Exploring research progress in studying serum exosomal miRNA-21 as a molecular diagnostic marker for breast cancer.

Breast cancer is one of the most prevalent malignancies affecting women globally and poses a significant public health challenge. Early clinical detection plays a pivotal role in providing optimal treatment opportunities and favorable prognoses, crucial for reducing breast cancer mortality and enhancing patients' quality of life. Therefore, the timely identification and diagnosis of breast cancer are imperative. Conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3), serve as reliable methods for actively monitoring disease progression and have become a routine auxiliary diagnostic approach in clinical settings. However, these biomarkers exhibit limitations in sensitivity and specificity, particularly in the early screening and diagnosis of tumors, often yielding results inconsistent with clinical manifestations. In recent years, research has increasingly focused on exosomes released by tumor cells as potential new biomarkers for early stage breast cancer screening. Exosomes carry various components, including tumor-derived proteins, nucleic acids, and lipids. This paper delves into the specific utilization of serum exosomal microRNA-21 (miR-21) as a biomarker for early detection and diagnosis of breast cancer, evaluating its efficacy within this framework.

Impacts of ABCG2 loss of function variant (p. Gln141Lys, c.421 C > A, rs2231142) on lipid levels and statin efficiency: a systematic review and meta-analysis.

BACKGROUND: The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. METHODS: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. RESULTS: Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. CONCLUSIONS: The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

Exosomes based strategies for cardiovascular diseases: Opportunities and challenges.

Exosomes, as nanoscale extracellular vesicles (EVs), are secreted by all types of cells to facilitate intercellular communication in living organisms. After being taken up by neighboring or distant cells, exosomes can alter the expression levels of target genes in recipient cells and thereby affect their pathophysiological outcomes depending on payloads encapsulated therein. The functions and mechanisms of exosomes in cardiovascular diseases have attracted much attention in recent years and are thought to have cardioprotective and regenerative potential. This review summarizes the biogenesis and molecular contents of exosomes and details the roles played by exosomes released from various cells in the progression and recovery of cardiovascular disease. The review also discusses the current status of traditional exosomes in cardiovascular tissue engineering and regenerative medicine, pointing out several limitations in their application. It emphasizes that some of the existing emerging industrial or bioengineering technologies are promising to compensate for these shortcomings, and the combined application of exosomes and biomaterials provides an opportunity for mutual enhancement of their performance. The integration of exosome-based cell-free diagnostic and therapeutic options will contribute to the further development of cardiovascular regenerative medicine.

Solvent-tuned perovskite heterostructures enable visual linoleic acid assay and edible oil species discrimination via wavelength shift.

Linoleic acid (LA) detection and edible oils discrimination are essential for food safety. Recently, CsPbBr3@SiO2 heterostructures have been widely applied in edible oil assays, while deep insights into solvent effects on their structure and performance are often overlooked. Based on the suitable polarity and viscosity of cyclohexane, we prepared CsPbBr3@SiO2 Janus nanoparticles (JNPs) with high stability in edible oil and fast halogen-exchange (FHE) efficiency with oleylammonium iodide (OLAI). LA is selectively oxidized by lipoxidase to yield hydroxylated derivative (oxLA) capable of reacting with OLAI, thereby bridging LA content to naked-eye fluorescence color changes through the anti-FHE reaction. The established method for LA in edible oils exhibited consistent results with GC-MS analysis (p > 0.05). Since the LA content difference between edible oils, we further utilized chemometrics to accurately distinguish (100%) the species of edible oils. Overall, such elaborated CsPbBr3@SiO2 JNPs enable a refreshing strategy for edible oil discrimination.

Colorimetry/fluorescence dual-mode detection of Salmonella typhimurium based on a "three-in-one" nanohybrid with high oxidase-like activity for AIEgen.

A colorimetry/fluorescence dual-mode assay based on the aptamer-functionalized magnetic covalent organic framework-supported CuO and Au NPs (MCOF-CuO/Au@apt) was developed for Salmonella typhimurium (S. typhimurium) biosensing. The nanohybrid combined three functions in one: good magnetic separation characteristic, excellent oxidase-mimic activity for tetrap-aminophenylethylene (TPE-4A), and target recognition capability. The attachment of MCOF-CuO/Au@apt onto the surface of S. typhimurium resulted in a significant reduction in the oxidase-mimicking activity of the nanohybrid, which could generate dual-signal of colorimetry and fluorescence through the catalytic oxidation of TPE-4A. Based on this, S. typhimurium could be specifically detected in the linear ranges of 102- 106 CFU·mL-1 and 101- 106 CFU·mL-1, with LODs of 7.6 and 2.1 CFU·mL-1, respectively in colorimetry/fluorescence modes. Moreover, the smartphone and linear discrimination analysis-based system could be used for on-site and portable testing. In addition, this platform showed applicability in detecting S. typhimurium in milk, egg liquid and chicken samples.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Synthesis of Size-Adjustable CsPbBr3 Perovskite Quantum Dots for Potential Photoelectric Catalysis Applications.

As a direct band gap semiconductor, perovskite has the advantages of high carrier mobility, long charge diffusion distance, high defect tolerance and low-cost solution preparation technology. Compared with traditional metal halide perovskites, which regulate energy band and luminescence by changing halogen, perovskite quantum dots (QDs) have a surface effect and quantum confinement effect. Based on the LaMer nucleation growth theory, we have synthesized CsPbBr3 QDs with high dimensional homogeneity by creating an environment rich in Br- ions based on the general thermal injection method. Moreover, the size of the quantum dots can be adjusted by simply changing the reaction temperature and the concentration of Br- ions in the system, and the blue emission of strongly confined pure CsPbBr3 perovskite is realized. Finally, optical and electrochemical tests suggested that the synthesized quantum dots have the potential to be used in the field of photocatalysis.

Vascular endothelial cells-derived exosomes synergize with curcumin to prevent osteoporosis development.

Osteoporosis has gradually become a major public health problem. Further elucidation of the pathophysiological mechanisms that induce osteoporosis and identification of more effective therapeutic targets will have important clinical significance. Experiments in vitro on bone marrow stem cells (BMSCs) subjected to osteogenic and adipogenic differentiation and in vivo on surgical bilateral ovariectomy (OVX) mouse models revealed that exosomes of vascular endothelial cells (EC-EXOs) can promote osteogenic differentiation of BMSCs and inhibit BMSC adipogenic differentiation through miR-3p-975_4191. Both miR-3p-975_4191 and curcumin can target tumor necrosis factor (TNF) and act synergistically to regulate BMSCs fate differentiation and delay the progression of osteoporosis. Our findings suggest that EC-EXOs may exert a synergistic effect with curcumin in reversing the progression of osteoporosis by targeting TNF via miR-3p-975_4191. Our study may provide therapeutic options and potential therapeutic targets for osteoporosis and thus has important clinical implications.

Rapid and multi-target genotyping of Helicobacter pylori with digital microfluidics.

Helicobacter pylori (H. pylori) infection correlates closely with gastric diseases such as gastritis, ulcers, and cancer, influencing more than half of the world's population. Establishing a rapid, precise, and automated platform for H. pylori diagnosis is an urgent clinical need and would significantly benefit therapeutic intervention. Recombinase polymerase amplification (RPA)-CRISPR recently emerged as a promising molecular diagnostic assay due to its rapid detection capability, high specificity, and mild reaction conditions. In this work, we adapted the RPA-CRISPR assay on a digital microfluidics (DMF) system for automated H. pylori detection and genotyping. The system can achieve multi-target parallel detection of H. pylori nucleotide conservative genes (ureB) and virulence genes (cagA and vacA) across different samples within 30 min, exhibiting a detection limit of 10 copies/rxn and no false positives. We further conducted tests on 80 clinical saliva samples and compared the results with those derived from real-time quantitative polymerase chain reaction, demonstrating 100% diagnostic sensitivity and specificity for the RPA-CRISPR/DMF method. By automating the assay process on a single chip, the DMF system can significantly reduce the usage of reagents and samples, minimize the cross-contamination effect, and shorten the reaction time, with the additional benefit of losing the chance of experiment failure/inconsistency due to manual operations. The DMF system together with the RPA-CRISPR assay can be used for early detection and genotyping of H. pylori with high sensitivity and specificity, and has the potential to become a universal molecular diagnostic platform.

The role of soluble adenylyl cyclase in sensing and regulating intracellular pH.

Soluble adenylyl cyclase (sAC) differs from transmembrane adenylyl cyclases (tmAC) in many aspects. In particular, the activity of sAC is not regulated by G-proteins but by the prevailing bicarbonate concentrations inside cells. Therefore, sAC serves as an exquisite intracellular pH sensor, with the capacity to translate pH changes into the regulation of localization and/or activity of cellular proteins involved in pH homeostasis. In this review, we provide an overview of literature describing the regulation of sAC activity by bicarbonate, pinpointing the importance of compartmentalization of intracellular cAMP signaling cascades. In addition, examples of processes involving proton and bicarbonate transport in different cell types, in which sAC plays an important regulatory role, were described in detail.

Domino Michael/Oxa-Michael Reactions of the Unsymmetric Double Michael Acceptor for Access to Bicyclic Furo[2,3-b]pyrrole.

By creating an unsymmetric double Michael acceptor 1, we were able to synthesize the nonaromatic-fused bicyclic furo[2,3-b]pyrrole nucleus using a domino Michael/oxa-Michael reaction. Adopting benzoyl acetonitrile 2d (CN as the electron-withdrawing group) as a substrate, we discovered a (DHQ)2AQN-catalyzed method for high diastereo- and enantioselectivity of those products. The reaction path has been determined by isolating the reaction intermediates, and density functional theory calculations support these findings. Beyond providing a synthetic approach, this work illustrated the compounds' possible use in antitumor activity.

A Smartphone-Enabled Colorimetric Platform Based on Enzyme Cascade Amplification Strategy for Detection of Staphylococcus aureus in Milk.

Staphylococcus aureus (S. aureus) is a pathogenic bacterium-contaminating milk and dairy foods causing food poisoning and foodborne pathogens. In this work, a smartphone-enabled enzyme cascade-triggered colorimetric platform was constructed using cascade bio-nanozyme formed by immobilized glucose oxidase (GOx) on the Fe3O4@Ag for rapid detection of S. aureus. Benefiting from reasonable experimental design, a bio-nanozyme cascade-triggered reaction was achieved through H2O2 produced by GOx oxidation of glucose, followed by in situ catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) by the inherent peroxidase-like activity of Fe3O4@Ag to produce color signals. S. aureus detection could be performed through naked-eye observation and smartphone measurement, the developed assay can achieve quantitative and qualitative detection of S. aureus. The on-site nanoplatform had satisfactory specificity and sensitivity with a low detection limit of 6.9 cfu·mL-1 in 50 min. Moreover, the nanoplatform has good practicality in the detection of S. aureus in milk samples. Therefore, the assay has potential application prospects in food safety inspection.

Cobalt Ion-Stabilized VO2 for Aqueous Ammonium Ion Hybrid Supercapacitors.

Aqueous ammonium ion hybrid supercapacitor (A-HSC) is an efficient energy storage device based on nonmetallic ion carriers (NH4+), which combines advantages such as low cost, safety, and sustainability. However, unstable electrode structures are prone to structural collapse in aqueous electrolytes, leading to fast capacitance decay, especially in host materials represented by vanadium-based oxidation. Here, the Co2+ preintercalation strategy is used to stabilize the VO2 tunnel structure and improve the electrochemical stability of the fast NH4+ storage process. In addition, the understanding of the NH4+ storage mechanism has been deepened through ex situ structural characterization and electrochemical analysis. The results indicate that Co2+ preintercalation effectively enhances the conductivity and structural stability of VO2, and inhibits the dissolution of V in aqueous electrolytes. In addition, the charge storage mechanisms of NH4+ intercalation/deintercalation and the reversible formation/fracture of hydrogen bonds were revealed.

Two-Photon FRET/FLIM Imaging of Cerebral Neurons.

Two-photon FRET (Förster resonance energy transfer) and FLIM (fluorescence lifetime imaging microscopy) enable the detection of FRET changes of fluorescence reporters in deep brain tissues, which provide a valuable approach for monitoring target molecular dynamics and functions. Here, we describe two-photon FRET and FLIM imaging techniques that allow us to visualize endogenous and optogenetically induced cAMP dynamics in living neurons with genetically engineered FRET-based cAMP reporters.

Identification and validation of biomarkers related to lipid metabolism in osteoarthritis based on machine learning algorithms.

BACKGROUND: Osteoarthritis and lipid metabolism are strongly associated, although the precise targets and regulatory mechanisms are unknown. METHODS: Osteoarthritis gene expression profiles were acquired from the GEO database, while lipid metabolism-related genes (LMRGs) were sourced from the MigSB database. An intersection was conducted between these datasets to extract gene expression for subsequent differential analysis. Following this, functional analyses were performed on the differentially expressed genes (DEGs). Subsequently, machine learning was applied to identify hub genes associated with lipid metabolism in osteoarthritis. Immune-infiltration analysis was performed using CIBERSORT, and external datasets were employed to validate the expression of these hub genes. RESULTS: Nine DEGs associated with lipid metabolism in osteoarthritis were identified. UGCG and ESYT1, which are hub genes involved in lipid metabolism in osteoarthritis, were identified through the utilization of three machine learning algorithms. Analysis of the validation dataset revealed downregulation of UGCG in the experimental group compared to the normal group and upregulation of ESYT1 in the experimental group compared to the normal group. CONCLUSIONS: UGCG and ESYT1 were considered as hub LMRGs in the development of osteoarthritis, which were regarded as candidate diagnostic markers. The effects are worth expected in the early diagnosis and treatment of osteoarthritis.

Ultrasound-guided microwave ablation for the treatment of idiopathic granulomatous mastitis: comparison with surgical excision.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) results in notable clinical symptoms and breast deformity. This study aimed to evaluate the clinical feasibility of microwave ablation (MWA) for the treatment of IGM through comparison with surgical excision. METHODS: From June 2016 to December 2020, a total of 234 consecutive patients admitted to the hospital were retrospectively included in this study. IGM was pathologically confirmed via breast biopsy in all included patients. These patients were divided into the MWA group (n = 91) and surgical group (n = 143) based on the type of treatment. Patients in both groups received oral prednisone prior to intervention. The clinical remission rate, recurrence rate, operative pain, complications, and BREAST Q score were compared between the two groups. RESULTS: There were 340 lesions in the MWA group, and 201 lesions in the surgical group were ultimately included. Significant differences in the complete remission rate (96.7% vs. 86.7%, p = 0.020), recurrence rate (3.3% vs. 13.3%, p = 0.020), operation time (48.7±14.6 min vs. 68.1±36.4 min, p < 0.001), postoperative pain (p < 0.001) and postoperative BREAST Q score (p < 0.001) were observed between the MWA and surgical groups. CONCLUSIONS: Microwave ablation is feasible for the treatment of IGM, due to its high curative rate and low recurrence rate. Because of the minimal invasiveness of MWA and sufficient preservation of the gland and contour of the breast, patients are more satisfied with the appearance of the breast. Therefore, for patients with complex conditions requiring surgery, MWA is a good alternative treatment.

Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

BACKGROUND: Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. METHODS: The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. RESULTS: Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. CONCLUSIONS: In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. PLAIN LANGUAGE SUMMARY: Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

The prognostic biomarker TPGS2 is correlated with immune infiltrates in pan-cancer: a bioinformatics analysis.

Background: Tubulin polyglutamylase complex subunit 2 (TPGS2) is an element of the neuronal polyglutamylase complex that plays a role in the post-translational addition of glutamate residues to C-terminal tubulin tails. Recent research has shown that TPGS2 is associated with some tumors, but the roles of TPGS2 in tumor immunity remain unclear. Methods: The research data were mainly sourced from The Cancer Genome Atlas. The data were analyzed to identify potential correlations between TPGS2 expression and survival, gene alterations, the tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltration, and various immune-related genes across various cancers. The Wilcoxon rank-sum test was used to identify the significance. A log-rank test and univariate Cox regression analysis were performed to assess the survival state of the patients. Spearman's correlation coefficients were used to show the correlations. Results: TPGS2 exhibited abnormal expression patterns in most types of cancers, and has promising prognostic potential in adrenocortical carcinoma and liver hepatocellular carcinoma. Further, TPGS2 expression was significantly correlated with molecular and immune subtypes. Moreover, the single-cell analyses showed that the expression of TPGS2 was associated with the cell cycle, metastasis, invasion, inflammation, and DNA damage. In addition, the immune cell infiltration analysis and gene-set enrichment analysis demonstrated that a variety of immune cells and immune processes were associated with TPGS2 expression in various cancers. Further, immune regulators, including immunoinhibitors, immunostimulators, the major histocompatibility complex, chemokines, and chemokine receptors, were correlated with TPGS2 expression in different cancer types. Finally, the TMB and MSI, which have been identified as powerful predictors of immunotherapy, were shown to be correlated with the expression of TPGS2 across human cancers. Conclusions: TPGS2 is aberrantly expressed in most cancer tissues and might be associated with immune cell infiltration in the tumor microenvironment. TPGS2 could serve not only as a biomarker for predicting clinical outcomes, but also as a promising biomarker for evaluating and developing new approaches to immunotherapy in many types of cancers, especially colon adenocarcinoma and stomach adenocarcinoma.

Osteomyelitis of the femur caused by Metamycoplasma orale in an immunocompromised patient using metagenomic next-generation sequencing: A case report.

Background: Metamycoplasma orale (M.orale), a symbiotic bacterium observed in the human oral cavity, is generally regarded as non-pathogenic to humans. Although infrequent, symptomatic infections caused by M.orale may occur in individuals with compromised humoral immunity. Accurate identification and early diagnosis of M.orale still present significant challenges due the limitations associated with conventional detection methods. Although metagenomic next-generation sequencing (mNGS) is currently widely utilized in clinical practices and exhibits a remarkable specificity and sensitivity for detecting various pathogens, its application in the diagnosis of M.orale-induced osteomyelitis remains largely unexplored. Case description: In this report, we present a case study of osteonecrosis caused by M.orale in a 20-year-old female patient with nephrotic syndrome and other comorbidities. She was administered long-term hormone therapy and immunosuppressants, leading to her admission to the hospital due to recurrent fever, hip abscess and left thigh pain. Imaging examination revealed bilateral mid-femoral lesions, with the extensive nature of the left femoral lesion suggesting a potential secondary infection. Although no pathogen was detected in pus culture, mNGS analysis identified M.orale in the sample. Following treatment with doxycycline and levofloxacin, the patient's symotoms improved and she was discharged with favorable outcomes. Conclusion: mNGS enables rapid identification of etiology in patients with osteomyelitis caused by the rare pathogen M.orale. This case accentuate the strength of mNGS for early detection and targeted clinical treatment of infectious diseases caused by uncommon pathogens.