bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus cluster analysis of apoptosis-related genes in patients with osteoarthritis and their correlation with immune cell infiltration
Authors: Yu Enming , Zhang Mingshu , Xu Gongping , Liu Xiaoqi , Yan Jinglong
Published: October 2023

Background

Osteoarthritis (OA) progression involves multiple factors, including cartilage erosion as the basic pathological mechanism of degeneration, and is closely related to chondrocyte apoptosis. To analyze the correlation between apoptosis and OA development, we selected apoptosis genes from the differentially expressed genes (DEGs) between OA and normal samples from the Gene Expression Omnibus (GEO) database, used lasso regression analysis to identify characteristic genes, and performed consensus cluster analysis to further explore the pathogenesis of this disease.

Methods

The Gene expression profile datasets of OA samples, GSE12021 and GSE55235, were downloaded from GEO. The datasets were combined and analyzed for DEGs. Apoptosis-related genes (ARGs) were collected from the GeneCards database and intersected with DEGs for apoptosis-related DEGs (ARDEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to obtain characteristic genes, and a nomogram was constructed based on these genes. A consensus cluster analysis was performed to divide the patients into clusters. The immune characteristics, functional enrichment, and immune infiltration statuses of the clusters were compared. In addition, a protein–protein interaction network of mRNA drugs, mRNA-transcription factors (TFs), and mRNA-miRNAs was constructed.

Results

A total of 95 DEGs were identified, of which 47 were upregulated and 48 were downregulated, and 31 hub genes were selected as ARDEGs. LASSO regression analysis revealed nine characteristic genes: growth differentiation factor 15 (GDF15),NAMPT,TLR7,CXCL2,KLF2,REV3L,KLF9,THBD, andMTHFD2. Clusters A and B were identified, andneutrophil activationandneutrophil activation involved in the immune responsewere highly enriched in Cluster B, whereasprotein repairand purine salvagesignal pathways were enriched in Cluster A. The number of activated natural killer cells in Cluster B was significantly higher than that in Cluster A.GDF15andKLF9interacted with 193 and 32 TFs, respectively, andCXCL2andREV3Linteracted with 48 and 82 miRNAs, respectively.

Conclusion

ARGs could predict the occurrence of OA and may be related to different degrees of OA progression.
Eotaxin-1/CCL11 promotes cellular senescence in human-derived fibroblasts through pro-oxidant and pro-inflammatory pathways
Authors: Lavandoski Patrícia , Pierdoná Vinícius , Maurmann Rafael Moura , Grun Lucas Kich , Guma Fatima T. C. R. , Barbé-Tuana Florencia María
Published: October 2023

Introduction

Eotaxin-1/CCL11 is a pivotal chemokine crucial for eosinophil homing to the lungs of asthmatic patients. Recent studies also suggest that CCL11 is involved in the aging process, as it is upregulated in elderly, and correlated with shorter telomere length in leukocytes from asthmatic children. Despite its potential pro-aging effects, the precise contribution of CCL11 and the underlying mechanisms involved in the promotion of cellular senescence remains unclear. Therefore, the primary goal of this study was to explore the role of CCL11 on senescence development and the signaling pathways activated by this chemokine in lung fibroblasts.

Methods

To investigate the targets potentially modulated by CCL11, we performed an in silico analysis using PseudoCell. We validated in vitro the activation of these targets in the human lung fibroblast cell line MRC-5 following rhCCL11 exposure. Finally, we performed differential gene expression analysis in human airway epithelial cells of asthmatic patients to assess CCL11 signaling and activation of additional senescent markers.

Results

Our study revealed that eotaxin-1/CCL11 promote reactive oxygen secretion (ROS) production in lung fibroblasts, accompanied by increased activation of the DNA damage response (DDR) and p-TP53 and γH2AX. These modifications were accompanied by cellular senescence promotion and increased secretion of senescence-associated secretory phenotype inflammatory cytokines IL-6 and IL-8. Furthermore, our data show that airway epithelial lung cells from atopic asthmatic patients overexpress CCL11 along with aging markers such as CDKN2A (p16INK4a) and SERPINE1.

Discussion

These findings provide new insights into the mechanisms underlying the pro-aging effects of CCL11 in the lungs of asthmatic patients. Understanding the role of CCL11 on senescence development may have important implications for the treatment of age-related lung diseases, such as asthma.
The role of miRNAs in Behçet’s disease
Authors: Gu Feihan , Huang Xu , Huang Wenkai , Zhao Mingyu , Zheng Hu , Wang Yuanyin , Chen Ran
Published: October 2023

The symptoms of Behçet’s disease (BD), a multisystemic condition with autoimmune and inflammation as hallmarks, include arthritis, recurring oral and vaginal ulcers, skin rashes and lesions, and involvement of the nervous, gastrointestinal, and vascular systems. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), may be important regulators of inflammation and autoimmune disease. These ncRNAs are essential to the physiological and pathophysiological disease course, and miRNA in particular has received significant attention for its role and function in BD and its potential use as a diagnostic biomarker in recent years. Although promising as therapeutic targets, miRNAs must be studied further to fully comprehend how miRNAs in BD act biologically.
Macrophage metabolism in nonalcoholic fatty liver disease
Authors: Zhang Wenhui , Lang Ren
Published: October 2023

Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, and remains incompletely understood. The pivotal role of liver-resident and recruited macrophages in the pathogenesis of NAFLD and NASH is widely acknowledged as a crucial factor in innate immunity. The remarkable plasticity of macrophages enables them to assume diverse activation and polarization states, dictated by their immunometabolism microenvironment and functional requirements. Recent studies in the field of immunometabolism have elucidated that alterations in the metabolic profile of macrophages can profoundly influence their activation state and functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating the polarization and activation states of macrophages, highlighting the correlation between their metabolic characteristics and the transition from pro-inflammatory to anti-inflammatory phenotypes. Additionally, we explore the potential of targeting macrophage metabolism as a promising therapeutic approach for the management of NAFLD/NASH.
Comparison of cataract patients with regular corneal astigmatism after implantation of extended range-of-vision and bifocal toric intraocular lenses
Authors: Li Zhuoya , Guo Rong , Hu Xiaomin , Yang Xinyue , Wen Ziyuan , Lin Yi , Zhang Hui
Published: October 2023

Purpose

To compare the postoperative visual acuity and visual quality between extended range-of-vision and multifocal toric intraocular lens (IOLs) after implantation in cataract patients with regular corneal astigmatism.

Setting

Department of Ophthalmology, the Second Hospital of Jilin University, Changchun, Jilin Province, China.

Design

Retrospective and single-center study.

Methods

The study involved implanting the Tecnis Symphony (ZXR00IOL) or the bifocal toric (ZMTIOL) in patients undergoing cataract surgery. Three months after surgery, lens performance was evaluated using distance, intermediate, and near visual acuity tests, defocus curves, the modulation transfer function (MTF), a visual function index questionnaire (VF-14), and the adverse optical interference phenomena.

Results

The 3-month postoperative follow-up found that both groups had good corrected distance vision. The ZMT group had better-uncorrected distance visual acuity and near visual acuity (p < 0.05). However, the ZXR group showed better uncorrected intermediate visual acuity (p < 0.05) and visual continuity. Overall astigmatism in the postoperative ZMT group was significantly lower than that in the pre-operative group (p < 0.05). The ZMT group had lower total high-order aberrations (tHOs), higher MTF values, and higher VF-14 scores (p < 0.05). Finally, the ZXR group exhibited reduced halo and glare phenomena (p < 0.05).

Conclusion

We found that ZMT can effectively correct a corneal astigmatism of 1.0–1.5 D and ZXR can improve patient outcomes regarding subjective optical quality and range of vision. These findings have the potential to improve future astigmatism treatment options.
Advanced materials and biofabrication technologies to design in vitro functional central nervous system models
Authors: Traldi Cecilia , Chiappini Vanessa , Menduti Giovanna , Tonda-Turo Chiara , Boido Marina
Published: October 2023

Nowadays, the pathophysiology of several central nervous system (CNS) disorders is still poorly understood, making difficult the identification of efficient treatments. CNS damages, due to neurodegenerative conditions or injuries, often result in permanent neuronal dysfunctions and serious impairments of motor, sensory and cognitive capacities. Despite the many attempts of pharmaceutical research to promote neural regeneration, poor progresses have been made in effectively restoring nervous functionality. Indeed, most of the experimental drugs show limited efficacy in the clinical trials, also due to existing preclinical models’ inability in fully replicating the complexity of CNS pathophysiology. Therefore, tissue-engineered three-dimensional (3D) models are being extensively explored to develop novel representative in vitro platforms, which more carefully replicate the architecture of neural microenvironment, including both cellular and extracellular components. In this respect, 3D in vitro models are expected to be promising and comprehensive tools for investigating CNS diseases and testing new drug compounds, as they overcome some of the common limitations of traditional two-dimensional (2D) cultures. This review discusses the main challenges to be addressed in CNS modeling, analyzing the key elements involved in neural tissue engineering. Specifically, an overview of the mostly used neural cell sources and biomaterials is provided, focusing on the critical aspects to consider in selecting the appropriate components according to the application. Different methods adopted to modulate the structural and functional properties of the engineered microenvironment are also presented, aimed at fostering in vitro tissue maturation. Lastly, the latest advances in biofabrication technologies are outlined, reviewing the most recent 3D bioprinted in vitro systems and microfluidic-based 3D platforms, starting from the modeling of distinctive CNS pathophysiological mechanisms to the designing of refined and functional in vivo-like neural microtissues.
Analysis of distribution and antibiotic resistance of Gram-positive bacteria isolated from a tertiary-care hospital in southern China: an 8-year retrospective study
Authors: Zhang Xiao , Tan Liming , Ouyang Pengwen , Ma Haiyan , Peng Jianqiao , Shi Ting , Xie Liangyi
Published: October 2023

Objective

Due to the severe drug resistance situation of Gram-negative bacteria, especially Gram-negative enterobacter, relatively little attention has been paid to the changes in Gram-positive bacteria species and drug resistance. Therefore, this study analyzed the prevalence and drug resistance of Gram-positive bacteria in a general tertiary-care hospital from 2014 to 2021, in order to discover the changes in Gram-positive bacteria distribution and drug resistance that cannot be easily identified, inform clinicians in their respective regions when selecting antimicrobial agents, and to provide the basis for the diagnosis of Gram-positive bacterial infection, and for the comprehensive and multi-pronged prevention and control of drug-resistant bacteria.

Methods

A retrospective study was conducted on Gram-positive bacteria isolated from patients presented to a general tertiary-care hospital from January 2014 to December 2021. A total of 15,217 Gram-positive strains were analyzed.

Results

During the 8-year period, the total number and the species of Gram-positive bacteria isolated from clinic increased continuously. The seven most common species were Streptococcus pneumoniae (21.2%), Staphylococcus aureus (15.9%), Enterococcus faecium (20.6%), Enterococcus faecalis (14.0%), and Staphylococcus epidermidis (7.8%), Staphylococcus haemolyticus (4.8%), Streptococcus agalactiae (3.6%). The isolation rates of Staphylococcus aureus and Streptococcus agalactiae increased, and the isolation rate of Enterococcus faecium decreased. The resistance rates of Staphylococcus aureus to erythromycin, clindamycin, tetracycline, rifampicin and furantoin decreased obviously. The resistance rates of Streptococcus pneumoniae to cefepime (non-meningitis) and ceftriaxone (meningitis) decreased significantly. The resistance rates of Enterococcus faecium to penicillin, ampicillin, erythromycin, levofloxacin, ciprofloxacin and furantoin rose rapidly from 50.3, 47.6, 71.5, 44.9, 52.3, and 37.5% in 2014 to 93.1, 91.6, 84.9, 86.8, 86.8, and 60.0% in 2021, respectively.

Conclusion

The total number and the species of Gram-positive bacteria isolated during the 8-year period increased continuously. Streptococcus pneumoniae and Staphylococcus aureus are the main causes of positive bacterial infections in this hospital. The resistance rates of Enterococcus faecium to a variety of commonly used antibiotics increased significantly. Therefore, it is very important to monitor the distribution of bacteria and their resistance to antibiotics to timely evaluate and identify changes in drug resistance that are not easily detected.
Advancing tuberculosis management: the role of predictive, preventive, and personalized medicine
Authors: Dohál Matúš , Porvazník Igor , Solovič Ivan , Mokrý Juraj
Published: October 2023

Tuberculosis is a major global health issue, with approximately 10 million people falling ill and 1.4 million dying yearly. One of the most significant challenges to public health is the emergence of drug-resistant tuberculosis. For the last half-century, treating tuberculosis has adhered to a uniform management strategy in most patients. However, treatment ineffectiveness in some individuals with pulmonary tuberculosis presents a major challenge to the global tuberculosis control initiative. Unfavorable outcomes of tuberculosis treatment (including mortality, treatment failure, loss of follow-up, and unevaluated cases) may result in increased transmission of tuberculosis and the emergence of drug-resistant strains. Treatment failure may occur due to drug-resistant strains, non-adherence to medication, inadequate absorption of drugs, or low-quality healthcare. Identifying the underlying cause and adjusting the treatment accordingly to address treatment failure is important. This is where approaches such as artificial intelligence, genetic screening, and whole genome sequencing can play a critical role. In this review, we suggest a set of particular clinical applications of these approaches, which might have the potential to influence decisions regarding the clinical management of tuberculosis patients.
Immuno-profiling of Brucella proteins for developing improved vaccines and DIVA capable serodiagnostic assays for brucellosis
Authors: Nandini Prachita , Jakka Padmaja , Murugan Subathra , Mazumdar Varadendra , Kumar Deepak , Prakash Richa , Barbuddhe Sukhadeo B. , Radhakrishnan Girish
Published: October 2023

Brucellosis remains a worldwide zoonotic disease with a serious impact on public health and livestock productivity. Controlling brucellosis in livestock is crucial for limiting human infections in the absence of effective human vaccines. Brucellosis control measures are majorly dependent on rigorous monitoring of disease outbreaks and mass vaccination of livestock. Live attenuated vaccines are available for livestock vaccination that play a vital role in brucellosis control programs in many countries. Even though the existing animal vaccines confer protection against brucellosis, they carry some drawbacks, including their infectivity to humans and interference with sero-monitoring. The available serodiagnostic assays for brucellosis depend on detecting anti-LPS antibodies in the serum. Since diagnosis plays a vital role in controlling brucellosis, developing improved serodiagnostic assays with enhanced specificity, sensitivity and DIVA capability is required. Therefore, it is essential to identify novel antigens for developing improved vaccines and serodiagnostic assays for brucellosis. In the present study, we performed a high throughput immunoprofiling of B. melitensis protein microarray using brucellosis-positive human and animal serum samples. The screening identified several serodominant proteins of Brucella that exhibited common or differential reactivity with sera from animals and humans. Subsequently, we cloned, expressed, and purified ten serodominant proteins, followed by analyzing their potential to develop next-generation vaccines and improved serodiagnostic assays for brucellosis. Further, we demonstrated the protective efficacy of one of the serodominant proteins against the B. melitensis challenge in mice. We found that the seroreactive protein, Dps (BMEI1980), strongly reacted with brucellosis-positive serum samples, but it did not react with sera from B. abortus S19-vaccinated cattle, indicating DIVA capability. A prototype lateral flow assay and indirect ELISA based on Dps protein exhibited high sensitivity, specificity, and DIVA capability. Thus, the present study identified promising candidates for developing improved vaccines and affordable, DIVA-capable serodiagnostic assays for animal and human brucellosis.
Strip steel surface defect detection based on lightweight YOLOv5
Authors: Zhang Yongping , Shen Sijie , Xu Sen
Published: October 2023

Deep learning-based methods for detecting surface defects on strip steel have advanced detection capabilities, but there are still problems of target loss, false alarms, large computation, and imbalance between detection accuracy and detection speed. In order to achieve a good balance between detection accuracy and speed, a lightweight YOLOv5 strip steel surface defect detection algorithm based on YOLOv5s is proposed. Firstly, we introduce the efficient lightweight convolutional layer called GSConv. The Slim Neck, designed based on GSConv, replaces the original algorithm's neck, reducing the number of network parameters and improving detection speed. Secondly, we incorporate SimAM, a non-parametric attention mechanism, into the improved neck to enhance detection accuracy. Finally, we utilize the SIoU function as the regression prediction loss instead of the original CIoU to address the issue of slow convergence and improve efficiency. According to experimental findings, the YOLOv5-GSS algorithm outperforms the YOLOv5 method by 2.9% on the NEU-DET dataset and achieves an average accuracy (mAP) of 83.8% with a detection speed (FPS) of 100 Hz, which is 3.8 Hz quicker than the YOLOv5 algorithm. The proposed model outperforms existing approaches and is more useful, demonstrating the efficacy of the optimization strategy.
Significant changes in advanced lung cancer survival during the past decade in Hungary: impact of modern immunotherapy and the COVID-19 pandemic
Authors: Kiss Zoltán , Gálffy Gabriella , Müller Veronika , Moldvay Judit , Sárosi Veronika , Pápai-Székely Zsolt , Csada Edit , Kerpel-Fronius Anna , Király Zsolt , Szász Zoltán , Hódi Gábor , Polányi Zoltán , Kovács Krisztina , Karamousouli Eugenia , Knollmajer Kata , Szabó Tamás G. , Berta Andrea , Vokó Zoltán , Rokszin György , Abonyi-Tóth Zsolt , Barcza Zsófia , Tamási Lilla , Bogos Krisztina
Published: October 2023

Objective

The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database.

Methods

This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology.

Results

In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1–66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011–2012 (28.7% [95% CI: 26.4%–30.9%] vs. 14.45% [95% CI: 13.21%–15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%–25.2%) and 13.37% (95% CI: 11.8%–15.0%) in 2019 and 2011–2012, respectively, the change was statistically significant. Compared to 2011–2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015–2016, 2017–2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020–2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period.

Conclusion

3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic.
A prognostic mathematical model based on tumor microenvironment-related genes expression for breast cancer patients
Authors: Chen Hong , Wang Shan , Zhang Yuting , Gao Xue , Guan Yufu , Wu Nan , Wang Xinyi , Zhou Tianyang , Zhang Ying , Cui Di , Wang Mijia , Zhang Dianlong , Wang Jia
Published: October 2023

Background

Tumor microenvironment (TME) status is closely related to breast cancer (BC) prognosis and systemic therapeutic effects. However, to date studies have not considered the interactions of immune and stromal cells at the gene expression level in BC as a whole. Herein, we constructed a predictive model, for adjuvant decision-making, by mining TME molecular expression information related to BC patient prognosis and drug treatment sensitivity.

Methods

Clinical information and gene expression profiles were extracted from The Cancer Genome Atlas (TCGA), with patients divided into high- and low-score groups according to immune/stromal scores. TME-related prognostic genes were identified using Kaplan-Meier analysis, functional enrichment analysis, and protein-protein interaction (PPI) networks, and validated in the Gene Expression Omnibus (GEO) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to construct and verify a prognostic model based on TME-related genes. In addition, the patients’ response to chemotherapy and immunotherapy was assessed by survival outcome and immunohistochemistry (IPS). Immunohistochemistry (IHC) staining laid a solid foundation for exploring the value of novel therapeutic target genes.

Results

By dividing patients into low- and high-risk groups, a significant distinction in overall survival was found (p < 0.05). The risk model was independent of multiple clinicopathological parameters and accurately predicted prognosis in BC patients (p < 0.05). The nomogram-integrated risk score had high prediction accuracy and applicability, when compared with simple clinicopathological features. As predicted by the risk model, regardless of the chemotherapy regimen, the survival advantage of the low-risk group was evident in those patients receiving chemotherapy (p < 0.05). However, in patients receiving anthracycline (A) therapy, outcomes were not significantly different when compared with those receiving no-A therapy (p = 0.24), suggesting these patients may omit from A-containing adjuvant chemotherapy. Our risk model also effectively predicted tumor mutation burden (TMB) and immunotherapy efficacy in BC patients (p < 0.05).

Conclusion

The prognostic score model based on TME-related genes effectively predicted prognosis and chemotherapy effects in BC patients. The model provides a theoretical basis for novel driver-gene discover in BC and guides the decision-making for the adjuvant treatment of early breast cancer (eBC).
Comparison of lobectomy and sublobar resection for stage I non-small cell lung cancer: a meta-analysis based on randomized controlled trials
Authors: Lu Genlin , Xiang Zhiyi , Zhou Yan , Dai Senjie , Tong Fei , Jiang Renya , Dai Min , Zhang Qiufeng , Zhang Difeng
Published: October 2023

Background

This meta-analysis aimed to compare the prognostic between lobectomy and sublobar resection in patients with stage I non-small cell lung cancer (NSCLC).

Methods

We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) comparing the prognosis of lobectomy and sublobar resection for stage I NSCLC, with the primary outcomes being overall survival (OS) and disease-free survival (DFS).

Results

A total of 2222 patients were included in the 5 RCTs. The results showed no statistical difference in OS (HR=0.87, p=0.445) and DFS (HR=0.99, p=0.918) between patients who underwent lobectomy and sublobar resection during the total follow-up period. In terms of dichotomous variables, there were no statistical differences in OS (relative ratio [RR]=1.05, p=0.848) and DFS (RR=1.21, p=0.075) between the two groups during the total follow-up period, as well as 5-year OS (RR=0.96, p=0.409) and 5-year DFS (RR=0.95, p=0.270). In addition, subgroup analysis showed a better prognosis for non-adenocarcinoma patients with sublobar resection than lobectomy (HR=0.53, p=0.037), but also an increased cause of cancer death (not limited to lung cancer) (RR=1.56, p=0.004).

Conclusion

Our results showed that for stage I NSCLC, lobectomy is usually not a justified operation.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023407301, identifier CRD42023407301.
Association between family income to poverty ratio and HPV infection status among U.S. women aged 20 years and older: a study from NHANES 2003-2016
Authors: Zhao Yuan , Zhao Jing , Xie Ruijie , Zhang Yu , Xu Ya , Mao Jing , Yan Cheng , Sun Yi
Published: October 2023

Background

HPV infection is closely related to the occurrence of cervical cancer and has an important adverse effect on human life and health. This study used data from the NHANES 2003–2016 to investigate the relationship between PIR and HPV infection status among Americans aged 20 and older.

Methods

The data for this cross-sectional investigation came from the 2003–2016 National Health and Nutrition Examination Survey (NHANES), which included 9580 women who were 20 years of age or older. The linear and nonlinear correlations between PIR and the presence of HPV infection were investigated using multiple linear regression and smooth curve fitting. The stability of the relationship across groups was examined using subgroup analysis and interaction tests.

Results

There were 2232 impoverished homes and 2543 rich households among the 9580 adult participants aged 20 and above. PIR (ratio of income to poverty) was found to be significantly inversely related to the presence of HPV infection [0.91 (0.89, 0.94)] after adjusting for all other covariates, and the trend persisted even after categorizing PIR into high- and low-income groups (PIR>4 and PIR<1). In addition, significant negative relationships were discovered in subgroup analyses for women aged 25 to 59 [0.90 (0.88, 0.93)], non-Hispanic whites [0.80 (0.70, 0.92)], non-diabetics [0.91 (0.88, 0.94)], and those who had ever engaged in sex [0.91 (0.89, 0.94)].

Conclusions

PIR was highly and negatively correlated with the presence of HPV infection in American women aged 20 and older. The results of this study are of great significance for preventing HPV infection and improving the accuracy of HPV screening.
Coadministration of bedaquiline and pyrifazimine reduce exposure to toxic metabolite N-desmethyl bedaquiline
Authors: Ding Yangming , Liu Haiting , Wang Furun , Fu Lei , Zhu Hui , Fu Shuang , Wang Ning , Zhuang Xiaomei , Lu Yu
Published: October 2023

Background: A new, effective anti-tuberculosis (TB) regimen containing bedaquiline (BDQ) and pyrifazimine (TBI-166) has been recommended for a phase IIb clinical trial. Preclinical drug–drug interaction (DDI) studies of the combination of BDQ and TBI-166 have been designed to support future clinical trials. In this study, we investigated whether a DDI between BDQ and TBI-166 affects the pharmacokinetics of BDQ.

Methods: We performed in vitro quantification of the fractional contributions of the fraction of drug metabolism by individual CYP enzymes (fm) of BDQ and the inhibition potency of key metabolic pathways of TBI-166. Furthermore, we conducted an in vivo steady-state pharmacokinetics study in a murine TB model and healthy BALB/c mice.

Results: The in vitro fm value indicated that the CYP3A4 pathway contributed more than 75% to BDQ metabolism to N-desmethyl-bedaquiline (M2), and TBI-166 was a moderate (IC50 2.65 µM) potential CYP3A4 inhibitor. Coadministration of BDQ and TBI-166 greatly reduced exposure to metabolite M2 (AUC0-t 76310 vs 115704 h ng/mL, 66% of BDQ alone), whereas the exposure to BDQ and TBI-166 did not changed. The same trend was observed both in healthy and TB model mice. The plasma concentration of M2 decreased significantly after coadministration of BDQ and TBI-166 and decreased further during treatment in the TB model.

Conclusions: In conclusion, our results showed that the combination of BDQ and TBI-166 significantly reduced exposure to the toxic metabolite M2 by inhibiting the activity of the CYP3A4 pathway. The potential safety and efficacy benefits demonstrated by the TB treatment highly suggest that coadministration of BDQ and TBI-166 should be studied further.
In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban
Authors: Wang Zhi , Li Ying , He Xueru , Fu Yuhao , Li Yajing , Zhou Xin , Dong Zhanjun
Published: October 2023

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment.

Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR).

Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.
Prediction of an epidemic spread based on the adaptive genetic algorithm
Authors: Chen Bolun , Han Shuai , Liu Xiaoluan , Li Zhe , Chen Ting , Ji Min
Published: October 2023

In recent years, coronavirus disease 2019 (COVID-19) has plagued the world, causing huge losses to the lives and property of people worldwide. How to simulate the spread of an epidemic with a reasonable mathematical model and then use it to analyze and to predict its development trend has attracted the attention of scholars from different fields. Based on the susceptible–infected–recovered (SIR) propagation model, this work proposes the susceptible–exposed–infected–recovered–dead (SEIRD) model by introducing a specific medium having many changes such as the self-healing rate, lethality rate, and re-positive rate, considering the possibility of virus propagation through objects. Finally, this work simulates and analyzes the propagation process of nodes in different states within this model, and compares the model prediction results optimized by the adaptive genetic algorithm with the real data. The experimental results show that the susceptible–exposed–infected–recovered–dead model can effectively reflect the real epidemic spreading process and provide theoretical support for the relevant prevention and control departments.
Myocardial stretch-induced compliance is abrogated under ischemic conditions and restored by cGMP/PKG-related pathways
Authors: Leite-Moreira André M. , Almeida-Coelho João , Neves João S. , Castro-Ferreira Ricardo , Ladeiras-Lopes Ricardo , Leite-Moreira Adelino F. , Lourenço André P.
Published: October 2023

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI.

Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure–volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats.

Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading.

Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia.
Metabolomic and transcriptomic analyses identify external conditions and key genes underlying high levels of toxic glycoalkaloids in tubers of stress-sensitive potato cultivars
Authors: Merino Irene , Guasca Alexandra Olarte , Krmela Ales , Arif Usman , Ali Ashfaq , Westerberg Erik , Jalmi Siddhi Kashinanth , Hajslova Jana , Schulzova Vera , Sitbon Folke
Published: October 2023

Introduction

High levels of toxic steroidal glycoalkaloids (SGAs) in potato tubers constitute a recognized food quality problem. Tuber SGA levels vary between potato cultivars and can increase after post-harvest stresses such as wounding and light exposure. A few cultivars, e.g., ‘Magnum Bonum’ and ‘Lenape,’ have been withdrawn from commercial sales due to excessive SGA levels during some cultivation years. However, these sudden SGA increases are diffucult to predict, and their causes are not understood. To identify external and genetic factors that underlie sudden SGA increases in certain potato cultivars, we have here in a 2-year study investigated ‘Magnum Bonum’ and five additional table potato cultivars for their SGA levels after wounding and light exposure.

Results and methods

Results showed that ‘Magnum Bonum’ has an unusual strong SGA response to light exposure, but not to wounding, whereas ‘Bintje’ displayed an opposite regulation. Levels of calystegine alkaloids were not significantly altered by treatments, implicating independent metabolic regulation of SGA and calystegine levels also under conditions of high SGA accumulation. Metabolomic and transcriptomic analyses identified a small number of key genes whose expression correlated with SGA differences between cultivars. Overexpression of two key genes in transgenic low-SGA potato cultivars increased their leaf SGA levels significantly.

Discussion

The results show that a strong response to light can underlie the SGA peaks that occasionally occur in certain potato cultivars and indicate that a between-cultivar variation in the expression of single SGA key genes can account for cultivar SGA differerences. We propose that current attempts to mitigate the SGA hazard will benefit from an increased consideration of cultivar-dependent SGA responses to post-harvest conditions, particularly light exposure. The identified key SGA genes can now be used as a molecular tool in this work.
Genome-wide association mapping and genomic prediction for late blight and potato cyst nematode resistance in potato (Solanum tuberosum L.)
Authors: Sood Salej , Bhardwaj Vinay , Bairwa Aarti , Dalamu  , Sharma Sanjeev , Sharma Ashwani K. , Kumar Ashwani , Lal Mehi , Kumar Vinod
Published: October 2023

Potatoes are an important source of food for millions of people worldwide. Biotic stresses, notably late blight and potato cyst nematodes (PCN) pose a major threat to potato production worldwide, and knowledge of genes controlling these traits is limited. A genome-wide association mapping study was conducted to identify the genomic regulators controlling these biotic stresses, and the genomic prediction accuracy was worked out using the GBLUP model of genomic selection (GS) in a panel of 222 diverse potato accessions. The phenotype data on resistance to late blight and two PCN species (Globodera pallida and G. rostochiensis) were recorded for three and two consecutive years, respectively. The potato panel was genotyped using genotyping by sequencing (GBS), and 1,20,622 SNP markers were identified. A total of 7 SNP associations for late blight resistance, 9 and 11 for G. pallida and G. rostochiensis, respectively, were detected by additive and simplex dominance models of GWAS. The associated SNPs were distributed across the chromosomes, but most of the associations were found on chromosomes 5, 10 and 11, which have been earlier reported as the hotspots of disease-resistance genes. The GS prediction accuracy estimates were low to moderate for resistance to G. pallida (0.04-0.14) and G. rostochiensis (0.14-0.21), while late blight resistance showed a high prediction accuracy of 0.42-0.51. This study provides information on the complex genetic nature of these biotic stress traits in potatoes and putative SNP markers for resistance breeding.
Plant salinity stress, sensing, and its mitigation through WRKY
Authors: Rai Gyanendra Kumar , Mishra Sonal , Chouhan Rekha , Mushtaq Muntazir , Chowdhary Aksar Ali , Rai Pradeep K. , Kumar Ranjeet Ranjan , Kumar Pradeep , Perez-Alfocea Francisco , Colla Giuseppe , Cardarelli Mariateresa , Srivastava Vikas , Gandhi Sumit G.
Published: October 2023

Salinity or salt stress has deleterious effects on plant growth and development. It imposes osmotic, ionic, and secondary stresses, including oxidative stress on the plants and is responsible for the reduction of overall crop productivity and therefore challenges global food security. Plants respond to salinity, by triggering homoeostatic mechanisms that counter salt-triggered disturbances in the physiology and biochemistry of plants. This involves the activation of many signaling components such as SOS pathway, ABA pathway, and ROS and osmotic stress signaling. These biochemical responses are accompanied by transcriptional modulation of stress-responsive genes, which is mostly mediated by salt-induced transcription factor (TF) activity. Among the TFs, the multifaceted significance of WRKY proteins has been realized in many diverse avenues of plants’ life including regulation of plant stress response. Therefore, in this review, we aimed to highlight the significance of salinity in a global perspective, the mechanism of salt sensing in plants, and the contribution of WRKYs in the modulation of plants’ response to salinity stress. This review will be a substantial tool to investigate this problem in different perspectives, targeting WRKY and offering directions to better manage salinity stress in the field to ensure food security.
Serendipita indica mitigates drought-triggered oxidative burst in trifoliate orange by stimulating antioxidant defense systems
Authors: Wang Yu , Cao Jin-Li , Hashem Abeer , Abd_Allah Elsayed Fathi , Wu Qiang-Sheng
Published: October 2023

Soil drought is detrimental to plant growth worldwide, particularly by triggering reactive oxygen species (ROS) burst. Serendipita indica (Si), a culturable root-associated endophytic fungus, can assist host plants in dealing with abiotic stresses; however, it is unknown whether and how Si impacts the drought tolerance of citrus plants. To unravel the effects and roles of Si on drought-stressed plants, trifoliate orange (Poncirus trifoliata L. Raf.; a citrus rootstock) seedlings were inoculated with Si and exposed to soil drought, and growth, gas exchange, ROS levels, antioxidant defense systems, and expression of genes encoding antioxidant enzymes and fatty acid desaturases in leaves were measured. Soil drought suppressed plant biomass, whereas Si inoculation significantly increased plant biomass (10.29%-22.47%) and shoot/root ratio (21.78%-24.68%) under ample water and drought conditions, accompanied by improved net photosynthetic rate (105.71%), water use efficiency (115.29%), chlorophyll index (55.34%), and nitrogen balance index (63.84%) by Si inoculation under soil drought. Soil drought triggered an increase in leaf hydrogen peroxide and superoxide anion levels, while Si inoculation significantly reduced these ROS levels under soil drought, resulting in lower membrane lipid peroxidation with respect to malondialdehyde changes. Furthermore, Si-inoculated seedlings under soil drought had distinctly higher levels of ascorbate and glutathione, as well as catalase, peroxidase, and glutathione peroxidase activities, compared with no-Si-inoculated seedlings. Si inoculation increased the expression of leaf PtFAD2, PtFAD6, PtΔ9, PtΔ15, PtFe-SOD, PtCu/Zn-SOD, PtPOD, and PtCAT1 genes under both ample water and soil drought conditions. Overall, Si-inoculated trifoliate orange plants maintained a low oxidative burst in leaves under drought, which was associated with stimulation of antioxidant defense systems. Therefore, Si has great potential as a biostimulant in enhancing drought tolerance in plants, particularly citrus.
Unlocking the hidden potential of Mexican teosinte seeds: revealing plant growth-promoting bacterial and fungal biocontrol agents
Authors: De-la-Vega-Camarillo Esaú , Hernández-García Juan Alfredo , Villa-Tanaca Lourdes , Hernández-Rodríguez César
Published: October 2023

The bacterial component of plant holobiont maintains valuable interactions that contribute to plants’ growth, adaptation, stress tolerance, and antagonism to some phytopathogens. Teosinte is the grass plant recognized as the progenitor of modern maize, domesticated by pre-Hispanic civilizations around 9,000 years ago. Three teosinte species are recognized: Zea diploperennis, Zea perennis, and Zea mays. In this work, the bacterial diversity of three species of Mexican teosinte seeds was explored by massive sequencing of 16S rRNA amplicons. Streptomyces, Acinetobacter, Olivibacter, Erwinia, Bacillus, Pseudomonas, Cellvibrio, Achromobacter, Devosia, Lysobacter, Sphingopyxis, Stenotrophomonas, Ochrobactrum, Delftia, Lactobacillus, among others, were the bacterial genera mainly represented. The bacterial alpha diversity in the seeds of Z. diploperennis was the highest, while the alpha diversity in Z. mays subsp. mexicana race was the lowest observed among the species and races. The Mexican teosintes analyzed had a core bacteriome of 38 bacterial genera, including several recognized plant growth promoters or fungal biocontrol agents such as Agrobacterium, Burkholderia, Erwinia, Lactobacillus, Ochrobactrum, Paenibacillus, Pseudomonas, Sphingomonas, Streptomyces, among other. Metabolic inference analysis by PICRUSt2 of bacterial genera showed several pathways related to plant growth promotion (PGP), biological control, and environmental adaptation. The implications of these findings are far-reaching, as they highlight the existence of an exceptional bacterial germplasm reservoir teeming with potential plant growth promotion bacteria (PGPB). This reserve holds the key to cultivating innovative bioinoculants and formidable fungal antagonistic strains, thereby paving the way for a more sustainable and eco-friendly approach to agriculture. Embracing these novel NGS-based techniques and understanding the profound impact of the vertical transference of microorganisms from seeds could revolutionize the future of agriculture and develop a new era of symbiotic harmony between plants and microbes.