Biomass chitosan/sodium alginate colorimetric imprinting hydrogels with integrated capture and visualization detection for cadmium(II).

Due to Cd(II) with highly toxic, persistent and bioaccumulative, the discharge of it into the environment brings serious pollution. Developing strategies that are efficient, low-cost, pollution-free and specific to removing Cd(II) from wastewater is therefore of great urgency and prime importance. A novel chitosan/sodium alginate ionic imprinting(IICA) hydrogels with specific adsorption capacity for Cd(II) was prepared through freeze-thaw and ion imprinting, and finally the colorimetric sensor (IICAS) was prepared via introducing Rhodamine B(RhB) and Victoria blue(VBB) by immersion to achieve visual detection of Cd(II). The IICA hydrogels with imprinted hole structure had higher adsorption capacity and better specific selectivity for Cd(II). As well as internal diffusion, coordination, ion exchange, and hydrogen bonding influenced the adsorption rate. Moreover, the IICAS exhibited good selective detection ability and linearity for Cd(II) with the fitted correlation coefficient (R2) = 0.98, limit of detection (LOD) = 35 nmol/L. Combined with the smartphone platform, portable and quantitative detection of Cd(II) can be achieved, Within the 0-100 mg/L range, R2 remained 0.94, and LOD was 75 nmol/L. This strategy of preparing a novel whole biomass IICAS integrating capture and visual detection provides a new insight into the construction of a promising candidate sensor for the removal and detection of Cd(II).

Factors influencing the diagnostic and prognostic values of circulating tumor cells in breast cancer: a meta-analysis of 8,935 patients.

Background: Circulating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging. Methods: We searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages. Results: In this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17-4.39; HRPFS/DFS, 2.06; 95% CI, 1.72-2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85-3.19; HRPFS/DFS, 1.82; 95% CI, 1.66-1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85-3.19). Conclusion: Our study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.

Identification of miRNAs Involved in Intracranial Aneurysm Rupture in Cigarette-Smoking Patients.

INTRODUCTION: Smoking is an independent risk factor for the formation and rupture of intracranial aneurysms (IA). However, the underlying mechanism remains unclear. METHODS: In this study, we performed miRNA sequencing on plasma from 10 smoking patients with IA, 10 non-smoking patients with IA, and 10 healthy controls. The differentially expressed miRNAs (DE miRNAs) between smoking and non-smoking patients with IA were identified. Functional and pathway enrichment analysis is employed to investigate the potential functions of those DE miRNA target genes. The correlations with the clinical parameters were assessed using receiver operating characteristic curve (ROC) analysis. RESULTS: In total, we identified 428 DE miRNAs. Functional enrichment analysis showed the target genes were significantly enriched in biological aspects related to cell characteristics, such as cell cycle, cell differentiation, and cell migration. Pathway analysis showed DE miRNAs mainly enriched in the PI3K-Akt signaling pathway, Focal adhesion, and JAK-STAT signaling pathway. The expressions of miR-574-5p, miR-151a-3p, and miR-652-3p correlated well with aneurysm parameters. The AUC of miR-574-5p, miR-151a-3p, and miR-652-3p were 97%, 92%, and 99%, respectively. CONCLUSION: Our study indicated that smoking significantly altered the plasma miRNA profile in patients with IA. The expression of miR-574-5p, miR-151a-3p, and miR-652-3p correlated with aneurysm parameters, which may play a significant role in the formation and rupture of IA.

Radionecrosis mimicking pseudo­progression in a patient with lung cancer and brain metastasis following the combination of anti­PD­1 therapy and stereotactic radiosurgery: A case report.

Brain metastases (BMs) usually develop in patients with non-small cell lung cancer. In addition to systemic therapy, radiation therapy and surgery, anti-programmed cell death-ligand 1 (PD-L1) therapy is another promising clinical anticancer treatment modality. However, the optimal timing and drug-drug interactions of anti-PD-L1 therapy with other combined treatments remain to be elucidated. Treatment with anti-PD-L1 therapy is associated with an increased risk of radionecrosis (RN) regardless of tumor histology. The present study described a case of RN in a patient with lung adenocarcinoma and with BM who received anti-PD-L1 therapy. Before anti-PD-L1 treatment, the patient received whole brain radiotherapy. During durvalumab treatment, the intracranial metastases regressed. The progression of intracranial lesions 9 months later prompted a second-line of therapy with PD-L1 inhibitor durvalumab and stereotactic radiotherapy (SRT). Despite stereotactic irradiation, the lesions progressed further, leading to surgical resection. On examination, RN was detected, but there was no evidence of metastatic lung cancer. The aim of the present study was to present the longitudinal change in magnetic resonance imaging in RN following STR and anti-PD-L1 combined therapy. The atypical image of RN is conditionally important for making an accurate preoperative diagnosis.

Biology of breast cancer brain metastases and novel therapies targeting the blood brain barrier: an updated review.

Brain metastasis (BM) is a critical cause of morbidity and mortality in patients with breast cancer (BC). Compared with other cancer cells, BC cells (BCs) exhibit special features in the metastatic process. However, the underlying mechanisms are still unclear, especially the crosstalk between tumour cells and the microenvironment. To date, novel therapies for BM, including targeted therapy and antibody‒drug conjugates, have been developed. Due to an improved understanding of the blood‒brain barrier (BBB) and blood-tumour barrier (BTB), the development and testing of therapeutic agents in clinical phases have substantially increased. However, these therapies face a major challenge due to the low penetration of the BBB or BTB. As a result, researchers have increasingly focused on finding ways to promote drug penetration through these barriers. This review provides an updated overview of breast cancer brain metastases (BCBM) and summarizes the newly developed therapies for BCBM, especially drugs targeting the BBB or BTB.

Phosphorylation at Ser289 Enhances the Oligomerization of Tau Repeat R2.

In tauopathies such as Alzheimer's disease (AD), aberrant phosphorylation causes the dissociation of tau proteins from microtubules. The dissociated tau then aggregates into sequent forms from soluble oligomers to paired helical filaments and insoluble neurofibrillary tangles (NFTs). NFTs is a hallmark of AD, while oligomers are found to be the most toxic form of the tau aggregates. Therefore, understanding tau oligomerization with regard to abnormal phosphorylation is important for the therapeutic development of AD. In this study, we investigated the impact of phosphorylated Ser289, one of the 40 aberrant phosphorylation sites of full-length tau proteins, on monomeric and dimeric structures of tau repeat R2 peptides. We carried out intensive replica exchange molecular dynamics simulation with a total simulation time of up to 0.1 ms. Our result showed that the phosphorylation significantly affected the structures of both the monomer and the dimer. For the monomer, the phosphorylation enhanced ordered-disordered structural transition and intramolecular interaction, leading to more compactness of the phosphorylated R2 compared to the wild-type one. As to the dimer, the phosphorylation increased intermolecular interaction and ß-sheet formation, which can accelerate the oligomerization of R2 peptides. This result suggests that the phosphorylation at Ser289 is likely to promote tau aggregation. We also observed a phosphorylated Ser289-Na+-phosphorylated Ser289 bridge in the phosphorylated R2 dimer, suggesting an important role of cation ions in tau aggregation. Our findings suggest that phosphorylation at Ser289 should be taken into account in the inhibitor screening of tau oligomerization.

Identification of key genes of anti-programmed death ligand 1 for meningioma immunotherapy by bioinformatic analysis.

Meningioma is one of the most common primary tumors in the central nervous system (CNS). A deeper understanding of its molecular characterization could provide potential therapeutic targets to reduce recurrence. In this study, we attempted to identify specific gene mutations in meningioma for immunotherapy. One GSE43290 dataset was obtained from the Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs) between meningioma tissues and normal meninges. In total, 420 DEGs were identified, including 15 up-regulated and 405 down-regulated genes. Functional enrichment analysis showed that these DEGs were mainly enriched in PI3K-Akt signaling pathway, Focal adhesion, and MAPK signaling pathway. We identified 20 hub genes by protein-protein interaction (PPI) analysis. Among the hub genes, the expression of FLT1, CXCL8, JUN, THBS1, FECAM1, CD34, and FGF13 were negatively correlated with Programmed Death Ligand-1 (PD-L1). Additionally, the expression of those genes was co-regulated by miR-155-5p. The findings suggest that miR-155-5p play an important role in the pathogenesis of meningioma and may represent potential therapeutic targets for its anti-PD-L1 immunotherapy.

The Biological Effects of Smoking on the Formation and Rupture of Intracranial Aneurysms: A Systematic Review and Meta-Analysis.

Background: Aneurysms of the cerebral vasculature are relatively common, which grow unpredictably, and even small aneurysms carry a risk of rupture. Rupture of intracranial aneurysms (IA) is a catastrophic event with a high mortality rate. Pieces of evidence have demonstrated that smoking is closely related to the formation and rupture of IA. However, the biological effect of smoking cigarettes on the formation and rupture of IA is still underrepresented. Methods: The study protocol was prospectively registered in PROSPERO, registration number CRD42020203634. We performed a systematic search in PubMed and CNKI for studies exploring the biological effects of smoking on intracranial aneurysms published up to December 2021, and all studies were included in the analysis. The RevMan software was used for data analysis. Results: A total of 6,196 patients were included in 14 original articles in this meta-analysis. The risk of ruptured IA in the current smoking group was significantly higher than that in the non-smoking group, with statistical significance (RRtotal = 1.23, 95% CI: 1.11-1.37). After heterogeneity among cohorts was removed by the sensitivity analysis, there was still a statistically significant difference in the risk of ruptured IA between the smoking and non-smoking groups (RR total = 1.26, 95% CI: 1.18-1.34). There was no statistically significant difference in the risk of ruptured IA between the former smoking (smoking cessation) group and the non-smoking group (RRtotal = 1.09, 95% CI: 0.50-2.38). After heterogeneity among cohorts was removed by sensitivity analysis, there was still no statistically significant difference in the risk of ruptured IA between the former smoking (smoking cessation) group and the non-smoking group (RRtotal = 0.75, 95% CI: 0.47-1.19). The risk of the ruptured IA in the current smoking group was significantly higher than that in the former smoking (smoking cessation) group, with a statistically significant difference (RRtotal=1.42, 95%CI: 1.27-1.59). Conclusion: Although the biological effects of smoking on the formation and rupture of IA are unknown, this study suggests that current smoking is a risk factor for ruptured IA. Quitting smoking is very important for patients with IA.

Comparison of the diagnostic value of liquid biopsy in leptomeningeal metastases: A systematic review and meta-analysis.

Background: Brain metastases (BM) include brain parenchymal (BPM) and leptomeningeal metastases (LM), which are associated with a poor prognosis and high mortality rate. Early and accurate diagnosis and timely, effective treatment are crucial for improving the overall survival of LM patients. Cerebrospinal fluid (CSF) biopsy technology has attracted widespread attention for its diagnostic value in diverse cancers, including LM. We summarized studies to compare the potential diagnostic value of CSF liquid biopsy techniques in BM patients with meta-analysis. Methods: The study protocol was prospectively registered in PROSPERO, registration number CRD42022373263. We obtained the literature on liquid biopsy for BM from 7 databases (PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang Data knowledge service platform). Then, a systematic review of those studies was performed according to PRISMA criteria. Results: Nine publications have been obtained, and we found CSF liquid biopsy techniques to be more suitable for diagnosing LM. We analyzed the sensitivity, specificity, and area under the curve (AUC) of CSF liquid biopsy. The overall sensitivity, specificity, and AUC of CSF liquid biopsy in the diagnosis of LM were 0.65 (95% CI: 0.48 - 0.79), 0.70 (95% CI: 0.50 - 0.86), and 0.69, respectively. Then, we compared the diagnostic advantages of CSF liquid biopsy techniques and CSF cytology in LM. The results show that CSF liquid biopsy is superior to CSF cytology in LM diagnosis. Conclusions: Our meta-analysis suggested that CSF liquid biopsy is more suitable for LM diagnosis and has higher accuracy than CSF cytology.

Identification of potential genes related to breast cancer brain metastasis in breast cancer patients.

Brain metastases (BMs) usually develop in breast cancer (BC) patients. Thus, the molecular mechanisms of breast cancer brain metastasis (BCBM) are of great importance in designing therapeutic strategies to treat or prevent BCBM. The present study attempted to identify novel diagnostic and prognostic biomarkers of BCBM. Two datasets (GSE125989 and GSE100534) were obtained from the Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs) in cases of BC with and without brain metastasis (BM). A total of 146 overlapping DEGs, including 103 up-regulated and 43 down-regulated genes, were identified. Functional enrichment analysis showed that these DEGs were mainly enriched for functions including extracellular matrix (ECM) organization and collagen catabolic fibril organization. Using protein-protein interaction (PPI) and principal component analysis (PCA) analysis, we identified ten key genes, including LAMA4, COL1A1, COL5A2, COL3A1, COL4A1, COL5A1, COL5A3, COL6A3, COL6A2, and COL6A1. Additionally, COL5A1, COL4A1, COL1A1, COL6A1, COL6A2, and COL6A3 were significantly associated with the overall survival of BC patients. Furthermore, COL6A3, COL5A1, and COL4A1 were potentially correlated with BCBM in human epidermal growth factor 2 (HER2) expression. Additionally, the miR-29 family might participate in the process of metastasis by modulating the cancer microenvironment. Based on datasets in the GEO database, several DEGs have been identified as playing potentially important roles in BCBM in BC patients.

MMGZ01, an anti-DLL4 monoclonal antibody, promotes nonfunctional vessels and inhibits breast tumor growth.

Increasing evidence suggests that DLL4 (Delta-like 4)-Notch signaling plays a critical role in cell fate determination and differentiation in tissues. Blocking DLL4-Notch signaling results in inhibition of tumor growth, which is associated with increased nonfunctional vessels and poor perfusion in the tumor. We successfully generated a human DLL4 monoclonal antibody MMGZ01 that binds specifically to DLL4 to disrupt the interaction between DLL4 and Notch1. MMGZ01 showed high affinity to DLL4 to inhibit the DLL4-mediated human umbilical vein endothelial cell (HUVEC) phenotype. Furthermore, MMGZ01 stimulated HUVEC vessel sprouting and tubule formation in vitro. In addition, MMGZ01 had a pronounced effect in promoting immature vessels and reduced breast cancer cell growth in vivo. Finally, MMGZ01 treatment inhibited the proliferation of breast cancer cells, induced tumor cell apoptosis, suppressed mammosphere formation, decreased CD44(+)/CD24(-) cell population, and reduced epithelial mesenchymal transition (EMT). These findings suggest that antagonism of the DLL4-Notch signaling pathway might provide a potential therapeutic approach for breast cancer treatment.