bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
Authors: Rojo Mailén , Pérez Hernán , Millán Andrea Liliana , Pautasso María Constanza , Duarte Alejandra , Abruzzese Giselle Adriana , Motta Alicia Beatriz , Frechtel Gustavo Daniel , Cerrone Gloria Edith
Published: January 2025

Introduction

Polycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contributing to cardiovascular disease and type 2 diabetes mellitus (T2D). Obesity and PCOS exacerbate each other, with central obesity driving metabolic changes. Mitochondrial dysfunction, characterized by oxidative stress and reduced antioxidant capacity, plays a key role in PCOS pathology.

Methods

In our study, we investigated 81 women with PCOS, and 57 control women aged 16 to 46 years old. Relative mitochondrial DNA (mtDNA) content and its oxidation level (8-oxoguanine, 8-OxoG) were determined in peripheral blood leukocytes by the SYBR Green method real-time PCR.

Results

Our findings showed that patients with PCOS had decreased mtDNA content and increased oxidation damage. Stratifying these patients by metabolic profile, revealed a progressive decline in mtDNA content from the normal-weight control group to the MHO-PCOS and MUO-PCOS groups, suggesting that lower mtDNA content is linked to obesity and worse metabolic profile. However, mtDNA oxidation levels did not differ significantly among these groups. Additionally, the decline in mtDNA content and the increase in oxidation levels between controls and patients with PCOS lost significance when these relationships were adjusted for the HOMA index.

Discussion

This finding suggests that IR could be the main factor contributing to mitochondrial dysfunction in PCOS. Maintaining optimal mtDNA copies are crucial for mitochondrial and cell function, suggesting potential therapeutic targets for PCOS-associated metabolic disturbances.
Antioxidant therapy for infertile couples: a comprehensive review of the current status and consideration of future prospects
Authors: Saleh Ramadan , Sallam Hassan , Elsuity Mohamad AlaaEldein , Dutta Sulagna , Sengupta Pallav , Nasr Ahmed
Published: January 2025

Oxidative stress (OS) is established as a key factor in the etiology of both male and female infertility, arising from an imbalance between reactive oxygen species (ROS) production and the endogenous antioxidant (AOX) defenses. In men, OS adversely affects sperm function by inducing DNA damage, reducing motility, significantly impairing sperm vitality through plasma membrane peroxidation and loss of membrane integrity, and ultimately compromising overall sperm quality. In women, OS is implicated in various reproductive disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian failure, leading to diminished oocyte quality, disrupted folliculogenesis, and poorer reproductive outcomes. Antioxidant therapy represents a promising intervention to mitigate the harmful effects of ROS on reproductive health in additions to its easy accessibility, safety, and low cost. Despite several findings suggesting improvements in fertility potential with AOX therapy, the data remains inconclusive regarding optimal dosage and combination, duration of treatment, and the specific patient populations most likely to benefit. In this review, we discuss the role of AOXs in the management of infertile couples, focusing on their biological mechanisms, potential adverse effects, therapeutic efficacy, and clinical applications in improving reproductive outcomes in both natural conception and medically assisted reproduction. Additionally, we highlight the current practice patterns and recommendations for AOX supplementation during the course of infertility treatment. Further, we provide an overview on the limitations of the current research on the topic and insights for future studies to establish standardized AOX regimens and to assess their long-term impact on key outcomes such as live birth rates and miscarriage rates.
Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction
Authors: Xu Junrui , Sadiq Ussama , Zhao Wangruizhi , Xia Hengbo , Liu Yiwei , Zhang Renquan , Xu Aman
Published: January 2025

Background

Adenocarcinoma of the esophagogastric junction (AEGJ) is a highly aggressive tumor that frequently metastasizes to the liver. Understanding the cellular and molecular mechanisms that drive this process is essential for developing effective therapies.

Methods

We employed single-cell RNA sequencing to analyze the tumor heterogeneity and microenvironmental landscape in patients with AEGJ liver metastases. This approach enabled us to characterize the diverse cell populations involved in the liver metastatic process.

Results

Our analysis revealed a significant involvement of fibroblasts and mural cells in AEGJ liver metastasis. We identified a specific fibroblast type in AEGJ liver metastasis and observed distinct gene expression patterns between adenocarcinoma of the esophagogastric junction and other stomach adenocarcinomas. Our study demonstrated high expression of the SFRP2 gene in pericyte cells during the liver metastasis of AEGJ. The incorporation of GEO, TCGA, and immunofluorescence staining of SFRP2 expression enhanced our study. High expression of SFRP2 in pericytes may influence vascular stability and angiogenesis through the Wnt pathway.

Conclusion

Our study provides novel insights into the cellular interactions and molecular mechanisms that underlie AEGJ liver metastasis. Targeting the identified subtype of fibroblasts or influencing SFRP2 gene expression in pericytes may offer new therapeutic strategies for combating this aggressive tumor.
Coexistence of immunoglobulin G4-related kidney disease and acute hematogenous disseminated pulmonary tuberculosis: a case report
Authors: Zhou Fangfang , Chu Hanqing , Xu Youjun , Zhang Yena , Tan Kuibi , Ge Jinxia , Shao Ningjun , Luo Qun
Published: January 2025

Background

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibrous inflammatory disease. Recently, an association between IgG4-RD and tuberculosis (TB) has been reported.

Case summary

We report a 56-year-old man complaining of a cough and poor appetite for 2 months and oliguria for 1 day. The patient was diagnosed with TB due to a manifestation of lymphatic TB and the radiological alterations of acute miliary pulmonary TB. He also presented with greatly elevated serum creatinine, non-albumin proteinuria, immunoglobulin subgroup IgG4, and immunoglobulin free light chain (FLC) levels. A diagnosis of IgG4-RKD was suggested by a renal biopsy. We then administered the patient glucocorticoid and anti-TB treatment for 4 months. The patient’s renal function was completely restored and the manifestations of TB were alleviated.

Conclusion

The necessity and complexity of differential diagnosis in patients with coexisting IgG4-RD and TB remains challenging. Early recognition and timely treatment are important for averting its progression. Long-term monitoring is required to assess for recurrence of IgG4-RD and TB activity.
Regulation of interferon alpha production by the MAGUK-family protein CASK under H5N1 infection
Authors: Huang Jing-Ying , Sung Pei-Shan , Hsieh Shie-Liang
Published: January 2025

CASK, a MAGUK family scaffold protein, regulates gene expression as a transcription co-activator in neurons. However, the mechanism of CASK nucleus translocation and the regulatory function of CASK in myeloid cells remains unclear. Here, we investigated its role in H5N1-infected macrophages. We found that H5N1 triggers CASK nuclear translocation via PKR and SRC signaling. HCK, a SRC family kinase, enhances CASK phosphorylation at S395 via CDK5, facilitating CASK’s nuclear entry. Knocking out CASK in myeloid cells specifically reduces interferon-alpha (IFNA) production by hindering the nuclear export of Ifna mRNA, while leaving its mRNA levels unchanged. Myeloid-specific CASK knockout (KO) mice display exacerbated lung inflammation, which correlates with reduced IFNA levels during H5N1 infection. Interactome studies show that H5N1 triggers associations between CASK and CCT4, STIP1, and TNK1. These associations recruit IRF7, POLR2C, TAF15, HNRNPs, and CRM1, enabling the CASK complex to bind to the Ifna promoter, bind co-transcriptionally to Ifna mRNA, and facilitate CRM1-dependent Ifna mRNA export. This underscores CASK’s critical role in the antiviral response.
Advancing precision cancer immunotherapy drug development, administration, and response prediction with AI-enabled Raman spectroscopy
Authors: Chadokiya Jay , Chang Kai , Sharma Saurabh , Hu Jack , Lill Jennie R. , Dionne Jennifer , Kirane Amanda
Published: January 2025

Molecular characterization of tumors is essential to identify predictive biomarkers that inform treatment decisions and improve precision immunotherapy development and administration. However, challenges such as the heterogeneity of tumors and patient responses, limited efficacy of current biomarkers, and the predominant reliance on single-omics data, have hindered advances in accurately predicting treatment outcomes. Standard therapy generally applies a “one size fits all” approach, which not only provides ineffective or limited responses, but also an increased risk of off-target toxicities and acceleration of resistance mechanisms or adverse effects. As the development of emerging multi- and spatial-omics platforms continues to evolve, an effective tumor assessment platform providing utility in a clinical setting should i) enable high-throughput and robust screening in a variety of biological matrices, ii) provide in-depth information resolved with single to subcellular precision, and iii) improve accessibility in economical point-of-care settings. In this perspective, we explore the application of label-free Raman spectroscopy as a tumor profiling tool for precision immunotherapy. We examine how Raman spectroscopy’s non-invasive, label-free approach can deepen our understanding of intricate inter- and intra-cellular interactions within the tumor-immune microenvironment. Furthermore, we discuss the analytical advances in Raman spectroscopy, highlighting its evolution to be utilized as a single “Raman-omics” approach. Lastly, we highlight the translational potential of Raman for its integration in clinical practice for safe and precise patient-centric immunotherapy.
ESAT-6 protein suppresses allograft rejection by inducing CD4+Foxp3+ regulatory T cells through IκBα/cRel pathway
Authors: Huang Xiaofei , Zeng Yuqun , Lin Jingru , Liu Huazhen , Liang Chun-Ling , Chen Yuchao , Qiu Feifei , Bromberg Jonathan S. , Dai Zhenhua
Published: January 2025

Background

Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells. ESAT-6 may be a potential alternative immunosuppressant that could be utilized to suppress allograft rejection although it remains unknown whether ESAT-6 actually regulates alloimmunity.

Methods

In this study, murine skin or heart allotransplantation was performed to determine the effects of ESAT-6 protein on allograft survival. Flow cytometric analyses were conducted to quantify CD4+Foxp3+ Tregs, while immunohistochemistry was carried out to observe allograft immunopathology. Western blotting was used to detect IĸBα/c-Rel signaling during Treg induction. Finally, CD4+CD25- conventional T cells were cultured to induce Tregs and their proliferation.

Results

Here we found that ESAT-6 significantly extended murine skin and heart allograft survival, alleviated CD3+ T cell infiltration and increased Foxp3+ Tregs in an allograft. ESAT-6 augmented the percentage of CD4+Foxp3+ Tregs, whereas it decreased the frequency of Th1 and CD4+/CD8+ effector T cells in spleen and lymph nodes (LNs) posttransplantation. ESAT-6 also induced CD4+Foxp3+ Tregs from CD4+CD25- T cells in vitro by activating IĸBα/c-Rel signaling pathway, whereas inhibition of c-Rel signaling blocked Treg induction. Moreover, it suppressed conventional CD4+CD25- T cell proliferation in vitro in the absence of antigen-presenting cells (APCs), with an increase in IL-10 and decrease in IFN-γ production. On the other hand, it did not significantly alter DC maturation after allotransplantation.

Conclusion

Thus, ESAT-6 suppresses alloimmunity and inhibits allograft rejection by inducing CD4+Foxp3+ Tregs through IĸBα/c-Rel signaling pathway.
Interactive effects of multiple stressors in coastal ecosystems
Authors: Krishna Shubham , Lemmen Carsten , Örey Serra , Rehren Jennifer , Pane Julien Di , Mathis Moritz , Püts Miriam , Hokamp Sascha , Pradhan Himansu Kesari , Hasenbein Matthias , Scheffran Jürgen , Wirtz Kai W.
Published: January 2025

Coastal ecosystems are increasingly experiencing anthropogenic pressures such as climate warming, CO2 increase, metal and organic pollution, overfishing, and resource extraction. Some resulting stressors are more direct like pollution and fisheries, and others more indirect like ocean acidification, yet they jointly affect marine biota, communities, and entire ecosystems. While single-stressor effects have been widely investigated, the interactive effects of multiple stressors on ecosystems are less researched. In this study, we review the literature on multiple stressors and their interactive effects in coastal environments across organisms. We classify the interactions into three categories: synergistic, additive, and antagonistic. We found phytoplankton and bivalves to be the most studied taxonomic groups. Climate warming is identified as the most dominant stressor which, in combination, with other stressors such as ocean acidification, eutrophication, and metal pollution exacerbate adverse effects on physiological traits such as growth rate, fitness, basal respiration, and size. Phytoplankton appears to be most sensitive to interactions between warming, metal and nutrient pollution. In warm and nutrient-enriched environments, the presence of metals considerably affects the uptake of nutrients, and increases respiration costs and toxin production in phytoplankton. For bivalves, warming and low pH are the most lethal stressors. The combined effect of heat stress and ocean acidification leads to decreased growth rate, shell size, and acid-base regulation capacity in bivalves. However, for a holistic understanding of how coastal food webs will evolve with ongoing changes, we suggest more research on ecosystem-level responses. This can be achieved by combining in-situ observations from controlled environments (e.g. mesocosm experiments) with modelling approaches.
Coverage path planning for multi-AUV considering ocean currents and sonar performance
Authors: Mu Xukai , Gao Wei
Published: January 2025

Coverage path planning (CPP) for target search by autonomous unmanned vehicle (AUV) involves two crucial aspects: (1) the sonar performance of the AUV is sensitive to ocean environment, such as changes in terrain; and (2) the ocean currents significantly influence AUV dynamics AUV dynamics. To address the CPP of multiple AUVs (multi-AUV) considering both sonar performance and ocean currents, we propose a new integrated algorithm based on the improved Dijkstra algorithm, Particle Swarm Optimization (PSO), and the ELKAI Solve. First, the necessary sampling points for the area coverage are identified based on the sonar detection range at different locations, which is calculated by combining the ocean acoustics model with the sonar equation. Second, an improved Dijkstra algorithm is presented to solve the adjacency matrix of the graph formed by all sampling points under the influence of ocean currents. Third, the PSO algorithm is utilized for task allocation, and the ELKAI solver determines the optimal path for each AUV. Finally, multi-AUV path planning is achieved through iterations of the PSO algorithm and the ELKAI solver. Simulation results demonstrate the outstanding performance and robustness of our integrated algorithm.
Predictive factors for clinical cure in the treatment of HBeAg(−) chronic hepatitis B or compensated cirrhosis: a prospective observational study
Authors: Lv Yan-Qing , Guo Ru-Hua , Liu Kun-Yu , Li Jia-Jie , Ji Hui-Fan
Published: January 2025

Background

Sequential or combined treatment with nucleos(t)ide analogs (NAs) and pegylated interferon alpha-2b (Peg-IFN-α-2b) can improve the clinical cure rate. However, its clinical application is limited due to the adverse reactions associated with IFN.

Methods

A multi-center prospective observational study was conducted involving 59 NAs-treated chronic hepatitis B (CHB) patients who were treated with a combination therapy of NAs and Peg-IFN-α-2b for 48 weeks. Another 327 NAs-treated patients received NAs monotherapy for 48 weeks. At the end of the treatment, patients were classified into either the clinically cured group or the non-clinically cured group based on clinical efficacy. The study aimed to analyze the clinical cure rate and the predictive factors.

Results

After propensity score matching (PSM), a total of 104 patients were included in the exposure and the control groups. After 48 weeks of treatment, 13 patients in the exposed group achieved clinical cure, with a cure rate of 25%. In contrast, in the control group was 1.92%. The clinical cure rate was greater in the population with CHB or compensated cirrhosis treated with sequential or combined Peg-IFN-α-2b and NAs than in the control group (p < 0.001). Patients treated with Peg-IFN-α-2b were divided into a clinical cure group and a non-clinical cure group for single-factor regression and multi-factor binary logistic regression. The results showed that baseline qHBsAg [relative ratio (RR) = 0.997, 95%CI: [0.995, 0.999], p = 0.031] and △TBiL (RR = 0.698, 95%CI: [0.555, 0.879], p = 0.002) were independent influencing factors for achieving clinical cure in patients with CHB or compensated cirrhosis.

Conclusion

A lower baseline qHBsAg and decrease in TBiL at 24 weeks of treatment are independent influencing factors for achieving clinical cure. The lower the baseline qHBsAg and the higher the △TBiL levels after 24 weeks of treatment, the higher the probability of patients achieving clinical cure.
Screening and identification of two novel phosphate-solubilizing Pyrenochaetopsis tabarestanensis strains and their role in enhancing phosphorus uptake in rice
Authors: Bao Xiaozhe , Lu Haifei , Zhao Jinyao , Yang Taotao , Wu Longmei , Zou Jixiang , Chen Qingchun , Zhang Bin
Published: January 2025

Low phosphorus (P) use efficiency significantly impacts rice yields. An environmentally friendly approach to increase phosphorus absorption and utilization in rice involves the exploration of phosphorus-solubilizing fungal resources. This study aimed to isolate and characterize fungal strains from the rice rhizosphere and assess their phosphate solubilization capabilities, plant-growth-promoting (PGP) traits, and mechanisms involved. An initial comparative sequence analysis of the hypervariable regions of the ITS rDNA and morphological analysis identified two strains belonging to the genus Pyrenochaetopsis, designated Pyrenochaetopsis tabarestanensis WFY-1 (PtWFY-1) and WFY-2 (PtWFY-2). Both strains demonstrated the ability to solubilize tricalcium phosphate, magnesium phosphate, phosphate rock powder, and calcium phytate phosphorus in vitro through acidification via the exudation of oxoglutaric acid, acetic acid, citric acid, and pyruvic acid. The amounts of oxoglutaric acid, acetic acid, citric acid, and pyruvic acid secreted were 1,900.03, 1,478.47, 579.11, and 685.90 mg L−1, respectively, for the PtWFY-1 strain and 2,441.67, 1,519.18, 867.65, and 888.30 mg L−1, respectively, for the PtWFY-2 strain relative to the control (0.00 mg L−1). These organic acids acidify the rhizosphere, increasing the availability of phosphorus for plant uptake. Inoculation with PtWFY-1 increased available soil P by 5.8% after 30 days, increasing the plant P concentration by 69.8% and the dry weight of the rice seedlings by 24.5%. Similarly, the PtWFY-2 strain increased these parameters by 7.7%, 60.3%, and 14.5%, respectively. PtWFY-1 showed slightly stronger effects on P availability and plant growth compared to PtWFY-2. The secretion of phytohormones was responsible for the growth promotion in rice by the PtWFY-1 and PtWFY-2 strains, along with P absorption The principal phytohormone in the PtWFY-1 and PtWFY-2 broths was L-tryptophan, which is a precursor substance for IAA synthesis, accounting for 84.68% and 83.46%, respectively. Assessment of the antifungal activities of the PtWFY-1 and PtWFY-2 strains against Magnaporthe oryzae demonstrated that rice grew healthier, indirectly promoting rice phosphorus absorption. These findings highlight the potential of using Pyrenochaetopsis strains as biofertilizers to sustainably improve phosphorus use efficiency in rice agriculture.
16S rRNA sequencing-based evaluation of the protective effects of key gut microbiota on inhaled allergen-induced allergic rhinitis
Authors: Tang Yi , She Yongchuan , Chen Danping , Zhou Yibo , Xie Dan , Liu Zhai
Published: January 2025

Introduction

Allergic rhinitis (AR) is a common respiratory disorder influenced by various factors in its pathogenesis. Recent studies have begun to emphasize the significant role of gut microbiota in immune modulation and its potential association with the development of AR. This research aims to characterize the gut microbiota of patients with AR who are sensitized via inhalation, utilizing 16S rRNA sequencing to shed light on the pathogenesis of AR and identify potential therapeutic targets.

Methods

To achieve the study’s objectives, we compared the microbiota profiles between patients with AR and healthy controls. Microbial diversity was assessed using alpha and beta diversity indices, and differential microbiota populations were identified through Linear discriminant analysis Effect Size (LEfSe) analysis. A Least Absolute Shrinkage and Selection Operator (LASSO) regression model was employed to pinpoint key species. Additionally, PICRUSt2 was utilized to predict the functional pathways associated with these identified species.

Results

The analysis identified a total of 1,122 common species, along with 1,803 species associated with AR and 1,739 species associated with healthy controls. LEfSe analysis revealed 20 significant discrepancies at the genus level. The LASSO regression model identified 8 key genera, including Prevotellaceae UCG-004 and Rhodococcus, which exhibited AUC values exceeding 0.7, indicating strong diagnostic potential. Furthermore, functional pathway analysis suggested that these pivotal species are involved in pathways such as L-lysine biosynthesis and photorespiration, potentially contributing to the pathogenesis of AR.

Discussion

This study identifies critical gut microbiota that could serve as potential biomarkers for allergic rhinitis, providing new insights into its pathogenesis and offering avenues for future therapeutic strategies. Further investigation into these microbiota may lead to enhanced understanding and management of AR.
Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis
Authors: Zhang Yan , Chen Xiujuan , Lin Yuan , Liu Xiaoqing , Xiong Xiumei
Published: January 2025

Background

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between women with PCOS and those without PCOS using bioinformatics and to investigate the related molecular mechanisms.

Methods

Two datasets were downloaded from GEO and analysed using the limma package to identify DEGs in two groups—PCOS and normal granulosa cells. Enrichment analyses, including GO, KEGG, and GSEA, were then conducted on the DEGs. Differential immune infiltration was assessed using CIBERSORT and correlations with immune cell biomarkers were evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target genes, and drug-target genes were constructed and visualized using Cytoscape to identify key hub gene nodes. Finally, key genes were analysed for differential expression and correlated.

Results

Overall, 127 co-DEGs were identified in the two datasets. Our study revealed that these DEGs were primarily associated with cell cycle arrest, p53-mediated signal transduction, drug response, and gland development, with molecular functions enriched in growth factor binding, collagen binding, and receptor protein kinase activity. GSEA revealed that the co-DEGs were primarily associated with immune and inflammatory pathways. Eleven hub genes—MMP9, SPI1, IGF2R, GPBAR1, PDGFA, BMPR1A, LIFR, PRKAA1, MSH2, CDC25C, and KCNH2—were identified through the PPI, TF target genes, miRNA target genes, and drug target gene networks.

Conclusion

We identified several crucial genes and pathways linked to the onset and development of PCOS. Our findings offer a clear connection between PCOS and GCERS, clarify the molecular mechanisms driving PCOS progression, and offer new perspectives for discovering valuable therapeutic targets and potential biomarkers for the condition.
Recent advances of lysine lactylation in prokaryotes and eukaryotes
Authors: Zhao Wenjuan , Xin Jiayi , Yu Xin , Li Zhifang , Li Nan
Published: January 2025

Lysine lactylation is a newly discovered protein post-translational modification that plays regulatory roles in cell metabolism, growth, reprogramming, and tumor progression. It utilizes lactate as the modification precursor, which is an end product of glycolysis while functioning as a signaling molecule in cells. Unlike previous reviews focused primarily on eukaryotes, this review aims to provide a comprehensive summary of recent knowledge about lysine lactylation in prokaryotes and eukaryotes. The current identification and enrichment strategies for lysine lactylation are introduced, and the known readers, writers, and erasers of this modification are summarized. In addition, the physiological and pathological implications of lysine lactylation are reviewed for different organisms, especially in prokaryotic cells. Finally, we end with a discussion of the limitations of the studies so far and propose future directions for lysine lactylation investigations.
Meridional anisotropy in contrast sensitivity and visual evoked potential in adults with high myopic astigmatism
Authors: Wu Siu Sang Anthony , Leung Tsz Wing
Published: January 2025

Purpose

Astigmatism can lead to meridional amblyopia, an orientation-specific visual deficit. This study investigated the effects of astigmatism on meridional anisotropy in contrast sensitivity (CS) and steady-state visual evoked potential (ssVEP) across a range of spatial frequencies.

Methods

Thirty-two young adults with a best-corrected distance visual acuity of logMAR 0 or better were categorized into two groups: highly astigmatic (HAS, n = 16) with spherical-equivalent error (SE) ≥ −6.00 D and a cylindrical error (Cyl) ≥ 2.00 DC, and non-astigmatic (NAS, n = 16) with SE ≥ −6.00 D but Cyl ≤ 0.50 DC. We assessed CS using a spatial four-alternative forced-choice procedure and recorded ssVEP at spatial frequencies ranging from 0.6 to 12 cycles per degree (cpd) for horizontal and vertical gratings. The Area Under Log Contrast Sensitivity Function (AULCSF) and spatial frequency cutoff for the CS were also calculated.

Results

The HAS group exhibited significantly lower CS for horizontal compared to vertical gratings at most spatial frequencies (p < 0.045 for 0.6–6 cpd), also reflected in a lower AULCSF (p = 0.01). This meridional anisotropy in CS was absent in the NAS group for both AULCSF and individual spatial frequencies, except at 0.6 cpd (p = 0.005). Spatial frequency cutoff did not differ between orientations for either group (p > 0.94). Conversely, ssVEP amplitudes were consistently lower for horizontal than vertical gratings in both groups, regardless of the presence of astigmatism (p < 0.05).

Conclusion

Meridional anisotropy in contrast sensitivity was observed only in highly astigmatic participants, whereas meridional anisotropy in ssVEP was present in both highly astigmatic and non-astigmatic groups. This discrepancy between psychophysical and electrophysiological measures may be related to the static versus flickering nature of the stimuli and warrants further investigation.
Efficacy analysis of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer: a retrospective study
Authors: Gong Zhijie , Zhou Liping , He Yinghao , Zhou Jun , Deng Yanjie , Huang Zudong , Wang WeiWei , Yang Qiangbang , Pan Jian , Li Yingze , Yuan Xiaolu , Ma Minghui
Published: January 2025

Purpose

This study aims to evaluate the effectiveness and safety of prophylactic hyperthermic intraperitoneal chemotherapy (P-HIPEC) in patients with locally advanced gastric cancer (AGC) after laparoscopic radical gastrectomy. Additionally, it explores how the frequency and timing of P-HIPEC influence treatment outcomes.

Methods

A retrospective analysis was conducted on 227 patients with locally AGC who underwent laparoscopic surgery at Maoming People’s Hospital from January 2016 to December 2022. Patients were stratified into the HIPEC group (n=101) and the non-HIPEC group (n=126), based on whether they received postoperative P-HIPEC. Propensity score matching (PSM) was used to adjust for baseline characteristics, facilitating a comparative analysis of survival outcomes, postoperative complications and recurrence patterns. Cox regression analysis was performed to identify prognostic factors. Furthermore, the impact of varying P-HIPEC frequencies and initiation timings was evaluated.

Results

No significant differences in overall survival (OS) or postoperative complication rates were observed between the two groups in the original and PSM cohorts. But the disease-free survival (DFS) of the HIPEC group was significantly higher than that of the non-HIPEC group (HR 0.569; 95% CI 0.362–0.894; p = 0.013) in the PSM cohort, with 1-year, 3-year, and 5-year DFS rates showing notable improvement (77.9% vs. 69.7%, 60.1% vs. 43.0%, and 46.2% vs. 25.5%). The incidence of isolated peritoneal metastasis (PM) was significantly lower in the HIPEC group (5.3% vs. 17.3%, p = 0.039). Multivariate Cox regression analysis identified P-HIPEC as an independent protective factor for DFS. Further analysis indicated that neither the number of P-HIPEC sessions had a significant impact on OS (p = 0.388) or DFS (p = 0.735), nor did the timing of P-HIPEC initiation affect OS (p = 0.620) or DFS (p = 0.488). Likewise, different P-HIPEC frequencies or initiation timings had no significant impact on postoperative complication rates or recurrence patterns.

Conclusion

P-HIPEC effectively reduces the risk of postoperative PM and improves DFS in patients with locally AGC without increasing postoperative complications. However, it does not significantly impact OS. Additionally, variations in the frequency and timing of P-HIPEC initiation do not significantly affect survival outcomes, postoperative complications, or recurrence patterns.
Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets
Authors: Sirek Tomasz , Król-Jatręga Katarzyna , Borawski Przemysław , Zmarzły Nikola , Boroń Dariusz , Ossowski Piotr , Nowotny-Czupryna Olga , Boroń Kacper , Janiszewska-Bil Dominika , Mitka-Krysiak Elżbieta , Grabarek Beniamin Oskar
Published: January 2025

Background

Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity of its various subtypes. This study aimed to investigate the differential expression of genes and miRNAs involved in the PI3K/AKT/mTOR signaling pathway, a critical regulator of cancer progression.

Methods

We analyzed tumor tissues from five breast cancer subtypes—luminal A, luminal B HER2-negative, luminal B HER2-positive, HER2-positive, and triple-negative breast cancer (TNBC)—and compared them with non-cancerous tissues. Microarray and qRT-PCR techniques were employed to profile mRNAs and miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed with a statistical significance threshold (p) < 0.05.

Results

We identified several upregulated genes across all subtypes, with TNBC and HER2-positive cancers showing the most significant changes. Key genes such as COL1A1, COL4A1, PIK3CA, PIK3R1, and mTOR were found to be overexpressed, correlating with increased cancer aggressiveness. miRNA analysis revealed that miR-190a-3p, miR-4729, and miR-19a-3p potentially regulate these genes, influencing the PI3K/AKT/mTOR pathway. For instance, reduced expression of miR-190a-3p may contribute to the overexpression of PIK3CA and other pathway components, enhancing metastatic potential.

Conclusion

Our findings suggest that the PI3K/AKT/mTOR pathway and its miRNA regulators play crucial roles in breast cancer progression, particularly in aggressive subtypes like TNBC. The identified miRNAs and mRNAs hold potential as biomarkers for diagnosis and treatment, but further validation in functional studies is required. This study provides a foundation for targeted therapies aimed at modulating this critical pathway to improve breast cancer outcomes.
Systematic review and bayesian network meta-analysis: comparative efficacy and safety of six commonly used biologic therapies for moderate-to-severe Crohn’s disease
Authors: Su Haohang , Xiao Shengwei , Liang Zhiqing , Xun Tianrong , Zhang Jinfang , Yang Xixiao
Published: January 2025

Background

In contrast to previous network meta-analysis using classical frequentist methods, we evaluated the efficacy and safety of six frequently-used biologics through a Bayesian method.

Methods

Web of Science, Scopus, CENTRAL, ClinicalTrials.gov and ICTRP were searched to collect randomized controlled trials (RCTs) in adults with moderate-to-severe Crohn’s disease, comparing Infliximab, Adalimumab, Certolizumab pegol, Ustekinumab, Risankizumab, or Vedolizumab, relative to placebo or an active comparator for induction of clinical response (two different definitions) and maintenance of clinical remission. A random-effects model was performed with rankings according to the surface under cumulative ranking curve (SUCRA) probability. Finally, we completed sensitivity and consistency analyses, and evaluated the certainty of evidence through GRADE working group guidance.

Results

We identified 22 and 20 RCTs for induction and maintenance therapy, respectively. Infliximab combined with azathioprine was most effective for inducing clinical response in TNF (tumor necrosis factor) antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab (SUCRA 86.19) and Risankizumab (SUCRA 62.56) have the largest SUCRA in induction of clinical response. Risankizumab has the lowest risk of adverse events (SUCRA 84.81), serious adverse events (SUCRA 94.23), and serious infections (SUCRA 79.73) in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab rank highest for maintaining clinical remission.

Conclusion

This analysis suggests that Infliximab in combination with azathioprine may be preferred biologic agents for induction therapy in TNF antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab and Risankizumab may be preferred biologic agents for induction therapy. Risankizumab potentially has the lowest safety risk worth exploring in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab have maintenance efficacy benefits for responders to induction therapy.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=458609, Identifier CRD42023458609.
Traditional uses, botanical description, phytochemistry, and pharmacological activities of Phytolacca acinosa: a review
Authors: Khalid Tooba , Chang Chieh-Wei , Ross Samir Anis , Naseer Faiza , Qadeer Abdul , Chen Chien-Chin , Rafey Hafiz Abdul
Published: January 2025

Background

Phytolacca acinosa is an herbaceous herb belonging to the Phytolaccaceae family. The plant has a long history of usage in traditional medicine for treating a variety of ailments including infectious diseases, edema, inflammation, gastric, and abdominal distress. The traditional use, phytochemistry, and pharmacological properties of Phytolacca acinosa are outlined in this article.

Main text

To date, few bioactive molecules have been identified and isolated from the plant, such as phytolacacinoside A, esculentoside H, jaligonic acid and esculentoside B, phytolaccanol and epiacetyl aleuritolic acid, esculentoside A, esculentoside C, esculentoside D, esculentoside T, esculentoside S, sitosterol. The literature related some of the reported ethnomedicinal uses of the plant to these compounds found in different parts of the plant.

Conclusion

The in-depth knowledge about the significance of Phytolacca acinosa presented in this review may open up opportunities for research development in drug discovery and a better comprehension of the therapeutic advantages of the plant.
Berberrubine protects against cisplatin-induced ototoxicity by promoting folate biosynthesis
Authors: Miao Zhuang , Chang Danyang , Du Xiaodong , Sun Changling
Published: January 2025

Objective

This research investigated the possible shielding properties of BB (Berberrubine) against the harmful auditory effects of cisplatin, preliminarily delving into the underlying mechanisms responsible for this protection.

Methods

HEI-OC1 cell viability was determined using a Cell Counting Kit-8 (CCK-8). The impact of BB on cochlear hair cells was studied through in vitro cochlear explants culture. Apoptosis levels were measured through Annexin V-PI, Cleaved Caspase-3, and TUNEL staining. The level of ROS (reactive oxygen species) was measured through the application of DCFH-DA, MitoSOX, and JC-1 fluorescent dyes for staining. Immunofluorescence analysis of cochlear samples from mice was conducted to quantify the hair cell count, and concurrently, ABR (Auditory Brainstem Response) testing was utilized to evaluate auditory function. The mechanism of action of BB was explored using RNA-Seq and qRT-PCR analysis.

Results

BB significantly improved cell survival rates under cisplatin treatment, reduced levels of apoptotic markers (TUNEL, Cleaved Caspase-3, Annexin V-PI), decreased ROS and MitoSOX levels, and improved JC-1 signals in both HEI-OC1 cells and cochlear hair cells in cochlear explants culture. Animal studies demonstrated that treatment with BB enhanced the survival of cochlear hair cells, reduced hearing impairment caused by cisplatin in mice. RNA-seq and qRT-PCR analysis revealed that BB influenced the expression levels of multiple genes (Ccnd2, Reln, Pgf, Mylk3, Ppplr12c, Thbsl), by promoting folate biosynthesis for hearing protection.

Conclusion

Our findings suggest that BB protects against cisplatin-induced hearing damage by enhancing folate biosynthesis, decreasing intracellular ROS levels, and inhibiting apoptosis.
Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer
Authors: Rogovskii Vladimir , Murugin Vladimir V. , Vorobyev Nikolay , Popov Sergey , Sturov Nikolay , Krasheninnikov Alexey , Morozov Alexander , Prokhorova Marina
Published: January 2025

Background

The natural killer (NK) activity of peripheral blood mononuclear cells (PBMCs) is a crucial defense against the onset and spread of cancer. Studies have shown that patients with reduced NK activity are more susceptible to cancer, and NK activity tends to decrease due to cancer-induced immune suppression. Enhancing the natural cytotoxicity of PBMCs remains a significant task in cancer research.

Methods

This study investigates the potential of urolithin A, a polyphenolic metabolite produced by the gut microbiota, to enhance the natural cytotoxicity of PBMCs in prostate cancer patients and healthy subjects. We investigated the possible role of aryl hydrocarbon receptor (AhR) in this capability of urolithin A. We analyzed the ability of PBMCs preincubated with urolithin A, AhR agonist or antagonist to kill K562 (human chronic myelogenous leukemia) target cells.

Results

Our results demonstrate that urolithin A enhances the natural cytotoxicity of PBMCs in a dose-dependent manner. Specifically, at a concentration of 10 μM, urolithin A increased the NK activity of PBMCs from prostate cancer patients by an average of 23% (95% CI, 7%–38%). In addition, urolithin A modulates the level of cytokine production by PBMCs, decreasing the level of fractalkine, IL-8, and MCP-3. An AhR antagonist (CH223191, 1 μM) also increased NK activity, while an AhR agonist (β-naphthoflavone, 10 μM) did not increase NK activity and partially inhibited the urolithin A-induced enhancement.

Conclusion

Urolithin A increases the NK activity of PBMCs from patients with prostate cancer and healthy subjects, and the AhR may be involved in this capability of urolithin A.
The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications
Authors: Du Jiangxia , Shen Minhui , Chen Jiajia , Yan Hao , Xu Zhifei , Yang Xiaochun , Yang Bo , Luo Peihua , Ding Kefeng , Hu Yuhuai , He Qiaojun
Published: January 2025

Carbohydrates, lipids, bile acids, various inorganic salt ions and organic acids are the main nutrients or indispensable components of the human body. Dysregulation in the processes of absorption, transport, metabolism, and excretion of these metabolites can lead to the onset of severe metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, gout and hyperbilirubinemia. As the second largest membrane receptor supergroup, several major families in the solute carrier (SLC) supergroup have been found to play key roles in the transport of substances such as carbohydrates, lipids, urate, bile acids, monocarboxylates and zinc ions. Based on common metabolic dysregulation and related metabolic substances, we explored the relationship between several major families of SLC supergroup and metabolic diseases, providing examples of drugs targeting SLC proteins that have been approved or are currently in clinical/preclinical research as well as SLC-related diagnostic techniques that are in clinical use or under investigation. By highlighting these connections, we aim to provide insights that may contribute to the development of improved treatment strategies and targeted therapies for metabolic disorders.
Case report: Multisystemic smooth muscle dysfunction syndrome: a rare genetic cause of infantile interstitial lung disease
Authors: Li Qianying , Cui Lidan , Su Jun , Shen Yuelin
Published: January 2025

Multisystemic smooth muscle dysfunction syndrome (MSMDS) is an autosomal dominant disorder caused by mutations in the ACTA2 gene, resulting in variable clinical manifestation and multi-organ dysfunction. Interstitial lung disease (ILD) is a rare phenotype of this condition. We describe a rare infant case of an 8-month-old boy who presented with progressively worsening dyspnea, along with intermittent episodes of respiratory distress and cyanosis since birth. A chest CT scan revealed typical signs of ILD. Additionally, the patient exhibited congenital mydriasis, aortic coarctation, PDA, and pulmonary hypertension. Whole-exome sequencing identified a de novo variant c.536G > A (p.Arg179His) in the ACTA2 gene. These findings confirmed the diagnosis of MSMDS. Despite intensive hospital-based pulmonary care and optimized therapy, the child passed away due to sudden cardiac and respiratory arrest on the 12th day of hospitalization. This case underscores the importance of considering MSMDS in the differential diagnosis of infantile ILD.
Estimation of the freezeout parameters using strange hadrons with changing multiplicity in pp collisions at 7 TeV
Authors: Ahmad Hilal , Zhu Hailong , Liu Fu-Hu , Waqas M. , Badshah Murad , Ghodhbani Refka
Published: January 2025

We explore the spectra of transverse momenta of hadrons with strange quark content (KS0, ϕ, Λ+Λ̄, Ξ̄+Ξ̄+, and Ω−+Ω̄+) produced in proton–proton collisions at sNN = 7 TeV. We applied Tsallis statistics in a blast wave model (TBW) to the ALICE Collaboration’s experimental data and extracted the freezeout parameters (Tsallis temperature, transverse flow velocity, and the parameter q, which is the non-extensive parameter). The changing trend of these parameters is studied with changing multiplicity. The parameter q decreases while the parameter T and βT increases toward higher multiplicities. βT is noted to drop to zero in the system with the lowest multiplicities. In addition, the interrelationships between the parameters T with βT and T with q are presented where the former correlation is positive and the latter one is negative.
Fertilizer potential of biochar and ryegrass productivity in metal-contaminated soil
Authors: Antonangelo Joao Arthur , Bigatao Souza Joao Luis , Zhang Hailin
Published: January 2025

Introduction

Response to fertilization with biochar in contaminated soils for forage crops lacks comprehensive understanding. This study delves into the role of biochar in enhancing soil pH and phosphorus (P) and potassium (K) availability for ryegrass (Lolium perenne) in clay and silt loam metal-contaminated soils.

Methods

Two pot experiments were conducted using switchgrass-derived biochar (SGB) and poultry litter-derived biochar (PLB) with varying biochar application rates: one without plants and the other with ryegrass.

Results

Results demonstrated a significant rise in soil pH with increasing biochar rates, particularly notable for the PLB experiment with plants, attributed to PLB’s superior buffer capacity. PLB significantly improved ryegrass productivity, evident in germination percentage, plant population, and biomass, especially at a 0.5-1% biochar application rate. However, excessive biochar application (2-4%) hindered plant growth.

Discussion

PLB at 1% application sufficed to barely surpass critical P and K thresholds for optimal ryegrass production, whereas SGB fell short of meeting these thresholds, highlighting the importance of biochar feedstock selection. While biochar shows promise for metal remediation and nutrient enhancement, caution is advised against excessive application, considering potential nutrient contamination risks based on feedstock variations.