bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of disulfidptosis related subtypes, characterization of tumor microenvironment infiltration, and development of DRG prognostic prediction model in RCC, in which MSH3 is a key gene during disulfidptosis
Authors: Xu Kai , Zhang Ye , Yan Zhiwei , Wang Yuchan , Li Yanze , Qiu Qiangmin , Du Yang , Chen Zhiyuan , Liu Xiuheng
Published: June 2023

Disulfidptosis is a newly discovered mode of cell death induced by disulfide stress. However, the prognostic value of disulfidptosis-related genes (DRGs) in renal cell carcinoma (RCC) remains to be further elucidated. In this study, consistent cluster analysis was used to classify 571 RCC samples into three DRG-related subtypes based on changes in DRGs expression. Through univariate regression analysis and LASSO-Cox regression analysis of differentially expressed genes (DEGs) among three subtypes, we constructed and validated a DRG risk score to predict the prognosis of patients with RCC, while also identifying three gene subtypes. Analysis of DRG risk score, clinical characteristics, tumor microenvironment (TME), somatic cell mutations, and immunotherapy sensitivity revealed significant correlations between them. A series of studies have shown that MSH3 can be a potential biomarker of RCC, and its low expression is associated with poor prognosis in patients with RCC. Last but not least, overexpression of MSH3 promotes cell death in two RCC cell lines under glucose starvation conditions, indicating that MSH3 is a key gene in the process of cell disulfidptosis. In summary, we identify potential mechanism of RCC progression through DRGs -related tumor microenvironment remodeling. In addition, this study has successfully established a new disulfidptosis-related genes prediction model and discovered a key gene MSH3. They may be new prognostic biomarkers for RCC patients, provide new insights for the treatment of RCC patients, and may inspire new methods for the diagnosis and treatment of RCC patients.
Differential impact of two major polychaete guilds on microbial communities in marine sediments: a microcosm study
Authors: Deng Longhui , Fiskal Annika , Bölsterli Damian , Meier Dimitri , Meile Christof , Lever Mark Alexander
Published: June 2023

Even though sediment macrofauna are widespread in the global seafloor, the influence of these fauna on microbial communities that drive sediment biogeochemical cycles remains poorly understood. According to recent field investigations, macrofaunal activities control bacterial and archaeal community structure in surface sediments, but the inferred mechanisms have not been experimentally verified. Here we use laboratory microcosms to investigate how activities of two major polychaete guilds, the lugworms, represented by Abarenicola pacifica, and the clamworms, represented by Nereis vexillosa, influence microbial communities in coastal sediments. A. pacifica treatments show >tenfold increases in microbial cell-specific consumption rates of oxygen and nitrate, largely due to the strong ventilation activity of A. pacifica. While ventilation resulted in clearly elevated percentages of nitrifying archaea (Nitrosopumilus spp.) in surface sediments, it only minorly affected bacterial community composition. By comparison, reworking – mainly by deposit-feeding of A. pacifica – had a more pronounced impact on microorganismal communities, significantly driving down abundances of Bacteria and Archaea. Within the Bacteria, lineages that have been linked to the degradation of microalgal biomass (e.g., Flavobacteriaceae and Rhodobacteraceae), were especially affected, consistent with the previously reported selective feeding of A. pacifica on microalgal detritus. In contrast, N. vexillosa, which is not a deposit feeder, did not significantly influence microbial abundances or microbial community structure. This species also only had a relatively minor impact on rates of oxygen and nitrogen cycling, presumably because porewater exchanges during burrow ventilation by this species were mainly restricted to sediments immediately surrounding the burrows. Collectively our analyses demonstrate that macrofauna with distinct bioturbation modes differ greatly in their impacts on microbial community structure and microbial metabolism in marine sediments.
A regional map of mangrove extent for Myanmar, Thailand, and Cambodia shows losses of 44% by 1996
Authors: Baltezar Priscilla , Murillo-Sandoval Paulo J. , Cavanaugh Kyle C. , Doughty Cheryl , Lagomasino David , Tieng Thida , Simard Marc , Fatoyinbo Temilola
Published: June 2023

Southeast Asia is home to some of the planet’s most carbon-dense and biodiverse mangrove ecosystems. There is still much uncertainty with regards to the timing and magnitude of changes in mangrove cover over the past 50 years. While there are several regional to global maps of mangrove extent in Southeast Asia over the past two decades, data prior to the mid-1990s is limited due to the scarcity of Earth Observation (EO) data of sufficient quality and the historical limitations to publicly available EO. Due to this literature gap and research demand in Southeast Asia, we conducted a classification of mangrove extent using Landsat 1-2 MSS Tier 2 data from 1972 to 1977 for three Southeast Asian countries: Myanmar, Thailand, and Cambodia. Mangrove extent land cover maps were generated using a Random Forest machine learning algorithm that effectively mapped a total of 15,420.51 km2. Accuracy assessments indicated that the classification for the mangrove and non-mangrove class had a producer’s accuracy of 80% and 98% user’s accuracy of 90% and 96%, and an overall accuracy of 95%. We found a decline of 6,830 km2 between the 1970s and 2020, showing that 44% of the mangrove area in these countries has been lost in the past 48 years. Most of this loss occurred between the 1970s and 1996; rates of deforestation declined dramatically after 1996. This study also elaborated on the nature of mangrove change within the context of the social and political ecology of each case study country. We urge the remote sensing community to empathetically consider the local need of those who depend on mangrove resources when discussing mangrove loss drivers.
Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort
Authors: Conticini Edoardo , Naveen R. , Sen Parikshit , Singh Mantabya , Rathore Upendra , Anuja Anamika Kumari , Rai Mohit Kumar , Yadav Brijesh , Prasad Narayan , Agarwal Vikas , Gupta Latika
Published: June 2023

Introduction

The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration.

Materials and methods

Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula.

Results

Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes.

Discussion

This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.
Analysis between ABO blood group and clinical outcomes in COVID-19 patients and the potential mediating role of ACE2
Authors: Zeng Xianfei , Fan Hongyan , Kou Jinxin , Lu Dongxue , Huang Fang , Meng Xi , Liu Haiying , Li Zhuo , Tang Mei , Zhang Jing , Liu Nannan , Hu Xingbin
Published: June 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most common coronavirus that causes large-scale infections worldwide. Currently, several studies have shown that the ABO blood group is associated with coronavirus disease 2019 (COVID-19) infection and some studies have also suggested that the infection of COVID-19 may be closely related to the interaction between angiotensin-converting enzyme 2 (ACE2) and blood group antigens. However, the relationship between blood type to clinical outcome in critically ill patients and the mechanism of action is still unclear. The current study aimed to examine the correlation between blood type distribution and SARS-CoV-2 infection, progression, and prognosis in patients with COVID-19 and the potential mediating role of ACE2. With 234 patients from 5 medical centers and two established cohorts, 137 for the mild cohort and 97 for the critically ill cohort, we found that the blood type A population was more sensitive to SARS-CoV-2, while the blood type distribution was not relevant to acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality in COVID-19 patients. Further study showed that the serum ACE2 protein level of healthy people with type A was significantly higher than that of other blood groups, and type O was the lowest. The experimental results of spike protein binding to red blood cells also showed that the binding rate of people with type A was the highest, and that of people with type O was the lowest. Our finding indicated that blood type A may be the biological marker for susceptibility to SARS-CoV-2 infection and may be associated with potential mediating of ACE2, but irrelevant to the clinical outcomes including ARDS, AKI, and death. These findings can provide new ideas for clinical diagnosis, treatment, and prevention of COVID-19.
Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus
Authors: Fenton Kristin Andreassen , Pedersen Hege Lynum
Published: June 2023

There are several autoimmune and rheumatic diseases affecting different organs of the human body. Multiple sclerosis (MS) mainly affects brain, rheumatoid arthritis (RA) mainly affects joints, Type 1 diabetes (T1D) mainly affects pancreas, Sjogren’s syndrome (SS) mainly affects salivary glands, while systemic lupus erythematosus (SLE) affects almost every organ of the body. Autoimmune diseases are characterized by production of autoantibodies, activation of immune cells, increased expression of pro-inflammatory cytokines, and activation of type I interferons. Despite improvements in treatments and diagnostic tools, the time it takes for the patients to be diagnosed is too long, and the main treatment for these diseases is still non-specific anti-inflammatory drugs. Thus, there is an urgent need for better biomarkers, as well as tailored, personalized treatment. This review focus on SLE and the organs affected in this disease. We have used the results from various rheumatic and autoimmune diseases and the organs involved with an aim to identify advanced methods and possible biomarkers to be utilized in the diagnosis of SLE, disease monitoring, and response to treatment.
Association between the mental domain of the comprehensive geriatric assessment and prolonged length of stay in hospitalized older adults with mild to moderate frailty
Authors: Yu Yung-Chen , Su Chien-Chou , Yang Deng-Chi
Published: June 2023

Introduction

Previous researches have shown the risk factors of prolonged length of stay (PLOS) in hospitalized older adults, but it is unclear what are the risk factors of PLOS in hospitalized older adults with mild to moderate frailty.

Objective

To identify the risk factors of PLOS in hospitalized older adults with mild to moderate frailty.

Methods

We recruited adults aged ≥65 years old with mild to moderate frailty admitted to a tertiary medical center in the southern Taiwan from June 2018 to September 2018. Each individual underwent a structural questionnaire interview within 72 h after admission and 72 h after discharge. The data were collected face-to-face, including demographic characteristics, comorbidities, length of stay (LOS), and multiple domains of the comprehensive geriatric assessment. The main outcome was PLOS.

Results

Individuals who had two or more drugs, were female, did not have cognitive impairment and had a Geriatric Depression Scale score ≥ 1 had a higher risk of PLOS (probability = 0.81), and these individuals accounted for 29% of the overall study population. Among male individuals younger than 87 years old, those with cognitive impairment had a higher risk of PLOS (probability = 0.76), and among male individuals without cognitive impairment, living alone was associated with a higher risk of PLOS (probability = 0.88).

Conclusion

Early detection and management of mood and cognition in older adults, together with comprehensive discharge planning and transition care, may be an important part of reducing LOS in hospitalized older adults with mild to moderate frailty.
Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis
Authors: Jud Philipp , Meinitzer Andreas , Strohmaier Heimo , Arefnia Behrouz , Wimmer Gernot , Obermayer-Pietsch Barbara , Foris Vasile , Kovacs Gabor , Odler Balazs , Moazedi-Fürst Florentine , Brodmann Marianne , Hafner Franz
Published: June 2023

Objectives

Pathways contributing to endothelial dysfunction in patients with limited cutaneous systemic sclerosis (lcSSc) are largely unknown. The aim of this study was to investigate potential associations of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathy-related changes in patients with lcSSc and early-stage vasculopathy.

Methods

Amino acids, calciotropic parameters, including 25-hydroxyvitamin D and parathyroid hormone (PTH), and bone turnover parameters, including osteocalcin and N-terminal peptide of procollagen-3 (P3NP), were measured in 38 lcSSc patients and 38 controls. Endothelial dysfunction was assessed by biochemical parameters, pulse-wave analysis, flow-mediated and nitroglycerine-mediated dilation. Additionally, vasculopathy-related and SSc-specific clinical changes including capillaroscopic, skin, renal, pulmonary, gastrointestinal and periodontal parameters were recorded.

Results

No significant differences in amino acids, calciotropic and bone turnover parameters were observed between lcSSc patients and controls. In patients with lcSSc, several significant correlations were found between selected amino acids, parameters of endothelial dysfunction, vasculopathy-related and SSc-specific clinical changes (all with p < 0.05). In addition, significant correlations were observed between PTH and 25-hydroxyvitamin D with homoarginine, and between osteocalcin, PTH and P3NP with modified Rodnan skin score and selected periodontal parameters (all with p < 0.05). Vitamin D deficiency defined as 25-hydroxyvitamin D < 20 ng/ml was associated with the presence of puffy finger (p = 0.046) and early pattern (p = 0.040).

Conclusion

Selected amino acids may affect endothelial function and may be associated to vasculopathy-related and clinical changes in lcSSc patients, while the association with parameters of bone metabolism seems to be minor.
Case report: Duodenal obstruction caused by gastroduodenal artery pseudoaneurysm with hematoma: an unusual case and literature review
Authors: Zhou Yan-Yuan , Wang Shao-Chung , Seak Chen-June , Huang Shu-Wei , Cheng Hao-Tsai
Published: June 2023

Visceral artery pseudoaneurysm is a rare disease that most commonly occurs in male patients in their 50s, with gastroduodenal artery (GDA) pseudoaneurysm accounting for only 1.5% of these. The treatment options generally include open surgery and endovascular treatment. In 40 cases of GDA pseudoaneurysm from 2001 to 2022, endovascular therapy was the mainstay of treatment in 30 cases, and most of them (77%) were treated by coil embolization. Our case report describes a 76-year-old female patient with a GDA pseudoaneurysm, which was treated by endovascular embolization using liquid embolic agent N-butyl-2-cyanoacrylate (NBCA) alone. This is the first time this treatment strategy has been used for GDA pseudoaneurysm. We demonstrate a successful outcome with this unique treatment. The successful experience of our case may provide a new treatment strategy for this rare disease.
Generation and characterization of chimeric Tembusu viruses containing pre-membrane and envelope genes of Japanese encephalitis virus
Authors: Xu Bangfeng , Liu Xingpo , Yan Dawei , Teng Qiaoyang , Yuan Chunxiu , Zhang Zhifei , Liu Qinfang , Li Zejun
Published: June 2023

Since its outbreak in 2010, Tembusu virus (TMUV) has spread widely throughout China and Southeast Asia, causing significant economic losses to the poultry industry. In 2018, an attenuated vaccine called FX2010-180P (180P) was licensed for use in China. The 180P vaccine has demonstrated its immunogenicity and safety in mice and ducks. The potential use of 180P as a backbone for flavivirus vaccine development was explored by replacing the pre-membrane (prM) and envelope (E) genes of the 180P vaccine strain with those of Japanese encephalitis virus (JEV). Two chimeric viruses, 180P/JEV-prM-E and 180P/JEV-prM-ES156P with an additional E protein S156P mutation were successfully rescued and characterized. Growth kinetics studies showed that the two chimeric viruses replicated to similar titers as the parental 180P virus in cells. Animal studies also revealed that the virulence and neuroinvasiveness of the 180P/JEV-prM-E chimeric virus was decreased in mice inoculated intracerebrally (i.c.) and intranasally (i.n.), respectively, compared to the wild-type JEV strain. However, the chimeric 180P/JEV-prM-E virus was still more virulent than the parent 180P vaccine in mice. Additionally, the introduction of a single ES156P mutation in the chimeric virus 180P/JEV-prM-ES156P further attenuated the virus, which provided complete protection against challenge with a virulent JEV strain in the mouse model. These results indicated that the FX2010-180P could be used as a promising backbone for flavivirus vaccine development.
Linking microbial contamination to food spoilage and food waste: the role of smart packaging, spoilage risk assessments, and date labeling
Authors: Karanth Shraddha , Feng Shuyi , Patra Debasmita , Pradhan Abani K.
Published: June 2023

Ensuring a safe and adequate food supply is a cornerstone of human health and food security. However, a significant portion of the food produced for human consumption is wasted annually on a global scale. Reducing harvest and postharvest food waste, waste during food processing, as well as food waste at the consumer level, have been key objectives of improving and maintaining sustainability. These issues can range from damage during processing, handling, and transport, to the use of inappropriate or outdated systems, and storage and packaging-related issues. Microbial growth and (cross)contamination during harvest, processing, and packaging, which causes spoilage and safety issues in both fresh and packaged foods, is an overarching issue contributing to food waste. Microbial causes of food spoilage are typically bacterial or fungal in nature and can impact fresh, processed, and packaged foods. Moreover, spoilage can be influenced by the intrinsic factors of the food (water activity, pH), initial load of the microorganism and its interaction with the surrounding microflora, and external factors such as temperature abuse and food acidity, among others. Considering this multifaceted nature of the food system and the factors driving microbial spoilage, there is an immediate need for the use of novel approaches to predict and potentially prevent the occurrence of such spoilage to minimize food waste at the harvest, post-harvest, processing, and consumer levels. Quantitative microbial spoilage risk assessment (QMSRA) is a predictive framework that analyzes information on microbial behavior under the various conditions encountered within the food ecosystem, while employing a probabilistic approach to account for uncertainty and variability. Widespread adoption of the QMSRA approach could help in predicting and preventing the occurrence of spoilage along the food chain. Alternatively, the use of advanced packaging technologies would serve as a direct prevention strategy, potentially minimizing (cross)contamination and assuring the safe handling of foods, in order to reduce food waste at the post-harvest and retail stages. Finally, increasing transparency and consumer knowledge regarding food date labels, which typically are indicators of food quality rather than food safety, could also contribute to reduced food waste at the consumer level. The objective of this review is to highlight the impact of microbial spoilage and (cross)contamination events on food loss and waste. The review also discusses some novel methods to mitigate food spoilage and food loss and waste, and ensure the quality and safety of our food supply.
Evaluation of Leptospira interrogans knockdown mutants for LipL32, LipL41, LipL21, and OmpL1 proteins
Authors: Fernandes Luis G. V. , Teixeira Aline F. , Nascimento Ana L. T. O.
Published: June 2023

Introduction

Leptospirosis is a worldwide zoonosis caused by pathogenic and virulent species of the genus Leptospira, whose pathophysiology and virulence factors remain widely unexplored. Recently, the application of CRISPR interference (CRISPRi) has allowed the specific and rapid gene silencing of major leptospiral proteins, favoring the elucidation of their role in bacterial basic biology, host-pathogen interaction and virulence. Episomally expressed dead Cas9 from the Streptococcus pyogenes CRISPR/Cas system (dCas9) and single-guide RNA recognize and block transcription of the target gene by base pairing, dictated by the sequence contained in the 5′ 20-nt sequence of the sgRNA.

Methods

In this work, we tailored plasmids for silencing the major proteins of L. interrogans serovar Copenhageni strain Fiocruz L1-130, namely LipL32, LipL41, LipL21 and OmpL1. Double- and triple-gene silencing by in tandem sgRNA cassettes were also achieved, despite plasmid instability.

Results

OmpL1 silencing resulted in a lethal phenotype, in both L. interrogans and saprophyte L. biflexa, suggesting its essential role in leptospiral biology. Mutants were confirmed and evaluated regarding interaction with host molecules, including extracellular matrix (ECM) and plasma components, and despite the dominant abundance of the studied proteins in the leptospiral membrane, protein silencing mostly resulted in unaltered interactions, either because they intrinsically display low affinity to the molecules assayed or by a compensation mechanism, where other proteins could be upregulated to fill the niche left by protein silencing, a feature previously described for the LipL32 mutant. Evaluation of the mutants in the hamster model confirms the augmented virulence of the LipL32 mutant, as hinted previously. The essential role of LipL21 in acute disease was demonstrated, since the LipL21 knockdown mutants were avirulent in the animal model, and even though mutants could still colonize the kidneys, they were found in markedly lower numbers in the animals' liver. Taking advantage of higher bacterial burden in LipL32 mutant-infected organs, protein silencing was demonstrated in vivo directly in leptospires present in organ homogenates.

Discussion

CRISPRi is now a well-established, attractive genetic tool that can be applied for exploring leptospiral virulence factors, leading to the rational for designing more effective subunit or even chimeric recombinant vaccines.
A genetic regulatory see-saw of biofilm and virulence in MRSA pathogenesis
Authors: Patel Hardi , Rawat Seema
Published: June 2023

Staphylococcus aureus is one of the most common opportunistic human pathogens causing several infectious diseases. Ever since the emergence of the first methicillin-resistant Staphylococcus aureus (MRSA) strain decades back, the organism has been a major cause of hospital-acquired infections (HA-MRSA). The spread of this pathogen across the community led to the emergence of a more virulent subtype of the strain, i.e., Community acquired Methicillin resistant Staphylococcus aureus (CA-MRSA). Hence, WHO has declared Staphylococcus aureus as a high-priority pathogen. MRSA pathogenesis is remarkable because of the ability of this “superbug” to form robust biofilm both in vivo and in vitro by the formation of polysaccharide intercellular adhesin (PIA), extracellular DNA (eDNA), wall teichoic acids (WTAs), and capsule (CP), which are major components that impart stability to a biofilm. On the other hand, secretion of a diverse array of virulence factors such as hemolysins, leukotoxins, enterotoxins, and Protein A regulated by agr and sae two-component systems (TCS) aids in combating host immune response. The up- and downregulation of adhesion genes involved in biofilm formation and genes responsible for synthesizing virulence factors during different stages of infection act as a genetic regulatory see-saw in the pathogenesis of MRSA. This review provides insight into the evolution and pathogenesis of MRSA infections with a focus on genetic regulation of biofilm formation and virulence factors secretion.
Characterization of an Enterococcus faecalis bacteriophage SFQ1 as a potential therapeutic agent
Authors: Song Fuqiang , Sheng Jun , Tan Jishan , Xie Huajie , Wang Xiaoyu , Guo Wenqiong
Published: June 2023

Enterococcus faecalis is a well-established resident of the human gastrointestinal tract and is also a major cause of human infections. Unfortunately, therapeutic options for E. faecalis infections remain limited, particularly with the emergence of vancomycin-resistant strains in hospital settings. Consequently, there has been a renewed interest in phage therapy as an alternative to antibiotics. In this study, we have isolated a bacteriophage, vB_EfaS-SFQ1, from hospital sewage, which effectively infects E. faecalis strain EFS01. Phage SFQ1 is a siphovirus and exhibits a relatively broad host range. Furthermore, it has a short latent period of approximately 10 min and a large burst size of about 110 PFU/cell at a multiplicity of infection (MOI) of 0.01, and it could effectively disrupt the biofilms formed by E. faecalis. Thus, this study provides a detailed characterization of E. faecalis phage SFQ1, which has great potential for treating E. faecalis infections.
P1 of turnip mosaic virus interacts with NOD19 for vigorous infection
Authors: Bello Esther O. , Yang Yingshuai , Fang Yue , Chai Mengzhu , Jiang Xue , Luan Yameng , Wang Yuting , Guo Yating , Wu Xiao-Yun , Cheng Xiaofei , Wu Xiao-Xia
Published: June 2023

P1 protein, the most divergent protein of virus members in the genus Potyvirus of the family Potyviridae, is required for robust infection and host adaptation. However, how P1 affects viral proliferation is still largely elusive. In this work, a total number of eight potential P1-interacting Arabidopsis proteins were identified by the yeast-two-hybrid screening using the turnip mosaic virus (TuMV)-encoded P1 protein as the bait. Among which, the stress upregulated NODULIN 19 (NOD19) was selected for further characterization. The bimolecular fluorescent complementation assay confirmed the interaction between TuMV P1 and NOD19. Expression profile, structure, and subcellular localization analyses showed that NOD19 is a membrane-associated protein expressed mainly in plant aerial parts. Viral infectivity assay showed that the infection of turnip mosaic virus and soybean mosaic virus was attenuated in the null mutant of Arabidopsis NOD19 and NOD19-knockdown soybean seedlings, respectively. Together, these data indicate that NOD19 is a P1-interacting host factor required for robust infection.
Pharmacological effects and mechanisms of YiYiFuZi powder in chronic heart disease revealed by metabolomics and network pharmacology
Authors: Wang Yuming , Li Xue , Qi Min , Li Xiaokai , Zhang Fangfang , Wang Yuyu , Wu Junke , Shu Lexin , Fan Simiao , Li Yunfei , Li Yubo
Published: June 2023

Introduction: YiYiFuZi powder (YYFZ) is a classical formula in Chinese medicine, which is commonly used clinically for the treatment of Chronic Heart Disease (CHD), but it’s pharmacological effects and mechanism of action are currently unclear.

Methods: An adriamycin-induced CHD model rat was established to evaluate the pharmacological effects of YYFZ on CHD by the results of inflammatory factor level, histopathology and echocardiography. Metabolomic studies were performed on rat plasma using UPLC-Q-TOF/MS to screen biomarkers and enrich metabolic pathways; network pharmacology analysis was also performed to obtain the potential targets and pathways of YYFZ for the treatment of CHD.

Results: The results showed that YYFZ significantly reduced the levels of TNF-α and BNP in the serum of rats, alleviated the disorder of cardiomyocyte arrangement and inflammatory cell infiltration, and improved the cardiac function of rats with CHD. The metabolomic analysis identified a total of 19 metabolites, related to amino acid metabolism, fatty acid metabolism, and other metabolic pathways. Network pharmacology showed that YYFZ acts through PI3K/Akt signaling pathway, MAPK signaling pathway and Ras signaling pathway.

Discussion: YYFZ treatment of CHD modulates blood metabolic pattern and several protein phosphorylation cascades but importance specific changes for therapeutic effect require further studies.
When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment
Authors: Wenger Mario , Grosse-Kathoefer Sophie , Kraiem Amin , Pelamatti Erica , Nunes Natalia , Pointner Lisa , Aglas Lorenz
Published: June 2023

Toll-like receptors of the human immune system are specialized pathogen detectors able to link innate and adaptive immune responses. TLR ligands include among others bacteria-, mycoplasma- or virus-derived compounds such as lipids, lipo- and glycoproteins and nucleic acids. Not only are genetic variations in TLR-related genes associated with the pathogenesis of allergic diseases, including asthma and allergic rhinitis, their expression also differs between allergic and non-allergic individuals. Due to a complex interplay of genes, environmental factors, and allergen sources the interpretation of TLRs involved in immunoglobulin E-mediated diseases remains challenging. Therefore, it is imperative to dissect the role of TLRs in allergies. In this review, we discuss i) the expression of TLRs in organs and cell types involved in the allergic immune response, ii) their involvement in modulating allergy-associated or -protective immune responses, and iii) how differential activation of TLRs by environmental factors, such as microbial, viral or air pollutant exposure, results in allergy development. However, we focus on iv) allergen sources interacting with TLRs, and v) how targeting TLRs could be employed in novel therapeutic strategies. Understanding the contributions of TLRs to allergy development allow the identification of knowledge gaps, provide guidance for ongoing research efforts, and built the foundation for future exploitation of TLRs in vaccine design.
Computational study of the binding orientation and affinity of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-1 considering the protein flexibility by using molecular dynamics and cross-docking
Authors: Castillo-Campos Luis , Velázquez-Libera José Luis , Caballero Julio
Published: June 2023

The papain-like protease (PLpro) from zoonotic coronaviruses (CoVs) has been identified as a target with an essential role in viral respiratory diseases caused by Severe Acute Respiratory Syndrome-associated coronaviruses (SARS-CoVs). The design of PLpro inhibitors has been proposed as an alternative to developing potential drugs against this disease. In this work, 67 naphthalene-derived compounds as noncovalent PLpro inhibitors were studied using molecular modeling methods. Structural characteristics of the bioactive conformations of these inhibitors and their interactions at the SARS-CoV-1 PLpro binding site were reported here in detail, taking into account the flexibility of the protein residues. Firstly, a molecular docking protocol was used to obtain the orientations of the inhibitors. After this, the orientations were compared, and the recurrent interactions between the PLpro residues and ligand chemical groups were described (with LigRMSD and interaction fingerprints methods). In addition, efforts were made to find correlations between docking energy values and experimentally determined binding affinities. For this, the PLpro was sampled by using Gaussian Accelerated Molecular Dynamics (GaMD), generating multiple conformations of the binding site. Diverse protein conformations were selected and a cross-docking experiment was performed, yielding models of the 67 naphthalene-derived compounds adopting different binding modes. Representative complexes for each ligand were selected to obtain the highest correlation between docking energies and activities. A good correlation (R2 = 0.948) was found when this flexible docking protocol was performed.
Larval zebrafish as a model for studying individual variability in translational neuroscience research
Authors: Jacobs Elina A. K. , Ryu Soojin
Published: June 2023

The larval zebrafish is a popular model for translational research into neurological and psychiatric disorders due to its conserved vertebrate brain structures, ease of genetic and experimental manipulation and small size and scalability to large numbers. The possibility of obtaining in vivo whole-brain cellular resolution neural data is contributing important advances into our understanding of neural circuit function and their relation to behavior. Here we argue that the larval zebrafish is ideally poised to push our understanding of how neural circuit function relates to behavior to the next level by including considerations of individual differences. Understanding variability across individuals is particularly relevant for tackling the variable presentations that neuropsychiatric conditions frequently show, and it is equally elemental if we are to achieve personalized medicine in the future. We provide a blueprint for investigating variability by covering examples from humans and other model organisms as well as existing examples from larval zebrafish. We highlight recent studies where variability may be hiding in plain sight and suggest how future studies can take advantage of existing paradigms for further exploring individual variability. We conclude with an outlook on how the field can harness the unique strengths of the zebrafish model to advance this important impending translational question.
Case report: Hypnic headache responds to agomelatine–a potential prophylactic treatment option
Authors: Xu Sui-yi , Li Ling , Sun Wen-xiu , Shen Jia-yu , Li Chang-xin
Published: June 2023

Introduction

Hypnic headache (HH) is a rare primary headache that is characterized by strict sleep-related attacks. However, the pathophysiology of HH remains unclear. The nocturnal nature of this activity suggests a hypothalamic involvement. The pathogenesis of HH may involve the brain structure that regulates circadian rhythms and is related to an imbalance between hormones, such as melatonin and serotonin. Currently, evidence-based medicine for HH pharmacotherapy is lacking. Acute and prophylactic treatment of HH is based on only a few case reports. Here, we report a case study in which agomelatine showed desirable responsiveness for the prophylactic treatment of HH for the first time.

Case description

We present the case of a 58-year-old woman with a 3-year history of nocturnal left temporal pain that awakened her during the wee hours. Brain magnetic resonance imaging did not reveal any midline structural abnormalities associated with circadian rhythms. Polysomnography revealed headache-related awakening at approximately 5:40 am, after the last rapid eye movement phase. No sleep apnea-hypopnea events were observed, without oxygen saturation or blood pressure abnormalities. The patient was prescribed agomelatine 25 mg at bedtime as a prophylactic treatment. In the following month, the frequency and severity of the headaches decreased by 80%. After 3 months, the patient’s headache completely resolved, and the medication was discontinued.

Conclusion

HH only occurs during sleep in the real world, leading to substantial sleep disturbances in older populations. Headache center neurologists need to focus on the prophylactic treatment of patients before bedtime to avoid nocturnal awakening. Agomelatine is a potential prophylactic treatment option for patients with HH.
Overt speech decoding from cortical activity: a comparison of different linear methods
Authors: Le Godais Gaël , Roussel Philémon , Bocquelet Florent , Aubert Marc , Kahane Philippe , Chabardès Stéphan , Yvert Blaise
Published: June 2023

Introduction

Speech BCIs aim at reconstructing speech in real time from ongoing cortical activity. Ideal BCIs would need to reconstruct speech audio signal frame by frame on a millisecond-timescale. Such approaches require fast computation. In this respect, linear decoder are good candidates and have been widely used in motor BCIs. Yet, they have been very seldomly studied for speech reconstruction, and never for reconstruction of articulatory movements from intracranial activity. Here, we compared vanilla linear regression, ridge-regularized linear regressions, and partial least squares regressions for offline decoding of overt speech from cortical activity.

Methods

Two decoding paradigms were investigated: (1) direct decoding of acoustic vocoder features of speech, and (2) indirect decoding of vocoder features through an intermediate articulatory representation chained with a real-time-compatible DNN-based articulatory-to-acoustic synthesizer. Participant's articulatory trajectories were estimated from an electromagnetic-articulography dataset using dynamic time warping. The accuracy of the decoders was evaluated by computing correlations between original and reconstructed features.

Results

We found that similar performance was achieved by all linear methods well above chance levels, albeit without reaching intelligibility. Direct and indirect methods achieved comparable performance, with an advantage for direct decoding.

Discussion

Future work will address the development of an improved neural speech decoder compatible with fast frame-by-frame speech reconstruction from ongoing activity at a millisecond timescale.
Inhibition of synaptic transmission by anandamide precursor 20:4-NAPE is mediated by TRPV1 receptors under inflammatory conditions
Authors: Spicarova Diana , Nerandzic Vladimir , Muzik David , Pontearso Monica , Bhattacharyya Anirban , Nagy Istvan , Palecek Jiri
Published: June 2023

Transient receptor potential ion channel, vanilloid subfamily, type 1 (TRPV1) cation channel, and cannabinoid receptor 1 (CB1) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological pain states. TRPV1 and CB1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20:4-NAPE). We investigated the effect of the anandamide precursor 20:4-NAPE on synaptic activity in naive and inflammatory conditions. Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) from superficial dorsal horn neurons in rat acute spinal cord slices were used. Peripheral inflammation was induced by subcutaneous injection of carrageenan. Under naive conditions, mEPSCs frequency (0.96 ± 0.11 Hz) was significantly decreased after 20 μM 20:4-NAPE application (55.3 ± 7.4%). This 20:4-NAPE-induced inhibition was blocked by anandamide-synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. In addition, the inhibition was prevented by the CB1 receptor antagonist PF 514273 (0.2 μM) but not by the TRPV1 receptor antagonist SB 366791 (10 μM). Under inflammatory conditions, 20:4-NAPE (20 μM) also exhibited a significant inhibitory effect (74.5 ± 8.9%) on the mEPSCs frequency that was prevented by the TRPV1 receptor antagonist SB 366791 but not by PF 514273 application. Our results show that 20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB1 presynaptic receptors, whereas peripheral inflammation changes the underlying mechanism. The switch between TRPV1 and CB1 receptor activation by the AEA precursor 20:4-NAPE during inflammation may play an important role in nociceptive processing, hence the development of pathological pain.
Vitamin D intake and determinants of vitamin D status during pregnancy in The Norwegian Mother, Father and Child Cohort Study
Authors: Amberntsson Anna , Bärebring Linnea , Winkvist Anna , Lissner Lauren , Meltzer Helle Margrete , Brantsæter Anne Lise , Papadopoulou Eleni , Augustin Hanna
Published: June 2023

Background

Norwegian data on vitamin D status among pregnant women indicate a moderate to high prevalence of insufficient vitamin D status (25-hydroxyvitamin D (25OHD) concentrations ≤50  nmol/L). There is a lack of population-based research on vitamin D intake and determinants of 25OHD in pregnant women from northern latitudes. The aims of this study were (1) to evaluate total vitamin D intake from both diet and supplements, (2) to investigate determinants of vitamin D status, and (3) to investigate the predicted response in vitamin D status by total vitamin D intake, in pregnant Norwegian women.

Methods

In total, 2,960 pregnant women from The Norwegian Environmental Biobank, a sub-study within The Norwegian Mother, Father and Child Cohort Study (MoBa), were included. Total vitamin D intake was estimated from a food frequency questionnaire in gestational week 22. Concentrations of plasma 25OHD was analyzed by automated chemiluminescent microparticle immunoassay method in gestational week 18. Candidate determinant variables of 25OHD were chosen using stepwise backward selection and investigated using multivariable linear regression. Predicted 25OHD by total vitamin D intake, overall and stratified by season and pre-pregnancy BMI, was explored using restricted cubic splines in an adjusted linear regression.

Results

Overall, about 61% of the women had a total vitamin D intake below the recommended intake. The main contributors to total vitamin D intake were vitamin D supplements, fish, and fortified margarine. Higher 25OHD concentrations were associated with (in descending order of the beta estimates) summer season, use of solarium, higher vitamin D intake from supplements, origin from high income country, lower pre-pregnancy BMI, higher age, higher vitamin D intake from foods, no smoking during pregnancy, higher education and energy intake. During October–May, a vitamin D intake according to the recommended intake was predicted to reach sufficient 25OHD concentrations >50  nmoL/L.

Conclusion

The findings from this study highlight the importance of the vitamin D intake, as one of few modifiable determinants, to reach sufficient 25OHD concentrations during months when dermal synthesis of vitamin D is absent.
Essential nutrients and cerebral small vessel diseases: a two-sample Mendelian randomization study
Authors: Li Jiayi , Xia Kailin , Wang Zhengrui , Liu Yanru , Tong Yicheng , Wang Yuwei , Zhou Yumou , Zhang Linjing , Tang Lu , Fan Dongsheng , Yang Qiong
Published: June 2023

Background

Previous studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed.

Object

We intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis.

Method

We obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR–Egger method were adopted for sensitivity analyses.

Results

For ICH or SVS, increased levels of phenylalanine (OR = 1.188, p < 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, p = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, p < 0.001), zinc (OR = 0.919, p < 0.001), and arachidonic acid (OR = 0.966, p = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, p < 0.001), zinc (OR = 0.918, p < 0.001), and retinol (OR = 0.753, p < 0.001) showed risk effects; DPA (OR = 0.682, p = 0.022), gamma-linolenic acid (OR = 0.120, p = 0.033) and 25(OH)D (OR = 0.874, p = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, p < 0.001) and phenylalanine (OR = 1.175, p = 0.001) showed risk effects.

Conclusion

Our study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.
Adherence to Mediterranean diet and its association with multiple colonic polyps of unknown origin: a case-control study
Authors: Bujanda-Miguel Gabriela , Martínez-Roca Alejandro , García-Heredia Anabel , Guill-Berbegal David , Roche Enrique , Jover Rodrigo
Published: June 2023

Introduction

Multiple colonic polyps do not have a genetic origin in most patients, and the cause of this phenotype remains elusive. Environmental factors, such as diet, could be related to this phenotype. Our aim was to investigate the relationship between the adherence to Mediterranean diet and multiple colonic polyps of unknown origin.

Methods

A case-control pilot study was carried out with a sample of 38 individuals, including 23 cases with more than 10 adenomatous or serrated polyps from the national multicenter project EPIPOLIP and 15 healthy controls with normal colonoscopy. A validated Spanish version of the MEDAS questionnaire was administered to cases and controls.

Results

Adherence to Mediterranean diet was higher in controls than in patients with multiple colonic polyps (MEDAS score: 8.6 ± 1.4 vs. 7.0 ± 1.6; p = 0.01). Optimal overall adherence to the Mediterranean diet pattern was significantly higher among the controls than among cases (MEDAS score >9: 46% vs. 13%; OR 0.17; 95% CI 0.03–0.83). Non-optimal adherence to the Mediterranean diet acts as a risk factor for developing colorectal cancer derived from colorectal polyps.

Conclusion

Our results suggest that environmental factors play a role in the pathogenesis of this phenotype.