bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis on the mediating effect and regulating impact of carbon finance on quality-focused economy advancement
Authors: Jiang Lili , Niu Huawei , Ru Yufan , Tong Aihua , Wang Yifeng
Published: July 2023

This article uses the entropy weight method to calculate China’s economic high-quality development index and carbon finance development index from 2000 to 2020. Additionally, it conducts empirical examinations to scrutinize impacts of carbon finance regarding quality-focused development of China’s economy through dynamic spatial models. The findings reveal that the advancement of carbon finance substantively promotes the quality-focused economy advancement through enhancing the overall factor productivity, thereby establishing a mediating effect. Concurrently, the allocation of resources in green fiscal expenditure assumes a moderating effect, subsequently amplifying the promoting effect of carbon finance regarding quality-focused economy advancement. Consequently, it is recommended that a robust financial milieu be established, energy efficiency be enhanced, scientific and technological progress be bolstered, total factor productivity be further augmented, and the expenditure on green conservation be escalated. These measures will effectively stimulate the quality-focused development of China’s economy.
Life-stage and geographic location determine the microbial assemblage in Eurasian spruce bark beetle, Ips typographus L. (Coleoptera: Curculionidae)
Authors: Chakraborty Amrita , Purohit Arnab , Khara Arunabha , Modlinger Roman , Roy Amit
Published: July 2023

Ips typographusL. (Coleoptera: Curculionidae) is one of the serious pests causing mass destruction of European spruce forests, with a substantial economic impact. Symbiotic microbes associated with bark beetles often play a definitive role in accomplishing their physiological and ecological functions by detoxifying chemicals, inhibiting pathogens, and offering nutrients. Although a few research works explored the microbes associated withI. typographus, much is yet to be studied to understand their adaptive ecology as holobionts comprehensively. The present study examined bacterial and fungal communities of larvae, adults, and feeding galleries from Austria and Czech Republic using high-throughput sequencing that elucidated the influence of geographic location, host, and life stage on the microbial assemblage in Eurasian spruce bark beetle,I. typographus. The most abundant bacterial genera inI. typographusincludedPseudoxanthomonas,Spiroplasma,Pseudomonas,Cellulomonas,Tyzzerella,Bacillus, andMycobacterium. Alternatively,Wickerhamomyces,Nakazawaea,Aspergillus,Ophiostoma,Cryptococcus,Rhexographium,Yamadazyma,Talaromyces, andKuraishiawere highly dominant fungal genera. Significant differences in bacterial and fungal community richness and diversity were detected among the tested samples. LEfSe analysis revealed species-specific bacterial and fungal biomarkers from different locations in the larvae, adults, and feeding gallery samples. PICRUSt2 and FUNGuild analysis documented putative roles of the bacterial and fungal communities in beetle holobiont and provided a foundation for downstream functional analyses. The current findings further enhanced our understanding of bark beetles as holobionts.
LINC01137/miR-186-5p/WWOX: a novel axis identified from WWOX-related RNA interactome in bladder cancer
Authors: Kołat Damian , Kałuzińska-Kołat Żaneta , Kośla Katarzyna , Orzechowska Magdalena , Płuciennik Elżbieta , Bednarek Andrzej K.
Published: July 2023

Introduction: The discovery of non-coding RNA (ncRNA) dates back to the pre-genomics era, but the progress in this field is still dynamic and leverages current post-genomics solutions. WWOX is a global gene expression modulator that is scarcely investigated for its role in regulating cancer-related ncRNAs. In bladder cancer (BLCA), the link between WWOX and ncRNA remains unexplored. The description of AP-2α and AP-2γ transcription factors, known as WWOX-interacting proteins, is more commonplace regarding ncRNA but still merits investigation. Therefore, this in vitro and in silico study aimed to construct an ncRNA-containing network with WWOX/AP-2 and to investigate the most relevant observation in the context of BLCA cell lines and patients.

Methods: RT-112, HT-1376, and CAL-29 cell lines were subjected to two stable lentiviral transductions. High-throughput sequencing of cellular variants (deposited in the Gene Expression Omnibus database under the GSE193659 record) enabled the investigation of WWOX/AP-2-dependent differences using various bioinformatics tools (e.g., limma-voom, FactoMineR, multiple Support Vector Machine Recursive Feature Elimination (mSVM-RFE), miRDB, Arena-Idb, ncFANs, RNAhybrid, TargetScan, Protein Annotation Through Evolutionary Relationships (PANTHER), Gene Transcription Regulation Database (GTRD), or Evaluate Cutpoints) and repositories such as The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia. The most relevant observations from cap analysis gene expression sequencing (CAGE-seq) were confirmed using real-time PCR, whereas TCGA data were validated using the GSE31684 cohort.

Results: The first stage of the whole study justified focusing solely on WWOX rather than on WWOX combined with AP-2α/γ. The most relevant observation of the developed ncRNA-containing network was LINC01137, i.e., long non-coding RNAs (lncRNAs) that unraveled the core network containing UPF1, ZC3H12A, LINC01137, WWOX, and miR-186-5p, the last three being a novel lncRNA/miRNA/mRNA axis. Patients’ data confirmed the LINC01137/miR-186-5p/WWOX relationship and provided a set of dependent genes (i.e., KRT18, HES1, VCP, FTH1, IFITM3, RAB34, and CLU). Together with the core network, the gene set was subjected to survival analysis for both TCGA-BLCA and GSE31684 patients, which indicated that the increased expression of WWOX or LINC01137 is favorable, similar to their combination with each other (WWOX↑ and LINC01137↑) or with MIR186 (WWOX↑/LINC01137↑ but MIR186↓).

Conclusion: WWOX is implicated in the positive feedback loop with LINC01137 that sponges WWOX-targeting miR-186-5p. This novel WWOX-containing lncRNA/miRNA/mRNA axis should be further investigated to depict its relationships in a broader context, which could contribute to BLCA research and treatment.
EMDL-ac4C: identifying N4-acetylcytidine based on ensemble two-branch residual connection DenseNet and attention
Authors: Jia Jianhua , Wei Zhangying , Cao Xiaojing
Published: July 2023

Introduction: N4-acetylcytidine (ac4C) is a critical acetylation modification that has an essential function in protein translation and is associated with a number of human diseases.

Methods: The process of identifying ac4C sites by biological experiments is too cumbersome and costly. And the performance of several existing computational models needs to be improved. Therefore, we propose a new deep learning tool EMDL-ac4C to predict ac4C sites, which uses a simple one-hot encoding for a unbalanced dataset using a downsampled ensemble deep learning network to extract important features to identify ac4C sites. The base learner of this ensemble model consists of a modified DenseNet and Squeeze-and-Excitation Networks. In addition, we innovatively add a convolutional residual structure in parallel with the dense block to achieve the effect of two-layer feature extraction.

Results: The average accuracy (Acc), mathews correlation coefficient (MCC), and area under the curve Area under curve of EMDL-ac4C on ten independent testing sets are 80.84%, 61.77%, and 87.94%, respectively.

Discussion: Multiple experimental comparisons indicate that EMDL-ac4C outperforms existing predictors and it greatly improved the predictive performance of the ac4C sites. At the same time, EMDL-ac4C could provide a valuable reference for the next part of the study. The source code and experimental data are available at: https://github.com/13133989982/EMDLac4C.
Noninvasive evaluation of neutrophil extracellular traps signature predicts clinical outcomes and immunotherapy response in hepatocellular carcinoma
Authors: Xin Hongjie , Lai Qianwei , Zhou Yuchen , He Jian , Song Yangda , Liao Minjun , Sun Jiarun , Li Meng , Zhang Mingxia , Liang Weifang , Bai Yang , Zhang Yongyuan , Zhou Yuanping
Published: July 2023

Background

Neutrophil extracellular traps (NETs) have been shown to play a pivotal role in promoting metastasis and immune escape in hepatocellular carcinoma (HCC). Therefore, noninvasive tests to detect the formation of NETs in tumors can have significant implications for the treatment and prognoses of patients. Here, we sought to develop and validate a computed tomography (CT)-based radiomics model to predict the gene expression profiles that regulate the formation of NETs in HCC.

Methods

This study included 1133 HCC patients from five retrospective cohorts. Based on the mRNA expression levels of 69 biomarkers correlated with NET formation, a 6-gene score (NETs score, NETS) was constructed in cohort 1 from TCIA database (n=52) and validated in cohort 2 (n=232) from ICGC database and cohort 3 (n=365) from TCGA database. And then based on the radiomics features of CT images, a radiomics signature (RNETS) was developed in cohort 1 to predict NETS status (high- or low-NETS). We further employed two cohorts from Nanfang Hospital (Guangzhou, China) to evaluate the predictive power of RNETS in predicting prognosis in cohort 4 (n=347) and the responses to PD-1 inhibitor of HCC patients in cohort 5 (n=137).

Results

For NETS, in cohort 1, the area under the curve (AUC) values predicting 1, 2, and 3-year overall survival (OS) were 0.836, 0.879, and 0.902, respectively. The low-NETS was associated with better survival and higher levels of immune cell infiltration. The RNETS yielded an AUC value of 0.853 in distinguishing between high-NETS or low-NETS and patients with low-RNETS were associated with significantly longer survival time in cohort 1 (P<0.001). Notably, the RNETS was competent in predicting disease-free survival (DFS) and OS in cohort 4 (P<0.001). In cohort 5, the RNETS was found to be an independent risk factor for progression-free survival (PFS) (P<0.001). In addition, the objective response rate of HCC patients treated with PD-1 inhibitor was significantly higher in the low-RNETS group (27.8%) than in the high-RNETS group (10.8%).

Conclusions

This study revealed that RNETS as a radiomics biomarker could effectively predict prognosis and immunotherapy response in HCC patients.
Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5
Authors: Bormann Maren , Brochhagen Leonie , Alt Mira , Otte Mona , Thümmler Laura , van de Sand Lukas , Kraiselburd Ivana , Thomas Alexander , Gosch Jule , Braß Peer , Ciesek Sandra , Widera Marek , Dolff Sebastian , Dittmer Ulf , Witzke Oliver , Meyer Folker , Lindemann Monika , Schönfeld Andreas , Rohn Hana , Krawczyk Adalbert
Published: July 2023

Background

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves.

Methods

The corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay.

Results

On a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT100) 640 versus 80, p<0.05). Omicron-BA.1 infection increased neutralization titers against BA.1 in double-vaccinated patients (median NT100 of 160 in patients versus 20 in controls, p=0.07) and patients that received booster vaccination (median NT100 of 50 in patients versus 20 in controls, p=0.68). For boosted patients with BA.5 breakthrough infection, we found no enhancing effect on humoral immunity against SARS-CoV-2 variants.

Conclusion

Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced in SARS-CoV-2 breakthrough infections. Delta and Omicron-BA.1 but not Omicron-BA.5 infections boosted the humoral immunity in double-vaccinated patients and patients with booster vaccination. Despite BA.5 breakthrough infection, those patients may still be vulnerable for reinfections with BA.5 or other newly emerging variants of concern.
Cerebrospinal fluid inflammatory biomarkers for disease progression in Alzheimer’s disease and multiple sclerosis: a systematic review
Authors: Temmerman Joke , Engelborghs Sebastiaan , Bjerke Maria , D’haeseleer Miguel
Published: July 2023

Inflammatory processes are involved in the pathophysiology of both Alzheimer’s disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Splenic SUMO1 controls systemic inflammation in experimental sepsis
Authors: Youssef Ayman , Mohammed Bilal Khan , Prasad Abhishek , del Aguila Angela , Bassi Gabriel , Yang Wei , Ulloa Luis
Published: July 2023

Introduction

The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting.

Methods

We used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis.

Results and discussion

Here, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia.

Conclusion

These results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection.
Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe
Authors: Del Pozo-Yauner Luis , Herrera Guillermo A. , Perez Carreon Julio I. , Turbat-Herrera Elba A. , Rodriguez-Alvarez Francisco J. , Ruiz Zamora Robin A.
Published: July 2023

The adaptive immune system of jawed vertebrates generates a highly diverse repertoire of antibodies to meet the antigenic challenges of a constantly evolving biological ecosystem. Most of the diversity is generated by two mechanisms: V(D)J gene recombination and somatic hypermutation (SHM). SHM introduces changes in the variable domain of antibodies, mostly in the regions that form the paratope, yielding antibodies with higher antigen binding affinity. However, antigen recognition is only possible if the antibody folds into a stable functional conformation. Therefore, a key force determining the survival of B cell clones undergoing somatic hypermutation is the ability of the mutated heavy and light chains to efficiently fold and assemble into a functional antibody. The antibody is the structural context where the selection of the somatic mutations occurs, and where both the heavy and light chains benefit from protective mechanisms that counteract the potentially deleterious impact of the changes. However, in patients with monoclonal gammopathies, the proliferating plasma cell clone may overproduce the light chain, which is then secreted into the bloodstream. This places the light chain out of the protective context provided by the quaternary structure of the antibody, increasing the risk of misfolding and aggregation due to destabilizing somatic mutations. Light chain-derived (AL) amyloidosis, light chain deposition disease (LCDD), Fanconi syndrome, and myeloma (cast) nephropathy are a diverse group of diseases derived from the pathologic aggregation of light chains, in which somatic mutations are recognized to play a role. In this review, we address the mechanisms by which somatic mutations promote the misfolding and pathological aggregation of the light chains, with an emphasis on AL amyloidosis. We also analyze the contribution of the variable domain (VL) gene segments and somatic mutations on light chain cytotoxicity, organ tropism, and structure of the AL fibrils. Finally, we analyze the most recent advances in the development of computational algorithms to predict the role of somatic mutations in the cardiotoxicity of amyloidogenic light chains and discuss the challenges and perspectives that this approach faces.
NLRP3: a new therapeutic target in alcoholic liver disease
Authors: Brahadeeswaran Subhashini , Dasgupta Tiasha , Manickam Venkatraman , Saraswathi Viswanathan , Tamizhselvi Ramasamy
Published: July 2023

The liver is in charge of a wide range of critical physiological processes and it plays an important role in activating the innate immune system which elicits the inflammatory events. Chronic ethanol exposure disrupts hepatic inflammatory mechanism and leads to the release of proinflammatory mediators such as chemokines, cytokines and activation of inflammasomes. The mechanism of liver fibrosis/cirrhosis involve activation of NLRP3 inflammasome, leading to the destruction of hepatocytes and subsequent metabolic dysregulation in humans. In addition, increasing evidence suggests that alcohol intake significantly modifies liver epigenetics, promoting the development of alcoholic liver disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, and DNA methylation are crucial in alcohol-evoked cell signaling that affects gene expression in the hepatic system. Though we are at the beginning stage without having the entire print of epigenetic signature, it is time to focus more on NLRP3 inflammasome and epigenetic modifications. Here we review the novel aspect of ALD pathology linking to inflammation and highlighting the role of epigenetic modification associated with NLRP3 inflammasome and how it could be a therapeutic target in ALD.
Cancer-associated fibroblasts drive CXCL13 production in activated T cells via TGF-beta
Authors: O’Connor Richard A. , Martinez Begoña Roman , Koppensteiner Lilian , Mathieson Layla , Akram Ahsan R.
Published: July 2023

Introduction

Tumour-reactive T cells producing the B-cell attractant chemokine CXCL13, in solid tumours, promote development of tertiary lymphoid structures (TLS) and are associated with improved prognosis and responsiveness to checkpoint immunotherapy. Cancer associated fibroblasts are the dominant stromal cell type in non-small cell lung cancer (NSCLC) where they co-localise with T cells and can influence T cell activation and exhaustion. We questioned whether CAF directly promote CXCL13-production during T cell activation.

Methods

We characterised surface markers, cytokine production and transcription factor expression in CXCL13-producing T cells in NSCLC tumours and paired non-cancerous lung samples using flow cytometry. We then assessed the influence of human NSCLC-derived primary CAF lines on T cells from healthy donors and NSCLC patients during activation in vitro measuring CXCL13 production and expression of cell-surface markers and transcription factors by flow cytometry.

Results

CAFs significantly increased the production of CXCL13 by both CD4+ and CD8+ T cells. CAF-induced CXCL13-producing cells lacked expression of CXCR5 and BCL6 and displayed a T peripheral helper cell phenotype. Furthermore, we demonstrate CXCL13 production by T cells is induced by TGF-β and limited by IL-2. CAF provide TGF-β during T cell activation and reduce availability of IL-2 both directly (by reducing the capacity for IL-2 production) and indirectly, by expanding a population of activated Treg. Inhibition of TGF-β signalling prevented both CAF-driven upregulation of CXCL13 and Treg expansion.

Discussion

Promoting CXCL13 production represents a newly described immune-regulatory function of CAF with the potential to shape the immune infiltrate of the tumour microenvironment both by altering the effector-function of tumour infiltrating T-cells and their capacity to attract B cells and promote TLS formation.
Culturing reef-building corals on a laboratory dish: a simple experimental platform for stony corals
Authors: Shikina Shinya , Lin Tzu-Chieh , Chu Yu-Ling , Cheng Yin-Chu , Chang Yu-En , Wada Naohisa , Tang Sen-Lin , Iizuka Yoshiyuki , Chiu Yi-Ling
Published: July 2023

Development and maintenance of coral reef ecosystems rely on daily micro-biological activities of healthy corals. Although a comprehensive understanding of coral biological properties, as well as factors negatively affecting coral growth, are essential to conserve existing corals, the current lack of a tractable culture and experimental platform has delayed acquisition of such knowledge. Here we show a highly versatile culture system, “coral-on-a-laboratory dish” (CLD), allowing long-term culturing of various corals in plastic/glass Petri dishes with maintenance of their biological properties. Under optimized conditions, coral microcolonies (~5 mm x 5 mm fragments) of Pocillopora damicornis were cultured for several months in dishes with high survivorship and characteristic growth. These microcolonies maintained their biological properties, such as reproduction, skeleton formation, coral-algal symbiosis, ingestion, and digestion. Thus far, CLD has been used to maintain at least 4 other coral species from 4 other families, including the Acroporidae, the Pocilloporidae, the Poritidae, and the Merulinidae for more than 2 months with 100% survivorship. CLD is applicable to a variety of biophysiological studies, including coral-algal symbiosis and impact assessment of marine pollutants, e.g., a sunscreen substance, oxybenzone, and an organic biocide, Irgarol 1051, at cellular-level resolution. The CLD platform, which allows easy and inexpensive coral maintenance in a laboratory incubator, represents a technological breakthrough that will greatly advance coral studies.
Climate change - induced hazards on touristic island beaches: Cyprus, Eastern Mediterranean
Authors: Monioudi Isavela N. , Velegrakis Adonis F. , Chatzistratis Dimitris , Vousdoukas Michalis I. , Savva Christos , Wang Dandan , Bove Gerald , Mentaschi Lorenzo , Paprotny Dominik , Morales-Nápoles Oswaldo , Chatzipavlis Antonis E. , Hasiotis Thomas , Manoutsoglou Evangelia
Published: July 2023

This contribution presents an assessment at a regional (island) scale of the beach erosion due to storm events under Climate Change. The approach adopted to assess beach erosion at the island scale consisted of three modules. First, the location, dimensions and other attributes of the Cypriot beaches were recorded on the basis of widely-available satellite imagery. Secondly, sea levels and waves were modeled along the coast under different climatic scenarios and dates in the 21st century. Finally, using these projections beach retreat due to the relative mean sea level rise (RSLR) and extreme sea levels (ESLs) was estimated using ensembles of analytical and numerical cross-shore morphodynamic models, respectively. Extreme sea levels (ESLs) were projected to (a) increase by up to 60% in 2100 from their baseline (2000) levels, and (b) vary along the coast, with the highest ESLs (and corresponding waves) projected for the southern and western coasts. The mostly narrow Cypriot beaches (91% recorded maximum widths of < 50 m) showed increased exposure to erosion. In 2100, about 47% and 72% (based on the median model estimates) of the 241 unprotected Cypriot beaches will be permanently eroded, due to mean sea level rise (SLR), to 50% of their present maximum width, depending on the scenario. In addition to the long-term erosion due to SLR, severe storm erosion is projected by 2050 even under the RCP4.5 scenario; the 100-year extreme sea level event (ESL100) may overwhelm (at least temporarily) 49% of the currently unprotected Cypriot beaches without effective adaptation responses, with the most exposed beaches located along the northern coast. As the beach carrying capacity and hedonic value will be severely compromised, effective adaptation policies and technical measures will be urgently required.
Glomerular hyperfiltration and hypertrophy: an evaluation of maximum values in pathological indicators to discriminate “diseased” from “normal”
Authors: Kataoka Hiroshi , Nitta Kosaku , Hoshino Junichi
Published: July 2023

The success of sodium-glucose cotransporter 2 inhibitors and bariatric surgery in patients with chronic kidney disease has highlighted the importance of glomerular hyperfiltration and hypertrophy in the progression of kidney disease. Sustained glomerular hyperfiltration and hypertrophy can lead to glomerular injury and progressive kidney damage. This article explores the relationship between obesity and chronic kidney disease, focusing on the roles of glomerular hyperfiltration and hypertrophy as hallmarks of obesity-related kidney disease. The pathological mechanisms underlying this association include adipose tissue inflammation, dyslipidemia, insulin resistance, chronic systemic inflammation, oxidative stress, and overactivation of the sympathetic nervous system, as well as the renin-angiotensin aldosterone system. This article explains how glomerular hyperfiltration results from increased renal blood flow and intraglomerular hypertension, inducing mechanical stress on the filtration barrier and post-filtration structures. Injured glomeruli increase in size before sclerosing and collapsing. Therefore, using extreme values, such as the maximal glomerular diameter, could improve the understanding of the data distribution and allow for better kidney failure predictions. This review provides important insights into the mechanisms underlying glomerular hyperfiltration and hypertrophy and highlights the need for further research using glomerular size, including maximum glomerular profile, calculated using needle biopsy specimens.
Bioinformatics identification of ferroptosis-related genes and therapeutic drugs in rheumatoid arthritis
Authors: Li Xianbin , He Andong , Liu Yue , Huang Yuye , Zhang Xueli
Published: July 2023

Introduction

Rheumatoid arthritis (RA) is a chronic immune disease characterized by synovial inflammation and bone destruction, with a largely unclear etiology. Evidence has indicated that ferroptosis may play an increasingly important role in the onset and development of RA. However, ferroptosis-related genes are still largely unexplored in RA. Therefore, this work focused on identifying and validating the potential ferroptosis-related genes involved in RA through bioinformatics analysis.

Methods

We screened differentially expressed ferroptosis-related genes (DEFGs) between RA patients and healthy individuals based on GSE55235 dataset. Subsequently, correlation analysis, protein-protein interaction (PPI) network analysis, GO, and KEGG enrichment analyses were performed using these DEFGs. Finally, our results were validated by GSE12021 dataset.

Results

We discovered 34 potential DEFGs in RA based on bioinformatics analysis. According to functional enrichment analysis, these genes were mainly enriched in HIF-1 signaling pathway, FoxO signaling pathway, and Ferroptosis pathway. Four genes (GABARPL1, DUSP1, JUN, and MAPK8) were validated to be downregulated by GSE12021 dataset and were diagnostic biomarkers and therapeutic targets for RA via the regulation of ferroptosis.

Discussion

Our results help shed more light on the pathogenesis of RA. Ferroptosis-related genes in RA are valuable diagnostic biomarkers and they will be exploited clinically as therapeutic targets in the future.
Adverse pregnancy outcomes and associated risk factors among pregnant women with syphilis during 2013–2018 in Hunan, China
Authors: Gao Jie , Chen Xia , Yang Min , Wu Yinglan , Liang Ting , Li Huixia , Xie Wanqin
Published: July 2023

Objective

To investigate the adverse pregnancy outcomes and associated risk factors among pregnant women with syphilis.

Design

Pregnant women with syphilis in the registry for the prevention of mother-to-child transmission of AIDS, syphilis and hepatitis B in Hunan Province, China, from January 1, 2013 to December 31, 2018 were included in the study.

Results

Among the 14,219 pregnant women with syphilis, 11,346 had definite pregnancy outcomes and were in singleton pregnancy. The risk factors related to adverse pregnancy outcomes include the age of pregnant women with syphilis <20 years old (aOR = 1.274, 95% CI: 1.088–1.493) or ≥ 35 years old (aOR = 1.402, 95% CI: 1.167–1.686), not married (aOR = 1.855, 95% CI: 1.453–2.367), initial syphilis detection in the late pregnancy (aOR = 1.266, 95% CI: 1.032–1.555), diagnosis of syphilis in the late pregnancy (aOR = 5.806, 95% CI: 1.796–18.770), diagnosis of syphilis during labor (aOR = 4.102, 95% CI: 1.263–13.330), husband/sexual partner infected with syphilis (aOR = 1.222, 95% CI: 1.068–1.398), untreated (aOR = 6.756, 95% CI: 5.586–8.197), and nonstandard medication (aOR = 3.300, 95% CI: 2.841–3.846).

Conclusion

The prevalence of adverse pregnancy outcomes among pregnant women with syphilis in Hunan Province, China from 2013 to 2018 was relatively high. The adverse pregnancy outcomes associated with syphilis could be reduced by early detection and standard treatment of syphilis for pregnant women and their husbands/sexual partners.
Primary diffuse large B-cell tumor of the uterus: a case report
Authors: Zhang Zhiming , Yang Qing
Published: July 2023

Primary diffuse large B-cell tumor of the uterus is a rare clinical condition with a similar clinical presentation to gynecologic tumors and is easily misdiagnosed. We report a case of a postmenopausal woman who presented with pelvic mass. Her ultrasound and MRI examinations suggested diffuse enlargement of the uterus, leading us to consider the diagnosis of lymphoma. The histological examination of the uterine mass confirmed the diagnosis of diffuse large B-cell lymphoma. The patient received 6 cycles of chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) and 2 cycles of consolidation therapy with R (rituximab). After treatment, the patient's uterus was significantly smaller than before and there was no sign of a recurrence.
Comparison of MRCP and ERCP in the evaluation of common bile duct and pancreatic duct pathologies
Authors: Kumar Anand , Mohanty Nihar Ranjan , Mohanty Madhusmita , Dash Sashibhusan
Published: July 2023

Background

Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive imaging modality that has high diagnostic accuracy for a wide range of bile duct and pancreatic duct pathologies. Endoscopic retrograde cholangiopancreatography (ERCP) is still the gold standard for the exploration of the biliopancreatic region.

Aim

The aim of the study was to compare the diagnostic accuracy of MRCP with that of ERCP in the diagnosis of bile duct and pancreatic duct pathologies.

Material and methods

A total of 60 patients with common bile duct (CBD) and pancreatic duct pathologies detected on MRCP were subsequently evaluated by ERCP in this observational study. A comparison of MRCP findings with ERCP was made.

Results

MRCP had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 88.1%, 94.4%, 97.3%, 72.7%, and 90%, respectively, in diagnosing choledocholithiasis in comparison to ERCP. For CBD dilation, the sensitivity was 90.91%, specificity was 93.75% and the PPV, NPV, and accuracy were 97.56%, 78.95%, and 91.67%, respectively, for MRCP. In CBD stricture, MRCP showed a sensitivity, specificity, PPV, NPV, and accuracy of 83.33%, 97.92%, 90.91%, 95.92%, and 95%, respectively. In pancreatic duct dilatation, the sensitivity, specificity, PPV, NPV, and accuracy were all 100%. Pancreatic duct stricture showed a sensitivity, specificity, PPV, NPV, and accuracy of 80%, 98%, 88.89%, 96.08%, and 95%, respectively. For the diagnosis of periampullary carcinoma, the sensitivity, specificity, PPV, NPV, and accuracy rate of MRCP were 80%, 98%, 88.89%, 96.08%, and 95%, respectively.

Conclusion

No significant difference was found between MRCP and ERCP in diagnosing those six pathologies.
Novel concepts and engineering strategies for heterologous expression of efficient hydrogenases in photosynthetic microorganisms
Authors: Schumann Conrad , Fernández Méndez Jorge , Berggren Gustav , Lindblad Peter
Published: July 2023

Hydrogen is considered one of the key enablers of the transition towards a sustainable and net-zero carbon economy. When produced from renewable sources, hydrogen can be used as a clean and carbon-free energy carrier, as well as improve the sustainability of a wide range of industrial processes. Photobiological hydrogen production is considered one of the most promising technologies, avoiding the need for renewable electricity and rare earth metal elements, the demands for which are greatly increasing due to the current simultaneous electrification and decarbonization goals. Photobiological hydrogen production employs photosynthetic microorganisms to harvest solar energy and split water into molecular oxygen and hydrogen gas, unlocking the long-pursued target of solar energy storage. However, photobiological hydrogen production has to-date been constrained by several limitations. This review aims to discuss the current state-of-the art regarding hydrogenase-driven photobiological hydrogen production. Emphasis is placed on engineering strategies for the expression of improved, non-native, hydrogenases or photosynthesis re-engineering, as well as their combination as one of the most promising pathways to develop viable large-scale hydrogen green cell factories. Herein we provide an overview of the current knowledge and technological gaps curbing the development of photobiological hydrogenase-driven hydrogen production, as well as summarizing the recent advances and future prospects regarding the expression of non-native hydrogenases in cyanobacteria and green algae with an emphasis on [FeFe] hydrogenases.
The optimized carbapenem inactivation method for objective and accurate detection of carbapenemase-producing Acinetobacter baumannii
Authors: Zhang Sirui , Mi Peng , Wang Jingdan , Li Pu , Luo Kai , Liu Shuyan , Al-Shamiri Mona Mohamed , Lei Jin’e , Lai Simin , Han Bei , Chen Yanjiong , Han Lei , Han Shaoshan
Published: July 2023

The modified carbapenem inactivation method (mCIM) recommended by the Clinical and Laboratory Standards Institute is not applicable for detecting carbapenemases in Acinetobacter baumannii. Four currently reported phenotypic detection methods, namely, the modified Hodge test, the mCIM, the adjusted mCIM, and the simplified carbapenem inactivation method (sCIM), did not perform well in our 90 clinical A. baumannii isolates. Thus, the minimal inhibitory concentrations (MICs) of carbapenems and the existence and expression of carbapenemase-encoding genes were detected to explain the results. According to the E-test, which was more accurate than the VITEK 2 system, 80.0 and 41.1% were resistant to imipenem (IPM) and meropenem (MEM), respectively, and 14.4 and 53.3% exhibited intermediate resistance, respectively. Five β-lactamase genes were found, of which blaOXA-51-like, blaTEM, and blaOXA-23-like were detected more frequently in 85 non-susceptible strains. The expression of blaOXA-23-like was positively correlated with the MIC values of IPM and MEM. Therefore, an improved approach based on the mCIM, designated the optimized CIM (oCIM), was developed in this study to detect carbapenemases more accurately and reproducibly. The condition was improved by evaluating the factors of A. baumannii inoculum, incubation broth volume, and MEM disk incubation time. Obvious high sensitivity (92.94%) and specificity (100.00%) were obtained using the oCIM, which was cost-effective and reproducible in routine laboratory work.
Function discovery of a non-ribosomal peptide synthetase-like encoding gene in the nematode-trapping fungus Arthrobotrys oligospora
Authors: Gu Tiantian , Lu Hengqian , Liu Huiwen , Zhang Guanghui , Wang Yongzhong
Published: July 2023

In this study, the function of a non-ribosomal peptide synthetase-like (NRPS-like) encoding gene AOL_s00188g306 (g306) was investigated to reveal the association between NRPS and nematocidal activity in the nematode-trapping fungus Arthrobotrys oligospora. Sequence analysis indicated that the encoded product of g306 is an adenylation domain of non-ribosomal peptide synthetases and extended short-chain dehydrogenase/reductase domain-containing proteins, and displays a wide substrate spectrum. The Δg306 mutants were more sensitive to chemical stressors than the wild type. Disruption of g306 impeded the nematocidal efficiency of A. oligospora. Metabolomics analysis showed that secondary metabolite biosynthesis and lipid metabolism were altered in the mutants. The phenotypic changes in the mutants can be attributed to the down-regulation of various metabolites, including fatty acyls, prenol lipids, steroidsand steroid derivative, and amino acid derivatives, identified in the present study. This study investigated the association between the non-ribosomal polypeptide-encoding gene g306 and nematicidal activity in A. oligospora, providing a reference for resolving the predation mechanism of nematode-trapping fungus.
Metabolomic analysis reveals a differential adaptation process of the larval stages of Anisakis simplex to the host environment
Authors: Polak Iwona , Stryiński Robert , Majewska Marta , Łopieńska-Biernat Elżbieta
Published: July 2023

Introduction:Anisakis simplex are parasitic nematodes that cause anisakiasis. The possibility of infection with this parasite is through consumption of raw or undercooked fish products. A. simplex infections are often misdiagnosed, especially in subclinical cases that do not present with typical symptoms such as urticaria, angioedema, and gastrointestinal allergy. The resulting allergic reactions range from rapid-onset and potentially fatal anaphylactic reactions to chronic, debilitating conditions. While there have been numerous published studies on the genomes and proteomes of A. simplex, less attention has been paid to the metabolomes. Metabolomics is concerned with the composition of metabolites in biological systems. Dynamic responses to endogenous and exogenous stimuli are particularly well suited for the study of holistic metabolic responses. In addition, metabolomics can be used to determine metabolic activity at different stages of development or during growth.

Materials and methods: In this study, we reveal for the first time the metabolomes of infectious stages (L3 and L4) of A. simplex using untargeted metabolomics by ultra-performance liquid chromatography-mass spectrometry.

Results: In the negative ionization mode (ESI-), we identified 172 different compounds, whereas in the positive ionization mode (ESI+), 186 metabolites were found. Statistical analysis showed that 60 metabolites were found in the ESI- mode with different concentration in each group, of which 21 were more enriched in the L3 larvae and 39 in the L4 stage of A. simplex. Comparison of the individual developmental stages in the ESI + mode also revealed a total of 60 differential metabolites, but 32 metabolites were more enriched in the L3 stage larvae, and 28 metabolites were more concentrated in the L4 stage.

Discussion: The metabolomics study revealed that the developmental stages of A. simplex differed in a number of metabolic pathways, including nicotinate and nicotinamide metabolism. In addition, molecules responsible for successful migration within their host, such as pyridoxine and prostaglandins (E1, E2, F1a) were present in the L4 stage. In contrast, metabolic pathways for amino acids, starch, and sucrose were mainly activated in the L3 stage. Our results provide new insights into the comparative metabolome profiles of two different developmental stages of A. simplex.
Dementia incidence and population-attributable fraction for dementia risk factors in Republic of Korea: a 12-year longitudinal follow-up study of a national cohort
Authors: Hwangbo Song , Lee Jin Young , Han Gyule , Chun Min Young , Jang Hyemin , Seo Sang Won , Na Duk L. , Won Sungho , Kim Hee Jin , Lim Dong Hui
Published: July 2023

Background

We aimed to investigate the incidence of dementia by age and year as well as the population-attributable fractions (PAFs) for known dementia risk factors in Republic of Korea.

Methods

A 12-year, nationwide, population-based, retrospective cohort study was conducted. We used customized health information from the National Health Insurance Service (NHIS) data from 2002 to 2017. We analyzed age- and sex-adjusted incidence rates and PAF of dementia for each risk factor such as depression, diabetes, hemorrhagic stroke, ischemic stroke, hypertension, osteoporosis and physical inactivity using Levin’s formula.

Results

Of the 794,448 subjects in the dementia-free cohort, 49,524 (6.2%) developed dementia. Dementia incidence showed annual growth from 1.56 per 1,000 person-years in 2006 to 6.94 per 1,000 person-years in 2017. Of all dementia cases, 34,544 subjects (69.8%) were female and 2,479 subjects (5.0%) were early onset dementia. AD dementia accounted for 66.5% of the total dementia incidence. Considering relative risk and prevalence, physical inactivity attributed the greatest to dementia (PAF, 8.1%), followed by diabetes (PAF, 4.2%), and hypertension (PAF, 2.9%). Altogether, the significant risk factors increased the risk of dementia by 18.0% (overall PAF).

Conclusion

We provided the incidence of dementia and PAFs for dementia risk factors in Republic of Korea using a 12-year, nationwide cohort. Encouraging lifestyle modifications and more aggressive control of risk factors may effectively prevent dementia.
Online physical exercise program with music improves working memory
Authors: Tabei Ken-ichi , Ogawa Jun-ichi , Kamikawa Chiaki , Abe Makiko , Ota Yoshinori , Satoh Masayuki
Published: July 2023

Objective

The spread of coronavirus disease (COVID-19) has limited the implementation of face-to-face non-pharmacological treatment for the prevention of dementia. As a result, online non-pharmacological treatment has become increasingly important. In this study, we used an online conferencing system to implement an online version of a physical exercise program with music, and examined its effect on cognitive function.

Methods

The participants were 114 healthy older adults [63 men and 51 women; mean age of 70.7 years (standard deviation = 4.6)]. Seventy-five participants were allocated to the physical exercise with music group (60 min, once a week, total 20 sessions), while the remaining 39 participants were assigned to the control group, and only underwent the examinations. In the physical exercise with music group, we performed neuropsychological examinations and brain tests both before and after the exercise program. Neuropsychological tests included the Mini-Mental State Examination, Raven’s Colored Progressive Matrices (RCPM), the Rivermead Behavioral Memory Test, graphic imitation, word fluency (WF) (animal names and initial sounds), and the Trail Making Test-A/B. As an assessment of brain function, we developed an online examination of subtle cognitive decline, including tests of number and word memory, spatial grasp, the N-back task, and change inference.

Results

In the N-back task, the physical exercise with music group improved significantly relative to the control group (p = 0.008).

Discussion

The present findings suggest that the online version of the physical exercise with music program improved working memory, which mainly involves the frontal lobe.