whether heat accumulation of forcing temperatures that trigger bud break in spring is a linear or non-linear process. Here, we aimed at experimentally quantifying the effect of chilling, forcing, photoperiod and their interactions on the budburst dates of nine different temperate tree species from East Asia (near Beijing, China) and Central Europe (near Zurich, Switzerland), including six phylogenetically related species (same genus). We conducted a full factorial experiment in climate chambers using two chilling (low and high, i.e., 0 vs. 56 days at 2°C after sampling at the end of December), four forcing (5, 10, 15, and 20°C), and two photoperiod (8 vs. 16 h) treatments simultaneously in Beijing and Zurich. We found that species growing near Beijing responded more readily to forcing conditions than species of the same genus growing near Zurich regardless of chilling treatment. Budburst timing of most species but European beech was marginally, if at all, affected by photoperiod. Furthermore, our results suggest that linear heat accumulation, as commonly used with the growing degree hours (GDH) model, could result in accurate prediction of budburst date depending on the temperature threshold used as a basis for heat accumulation. Our results also demonstrate the important role of chilling in shaping the sensitivity and rate of forcing accumulation to trigger budburst and suggest that species-specific sigmoid relationship for accumulating heat that accounts for prior chilling exposure may yield better predictions of budburst dates. Our results suggest that deciduous trees may have adapted their chilling and forcing requirements in regards to the predictability of winter-spring transition and late spring frosts. A less predictable winter-spring transition, as observed in Central Europe, could have driven species evolution towards higher chilling and forcing requirements compared to species growing in a more predictable climate of Northeastern Asia. Our cross-continental experiment therefore suggests that the spring phenology of East Asian species is tighter coupled to spring forcing temperature than Central European forests.
The cuproptosis related genes signature predicts the prognosis and correlates with the immune status of clear cell renal cell carcinoma
Authors: Sun Peng , Xu Hua , Zhu Ke , Li Min , Han Rui , Shen Jiran , Xia Xingyuan , Chen Xiaojuan , Fei Guanghe , Zhou Sijing , Wang Ran
Published: December 2022

Background: Clear cell renal cell carcinoma (CCRCC) has a high incidence and poor prognosis. Cuproptosis, an independent pattern of cell death associated with copper, plays an important role in cancer proliferation and metastasis. The role of cuproptosis-related genes (CRGs) in CCRCC is unclear.

Methods: Transcriptome and clinical information for CCRCC were downloaded from The Cancer Genome Atlas (TCGA) database. After dividing the training and testing cohort, a 4-CRGs risk signature (FDX1, DLD, DLAT, CDKN2A) was identified in the training cohort using Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. The effect of the 4-CRGs risk signature on prognosis was assessed using Kaplan-Meier (KM) curves and time-dependent receiver operating characteristic (ROC) curves and verified using the testing cohort. For different risk groups, the immune statue was assessed using the CIBERSORT algorithm, the ssGSEA method and immune checkpoint expression data. Finally, a competitive endogenous RNA (ceRNA) network was constructed using miRTarbase and starBase databases to identify molecules that may have a regulatory relationship with CRCCC.

Results: There were significant changes in the overall survival (OS), immune microenvironment, immune function, and checkpoint gene expression among the different risk groups. A ceRNA network consisting of one mRNA, two miRNAs, and 12 lncRNAs was constructed.

Conclusion: The 4-CRGs risk signature provides a new method to predict the prognosis of patients with CCRCC and the effect of immunotherapy. We propose a new cuproptosis-associated ceRNA network that can help to further explore the molecular mechanisms of CCRCC.
LFSC: A linear fast semi-supervised clustering algorithm that integrates reference-bulk and single-cell transcriptomes
Authors: Liu Qiaoming , Liang Yingjian , Wang Dong , Li Jie
Published: December 2022

The identification of cell types in complex tissues is an important step in research into cellular heterogeneity in disease. We present a linear fast semi-supervised clustering (LFSC) algorithm that utilizes reference samples generated from bulk RNA sequencing data to identify cell types from single-cell transcriptomes. An anchor graph is constructed to depict the relationship between reference samples and cells. By applying a connectivity constraint to the learned graph, LFSC enables the preservation of the underlying cluster structure. Moreover, the overall complexity of LFSC is linear to the size of the data, which greatly improves effectiveness and efficiency. By applying LFSC to real single-cell RNA sequencing datasets, we discovered that it has superior performance over existing baseline methods in clustering accuracy and robustness. An application using infiltrating T cells in liver cancer demonstrates that LFSC can successfully find new cell types, discover differently expressed genes, and explore new cancer-associated biomarkers.
TYK2 correlates with immune infiltration: A prognostic marker for head and neck squamous cell carcinoma
Authors: He Yaodong , Li Yunshan , Xiang Junwei , Huang Xu , Zhao Mingyu , Wang Yuanyin , Chen Ran
Published: December 2022

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in immune and inflammatory signaling. TYK2 is overexpressed in several types of cancers and promotes the invasion and proliferation of cancer cells. Nevertheless, the roles of TYK2 in the prognosis and immune infiltration of head and neck squamous cell carcinoma (HNSCC) remain to be elucidated. In this study, the expression of TYK2 in HNSCC was evaluated based on the data retrieved from multiple databases and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The prognostic potential of TYK2 in patients with HNSCC was analyzed by Kaplan-Meier curves and Cox regression analysis. A TYK2-related risk assessment model was subsequently constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and stepwise multivariate Cox regression analysis. The association between the expression of TYK2 and the tumor immune microenvironment, immune checkpoints, and drug sensitivity was explored various packages in R. Cell function assays were finally used for exploring the effects of TYK2 on the growth and metastasis of HNSCC tumors. The expression of TYK2 was significantly upregulated in HNSCC and was found to be closely correlated with HPV status, gender, clinical grade, and TP53 mutation status. Survival analysis suggested that TYK2 is associated with better survival outcomes and acts as an independent prognostic indicator of HNSCC. The model constructed herein also performed well in terms of predicting patient prognosis. The expression of TYK2 was positively associated with the population of tumor-infiltrating immune cells, expression of immune checkpoint genes, and antitumor drug susceptibility. Functionally, TYK2 knockdown significantly promoted the proliferation, migration, and invasion of HNSCC cell lines in vitro. The findings demonstrated that TYK2 could serve as a suppressor of tumor growth and holds significant promise as a novel biomarker for assessing the prognosis of patients with HNSCC and aid in immunotherapy against HNSCC.
Gender bias and menstrual blood in stem cell research: A review of pubmed articles (2008–2020)
Authors: Manica Daniela Tonelli , Asensi Karina Dutra , Mazzarelli Gaia , Tura Bernardo , Barata Germana , Goldenberg Regina Coeli Santos
Published: December 2022

Despite proven scientific quality of menstrual blood mesenchymal cells, research and science output using those cells is still incipient, which suggests there is a resistance to the study of this type of cell by scientists, and a lack of attention to its potential for cell therapy, regenerative medicine and bioengineering. This study analyzes the literature about the menstrual blood mesenchymal stromal/stem cells (mbMSC) on the PubMed database between 2008–2020 and the social attention it received on Twitter. A comparative analysis showed that mbMSC accounts for a very small portion of mesenchymal cell research (0.25%). Most first authors are women (53.2%), whereas most last authors are men (63.74%), reinforcing an already known, and still significant, gender gap between last and corresponding authors. Menstrual blood tends to be less used in experiments and its scientific value tends to be underestimated, which brings gender bias to a technical and molecular level. Although women are more positive in the mbMSC debate on Twitter, communication efforts toward visibility and public interest in menstrual cells has room to grow.
Quality of family planning counseling and associated factors among women attending family planning clinics at selected health centers in Akaki Kality sub-city, Addis Ababa, Ethiopia
Authors: Goyomsa Girma Garedew , Geleta Leta Adugna , Debela Sisay Abebe , Reshid Nejiba , Ogeto Luke Amana , Lamaro Abota Tafesse , Girma Derara , Dejene Hiwot
Published: December 2022

Background

Ethiopia has achieved a remarkable improvement in the provision of family planning. The modern contraceptive prevalence rate has shown a fivefold increment in the last two decades, yet the family planning service in the country is still deficient and characterized by poor counseling quality.

Objective

The aim of the study is to assess the quality of family planning counseling provided and the associated factors at selected health centers in Akaki Kality sub-city, Addis Ababa, Ethiopia.

Method

A cross-sectional study was conducted among 678 randomly selected women attending family planning services at health centers in Addis Ababa, Ethiopia. Multivariable logistic regression analysis was performed to identify factors associated with the quality of family planning counseling.

Result

A total of 678 women participated in the study. About 29.1% [95% confidence interval (CI): 25.7%–32.6%] of the respondents were adequately counseled. Age groups 37–49 [adjusted odds ratio (AOR) = 2.7; 95% CI: 1.1–6.6], being in marital union (AOR = 2.8; 95% CI: 1.2–6.7), attaining secondary education (AOR = 1.9; 95% CI: 1.1–3.6) or higher education (AOR = 2.2; 95% CI: 1.2–4.3), and visit status (AOR = 1.6; 95% CI: 1.1–2.4) were significantly associated with good counseling.

Conclusion

Less than one in three women was counseled adequately. Health professionals should give due attention to younger women, single clients, and clients with their first presentation to the health facility. It also indicates that promoting education among Ethiopian women is crucial for a positive outcome of family planning counseling.
Resolvin D2 induces anti-microbial mechanisms in a model of infectious peritonitis and secondary lung infection
Authors: Sundarasivarao Prem Y. Kadiyam , Walker Jean M. , Rodriguez Ana , Spur Bernd W. , Yin Kingsley
Published: December 2022

In severe bacterial infections, there is a pro-inflammatory response to promote bacterial clearance but this response can cause tissue injury. Later, the immune system becomes dysregulated and the host is unable to clear a secondary or a pre-existing infection. Specialized Pro-resolving Mediators (SPMs) such as resolvin D2 (RvD2) have been shown to be beneficial for inflammation/infection resolution in animal models of sepsis butin vivomechanisms by which RvD2 may promote bacterial clearance and/or attenuate deleterious effects of a secondary infection have not been fully established. In this study, we used the 2-hit model of cecal ligation and puncture (CLP) induced infectious peritonitis and secondary lung infection withPseudomonas aeruginosato find possible antimicrobial and immunomodulatory mechanisms of RvD2. We show that RvD2 given as late as 48h after CLP surgery reduced blood bacterial load without altering plasma cytokines compared to mice given saline vehicle. RvD2 increased splenic neutrophil accumulation as well as average reactive oxygen species (ROS) production. There was also an increase in an immature leukocyte population the myeloid derived suppressor cells (MDSCs) in the spleen of RvD2 treated mice. RvD2 reduced lung lavage bacterial load 24h afterP. aeruginosaadministration and significantly decreased lung lavage levels of IL-23, a cytokine essential in the Th-17 inflammatory response. In addition, we show that RvD2 increased the number of non-inflammatory alveolar macrophages afterP. aeruginosaadministration compared to saline treated mice. The study uncovered an antimicrobial mechanism of RvD2 where RvD2 increases mature neutrophil and MDSC accumulation into the spleen to promote blood bacterial clearance. The study showed that in this 2-hit model, RvD2 promotes lung bacterial clearance, increased non-inflammatory alveolar macrophage number and inhibits an adaptive immune pathway providing evidence of its resolution mechanism in secondary pulmonary infection.
Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers
Authors: Jin Wenyi , Yang Qian , Chi Hao , Wei Kongyuan , Zhang Pengpeng , Zhao Guodong , Chen Shi , Xia Zhijia , Li Xiaosong
Published: December 2022

Introduction

Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance.

Methods

We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predicting individual responses to immunotherapies. ELISE employed iterative univariable logistic regression to select genetic features of patients, using Monte Carlo Tree Search (MCTS) to tune hyperparameters. In each trial, ELISE selected multiple models for integration based on add or concatenate stacking strategies, including deep neural network, automatic feature interaction learning via self-attentive neural networks, deep factorization machine, compressed interaction network, and linear neural network, then adopted the best trial to generate a final approach. SHapley Additive exPlanations (SHAP) algorithm was applied to interpret ELISE, which was then validated in an independent test set.

Result

Regarding prediction of responses to atezolizumab within esophageal adenocarcinoma (EAC) patients, ELISE demonstrated a superior accuracy (Area Under Curve [AUC] = 100.00%). AC005786.3 (Mean [|SHAP value|] = 0.0097) was distinguished as the most valuable contributor to ELISE output, followed by SNORD3D (0.0092), RN7SKP72 (0.0081), EREG (0.0069), IGHV4-80 (0.0063), and MIR4526 (0.0063). Mechanistically, immunoglobulin complex, immunoglobulin production, adaptive immune response, antigen binding and others, were downregulated in ELISE-neg EAC subtypes and resulted in unfavorable responses. More encouragingly, ELISE could be extended to accurately estimate the responsiveness of various immunotherapeutic agents against other cancers, including PD1/PD-L1 suppressor against metastatic urothelial cancer (AUC = 88.86%), and MAGE−A3 immunotherapy against metastatic melanoma (AUC = 100.00%).

Discussion

This study presented deep insights into integrating ensemble deep learning with self-attention as a mechanism for predicting immunotherapy responses to human cancers, highlighting ELISE as a potential tool to generate reliable approaches to individualized treatment.
Bacteroides vulgatus attenuates experimental mice colitis through modulating gut microbiota and immune responses
Authors: Liu Liyun , Xu Mingchao , Lan Ruiting , Hu Dalong , Li Xianping , Qiao Lei , Zhang Suping , Lin Xiaoying , Yang Jing , Ren Zhihong , Xu Jianguo
Published: December 2022

Introduction

Bacteroides vulgatus is one of the predominant Bacteroides species in the human gut and exerts a series of beneficial effects. The aim of this study was to investigate the protective role of B. vulgatus Bv46 in a dextran sodium sulfate (DSS) induced colitis mouse model.

Methods

Female C57BL/6J mice were given 3% DSS in drinking water to induce colitis and simultaneously treated with B. vulgatus Bv46 by gavage for 7 days. Daily weight and disease activity index (DAI) of mice were recorded, and the colon length and histological changes were evaluated. The effects of B. vulgatus Bv46 on gut microbiota composition, fecal short chain fatty acids (SCFAs) concentration, transcriptome of colon, colonic cytokine level and cytokine secretion of RAW 264·7 macrophage cell line activated by the lipopolysaccharide (LPS) were assessed.

Results and Discussion

B. vulgatus Bv46 significantly attenuated symptoms of DSS-induced colitis in mice, including reduced DAI, prevented colon shortening, and alleviated colon histopathological damage. B. vulgatus Bv46 modified the gut microbiota community of colitis mice and observably increased the abundance of Parabacteroides, Bacteroides, Anaerotignum and Alistipes at the genus level. In addition, B. vulgatus Bv46 treatment decreased the expression of colonic TNF-α, IL-1β and IL-6 in DSS-induced mouse colitis in vivo, reduced the secretion of TNF-α, IL-1β and IL-6 in macrophages stimulated by LPS in vitro, and downregulated the expression of Ccl19, Cd19, Cd22, Cd40 and Cxcr5 genes in mice colon, which mainly participate in the regulation of B cell responses. Furthermore, oral administration of B. vulgatus Bv46 notably increased the contents of fecal SCFAs, especially butyric acid and propionic acid, which may contribute to the anti-inflammatory effect of B. vulgatus Bv46. Supplementation with B. vulgatus Bv46 serves as a promising strategy for the prevention of colitis.
A novel uveitis model induced by lipopolysaccharide in zebrafish
Authors: Xiao Xiao , Liu Zhangluxi , Su Guannan , Liu Huan , Yin Wenhui , Guan Yuxuan , Jing Shixiang , Du Liping , Li Fuzhen , Li Na , Yang Peizeng
Published: December 2022

Objective

Endotoxin-induced uveitis (EIU) is an important tool for human uveitis study. This study was designed to develop a novel EIU model in zebrafish.

Methods

An EIU model in zebrafish was induced by intravitreal lipopolysaccharide (LPS) injection and was assessed dynamically. Optical coherence tomography (OCT) was used to assess infiltrating cells in the vitreous body. The histological changes wereevaluated using HE staining and immune cells were measured by immunofluorescence. The retinal RNA Sequencing (RNA-Seq) was used to explore the transcriptional changes during inflammation. RNA-Seq data were analyzed using time-course sequencing data analysis (TCseq), ClueGO plugin in Cytoscape, and Gene Set Enrichment Analysis (GSEA) software. Flow cytometry and retinal flat mounts were used to dynamically quantify the immune cells.

Results

EIU was successfully induced in zebrafish following intravitreal LPS injection. Inflammation appeared at 4 hours post injection (hpi), reached its peak at 24 hpi, and then resolved at 72 hpi. Immunofluorescence confirmed that massive influx ofneutrophils into the iris and vitreous body, and activation of microglia as evidenced by ameboid-shaped appearance in the retina. Retinal RNA-seq during the EIU course identified four gene clusters with distinct expression characteristics related to Toll-likereceptor signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and extracellular matrix (ECM)-receptor interaction, respectively. Prednisone immersion inhibited the inflammatory response of EIU in zebrafish, whichwas confirmed by decreased neutrophils detected in flow cytometry and retinal flat mounts.

Conclusions

We developed a novel EIU model in zebrafish, which may be particularly useful for gene-editing and high-throughput screening of new drugs for the prevention and treatment of uveitis.
Clinical characteristics of myelin-oligodendrocyte glycoprotein antibody-positive pediatric autoimmune encephalitis without demyelination: A case series
Authors: Song Xiaojie , Ma Jiannan
Published: December 2022

Purpose

To facilitate the identification of myelin-oligodendrocyte glycoprotein (MOG) antibody-associated diseases in pediatric autoimmune encephalitis without demyelination, we explored the clinical characteristics of patients having MOG antibody-positive pediatric autoimmune encephalitis without demyelination in Children’s Hospital of Chongqing Medical University, China.

Methods

We reviewed patients’ medical records from January 2019 to June 2022 and retrospectively analyzed clinical manifestations, brain magnetic resonance imaging (MRI) findings, laboratory findings, treatments and outcomes of children with autoimmune encephalitis who tested positive for MOG antibodies in serum but for whom demyelination was not detected on MRI.

Results

Eighteen patients (6 boys, 12 girls; median age: 103.2 (range: 36–160) months) were included: 15 tested positive for MOG antibodies in both serum and cerebrospinal fluid (CSF); three tested positive only in serum. The most common clinical symptoms were altered mental status (18/18), fever (16/18), headache (14/18), seizures (6/18) and focal neurologic deficits (5/18). All patients had CSF pleocytosis (median count: 74/µL, range: 14–380/µL); five patients had elevated CSF protein levels (median: 0.85 g/L, range: 0.53–1.48 g/L) simultaneously. CSF glucose levels were normal in all patients. Abnormal electroencephalogram (EEG) results were found in 12 patients: generalized or focal slowing (9/12), focal epileptic discharges (2/12), and generalized slowing and focal epileptic discharges (1/12). Twelve of the 18 patients showed hyperintense T2-weighted lesions on brain MRI in the cortex (6), basal ganglia (5), thalamus (3), cerebellum (4), and brainstem (2). All patients received immunotherapy and had favorable outcomes at discharge (modified Rankin scale score: <2). Three children relapsed once; however, all children had good outcomes at the last follow-up.

Conclusion

MOG antibody-positive pediatric autoimmune encephalitis without demyelination is mainly characterized by prolonged fever, altered mental status, headache, mild-to-moderate increase in cell count in the CSF, and normal or abnormal brain MRI, which may involve any part outside the white matter without specificity. All patients with MOG antibody-positive pediatric autoimmune encephalitis without demyelination had favorable outcomes after immunotherapy, while a few patients relapsed once.
ADAR1 promotes systemic sclerosis via modulating classic macrophage activation
Authors: Sun Chenming , Cai Dunpeng , Chen Shi-You
Published: December 2022

Introduction

As a multisystem autoimmune disorder disease, systemic sclerosis (SSc) is characterized by inflammation and fibrosis in the skin and other internal organs. However, mechanisms underlying the inflammatory response that drives the development of SSc remain largely unknown.

Methods

ADAR1 heterozygous knockout (AD1+/-) mice and myeloid-specific ADAR1 knockout mice were used to determine the function of ADAR1 in SSc. Histopathological analyses and western blot confirmed the role of ADAR1 in bleomycin-induced increased skin and lung fibrosis.

Results

In this study, we discover that adenosine deaminase acting on RNA (ADAR1), a deaminase converting adenosine to inosine (i.e., RNA editing) in RNA, is abundantly expressed in macrophages in the early stage of bleomycin-induced SSc. Importantly, ADAR1 is essential for SSc formation and indispensable for classical macrophage activation because ADAR1 deficiency in macrophages significantly ameliorates skin and lung sclerosis and inhibits the expression of inflammation mediator inducible NO synthase (iNOS) and IL-1β in macrophages. Mechanistically, deletion of ADAR1 blocks macrophage activation through diminishing NF-κB signaling.

Discussion

Our studies reveal that ADAR1 promotes macrophage activation in the onset of SSc. Thus, targeting ADAR1 could be a potential novel therapeutic strategy for treating sclerosis formation.
Prognostic model of immune checkpoint inhibitors combined with anti-angiogenic agents in unresectable hepatocellular carcinoma
Authors: Li Xiaomi , Sun Wei , Ding Xiaoyan , Li Wei , Chen Jinglong
Published: December 2022

Background

The combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic agents has shown promising efficacy in unresectable hepatocellular carcinoma (HCC), but until now no clinical prognostic models or predictive biomarkers have been established.

Methods

From 2016 to 2021, a total of 258 HCCs treated with ICIs and tyrosine kinase inhibitors (TKIs) were retrospectively enrolled, as the study cohort. Patients’ baseline data was extracted by least absolute and shrinkage selection operator (LASSO) and Cox regression. Finally, a prognostic model in the form of nomogram was developed. Model performance was assessed in terms of discrimination, calibration, and clinical utility. A 5-fold cross-validation was used to evaluate the internal repeatability of the model. In addition, the patient cohort was divided into three subgroups according to nomogram scores. Their survivals were estimated by Kaplan-Meier methods and the differences were analyzed using log-rank tests.

Results

Seven clinical parameters were selected: Eastern Cooperative Oncology Group performance status (ECOG PS), combination of transarterial chemoembolization (TACE), extrahepatic metastasis (EHM), platelet to lymphocyte ratio (PLR), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and Child-Pugh score. The model had an area under the curve (AUC) of 0.777 at 1 year and 0.772 at 2 years. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) showed that the discrimination, consistency and applicability of the model were good. In addition, cross-validation validated the discrimination of the model, and the C index value of the model is 0.7405. The median overall survival (OS) of the high-, medium- and low-risk subgroups was 7.58, 17.50 and 53.17 months, respectively, with a significant difference between the groups (P < 0.0001).

Conclusion

We developed a comprehensive and simple prognostic model for the combination of ICIs plus TKIs. And it may predict the efficacy of the combination regimen for unresectable HCC.
Case report: Brain metastasis necrosis with immune checkpoint inhibitors plus chemotherapy for advanced non-small cell lung cancer
Authors: Niu Lishui , Li Xiang , Meng Li , Zhang Yingying , Wan Xin , Jing Di , Zhou Qin , Zhou Rongrong
Published: December 2022

The emergence of immune checkpoint inhibitors (ICIs) has reshaped the landscape of advanced lung cancer treatment. The brain is the most common metastatic site for lung cancer. Whether conventional criteria can evaluate the intracranial response of ICIs remains unclear. Here, we report a well-documented case of intracranial necrosis confirmed by post-operative pathology after only one cycle of chemo-immunotherapy without any radiation therapy, which suggests that immunotherapy elicits strong anti-tumor responses for intracranial metastasis and promotes intracranial necrosis, resulting in a temporary increase in size of the target lesions. Still, the specific mechanisms and management strategies need to be further explored.
The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications
Authors: Magalhães-Gama Fábio , Alves-Hanna Fabíola Silva , Araújo Nilberto Dias , Barros Mateus Souza , Silva Flavio Souza , Catão Claudio Lucas Santos , Moraes Júlia Santos , Freitas Izabela Cabral , Tarragô Andréa Monteiro , Malheiro Adriana , Teixeira-Carvalho Andréa , Costa Allyson Guimarães
Published: December 2022

The leukemic microenvironment has a high diversity of immune cells that are phenotypically and functionally distinct. However, our understanding of the biology, immunology, and clinical implications underlying these cells remains poorly investigated. Among the resident immune cells that can infiltrate the leukemic microenvironment are myeloid cells, which correspond to a heterogeneous cell group of the innate immune system. They encompass populations of neutrophils, macrophages, and myeloid-derived suppressor cells (MDSCs). These cells can be abundant in different tissues and, in the leukemic microenvironment, are associated with the clinical outcome of the patient, acting dichotomously to contribute to leukemic progression or stimulate antitumor immune responses. In this review, we detail the current evidence and the many mechanisms that indicate that the activation of different myeloid cell populations may contribute to immunosuppression, survival, or metastatic dissemination, as well as in immunosurveillance and stimulation of specific cytotoxic responses. Furthermore, we broadly discuss the interactions of tumor-associated neutrophils and macrophages (TANs and TAMs, respectively) and MDSCs in the leukemic microenvironment. Finally, we provide new perspectives on the potential of myeloid cell subpopulations as predictive biomarkers of therapeutical response, as well as potential targets in the chemoimmunotherapy of leukemias due to their dual Yin-Yang roles in leukemia.
CMV reactivation initiates long-term expansion and differentiation of the NK cell repertoire
Authors: Hassan Norfarazieda , Eldershaw Suzy , Stephens Christine , Kinsella Francesca , Craddock Charles , Malladi Ram , Zuo Jianmin , Moss Paul
Published: December 2022

Introduction

NK cells play an important role in suppression of viral replication and are critical for effective control of persistent infections such as herpesviruses. Cytomegalovirus infection is associated with expansion of ‘adaptive-memory’ NK cells with a characteristic CD56dimCD16bright NKG2C+ phenotype but the mechanisms by which this population is maintained remain uncertain.

Methods

We studied NK cell reconstitution in patients undergoing haemopoietic stem cell transplantation and related this to CMV reactivation.

Results

NK cells expanded in the early post-transplant period but then remained stable in the absence of viral reactivation. However, CMV reactivation led to a rapid and sustained 10-fold increase in NK cell number. The proportion of NKG2C-expressing cells increases on all NK subsets although the kinetics of expansion peaked at 6 months on immature CD56bright cells whilst continuing to rise on the mature CD56dim pool. Phenotypic maturation was observed by acquisition of CD57 expression. Effective control of viral reactivation was seen when the peripheral NK cell count reached 20,000/ml.

Discussion

These data show that short term CMV reactivation acts to reprogramme hemopoiesis to drive a sustained modulation and expansion of the NK cell pool and reveal further insight into long term regulation of the innate immune repertoire by infectious challenge.
H3K36 methyltransferase NSD1 is essential for normal B1 and B2 cell development and germinal center formation
Authors: Zhai Sulan , Cao Min , Zhou Han , Zhu Huamin , Xu Tongchang , Wang Yuliang , Wang Xiaoming , Cai Zhenming
Published: December 2022

B cells, which consist of two well-defined populations: B1 and B2 cells, which can produce antibodies that are essential for host protection against infections, through virus neutralization, opsonization and antibody-dependent cellular cytotoxicity. Epigenetic modifications, such as DNA methylation and histone modification could regulate immune cell differentiation and functions. In this study, we found a significant reduction of GC response in the B cell specific knockout of H3K36 methyltransferase NSD1 (Mb1-Cre+ NSD1fl/fl, NSD1B KO) mice compared with the wildtype control (Mb1-Cre+ NSD1+/+, NSD1B WT). We also demonstrated reduced production of high-affinity antibody, but increased production of low-affinity antibody in the NSD1B KO mice. Further analysis revealed that loss of NSD1 promoted the development of B1 cells by increasing the expression of Rap1b and Arid3a. In conclusion, our data suggest that NSD1 plays an important role in regulation the development of B1 and B2 cells, and the process of germinal center formation and high-affinity antibody production.
Nutrient dynamics and coupling with biological processes and physical conditions in the Bohai Sea
Authors: Liang Wen , Wang Yun , Liu Sumei , Wang Mengxue , Zhao Liang , Liu Chongcong , Zhang Xiaotong , Wu Nian , Wang Lingyan , Zhu Dongdong , Ma Yuwei , Luo Chang
Published: December 2022

The Bohai Sea is a habitat for economically important fish in China, but its ecological environment has changed significantly, and it is necessary to further clarify the dynamics and the internal resupply channels of nutrients in the Bohai Sea. Based on four field observations in the Bohai Sea from May to December 2019, the nutrient dynamics were addressed. The concentration of dissolved inorganic nutrients was depleted throughout the water column in spring and in the euphotic zone in summer and accumulated in the bottom water in summer and in the water column in autumn and winter. Relative phosphorus limitation was present in Laizhou Bay and its surrounding area in all seasons, while relative silicon limitation was evident in spring and relative nitrogen limitation was significant in summer in most other study aeras. The results of end-member mixing model illustrated significant seasonal differences in the nutrient uptake ratios, which may be related to various factors such as different phytoplankton composition and phosphorus turnover rates. Turbulent entrainment was an important nutrient pathway for primary production in the euphotic zone of Central Bohai Sea during the stratification season, with an estimated average nutrient flux of 6.04 ± 9.63, 0.22 ± 0.19 and 6.97 ± 6.61 mmol·m-2·d-1 for DIN, DIP and DSi, respectively.
Achieving greater equity in allocation of catch shares: A case study in China
Authors: Ding Qi , Shan Xiujuan , Jin Xianshi , Gorfine Harry
Published: December 2022

The allocation of catch shares among fishing entities is a key element of a total allowable catch control system. Current allocation schemes fall short in their ability in terms of ensuring fairness and feasibility and there is much scope for improvement. In this study, a new allocation method based on applying a relative deprivation coefficient is introduced into the allocation of catch shares, and demonstrated in a case study involving the 11 coastal provinces in China. Advantages of this process of quota allocation in comparison with well-established allocation methods were investigated. Compared with the conventional single-criterion approach and simple multi-criteria-based allocation with equal weights, the new allocation scheme integrating the new weighting method with multi-criteria allocation showed superior performance in rendering the outcomes in catch shares allocation fairer and more reasonable, with a Gini coefficient below 0.2. Quota proportions for the 11 coastal provinces under the newly developed allocation scheme were between maximum and minimum ratios of those under schemes using a single-criterion, which shows strong utility in reducing the rigidity of a single-criterion allocation approach and improving the acceptability of the allocation results. This study offers a viable yet fairer alternative for facilitating sustainable fisheries via quota management and provides a reference for fisheries policy makers in equitably allocating catch shares.
Satellite-detected phytoplankton blooms in the Japan/East Sea during the past two decades: Magnitude and timing
Authors: Wang Dingqi , Fang Guohong , Jiang Shumin , Xu Qinzeng , Wang Guanlin , Wei Zexun , Wang Yonggang , Xu Tengfei
Published: December 2022

The Japan/East Sea (JES) is known as a mid-latitude “Miniature Ocean” that features multiscale oceanic dynamical processes. Using principal component analysis (PCA), we investigate the variability of the sea surface chlorophyll-a concentration (SSC) and its bloom timing in the JES based on satellite remote sensing products spanning 1998–2019. The JES SSC exhibits strong seasonal variability and blooms twice annually. The spring bloom is induced under combined factors of increased photosynthetically active radiation (PAR), weakened wind speeds and sea ice melting, and terminated by the enhanced stratification. The fall bloom is induced by destratification and active dynamic processes (such as upwelling and front), and terminated by decreased PAR. The interannual variability of spring and fall bloom occur along the northwestern coast of the JES and in the deep Japan Basin, respectively. The positive SSC anomalies along the northwestern coast of the JES in spring is associated with more sea ice in the previous winter, weaker wind speed, and stronger stratification induced by the El Niño events. No significant relationship has been found between the fall bloom and the El Niño events. The bloom timing is controlled by the critical depth hypothesis. The initiation/termination timing of spring blooms has shifted earlier by 0.37/0.45 days, and the counterpart of fall blooms has shifted 0.49/1.28 days earlier per year. The duration and magnitude are independent with each other for spring bloom at interannual time scale. In contrast, they are positively correlated for fall bloom, because of both bloom timing and magnitude are dominated by active oceanic dynamical processes in fall.
Cadmium-induced toxicity in Meretrix meretrix ovary is characterized by oxidative damage with changes in cell morphology and apoptosis-related factors
Authors: Bai Binbin , Yang Yuqing , Wei Jinyan , Zheng Qi , Wang Mengci , Chang Alan Kueichieh , Ying Xueping
Published: December 2022

Cadmium (Cd) is one of the most common pollutants in the environment. It can cause irreversible tissue damage and apoptosis in invertebrates. This study investigated the relationship between Cd exposure and oxidative damage and apoptosis in the ovarian cell of the clam Meretrix meretrix. The clams were exposed to different concentrations of Cd2+ (0, 1.5, 3, 6 and 12 mg L−1) for 5 days, and the accumulated level of Cd2+ in the ovarian tissue, and the degree of oxidative damage, changes in morphology and the response of apoptosis-related factors in the ovarian cell were determined. The bioaccumulation of Cd2+ and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonylation (PCO), and DNA-protein crosslinking (DPC) in the ovary were found to increase significantly when the clams were exposed to increasing concentrations of Cd2+. The structure of the ovarian tissue was severely damaged, and the ovarian cells displayed an irregular arrangement. The results of AO/EB staining and flow cytometry showed that the apoptotic rate of the ovarian cells increased with increasing Cd2+ concentrations. The activities of caspase-3, -8, -9, and the mRNA levels of p53, Bax and Caspase-3 in the ovary were also significantly increased. Furthermore, the level of p53 mRNA was positively correlated with the levels of MDA, PCO, DPC and ROS, but negatively correlated with the levels of total antioxidant capacity (T-AOC) and Bcl-2 mRNA. Taken together, these results indicated that Cd2+ exposure would result in oxidative damage and apoptosis for the ovarian cells, suggesting that Cd2+ toxicity could negatively affect the reproductive capacity of M. meretrix, thus threatening the reproductive development of the shellfish.
Energy transport analysis in natural convective flow of water:Ethylene glycol (50:50)-based nanofluid around a spinning down-pointing vertical cone
Authors: Iqbal Zahoor , Yashodha S. , Hakeem A. K. Abdul , Alsawi Abdulrahman , Alyami Maryam Ahmed , Yousef El. Sayed , Amin Ali H. , Eldin Sayed M.
Published: December 2022

The influence of the magnetic field on H2O−C2H6O2 (50:50)-based nanofluid over a heated and spinning vertical cone is deliberated. Water: ethylene glycol (50:50) mixture-based nanofluid with Al2O3 and Fe3O4 as nanoparticles exhibits higher thermal conductivity enhancement. Heat transfer analysis for the spinning vertical cone with a prescribed surface temperature was investigated. The influence of magnetic parameter, spin parameter, and nanoparticle volume fraction on tangential velocity profile, spin velocity profile, and thermal profile is analyzed. The results accord strongly with the findings of previous research works in the special cases. Computation shows that as magnetic parameter increases, the thicknesses of hydrodynamic and thermal boundary layers decrease and increase, respectively. The addition of nanoparticles (Al2O3 and Fe3O4) effectively enhances the skin friction coefficient and Nusselt number.
Thermal system for a new flexible composite tank
Authors: Liu Yuxi , Li Qian , Zhu Haoyu
Published: December 2022

A flexible thermal insulation system is proposed in this study, which considers the application and promotion of flexible composite materials in the field of marine engineering. This system is designed to provide a cost-effective and convenient thermal insulation solution for avoiding impurity precipitation and formation of wax plugs caused by extremely low temperature during mining, transportation, and storage of oil. The thermal insulation system includes two main parts: the insulation layer and the heating source. In accordance with the laws of thermodynamics and the primary characteristics of the flexible structure, two different insulation systems were designed and model tests were performed to compare performance in heating efficiency, thermal insulation, and temperature field distribution under identical environmental conditions. Compared with the plan 1 thermal insulation system, the plan 2 system has lower requirements for heating power, more uniform temperature field distribution inside the flexible structure, and a difference of only 7.18°C between the highest and lowest temperatures.
Effect of fibre loading on the microstructural, electrical, and mechanical properties of carbon fibre incorporated smart cement-based composites
Authors: Zhang Jiacheng , Heath Andrew , Ball Richard J. , Paine Kevin
Published: December 2022

Carbon fibre incorporated smart cement-based composite has great potential for the multifunctional health monitoring of concrete structures. This paper presents the microstructural, electrical, and mechanical properties of smart cement-based composites incorporating chopped carbon fibres from low dosages at 0–0.1% by volume (vol%) with detailed intervals, to high dosages up to 2.4 vol%. In comparison to a plain mortar, smart cement-based composites at all fibre contents had higher flexural strength. A 95% improvement in flexural strength was obtained at a fibre content of 0.3 vol%, whereas compressive strength increased up to a fibre content of 1.0 vol%, with the highest improvement, 105%, at 0.2 vol%. The bulk conductivity of smart cement-based composites underwent a double percolation process where the percolation zone of the fibres was identified at fibre contents of 0–0.1 vol% and the percolation zone of the capillary pores resided at fibre contents of 2.1–2.4 vol% indicating an extremely low durability. This study presents the laboratory characterization on smart cement-based composites where the fundamentals of the transitional behaviours of the mechanical properties and the percolation in electrical property through fibre loading were studied, which is a necessary step prior to the assessment of the self-sensing performance. The impact of this study will enable the physical properties of carbon fibre incorporated smart cement-based composites to be optimized through the design and manufacturing process. This will lead to robust performance and superior in-situ multi-functional health monitoring of concrete structures.
Nitrogen inclusion in carbon nanotubes initiated by boron doping and chlorination: Their use as electrocatalysts for oxygen reduction reaction
Authors: Maboya Winny K. , Maubane-Nkadimeng Manoko S. , Jijana Abongile N. , Mmako Herry K.
Published: December 2022

The use of carbon nanostructures doped with heteroatoms as electrocatalysts for oxygen reduction reaction (ORR) has attracted intense research in recent years because they are highly conductive, have good durability, and are highly electro-active. One of the strategies to modify the characteristics of carbon nanomaterials (CNMs) to render them suitable for certain applications is to dope them with boron (B) and nitrogen (N). The effect of doping CNMs with boron has been a subject of little study, and hence, it is not well understood, as compared to nitrogen doping studies. In this study, nitrogen was unintentionally doped into carbon nanotubes (CNTs) by chlorination and decomposition of triphenylborane in a catalytic vapor deposition (CVD) reactor. N-doping resulted from the use of nitrogen as a carrier gas. Microscopic and spectroscopic techniques revealed that N bonding of carbon nanostructures together with the presence of defects played pivotal roles in determining the extent of ORR performance of produced CNMs. The introduction of N in the carbon matrix during B molecule decomposition resulted in the reduction in the amount of B doped into the matrix, due to competitive incorporation of N which inhibited B introduction. The presence of pyridinic N species was responsible for a 2e−ORR performance.
In vitro model for investigating aerosol dispersion in a simulated COVID-19 patient during high-flow nasal cannula treatment
Authors: McGrath James A. , O’Sullivan Andrew , Joyce Mary , Byrne Miriam A. , Li Jie , Fink James B. , MacLoughlin Ronan
Published: December 2022

The use of high-flow nasal cannula in the treatment of COVID-19 infected patients has proven to be a valuable treatment option to improve oxygenation. Early in the pandemic, there were concerns for the degree of risk of disease transmission to health care workers utilizing these treatments that are considered aerosol generating procedures. This study developed an in vitro model to examine the release of simulated patient-derived bioaerosol with and without high-flow nasal cannula at gas flow rates of 30 and 50 L/min. Aerosol dispersion was evaluated at 30 and 90 cm distances. Reduction of transmission risk was assessed using a surgical facemask on the manikin. Results indicated that the use of a facemask facilitated a 94–95% reduction in exhaled aerosol concentration at 30 cm and 22–60% reduction for 90 cm distance across both gas flow rates. This bench study confirms that this in vitro model can be used as a tool to assess the risk of disease transmission during aerosol generating procedures in a simulated patient and to test factors to mitigate the risk.