bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress decreases spermatozoa quality and induces molecular alterations in zebrafish progeny
Authors: Valcarce David G. , Riesco Marta F. , Cuesta-Martín Leyre , Esteve-Codina Anna , Martínez-Vázquez Juan Manuel , Robles Vanesa
Published: April 2023

Background

Chronic stress can produce a severe negative impact on health not only in the exposed individuals but also in their offspring. Indeed, chronic stress may be contributing to the current worldwide scenario of increasing infertility and decreasing gamete quality in human populations. Here, we evaluate the effect of chronic stress on behavior and male reproductive parameters in zebrafish. Our goal is to provide information on the impact that chronic stress has at molecular, histological, and physiological level in a vertebrate model species.

Results

We evaluated the effects of a 21-day chronic stress protocol covering around three full waves of spermatogenesis in Danio rerio adult males. The induction of chronic stress produced anxiety-like behavior in stressed males as assessed by a novel tank test. At a molecular level, the induction of chronic stress consistently resulted in the overexpression of two genes related to endoplasmic reticulum (ER) stress in the brain. Gene set enrichment analysis (GSEA) of testes suggested a dysregulation of the nonsense-mediated decay (NMD) pathway, which was also confirmed on qPCR analysis. Histological analysis of the testicle did not show significant differences in terms of the relative proportions of each germ-cell type; however, the quality of sperm from stressed males was compromised in terms of motility. RNA-seq analysis in stress-derived larval progenies revealed molecular alterations, including those predicted to affect translation initiation, DNA repair, cell cycle control, and response to stress.

Conclusions

Induction of chronic stress during a few cycles of spermatogenesis in the vertebrate zebrafish model affects behavior, gonadal gene expression, final gamete quality, and progeny. The NMD surveillance pathway (a key cellular mechanism that regulates the stability of both normal and mutant transcripts) is severely affected in the testes by chronic stress and therefore the control and regulation of RNAs during spermatogenesis may be affected altering the molecular status in the progeny.

Graphical Abstract
Guanine crystal formation by bacteria
Authors: Pavan María Elisa , Movilla Federico , Pavan Esteban E. , Di Salvo Florencia , López Nancy I. , Pettinari M. Julia
Published: April 2023

Background

Guanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles, and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes.

Results

In this work, we report the discovery of extracellular crystals formed by bacteria and reveal that they are composed of guanine monohydrate. This composition differs from that of biogenic guanine crystals found in other organisms, mostly composed of β anhydrous guanine. We demonstrate the formation of these crystals by Aeromonas and other bacteria and investigate the metabolic traits related to their synthesis. In all cases studied, the presence of the bacterial guanine crystals correlates with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation.

Conclusions

Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of organisms that produce these crystals to a new domain of life. Bacteria constitute a novel and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.
Identifying the causal effects of long-term exposure to PM2.5 and ground surface ozone on individual medical costs in China—evidence from a representative longitudinal nationwide cohort
Authors: Ju Ke , Lu Liyong , Yang Jingguo , Chen Ting , Lan Tianjiao , Duan Zhongxin , Xu Zongyou , Zhang En , Wang Wen , Pan Jay
Published: April 2023

Background

There is little evidence on whether PM2.5 and ground surface ozone have consistent effects on increased individual medical costs, and there is a lack of evidence on causality in developing countries.

Methods

This study utilized balanced panel data from 2014, 2016, and 2018 waves of the Chinese Family Panel Study. The Tobit model was developed within a counterfactual causal inference framework, combined with a correlated random effects and control function approach (Tobit-CRE-CF), to explore the causal relationship between long-term exposure to air pollution and medical costs. We also explored whether different air pollutants exhibit comparable effects.

Results

This study encompassed 8928 participants and assessed various benchmark models, highlighting the potential biases from failing to account for air pollution endogeneity or overlooking respondents without medical costs. Using the Tobit-CRE-CF model, significant effects of air pollutants on increased individual medical costs were identified. Specifically, margin effects for PM2.5 and ground-level ozone signifying that a unit increase in PM2.5 and ground-level ozone results in increased total medical costs of 199.144 and 75.145 RMB for individuals who incurred fees in the previous year, respectively.

Conclusions

The results imply that long-term exposure to air pollutants contributes to increased medical costs for individuals, offering valuable insights for policymakers aiming to mitigate air pollution’s consequences.
Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up
Authors: Hu Huamei , Huang Yulin , Hou Renke , Xu Huanhuan , Liu Yalan , Liao Xueqian , Xu Juchun , Jiang Lupin , Wang Dan
Published: April 2023

Background

Xp22.31 deletion and duplication have been described in various studies, but different laboratories interpret pathogenicity differently.

Objectives

Our study aimed to refine the genotype–phenotype associations between Xp22.31 copy number variants in fetuses, with the aim of providing data support to genetic counseling.

Methods

We retrospectively analyzed karyotyping and single nucleotide polymorphism array results from 87 fetuses and their family members. Phenotypic data were obtained through follow-up visits.

Results

The percentage of fetuses carrying the Xp22.31 deletions (9 females, 12 males) was 24.1% (n = 21), while duplications (38 females, 28 males) accounted for 75.9% (n = 66). Here, we noted that the typical region (from 6.4 to 8.1 Mb, hg19) was detected in the highest ratio, either in the fetuses with deletions (76.2%, 16 of 21) or duplications (69.7%, 46 of 66). In female deletion carriers, termination of pregnancy was chosen for two fetuses, and the remaining seven were born without distinct phenotypic abnormalities. In male deletion carriers, termination of pregnancy was chosen for four fetuses, and the remaining eight of them displayed ichthyosis without neurodevelopmental anomalies. In two of these cases, the chromosomal imbalance was inherited from the maternal grandfathers, who also only had ichthyosis phenotypes. Among the 66 duplication carriers, two cases were lost at follow-up, and pregnancy was terminated for eight cases. There were no other clinical findings in the rest of the 56 fetuses, including two with Xp22.31 tetrasomy, for either male or female carriers.

Conclusion

Our observations provide support for genetic counseling in male and female carriers of Xp22.31 copy number variants. Most of them are asymptomatic in male deletion carriers, except for skin findings. Our study is consistent with the view that the Xp22.31 duplication may be a benign variant in both sexes.
Potential diagnostic value of N1LR and SNHG1 in acute myocardial infarction
Authors: Zhu Wei , Luo Li , Ye Guangning , Ou Jiaman
Published: April 2023

Introduction

Acute myocardial infarction (AMI) is a common cardiovascular disease that can lead to myocardial necrosis and a poor prognosis. Clinical practice requires an accurate and quick diagnosis of AMI due to the inherent limitations of current biomarkers. Therefore, research into novel biomarkers is necessary. We aimed to explore the diagnostic potency of the long non-coding RNA (lncRNA) N1LR and SNHG1 in patients diagnosed with AMI.

Method

We measured lncRNA levels in 148 AMI patients and 50 healthy volunteers with quantitative RT-PCR method. Receiver operating characteristic (ROC) analysis was administered to detect the diagnostic power of selected lncRNAs. Correlation analysis was performed to explore the relationship between N1LR as well as SNHG1 and the conventional myocardial biomarkers (LDH, CK, CKMB and cTnI).

Results

ROC analysis reveals the possibility of N1LR and SNHG1 as biomarkers in AMI diagnosis (AUC of N1LR: 0.873; AUC of SNHG1: 0.890). Correlation analysis revealed that N1LR was negatively correlated with the conventional biomarkers and SNHG1 was positively correlated with the conventional biomarkers.

Conclusion

For the first time, we investigated the potential predictive diagnostic value of N1LR and SNHG1 in AMI diagnosis and substantial outcomes were obtained. Also, they may be capable of reflecting the progress of the disease during clinical practice from the correlation analysis.
Phenotypic and genotypic characterization of linezolid resistance and the effect of antibiotic combinations on methicillin-resistant Staphylococcus aureus clinical isolates
Authors: AbdAlhafiz Asmaa I. , Elleboudy Nooran S. , Aboshanab Khaled M. , Aboulwafa Mohammad M. , Hassouna Nadia A.
Published: April 2023

Background

Methicillin-Resistant Staphylococcus aureus (MRSA) causes life-threatening infections, with narrow therapeutic options including: vancomycin and linezolid. Accordingly, this study aimed to characterize phenotypically and genotypically, the most relevant means of linezolid resistance among some MRSA clinical isolates.

Methods

A total of 159 methicillin-resistant clinical isolates were collected, of which 146 were indentified microscopically and biochemically as MRSA. Both biofilm formation and efflux pump activity were assessed for linezolid-resistant MRSA (LR-MRSA) using the microtiter plate and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) methods, respectively. Linezolid resistance was further characterized by polymerase chain reaction (PCR) amplification and sequencing of domain V of 23 S rRNA; rplC; rplD;and rplV genes. Meanwhile, some resistance genes were investigated: cfr; cfr(B); optrA; msrA;mecA; and vanA genes. To combat LR-MRSA, the effect of combining linezolid with each of 6 different antimicrobials was investigated using the checkerboard assay.

Results

Out of the collected MRSA isolates (n = 146), 5.48% (n = 8) were LR-MRSA and 18.49% (n = 27) were vancomycin-resistant (VRSA). It is worth noting that all LR-MRSA isolates were also vancomycin-resistant. All LR-MRSA isolates were biofilm producers (r = 0.915, p = 0.001), while efflux pumps upregulation showed no significant contribution to development of resistance (t = 1.374, p = 0.212). Both mecA and vanA genes were detected in 92.45% (n = 147) and 6.92% (n = 11) of methicillin-resistant isolates, respectively. In LR-MRSA isolates, some 23 S rRNA domain V mutations were observed: A2338T and C2610G (in 5 isolates); T2504C and G2528C (in 2 isolates); and G2576T (in 1 isolate). Amino acids substitutions were detected: in L3 protein (rplC gene) of (3 isolates) and in L4 protein (rplD gene) of (4 isolates). In addition, cfr(B) gene was detected (in 3 isolates). In 5 isolates, synergism was recorded when linezolid was combined with chloramphenicol, erythromycin, or ciprofloxacin. Reversal of linezolid resistance was observed in some LR-MRSA isolates when linezolid was combined with gentamicin or vancomycin.

Conclusions

LR-MRSA biofilm producers’ phenotypes evolved in the clinical settings in Egypt. Various antibiotic combinations with linezolid were evaluated in vitro and showed synergistic effects.
Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging
Authors: Guan Xiaolin , Zhang Liyuan , Lai Shoujun , Zhang Jiaming , Wei Jingyu , Wang Kang , Zhang Wentao , Li Chenghao , Tong Jinhui , Lei Ziqiang
Published: April 2023

Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the “direct” reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0–4.0 nm. They exhibited well-separated dual emission in the visible region (500–590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from − 23.9 to − 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.
The effect of different types of migration on symptoms of anxiety or depression and experience of violence among people who use or inject drugs in Kachin State, Myanmar
Authors: Kyaw Khine Wut Yee , Platt Lucy , Bijl Murdo , Rathod Sujit D. , Naing Aung Yu , Roberts Bayard
Published: April 2023

Background

Evidence on the social determinants of mental health conditions and violence among people who inject or use drugs (PWUD) is limited, particularly in conflict-affected countries. We estimated the prevalence of symptoms of anxiety or depression and experience of emotional or physical violence among PWUD in Kachin State in Myanmar and examined their association with structural determinants, focusing on types of past migration (migration for any reason, economic or forced displacement).

Materials

A cross-sectional survey was conducted among PWUD attending a harm reduction centre between July and November 2021 in Kachin State, Myanmar. We used logistic regression models to measure associations between past migration, economic migration and forced displacement on two outcomes (1) symptoms of anxiety or depression (Patient Health Questionnaire-4) and (2) physical or emotional violence (last 12 months), adjusted for key confounders.

Results

A total of 406, predominantly male (96.8%), PWUD were recruited. The median age (IQR) was 30 (25, 37) years, most injected drugs (81.5%) and more commonly opioid substances such as heroin or opium (85%). Symptoms of anxiety or depression (PHQ4 ≥ 6) were high (32.8%) as was physical or emotional violence in the last 12 months (61.8%). Almost one-third (28.3%) had not lived in Waingmaw for their whole life (migration for any reason), 77.9% had left home for work at some point (economic migration) and 19.5% had been forced to leave home due to war or armed conflict (forced displacement). A third were in unstable housing in the last 3 months (30.1%) and reported going hungry in the last 12 months (27.7%). Only forced displacement was associated with symptoms of anxiety or depression [adjusted odds ratio, aOR 2.33 (95% confidence interval, CI 1.32–4.11)] and recent experience of violence [aOR 2.18 (95% CI 1.15–4.15)].

Conclusion

Findings highlight the importance of mental health services integrated into existing harm reduction services to address high levels of anxiety or depression among PWUD, particularly among those who have been displaced through armed conflict or war. Findings reinforce the need to address broader social determinants, in the form of food poverty, unstable housing and stigma, in order to reduce mental health and violence.
Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study
Authors: Querec Troy D. , Lin Jin-Mann S. , Chen Yang , Helton Britany , Kogelnik Andreas M. , Klimas Nancy G. , Peterson Daniel L. , Bateman Lucinda , Lapp Charles , Podell Richard N. , Natelson Benjamin H. , Unger Elizabeth R. ,   the MCAM Study Group, Unger Elizabeth , Lin Jin-Mann Sally , Cornelius Monica , Dimulescu Irina , Fall Elizabeth , Khin Maung , Rajeevan Mangalathu , Bland Jennifer , Jeys Patricia , Parkinson Veronica , Springs Wendy , Klimas Nancy , Balbin Elizabeth , Cournoyer Jeffry , Fernandez Melissa , Parnell Shuntae , Leaks-Gutierrez Precious , Natelson Benjamin , Blate Michelle , Lange Gudrun , Khan Sarah , Vu Diana , Kogelnik Andreas , Danver Joan , Kaufman David , Pa Macy , Phan Catt , Taleghani Sophia , Podell Richard N , Fitzpatrick Trisha , Licata Beverly , Peterson Daniel , Lascu Elena , Gottschalk Gunnar , Maynard Marco , Smith Janet
Published: April 2023

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted.

Methods

We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture.

Results

We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4–44.3%) and 33.6% (IQR 22.9–43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions.

Conclusion

These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS.
Phase separation in cancer at a glance
Authors: Xie Qingqing , Cheng Jiejuan , Mei Wuxuan , Yang Dexing , Zhang Pengfei , Zeng Changchun
Published: April 2023

Eukaryotic cells are segmented into multiple compartments or organelles within the cell that regulate distinct chemical and biological processes. Membrane-less organelles are membrane-less microscopic cellular compartments that contain protein and RNA molecules that perform a wide range of functions. Liquid–liquid phase separation (LLPS) can reveal how membrane-less organelles develop via dynamic biomolecule assembly. LLPS either segregates undesirable molecules from cells or aggregates desired ones in cells. Aberrant LLPS results in the production of abnormal biomolecular condensates (BMCs), which can cause cancer. Here, we explore the intricate mechanisms behind the formation of BMCs and its biophysical properties. Additionally, we discuss recent discoveries related to biological LLPS in tumorigenesis, including aberrant signaling and transduction, stress granule formation, evading growth arrest, and genomic instability. We also discuss the therapeutic implications of LLPS in cancer. Understanding the concept and mechanism of LLPS and its role in tumorigenesis is crucial for antitumor therapeutic strategies.
Differential Risk of SARS-CoV-2 Infection by Occupation: Evidence from the Virus Watch prospective cohort study in England and Wales
Authors: Beale Sarah , Hoskins Susan , Byrne Thomas , Fong Wing Lam Erica , Fragaszy Ellen , Geismar Cyril , Kovar Jana , Navaratnam Annalan M. D. , Nguyen Vincent , Patel Parth , Yavlinsky Alexei , Johnson Anne M. , Van Tongeren Martie , Aldridge Robert W. , Hayward Andrew ,   the Virus Watch Collaborative, Michie Susan , Hardelid Pia , Wijlaars Linda , Nastouli Eleni , Spyer Moira , Killingley Ben , Cox Ingemar , McKendry Rachel A , Cheng Tao , Liu Yunzhe , Gibbs Jo , Gilson Richard , Rodger Alison
Published: April 2023

Background

Workers across different occupations vary in their risk of SARS-CoV-2 infection, but the direct contribution of occupation to this relationship is unclear. This study aimed to investigate how infection risk differed across occupational groups in England and Wales up to April 2022, after adjustment for potential confounding and stratification by pandemic phase.

Methods

Data from 15,190 employed/self-employed participants in the Virus Watch prospective cohort study were used to generate risk ratios for virologically- or serologically-confirmed SARS-CoV-2 infection using robust Poisson regression, adjusting for socio-demographic and health-related factors and non-work public activities. We calculated attributable fractions (AF) amongst the exposed for belonging to each occupational group based on adjusted risk ratios (aRR).

Results

Increased risk was seen in nurses (aRR = 1.44, 1.25–1.65; AF = 30%, 20–39%), doctors (aRR = 1.33, 1.08–1.65; AF = 25%, 7–39%), carers (1.45, 1.19–1.76; AF = 31%, 16–43%), primary school teachers (aRR = 1.67, 1.42- 1.96; AF = 40%, 30–49%), secondary school teachers (aRR = 1.48, 1.26–1.72; AF = 32%, 21–42%), and teaching support occupations (aRR = 1.42, 1.23–1.64; AF = 29%, 18–39%) compared to office-based professional occupations. Differential risk was apparent in the earlier phases (Feb 2020—May 2021) and attenuated later (June—October 2021) for most groups, although teachers and teaching support workers demonstrated persistently elevated risk across waves.

Conclusions

Occupational differences in SARS-CoV-2 infection risk vary over time and are robust to adjustment for socio-demographic, health-related, and non-workplace activity-related potential confounders. Direct investigation into workplace factors underlying elevated risk and how these change over time is needed to inform occupational health interventions.
HER2 exon 20 insertion mutations and myelosuppression in lung adenocarcinoma patient: a case report and response to trastuzumab deruxtecan
Authors: Wang Bin , Song Yang , Yang Xin , Chen Chuan
Published: April 2023

Background

Human epidermal growth factor receptor 2 (HER2) mutations occur in 2% of lung cancers.

Case presentation

In this report, we presented a case of an Asian female who was diagnosed with lung adenocarcinoma. NGS results indicated HER2 exon 20 insertion mutation and PET/CT results showed multiple metastases in lower lobes of both lungs. Thereafter, she was treated with chemotherapy alone, combination of chemotherapy and targeted therapy and immunotherapy. Due to progressive disease, she was then received DS-8201. Imaging data indicated partial response to DS-8201 and tumor marker values decreased significantly, suggesting good efficacy. Nevertheless, DS-8201 was discontinued because of the development of myelosuppression (grade 3). Finally, she died at home due to platelet deficiency, white blood cell (grade 4), granulocytopenia, intracranial hemorrhage and gastrointestinal hemorrhage.

Conclusions

This was an important case since it exerted effective response to DS-8201. Meanwhile, myelosuppression is also found in the patient, which requires attention to pulmonary symptoms and careful monitoring.
Prognostic marker C3AR1 is associated with ovarian cancer cell proliferation and immunosuppression in the tumor microenvironment
Authors: Huang Jinfa , Zhou Lei , Deng Kaixian
Published: April 2023

Background

C3AR1 was reported in driving tumor immunity in multiple cancers. However, its roles in ovarian cancer remain unclear. This study aims to determine role of C3AR1 in prognosis and regulating tumor infiltrating immune cells of ovarian cancer (OC).

Materials and methods

The expression, prognosis and clinical data related to C3AR1 were collected from public databases such as The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Clinical Proteomics Tumor Analysis Alliance (CPTAC), and further analyze their relationship with immune infiltration. Immunohistochemistry verified the expression of C3AR1 in ovarian cancer and control tissues. C3AR1 was forced expressed in SKOV3 cells by plasmid transfection, and verified by qRT-PCR and Western blot. Cell proliferation were evaluated by EdU assay.

Results

Bioinformatics analysis (TCGA, CPTAC) and immunohistochemical staining of clinical samples confirmed higher C3AR1 expression in ovarian cancer than that in normal tissues. High C3AR1 expression predicted adverse clinical outcomes. KEGG and GO analysis showed that the biological processes of C3AR1 in ovarian cancer are mainly involved in T cell activation, cytokine and chemokine activation. C3AR1 expression was positively correlated with chemokines and their receptors in the tumor microenvironment, such as CCR1(R = 0.83), IL10RA (R = 0.92), and INFG (R = 0.74). In addition, increased C3AR1 expression predicted more infiltration of tumor-associated macrophages, dendritic cell and CD8 + T cell. Some important m6A regulators, such as IGF2BP2, ALKBH5, IGFBP3 and METL14, are significantly positively or negatively correlated with C3AR1. Finally, overexpression of C3AR1 significantly increased proliferation of SKOV3 cells.

Conclusion

In summary, our study suggested that C3AR1 is associated with the prognosis and immune cell infiltration of ovarian cancer, and is a promising immunotherapeutic target.
TrEMOLO: accurate transposable element allele frequency estimation using long-read sequencing data combining assembly and mapping-based approaches
Authors: Mohamed Mourdas , Sabot François , Varoqui Marion , Mugat Bruno , Audouin Katell , Pélisson Alain , Fiston-Lavier Anna-Sophie , Chambeyron Séverine
Published: April 2023

Transposable Element MOnitoring with LOng-reads (TrEMOLO) is a new software that combines assembly- and mapping-based approaches to robustly detect genetic elements called transposable elements (TEs). Using high- or low-quality genome assemblies, TrEMOLO can detect most TE insertions and deletions and estimate their allele frequency in populations. Benchmarking with simulated data revealed that TrEMOLO outperforms other state-of-the-art computational tools. TE detection and frequency estimation by TrEMOLO were validated using simulated and experimental datasets. Therefore, TrEMOLO is a comprehensive and suitable tool to accurately study TE dynamics. TrEMOLO is available under GNU GPL3.0 at https://github.com/DrosophilaGenomeEvolution/TrEMOLO.
A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer
Authors: Mayoh Chelsea , Gifford Andrew J. , Terry Rachael , Lau Loretta M. S. , Wong Marie , Rao Padmashree , Shai-Hee Tyler , Saletta Federica , Khuong-Quang Dong-Anh , Qin Vicky , Mateos Marion K. , Meyran Deborah , Miller Katherine E. , Yuksel Aysen , Mould Emily V. A. , Bowen-James Rachel , Govender Dinisha , Senapati Akanksha , Zhukova Nataliya , Omer Natacha , Dholaria Hetal , Alvaro Frank , Tapp Heather , Diamond Yonatan , Pozza Luciano Dalla , Moore Andrew S. , Nicholls Wayne , Gottardo Nicholas G. , McCowage Geoffrey , Hansford Jordan R. , Khaw Seong-Lin , Wood Paul J. , Catchpoole Daniel , Cottrell Catherine E. , Mardis Elaine R. , Marshall Glenn M. , Tyrrell Vanessa , Haber Michelle , Ziegler David S. , Vittorio Orazio , Trapani Joseph A. , Cowley Mark J. , Neeson Paul J. , Ekert Paul G.
Published: April 2023

Background

Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers.

Methods

We combined immunohistochemistry (IHC) with RNA sequencing and whole-genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+T-cell infiltration of the TIME. Furthermore, we explored transcriptional features of immune archetypes and T-cell receptor sequencing diversity, assessed the relationship between CD8+and CD4+abundance by IHC and deconvolution predictions and assessed the common adult biomarkers such as neoantigen load and TMB.

Results

A novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells.

Conclusions

Our data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME.
Crotonylation of GAPDH regulates human embryonic stem cell endodermal lineage differentiation and metabolic switch
Authors: Zhang Jingran , Shi Guang , Pang Junjie , Zhu Xing , Feng Qingcai , Na Jie , Ma Wenbin , Liu Dan , Songyang Zhou
Published: April 2023

Background

Post-translational modifications of proteins are crucial to the regulation of their activity and function. As a newly discovered acylation modification, crotonylation of non-histone proteins remains largely unexplored, particularly in human embryonic stem cells (hESCs).

Methods

We investigated the role of crotonylation in hESC differentiation by introduce crotonate into the culture medium of GFP tagged LTR7 primed H9 cell and extended pluripotent stem cell lines. RNA-seq assay was used to determine the hESC transcriptional features. Through morphological changes, qPCR of pluripotent and germ layer-specific gene markers and flow cytometry analysis, we determined that the induced crotonylation resulted in hESC differentiating into the endodermal lineage. We performed targeted metabolomic analysis and seahorse metabolic measurement to investigate the metabolism features after crotonate induction. Then high-resolution tandem mass spectrometry (LC–MS/MS) revealed the target proteins in hESCs. In addition, the role of crotonylated glycolytic enzymes (GAPDH and ENOA) was evaluated by in vitro crotonylation and enzymatic activity assays. Finally, we used knocked-down hESCs by shRNA, wild GAPDH and GAPDH mutants to explore potential role of GAPDH crotonylation in regulating human embryonic stem cell differentiation and metabolic switch.

Result

We found that induced crotonylation in hESCs resulted in hESCs of different pluripotency states differentiating into the endodermal lineage. Increased protein crotonylation in hESCs was accompanied by transcriptomic shifts and decreased glycolysis. Large-scale crotonylation profiling of non-histone proteins revealed that metabolic enzymes were major targets of inducible crotonylation in hESCs. We further discovered GAPDH as a key glycolytic enzyme regulated by crotonylation during endodermal differentiation from hESCs.

Conclusions

Crotonylation of GAPDH decreased its enzymatic activity thereby leading to reduced glycolysis during endodermal differentiation from hESCs.
Human cerebral organoids: the ethical stance of scientists
Authors: Lavazza Andrea , Chinaia Alice Andrea
Published: April 2023

Background

Human cerebral organoids (HCOs) offer unprecedented opportunities to study the human brain in vitro, but they also raise important ethical concerns. Here we report the first systematic analysis of scientists’ stance within the ethical debate.

Method

Twenty-one in-depth semi-structured interviews were analyzed through a constant comparative method to highlight how the ethical concerns filter in the laboratory.

Results

The results suggest that the potential emergence of consciousness is not yet seen with concern. However, there are some features of HCO research that need to be better accounted for. Communication to the public, the use of terms such as “mini-brains”, and informed consent appear to be the most pressing concerns of the scientific community. Nonetheless, respondents generally showed a positive attitude toward the ethical discussion, recognizing its value and the necessity of constant ethical scrutiny over scientific advancements.

Conclusions

This research paves the way for a better-informed dialogue between scientists and ethicists, highlighting the issues to be addressed whenever scholars of different backgrounds and interests meet.
Albumin-to-fibrinogen ratio is an independent predictor of corticosteroid response and prognosis in patients with IgA nephropathy
Authors: Zhang Yu , Man Liping
Published: April 2023

Background

The objective of this study was to investigate whether the albumin-to-fibrinogen ratio (AFR) can predict corticosteroid response and prognosis prediction among IgA nephropathy (IgAN) patients.

Methods

Eligible participants with diagnosed IgAN who were scheduled to receive corticosteroid therapy for persistent proteinuria were recruited. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of AFR or estimated glomerular filtration rate (eGFR) for corticosteroid response in IgAN patients. Risk factors for corticosteroid response and prognosis were validated using univariate and multivariate Cox proportional analyses.

Results

AFR and eGFR were both effective predictors of corticosteroid response in IgAN patients, with area under the curve (AUC) values of 0.686 and 0.643, respectively (P < 0.001 and P = 0.002). Baseline AFR level at biopsy was an independent risk factor for remission after corticosteroid therapy (HR: 2.38, 95% CI 1.32–4.07, P = 0.015), 50% decline in eGFR (HR: 0.78, 95% CI 0.69–0.89, P = 0.025), kidney failure (HR: 2.46, 95%CI 1.16–3.71, P = 0.016), and a composite event (HR: 2.13, 95%CI 1.28–3.34, P = 0.009) in IgAN patients.

Conclusions

AFR level at biopsy was a potential predictor of corticosteroid response and prognosis among IgAN patients.
Differential pathways to disordered eating for immigrant and native adolescents in Taiwan
Authors: Chen Duan-Rung , Lin Li-Yin , Levin Brianna
Published: April 2023

Background

Few studies have investigated disparities in disordered eating between new immigrant and native adolescents in Taiwan. This study examines the differential pathways to disordered eating in these two populations.

Methods

This cross-sectional study analyzed data collected from March to June 2019. In total, 729 adolescents aged between 13 and 16 years recruited from 37 classes in 3 middle schools in New Taipei City were included in the final analysis. Standardized assessment tools measured disordered eating (EAT-26) and psychological distress (BSRS-5). Generalized structural equation modeling was used to conduct the path analysis.

Results

The prevalence of disordered eating was significantly higher in immigrant adolescents than in their native counterparts. Multipath models indicated that weight-teasing driven by overweight and obese status and weight overestimation could lead to disordered eating through psychological distress; however, the pathways differed for the two groups studied. Family weigh-teasing indirectly leads to disordered eating through psychological distress for native adolescents; by contrast, for immigrant adolescents, friend weigh-teasing indirectly leads to disordered eating through psychological distress. Additionally, weight overestimation directly leads to disordered eating and indirectly through psychological distress to disordered eating for immigrant adolescents.

Conclusion

This study offers a plausible explanation of the differences in the paths to disordered eating between immigrant and native adolescents in Taiwan, which was not reported previously. The study urges the need for school-based prevention programs to improve immigrant students’ mental health.
Transcriptomic analysis: the protection of over-expression thioredoxin reductase 1 in Parkinson’s disease
Authors: Liu Zihua , Ye Qiang , Jiang Ying
Published: April 2023

Background

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The pathologic characteristic feature is the loss of dopaminergic neurons in the substantia nigra (SN). However, the biochemical mechanisms are unclear.

A large number of studies have shown that oxidative damage is the primary cause of PD. Hence, antioxidants could become a suitable option to treat PD. The thioredoxin (Trx) system represents a useful, potentially disease-relevant oxidation–reduction system. Thioredoxin reductase 1 (TR1) is a significant component of the Trx system.

Methods

The overexpression lentivirus (LV) or LV-TR1 in the TR1-A53T model of PD by the stereotactic brain, and successful overexpression of LV or LV-TR1 in the MPP+-induced cellular model by LV or LV-TR1 transfection.

Results

We confirmed that interleukin-7 mRNA levels increased in MPP+ compared to that in the control and MPP+-TR1 groups using quantitative polymerase chain reaction. The γ-H2AX level was increased in the Tg-A53T group compared to that in the TR1-A53T group by western blotting. The expression of Na+-K+-ATP was decreased in the MPP+ group compared to that in the control and MPP+-TR1 groups by high content screening. Tg-A53T(the C57BL/6 mice transferred with mutant human a-syn); TR1-A53T(A53T mice which were injected TR1-LV 2 µl in SNc on two sides with minipump).The mice were fed for 10 months. control (the N2a cells cultivated with DMEM); MPP+(the N2a cells dealt with MPP+(1 mM) 48 h), MPP+-LV (the N2a cells over-expressed LV for 24 h then dealt with MPP+(1 mM) 48 h). MPP+-TR1(the N2a cell over-expressed TR1-LV for 24 h then dealt with MPP+(1 mM) 48 h).

From the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we confirmed that the overexpression of TR1 in SN pars compacta cells decreased oxidative stress, apoptosis, DNA damage, and inflammatory response and increased NADPH, Na+-K+-ATP, and immune response in this PD model.

Conclusions

Our study shows that overexpressed TR1 can be developed as a neuroprotective agent for PD. Therefore, our findings demonstrate a new targeted protein for the treatment of PD.
Urban freight policy maturity and sustainable logistics: are they related?
Authors: Cowie Jonathan , Fisken Keith
Published: April 2023

Problems associated with urban freight are well known and documented in the academic literature, particularly with regards to the impact on air quality and general intrusion of public space. As a defining principle however, urban freight has generally been left solely to operate on free market principles, with policy interventions generally being solely ‘problem’ focused. Given the underlying economics of freight transport, and particularly the cost advantages of road-based transport, intervention by public bodies is clearly a critical issue, however to date has received limited attention in the urban freight research literature. The aim of the current research is to examine if there is any relationship between the extent of local authorities’ freight policy development and the success of a policy driven (green) urban freight pilot initiative. This is based on five city case studies located across Northern Europe and uses an adapted form of Kiba-Janiak (Res Transp Bus Manag 24:4–16, 2017, https://doi.org/10.1016/j.rtbm.2017.05.003) five stages of ‘city maturity’ with regards to urban freight policy development. Each city’s policy framework is mapped onto one of these states of maturity. The success of the pilots in each city is then matched against the maturity of the policy framework. Taken at face value, the results show little correlation between the two, and hence the success of any initiative would appear to be independent of the policy framework. The real issue however is found to be low urban freight transport policy maturities within the case study sample, specifically a lack of tactical and operational functions, i.e. the ability to actually do something. The concern at the more general level is that what this leads to is policy stagnation.
Kimchi throughout millennia: a narrative review on the early and modern history of kimchi
Authors: Surya Reggie , Nugroho David
Published: April 2023

Kimchi, the traditional fermented vegetable dish from Korea, has been an integral part of the Korean food culture for thousands of years. Today, it is considered as a symbol of identity for Korean people and is globally appraised as a healthy food. The international standard of kimchi was stipulated by the Codex Alimentarius Commission in 2001, and kimjang, the traditional Korean communal activity of making kimchi, was listed as a UNESCO’s Intangible Cultural Heritage of Humanity in 2013. The international recognition that kimchi has today was not obtained easily since there have been international disputes with regard to its standard and originality. Many historical events have shaped the face of kimchi as it is today. Thus, it appears primordial to understand the hallmark historical events defining the development of kimchi from a traditional food consumed by only Koreans in the past to a renowned global healthy food today. This review explores the historical values of kimchi by focusing on both its early and modern history. The early history of kimchi gathered from different classical literature works suggests the existence of kimchi in Korea since thousands of years ago. The modern history of kimchi highlights different events, including the globalization and commercialization of kimchi, the “kimchi wars” against neighboring countries and the international branding of kimchi as a healthy food. Furthermore, this review also discusses the polemics of kimchi, particularly in terms of its originality. Understanding the historical values of kimchi would make people see kimchi not only as an ethnic food from Korea, but also as a valuable global heritage for the world that needs preserving.
Critical pedagogical designs for SETS knowledge co-production: online peer- and problem-based learning by and for early career green infrastructure experts
Authors: Feagan Mathieu , Fork Megan , Gray Geneva , Hamann Maike , Hawes Jason K. , Hiroyasu Elizabeth H. T. , Wilkerson Brooke
Published: April 2023

Despite a growing understanding of the importance of knowledge co-production for just and sustainable urban transformations, early career green infrastructure experts typically lack opportunities to practice transdisciplinary knowledge co-production approaches within their normal training and professional development. However, using online collaboration technologies combined with peer- and problem-based learning can help address this gap by putting early career green infrastructure experts in charge of organizing their own knowledge co-production activities. Using the case study of an online symposia series focused on social-ecological-technological systems approaches to holistic green infrastructure implementation, we discuss how critical pedagogical designs help create favorable conditions for transdisciplinary knowledge co-production. Our work suggests that the early career position offers a unique standpoint from which to better understand the limitations of current institutional structures of expertise, with a view towards their transformation through collective action.
Double-edged sword of biofouling potentials associated with haemocompatibility behaviour: titania nanotube arrays for medical implant surface technology
Authors: Palaniyappan Keethaanjali , S. M. N. Mydin Rabiatul Basria , Widera Darius , Noordin Siti Salmah , Harun Nor Hazliana , Wan Eddis Effendy Wan Nuramiera , Hazan Roshasnorlyza , Sreekantan Srimala
Published: April 2023

Background

Medical implant failures are frequently associated with limitations of the surface technology that lead to biofouling and haemocompatibility issues. Titania nanotube array technology could provide a solution for this existing limitation. The present study describes the biofouling potential using the simulated body fluid model according to ISO 23317-2007 and haemocompatibility profiles according to ISO 10993-4 guidelines. Further haemocompatibility profiles were also assessed by evaluating full blood count, coagulation assays, haemolytic rate, whole blood clotting factor, platelet profiles, and FESEM characterization.

Result

Titania nanotube array nanosurface was found to present with better apatite biofouling and hydrophilic potential compared to bare titanium foil. Furthermore, good compatibility behaviour was observed based on the haemocompatibility profiles where no signs of thrombogenesis and haemolysis risks were observed. Titania nanotube array reduced fibrinogen adsorption, red blood cell and platelet adhesion and activation, which could be associated with detrimental biofouling properties.

Conclusion

Titania nanotube array could possess a double-edged sword of biofouling potentials that resist detrimental biofouling properties associated with thrombogenesis and haemolysis risk. It also provides better apatite biofouling potential for improved tissue and osseointegration activities. Knowledge from this study provides a better understanding of medical implant surface technology.

Graphical Abstract
President's Page: Energy transition as an opportunity for Latin American geoscientists, companies, and the people
Authors: Gristo Pablo
Published: April 2023

I am old enough to have experienced a change in thinking among oil and gas (O&G) executives and professionals — from a general skepticism, or even denial, to a more open mind toward climate change and carbon emissions. Perhaps arising as a late and uncomfortable reaction to scientific consensus and demands from consumers, shareholders, and the government, the energy industry nevertheless has come to acknowledge the impact it has on the environment and is taking proactive steps to counter the impact. This change in thinking also represents a business opportunity. O&G and service companies have a unique competence in dealing with the large uncertainty and extreme capital intensity of energy projects. They are experienced in scaling up technologies and developing cost-effective solutions. As such, they can make a big difference in a low-carbon and renewable future. In what some might view as a paradox, O&G practitioners can become the champions of the energy transition.