Heterogeneity analysis of low-risk HPV infection and high-risk HPV infection, HPV-positive and HPV-negative cancers

Zahlreiche Studien belegen, dass humane Papillomaviren (HPV) Krebs verursachen können. Allerdings haben nur wenige Studien die Heterogenität von HPV-infizierten oder nicht-infizierten (HPV-pos. und HPV-neg.) Krebserkrankungen untersucht. Zu-dem werden HPV-Infektionen mit niedrigem Risiko in der Regel mit gutartigen Läsio-nen in Verbindung gebracht, wobei sich nur wenige Studien mit der Heterogenität von HPV-Infektionen mit niedrigem und hohem Risiko befasst haben. Mit der Ent-wicklung von Next-Generation-Sequenzierung ist es möglich, Genome auf Einzelzel-lebene zu amplifizieren und zu sequenzieren, so dass die Heterogenität der Zellen mithilfe der Einzelzellsequenzierungstechnologie beobachtet werden kann. Auf die-ser Grundlage werden zukünftig eine genauere Diagnose und Behandlung von HPV-Patienten möglich sein. In dieser Studie wurde versucht, dieses Problem zu lösen, indem die Einzelzellse-quenzierung mit der bulk-RNA-Sequenzierung kombiniert wurde, wobei die Einzel-zellsequenzierungsdaten Veränderungen auf zellulärer Ebene lieferten und die bulk-RNA-Sequenzierungsdaten große Stichprobengrößen mit passenden klinischen In-formationen enthielten. Die beiden wurden kombiniert, um mit Hilfe mehrerer Me-thoden wie Seurat für Zellcluster, CIBERSORT für Variationen der Immuninfiltration, WGCNA für charakteristische assoziierte Gencluster usw. zu analysieren. Zunächst wurde die Hypothese aufgestellt, dass es eine Heterogenität zwischen HPV-pos. und HPV-neg.-Karzinomen gibt, und zwar von der Transkriptionsebene bis hin zur Immuninfiltration. Durch die Untersuchung von Gebärmutterhalskrebs, die mit Hochrisiko-HPV-Infektionen assoziiert ist, wurde bestätigt, dass CD8+ T-Zellen und B-Zellen herunterreguliert wurden, während T-Reg-Zellen, CD4+ T-Zellen und Epithelzellen in der HPV-pos.-Zervixkrebsgruppe hochreguliert waren. Die Analyse gutartiger Läsionen, die mit einer Niedrigrisiko-HPV-Infektion assoziiert sind, ergab Folgendes: Eine Niedrigrisiko-HPV-Infektion weist ähnliche genetische Veränderun-gen auf wie eine Hochrisiko-HPV-Infektion. Genetische Veränderungen, die durch eine Niedrigrisiko-HPV-Infektion verursacht werden, können auch die Prognose von Krebspatienten beeinflussen. Die Analyse von AIN3 und ASCC, CIN3 und CESC, präkanzerösen Läsionen und Tumoren, die in engem Zusammenhang mit Hochrisiko-HPV-Infektionen stehen, bestätigte auch, dass die Auswirkungen von Niedrigrisiko-HPV-Infektionen und Hochrisiko-HPV-Infektionen Ähnlichkeiten und Unterschiede aufweisen. Die Veränderungen in den Immunzellen waren bei den verschiedenen HPV-Infektionen teilweise gleich, während der Rest der Veränderungen in den Im-munzellen durch die Krankheit selbst verursacht werden kann. Die Induktion von oxidativem Stress ist bei den verschiedenen HPV-Infektionen gleich, was zu oxidati-vem Stress führt, der DNA-Schäden verursacht und das optimale Umfeld für eine maligne Transformation schafft. Schließlich wurde diese Erkenntnis durch in-vitro-Experimente bestätigt, bei denen sowohl normale als auch Krebszelllinien, die mit HPV transfiziert wurden, eine erhöhte Proliferation und eine hohe Expression von mit oxidativem Stress verbundenen Genen aufwiesen, und die hoch exprimierten Gene waren in der Lage, die Empfindlichkeit von mit oxidativem Stress assoziierten Inhibitoren zu erhöhen. Die Bedeutung dieser Studie liegt in der Erklärung der Heterogenität zwischen HPV-pos. und HPV-neg.-Karzinomen und in der Entdeckung, dass die Gemeinsamkeit zwi-schen Niedrigrisiko-HPV-Infektionen und Hochrisiko-HPV-Infektionen im oxidativen Stress liegt. Dies könnte eine wichtige Entdeckung für eine künftige Präzisionsmedi-zin sein, damit Patienten mit HPV-assoziierten Krebserkrankungen präzise gezielte Behandlungen erhalten können.Numerous studies have established the causal relationship between Human Papil-lomavirus (HPV) and cancer development. Nevertheless, there exists a paucity of research efforts dedicated to investigating the heterogeneity observed in HPV-associated cancers, differentiating between HPV-positive (HPV-pos.) and HPV-negative (HPV-neg.) cases. Furthermore, while low-risk HPV infections have tradi-tionally been linked to benign lesions, investigations exploring the intricacies within both low-risk and high-risk HPV infections have been limited in scope. The advent of next-generation sequencing technologies, particularly single-cell sequencing, has revolutionized the field by facilitating genome amplification and sequencing at the single-cell level. This cutting-edge technology offers the unique capability to eluci-date cellular heterogeneity, presenting a promising avenue for enhancing the preci-sion of diagnostic and therapeutic approaches for HPV-infected patients, capitalizing on this newfound understanding of variability within the disease. This study aimed to address this issue by integrating single-cell sequencing with bulk-RNA sequencing and DNA methylation sequencing. Single-cell sequencing data illuminated cellular-level alterations, while bulk-RNA sequencing and DNA methyla-tion sequencing data encompassed larger sample sizes with accompanying clinical information. The analytical toolbox included methods such as Seurat for cell cluster-ing, CIBERSORT for assessing immune infiltration variations, and WGCNA for identi-fying clusters of genes with characteristic associations. Initially, we hypothesized that heterogeneity exists between HPV-pos. and HPV-neg. cancers, spanning from the transcriptional level to immune infiltration. In the con-text of the most well-established high-risk HPV infection-associated cancer, cervical cancer, CD8+ T cells and B cells were observed to be down-regulated, whereas T-reg cells, CD4+ T cells, and epithelial cells were up-regulated in the HPV-pos. cervical can-cer group. Subsequent analysis of benign lesions associated with low-risk HPV infec-tion revealed shared genetic alterations with high-risk HPV infection, and these ge-netic alterations impacted the prognosis of cancer patients. Furthermore, the exam-ination of AIN3 and ASCC, CIN3 and CESC, precancerous lesions, and tumors firmly linked to high-risk HPV infection reaffirmed that while low-risk HPV infection and high-risk HPV infection share similarities, differences also exist. Changes in immune cells were partially consistent across different HPV infections, while other immune cell alterations may be attributed to the disease itself. It was observed that oxida-tive stress, common to various HPV infections, induced DNA damage, creating an environment conducive to malignant transformation. This finding was further cor-roborated by in vitro experiments, where both normal and cancer cell lines trans-fected with HPV exhibited increased proliferation and upregulated expression of oxidative stress-related genes. These highly expressed genes increased sensitivity to oxidative stress-associated inhibitors. The significance of this study lies in elucidating the heterogeneity between HPV-pos. and HPV-neg. cancers and identifying oxidative stress as a common factor in low-risk and high-risk HPV infections. Additionally, the altered sensitivity to genetic inhibi-tors resulting from HPV-induced genetic changes offers novel prospects for the treatment of HPV-pos. cancers, potentially paving the way for precision medicine approaches tailored to patients with HPV-associated cancers

Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models

Background: Numerous studies support that Human papillomavirus (HPV) can cause cervical cancer. However, few studies have surveyed the heterogeneity of HPV infected or uninfected (HPV+ and HPV-) cervical cancer (CESC) patients. Integration of scRNA-seq and TCGA data to analyze the heterogeneity of HPV+ and HPV- cervical cancer patients on a single-cell level could improve understanding of the cellular mechanisms during HPV-induced cervical cancer. Methods: CESC scRNA-seq data obtained from the Gene Expression Omnibus (GEO) database and the Seurat, Monocle3 package were used for scRNA-seq data analysis. The ESTIMATE package was used for single-sample gene immune score, CIBERSORT package was used to identify immune scores of cells, and the “WGCNA” package for the weighted correlation network analysis. Univariate Cox and LASSO regression were performed to establish survival and relapse signatures. KEGG and GO analyses were performed for the signature gene. Gene Expression Profiling Interactive Analysis was used for Pan-cancer analysis. Results: In the HPV+ CESC group, CD8+ T cells and B cells were down-regulated, whereas T reg cells, CD4+ T cells, and epithelial cells were up-regulated according to scRNA-seq data. Survival analysis of TCGA-CESC revealed that increased expression of naive B cells or CD8+ T cells favors the survival probability of CESC patients. WGCNA, univariate Cox, and LASSO Cox regression established a 9-genes survival signature and a 7-gene relapse model. Pan-cancer analysis identified IKZF3, FOXP3, and JAK3 had a similar distribution and effects in HPV-associated HNSC. Conclusion: Analysis of scRNA-seq and bulk RNA-seq of HPV+ and HPV- CESC samples revealed heterogeneity from transcriptional state to immune infiltration. Survival and relapse models were adjusted according to the heterogeneity of HPV+ and HPV- CESC immune cells to assess the prognostic risk accurately. Hub genes represent similar protection in HPV- associated HNSC while showing irrelevant to other potential HPV-related cancer

Enhancement of the Wettability and Lubrication of Shale Rock via Nanoemulsions

Nanoemulsions have been widely used as additives for drilling fluids in recent years. With the development of nanotechnology, multifunctional nanomaterials have been added to nanoemulsions. The improvement of wettability of the surfaces, alteration of oil-wet on shale rock surfaces, and environmentally friendly conditions are considered as the future development directions of nanoemulsions. In this work, a novel nanoemulsion was prepared by using hydrocarbon-based polyoxyethylene ether, oil (hydrocarbon), distilled water, and formation crude oil as the main raw materials. The shale rocks before and after immersion with as-prepared nanoemulsion were characterized by contact angle measurement, atomic force microscope (AFM), and Fourier transform infrared spectroscopy (FTIR). It is clearly observed that the nanoemulsion greatly improved the wettability of the sandstone and rock surface by forming a layer of active agent film on the surface of the rock. The as-prepared nanoemulsion had good ability to curb the anticollapse and lubricate and protect the oil and gas layer

Comprehensive genomic profiling reveals prognostic signatures and insights into the molecular landscape of colorectal cancer

BackgroundColorectal cancer (CRC) is a prevalent malignancy with diverse molecular characteristics. The NGS-based approach enhances our comprehension of genomic landscape of CRC and may guide future advancements in precision oncology for CRC patients.MethodIn this research, we conducted an analysis using Next-Generation Sequencing (NGS) on samples collected from 111 individuals who had been diagnosed with CRC. We identified somatic and germline mutations and structural variants across the tumor genomes through comprehensive genomic profiling. Furthermore, we investigated the landscape of driver mutations and their potential clinical implications.ResultsOur findings underscore the intricate heterogeneity of genetic alterations within CRC. Notably, BRAF, ARID2, KMT2C, and GNAQ were associated with CRC prognosis. Patients harboring BRAF, ARID2, or KMT2C mutations exhibited shorter progression-free survival (PFS), whereas those with BRAF, ARID2, or GNAQ mutations experienced worse overall survival (OS). We unveiled 80 co-occurring and three mutually exclusive significant gene pairs, enriched primarily in pathways such as TP53, HIPPO, RTK/RAS, NOTCH, WNT, TGF-Beta, MYC, and PI3K. Notably, co-mutations of BRAF/ALK, BRAF/NOTCH2, BRAF/CREBBP, and BRAF/FAT1 correlated with worse PFS. Furthermore, germline AR mutations were identified in 37 (33.33%) CRC patients, and carriers of these variants displayed diminished PFS and OS. Decreased AR protein expression was observed in cases with AR germline mutations. A four-gene mutation signature was established, incorporating the aforementioned prognostic genes, which emerged as an independent prognostic determinant in CRC via univariate and multivariate Cox regression analyses. Noteworthy BRAF and ARID2 protein expression decreases detected in patients with their respective mutations.ConclusionThe integration of our analyses furnishes crucial insights into CRC’s molecular characteristics, drug responsiveness, and the construction of a four-gene mutation signature for predicting CRC prognosis

Characterization and Antioxidant Activity of the Complex of Phloridzin and Hydroxypropyl-β- cyclodextrin

Purpose: To improve the aqueous solubility of phloridzin by complexing it with hydroxypropyl-β-cyclodextrin (HP-β-CD). Methods: The complex of phloridzin with HP-β-CD was prepared by freeze-drying method. The physicochemical properties of the complex were investigated by ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), differential scanning calorimetry (DSC) and x-ray diffractometry (XRD). The antioxidant activity was examined by DPPH and ABTS radical-scavenging activities. Results: Phloridzin in the complex was molecularly dispersed in HP-β-CD matrix. The complex was an effective scavenger of DPPH and ABTS radicals. At a concentration of 0.8 mg/mL and 30 μg/mL, DPPH and ABTS radical scavenging activities of the complex were 83.7 and 74.9 %, respectively. Conclusion: By forming inclusion complex with HP-β-CD, the solubility of phloridzin in water was significantly enhanced. The complex showed strong DPPH and ABTS radical scavenging activities

Numerical and Constitutive Modeling of Quasi-static and Dynamic Mechanical Behavior in Graded Additively Manufactured Lattice Structures

10.1080/17452759.2023.2283027Virtual and Physical Prototyping181(1)-(23

Characterization of the complete chloroplast genome of Cynanchum acutum subsp. sibiricum (Apocynaceae)

In this study, we assembled the complete chloroplast (cp) genome of Cynanchum acutum subsp. sibiricum using high-throughput Illumina sequencing reads. The resulting chloroplast genome assembly displayed a typical quadripartite structure with a total length of 158,283 bp, which contained a pair of inverted repeat regions (IRs) of 24,459 bp. These two IRs were separated by a large single-copy region (LSC) and a small single-copy region (SSC) of 89,424 bp and 19,941 bp in length, respectively. The C. acutum subsp. sibiricum cp genome contained 130 genes, and its overall GC content was 37.87%. Phylogenetic analysis among C. acutum subsp. sibiricum and nine other Cynanchum species demonstrated that C. acutum subsp. sibiricum was closely related to C. chinense. The C. acutum subsp. sibiricum cp genome presented in this study lays a good foundation for further genetic and genomic studies of the Cynanchum as well as Apocynaceae

Design of an industrial chemical looping gasification system

A design methodology for an industrial Chemical Looping Gasification (CLG) unit is proposed, including the reactor system, oxygen carrier, solid fuel, key parameters, mass and energy balance, reactor dimension, and emissions. To determine a reactor system for CLG, the first design step is to choose between four types of systems and their applicability. The selection of a circulating material and a particle size of the oxygen carrier and the solid fuel is discussed. Determination of the key operating parameters comprises oxygen-to-fuel ratio, steam-to-fuel ratio, charging/discharging of the oxygen carrier and the conversion difference between an air reactor and a fuel reactor, their temperatures, velocities in each reactor, and cyclone efficiency. As design basis, the mass and energy balance of the system is computed based on the distribution of syngas composition and oxygen transportation over the system. It is not critical to obtain an adequate circulation for a CLG unit. But to satisfy the heat balance, oxygen transport and reasonable efficiency of syngas production at the same time makes CLG technology challenging. More work is needed for the introduced design items in the case of commercial-scale units