Global biomarker trends in Parkinson's disease research: A bibliometric analysis.

As the second most common neurodegenerative disease globally, Parkinson's disease (PD) affects millions of people worldwide. In recent years, the scientific publications related to PD biomarker research have exploded, reflecting the growing interest in unraveling the complex pathophysiology of PD. In this study, we aim to use various bibliometric tools to identify key scientific concepts, detect emerging trends, and analyze the global trends and development of PD biomarker research.The research encompasses various stages of biomarker development, including exploration, identification, and multi-modal research. MOVEMENT DISORDERS emerged as the leading journal in terms of publications and citations. Key authors such as Mollenhauer and Salem were identified, while the University of Pennsylvania and USA stood out in collaboration and research output. NEUROSCIENCES emerged as the most important research direction. Key biomarker categories include α-synuclein-related markers, neurotransmitter-related markers, inflammation and immune system-related markers, oxidative stress and mitochondrial function-related markers, and brain imaging-related markers. Furthermore, future trends in PD biomarker research focus on exosomes and plasma biomarkers, miRNA, cerebrospinal fluid biomarkers, machine learning applications, and animal models of PD. These trends contribute to early diagnosis, disease progression monitoring, and understanding the pathological mechanisms of PD.

Neutrophil hitchhiking nanoparticles enhance bacteria-mediated cancer therapy via NETosis reprogramming.

Bacteria have shown great potential in anti-tumor treatment, and an attenuated strain of Salmonella named VNP20009 has been shown to be safe in clinical trials. However, colonized bacteria recruit neutrophils into the tumor, which release NETs to capture and eliminate bacteria, compromising bacterial-based tumor treatment. In this study, we report a neutrophil hitchhiking nanoparticles (SPPS) that block the formation of NET to enhance bacteria-mediated tumor therapy. In the 4 T1 tumor-bearing mouse model, following 24 h of bacterial therapy, there was an approximately 3.0-fold increase in the number of neutrophils in the bloodstream, while the amount of SPPS homing to tumor tissue through neutrophil hitchhiking increased approximately 2.0-fold. It is worth noting that the NETs in tumors significantly decreased by approximately 2.0-fold through an intracellular ROS scavenging-mediated NETosis reprogramming, thereby increasing bacterial vitality by 1.9-fold in tumors. More importantly, the gene drug (siBcl-2) loaded in SPPS can be re-encapsulated in apoptotic bodies by reprogramming neutrophils from NETosis to apoptosis, and enable the redelivery of drugs to tumor cells, further boosting the antitumor efficacy with a synergistic effect, resulting in about 98% tumor inhibition rate and 90% survival rate.

Heat shock induces HuR-dependent MKP-1 posttranslational regulation through the p38 MAPK signaling cascade.

Previous studies demonstrated that phosphatases play a pivotal role in modulating inflammation-associated signal transduction, particularly in the context of heat shock, where Mitogen-Activated Protein Kinase Phosphatase-1 (MKP-1) appears to have a central role. Recently, Human Antigen R (HuR) has also been identified as a factor that enhances stress-response protein MKP-1 levels. Consequently, we have directed our interest towards elucidating the mechanisms by which heat shock induces MKP-1 mRNA stabilization, dependent on HuR via the p38 MAPK Signaling Cascade. In this study, we subjected Mouse Embryonic Fibroblast (Mef) cells to heat shock treatment, resulting in a potent stabilization MKP-1 mRNA. The RNA-binding protein HuR, known to influence mRNA, was observed to bind to the MKP-1 AU-rich 3 ´untranslated region. Transfection of p38 wild-type Mef cells with a flag-HuR plasmid resulted in a significant increase in MKP-1 mRNA stability. Interestingly, transfection of the siRNA for HuR into Mef cells resulted in diminished MKP-1 mRNA stability following heat shock, inhibition of p38 MAPK activity effectively curtailed heat shock-mediated MKP-1 mRNA stability. Immunofluorescence analyses further revealed that the translocation of HuR was contingent on p38 MAPK Signaling Cascade. Collectively, these findings underscore the regulatory role of heat shock in MKP-1 gene expression at posttranscriptional levels. The mechanisms underlying the observed increased MKP-1 mRNA stability are shown to be partially dependent on HuR through the p38 MAPK Signaling Cascade.

Deoxynivalenol (DON)-Triggered Dual-Color Composite Probe Based on Gold Nanoclusters for Simultaneous Imaging of DON and miR-34a in Living Cells.

Deoxynivalenol (DON) is a mycotoxin secreted by Fusarium species, posing great harm to food safety and human health. Therefore, it is of great significance to study its toxic effects and mechanism. miR-34a is a representative biomarker during the process of DON-induced apoptosis. Herein, a DON-triggered dual-color composite probe was constructed for simultaneous imaging of DON and miR-34a in living cells. The aptamer blocks the recognition sequence of miR-34a to realize DON-triggered cell imaging. The specific binding of DON with its aptamer and HCR induced by miR-34a resulted in the recovery of fluorescence of the dual-color Au NCs. Under the optimal conditions, the correlation between the relative fluorescence intensities of dual-color Au NCs showed good linear relationships with the logarithm of DON and miR-34a concentration, respectively. With the increase in DON concentration (0-20 µg/mL) and stimulation time (0-12 h), the fluorescence of dual-color Au NCs gradually recovered. This dual-color Au NCs composite probe can realize simultaneous detection of DON and miR-34a induced by DON, which is significant for verifying the cytotoxic mechanism of DON.

Unveiling the hidden clues: Döhle body-like inclusions as morphological markers for MYH9-related disorders: A case report.

RATIONALE: This study aimed to address the diagnostic challenges associated with MYH9-related disorders (MYH9-RDs) and highlight the importance of recognizing Döhle body-like inclusions as crucial diagnostic markers for this condition. PATIENT CONCERNS: Patients with MYH9-RDs often present with mild and diverse clinical characteristics, leading to misdiagnosis, delayed diagnosis, and inappropriate treatments, such as hormonal therapy and splenectomy. This section highlights the significance of understanding atypical clinical presentations and their impact on patients' well-being. DIAGNOSES: This section emphasizes the misdiagnosis of MYH9-RDs as immune thrombocytopenia due to overlapping clinical features. This highlights the need for a comprehensive approach, including detailed personal and family history, careful review of peripheral blood smears, and identification of Döhle body-like inclusions to differentiate MYH9-RDs from other conditions. INTERVENTION: This study advocates for a shift in the diagnostic approach, urging physicians to pay closer attention to the morphological features observed in peripheral blood smears, particularly the presence of Döhle body-like inclusions and large platelets. This emphasizes the importance of avoiding unnecessary diagnostic studies through effective utilization of this simple and reliable method. OUTCOMES: By adopting a comprehensive approach that combines gene sequencing with morphological analysis, an accurate diagnosis of MYH9-RDs can be achieved. Early identification of MYH9-RDs allows for appropriate management strategies, genetic counseling, and prevention of complications associated with the condition. LESSONS: This section highlights the lessons learned from this study, emphasizing the need for increased awareness among healthcare professionals about MYH9-RDs and the importance of incorporating peripheral blood smear evaluations into the diagnostic process. This emphasizes the significance of accurate diagnosis to prevent unnecessary treatments and ensure appropriate patient care.

Du-Moxibustion in a Mouse Model of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a progressively worsening and disabling form of arthritis that primarily affects the axial skeleton. This disease mainly involves the spine and the sacroiliac joint. Fusion of the spine and the sacroiliac joint may occur in the later stage of the disease, resulting in spinal stiffness and kyphosis, as well as difficulty in walking, which seriously affects the quality of work and daily living activities and imposes a heavy burden on the patient, the family, and society. Increasing attention has been paid to non-pharmacotherapy as an alternative therapy for AS. Moxibustion is an ancient therapeutic technique used in Traditional Chinese Medicine (TCM). Du-moxibustion therapy, a unique and innovative external treatment developed on the basis of ordinary moxibustion, has a definite therapeutic effect on AS. Du-moxibustion skillfully combines the compatible techniques of TCM to integrate meridians, acupoints, Chinese herbal medicine, and moxibustion. This paper describes the operation procedures and precautions to be taken during Du-moxibustion in experimental mice in detail to provide an experimental basis for the study of the mechanism of Du-moxibustion in the treatment of AS.

Frontiers in chronic fatigue syndrome research: An analysis of the top 100 most influential articles in the field.

Chronic fatigue syndrome (CFS) is a complex constellation of symptoms that significantly reduces the quality of life among affected individuals and increases public health expenditures. We conducted a search on the Web of Science Core Collection database and selected the top 100 cited articles in the field of CFS. Several literature analysis tools, including CiteSpace 6.1.R6, VOSviewer 1.6.19, and Scimago Graphica 1.0.30, were utilized to integrate the most influential research papers and academic journals in order to obtain a comprehensive understanding of the CFS field. The top 100 highly-cited publications were published in 67 reputable journals, with contributions from 250 institutions across 26 countries/regions involved in CFS research. This demonstrates the extensive attention and coverage of CFS research by high-quality academic journals and institutions, highlighting the interdisciplinary and multidisciplinary nature of CFS studies. The journal with the highest publication volume and total citations was Lancet. The top 5 co-occurring keywords were chronic fatigue syndrome, cognitive behavior therapy, epidemiology, definition, and disorders, indicating the ongoing attention researchers have devoted to the diagnostic criteria and clinical studies of CFS. Cluster analysis results suggested that primary care, infectious retrovirus, gene expression, and metabolomics may become the focal points and trends in future CFS research. The prospective research directions in this field include the search for biological markers, with a particular focus on immunology; the advancement of diagnostic techniques; the screening of risk genes associated with CFS; and the conduct of epidemiological investigations.

Frontiers of monkeypox research: An analysis from the top 100 most influential articles in the field.

Background: Monkeypox (MPX) has made recurrence after decades as a neglected zoonotic disease. More nations have reported endemic monkeypox in the past decade than in the previous forty. The World Health Organization has warned that the world may face another significant challenge after dealing with COVID-19, a pandemic, and the Monkeypox outbreak. Early appraisal of monkeypox research and development allows researchers to anticipate solutions for large outbreaks. We conducted a bibliometric analysis of this study's top 100 cited papers to identify regional research patterns. Methods: Our method was to search the SCI-Expanded database on Web of Science (WOS) for the top 100 papers that were cited in MPX on this database. We examined relevant literature from different years, journals, countries/regions, institutions, authors, and keywords.In order to create knowledge maps, we used the programs VOSviewer, Citespace, Scimago Graphica and the bibliometric online analysis platform. After compiling the relevant literature in Excel, we could estimate the field's focus and trends. Results: A total of 47 journals from 36 countries and regions published the top 100 cited papers between 1999 and 2023. The majority of articles were published in EMERGING INFECTIOUS DISEASES, while the highest average number of citations per paper were found in the NEW ENGLAND JOURNAL OF MEDICINE. The UNITED STATES contributed the most publications, followed by ENGLAND and SWITZERLAND. As far as the total number of publications goes, the Centers for Disease Control & Prevention in the USA, the National Institute of Health in the USA, and the World Health Organization each contributed the most papers. The major categories are immunology, virology and infectious diseases. The top five keywords were infection, Congo, virus, smallpox, and transmission. The cluster analysis suggests MPX research will focus on safe and effective vaccines and epidemic prevention. Conclusion: By using bibliometric analysis, MPX researchers can quickly and visually identify their research focus and boundaries. Although studies suggest that antiviral medicine is the best treatment, creating an effective vaccine might lessen and avoid MPX pandemics in the long term. Our findings imply that safe and effective vaccines may be the focus and trends for future MPX research. International coordination for case monitoring and identification is essential to understand monkeypox disease's ever-changing epidemiology.

Insights into electrochemical oxidation of tris(2-butoxyethyl) phosphate (TBOEP) in aquatic media: Degradation performance, mechanisms and toxicity changes of intermediate products.

Tris (2-butoxyethyl) phosphate (TBOEP) has gained significant attention due to its widespread presence and potential toxicity in the environment. In this study, the degradation of TBOEP in aquatic media was investigated using electrochemical oxidation technology. The anode Ti/SnO2-Sb/La-PbO2 demonstrated effective degradation performance, with a reaction constant (k) of 0.6927 min-1 and energy consumption of 1.24 kW h/m3 at 10 mA/cm2. CV tests, EPR tests, and quenching experiments confirmed that indirect degradation is the main degradation mechanism and ·OH radicals were the predominant reactive species, accounting for up to 93.8%. The presence of various factors, including Cl-, NO3-, HCO3- and humic acid (HA), inhibited the degradation of TBOEP, with the inhibitory effect dependent on the concentrations. A total of 13 intermediates were identified using UPLC-Orbitrap-MS/MS, and subsequent reactions led to their further degradation. Two main degradation pathways involving bond breaking, hydroxylation, and oxidation were proposed. Both Flow cytometry and the ECOSAR predictive model indicated that the intermediates exhibited lower toxic than the parent compound, resulting in a high detoxification rate of 95.9% for TBOEP. Although the impact of TBOEP on the phylum-level microbial community composition was found to be insignificant, substantial alterations in bacterial abundance were noted when examining the genus level. The dominant genus Methylotenera, representing 17.4% in the control group, decreased to 6.9% in the presence of TBOEP and slightly increased to 8.7% in the 4-min exposure group of degradation products. Electrochemical oxidation demonstrated its effectiveness for the degradation and detoxification of TBOEP in aqueous solutions, while it is essential to consider the potential impact of degradation products on sediment microbial communities.

The activation of SIRT1 by resveratrol reduces breast cancer metastasis to lung through inhibiting neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) play a crucial role in breast cancer metastasis. However, the therapeutic target of NETs in breast cancer metastasis is still unknown. Using a natural metabolite library and single-cell sequencing data analysis, we identified resveratrol (RES), a polyphenolic natural phytoalexin, and agonist of silent information regulator-1 (SIRT1) that suppressed NETs formation after cathepsin C (CTSC) treatment. In vivo, RES significantly hindered breast cancer metastasis in a murine orthotopic 4T1 breast cancer model. Serum levels of myeloperoxidase-DNA and neutrophil elastase-DNA in mouse breast cancer model were significantly lower after RES treatment. Correspondingly, the tumour infiltrated CD8+T cells in the lungs increased after the treatment. Mechanistically, RES targets SIRT1 in neutrophils and significantly inhibits the citrullination of histones H3, which is essential for chromatin decondensation and NETs formation. Furthermore, we identified that the NETs were suppressed by RES in bone marrow neutrophils after CTSC treatment, while specific deficiency of SIRT1 in neutrophils promoted NETs formation and breast cancer to lung metastasis. Thus, our results revealed that RES could be potentially identified as a viable therapeutic drug to prevent neutrophil cell death and breast cancer metastasis.

Partial response to RC-48 as palliative treatment in a patient with locallocally advanced carcinoma ex pleomorphic adenoma harboring a HER2 mutation: a case report.

BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is a neoplasm of the salivary gland that causes 3.6% of salivary gland tumors and 12% of salivary gland malignancies. Its prognosis is determined by the histological progression beyond the adenoma capsule. CXPA is thought to be a malignant transformation of a primary or recurrent pleomorphic adenoma and is associated with both benign and malignant lesions. Salivary gland cancers represent a rare heterogeneous group of neoplasms with complex clinicopathological characteristics and distinct biological behavior. CASE DESCRIPTION: This case report summarizes the treatment of a 57-year-old male patient with CXPA of the left parotid gland, harboring HER2 amplification with poor prognosis. The overall survival of the patient has been > 3.5 years. The application and outcome of an immune checkpoint inhibitor and targeted therapy combination regimens in the treatment of CXPA carcinoma are discussed. CONCLUSION: Targeted therapy combined with immunotherapy has long-term clinical benefits and targeted therapy which has a high clinical response rate (immunotherapy + dual-targeting three-drug regimens) may present an ideal choice for the treatment of patients with rare and/or refractory tumors without compromising patient safety.

Metagenomic insights into the mechanisms of triphenyl phosphate degradation by bioaugmentation with Sphingopyxis sp. GY.

Biodegradation of triphenyl phosphate (TPHP) by Sphingopyxis sp. GY was investigated, and results demonstrated that TPHP could be completely degraded in 36 h with intracellular enzymes playing a leading role. This study, for the first time, systematically explores the effects of the typical brominated flame retardants, organophosphorus flame retardants, and heavy metals on TPHP degradation. Our findings reveal that TCPs, BDE-47, HBCD, Cd and Cu exhibit inhibitory effects on TPHP degradation. The hydrolysis-, hydroxylated-, monoglucosylated-, methylated products and glutathione (GSH) conjugated derivative were identified and new degradation pathway of TPHP mediated by microorganism was proposed. Moreover, toxicity evaluation experiments indicate a significant reduction in toxicity following treatment with Sphingopyxis sp. GY. To evaluate its potential for environmental remediation, we conducted bioaugmentation experiments using Sphingopyxis sp. GY in a TPHP contaminated water-sediment system, which resulted in excellent remediation efficacy. Twelve intermediate products were detected in the water-sediment system, including the observation of the glutathione (GSH) conjugated derivative, monoglucosylated product, (OH)2-DPHP and CH3-O-DPHP for the first time in microorganism-mediated TPHP transformation. We further identify the active microbial members involved in TPHP degradation within the water-sediment system using metagenomic analysis. Notably, most of these members were found to possess genes related to TPHP degradation. These findings highlight the significant reduction of TPHP achieved through beneficial interactions and cooperation established between the introduced Sphingopyxis sp. GY and the indigenous microbial populations stimulated by the introduced bacteria. Thus, our study provides valuable insights into the mechanisms, co-existed pollutants, transformation pathways, and remediation potential associated with TPHP biodegradation, paving the way for future research and applications in environmental remediation strategies.

Frontiers of ankylosing spondylitis research: an analysis from the top 100 most influential articles in the field.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that frequently results in disability. It has a negative impact on patients' quality of life and puts an enormous budgetary and societal burden on society. The most effective treatment for AS has grown to be a significant issue worldwide. In order to pinpoint research focus and trends in this region, we performed a bibliometric analysis of the top 100 cited papers in this study. We searched the Science Citation Index Expanded (SCI-Expanded) on the Web of Science (WOS) and selected the top 100 cited papers based on AS. The pertinent literature from various years, journals, nations/regions, institutions, authors, keywords, and references were then examined. To construct knowledge maps, we used the VOSviewer, CiteSpace, and Scimago Graphica programs. Excel was then used to compile the information from the pertinent literature that we had retrieved, and we were able to make predictions about the focus and trends that were currently occurring in the field. Between 1999 and 2019, the top 100 cited papers appeared in 23 journals from 36 different nations and regions. Annals of the rheumatic diseases published the majority of the articles, while Lancet had the highest average number of citations per paper. Germany contributed the most publications, followed by the Netherlands and the USA. In terms of the total number of publications, Rheumazentrum Ruhrgebiet contributed the most papers, followed by University Hospital Maastricht and Leiden University. The three major categories are Rheumatology, Medicine, General & Internal, and Genetics & Heredity, whereas the top 5 co-occurrence of keywords included rheumatoid arthritis, double-blind, disease activity, efficacy, and infliximab. The cluster analysis results indicate that inflammation and immunology, safe and effective therapies, and placebo-controlled trials may be focus and trends for future AS research. Bibliometric analysis can swiftly and visually identify the focus and boundaries of AS research. Our findings imply that inflammation and immunology, safe and effective therapies, and placebo-controlled trials may be focus and trends for future AS research.

AURKA Identified as Potential Lung Cancer Marker through Comprehensive Bioinformatic Analysis and Experimental Verification.

Non-small-cell lung cancer (NSCLC) is a malignancy with high overall morbidity and mortality due to a lack of reliable methods for early diagnosis and successful treatment of the condition. We identified genes that would be valuable for the diagnosis and prognosis of lung cancer. Common DEGs (DEGs) in three GEO datasets were selected for KEGG and GO enrichment analysis. A protein-protein interaction (PPI) network was constructed using the STRING database, and molecular complex detection (MCODE) identified hub genes. Gene expression profiling interactive analysis (GEPIA) and the Kaplan-Meier method analyzed hub genes expression and prognostic value. Quantitative PCR and western blotting were used to test for differences in hub gene expression in multiple cell lines. The CCK-8 assay was used to determine the IC50 of the AURKA inhibitor CCT137690 in H1993 cells. Transwell and clonogenic assays validated the function of AURKA in lung cancer, and cell cycle experiments explored its possible mechanism of action. Overall, 239 DEGs were identified from three datasets. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 had shown great potential for lung cancer diagnosis and prognosis. In vitro experiments suggested that AURKA significantly influenced the proliferation and migration of lung cancer cells and activities related to the dysregulation of the cell cycle. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 may be critical genes that influence the occurrence, development, and prognosis of NSCLC. AURKA significantly affects the proliferation and migration of lung cancer cells by disrupting the cell cycle.

Real-World Experience of PD-1 Inhibitors for Relapsed and Refractory Hodgkin Lymphoma: A Multicenter Retrospective Analysis of Patients in China.

INTRODUCTION: Despite the promising clinical trial data regarding programmed death 1 (PD-1) inhibitors in relapsed/refractory classical Hodgkin lymphoma (R/R cHL), there remains a paucity of studies describing the outcomes of patients in a real-world setting, especially for Asian cohort. METHODS: We present a multicenter retrospective analysis of patients with R/R cHL who had failed ≥2 prior lines of therapies and received sintilimab or tislelizumab developed in China (sintilimab or tislelizumab monotherapy) at 3 medical centers from January 2019 to September 2021. Efficacy was evaluated with progression-free survival (PFS), overall survival, duration of response (DOR), best overall response (BOR) including objective response rate (ORR), complete response rate (CRR). Safety data were also recorded. RESULTS: 74 patients were reviewed. The median age was 38 years (range, 14-85 years). The ORR, CRR, and disease control rate were 78.3%, 52.7%, and 91.9%, respectively. The median duration of follow-up was 22 (4-36) months. Four patients (5.4%) died of disease progression. The median PFS and DOR was 22.1 and 23.5 months. BOR as a new emergent endpoint was found to be the only independent prognostic factor for PFS in our study (HR = 6.234, p = 0.005), suggesting this endpoint carries stronger prognostic value over traditional endpoints in the immunotherapy era. 66 (89.2%) patients reported adverse event (AE) with any grade, with the majority of AEs being grade 1 or 2. CONCLUSION: We presented a unique real-life experience and conducted a relatively long follow-up of PD-1 antibodies developed in China for R/R HL patients which confirmed their promising effectiveness and manageable side effects given in real world in an Asian cohort. Even for those who would usually be excluded in most of clinical trials such as elderly or minor patients, anti-PD-1 monotherapy also showed a significant improvement of outcomes. Furthermore, the depth of response seemed to be a more powerful predictive tool in new era, which might serve as a basis for future immune risk-adapted strategies.

Integrative bioinformatics approaches to establish potential prognostic immune-related genes signature and drugs in the non-small cell lung cancer microenvironment.

Introduction: Research has revealed that the tumor microenvironment (TME) is associated with the progression of malignancy. The combination of meaningful prognostic biomarkers related to the TME is expected to be a reliable direction for improving the diagnosis and treatment of non-small cell lung cancer (NSCLC). Method and Result: Therefore, to better understand the connection between the TME and survival outcomes of NSCLC, we used the "DESeq2" R package to mine the differentially expressed genes (DEGs) of two groups of NSCLC samples according to the optimal cutoff value of the immune score through the ESTIMATE algorithm. A total of 978 up-DEGs and 828 down-DEGs were eventually identified. A fifteen-gene prognostic signature was established via LASSO and Cox regression analysis and further divided the patients into two risk sets. The survival outcome of high-risk patients was significantly worse than that of low-risk patients in both the TCGA and two external validation sets (p-value < 0.05). The gene signature showed high predictive accuracy in TCGA (1-year area under the time-dependent ROC curve (AUC) = 0.722, 2-year AUC = 0.708, 3-year AUC = 0.686). The nomogram comprised of the risk score and related clinicopathological information was constructed, and calibration plots and ROC curves were applied, KEGG and GSEA analyses showed that the epithelial-mesenchymal transition (EMT) pathway, E2F target pathway and immune-associated pathway were mainly involved in the high-risk group. Further somatic mutation and immune analyses were conducted to compare the differences between the two groups. Drug sensitivity provides a potential treatment basis for clinical treatment. Finally, EREG and ADH1C were selected as the key prognostic genes of the two overlapping results from PPI and multiple Cox analyses. They were verified by comparing the mRNA expression in cell lines and protein expression in the HPA database, and clinical validation further confirmed the effectiveness of key genes. Conclusion: In conclusion, we obtained an immune-related fifteen-gene prognostic signature and potential mechanism and sensitive drugs underling the prognosis model, which may provide accurate prognosis prediction and available strategies for NSCLC.

A fluorescence and surface-enhanced Raman scattering dual-mode aptasensor for sensitive detection of deoxynivalenol based on gold nanoclusters and silver nanoparticles modified metal-polydopamine framework.

Deoxynivalenol (DON), a common mycotoxin produced by Fusarium species, poses a great threat to human and animal body. Hence, it is of significance to develop an ultrasensitive and reliable method for DON detection. Herein, a fluorescence and surface-enhanced Raman scattering (FL-SERS) dual-mode aptasensor was designed for the detection of DON based on gold nanoclusters (Au NCs) and silver nanoparticles modified metal-polydopamine framework (Ag NPs/MPDA). In this aptasensor, complementary DNA modified Au NCs (cDNA-Au NCs) was selected as fluorescence probe, and 6-carboxytetramethylrhodamine (TAMRA)-labeled aptamer modified Ag NPs/MPDA (Ag NPs/MPDA-Apt-TAMRA) was employed as SERS probe, in which Ag NPs/MPDA acted as SERS substance and fluorescence quencher, and TAMRA acted as Raman label. The superior binding affinity of the aptamer with DON to cDNA can regulate the fluorescence and Raman signal intensities and realize the quantitative determination of DON. Under the optimal conditions, the aptasensor exhibited a low detection limit of 0.08 ng mL-1 (0.1-100 ng mL-1) in FL mode and 0.06 ng mL-1 (0.1-100 ng mL-1) in SERS mode. In addition, it was successfully applied for DON detection in wheat flour. We believe that the proposed FL-SERS strategy has a promising application in the detection of mycotoxins.

The Development of Drug Delivery Systems for Efficient Intracranial Hemorrhage Therapy.

Intracerebral hemorrhage (ICH) is the most devastating form of stroke, which accounts for 10-15% of cases and causes high morbidity and mortality. With the continuous exploration of the pathological mechanism of ICH, extensive research focusing on ICH therapy has been conducted. However, the traditional treatment methods, such as surgery for removing the hematoma and pharmacotherapy for improving the clearance of the hematoma and neuroprotection, are greatly limited due to their poor practicality and treatment efficiency. The rapid development of drug delivery systems offers an important prospect for treating ICH as they exhibit great versatility, which can improve the pharmacokinetic behavior of drugs in vivo, increase the drug accumulation in specific cell types or tissues, and enhance the therapeutic effect with diminished toxic effect. In this review, the main molecular pathological mechanisms of ICH are comprehensively described and the limitation of traditional pharmacotherapy are also discussed. Then the development based on drug delivery systems for treating ICH is highlighted. Finally, based on these discussions the challenges of drug delivery systems with a view to providing a new feasible path for the treatment of ICH are summarized.

FBP1 induced by ß-elemene enhances the sensitivity of gefitinib in lung cancer.

BACKGROUND: ß-elemene is known to play a critical role in tumorigenesis as well as tyrosine kinase inhibitor (TKI) resistance in lung cancer. However, the biological function and molecular mechanism remain largely unknown. METHODS: In this study, the common genes involved in gefitinib resistance and ß-elemene were identified using bioinformatic analysis. The expression of FBP1 was examined by qRT-PCR and Western blot analysis. Cell proliferation, flow cytometry, clone formation and IC50 assays were performed to assess the effects of ß-elemene and FBP1. Western blot analysis was used to evaluate apoptosis-related gene expression. Finally, in vivo experiments were conducted to assess the crucial role of FBP1 in gefitinib-resistant HCC827/GR cells in nude mice. RESULTS: Screening analysis demonstrated that fructose-1,6-bisphosphatase (FBP1) was induced by ß-elemene and downregulated in gefitinib-resistant lung cells. Functionally, overexpression of FBP1 inhibited proliferation and gefitinib resistance and promoted apoptosis of PC9/GR and HCC827/GR cells in vitro. Mechanistically, FBP1 impeded the nuclear translocation of p-STAT3. The FBP1/STAT3 axis was required for FBP1-mediated apoptosis-related gene expression. In vivo experiments further confirmed the enhanced effects of FBP1 on lung cancer cell sensitivity to gefitinib. CONCLUSION: Our research indicated that ß-elemene suppressed proliferation and enhanced sensitivity to gefitinib by inducing apoptosis through the FBP1/STAT3 axis in gefitinib-resistant lung cancer cells.

Oxygen-independent alkyl radical nanogenerator enhances breast cancer therapy.

The hypoxic microenvironment of breast cancer substantially reduces oxygen-dependent free radical generation. Overexpression of glutathione (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2'-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical treatment. In vivo and in vitro assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.