bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between pathogenic E.coli O78-induced intestinal epithelial barrier damage and Zonulin expression levels in yaks
Authors: Ren Xiaoli , Shi Bin , Chang Zhenyu , Zhang Jingbo , Wang Shuo , Liu Ruidong , Sang Mudan , Dong Hailong , Wu Qingxia
Published: September 2024

To explore whether the intestinal damage of yak colibacillosis resulted from the regulation of Zonulin expression by its pathogenic bacteria, the overexpression and interference plasmids of Zonulin were designed and cultured in Tranwell after cell transfection. Then qRT-PCR and Western blot were used to detect the results of cell transfection, 200 mL 1×105 CFU/mL E.coli O78 was added for 4 hours, transmembrane resistance was measured by transmembrane resistance meter, FD4 fluorescence concentration in the lower chamber was detected by enzyme labeling instrument, bacterial translocation was measured by CFU counting method, and epithelial mucin (MUC1, MUC2) and tight junction protein (FABP2, Occludin, ZO-1) were detected by qRT-PCR.

Results

The Zonulin gene overexpression and knockout cell lines were successfully constructed, the TEER value of the barrier of Zonulin overexpression cell lines began to decrease at 1 h after the addition of E.coli O78 and reached the lowest value at 4 h, and the TEER value of Zonulin interference cell lines decreased within 1-4 h after the addition of E.coli O78. At 4 h, the FD4 passing capacity of Zonulin overexpression cell lines was significantly higher than that of interfering cell lines, reaching twice as much as siRNA-1. The amount of bacterial translocation in overexpressed cell lines increased rapidly within 1-4 h, and the concentration of E.coli in the lower chamber was significantly higher than that in the siRNA-1 group at 4 h, but there was no significant change in the siRNA-1 group in the 1-4 h. There was no significant change in the mRNA level of MUC1 in Zonulin overexpression and interference cell lines after the addition of E.coli O78. In the overexpression group, the mRNA levels of MUC2, Occludin, and ZO-1 were significantly decreased, and the mRNA level of FABP2 was increased considerably. These results suggest stimulate epithelial cells to secrete Zonulin protein. Many Zonulin proteins regulate the opening of tight junction structures, reduce the transmembrane resistance of the cell barrier, and improve the permeability of the cell barrier and the amount of bacterial translocation.
Climate variability through the lens of applied weather index insurance in Senegal-a novel perspective on the implications of decadal variation
Authors: Osgood Daniel , Blakeley S. Lucille , Ouni Souha , Enenkel Markus , Braun Melody , Lebel Thierry , Giannini Alessandra
Published: September 2024

Introduction

Weather-based index insurance is a financial instrument which allows smallholder farmers to protect themselves against climate shocks such as droughts and floods. In many cases, insurance indices are based on one or more earth observation datasets (e.g., rainfall, soil moisture, vegetative health) which are partly covering periods of more than 40 years. While remote sensing products and their associated data have improved over this time, understanding the historical climate variability and trends remains an essential piece in ensuring the development of indexes that best represent farmers’ risks. From a practical perspective, shortening time series to limit the risk of understudied climate variability, such as the Atlantic Multidecadal Variability, sometimes seems to be a quick solution. However, shorter time series jeopardize the overall robustness of the index. Therefore, understanding the links between climate variability, index design, and implications for farmers is key. Weather-based index insurance products in Sahelian West Africa usually face a challenge in robustly quantify underlying climatic decadal variation in seasonal rainfall.

Methods

This study analyzes the influence of decadal shifts in rainfall patterns in Sahelian West Africa, in particular Senegal, on index insurance calibration and design, concluding with practical recommendations for the next generation of drought risk finance instruments in the region.

Results

Our findings indicate that decadal variability has not led to a clear decrease in payouts in recent years compared to earlier years, despite an overall increase in seasonal rainfall. Rather, we find that interannual variability has increased which may be a more critical factor for assessing farmers’ agricultural risk than the increase in total rainfall.

Discussion

Focusing on key moments of the cropping calendar in the design of an index shows that an increase in the total average rainfall per season does not result in fewer payouts.
Mobile health apps for cardiovascular risk assessment: a systematic review
Authors: Chavez-Ecos Fabian A. , Chavez-Ecos Rodrigo , Vergara Sanchez Carlos , Chavez-Gutarra Miguel A. , Agarwala Anandita , Camacho-Caballero Kiara
Published: September 2024

Introduction

mHealth apps (MHA) are emerging as promising tools for cardiovascular risk assessment, but few meet the standards required for clinical use. We aim to evaluate the quality and functionality of mHealth apps for cardiovascular risk assessment by healthcare professionals.

Methods

We conducted a systematic review of MHA for cardiovascular risk assessment in the Apple Store, Play Store, and Microsoft Store until August 2023. Our eligibility criteria were based on the 2021 European Society Cardiology Guidelines on Cardiovascular Disease Prevention in Clinical Practice, the Framingham Risk Score, and the Atherosclerotic Cardiovascular Disease score. Our protocol was drafted using the Preferred Reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. To assess quality, we used the validated Mobile Apps Rating Scale (MARS) score, which includes 19 items across four objective scales (engagement, functionality, aesthetics, and information quality) and one additional subjective scale. For functionality evaluation, we used the IMS Institute for Healthcare Informatics functionality scale. We performed data synthesis by generating descriptive statistics.

Results

A total of 18 MHA were included in the review. The most common scores used were the Framingham score, ASCVD score, and Score 2. Only six apps achieved an overall score of 4 or greater in the MARS evaluation. The MHA with the highest MARS score was ESC CVD Risk Calculation (5 points), followed by ASCVD Risk Estimator Plus (4.9 points). In the IMS scale, four MHA had a high functionality score: ASCVD Risk Estimator Plus (5 points), ESC CVD Risk Calculation (5 points), MDCalc Medical Calculator (4 points), and Calculate by QsMD (4 points).

Discussion

A gap exists in the availability of high-quality MHA designed for healthcare professionals to facilitate shared decision-making in cardiovascular risk assessment.

Systematic Review Registration

The International Prospective Register of Systematic Reviews, identifier CRD42023453807.
A comprehensive review of finerenone—a third-generation non-steroidal mineralocorticoid receptor antagonist
Authors: Zhai Shuhui , Ma Baisheng , Chen Weiwei , Zhao Qini
Published: September 2024

Multiple studies have shown that finerenone (BAY 94-8862), a third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), possesses different or superior mechanisms of action to traditional MRAs. Specifically, animal and cell-based experiments have demonstrated that this compound exerts multiple effects including fibrosis inhibition, reduced pulmonary artery pressure, improved diabetic retinopathy, enhanced endothelial functions, metabolic optimization as well as reduced oxidative stress, thereby exerting overall positive effects on renal and cardiovascular diseases. Consequently, clinical research, such as the FIGARO-DKD and FIDELIO-DKD trials, has demonstrated dual benefits for patients with type 2 diabetes mellitus and chronic kidney disease (T2DM-CKD), especially by validating MRAs’ potential in reducing risks of renal and cardiovascular composite endpoints. Currently, cardiovascular indications for finerenone are limited to patients with T2DM-CKD, while its use in non-T2DM CKD patients remains at clinical trial stages. Despite showing good safety and efficacy in T2DM-CKD patients, there are insufficient corresponding data for those presenting chronic kidney disease without diabetes (ndCKD). Furthermore, the application of this compound in diseases such as primary aldosteronism and its association with cancer risk need to be further validated through larger-scale and longer-term clinical studies. Nevertheless, the development of finerenone provides an additional option for treating cardiovascular and renal diseases. With further research, it is expected that finerenone will be relevant to a broader range of CKD patient populations by addressing current knowledge gaps to comprehensively evaluate its clinical value and potentially alter existing treatment strategies. The current review aims to comprehensively analyze the basic research and clinical advancements involving finerenone in order to explore its prospects for treating cardiovascular and renal diseases, while addressing unmet needs in current treatment strategies. Additionally, through a comprehensive analysis of relevant research findings, a deeper understanding of finerenone's drug characteristics will be provided alongside scientific guidance for future treatment strategies and their clinical significance.
Adipose tissue insulin resistance in young Japanese women is associated with metabolic abnormalities and dehydroepiandrosterone-sulfate
Authors: Sato Motonori , Tamura Yoshifumi , Kaga Hideyoshi , Yamasaki Nozomu , Kadowaki Satoshi , Sugimoto Daisuke , Nakagata Takashi , Someya Yuki , Nishida Yuya , Kawamori Ryuzo , Watada Hirotaka
Published: September 2024

Objective

The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population.

Participants

Ninety-eight young, healthy, underweight women participated in this study.

Design

To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively.

Results

Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR.

Conclusions

Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels.
Experimental investigation of emissions from a single-cylinder diesel engine using methanol–diesel blends
Authors: Kadhim Mohammed Qays , Oshchepkov Petr Platonovich
Published: September 2024

This study examines the effects of methanol–diesel blends on the emissions of a diesel engine, concentrating on carbon monoxide (CO), carbon dioxide (CO2), nitrogen oxides (NOx), hydrocarbons (HCs), and particulate matter (PM). Using a single-cylinder four-stroke diesel engine at varying torque settings (2 N m–6 N m), significant reductions in CO, CO2, HC, and PM emissions were observed with increasing methanol content. CO emissions reduced by up to 81.8%, CO2 by up to 64.2%, HC by up to 80.4%, and PM by up to 23.5% with the MD11 blend. NOx emissions initially increased but decreased by up to 20% at higher torques with the same blend. These results highlight the environmental benefits of methanol–diesel blends and the need for effective NOx reduction strategies.
Integration of remote sensing and artificial neural networks for prediction of soil organic carbon in arid zones
Authors: Gouda Mohamed , Abu-hashim Mohamed , Nassrallah Attyat , Khalil Mohamed N. , Hendawy Ehab , benhasher Fahdah F. , Shokr Mohamed S. , Elshewy Mohamed A. , Mohamed Elsayed said
Published: September 2024

Introduction

Mapping soil organic carbon (SOC) with high precision is useful for controlling soil fertility and comprehending the global carbon cycle. Low-relief locations are characterized by minimal variability in traditional soil-forming elements, such as terrain and climatic conditions, which make it difficult to reflect the spatial variation of soil properties. In the meantime, vegetation cover makes it more difficult to obtain direct knowledge about agricultural soil. Crop growth and biomass are reflected by the normalized difference vegetation index (NDVI), a significant indicator. Rather than using conventional soil-forming variables.

Methods

In this study, a novel model for predicting SOC was developed using Landsat-8 Operational Land Imager (OLI) band data (Blue (B), Green (G), Red (R), and Near Infrared (NIR), NDVI data as the supporting variables, and Artificial Neural Networks (ANNs). A total of 120 surface soil samples were collected at a depth of 25 cm in the northeastern Nile Delta near Damietta City. Of these, 80% (96 samples) were randomly selected for model training, while the remaining 24 samples were used for testing and validation. Additionally, Gaussian Process Regression (GPR) models were trained to estimate SOC levels using the Matern 5/2 kernel within the Regression Learner framework.

Results and discussion

The results demonstrate that both the ANN with a multilayer feedforward network and the GPR model offer effective frameworks for SOC prediction. The ANN achieved an R2 value of 0.84, while the GPR model with the Matern 5/2 kernel achieved a higher R2 value of 0.89. These findings, supported by visual and statistical evaluations through cross-validation, confirm the reliability and accuracy of the models.

Conclusion

The systematic application of GPR within the Regression Learner framework provides a robust tool for SOC prediction, contributing to sustainable soil management and agricultural practices.
Phosphatidylcholine’s influence on Dysmenorrhea: conclusive insights from Mendelian randomization analysis
Authors: Li Yuzheng , Zhou Shiyao , Huang Yuchen , Yu Qiuhao , Wu Qibiao
Published: September 2024

Introduction

This study aimed to investigate the causal relationship between phosphatidylcholine (PC) levels and dysmenorrhea using Mendelian randomization (MR) analysis.

Methods

We conducted a two-sample MR analysis using GWAS data on PC levels and dysmenorrhea. Single nucleotide polymorphisms (SNPs) associated with PC levels were used as instrumental variables. MR-Egger regression and inverse variance weighting (IVW) were used to estimate the causal effect of PC levels on dysmenorrhea. Sensitivity analyses were performed to assess the robustness of the results.

Results

The IVW analysis revealed a significant positive association between higher PC levels and dysmenorrhea (OR: 1.533, 95% CI: 1.039–2.262, P = 0.031). The MR-Egger regression did not detect pleiotropy. Sensitivity analyses confirmed the robustness of the results.

Conclusion

This study provides evidence suggesting a causal link between increased PC levels and dysmenorrhea. Further research is needed to understand the biological mechanisms underlying this relationship and to explore potential therapeutic implications.
A comprehensive in silico analysis and experimental validation of miRNAs capable of discriminating between lung adenocarcinoma and squamous cell carcinoma
Authors: Javanmardifard Zahra , Rahmani Saeid , Bayat Hadi , Mirtavoos-Mahyari Hanifeh , Ghanei Mostafa , Mowla Seyed Javad
Published: September 2024

Background

Accurate differentiation between lung adenocarcinoma (AC) and lung squamous cell carcinoma (SCC) is crucial owing to their distinct therapeutic approaches. MicroRNAs (miRNAs) exhibit variable expression across subtypes, making them promising biomarkers for discrimination. This study aimed to identify miRNAs with robust discriminatory potential between AC and SCC and elucidate their clinical significance.

Methods

MiRNA expression profiles for AC and SCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and supervised machine learning methods (Support Vector Machine, Decision trees and Naïve Bayes) were employed. Clinical significance was assessed through receiver operating characteristic (ROC) curve analysis, survival analysis, and correlation with clinicopathological features. Validation was conducted using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, signaling pathway and gene ontology enrichment analyses were conducted to unveil biological functions.

Results

Five miRNAs (miR-205-3p, miR-205-5p, miR-944, miR-375 and miR-326) emerged as potential discriminative markers. The combination of miR-944 and miR-326 yielded an impressive area under the curve of 0.985. RT-qPCR validation confirmed their biomarker potential. miR-326 and miR-375 were identified as prognostic factors in AC, while miR-326 and miR-944 correlated significantly with survival outcomes in SCC. Additionally, exploration of signaling pathways implicated their involvement in key pathways including PI3K-Akt, MAPK, FoxO, and Ras.

Conclusion

This study enhances our understanding of miRNAs as discriminative markers between AC and SCC, shedding light on their role as prognostic indicators and their association with clinicopathological characteristics. Moreover, it highlights their potential involvement in signaling pathways crucial in non-small cell lung cancer pathogenesis.
Gut microbiota and functional outcome after ischemic stroke: a Mendelian randomization study
Authors: Qu Dian , Jiang Deming , Xin Yan , Yang Guichun , Liang Huan , Wang Linlin
Published: September 2024

Background

Previous studies have shown that gut microbiota dysbiosis could affect clinical prognosis through an unknown mechanism. However, the causal relationship between the gut microbiota and the functional outcome after ischemic stroke remains unclear. We aimed to investigate the causal association between the gut microbiota and the functional outcome after ischemic stroke using Mendelian randomization (MR).

Methods

Genetic instrumental variables associated with 211 bacterial traits were obtained from the MiBioGen consortium (N = 18,340). Data from genome-wide association studies (GWAS) for functional outcome after ischemic stroke were obtained from two phenotypes (i.e., overall stroke outcome and motor recovery). The inverse variance weighted method was used to estimate the causal association. Enrichment analysis was conducted based on the results of the MR analyses.

Results

The genetically predicted family Peptostreptococcaceae (OR = 0.63, 95% CI = 0.41–0.98, p = 0.038) and the genera LachnospiraceaeNK4A136 group (OR = 0.65, 95% CI = 0.43–1.00, p = 0.048), LachnospiraceaeUCG004 (OR = 0.54, 95% CI = 0.33–0.90, p = 0.017), and Odoribacter (OR = 0.40, 95% CI = 0.21–0.77, p = 0.006) presented a suggestive association with favorable functional outcome, while the genera Eubacterium oxidoreducens group (OR = 1.77, 95% CI = 1.11–2.84, p = 0.018) and RuminococcaceaeUCG005 (OR = 1.85, 95% CI = 1.15–2.96, p = 0.010) were associated with unfavorable functional outcome. The genetically predicted family Oxalobacteraceae (OR = 2.12, 95% CI = 1.10–4.11, p = 0.025) and the genus RuminococcaceaeUCG014 (OR = 4.17, 95% CI = 1.29–13.52, p = 0.017) showed a suggestive association with motor recovery, while the order Enterobacteriales (OR = 0.14, 95% CI = 0.02–0.87, p = 0.035) and the family Enterobacteriaceae (OR = 0.14, 95% CI = 0.02–0.87, p = 0.035) were associated with motor weakness. Enrichment analysis revealed that regulation of the synapse structure or activity may be involved in the effect of the gut microbiota on the functional outcome after ischemic stroke.

Conclusions

This study provides genetic support that the gut microbiota, especially those associated with short-chain fatty acids, could affect stroke prognosis by mediating synapse function. Our findings suggest that modifying the composition of the gut microbiota could improve the prognosis of ischemic stroke.
Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis
Authors: Cha Jung Hoon , Park Na Ri , Cho Sung Woo , Nam Heechul , Yang Hyun , Jung Eun Sun , Jang Jeong Won , Choi Jong Young , Yoon Seung Kew , Sung Pil Soo , Bae Si Hyun
Published: September 2024

Background

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by persistent inflammatory cascades, with macrophage activation playing a pivotal role. Chitinase 1 (CHIT1), produced by activated macrophages, is a key player in this cascade. In this study, we aimed to explore the role of CHIT1 in MASH with progressive liver fibrosis.

Methods

Fibrotic liver tissue and serum from distinct patient groups were analyzed using nCounter MAX, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. A MASH mouse model was constructed to evaluate the effectiveness of OATD-01, a chitinase inhibitor. Macrophage profiling was performed using single-nuclei RNA sequencing and flow cytometry.

Results

CHIT1 expression in fibrotic liver tissues was significantly correlated with the extent of liver fibrosis, macrophages, and inflammation. Single-nuclei RNA sequencing demonstrated a notable increase in macrophages numbers, particularly of lipid-associated macrophages, in MASH mice. Treatment with OATD-01 reduced non-alcoholic fatty liver disease activity score and Sirius red-positive area. Additionally, OATD-01-treated mice had lower CHIT1, F4/80, and α-smooth muscle actin positivity, as well as significantly lower levels of inflammatory markers, pro-fibrotic genes, and matrix remodeling-related mRNAs than vehicle-treated mice. Although the population of F4/80+CD11b+ intrahepatic mononuclear phagocytes remained unchanged, their infiltration and activation (CHIT1+MerTK+) significantly decreased in OATD-01-treated mice, compared with that observed in vehicle-treated mice.

Conclusions

Our study underscores the pivotal role of CHIT1 in MASH. The observed significant improvement in inflammation and hepatic fibrosis, particularly at higher doses of the CHIT1 inhibitor, strongly suggests the potential of CHIT1 as a therapeutic target in MASH accompanied by progressive liver fibrosis.
Case report: Refractory focal motor seizure associated with cerebrospinal fluid neurochondrin antibody
Authors: Ahmad Rowaid , Huang Yumeng , Wang Peter R. , Masel Todd , Li Xiangping
Published: September 2024

Background

Focal onset seizures, characterized by localized neuronal hyperexcitability in the brain, can be related to various structural, immune, genetic, or metabolic abnormalities. Autoimmune epilepsies are increasingly recognized. Neurochondrin antibody has been reported in a variety of rare autoimmune neurological disorders. This article aims to highlight the relevance of anti-neurochondrin in autoimmune epilepsy.

Methods

This is a case presentation and literature review of autoimmune epilepsy associated with anti-neurochondrin antibody.

Case presentation

A 26-year-old African American right-handed man with a history of Sjogren’s syndrome presented with near constant, rhythmic left-sided facial twitching movements, and one episode of generalized tonic clonic seizure. Magnetic resonance imaging (MRI) of the brain revealed borderline low volume right hippocampus. Cerebrospinal fluid (CSF) studies yielded elevated protein and mild lymphocytic pleocytosis. Antibody Prevalence in Epilepsy 2 (APE2) score was 6, and autoimmune workup was initiated. Anti-neurochondrin antibody returned positive in the CSF autoimmune encephalitis panel with a titer of 1:512 (Mayo Clinic TEST ID: ENC2). Seizures remained refractory to anti-seizure medications including divalproex, lacosamide, and oxcarbazepine. Immunotherapy with methylprednisolone and immunoglobulin improved his epileptic seizures.

Conclusion

This is the first reported case of refractory autoimmune epilepsy with positive CSF anti-neurochondrin antibody. This study contributes to the body of evidence supporting the role of neurochondrin antibody in epilepsy. Considering autoimmune testing in individuals with seizures having APE2 score > 4 can aid in timely diagnosis of immune-mediated epilepsy and initiation of immunotherapy, which can result in favorable clinical outcomes. Diagnosis of autoimmune epilepsy, in most cases, is based on clinical characteristics, MRI results, and CSF findings. In addition to the traditional antibody panel for autoimmune encephalitis, some novel antibodies, such as anti-neurochondrin, should also be considered.
Overview of mechanisms and novel therapies on rheumatoid arthritis from a cellular perspective
Authors: Han Peng , Liu Xiaoying , He Jiang , Han Luyang , Li Jinyao
Published: September 2024

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of joints in response to autoimmune disorders. Once triggered, many factors were involved in the development of RA, including both cellular factors like osteoclasts, synovial fibroblasts, T cells, B cells, and soluble factors like interleukin-1 (IL-1), IL-6, IL-17 and tumor necrosis factor-α (TNF-α), etc. The complex interplay of those factors results in such pathological abnormality as synovial hyperplasia, bone injury and multi-joint inflammation. To treat this chronic life-affecting disease, the primary drugs used in easing the patient’s symptoms are disease-modifying antirheumatic drugs (DMARDs). However, these traditional drugs could cause serious side effects, such as high blood pressure and stomach ulcers. Interestingly, recent discoveries on the pathogenesis of RA have led to various new kinds of drugs or therapeutic strategies. Therefore, we present a timely review of the latest development in this field, focusing on the cellular aspects of RA pathogenesis and new therapeutic methods in clinical application. Hopefully it can provide translational guide to the pre-clinical research and treatment for the autoimmune joint disease.
Deciphering the impact of TERT/telomerase on immunosenescence and T cell revitalization
Authors: Huang Lingyi , Zhang Mingfu , Bai Ding , Qu Yi
Published: September 2024

Immunosenescence impacts both the innate and adaptive immune systems, predominantly affecting certain immune cell types. A notable manifestation of immunosenescence is the diminished efficacy of adaptive immunity. The excessive senescence of immune cells, particularly T cells, leads to marked immune deficiency, consequently escalating the risk of infections, tumors, and age-associated disorders. Lymphocytes, especially T cells, are subject to both replicative and premature senescence. Telomerase reverse transcriptase (TERT) and telomerase have multifaceted roles in regulating cellular behavior, possessing the ability to counteract both replicative and premature senescence in lymphocytes. This review encapsulates recent advancements in understanding immunosenescence, with a focus on T cell senescence, and the regulatory mechanisms involving TERT/telomerase. Additionally, it comprehensively discusses strategies aimed at inhibiting immunosenescence by augmenting TERT/telomerase activity.
Regulating the lncRNA DSCR9/RPLP2/PI3K/AKT axis: an important mechanism of Xinfeng capsules in improving rheumatoid arthritis
Authors: Wang Fanfan , Liu Jian
Published: September 2024

Background

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetrical polyarthritis. RA patients often experience inflammatory reaction and hypercoagulable state, which together affect the self-perception of patient (SPP). Currently, inhibiting inflammation and hypercoagulable state are common treatment methods for alleviating RA symptoms. Xinfeng Capsules (XFC) has a long history of treating RA, and can effectively improve the inflammatory response and hypercoagulable state of RA. However, the potential mechanisms have not yet been determined.

Purpose and study design

This study elucidated the action mechanism of XFC in RA inflammation and hypercoagulability through the lncDSCR9/RPLP2/PI3K/AKT axis.

Results

Clinical observations indicated that there was a strong link between XFC therapy and improvements in inflammatory and coagulation biomarkers, as well as SPP among RA patients. The subsequent network pharmacology analysis results identified the PI3K/AKT signaling pathway as a potential mediator for XFC treatment of RA. Furthermore, clinical validation and sequencing results revealed that lncRNA DSCR9 expression (a gene implicated in inflammation and coagulation) was negatively correlated with clinical markers of inflammation and coagulation, while positively correlated with SF-36 indicators. Notably, XFC treatment remarkably upregulated lncRNA DSCR9 expression and downregulated PI3K and AKT expressions, showing opposite expression trends to the untreated cases.The regulatory effect of XFC on the lncRNA DSCR9/RPLP2/PI3K/AKT axis in RA was investigated using techniques such as RNA pull-down assay, Western blot analysis, RT-PCR, and EdU assay. Moreover, the administration of the PI3K/AKT agonist RMH can counteract the effects of XFC on p-PI3K, p-AKT, inflammation, and hypercoagulability, reinforcing the role of pathway. Finally, animal studies utilizing HE staining and transmission electron microscopy (TEM) demonstrated that XFC notably decreased PI3K and AKT expressions in adjuvant-induced arthritis (AA) rats, mitigated inflammation and hypercoagulability, and enhanced the ultrastructure of synovial cells. These findings underscored the potential mechanisms of XFC in the treatment of RA.

Conclusion

Regulating the lncRNA DSCR9/RPLP2/PI3K/AKT axis may be an important mechanism by which XFC improved RA inflammatory response and hypercoagulable state.
Identification of Yarrowia lipolytica as a platform for designed consortia that incorporate in situ nitrogen fixation to enable ammonia-free bioconversion
Authors: Pomraning Kyle R. , Deng Shuang , Duong Rylan D. , Czajka Jeffrey J. , Bohutskyi Pavlo
Published: September 2024

Bioconversion processes require nitrogen for growth and production of intracellular enzymes to produce biofuels and bioproducts. Typically, this is supplied as reduced nitrogen in the form of ammonia, which is produced offsite from N2 and H2 via the Haber-Bosch process. While this has revolutionized industries dependent on fixed nitrogen (e.g., modern agriculture), it is highly energy-intensive and its reliance on natural gas combustion results in substantial global CO2 emissions. Here we investigated the feasibility of in situ biological nitrogen fixation from N2 gas as a strategy to reduce greenhouse gas impacts of aerobic bioconversion processes. We developed an efficient and cost-effective method to screen fungal bioconversion hosts for compatibility with the free-living diazotrophic bacterium Azotobacter vinelandii under nitrogen fixing conditions. Our screening revealed that the genus Yarrowia is particularly enriched during co-culture experiments. Follow-up experiments identified four Y. lipolytica strains (NRRL Y-11853, NRRL Y-7208, NRRL Y-7317, and NRRL YB-618) capable of growth in co-culture with A. vinelandii. These strains utilize ammonium secreted during diazotrophic fixation of N2, which is provided as a component of the air input stream during aerobic fermentation. This demonstrates the feasibly of in situ biological nitrogen fixation to support heterotrophic fermentation processes for production of fuels and chemicals.
Coastal exotic plant serves as a habitat for a notorious wetland pest in unfavorable seasons: A case study of exotic Spartina alterniflora in China
Authors: Xu Tianping , Ma Xu , Li Yunjing , Xue Hao , Zhao Shilin , Liu Zezheng
Published: September 2024

Coastal biological invasions pose a wide-reaching threat to various ecosystems, affecting both vegetation and herbivores in native communities. Although herbivores often exert strong top-down control on vegetation, the impact of invasive species on consumers that strongly regulate native species in invaded ecosystems remains unclear. Therefore, through field surveys and feeding preference experiments, this study examined the effects of the invasive Spartina alterniflora Loisel. (hereafter, Spartina) on the native moth Laelia coenosa Hübner (hereafter, Laelia), a notorious pest that has been documented to cause significant damage to native Phragmites australis (Cav.) Trin. ex Steud. (hereafter, Phragmites) marshes in coastal wetlands of China. Field surveys showed that Laelia larvae were more abundant and had higher grazing rates in Phragmites than in Spartina marshes in summer, but these patterns reversed in autumn. Feeding experiments consistently showed that the dietary preference of Laelia larvae switched from Phragmites in summer to Spartina in autumn, likely because Spartina has a longer growing season and relatively higher nutritional quality than Phragmites in autumn. Thus, by providing shelters (i.e., dietary sources and habitats) during unfavorable seasons, Spartina invasions may facilitate this insect pest Laelia and potentially amplify its damage to native wetland vegetation. Our work reveals a novel, indirect mechanism of coastal invasion impacts and highlights the importance of incorporating seasonal variation in plant-herbivore interactions.
Application of modified and toughened admixtures in well cementing slurry: Progress and challenges
Authors: Zhang Yihang
Published: September 2024

Cementing, as an important part of the petroleum industry, plays a crucial role in ensuring the normal production and development of oil and gas resources. However, due to the brittle nature of Portland cement, it is prone to micro-cracks when subjected to downhole impact or vibration, which affects normal operations. Moreover, conventional elastic particles have a significant impact on the performance of cement paste, prompting people to continuously research new toughening admixtures. This article reviews the mechanism of toughening additives for oil well cement, the research status of physical toughening agents (fibers/whiskers, graphene) and polymer toughening agents (latex, epoxy resin, asphalt), aiming to provide reference and guidance for the development of new toughening additives.
Rapid diagnosis of Aspergillus flavus infection in acute very severe aplastic anemia with metagenomic next-generation sequencing: a case report and literature review
Authors: Kang Ying , Zhang Xiaojing , Qin Cao , Zheng Yafeng , Gai Wei , Jia Xiaofei , Shao Bo , Zhang Shuai , Jiang Hao , Huang XiaoJun , Jia Jinsong
Published: September 2024

Infection remains the leading cause of mortality in severe aplastic anemia (SAA) patients, with invasive fungal infections being the great threat. Aspergillus fumigatus accounts for most of the reported fungal infection cases. Here, we present a case of A. flavus infection in a patient with acute very severe aplastic anemia (VSAA) despite persistently negative clinical fungal tests. The patient was admitted to the hospital due to pancytopenia presisting for over a month and intermittent fever for 10 days. Elevated inflammatory indicators and abnormal lung imaging suggested infection, prompting consideration of fungal involvement. Despite negative results from multiple blood, sputum fungal cultures and the serum (1,3)-β-D-glucan/galactomannan tests. Metagenomic next-generation sequencing (mNGS) on multiple blood samples, alongside clinical symptoms, confirmed A. flavus infection. Targeted antifungal treatment with liposomal amphotericin B and voriconazole significantly ameliorated pulmonary symptoms. Additionally, this study reviewed and compared the symptoms, diagnostic approaches, and treatments from prior Aspergillus infections in AA patients. It emphasizes critical role of early mNGS utilization in diagnosing and managing infectious diseases, offering insights for diagnosing and treating fungal infections in VSAA.
Petaloid technique and prognostic significance of macular hole shapes by optical coherence tomography for full thickness macular hole
Authors: Keyal Khusbu , Li Bing , Liu Chunyu , Tian Zhongping , Li Houshuo , Bi Yanlong
Published: September 2024

Surgical advancements for full-thickness macular hole (FTMH) treatment include vitrectomy, membrane peeling, and the inverted flap technique (IFT). IFT, which involves inverting the internal limiting membrane (ILM) flap over the macular hole (MH) or into the MH, improves success rates and visual recovery. However, issues like mis-aspiration during flap handling have been problematic. We introduce the petaloid technique, to position the ILM flap under air during FTMH surgery to evaluate its outcomes. This retrospective study included 28 eyes, with a mean minimum linear diameter (MLD) 472.04 ± 199.7 μm and basal diameter (BD) of 834.95 ± 593.54 μm. Primary closure of MH was achieved in 96.42% of patients, with 3.57% showing persistent MH during the 6-month follow-up. The VA improved significantly from preoperative levels at each postoperative stage, with notable increases at 3 months (0.86 ± 0.49 logMAR; p = 0.0132) and 6 months (0.77 ± 0.41 logMAR; p = 0.000081). The new closure patterns showed Type A in 28.6%, B in 14.3%, C in 28.6%, and D in 25%. Among different types of closure patterns, although VA improved in all types, significant improvement in VA was noted for type A and type C, with notable improvements at the 6-month follow-up for Type A (0.60 ± 0.23 logMAR; p = 0.02) and at the 1-month follow-up for Type C (0.62 ± 0.28 logMAR; p = 0.02). For macular hole retinal detachment in 5 eyes, the average preoperative VA was 1.86 ± 0.19 logMAR, while the final mean postoperative VA showed a significant improvement to 1.1 ± 0.40 logMAR (p = 0.021, paired t-tests). Retinal reattachment was achieved in all cases (5/5) without recurrent detachment post-silicone oil removal. For the prognostic significance of MH shapes identified by OCT, it can be concluded that the shape of macular holes significantly influences visual acuity outcomes at 6 months post-surgery (p = 0.037). The shape of macular holes, particularly Flask-shaped, significantly impacts visual acuity compared to other shape. The modified petaloid technique for treating FTMH proved safe and effective, with no significant complications noted.
A systematic review and meta-analysis of the globally reported International Classification of Diseases to Perinatal Mortality (ICD-PM)
Authors: Kumsa Henok , Mislu Esuyawkal , Yimer Nigus Bililign
Published: September 2024

Introduction

Accurate recording and identification of perinatal mortality causes are crucial to reducing the global burden of perinatal mortality through targeted interventions. However, existing studies on the International Classifications of Diseases to Perinatal Mortality (ICD-PM) are limited by inconsistent results and variations by gestational age. Thus, this review aims to synthesize and document updated data on the causes of death using the ICD-PM classification.

Methods

Electronic databases such as the PubMed via MEDLINE, SCOPUS, Web of Sciences, EMBASE, Cochrane Library, and PROSPERO were searched to retrieve studies published from 2016 to February 2024. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included studies, and heterogeneity between the studies was assessed using I2 statistics. ICD-PM coded reported data were extracted to Microsoft Excel, and aggregate data of frequencies and percentages were reported.

Results

Out of the 23 included studies, 48,596 perinatal mortalities were reported, and approximately 96% (46,816 deaths) were classified according to the ICD-PM. The pooled rate of stillbirths in high-income countries was 23/1,000 births; in low-income countries, it was found to be approximately twice as in high-income countries. Regarding the category of deaths, 25,563 (54.6%) deaths were recorded in the antepartum period, and more than half, 14,887 (58.2%), were classified under unspecified causes (A6). Moreover, 6,148 (13.7%) and 14,835 (31.7%) deaths were coded with intrapartum and neonatal period causes, respectively. The leading causes of perinatal mortality during the intrapartum were acute intrapartum events (I3) 3,712 (57.8%). Furthermore, neonatal death was caused by low birth weight and prematurity (N9) 4,091 (27.6%), congenital malformations, and chromosomal abnormalities (N1) 2,512(16.9%).

Conclusion

Congenital malformations, and chromosomal abnormalities contribute to 1 in every 10 perinatal deaths and 1 in every 4 neonatal deaths. Other specified antepartum disorders are responsible for over half of antepartum deaths, while acute intrapartum events are the leading cause of intrapartum deaths, with a significant proportion remaining unexplained. Maternal complications related to the placenta, membranes, cord, labor, and delivery play a significant role in antepartum and intrapartum deaths. Targeted interventions and improved monitoring of high-risk pregnancies are crucial to reducing perinatal mortality rates. Further investigation is needed to enhance understanding and address unexplained perinatal deaths.

Systematic review registration

[https://clinicaltrials.gov/], identifier [CRD4202452549].
WHO-listed authorities (WLA) framework: transparent evidence-based approach for promoting regulatory reliance towards increased access to quality-assured medical products
Authors: Broojerdi Alireza Khadem , Salvati Anna Laura , Abdelfattah Mohammed Refaat , Dehaghi Razieh Ostad Ali , Sillo Hiiti B. , Gaspar Rogerio
Published: September 2024

Background

Increased global access to safe, effective and quality-assured medical products remains a primary goal for the full realization of the World Health Assembly Resolution WHA 67.20 on regulatory systems strengthening for medical products as well as target 3.8 of the Sustainable Development Goals (SDG). To promote the development of efficient regulatory systems, the WHO introduced the Global Benchmarking Tool (GBT) in 2016, upon which the WHO–Listed Authority (WLA) framework was later established. This study aimed to appraise the development of the WLA framework across various phases while highlighting its achievements, challenges, and areas for improvement.

Methods

An exploratory study design using a qualitative approach was used to gather information from relevant documents as well as views and experiences from purposefully selected participants from diverse backgrounds. Data was collected using a combination of desk reviews and In-depth one-to-one or small group interviews employing semi-structured interview guides with open-ended questions. Data was analysed using an inductive thematic analysis approach.

Results

The leading role of the WHO was noted in developing and implementing essential documents and mediating consultative processes among stakeholders. The framework was revealed to bring an evidence-based, inclusive, and transparent approach to recognizing regulatory authorities (RAs) operating at the highest standards of performance. The framework was anticipated to promote regulatory reliance among all RAs, the WHO’s prequalification programme, and procurement agencies. Furthermore, remarkable progress towards WLA listing was noted among transitional WLAs including the Stringent Regulatory Authorities (SRAs). Challenges related to the availability of resources, resistance to change, and complexity were associated with the framework.

Conclusion

The study provides a well-rounded view with regard to the roles of the WHO, Member States and other stakeholders in establishing and operationalizing the WLA framework. Furthermore, evaluating the performance and possible WLA designation of RAs operating at international regulatory standards underscores its high relevance in contributing to public health globally. Maintenance along with timely addressing of highlighted next steps to improve the framework particularly in creating better understanding, more communication, and coordination are highly encouraged.
Navigating the archaeal frontier: insights and projections from bioinformatic pipelines
Authors: Karavaeva Val , Sousa Filipa L.
Published: September 2024

Archaea continues to be one of the least investigated domains of life, and in recent years, the advent of metagenomics has led to the discovery of many new lineages at the phylum level. For the majority, only automatic genomic annotations can provide information regarding their metabolic potential and role in the environment. Here, genomic data from 2,978 archaeal genomes was used to perform automatic annotations using bioinformatics tools, alongside synteny analysis. These automatic classifications were done to assess how good these different tools perform in relation to archaeal data. Our study revealed that even with lowered cutoffs, several functional models do not capture the recently discovered archaeal diversity. Moreover, our investigation revealed that a significant portion of archaeal genomes, approximately 42%, remain uncharacterized. In comparison, within 3,235 bacterial genomes, a diverse range of unclassified proteins is obtained, with well-studied organisms like Escherichia coli having a substantially lower proportion of uncharacterized regions, ranging from <5 to 25%, and less studied lineages being comparable to archaea with the range of 35–40% of unclassified regions. Leveraging this analysis, we were able to identify metabolic protein markers, thereby providing insights into the metabolism of the archaea in our dataset. Our findings underscore a substantial gap between automatic classification tools and the comprehensive mapping of archaeal metabolism. Despite advances in computational approaches, a significant portion of archaeal genomes remains unexplored, highlighting the need for extensive experimental validation in this domain, as well as more refined annotation methods. This study contributes to a better understanding of archaeal metabolism and underscores the importance of further research in elucidating the functional potential of archaeal genomes.