bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotype-Genotype analysis of caucasian patients with high risk of osteoarthritis
Authors: Wang Yanfei , Chyr Jacqueline , Kim Pora , Zhao Weiling , Zhou Xiaobo
Published: August 2022

Background: Osteoarthritis (OA) is a common cause of disability and pain around the world. Epidemiologic studies of family history have revealed evidence of genetic influence on OA. Although many efforts have been devoted to exploring genetic biomarkers, the mechanism behind this complex disease remains unclear. The identified genetic risk variants only explain a small proportion of the disease phenotype. Traditional genome-wide association study (GWAS) focuses on radiographic evidence of OA and excludes sex chromosome information in the analysis. However, gender differences in OA are multifactorial, with a higher frequency in women, indicating that the chromosome X plays an essential role in OA pathology. Furthermore, the prevalence of comorbidities among patients with OA is high, indicating multiple diseases share a similar genetic susceptibility to OA.

Methods: In this study, we performed GWAS of OA and OA-associated key comorbidities on 3366 OA patient data obtained from the Osteoarthritis Initiative (OAI). We performed Mendelian randomization to identify the possible causal relationship between OA and OA-related clinical features.

Results: One significant OA-associated locus rs2305570 was identified through sex-specific genome-wide association. By calculating the LD score, we found OA is positively correlated with heart disease and stroke. A strong genetic correlation was observed between knee OA and inflammatory disease, including eczema, multiple sclerosis, and Crohn’s disease. Our study also found that knee alignment is one of the major risk factors in OA development, and we surprisingly found knee pain is not a causative factor of OA, although it was the most common symptom of OA.

Conclusion: We investigated several significant positive/negative genetic correlations between OA and common chronic diseases, suggesting substantial genetic overlaps between OA and these traits. The sex-specific association analysis supports the critical role of chromosome X in OA development in females.
Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases
Authors: Dong Rui , Wei Xuxia , Zhang Kaihui , Song Fengling , Lv Yuqiang , Gao Min , Wang Dong , Ma Jian , Gai Zhongtao , Liu Yi
Published: August 2022

Background: Glycogen storage diseases (GSDs) are known as a group of disorders characterized by genetic errors leading to accumulation of glycogen in various tissues. Since different types of GSD can sometimes be clinically indistinguishable, next generation sequencing is becoming a powerful tool for clinical diagnosis.

Methods: 12 patients with suspected GSDs and their parents were enrolled in this study. The clinical and laboratory data of the patients were reviewed. Causative gene variants were identified in the patients using whole exome sequencing (WES) and verified by Sanger sequencing.

Results: Genetic testing and analysis showed that 7 patients were diagnosed with GSD II (Pompe disease), 2 patients with GSD III, 1 patient with GSD VI, and 2 patients with GSD IXα. A total number of 18 variants were identified in 12 patients including 11 variants in GAA gene, 3 variants in AGL gene, 2 variants in PYGL gene and 2 variants in PHKA2 gene, of which 9 variants were reported and 9 variants were novel. SIFT, Polyphen-2, Mutation Taster, and REVEL predicted the novel variants (except GAA c.1052_1075 + 47del) to be disease-causing. The 3D structures of wild/mutant type GAA protein were predicted indicating that variants p. Trp621Gly, p. Pro541Leu, p. Ser800Ile and p. Gly293Trp might affect the proteins function via destroying hydrogen bonds or conformational constraints. Neither liver size nor laboratory findings allow for a differentiation among GSD III, GSD VI and GSD IXα.

Conclusion: Our study expanded the variation spectrum of genes associated with GSDs. WES, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate results for diagnosing and sub-typing GSD and related diseases in clinical setting.
Identification of N7-methylguanosine-related IncRNA signature as a potential predictive biomarker for colon adenocarcinoma
Authors: Ma Xiaomei , Yang Baoshun , Yang Yuan , Wu Guozhi , Ma Xiaoli , Yu Xiao , Li Yingwen , Wang Yuping , Guo Qinghong
Published: August 2022

N7-Methylguanosine (m7G) is an RNA modification serving as a key part of colon cancer development. Thus, a comprehensive analysis was executed to explore prognostic roles and associations with the immune status of the m7G-related lncRNA (m7G-RNAs) in colon adenocarcinoma (COAD). Identification of m7G-RNAs was achieved via Pearson’s correlation analysis of lncRNAs in the TCGA-COAD dataset and m7G regulators. A prognostic signature was developed via LASSO analyses. ESTIMATE, CIBERSORT, and ssGSEA algorithms were utilized to assess immune infiltration between different risk groups. Survival analysis suggested the high-risk group possesses poor outcomes compared with the low-risk group. According to the ROC curves, the m7G-RNAs signature exhibited a reliable capability of prediction (AUCs at 1, 3, and 5 years were 0.770, 0.766, and 0.849, respectively). Multivariate hazard analysis proved that the signature was an independent predictive indicator for OS. Moreover, the risk score was related to infiltration levels of naïve B cells, CD4+ memory T cells, and resting NK cells. The result revealed the prognostic value of m7G modification in COAD and provided a novel perspective on personalized immunotherapy strategies.
Construction and validation of a novel coagulation-related 7-gene prognostic signature for gastric cancer
Authors: Wang Bofang , Zou Dan , Wang Na , Wang Haotian , Zhang Tao , Gao Lei , Ma Chenhui , Zheng Peng , Gu Baohong , Li Xuemei , Wang Yunpeng , He Puyi , Ma Yanling , Wang Xueyan , Chen Hao
Published: August 2022

Background: Gastric cancer (GC) is the most common malignant tumor. Due to the lack of practical molecular markers, the prognosis of patients with advanced gastric cancer is still poor. A number of studies have confirmed that the coagulation system is closely related to tumor progression. Therefore, the purpose of this study was to construct a coagulation-related gene signature and prognostic model for GC by bioinformatics methods.

Methods: We downloaded the gene expression and clinical data of GC patients from the TCGA and GEO databases. In total, 216 coagulation-related genes (CRGs) were obtained from AmiGO 2. Weighted gene co-expression network analysis (WGCNA) was used to identify coagulation-related genes associated with the clinical features of GC. Last absolute shrinkage and selection operator (LASSO) Cox regression was utilized to shrink the relevant predictors of the coagulation system, and a Coag-Score prognostic model was constructed based on the coefficients. According to this risk model, GC patients were divided into high-risk and low-risk groups, and overall survival (OS) curves and receiver operating characteristic (ROC) curves were drawn in the training and validation sets, respectively. We also constructed nomograms for predicting 1-, 2-, and 3-year survival in GC patients. Single-sample gene set enrichment analysis (ssGSEA) was exploited to explore immune cells’ underlying mechanisms and correlations. The expression levels of coagulation-related genes were verified by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).

Results: We identified seven CRGs employed to construct a Coag-Score risk model using WGCNA combined with LASSO regression. In both training and validation sets, GC patients in the high-risk group had worse OS than those in the low-risk group, and Coag-Score was identified as an independent predictor of OS, and the nomogram provided a quantitative method to predict the 1-, 2-, and 3-year survival rates of GC patients. Functional analysis showed that Coag-Score was mainly related to the MAPK signaling pathway, complement and coagulation cascades, angiogenesis, epithelial–mesenchymal transition (EMT), and KRAS signaling pathway. In addition, the high-risk group had a significantly higher infiltration enrichment score and was positively associated with immune checkpoint gene expression. Conclusion: Coagulation-related gene models provide new insights and targets for the diagnosis, prognosis prediction, and treatment management of GC patients.
Insight of vitellogenesis patterns: A comparative analysis of the differences between the primary and secondary vitellogenesis period in the ovary, hepatopancreas, and muscle of mud crab, scylla paramamosain
Authors: Ren Yuanhao , Wang Wei , Liu Zhiqiang , Luo Minghao , Fu Yin , Zhang Fengying , Ma Chunyan , Zhao Ming , Chen Wei , Jiang Keji , Ma Lingbo
Published: August 2022

The mud crab,Scylla paramamosain, has abundant nutrients in its edible parts, ovary, hepatopancreas, and muscle during the ovarian maturation stage. The ovary ofS. paramamosaincan re-mature after spawning during the secondary ovarian maturation period. We aimed to analyze the characteristics of the first vitellogenesis period (FVP)1and second vitellogenesis period (SVP)2ofS. paramamosainduring ovarian maturation to understand the differences in vitellogenesis patterns between the first and second ovarian maturation periods. Accordingly, the gonadosomatic index (GSI) and hepatopancreatic index (HSI), the external and histological characteristics of the ovary and hepatopancreas, theSp-Vg(vitellogenin, Vg) expression levels in the hepatopancreas and ovary, and the dynamics of the biochemical components in the ovary, hepatopancreas, and muscle were determined. Based on the results, the GSI was significantly positively correlated with HSI during the FVP and significantly negatively correlated with HSI from stage Ⅳ to stage Ⅴ of the SVP. A significant difference was found between the FVP and SVP in the hepatopancreas. Notably, the hepatopancreas displayed a gradual degeneration trend during the SVP. The expression level ofSp-Vgwas significantly higher in the hepatopancreas than that in the ovary during the FVP and SVP. Seventeen amino acids were detected in the hepatopancreas, ovary, and muscle during the FVP and SVP, with glutamate as the predominant amino acid. During the FVP and SVP, the C16:0 and C18:1n9c were the dominant fatty acids in the hepatopancreas and ovary, the MUFA gradually increased in the ovary and hepatopancreas, and a significant difference was found in the dynamic trend of the HUFA and SFA contents from stage Ⅳ to stage Ⅴ between the FVP and SVP. These findings indicate that the ovary can re-mature after spawning inS. paramamosainand can maintain the status of the first ovarian maturation; however, the hepatopancreas gradually degenerate during the SVP.
Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
Authors: Arrobas Velilla Teresa , Brea Ángel , Valdivielso Pedro
Published: August 2022

Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units.

Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels >250 mg/dl were identified in subjects >18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained.

Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels >250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant.

Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine.
Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: A retrospective chart review
Authors: Li Hong-Shuai , Lei Si-Yu , Li Jun-Ling , Xing Pu-Yuan , Hao Xue-Zhi , Xu Fei , Xu Hai-Yan , Wang Yan
Published: August 2022

Background

Synergistic anti-tumor effects were observed in vivo and in vitro when immune checkpoint inhibitors (ICIs) were combined with denosumab. However, the clinical benefit and safety of this synergy have not been adequately evaluated in non-small cell lung cancer (NSCLC).

Methods

Consecutive charts of NSCLC patients with bone metastases between December 2020 and December 2021 in the Chinese National Cancer Center were reviewed. The entire cohort was divided into one experimental group (denosumab + ICIs [DI]) and three control groups (denosumab + non-ICIs [DnI], phosphates + ICIs [PI], phosphates + non-ICIs [PnI]). Real-world objective response rates (ORRs), median progression-free survival (mPFS), skeletal-related events (SREs), and adverse events (AEs) were compared between groups.

Results

A total of 171/410 (41.7%) patients with advanced or recurrent NSCLC carrying bone metastases who received bone-targeted therapy were eligible for analysis. Although the DI group showed a better benefit trend, differences were not statistically significant concerning the therapeutic efficacy among the DI group (n = 40), PI group (n = 74), DnI group (n = 15), and PnI group (n = 42) (ORRs: 47.5%, 43.2%, 33.3%, and 40.5%, respectively, p = 0.799; and mPFS: 378, 190, 170, and 172 days, respectively, p = 0.115; SREs: 5%, 10.8%, 13.3%, and 11.9%, respectively, p = 0.733). Nevertheless, further analysis in the NON-DRIVER cohort revealed a greater benefit for the DI group (p = 0.045). Additionally, the AEs of the DI group were not significantly different from those of the PI, DnI, and PnI groups (AEs: 27.5%, 39.2%, 26.7%, and 28.6%, respectively, p = 0.742). Furthermore, the multivariate analysis revealed the independent prognostic role of DI treatment for PFS in the overall cohort. Within the DI group, we did not observe differences in benefit among different mutational subgroups (p = 0.814), but patients with single-site bone metastasis (p = 0.319) and high PD-L1 expression (p = 0.100) appeared to benefit more, though no significant differences were observed.

Conclusions

Denosumab exhibited synergistic antitumor efficacy without increasing toxicity when used concomitantly with ICIs in patients with advanced non-small cell lung cancer carrying bone metastases.
Case report: A STAT1 gain-of-function mutation causes a syndrome of combined immunodeficiency, autoimmunity and pure red cell aplasia
Authors: Xie Yifan , Shao Fenli , Lei Juan , Huang Na , Fan Zhidan , Yu Haiguo
Published: August 2022

Inherited autosomal dominant gain-of-function (GOF) mutations of signal transducer and activator of transcription 1 (STAT1) cause a wide range of symptoms affecting multiple systems, including chronic mucocutaneous candidiasis (CMC), infections, and autoimmune disorders. We describe a rare case of STAT1 mutation with recurrent CMC, lung infections, and anemia. According to the whole-exome sequencing (WES), the patient was genetically mutated in STAT1 GOF (c.854A>G, p.Q285R), and bone marrow biopsy suggested pure red cell aplasia (PRCA). As a functional verification, STAT1 levels and phosphorylation (p-STAT1) of peripheral blood mononuclear cells (PBMCs) following IFN-γ stimulation in STAT1 GOF patient was higher than in the healthy control. Combination therapy of blood transfusion, antimicrobials, intravenous immunoglobulin, methylprednisolone, and the Janus Kinase (JAK) specific inhibitor ruxolitinib was used during treatment of patients. The patient also received a hematopoietic stem cell transplant (HSCT) to help with infections and anemia. This is the first reported case of STAT1 GOF disease complicated with PRCA. This complication might be attributed to immune disorders caused by STAT1 GOF. Furthermore, ruxolitinib may be a viable therapeutic option before HSCT to improve disease management.
Gastric DLBCL clonal evolution as function of patient age
Authors: Iosselevitch Irina , Tabibian-Keissar Hilla , Barshack Iris , Mehr Ramit
Published: August 2022

Diffuse large B cell lymphoma (DLBCL) is the most common type of NHL, accounting for about 40% of NHL cases, and is one of the most aggressive lymphomas. DLBCL is widespread in individuals aged more than 50 years old, with a maximum incidence in the seventh decade, but it may also occur in younger patients. DLBCL may occur in any immune system tissue, including those around the gastrointestinal tract, and even in the stomach, though gastric DLBCL has yet to be sufficiently investigated. This study aimed to understand changes in gastric Diffuse Large B cell lymphoma (gastric DLBCL) development with age. Immunoglobulin (Ig) heavy chain variable region genes were amplified from sections of nine preserved biopsies, from patients whose age varied between 25 and 89 years, sequenced and analyzed. We show first that identification of the malignant clone based on the biopsies is much less certain than was previously assumed; and second that, contrary to expectations, the repertoire of gastric B cell clones is more diverse among the elderly DLBCL patients than among the young.
IGF1R signalling is a guardian of self-tolerance restricting autoantibody production
Authors: Erlandsson Malin C. , Erdogan Seval , Wasén Caroline , Andersson Karin M. E. , Silfverswärd Sofia T. , Pullerits Rille , Bemark Mats , Bokarewa Maria I.
Published: August 2022

Objective

Insulin-like growth factor 1 receptor (IGF1R) acts at the crossroad between immunity and cancer, being an attractive therapeutic target in these areas. IGF1R is broadly expressed by antigen-presenting cells (APC). Using mice immunised with the methylated albumin from bovine serum (BSA-immunised mice) and human CD14+ APCs, we investigated the role that IGF1R plays during adaptive immune responses.

Methods

The mBSA-immunised mice were treated with synthetic inhibitor NT157 or short hairpin RNA to inhibit IGF1R signalling, and spleens were analysed by immunohistology and flow cytometry. The levels of autoantibody and cytokine production were measured by microarray or conventional ELISA. The transcriptional profile of CD14+ cells from blood of 55 patients with rheumatoid arthritis (RA) was analysed with RNA-sequencing.

Results

Inhibition of IGF1R resulted in perifollicular infiltration of functionally compromised S256-phosphorylated FoxO1+ APCs, and an increased frequency of IgM+CD21+ B cells, which enlarged the marginal zone (MZ). Enlargement of MHCII+CD11b+ APCs ensured favourable conditions for their communication with IgM+ B cells in the MZ. The reduced expression of ICOSL and CXCR5 by APCs after IGF1R inhibition led to impaired T cell control, which resulted in autoreactivity of extra-follicular B cells and autoantibody production. In the clinical setting, the low expression of IGF1R on CD14+ APCs was associated with an involuted FOXO pathway, non-inflammatory cell metabolism and a high IL10 production characteristic for tolerogenic macrophages. Furthermore, autoantibody positivity was associated with low IGF1R signalling in CD14+ APCs.

Conclusions

In experimental model and in patient material, this study demonstrates that IGF1R plays an important role in preventing autoimmunity. The study raises awareness of that immune tolerance may be broken during therapeutic IGF1R targeting.
Detrimental NFKB1 missense variants affecting the Rel-homology domain of p105/p50
Authors: Fliegauf Manfred , Kinnunen Matias , Posadas-Cantera Sara , Camacho-Ordonez Nadezhda , Abolhassani Hassan , Alsina Laia , Atschekzei Faranaz , Bogaert Delfien J. , Burns Siobhan O. , Church Joseph A. , Dückers Gregor , Freeman Alexandra F. , Hammarström Lennart , Hanitsch Leif Gunnar , Kerre Tessa , Kobbe Robin , Sharapova Svetlana O. , Siepermann Kathrin , Speckmann Carsten , Steiner Sophie , Verma Nisha , Walter Jolan E. , Westermann-Clark Emma , Goldacker Sigune , Warnatz Klaus , Varjosalo Markku , Grimbacher Bodo
Published: August 2022

Most of the currently known heterozygous pathogenic NFKB1 (Nuclear factor kappa B subunit 1) variants comprise deleterious defects such as severe truncations, internal deletions, and frameshift variants. Collectively, these represent the most frequent monogenic cause of common variable immunodeficiency (CVID) identified so far. NFKB1 encodes the transcription factor precursor p105 which undergoes limited proteasomal processing of its C-terminal half to generate the mature NF-κB subunit p50. Whereas p105/p50 haploinsufficiency due to devastating genetic damages and protein loss is a well-known disease mechanism, the pathogenic significance of numerous NFKB1 missense variants still remains uncertain and/or unexplored, due to the unavailability of accurate test procedures to confirm causality. In this study we functionally characterized 47 distinct missense variants residing within the N-terminal domains, thus affecting both proteins, the p105 precursor and the processed p50. Following transient overexpression of EGFP-fused mutant p105 and p50 in HEK293T cells, we used fluorescence microscopy, Western blotting, electrophoretic mobility shift assays (EMSA), and reporter assays to analyze their effects on subcellular localization, protein stability and precursor processing, DNA binding, and on the RelA-dependent target promoter activation, respectively. We found nine missense variants to cause harmful damage with intensified protein decay, while two variants left protein stability unaffected but caused a loss of the DNA-binding activity. Seven of the analyzed single amino acid changes caused ambiguous protein defects and four variants were associated with only minor adverse effects. For 25 variants, test results were indistinguishable from those of the wildtype controls, hence, their pathogenic impact remained elusive. In summary, we show that pathogenic missense variants affecting the Rel-homology domain may cause protein-decaying defects, thus resembling the disease-mechanisms of p105/p50 haploinsufficiency or may cause DNA-binding deficiency. However, rare variants (with a population frequency of less than 0.01%) with minor abnormalities or with neutral tests should still be considered as potentially pathogenic, until suitable tests have approved them being benign.
Advances in the study of HLA class Ib in maternal-fetal immune tolerance
Authors: Yang Yiran , Wang Wanning , Weng Jing , Li Huifang , Ma Yanmin , Liu Lingyan , Ma Wei
Published: August 2022

The HLA class Ib molecule is an alloantigen that causes transplant rejection on behalf of individual human and plays an important role in maternal-fetal immune tolerance. Early studies on HLA class Ib focused on the mechanism of HLA-G-induced immune escape, but in recent years, studies on the mechanism of HLA-G have deepened and gradually explored the mechanism of HLA-E and HLA-F, which are also HLA class Ib molecules. In the maternal-fetal interface, trophoblast cells express HLA class Ib molecules to protect the fetus from maternal immune cells by binding to inhibitory receptors of decidual immune cells (DICs) and shifting Th1/Th2 balance toward Th2 bias. Further studies on the molecular mechanism of HLA class Ib molecules provide a reference for its application in the field of clinical assisted reproduction.
The collectin SP-A and its trimeric recombinant fragment protect alveolar epithelial cells from the cytotoxic and proinflammatory effects of human cathelicidin in vitro
Authors: de Tapia Lidia , García-Fojeda Belén , Kronqvist Nina , Johansson Jan , Casals Cristina
Published: August 2022

Human cathelicidin (LL-37) is a defense peptide with antimicrobial activity against various pathogens. However, LL-37 can also trigger tissue injury by binding to host cell membranes. The cytotoxic effects of LL-37 may be especially relevant in chronic respiratory diseases characterized by increased LL-37. The aim of this study was to investigate whether the human collectin SP-A and a trimeric recombinant fragment thereof (rfhSP-A) can regulate the activities of LL-37. To this end, we studied the interaction of LL-37 with SP-A and rfhSP-A by intrinsic fluorescence, dynamic light scattering, and circular dichroism, as well as the effects of these proteins on the antimicrobial and cytotoxic activities of LL-37. Both SP-A and rfhSP-A bound LL-37 with high affinity at physiological ionic strength (KD= 0.45 ± 0.01 nM for SP-A and 1.22 ± 0.7 nM for rfhSP-A). Such interactions result in the reduction of LL-37-induced cell permeability and IL-8 release in human pneumocytes, mediated by P2X7 channels. Binding of LL-37 to SP-A did not modify the properties of SP-A or the antibacterial activity of LL-37 against respiratory pathogens (Klebsiella pneumoniae,Pseudomonas aeruginosa, and nontypeableHaemophilus influenzae). SP-A/LL-37 complexes showed a greater ability to aggregate LPS vesicles than LL-37, which reduces endotoxin bioactivity. These results reveal the protective role of native SP-A in controlling LL-37 activities and suggest a potential therapeutic effect of rfhSP-A in reducing the cytotoxic and inflammatory actions of LL-37, without affecting its microbicidal activity against Gram-negative pathogens.
Succession of protistan functional traits is influenced by bloom timing
Authors: Péquin Bérangère , LaBrie Richard , St-Gelais Nicolas Fortin , Maranger Roxane
Published: August 2022

Surface ocean eukaryotic phytoplankton biogeography can be determined as chlorophyll-a using remote sensing techniques yet evaluating its community composition remains limited. Given our ability to track site-specific chlorophyll-a concentration, we tested which factors influenced protistan functional trait distribution, and whether the distributions can be inferred from bloom succession. Here we surveyed the Labrador Sea during spring over three consecutive years, sequenced 18S data over 15 stations and collected satellite-derived chlorophyll-a concentration from March to July for each year. We evaluated changes in distribution of taxonomic composition as well as the functional traits of protistan size, trophic strategy (defined as phototrophy, phagotrophy, and mixotrophy as capable of both), motility and dimethylsulfoxide or dimethylsulfoniopropionate production by building a functional trait database after an extensive literature review. More variability in the biogeography of protistan functional traits was explained across water masses, and among years than taxonomic composition and patterns in trait variability were more apparent when site-specific timing of peak chlorophyll-a was considered. We found that reconstructing bloom phenology using days before peak (DBP) chlorophyll explained a significant amount of variability in functional trait community structure that was previously attributed to water masses or years, suggesting that spatial and interannual variations can be explained by the sampling moment during succession. Approximately 30 days prior to peak, mixotrophy as a trophic strategy was replaced by phototrophic protists of typically larger size classes. Our work suggests DBP influences protistan community trait succession that could inform biogeochemical models, and likely acts a proxy for the onset of stratification.
Spatial assessment of coastal flood risk due to sea level rise in China’s coastal zone through the 21st century
Authors: Xu He , Hou Xiyong , Li Dong , Wang Xiaoli , Fan Chao , Du Peipei , Song Baiyuan
Published: August 2022

Among the climate change-induced threats to coastal regions, coastal flooding caused by sea level rise (SLR) is considered one of the most serious and presents an intensifying trend over time. The negative impacts and risks associated with coastal flooding are difficult to visualize spatially and cause great inconvenience to policy-makers in understanding the distribution of different risk levels and developing adaptation policies. Our study proposes a framework for coastal flood risk (CFR) based on the hazard, exposure & sensitivity, and adaptive capacity of China’s coastal zone (CCZ) and maps the spatial distribution of CFR by GIS in 2030, 2050, and 2100 under RCP2.6-SSP1, RCP4.5-SSP2, and RCP8.5-SSP5, respectively. Our results reveal that (1) low-lying coastal areas with densely populated, economically developed, or industrially diverse are faced with serious CFRs, such as the Yellow River Delta, the Yangtze River Delta, the Pearl River Delta, and the coastal areas in Jiangsu. (2) The area of “Very high” CFR level in the CCZ reaches a peak of 44.10×103 km2 in 2100 under RCP8.5-SSP5. And under the higher emission scenario, the areas of five CFR levels would change dramatically in the future. (3) The coastal area of Guangdong is significantly faced with the massive expected population and GDP affected due to CFR among scenarios and years. (4) As threatened by CFR mostly, built-up and farmland are particularly required to guard against the negative impact of coastal flooding, especially in Guangdong and Jiangsu. Results in this study are expected to provide the intuitive information and basis for governments, policy-makers, and local communities in addressing the increased CFR over the CCZ. Besides, our framework of CFR and methodology are flexible and can be adapted for other countries facing the threat of SLR.
On the influences of the continental shelf bathymetry correction in Prydz Bay, East Antarctica
Authors: Sun Chong , Liu Chengyan , Wang Zhaomin , Yan Liangjun , Tao Yixuan , Qin Qing , Qian Jiangchao
Published: August 2022

The bathymetry around Antarctica can govern the shelf sea circulations and play a key role in conditioning water masses. In Prydz Bay, the Prydz Bay Gyre and coastal currents are also determined by the continental shelf topography. However, due to the paucity of beam echo sounding data, the bathymetric datasets in Prydz Bay still have large uncertainties. With the aid of in situ hydrographic observations, this study focuses on the correction of an up-to-date bathymetric dataset and the resultant influences on the shelf circulation and the basal melting of the ice shelves. The corrected bathymetry mainly improves the biased shallow representations in the uncorrected bathymetric data set, with a maximum change of ~500 m deepening in the eastern flank of Prydz Bay. Sensitivity numerical experiments show that the bathymetric corrections in Prydz Bay have a significant impact on the circulation pattern and onshore warm water intrusions. In addition, the corrected bathymetry markedly decreases the heat transport towards the calving front of the Amery Ice Shelf. The onshore heat transport reduces by ~22.18% from ~5.23×1013 J s-1 to ~4.07×1013 J s-1 over the outer shelf. Over the inner shelf, the heat transport towards the Amery Ice Shelf reduces by ~18.15% from ~5.95×1013 J s-1 to ~4.87×1013 J s-1. Consequently, the temporally and spatially averaged basal melting rate of the Amery Ice Shelf reduces by ~13.04% from ~0.69 m yr-1 to ~0.60 m yr-1.
Nano-architectured cobalt selenide spheres anchored on graphene oxide sheets for sodium ion battery anode
Authors: Ali Zeeshan , Ali Muhammad , Mehmood Ahtisam , Ishfaq Ayesha , Akram Muhammad Aftab , Zeb Akif , Lin Xiaoming
Published: August 2022

Aimed at commercializing the technology of sodium-ion batteries (SIBs), researchers have been trying to produce electrode materials with optimally high charge storage capacity, superior rate capability, extended life, and cost-effective components. Herein, we synthesized an electrode of cobalt selenides loaded in carbon spheres and anchored on reduced graphene (CSSs@rGO) for high-performance SIBs. This improved structure of CSSs@rGO permits the pseudocapacitive storage of charge, thus enhancing the electrical characteristics. It was discovered that the diameter of the carbon sphere had a significant impact on the charge storage capacities of the developed electrode materials, suggesting the probable depth of sodium-ion (Na-ion) movement in the electrode materials during charge and discharge. For instance, CSSs@rGO with an average diameter of ∼70 nm presented the best electrochemical performance as an anode of SIBs. The nano-architecture CSSs@rGO exhibits excellent ion storage capability with a reversible capacity of 600 mA h g-1 at a discharge rate of 100 mA g−1 after 50 cycles. However, at a higher discharge rate (e.g., 1,000 mA g−1), a storage capacity as high as 380 mA h g−1 was achieved. In addition to higher charge storage capability and efficient charge storage at higher discharge rates, the developed CSSs@rGO exhibited stable cycling performance for over 3,000 cycles, which clearly shows the feasibility of our products. This work will open new approaches for developing advanced electrode materials for high-performance sodium-ion batteries.
The mechanical properties of concrete in water environment: A review
Authors: Wang Juan , Sun Ke , Hu Yu , Guan Qiaoyan , Li Qingbin
Published: August 2022

The service performance of concrete structures in a water environment differs from that in a normal environment. An accurate evaluation of the mechanical properties and service status of wet concrete is related to the reliable design and safe operation of concrete structures, e.g., hydraulics, marine engineering, bridges, and tunnels. To promote the application of new and high-performance concrete to complex water environments and grasp the future development trend, the research progress on the service performance of concrete in water environments was reviewed worldwide. Starting from the internal water content of concrete, the existing research is combed, the influence of water content, water pressure, and loading rate on the static and dynamic characteristics of concrete in a water environment is summarized, and the influence mechanism is analyzed. The literature review demonstrates that the static compressive strength of wet concrete is lower than that of dry concrete; however, the elastic modulus improves. With an increase in the strain rate, the compressive strength of wet and dry concretes improves, and the rate sensitivity of the wet concrete is greater than that of the normal concrete. Pore structure characteristics mainly affect the static strength of the wet concrete. The improvement in the dynamic strength of the wet concrete is caused by the combined effect of the concrete rate sensitivity, “Stefan” effect, and water pressure.
Exploring the effect of a microencapsulated citrus essential oil on in vitro fermentation kinetics of pig gut microbiota
Authors: Ambrosio Carmen M. S. , Alvim Izabella D. , Wen Caifang , Gómez Expósito Ruth , Aalvink Steven , Contreras Castillo Carmen J. , Da Gloria Eduardo M. , Smidt Hauke
Published: August 2022

Essential oils (EOs) have emerged as a potential alternative to antibiotics in pig breeding due to their antimicrobial properties. Citrus EOs, a common by-product of the orange juice industry, can be an interesting alternative from a financial perspective due to their huge offer in the global market. Thus, the effect of a citrus EO, and specifically different formulations of Brazilian Orange Terpenes (BOT), on pig gut microbiota was evaluated by means of an in vitro fermentation model simulating different sections of the pig gut (stomach, ileum, and colon). Treatments consisted in: BOT in its unprotected form (BOT, 1.85 and 3.70 mg/mL), microencapsulated BOT (MBOT, 3.50 and 7.00 mg/mL), colistin (2 μg/mL), and a control. BOT and MBOT altered in a similar way the total bacterial 16S rRNA gene copies in the stomach only from 18 h of incubation onwards, and no metabolite production in terms of short-chain fatty acids (SCFAs) was detected. In ileal and colonic fermentations, BOT and MBOT affected ileal and colonic microbiota in terms of total bacterial 16S rRNA gene copies, reduced phylogenetic diversity, and altered composition (p < 0.05) as evidenced by the significant reduction of certain bacterial taxa. However, more pronounced effects were found for MBOT, indicating its higher antimicrobial effects compared to the unprotected BOT, and suggesting that the antibacterial efficiency of the unprotected BOT was probably enhanced by microencapsulation. Furthermore, MBOT stimulated lactate production in ileal fermentations and greatly stimulated overall SCFA production in colonic fermentations. This indicates that besides the shifts in ileal and colonic microbiota by the delivered EO (BOT), the wall material of microcapsules (chitosan/modified starch) might have worked as an additional carbon source with prebiotic functioning, stimulating growth and metabolic activity (SCFAs) of colonic bacteria.
Efficient dealkalization of red mud and recovery of valuable metals by a sulfur-oxidizing bacterium
Authors: Zhang Duo-rui , Chen Hong-rui , Xia Jin-lan , Nie Zhen-yuan , Zhang Rui-Yong , Pakostova Eva
Published: August 2022

Red mud (RM) is a highly alkaline polymetallic waste generated via the Bayer process during alumina production. It contains metals that are critical for a sustainable development of modern society. Due to a shortage of global resources of many metals, efficient large-scale processing of RM has been receiving increasing attention from both researchers and industry. This study investigated the solubilization of metals from RM, together with RM dealkalization, via sulfur (S0) oxidation catalyzed by the moderately thermophilic bacterium Sulfobacillus thermosulfidooxidans. Optimization of the bioleaching process was conducted in shake flasks and 5-L bioreactors, with varying S0:RM mass ratios and aeration rates. The ICP analysis was used to monitor the concentrations of dissolved elements from RM, and solid residues were analyzed for surface morphology, phase composition, and Na distribution using the SEM, XRD, and STXM techniques, respectively. The results show that highest metal recoveries (89% of Al, 84% of Ce, and 91% of Y) were achieved with the S0:RM mass ratio of 2:1 and aeration rate of 1 L/min. Additionally, effective dealkalization of RM was achieved under the above conditions, based on the high rates (>95%) of Na, K, and Ca dissolution. This study proves the feasibility of using bacterially catalyzed S0 oxidation to simultaneously dealkalize RM and efficiently extract valuable metals from the amassing industrial waste.
Anti-inflammatory compounds from the mangrove endophytic fungus Amorosia sp. SCSIO 41026
Authors: Ren Xue , Chen Chunmei , Ye Yuxiu , Xu Ziying , Zhao Qingliang , Luo Xiaowei , Liu Yonghong , Guo Peng
Published: August 2022

Three new chlorinated compounds, including two propenylphenol derivatives, chlorophenol A and B (1 and 2), and one benzofuran derivative, chlorophenol C (3), together with 16 known compounds, were isolated from the mangrove endophytic fungus Amorosia sp. SCSIO 41026. 7-Chloro-3,4-dihydro-6,8-dihydroxy-3-methylisocoumarine (4) and 2,4-dichloro-3-hydroxy-5-methoxy-toluene (5) were obtained as new natural products. Their structures were elucidated by physicochemical properties and extensive spectroscopic analysis. Compounds 1, 4, 7, 9, 13, 15, 16, and 19 possessed inhibitory effects against the excessive production of nitric oxide (NO) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-challenged RAW264.7 macrophages without obvious cytotoxicity. Moreover, 5-chloro-6-hydroxymellein (13) further alleviated the pathological lung injury of LPS-administrated mice and protected RAW264.7 macrophages against LPS-induced inflammation through PI3K/AKT pathway in vivo. Our research laid the foundation for the application of compound 13 as a potential anti-inflammatory candidate.
The role of long noncoding RNAs as regulators of the epithelial–Mesenchymal transition process in oral squamous cell carcinoma cells
Authors: Shao Zifei , Wang Xiang , Li Yiyang , Hu Yanjia , Li Kun
Published: August 2022

Oral squamous cell carcinoma (OSCC) is a highly invasive and relatively prevalent cancer, accounting for around 3% of all cancers diagnosed. OSCC is associated with bad outcomes, with only 50% overall survival (OS) after five years. The ability of OSCC to invade local and distant tissues relies on the induction of the epithelial–mesenchymal transition (EMT), wherein epithelial cells shed their polarity and cell-to-cell contacts and acquire mesenchymal characteristics. Consequently, a comprehensive understanding of how tumor cell EMT induction is regulated has the potential of direct attempts to prevent tumor progression and metastasis, resulting in better patient outcomes. Several recent studies have established the significance of particular long noncoding RNAs (lncRNAs) in the context of EMT induction. Moreover, lncRNAs regulate a vast array of oncogenic pathways. With a focus on the mechanisms by which the underlined lncRNAs shape the metastatic process and a discussion of their potential utility as clinical biomarkers or targets for therapeutic intervention in patients with OSCC, the present review thus provides an overview of the EMT-related lncRNAs that are dysregulated in OSCC.
Nanoparticle-based immunotherapy of pancreatic cancer
Authors: Noubissi Nzeteu Gaetan Aime , Gibbs Bernhard F. , Kotnik Nika , Troja Achim , Bockhorn Maximilian , Meyer N. Helge
Published: August 2022

Pancreatic cancer (PC) has a complex and unique tumor microenvironment (TME). Due to the physical barrier formed by the desmoplastic stroma, the delivery of drugs to the tumor tissue is limited. The TME also contributes to resistance to various immunotherapies such as cancer vaccines, chimeric antigen receptor T cell therapy and immune checkpoint inhibitors. Overcoming and/or modulating the TME is therefore one of the greatest challenges in developing new therapeutic strategies for PC. Nanoparticles have been successfully used as drug carriers and delivery systems in cancer therapy. Recent experimental and engineering developments in nanotechnology have resulted in increased drug delivery and improved immunotherapy for PC. In this review we discuss and analyze the current nanoparticle-based immunotherapy approaches that are at the verge of clinical application. Particularly, we focus on nanoparticle-based delivery systems that improve the effectiveness of PC immunotherapy. We also highlight current clinical research that will help to develop new therapeutic strategies for PC and especially targeted immunotherapies based on immune checkpoint inhibitors.
ST6Gal1: Oncogenic signaling pathways and targets
Authors: GC Sajina , Bellis Susan L. , Hjelmeland Anita B.
Published: August 2022

The Golgi-sialyltransferase ST6Gal1 (βgalactosidase α2,6 sialyltransferase 1), adds the negatively charged sugar, sialic acid, to the terminal galactose of N-glycosylated proteins. Upregulation of ST6Gal1 is observed in many malignancies, and a large body of research has determined that ST6Gal1-mediated α2,6 sialylation impacts cancer hallmarks. ST6Gal1 affects oncogenic behaviors including sustained proliferation, enhanced self-renewal, epithelial-to-mesenchymal transition, invasion, and chemoresistance. However, there are relatively few ST6GaL1 related signaling pathways that are well-established to mediate these biologies: greater delineation of specific targets and signaling mechanisms that are orchestrated by ST6Gal1 is needed. The aim of this review is to provide a summary of our current understanding of select oncogenic signaling pathways and targets affected by ST6Gal1.
Effect of hypoalbuminemia on short-term outcomes after colorectal cancer surgery: A propensity score matching analysis
Authors: Kang Bing , Zhao Zhi-Qiang , Liu Xiao-Yu , Cheng Yu-Xi , Tao Wei , Wei Zheng-Qiang , Peng Dong
Published: August 2022

Purpose

The purpose of our study was to investigate the effect of pre-operative hypoalbuminemia on the short-term outcomes after primary colorectal cancer (CRC) surgery.

Materials and methods

The retrospective study enrolled CRC patients who underwent primary surgery from January 2011 to December 2021 in a single teaching hospital. The short-term outcomes were compared between the hypoalbuminemia group and the normal group using propensity score matching (PSM). Univariate and multivariate logistic regression analyses were used for analyzing independent predictors of overall complications and major complications.

Results

A total of 7,072 patients from a single center were enrolled in this study. There were 1,078 (15.2%) patients in the pre-operative hypoalbuminemia group and 5,994 (84.8%) patients in the normal pre-operative albumin group. After 1:1 PSM, there were 1,028 patients in the hypoalbuminemia group and 1,028 patients in the normal group. No significant differences were found in baseline information between the two groups after PSM. In terms of short-term outcomes, the hypoalbuminemia group had a longer operation time (p = 0.003), greater volume of blood loss (p = 0.036), longer hospital stays (p < 0.01), higher proportion of overall complications (p = 0.003), major complications (p = 0.016), higher incidence of pneumonia and abdominal infection (p = 0.001) than the normal group after PSM. Furthermore, hypoalbuminemia was an independent predictor for overall complications (p = 0.008) and major complications (p = 0.016).

Conclusion

Pre-operative hypoalbuminemia increased overall complications and major complications after primary CRC surgery. Furthermore, hypoalbuminemia was an independent predictor for overall complications and major complications.
Comparison of techno-functional and sensory properties of sponge cakes made with egg powder and different quality of powdered blood products for substituting egg allergen and developing functional food
Authors: Csurka Tamás , Varga-Tóth Adrienn , Kühn Dorottya , Hitka Géza , Badak-Kerti Katalin , Alpár Boglárka , Surányi József , Friedrich László Ferenc , Pásztor-Huszár Klára
Published: August 2022

Animal blood is a valuable resource, which is usually not utilized in a value-added way by the industry like other animal by-products, even though it has plenty of benefits in terms of sustainability and human health, particularly against iron deficiency anemia. Animal blood is perfectly suitable for providing special functions, which are necessary for functional foods, and improving techno-functional properties based on the previous reports published in the literature. In this paper, egg powder was substituted by powdered animal blood products (whole blood powder, blood plasma powder, and hemoglobin powder) in sponge cake. Techno-functional and sensory properties (texture by texture profile analysis and three-point breaking test, water activity, dry matter content, and color) were instrumentally measured and then a sensory evaluation was carried out by unskilled panelists. Quality characteristics (texture, color, and dry matter content) were daily measured on the day of baking and then every 24 h for 3 additional days because freshly baked cakes are usually consumed within 3 days. Based on the results, powdered blood products are suitable for substituting the egg powder in sponge cakes and developing functional foods. Blood powders can increase the hardness, chewiness, and breaking force of cakes, giving them the ability to be stuffed with more fillings and molded into special shapes without compromising on the sensory characteristics. They can also increase the intensity of the cocoa flavor, which results in a richer, darker color without deceiving the consumers.