Exosomal microRNAs associated with tuberculosis among people living with human immunodeficiency virus.

Objective: To investigate the diagnostic value of selected exosomal miRNAs for Tuberculosis (TB) among people living with human immunodeficiency virus (PLHIV). Methods: A total of 43 adult HIV patients, including 20 diagnosed with TB and 23 controls, were enrolled. The levels of six exosomal miRNAs (miR-20a, miR-20b, miR-26a, miR-106a, miR-191, and miR-486) were measured using qRT-PCR. Results: The levels of these six exosomal miRNAs (miR-20a, miR-20b, miR-26a, miR-106a, miR-191, and miR-486) were significantly higher in the plasma of TB patients compared to controls among PLHIV. The Receiver Operating Characteristic (ROC) curve of these six miRNAs showed a fair performance in distinguishing TB patients from controls, with Area Under Curve (AUC) values of 0.78 (95 %CI 0.63-0.93), 0.81 (95 %CI 0.67-0.95), 0.77 (95 %CI 0.61-0.93), 0.84 (95 %CI 0.70-0.98), 0.82 (95 %CI 0.68-0.95) and 0.79 (95 %CI 0.65-0.93), respectively. These miRNAs showed higher AUC values for extrapulmonary tuberculosis compared to pulmonary tuberculosis. An analysis of subgroups was performed based on CD4 + T cell count (＜200 and ≥ 200 cells·µL-1). In the high CD4 count group, all these six exosomal miRNAs appeared to have higher AUC values compared to the low CD4 count group. Conclusions: These six exosomal miRNAs could serve as potential biomarkers for diagnosing TB among PLHIV.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

Global biomarker trends in triple-negative breast cancer research: a bibliometric analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in cancer tissue. The lack of specific biomarkers makes the diagnosis and prognosis of TNBC challenging. METHOD: A comprehensive literature review and bibliometric analysis was performed using CiteSpace, VOSviewer and Scimago Graphica. RESULTS: TNBC biomarker research has been growing rapidly in recent years, reflecting the enormous academic interest in TNBC biomarker research. A total of 127 journals published relevant studies and 1749 authors were involved in the field, with developed countries such as the United States, France, and the United Kingdom contributing greatly to the field. Collaborative network analysis found that the research in this field has not yet formed good communication and interaction, and the partnership should be strengthened in the future in order to promote the in-depth development of TNBC biomarker research. Comprehensive analysis of keywords and co-cited literature, etc. found that TNBC biomarker research mainly focuses on immune checkpoint markers, microenvironment-related markers, circulating tumour DNA, metabolic markers, genomics markers and so on. These research hotspots will help to better understand the molecular characteristics and biological processes of TNBC, and provide more accurate biomarkers for its diagnosis, treatment and prognosis. CONCLUSIONS: The bibliometric analysis highlighted global trends and key directions in TNBC biomarker research. Future developments in TNBC biomarker research are likely to be in the direction of multi-omics integration, meticulous study of the microenvironment, targeted therapeutic biomarkers, application of liquid biopsy, application of machine learning and artificial intelligence, and individualised therapeutic strategies. Young scholars should learn and collaborate across disciplines, pay attention to new technologies and methods, improve their data analysis skills, and continue to follow up on the latest research trends in order to meet the challenges and opportunities in the field of TNBC biomarkers.

The mechanism and clinical application of farnesyl diphosphate farnesyltransferase 1 in cancer metabolism.

Cancer poses a significant risk to human well-being. Among the crucial characteristics of cancer is metabolic reprogramming. To meet the relentless metabolic needs, cancer cells enhance cholesterol metabolism within the adverse tumor microenvironment. Reprograming cholesterol metabolism includes a series of modifications in the synthesis, absorption, esterification, and metabolites associated with cholesterol. These adjustments have a strong correlation with the proliferation, invasion, metastasis, and other characteristics of malignant tumors. FDFT1, also known as farnesyl diphosphate farnesyltransferase 1, is an enzyme crucial in the process of cholesterol biosynthesis. Its significant involvement in tumor metabolism has garnered considerable interest. The significance of FDFT1 in cancer metabolism cannot be overstated, as it actively interacts with cancer cells. This paper aims to analyze and consolidate the mechanism of FDFT1 in cancer metabolism and explore its clinical application. The goal is to contribute new strategies and targets for the prevention and treatment of cancer metabolism.

Du-moxibustion ameliorates depression-like behavior and neuroinflammation in chronic unpredictable mild stress-induced mice.

BACKGROUND: Neuroinflammation is involved in the advancement of depression. Du-moxibustion can treat depression. Here, we explored whether Du-moxibustion could alleviate neuroglia-associated neuro-inflammatory process in chronic unpredictable mild stress (CUMS) mice. METHODS: C57BL/6J mice were distributed into five groups. Except for the CON group, other four groups underwent CUMS for four consecutive weeks, and Du-moxibustion was given simultaneously after modeling. Behavioral tests were then carried out. Additionally, Western blot was conducted to measure the relative expression levels of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). Immunofluorescence was employed to evaluate the positive cells of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were analyzed using an ELISA assay. RESULTS: We found that CUMS induced depression-like behaviors, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, decreased the time in open arms and prolonged immobility. Furthermore, versus the CON group, the expression of HMGB1, TLR4, MyD88, NF-κB, positive cells of Iba-1, IL-1ß and TNF-α were increased but positive cells of GFAP were decreased in CUMS group. However, the detrimental effects were ameliorated by treatment with CUMS+FLU and CUMS+DM. LIMITATIONS: A shortage of this study is that only CUMS model of depression were used, while other depression model were not included. CONCLUSIONS: Du-moxibustion alleviates depression-like behaviors in CUMS mice mainly by reducing neuroinflammation, which offers novel insights into the potential treatment of depression.

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China.

BACKGROUND: Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the "real-world" use of relma-cel, especially for patients with CNS involvement. PATIENTS AND METHODS: Retrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events. RESULTS: Among the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55-618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12-32 days). CONCLUSIONS: This study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.

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.