bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation and high temperature strengthening mechanism of alkali activated biological-ash hybrid glass fiber-carbon fiber cement slurry system
Authors: Zhang Yihang , Wen Jiaxin , Yin Xuejiao
Published: September 2022

In recent years, with the rapid development of biomass combustion power generation and heat generation as the main application industry, the amount of byproduct biological ash is also increasing year by year. How to effectively utilize the biological ash in a more green, environmental friendly and economic way has become a research hotspot. In view of the problem that the mechanical properties of the cement stone decreased when the conventional latex was used as the toughening agent, based on the introduction of high dispersive composite modified fiber to enhance the toughness of the cement stone, this paper analyzed the physical and chemical properties and application status of the biological ash, and further explored the influence and role of the biological ash as the cement stone admixture on the high-temperature mechanical properties of the composite fiber cement stone Mechanism. The results show that when the dosage of biological ash is in the range of 0–10% (wt%), it has little effect on the basic slurry properties of cement stone, and has a certain preventive effect on the gas channeling of cement stone. In the analysis of comprehensive mechanical properties, the activated biological ash can enhance the compactness of cement matrix under high temperature by reducing the Ca/Si ratio through the secondary pozzolanic effect, stimulate the formation of a large number of hydration products, and strengthen the later strength growth rate of cement. The high temperature resistance of cement paste can be effectively improved by hybrid high dispersion composite fiber.
Does digitalization drive corporate green transformation?—Based on evidence from Chinese listed companies
Authors: Peng Cheng , Jia Xinyuan , Zou Yu
Published: September 2022

Accelerating the digital transformation of enterprises, enabling enterprise operation and management with digitalization, and driving green transformation are important tasks to further promote the digital construction of a country. Based on the text data mining method, this paper investigates digitalization’s impact on enterprises’ green transformation and its mechanisms, using A-share listed companies in Shanghai and Shenzhen as research samples from 2011 to 2020. The results show that digitalization has the effect of “inhibiting” and then “promoting” on the green transformation of enterprises, i.e., the relationship between the two is U-shaped. The heterogeneity analysis shows that this U-shaped relationship exists among non-heavy polluting enterprises, eastern enterprises, main-board enterprises, GEM enterprises, and enterprises with high digitization speed. As far the influence mechanism, the dynamic capability acts as a partial mediator in the relationship between digitalization and green transformation. This study provides a useful reference for enterprises to drive sustainable development and promote the construction of national ecological civilization.
How does foreign trade affect green total factor energy efficiency? Evidence from China
Authors: Xu Jun , Li Jinye , Liu Chunyan
Published: September 2022

As the largest trading nation in the world, there have been substantial foreign trades (export and import) between China and other countries. Meanwhile, it is also one of the major forces for China’s emission reduction. This article applies the panel data of 30 provinces for the period 2004–2017 to investigate the effect of foreign trade on China’s green total factor energy efficiency (GTFEE). The slack-based measure (SBM) model is employed to calculate the provincial GTFEEs. Subsequently, the empirical results of the basic linear regression model revealed that both export and import promoted the region’s GTFEE, on which the import particularly has more effects than the export. Moreover, the spatial Durbin model (SDM) exhibited that the increase in import will not only present a positive influence on the GTFEE of the region, but also will improve the GTFEEs of the surrounding provinces through the spatial spillover mechanism. Although the increase in export will also exert a positive influence on the GTFEE of the local area, it will impose a significant negative impact on the GTFEEs of the surrounding regions. The results of this study provide important policy implications for the optimization of trade structure and high-quality development of the Chinese economy.
The impact of the COVID-19 pandemic outbreak on the sustainable development of the Turkish banking sector
Authors: Erden Bahattin , Aslan Ömer Faruk
Published: September 2022

This study tries to investigate the development in the banking sector by considering the correlation values before and after March 2020 including the COVID-19 pandemic period in the case of Turkey. However, the full influence of the pandemic will take place in the long term. The number of banks in Turkey, the number of domestic/foreign branches, the number of deposit/participation banks, the volume of the financial sector in gross domestic product (GDP), the number of personnel working in banks, the total number of savings deposits of banks, the total amount of savings deposits of banks, the total number of automatic teller machines (ATMs)/point of sale (POS) owned by the banks, and their relations with the data of the number of establishments are the members of the bank. In Spearman’s correlation, these will be reviewed in the course of correlations. As a result of the analysis, a high level of positive correlation was detected in most of the variables, while an admirable level of positive correlation was determined between the two variables.
Soil column experiment and numerical simulation research of Pb migration process in the groundwater fluctuation zone based on HYDRUS
Authors: Qu Jihong , Jiang Jueyan , Zhang Yifeng , Li Yuepeng , Yan Tiangang , Guo Wei , Lu Shibao
Published: September 2022

Groundwater level fluctuation alters hydrodynamic conditions and hydrogeochemical action, thus affecting the migration and transformation of pollutants. This study investigated the effect of groundwater level fluctuations on Pb migration processes. We selected two typical media, coarse sand and medium sand, for the soil column experiments and numerical simulations of the Pb migration process in the groundwater level fluctuation zone. The soil column experiments showed that when the contaminants were distributed at a 30–40 cm depth in the soil column, the Pb migrated into the water in the range of 20–45 cm in coarse sand, while the range of Pb migration in medium sand decreased to 30 cm–40 cm. We constructed a numerical model of Pb migration in the aeration zone–saturation zone coupled with water transport and solute transport by HYDRUS-1D. The model simulated the migration process of Pb in different amplitude and frequency of water level fluctuation and initial concentration of pollutants. The results showed that the coarse sand column and medium sand column showed relatively noticeable changes in Pb concentration in water at 30–40 cm and 30–35 cm, respectively. The migration range and concentration of Pb in water are proportional to the medium particle size and the frequency of water level fluctuation, and inversely proportional to the magnitude of water level fluctuation. The Pb concentration in the water increased or decreased as the initial pollutant concentration of the medium increased or decreased. Its variation is basically the same as the variation of the initial contaminant concentration. The research results can provide a scientific basis for the remediation of heavy metal pollution in groundwater.
Evolutionary rates of body-size-related genes and ecological factors involved in driving body size evolution of squamates
Authors: Wu Haixia , Gao Shuo , Xia Longjie , Li Peng
Published: September 2022

Body size is one of the most important traits of an organism. Among reptiles, both lizards and snakes show body size differences that span a similar six orders of magnitude variation. However, the molecular mechanisms underlying body size variation in squamates remain obscure. Here, we performed comparative genomic analyses of 101 body-size-related genes from 28 reptilian genomes. Phylogenetic analysis by maximum likelihood (PAML) revealed that snakes showed higher evolutionary rates in body-size-related genes, and had an almost two-fold increase in the number of positively selected genes (∼20.3%) compared with lizards (∼8.9%). The high similarities in dN/dS values were obtained between the branches of large-bodied lizards and large-bodied snakes by Spearman correlation analysis. Combining the results from site model, branch-site model and clade model analyses, we found some key genes regulating the evolution of body size in squamates, such as COL10A1, GHR, NPC1, GALNS, CDKN2C, FBN1, and LCORL. Phylogenetic generalized least squares (PGLS) indicated that AKT1, BMP1, IGF1, SOX5, SOX7 in lizards and BMP5, BMP7, GPC6, SH2B3, SOX17 in snakes were significantly correlated with body length and body mass. Furthermore, ecological factors had varying degrees of impact on body size and the evolutionary rate of body-size-related genes in squamates. Intriguingly, climate had little effect on body size of lizards and snakes, but the contribution of climate-related factors to the variation in evolutionary rate of body-size-related genes were relatively higher. Our study lays a foundation for a comprehensive understanding of genetic mechanisms of body size evolution in squamates during the process of adapting to terrestrial life.
A high scale SARS-CoV-2 profiling by its whole-genome sequencing using Oxford Nanopore Technology in Kazakhstan
Authors: Kairov Ulykbek , Amanzhanova Amina , Karabayev Daniyar , Rakhimova Saule , Aitkulova Akbota , Samatkyzy Diana , Kalendar Ruslan , Kozhamkulov Ulan , Molkenov Askhat , Gabdulkayum Aidana , Sarbassov Dos , Akilzhanova Ainur
Published: September 2022

Severe acute respiratory syndrome (SARS-CoV-2) is responsible for the worldwide pandemic, COVID-19. The original viral whole-genome was sequenced by a high-throughput sequencing approach from the samples obtained from Wuhan, China. Real-time gene sequencing is the main parameter to manage viral outbreaks because it expands our understanding of virus proliferation, spread, and evolution. Whole-genome sequencing is critical for SARS-CoV-2 variant surveillance, the development of new vaccines and boosters, and the representation of epidemiological situations in the country. A significant increase in the number of COVID-19 cases confirmed in August 2021 in Kazakhstan facilitated a need to establish an effective and proficient system for further study of SARS-CoV-2 genetic variants and the development of future Kazakhstan’s genomic surveillance program. The SARS-CoV-2 whole-genome was sequenced according to SARS-CoV-2 ARTIC protocol (EXP-MRT001) by Oxford Nanopore Technologies at the National Laboratory Astana, Kazakhstan to track viral variants circulating in the country. The 500 samples kindly provided by the Republican Diagnostic Center (UMC-NU) and private laboratory KDL “Olymp” were collected from individuals in Nur-Sultan city diagnosed with COVID-19 from August 2021 to May 2022 using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). All samples had a cycle threshold (Ct) value below 20 with an average Ct value of 17.03. The overall average value of sequencing depth coverage for samples is 244X. 341 whole-genome sequences that passed quality control were deposited in the Global initiative on sharing all influenza data (GISAID). The BA.1.1 (n = 189), BA.1 (n = 15), BA.2 (n = 3), BA.1.15 (n = 1), BA.1.17.2 (n = 1) omicron lineages, AY.122 (n = 119), B.1.617.2 (n = 8), AY.111 (n = 2), AY.126 (n = 1), AY.4 (n = 1) delta lineages, one sample B.1.1.7 (n = 1) belongs to alpha lineage, and one sample B.1.637 (n = 1) belongs to small sublineage were detected in this study. This is the first study of SARS-CoV-2 whole-genome sequencing by the ONT approach in Kazakhstan, which can be expanded for the investigation of other emerging viral or bacterial infections on the country level.
Signature based on RNA-binding protein-related genes for predicting prognosis and guiding therapy in non-small cell lung cancer
Authors: Miao Ti-Wei , Chen Fang-Ying , Du Long-Yi , Xiao Wei , Fu Juan-Juan
Published: September 2022

Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value.

Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature.

Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group (p < 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease (p < 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage (p < 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53, focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value <0.05). The high-risk group was correlated with increased immune infiltration (p < 0.05), upregulated relative expression levels of programmed cell death 1 (PD1) (p = 0.015), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (p = 0.042), higher gene mutation frequency, higher tumor mutational burden (p = 0.034), and better chemotherapy response (p < 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort (p < 0.05).

Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy.
T cell proliferation-related genes: Predicting prognosis, identifying the cold and hot tumors, and guiding treatment in clear cell renal cell carcinoma
Authors: Huang Haoran , Cai Yanmin , Hong Xitao , Gao Wenzong , Tang Jun , Zhang Shujuan , Xu Zhe
Published: September 2022

Background: Immunotherapy has become a new direction of current research because the effect of traditional radiotherapy and chemotherapy on clear cell renal cell carcinoma (ccRCC) is not satisfactory. T cell proliferation-related genes (TRGs) play a pivotal role in tumor progression by regulating the proliferation, activity, and function of immune cells. The purpose of our study is to construct and verify a prognostic model based on TRGs and to identify tumor subtypes that may guide treatment through comprehensive bioinformatics analyses.

Methods: RNA sequencing data, clinical information, and somatic mutation data of ccRCC are obtained from The Cancer Genome Atlas (TCGA) database. We identified the prognosis-related TRGs which were differentially expressed between normal and tumor tissues. After dividing the patients into a train set and a test set according to proportion 1:1 randomly, the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were performed to construct a risk-stratified model. Its prediction performance was verified. Then, Gene Set Enrichment Analysis (GSEA), principal component analysis (PCA), tumor microenvironment (TME) analysis, and the half-maximal inhibitory concentration (IC50) prediction were performed between the different groups of patients. To further discuss the immunotherapy between hot and cold tumors, we divided all patients into two clusters based on TRGs through unsupervised learning. Analyzing the gene mutation and calculating the tumor mutation burden (TMB), we further explored the relationship between somatic mutations and grouping or clustering.

Results: Risk-stratified model and nomogram predict the prognosis of ccRCC patients accurately. Functional enrichment analyses suggested that TRGs mainly focused on the biological pathways related to tumor progression and immune response. Different tumor microenvironment, drug resistance, and TMB can be distinguished clearly according to both risk stratification and tumor subtype clustering.

Conclusion: In this study, a new stratification model of ccRCC based on TRGs was established, which can accurately predict the prognosis of patients. IC50 prediction may guide the application of anti-tumor drugs. The distinction between hot and cold tumors provides a reference for clinical immunotherapy.
Genome architecture plasticity underlies DNA replication timing dynamics in cell differentiation
Authors: Yu Wenjun , Zhong Quan , Wen Zi , Zhang Weihan , Huang Yanrong
Published: September 2022

During the S-phase of eukaryotic cell cycle, DNA is replicated in a dedicatedly regulated temporal order, with regions containing active and inactive genes replicated early and late, respectively. Recent advances in sequencing technology allow us to explore the connection between replication timing (RT), histone modifications, and three-dimensional (3D) chromatin structure in diverse cell types. To characterize the dynamics during cell differentiation, corresponding sequencing data for human embryonic stem cells and four differentiated cell types were collected. By comparing RT and its extent of conservation before and after germ layer specification, the human genome was partitioned into distinct categories. Each category is then subject to comparisons on genomic, epigenetic, and chromatin 3D structural features. As expected, while constitutive early and late replication regions showed active and inactive features, respectively, dynamic regions with switched RT showed intermediate features. Surprisingly, although early-to-late replication and late-to-early replication regions showed similar histone modification patterns in hESCs, their structural preferences were opposite. Specifically, in hESCs, early-to-late replication regions tended to appear in the B compartment and large topologically associated domains, while late-to-early replication regions showed the opposite. Our results uncover the coordinated regulation of RT and 3D genome structure that underlies the loss of pluripotency and lineage commitment and indicate the importance and potential roles of genome architecture in biological processes.
An additional whole-exome sequencing study in 102 panel-undiagnosed patients: A retrospective study in a Chinese craniosynostosis cohort
Authors: Chen Jieyi , Zhang Ping , Peng Meifang , Liu Bo , Wang Xiao , Du Siyuan , Lu Yao , Mu Xiongzheng , Lu Yulan , Wang Sijia , Wu Yingzhi
Published: September 2022

Craniosynostosis (CRS) is a disease with prematurely fused cranial sutures. In the last decade, the whole-exome sequencing (WES) was widely used in Caucasian populations. The WES largely contributed in genetic diagnosis and exploration on new genetic mechanisms of CRS. In this study, we enrolled 264 CRS patients in China. After a 17-gene-panel sequencing designed in the previous study, 139 patients were identified with pathogenic/likely pathogenic (P/LP) variants according to the ACMG guideline as positive genetic diagnosis. WES was then performed on 102 patients with negative genetic diagnosis by panel. Ten P/LP variants were additionally identified in ten patients, increasing the genetic diagnostic yield by 3.8% (10/264). The novel variants in ANKH, H1-4, EIF5A, SOX6, and ARID1B expanded the mutation spectra of CRS. Then we designed a compatible research pipeline (RP) for further exploration. The RP could detect all seven P/LP SNVs and InDels identified above, in addition to 15 candidate variants found in 13 patients with worthy of further study. In sum, the 17-gene panel and WES identified positive genetic diagnosis for 56.4% patients (149/264) in 16 genes. At last, in our estimation, the genetic testing strategy of “Panel-first” saves 24.3% of the cost compared with “WES only”, suggesting the “Panel-first” is an economical strategy.
Disruption of cellular immune response among male rotating night shift workers in Spain– The HORMONIT study
Authors: Harding Barbara N. , Aguilar Ruth , Espinosa Ana , Castaño-Vinyals Gemma , Papantoniou Kyriaki , Navarrete José Maria , Such Faro Patricia , Torrejón Antonio , Dobaño Carlota , Moncunill Gemma , Kogevinas Manolis
Published: September 2022

Introduction

Preliminary studies suggest that night shift work is associated with a desynchronization of rhythmic immune markers, possibly explaining the increased risk of infection, cardiometabolic disorders, and cancer in shift workers.

Methods

This study included 51 male rotating shift workers from a car industry in Barcelona, Spain, sampled twice toward the end of a 3-week night shift (22:00-06:00 h) and a 3-week day shift (06:00-14:00 h) rotation. We collected four blood samples per worker, at the start and end of each shift. We measured 27 cytokines, chemokines and growth factors in plasma samples by luminex using the Cytokine Human Magnetic 30-Plex Panel LHC6003M and applied linear mixed models to examine within-person associations between shift work and analytes’ concentrations, comparing samples taken at 06:00 h on a day and night shift. We also conducted a factor analysis using analyte concentrations from all 4 time points for each individual to identify common factors and determine if these factors were altered by shift work.

Results

We observed lower levels of 15 analytes in the night shift compared to the day shift including cytokines (pro-inflammatory TNF-α, IL-2R; anti-inflammatory IL1-RA; Th1 IL-2, Th2 IL-4 and Th17 Il-17), chemokines (IP-10, MIP-1α, MIP-1β, RANTES) and growth factors (EGF, G-CSF, HGF, VEGF, FGF). In a factor analysis, three factors were identified. The main factor (Factor 1), explaining 57% of the variance and including IL-1β, IL-12, IL-15, MIP-1α, MIP-1β, EGF and FGF; and another factor (Factor 3) explaining 10% of the variance and including the Th1 cytokine IL-12, were inversely associated with the night shift (coefficient: -0.17, 95%CI -0.32 to -0.01 and coefficient: -0.22, 95%CI -0.38, -0.06, for Factors 1 and 3, respectively). Our results indicate that night shift disrupts the levels of several immune markers, which could contribute to the increased risk of infections and cancer reported in night shift workers.

Conclusion

Night shift is associated with disruption of multiple immune response pathways.
The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment
Authors: Lian Jiachun , Liang Yanfang , Zhang Hailiang , Lan Minsheng , Ye Ziyu , Lin Bihua , Qiu Xianxiu , Zeng Jincheng
Published: September 2022

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamine metabolism plays essential roles in remodeling the tumor immune microenvironment (TIME), particularly treatment of DFMO, an inhibitor of ODC, alters the immune cell population in the tumor microenvironment. Tumor immunosuppression is a major problem in cancer treatment. More and more studies have shown that the immunosuppressive effect of polyamines can help cancer cells to evade immune surveillance and promote tumor development and progression. Therefore, targeting polyamine metabolic pathways is expected to become a new avenue for immunotherapy for cancer.
SARS-CoV-2 vaccination in androgen sensitive phenotypes – A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients
Authors: Fan Zhihua , Duan Shixin , Liu Fangfen , Shi Wei , Yang Ziye , Bai Ruiyang , Li Tao , Chen Jingxian , Xie Hongfu , Li Ji , Tang Yan
Published: September 2022

Background

Androgen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection.

Purpose

We aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH.

Method

We collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of anti-androgen therapy.

Result

A total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p < 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p < 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019).

Conclusion

Co-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes.
Host inflammatory response is the major factor in the progression of Chlamydia psittaci pneumonia
Authors: Zhang Zhenjie , Wang Peihan , Ma Chuanmin , Wang Jing , Li Wenxin , Quan Chuansong , Cao Huae , Guo Hongfeng , Wang Liang , Yan Chengxin , Carr Michael J. , Meng Ling , Shi Weifeng
Published: September 2022

Purpose

Chlamydia psittaci(C. psittaci) has caused sporadic, but recurring, fatal community-acquired pneumonia outbreaks worldwide, posing a serious threat to public health. Our understanding of host inflammatory responses toC. psittaciis limited, and many bronchitis cases of psittaci have rapidly progressed to pneumonia with deterioration.

Methods

To clarify the host inflammatory response in psittacosis, we analyzed clinical parameters, and compared transcriptomic data, concentrations of plasma cytokines/chemokines, and changes of immune cell populations in 17 laboratory-confirmed psittacosis cases, namely, 8 pneumonia and 9 bronchitis individuals, in order to assess transcriptomic profiles and pro-inflammatory responses.

Results

Psittacosis cases with pneumonia were found to have abnormal routine blood indices, liver damage, and unilateral pulmonary high-attenuation consolidation. Transcriptome sequencing revealed markedly elevated expression of several pro-inflammatory genes, especially interleukins and chemokines. A multiplex-biometric immunoassay showed that pneumonia cases had higher levels of serum cytokines (G-CSF, IL-2, IL-6, IL-10, IL-18, IP-10, MCP-3, and TNF-α) than bronchitis cases. Increases in activated neutrophils and decreases in the number of lymphocytes were also observed in pneumonia cases.

Conclusion

We identified a number of plasma biomarkers distinct toC. psittacipneumonia and a variety of cytokines elevated with immunopathogenic potential likely inducing an inflammatory milieu and acceleration of the disease progression of psittaci pneumonia. This enhances our understanding of inflammatory responses and changes in vascular endothelial markers in psittacosis with heterogeneous symptoms and should prove helpful for developing both preventative and therapeutic strategies.
The influence of antibody humanization on shark variable domain (VNAR) binding site ensembles
Authors: Fernández-Quintero Monica L. , Fischer Anna-Lena M. , Kokot Janik , Waibl Franz , Seidler Clarissa A. , Liedl Klaus R.
Published: September 2022

Sharks and other cartilaginous fish produce new antigen receptor (IgNAR) antibodies, as key part of their humoral immune response and are the phylogenetically oldest living organisms that possess an immunoglobulin (Ig)-based adaptive immune system. IgNAR antibodies are naturally occurring heavy-chain-only antibodies, that recognize antigens with their single domain variable regions (VNARs). In this study, we structurally and biophysically elucidate the effect of antibody humanization of a previously published spiny dogfish VNAR (parent E06), which binds with high affinity to the human serum albumin (HSA). We analyze different humanization variants together with the parental E06 VNAR and the human Vκ1 light chain germline DPK9 antibody to characterize the influence of point mutations in the framework and the antigen binding site on the specificity of VNARs as reported by Kovalenko et al. We find substantially higher flexibility in the humanized variants, reflected in a broader conformational space and a higher conformational entropy, as well as population shifts of the dominant binding site ensembles in solution. A further variant, in which some mutations are reverted, largely restores the conformational stability and the dominant binding minimum of the parent E06. We also identify differences in surface hydrophobicity between the human Vκ1 light chain germline DPK9 antibody, the parent VNAR E06 and the humanized variants. Additional simulations of VNAR-HSA complexes of the parent E06 VNAR and a humanized variant reveal that the parent VNAR features a substantially stronger network of stabilizing interactions. Thus, we conclude that a structural and dynamic understanding of the VNAR binding site upon humanization is a key aspect in antibody humanization.
Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia
Authors: Gan Chai Phei , Lee Bernard Kok Bang , Lau Shin Hin , Kallarakkal Thomas George , Zaini Zuraiza Mohamad , Lye Bryan Kit Weng , Zain Rosnah Binti , Sathasivam Hans Prakash , Yeong Joe Poh Sheng , Savelyeva Natalia , Thomas Gareth , Ottensmeier Christian H. , Ariffin Hany , Cheong Sok Ching , Lim Kue Peng
Published: September 2022

Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progression; however, the underlying immune mechanisms remain elusive. In this study, we used immune signatures established from cancer to delineate the immune profiles of moderate and severe OED, which are considered high-risk OPMD. We demonstrated that moderate and severe OEDs exhibit high lymphocyte infiltration and upregulation of genes involved in both immune surveillance (major histocompatibility complex-I, T cells, B cells and cytolytic activity) and immune suppression (immune checkpoints, T regulatory cells, and tumor-associated macrophages). Notably, we identified three distinct subtypes of moderate and severe OED: immune cytotoxic, non-cytotoxic and non-immune reactive. Active immune surveillance is present in the immune cytotoxic subtype, whereas the non-cytotoxic subtype lacks CD8 immune cytotoxic response. The non-immune reactive subtype showed upregulation of genes involved in the stromal microenvironment and cell cycle. The lack of T cell infiltration and activation in the non-immune reactive subtype is due to the dysregulation of CTNNB1, PTEN and JAK2. This work suggests that moderate and severe OED that harbor the non-cytotoxic or non-immune reactive subtype are likely to progress to cancer. Overall, we showed that distinct immune responses are present in high-risk OPMD, and revealed targetable pathways that could lead to potential new approaches for non-surgical management of OED.
Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma – There’s room for Immune Checkpoint Blockage?
Authors: Madureira Ana C.
Published: September 2022

Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is a carcinogen type 1 since 1994. It is strongly associated with bladder squamous-cell carcinoma in endemic regions, where it accounts for 53-69% of bladder-carcinoma cases. This histological subtype is associated with chronic inflammation being more aggressive and resistant to conventional chemo and radiotherapy. Immune-Checkpoint-Blockage (ICB) therapies targeting the Programmed-Cell-Death-Protein-1(PD-1)/Programmed-Cell-Death-Ligand-1(PD-L1) axis showed considerable success in treating advanced bladder urothelial carcinoma. PD-L1 is induced by inflammatory stimuli and expressed in immune and tumor cells. The binding of PD-L1 with PD-1 modulates immune response leading to T-cell exhaustion. PD-L1 presents in several isoforms and its expression is dynamic and can serve as a companion marker for patients’ eligibility, allowing the identification of positive tumors that are more likely to respond to ICB therapy. The high PD-L1 expression in bladder-urothelial-carcinoma and squamous-cell carcinoma may affect further ICB-therapy application and outcomes. In general, divergent histologies are ineligible for therapy. These treatments are expensive and prone to auto-immune side effects and resistance. Thus, biomarkers capable of predicting therapy response are needed. Also, the PD-L1 expression assessment still needs refinement. Studies focused on squamous cell differentiation associated with S. haematobium remain scarce. Furthermore, in low and middle-income-regions, where schistosomiasis is endemic, SCC biomarkers are needed. This mini-review provides an overview of the current literature regarding PD-L1 expression in bladder-squamous-cell-carcinoma and schistosomiasis. It aims to pinpoint future directions, controversies, challenges, and the importance of PD-L1 as a biomarker for diagnosis, disease aggressiveness, and ICB-therapy prognosis in bladder-schistosomal-squamous-cell carcinoma.
Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer
Authors: Zhao Yujie , Liu Xu , Liu Xinyu , Yu Jing , Bai Xin , Wu Xi , Guo Xinyu , Liu Zhihui , Liu Xiaowei
Published: September 2022

Immune checkpoint blockade (ICB) therapy has evolved as a revolutionized therapeutic modality to eradicate tumor cells by releasing the brake of the antitumor immune response. However, only a subset of patients could benefit from ICB treatment currently. Phototherapy usually includes photothermal therapy (PTT) and photodynamic therapy (PDT). PTT exerts a local therapeutic effect by using photothermal agents to generate heat upon laser irradiation. PDT utilizes irradiated photosensitizers with a laser to produce reactive oxygen species to kill the target cells. Both PTT and PDT can induce immunogenic cell death in tumors to activate antigen-presenting cells and promote T cell infiltration. Therefore, combining ICB treatment with PTT/PDT can enhance the antitumor immune response and prevent tumor metastases and recurrence. In this review, we summarized the mechanism of phototherapy in cancer immunotherapy and discussed the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. Moreover, we also outlined the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB in preclinical and clinical studies. Finally, we analyzed the current challenges of this novel combination treatment regimen. We believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.
Altered intraperitoneal immune microenvironment in patients with peritoneal metastases from gastric cancer
Authors: Takahashi Kazuya , Kurashina Kentaro , Yamaguchi Hironori , Kanamaru Rihito , Ohzawa Hideyuki , Miyato Hideyo , Saito Shin , Hosoya Yoshinori , Lefor Alan Kawarai , Sata Naohiro , Kitayama Joji
Published: September 2022

Background

The peritoneal cavity contains many site-specific immune cells which constitute a unique immune microenvironment. However, it is unclear how the local immune signature is altered in patients with peritoneal metastases (PM).

Methods

Peritoneal lavage fluid or ascites were obtained from 122 patients with various stages of gastric cancer (GC). Cells recovered from peritoneal fluids were immunostained with mAbs for lymphocyte-, macrophage- and tumor cell-specific antigens and the frequencies of leukocyte subsets and antigen expression levels were evaluated with multi-color flowcytometry.

Results

The proportions of CD8(+) T cells, CD3(+)CD56(+) NKT-like cells, and CD3(-)CD56(+) NK cells to CD45(+) leukocytes were significantly reduced in patients with PM compared to those without PM. In patients with PM, the rates of CD8 (+) T cells and NKT-like cells correlated inversely with the tumor leukocyte ratio (TLR), the relative frequency of CD326(+) tumor cells to CD45(+) leukocytes. In contrast, the proportion of CD19(+) B cells was significantly increased in patients with PM, and their proportion correlated positively with the TLR and peritoneal carcinomatosis index (PCI) score. In patients with PM, CD14(+) macrophages tended to be increased with enhanced expression of CD14, CD16 and a M2-macrophage marker, CD163. In particular, macrophages in patients with high TLR contained many granules with high side scatter and CD14 expression in their flow profile compared to those without PM.

Conclusion

PM are accompanied by a drastic change in phenotypes of lymphocyte and macrophage in the peritoneal cavity, which might be involved in the development and progression of intraperitoneal tumor growth.
COVID-19 vaccine type-dependent differences in immunogenicity and inflammatory response: BNT162b2 and ChAdOx1 nCoV-19
Authors: Heo Jung Yeon , Seo Yu Bin , Kim Eun Jin , Lee Jacob , Kim Young Rong , Yoon Jin Gu , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Yoon Soo-Young , Choi Ju-Yeon , Lee Young Jae , Lee Hye Won , Kim Sung Soon , Kim Byoungguk , Song Joon Young
Published: September 2022

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.
Ferulic acid alleviates retinal neovascularization by modulating microglia/macrophage polarization through the ROS/NF-κB axis
Authors: Sun Xiaowei , Ma Lusheng , Li Xiao , Wang Jiao , Li Yuanbin , Huang Zijing
Published: September 2022

Inflammation plays a pivotal role in ischemia-induced retinal neovascularization. Targeting microglia/macrophage-based neuroinflammation presents a promising therapeutic strategy. Ferulic acid (FA), a natural and active ingredient in plants, exerts favorable anti-oxidative and anti-inflammatory activities. In this study, we investigated the inhibitory effect of FA against hypoxia-induced retinal angiogenesis using cultured retinal vascular endothelial cells and an oxygen-induced retinopathy mouse (OIR) model. The immunoregulatory effect of FA on microglia/macrophage polarization was evaluated by detecting the expression of specific markers for both pro-inflammatory “M1” and anti-inflammatory “M2” phenotypes using co-immunostaining and polymerase chain reaction assays. The underlying molecular mechanism upon FA treatment was also explored. The results showed that FA supplement markedly inhibited retinal pathological angiogenesis both in vivo and in vitro. In addition, FA switched microglia/macrophage polarization from “M1” towards “M2” phenotype and alleviated the inflammatory response. Mechanically, the anti-angiogenic and anti-inflammatory properties of FA were mainly due to blockade of the ROS/NF-κB pathway. Our data demonstrated an anti-angiogenic effect of FA through regulating M1-to-M2 microglia/macrophage polarization, suggesting a potential therapeutic strategy for retinal neovascular diseases.
Water temperature variability in the Coos Estuary and its potential link to eelgrass loss
Authors: Marin Jarrin Maria Jose , Sutherland David A. , Helms Alicia R.
Published: September 2022

Subtidal water temperatures in estuaries influence where organisms can survive and are determined by oceanic, atmospheric and riverine heat fluxes, modulated by the distinct geometry and bathymetry of the system. Here, we use 14 years of data from the Coos Estuary, in southwest Oregon, USA, to explore the impact of anomalously warm oceanic and atmospheric conditions during 2014-2016 on the estuary temperature. The arrival of a marine heatwave in September 2014 increased water temperature in the greater Pacific Northwest region until March 2015, and again from July to August 2015. Additionally, in 2014-2016, the Equatorial Pacific showed increased temperatures due to El Niño events. In the Coos Estuary, this warming was observed at all the water quality stations, producing more than 100 days with temperatures at least 1.5°C warmer than normal, and notably, a higher prevalence during Fall and Winter seasons. Larger temperature variations occurred at shallower stations located further away from the mouth of the estuary, changing the along-estuary temperature gradient and potentially the advection of heat through the estuary. After the onset of these increased temperatures, eelgrass declined sharply, but only in certain stations in the shallow estuary South Slough and has not yet returned to long term average values. As global temperatures continue rising due to climate change, increased numbers of marine heatwaves and El Niño events are expected, leading to higher temperature stress on the marine ecosystem within estuaries.
Sex- and age-specific migratory strategies of blue whales in the northeast Pacific Ocean
Authors: Blevins Christina , Busquets-Vass Geraldine , Pardo Mario A. , Gendron Diane , Jacobsen Jeff K. , Gómez-Díaz Francisco , Pérez-Puig Héctor , Ortega-Ortiz Christian Daniel , Heckel Gisela , Urbán R Jorge , Viloria-Gómora Lorena , Newsome Seth D.
Published: September 2022

Migration is a complex behavior that has evolved in multiple taxonomic groups as a means of accessing productive foraging grounds and environmentally stable areas suitable for reproduction. For migratory whales that forage throughout the year because of their high energetic demands, changes in the abundance of prey in different areas along their migratory route(s) can have serious implications for individual fitness and population viability. Thus, identifying the regions these species use to forage and breed while evaluating their migratory plasticity at the individual level can provide key information for their management and conservation. Serial stable isotope analysis of whale baleen, a continuously growing but metabolically inert tissue, has proven useful in generating individual migratory and foraging records over several years prior to death. We measured carbon (δ13C) and nitrogen (δ15N) isotope values along the length of baleen plates collected from thirteen blue whales of different sex and age classes, representing the largest collection analyzed to date in the northeast Pacific Ocean. Adult females exhibited relatively stable seasonal movements between temperate latitude foraging grounds and subtropical breeding grounds, although two skipped migration one year and subsequently moved to the same subtropical breeding ground near the Costa Rica Dome, potentially to give birth. Adult males exhibited two movement strategies with most remaining at temperate latitudes for 3-4 years before death, while two migrated to subtropical breeding grounds. In contrast, movement patterns in juveniles were erratic. These results are potentially driven by the energetic requirements during pregnancy and nursing in adult females, intra-specific competition among adult males, and inexperience in locating prey in juveniles. We also describe baleenδ15N patterns in recently weaned whales (<16.5m) that reflect switching from the consumption of milk to solid food (krill). In addition, baleenδ13C data suggest that weaned whales continue to use stored nutrients (blubber) acquired during the nursing period long after they are weaned. These results broaden our understanding of habitat selection in this species, highlight the importance of nursing for the critical period after weaning, and indicate that the Costa Rica Dome is an important calving region for this endangered population.