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1.
Histopathology ; 84(7): 1199-1211, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38409885

ABSTRACT

AIMS: Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. METHODS AND RESULTS: In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression-free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance. CONCLUSION: This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.


Subject(s)
Brain Neoplasms , Exome Sequencing , Neoplasms, Germ Cell and Embryonal , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Young Adult , Asian People/genetics , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , China/epidemiology , DNA Copy Number Variations , East Asian People , Mutation , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Reelin Protein
2.
Acta Neurochir (Wien) ; 166(1): 72, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38329556

ABSTRACT

PURPOSE: Medulloblastoma is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. Recent transcriptional studies have shown that medulloblastomas comprise at least four molecular subgroups, each with distinct demographics, genetics, and clinical outcomes. Medulloblastoma subtyping has become critical for subgroup-specific therapies. The use of gene expression assays to determine the molecular subgroup of clinical specimens is a long-awaited application of molecular biology for this pediatric cancer. METHODS: In the current study, we established a medulloblastoma transcriptome database of 460 samples retrieved from three published datasets (GSE21140, GSE37382, and GSE37418). With this database, we identified a 23-gene signature that is significantly associated with the medulloblastoma subgroups and achieved a classification accuracy of 95.2%. RESULTS: The 23-gene signature was further validated in a long-term cohort of 142 Chinese medulloblastoma patients. The 23-gene signature classified 21 patients as WNT (15%), 41 as SHH (29%), 16 as Group 3 (11%), and 64 as Group 4 (45%). For patients of WNT, SHH, Group 3, and Group 4, 5-year overall-survival rate reached 80%, 62%, 27%, and 47%, respectively (p < 0.0001), meanwhile 5-year progression-free survival reached 80%, 52%, 27%, and 45%, respectively (p < 0.0001). Besides, SHH/TP53-mutant tumors were associated with worse prognosis compared with SHH/TP53 wild-type tumors and other subgroups. We demonstrated that subgroup assignments by the 23-gene signature and Northcott's NanoString assay were highly comparable with a concordance rate of 96.4%. CONCLUSIONS: In conclusion, we present a novel gene signature that is capable of accurately and reliably assigning FFPE medulloblastoma samples to their molecular subgroup, which may serve as an auxiliary tool for medulloblastoma subtyping in the clinic. Future incorporation of this gene signature into prospective clinical trials is warranted to further evaluate its clinical.


Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Humans , Child , Medulloblastoma/diagnosis , Medulloblastoma/genetics , Transcriptome/genetics , Prospective Studies , Cerebellar Neoplasms/genetics , China
3.
Angew Chem Int Ed Engl ; 63(6): e202318115, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38116913

ABSTRACT

The non-noble-metal catalysed-multicomponent reactions between flue gas CO2 and cheap industrial raw stocks into high value-added fine chemicals is a promising manner for the ideal CO2 utilization route. To achieve this, the key fundamental challenge is the rational development of highly efficient and facile reaction pathway while establishing compatible catalytic system. Herein, through the stepwise solvent-assisted linker installation, post-synthetic fluorination and metalation, we report the construction of a series of perfluoroalkyl-decorated noble-metal-free metal-organic frameworks (MOFs) PCN-(BPY-CuI)-(TPDC-Fx ) [BPY=2,2'-bipyridine-5,5'-dicarboxylate, TPDC-NH2 =2'-amino-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid] that can catalyze the one-pot four-component reaction between alkyne, aldehyde, amine and flue gas CO2 for the preparation of 2-oxazolidinones. Such assembly endows the MOFs with superhydrophobic microenvironment, superior water resistance and highly stable catalytic site, leading to 21 times higher turnover numbers than that of homogeneous counterparts. Mechanism investigation implied that the substrates can be efficiently enriched by the MOF wall and then the adsorbed amine species act as an extrinsic binding site towards dilute CO2 through their strong preferential formation to carbamate acid. Moreover, density functional theory calculations suggest the tetrahedral geometry of Cu in MOF offers special resistance towards amine poisoning, thus maintaining its high efficiency during the catalytic process.

4.
J Neurooncol ; 164(1): 127-139, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37462801

ABSTRACT

BACKGROUND: Glioma is the most malignant primary brain tumor with a poor survival time. The tumour microenvironment, especially glioma-associated microglia/macrophages (GAMs), plays an important role in the pathogenesis of glioma. Currently, microglia (CD11b+/CD45Low) and macrophages (CD11b+/CD45High) are distinguished as distinct cell types due to their different origins. Moreover, signal-transducing adaptor protein 1 (STAP1) plays a role in tumourigenesis and immune responses. However, to date, no studies have been reported on STAP1 in GAMs. METHODS: The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to investigate the association between STAP1 mRNA levels and clinical parameters (grades, mutations in isocitrate dehydrogenase, and overall survival). RNA-sequencing, qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence analyses were performed to detect the expression level of STAP1 and related proteins. BV-2 cells were used to construct a STAP1-overexpressing cell line. Phagocytosis of BV-2 cells was assessed by flow cytometry and fluorescence microscopy. C57BL/6 mice were used to establish orthotopic and subcutaneous glioma mouse models. Glioma growth was monitored by bioluminescence imaging. RESULTS: STAP1 expression in glioma-associated microglia is positively correlated with the degree of malignancy and poor prognosis of glioma. Moreover, STAP1 may promote M2-like polarisation by increasing ARG1 expression and inhibiting microglial phagocytosis of microglia. Increased ARG1 may be associated with the IL-6/STAT3 pathway. Impaired phagocytosis may be associated with decreased cofilin and filopodia. CONCLUSION: STAP1 is positively associated with the degree of glioma malignancy and may represent a potential novel therapeutic target for glioma.


Subject(s)
Brain Neoplasms , Glioma , Mice , Animals , Microglia , Cell Line, Tumor , Mice, Inbred C57BL , Glioma/metabolism , Macrophages , Brain Neoplasms/metabolism , Tumor Microenvironment
5.
Mol Cancer ; 20(1): 168, 2021 12 18.
Article in English | MEDLINE | ID: mdl-34922552

ABSTRACT

BACKGROUND: Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. METHODS: In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. RESULTS: We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer ß-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. CONCLUSIONS: Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of ß-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.


Subject(s)
Craniopharyngioma/genetics , Mutation , Pituitary Neoplasms/genetics , beta Catenin/genetics , Biomarkers, Tumor , Computational Biology/methods , Craniopharyngioma/diagnosis , Humans , INDEL Mutation , Pituitary Neoplasms/diagnosis , Polymorphism, Single Nucleotide , Prognosis , Tumor Cells, Cultured , Whole Genome Sequencing , Wnt Signaling Pathway
6.
Cancer Immunol Immunother ; 70(9): 2453-2465, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33543339

ABSTRACT

BACKGROUND: T cell with chimeric antigen receptors (CAR-T) has presented remarkable efficacy for blood cancer as an emerging immunotherapy. However, for solid tumors, the therapeutic efficacy is much impaired due to the lack of infiltration and persistence of CAR-T in tumor tissue. Thus, we constructed an interleukin-7-loaded oncolytic adenovirus and combined the use of oncolytic virus and CAR-T to improve the therapeutic outcome. METHODS: We constructed an interleukin-7-loaded oncolytic adenovirus (oAD-IL7) and a B7H3-targeted CAR-T and explored the efficacy of the single use of oAD-IL7, B7H3-CAR-T, or the combined therapy for glioblastoma in vitro and in vivo. The improved CAR-T anti-tumor efficacy was evaluated according to the proliferation, survival, persistence, exhaustion of T cells, and tumor regression. RESULTS: Constructed oAD-IL7 and B7H3-CAR-T presented moderate cytotoxicity during in vitro study, but failed to induce a thorough and persistent anti-tumor therapeutic efficacy in vivo. The combination of oAD-IL7 and B7H3-CAR-T in vitro resulted in enhanced T cell proliferation and reduced T cell apoptosis. The joint efficacy was further confirmed using tumor-bearing xenograft mice. During in vivo study, the mice treated with both oAD-IL7 and B7H3-CAR-T showed prolonged survival and reduced tumor burden. According to the ex vivo study, oAD-IL7 improved the proliferation and persistence of tumor-infiltrating B7H3-CAR-T, but failed to reverse the exhaustion. CONCLUSIONS: Our results indicated that oAD-IL7 is a promising auxiliary therapy to improve the therapeutic efficacy of B7H3-CAR-T in glioblastoma by providing the activating signals for tumor-infiltrating T cells. Our results also lay the basis for the future clinical trials for the combination of IL7-loaded oncolytic adenovirus and CAR-T therapy for glioblastoma.


Subject(s)
Genetic Therapy , Genetic Vectors/genetics , Immunotherapy, Adoptive , Interleukin-7/genetics , Oncolytic Virotherapy , Oncolytic Viruses/genetics , Adenoviridae/genetics , Animals , Apoptosis/genetics , Apoptosis/immunology , B7 Antigens/antagonists & inhibitors , B7 Antigens/immunology , B7 Antigens/metabolism , Cytokines/metabolism , Cytotoxicity, Immunologic , Disease Models, Animal , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Glioblastoma/etiology , Glioblastoma/metabolism , Glioblastoma/pathology , Glioblastoma/therapy , Humans , Immunophenotyping , Immunotherapy, Adoptive/methods , Lymphocyte Activation/genetics , Lymphocyte Activation/immunology , Mice , Oncolytic Virotherapy/methods , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Xenograft Model Antitumor Assays
7.
Biochem Biophys Res Commun ; 516(2): 515-520, 2019 08 20.
Article in English | MEDLINE | ID: mdl-31230744

ABSTRACT

Glioma is the most common primary brain tumor with high mortality. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. Oncolytic viral therapy for glioma has developed as an exciting therapeutic method in recent years. Zika virus, a member of flavivirus family, has oncolytic activity against glioma cells but the mechanism is unknown. Here, we aimed to determine which viral protein might play a critical role in mitigating glioma cell growth. We examined the tumor suppressor function of four nonstructural proteins NS1, NS3, NS4B and NS5 in human glioma cell line U87. As a result, we found that only NS5 significantly inhibited proliferation, migration and invasion of U87 cells. Moreover, expression of NS5 suppressed tumorigenicity of mouse GL261 glioma cell in vivo. Our findings provide some clues for further exploration of oncolytic Zika virus in the treatment of glioma.


Subject(s)
Glioma/pathology , Viral Nonstructural Proteins/pharmacology , Zika Virus/metabolism , Animals , Carcinogenesis/drug effects , Carcinogenesis/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , HEK293 Cells , Humans , Male , Mice, Inbred C57BL , Neoplasm Invasiveness , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathology
8.
Anal Chem ; 88(18): 9136-42, 2016 09 20.
Article in English | MEDLINE | ID: mdl-27553903

ABSTRACT

Merocyanine dyes, owing to their unique photochemical properties, are widely used to fabricate probes for the detection of biologically active small molecules and bioimaging. In this paper, merocyanine-based probes were proved of undergoing unwanted hydrolysis. To explore the strategies toward avoiding the hydrolysis, the detailed hydrolysis mechanism was first investigated, which was also confirmed by density functional theory (DFT) calculation. Then a series of merocyanine dyes were rationally designed. Influences of molecular structures of the probes, the analytical media such as pH and components of the solution on the hydrolysis were systematically studied. The experimental results suggest that merocyanine based probes with low electron density are more likely to suffer the hydrolysis, which could be exacerbated by the well-accepted strategy for constructing type-II probes. It is worth noting that chemical surroundings could also exert distinctive influence on the hydrolysis. The hydrolysis could be obviously aggravated when fetal calf serum or DMSO was deployed. Our findings will definitely provide an effective and reliable approach for guiding the rational design of highly robust merocyanine-based probes and the optimization of the analytical media, which is helpful in terms of avoiding the hydrolysis of the probes and hydrolysis caused analytical errors.


Subject(s)
Benzopyrans/chemistry , Coloring Agents/chemistry , Indoles/chemistry , Pyrimidinones/chemistry , Animals , Biosensing Techniques , Cattle , Dimethyl Sulfoxide/chemistry , Hydrolysis , Models, Molecular , Quantum Theory , Serum/chemistry
9.
Zhongguo Gu Shang ; 37(8): 796-800, 2024 Aug 25.
Article in Zh | MEDLINE | ID: mdl-39183004

ABSTRACT

OBJECTIVE: To investigate the effect of locking plate internal fixation for the treatment of proximal lateral femoral wall fracture. METHODS: From January 2021 to June 2022, 31 patients with intertrochanteric fractures and lateral wall fractures were treated. Among them, 15 patients were treated with proximal femoral nail antirotation (PFNA) fixation including 3 males and 12 females with an average age of (75.87±7.46) years old;the other 16 patients were treated with 3.5 mm pre-curved screw locking plate fixtion for lateral wall fracture including 4 males and 12 females with an average age of (76.15±9.47) years old. After surgery, the surgical index, tip-apical distance(TAD), postoperative standing weight-bearing time, and fracture reduction were compared between two groups. Postoperative hip function was evaluated according to Harris hip score. RESULTS: All patients were followed up for an average of (12±5) months ranging from 7 to 17 months. The immediate postoperative neck angle ranged from 111° to 132°(119.3±8.3)°. Fracture reduction results were excellent in 11 cases, fair in 2, worse in 1 in PFNA group;excellent in 12, fair in 3, worse in 1 in PFNA+locking plate group. One case of the PFNA group had a spiral blade cut out through the femoral head. There were significant differences in the time of operation, the amount of blood loss during the operation, the length of incision between two groups(P<0.05). There was no significant difference in TAD and postoperative standing weight-bearing time between two groups(P>0.05). There were significant differences in Harris scores at 6 months after surgery between two groups(P<0.05). CONCLUSION: The application of PFNA-assisted locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures is effective, and can restore the integrity of lateral wall, improve the stability of PFNA internal fixation, and reduce postoperative complications.


Subject(s)
Bone Nails , Bone Plates , Fracture Fixation, Internal , Hip Fractures , Humans , Female , Male , Aged , Hip Fractures/surgery , Fracture Fixation, Internal/methods , Aged, 80 and over , Middle Aged
10.
Environ Sci Technol ; 47(10): 5474-80, 2013 May 21.
Article in English | MEDLINE | ID: mdl-23688273

ABSTRACT

Separation of CO2 and N2 from CH4 is significantly important in natural gas upgrading, and capture/removal of CO2, CH4 from air (N2) is essential to greenhouse gas emission control. Adsorption equilibrium and kinetics of CO2, CH4, and N2 on an ordered mesoporous carbon (OMC) sample were systematically investigated to evaluate its capability in the above two applications. The OMC was synthesized and characterized with TEM, TGA, small-angle XRD, and nitrogen adsorption/desorption measurements. Pure component adsorption isotherms of CO2, CH4, and N2 were measured at 278, 298, and 318 K and pressures up to 100 kPa, and correlated with the Langmuir model. These data were used to estimate the separation selectivities for CO2/CH4, CH4/N2, and CO2/N2 binary mixtures at different compositions and pressures according to the ideal adsorbed solution theory (IAST) model. At 278 K and 100 kPa, the predicted selectivities for equimolar CO2/CH4, CH4/N2, and CO2/N2 are 3.4, 3.7, and 12.8, respectively; and the adsorption capacities for CH4 and CO2 are 1.3 and 3.0 mmol/g, respectively. This is the first report of a versatile mesoporous material that displays both high selectivities and large adsorption capacities for separating CO2/CH4, CH4/N2, and CO2/N2 mixtures.


Subject(s)
Biofuels , Carbon Dioxide/chemistry , Carbon/chemistry , Greenhouse Effect , Methane/chemistry , Nitrogen/chemistry , Adsorption , Microscopy, Electron, Transmission , Thermogravimetry , X-Ray Diffraction
11.
J Nanosci Nanotechnol ; 13(3): 2218-23, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23755669

ABSTRACT

Adsorption equilibria and kinetics of p-nitrophenol adsorbed on HJ-01 were investigated in this study. The result indicated that phenoxy groups were uploaded on the skeleton of HJ-01 successfully, the Friedel-Crafts reaction brought on prodigious changes for the Brunauer-Emmett-Teller (BET) specific surface area and pore structure while the nucleophilic substitution reaction had few effects. The adsorption experiments revealed that the acidic solution was suitable for p-nitrophenol adsorption, the adsorption isotherms could be characterized by the Freundlich isotherm equation and the adsorption thermodynamic parameters were all negative, the adsorption kinetic curves obeyed the pseudo-second-order rate equation.


Subject(s)
Nitrophenols/chemistry , Polystyrenes/chemistry , Adsorption , Hydrogen-Ion Concentration , Kinetics , Thermodynamics
12.
World J Clin Cases ; 11(29): 7179-7186, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37946772

ABSTRACT

BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic disease that primarily affects the spine and the sacroiliac and peripheral joints. Juvenile-onset AS (JoAS) patients will likely present with peripheral joint symptoms. Knee flexion contracture (KFC) and hip flexion contracture (HFC) are common in these patients due to subchondral bone inflammation. The Ilizarov technique is the most commonly used technique for treating KFC. However, its use to treat JoAS-associated KFC has not been reported. CASE SUMMARY: This report presents a case study of a 31-year-old male patient with a squatting gait due to severe bilateral KFC and HFC. The patient had a normal walking pattern until the age of eight, after which he experienced knee and hip pain, leading to the gradual development of KFC and HFC. The patient's primary complaint was an inability to walk upright. The patient was diagnosed with JoAS and underwent hip dissection and release, limited soft tissue release of the hamstring, and gradual traction using the Ilizarov method. Ultimately, the patient was able to walk upright. CONCLUSION: The incidence of squatting gait due to KFC in individuals diagnosed with JoAS was low. Utilizing the Ilizarov technique has proven to be a secure and effective method for managing KFC in JoAS patients. Although the Ilizarov technique cannot substitute for total knee arthroplasty (TKA), its application can delay the need for primary TKA in JoAS patients and alleviate the intricacy and potential complications associated with the procedure.

13.
J Colloid Interface Sci ; 637: 1-9, 2023 May.
Article in English | MEDLINE | ID: mdl-36682113

ABSTRACT

Herein, the covalently connected core-shell metal-organic frameworks (MOFs)@covalent-organic frameworks (COFs) hybrid materials were successfully constructed by coating the stable COF-OH shell on the NH2-MIL-125 core. The introduction of the NH2-MIL-125 core endowed the hybrid materials with high Brunauer-Emmett-Teller (BET) surface area (SBET) and abundant unsaturated metal sites. And the coating of COF-OH shell endowed the hybrid materials outstanding physicochemical stability and visible-light response, and suitable band gaps. Moreover, the thickness of the COF-OH shell was carefully adjusted according to the feeding amount of NH2-MIL-125. Impressively, the electron transfer pathway in the formed heterostructure was clarified and it was proven that a type-II heterojunction was generated between the MOFs and the COFs. The formed stable CN covalent bonds in the interfacial layer was beneficial to the photogenerated electron transfer and the electron-hole pairs separation, which greatly enhanced the CO2 photocatalytic reduction. The product NH2-MIL-125@COF-3 exhibited the highest CO yield of 22.93 µmol·g-1·h-1, about 2 times higher than NH2-MIL-125 (11.82 µmol·g-1·h-1) and 3 times greater than COF-OH (7.26 µmol·g-1·h-1). This work can provide helpful ideas for the careful design of the novel MOFs@COFs hybrid materials as well as useful exploration for the CO2 photocatalytic reduction.

14.
ACS Nano ; 17(10): 9126-9139, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37097811

ABSTRACT

Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member of the B7 superfamily, is associated with poor survival in glioblastoma (GBM) patients. Moreover, a dimer of EGCG (dEGCG) synthesized in this work enhanced the IFN-γ-induced ferroptosis of tumor cells in vitro and in vivo. Herein, we prepared recombinant anti-B7-H3×CD3 biAbs and constructed MMP-2-sensitive S-biAb/dEGCG@NPs to offer a combination treatment strategy for efficient and systemic GBM elimination. Given their GBM targeted delivery and tumor microenvironment responsiveness, S-biAb/dEGCG@NPs displayed enhanced intracranial accumulation, 4.1-, 9.5-, and 12.3-fold higher than that of biAb/dEGCG@NPs, biAb/dEGCG complexes, and free biAbs, respectively. Furthermore, 50% of GBM-bearing mice in the S-biAb/dEGCG@NP group survived longer than 56 days. Overall, S-biAb/dEGCG@NPs can induce GBM elimination by boosting the ferroptosis effect and enhancing immune checkpoint blockade (ICB) immunotherapy and may be successful antibody nanocarriers for enhanced cancer therapy.


Subject(s)
Antibodies, Bispecific , Ferroptosis , Glioblastoma , Mice , Animals , Antibodies, Bispecific/pharmacology , Antibodies, Bispecific/therapeutic use , Glioblastoma/drug therapy , Matrix Metalloproteinase 2 , Immunotherapy , Tumor Microenvironment
15.
J Hazard Mater ; 429: 128303, 2022 05 05.
Article in English | MEDLINE | ID: mdl-35101759

ABSTRACT

In this paper, thioether-functionalized porphyrin-based polymers (TPPs) were constructed according to two different "bottom-up" and "top-down" strategies and they were applied for Hg2+ capture in aqueous solution. TPP1, which was constructed by one-step polycondensation of 2,5-bis(methylthio) terephthalaldehyde (BMTA) with pyrrole according to the "bottom-up" strategy, owned high Brunauer-Emmett-Teller (BET) surface area (SBET, 554 m2/g), pore volume (Vtotal, 0.32 cm3/g), and S content (16.8%), resulting in high Hg2+ capture (913 mg/g) with high removal efficiency (> 99%). The adsorption mechanism clarified that the strong coordination between the S species and Hg2+ was the main driving force. In comparison, TPP2 and TPP3 were fabricated by the thioether functionalization of the porphyrin-based polymers according to the "top-down" strategy. They showed much lower SBET, Vtotal, and S content for the reason that the post-functionalization process greatly blocked the pores and the functional sites were hardly fully post-functionalized, resulting in much lower Hg2+ capture (555 mg/g and 609 mg/g, respectively). This work reveals the advantage of the "bottom-up" strategy for the construction of the thioether-functionalized polymers and it offers the guidance for the construction of some other thioether-functionalized polymers.


Subject(s)
Mercury , Porphyrins , Adsorption , Polymers , Sulfides
16.
J Cereb Blood Flow Metab ; 42(8): 1364-1382, 2022 08.
Article in English | MEDLINE | ID: mdl-35484910

ABSTRACT

The recent discovery of the meningeal lymphatic vessels (mLVs) and glymphatic pathways has challenged the long-lasting dogma that the central nervous system (CNS) lacks a lymphatic system and therefore does not interact with peripheral immunity. This discovery has reshaped our understanding of mechanisms underlying CNS drainage. Under normal conditions, a close connection between mLVs and the glymphatic system enables metabolic waste removal, immune cell trafficking, and CNS immune surveillance. Dysfunction of the glymphatic-mLV system can lead to toxic protein accumulation in the brain, and it contributes to the development of a series of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. The identification of precise cerebral transport routes is based mainly on indirect, invasive imaging of animals, and the results cannot always be applied to humans. Here we review the functions of the glymphatic-mLV system and evidence for its involvement in some CNS diseases. We focus on emerging noninvasive imaging techniques to evaluate the human glymphatic-mLV system and their potential for preclinical diagnosis and prevention of neurodegenerative diseases. Potential strategies that target the glymphatic-mLV system in order to treat and prevent neurological disorders are also discussed.


Subject(s)
Central Nervous System Diseases , Glymphatic System , Animals , Brain/metabolism , Central Nervous System , Glymphatic System/metabolism , Lymphatic System
17.
Chemosphere ; 288(Pt 1): 132499, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34626649

ABSTRACT

Lignin is a natural O-containing aromatic amorphous polymers from the residues of biorefinery and industrial papermaking, it can derive lots of aromatic phenol chemicals used as industrial raw materials by an efficient depolymerization, and then produce synthetic polymers. Here, we selected six aromatic units from the liquid products of lignin depolymerization, and tried to prepare diversified O-rich hyper-cross-linked polymers (HCPs) by one-pot Friedel-Crafts alkylation reaction for CO2 and iodine vapor capture. HCP1, HCP2, and HCP3 microspheres possessed similar porous structure with Brunauer-Emmett-Teller (BET) surface areas (SBET) of 14.1-20.6 m2/g and high O content (26.34-30.68 wt%), while HCP4, HCP5, and HCP6 were composed of many bulks with 3D networks structure, and showed larger SBET of 15.4-246.9 m2/g and relatively low O content (18.48-26.38 wt%). The results indicated that the chemical position and quantities of substituent groups (methoxy and alkyl) into lignin-derived units had evident impact on their morphology and textural parameters. These HCPs exhibited considerable CO2 uptake (64.1 mg/g) and selectivity (35.2) at 273 K, and high iodine vapor uptake (192.3 wt%). Moreover, the performance analysis implied that the SBET and pore volume of these HCPs had not played the dominated roles in the CO2 and I2 adsorption, while their pore size distribution, O-functional groups, and electron density will be more important for the capture of the both. This study will offer a facile synthesis of O-rich polymer microsphere adsorbents based on the green and sustainable lignin.


Subject(s)
Iodine , Lignin , Adsorption , Carbon Dioxide , Microspheres , Oxygen , Phenols , Polymers , Porosity
18.
Environ Technol ; 42(9): 1402-1410, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31550211

ABSTRACT

The polar modified dendritic post-cross-linked polymer, namely HCPD was synthesized and used for adsorptive removal of Cu2+ from aqueous solution. The results showed that 5.12 mmol/g of amino and 2.25 mmol/g of carbonyl groups were uploaded on the polymer and these groups were significantly beneficial for Cu2+ removal. The maximum capacity reached 157.8 mg/g at 313 K and increased as the temperature increased. The Langmuir model characterized the equilibrium data well and a chemical interaction was involved with the enthalpy change of 49.50 kJ/mol. The pseudo-second-order kinetic model described the kinetic data well and the intra-particle diffusion model was appropriate for characterizing the kinetic adsorption. HCPD could be easily regenerated and the regenerated polymers were effectively recycled for five times without significant loss of the equilibrium capacity. Moreover, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) results revealed that the chelating coordination of the amino and carbonyl groups with Cu2+ was the main driving force for the adsorption.


Subject(s)
Polymers , Water Pollutants, Chemical , Adsorption , Copper , Hydrogen-Ion Concentration , Kinetics , Spectroscopy, Fourier Transform Infrared , Thermodynamics , Water Pollutants, Chemical/analysis
19.
Chem Commun (Camb) ; 57(10): 1234-1237, 2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33416808

ABSTRACT

The hydrogen evolution reaction is a huge challenge for CO2 electroreduction. Herein, an inside-mode indium oxide/carbon nanotube compound (MWCNTs@In2O3) is developed to maximize the catalytic effect and suppress hydrogen evolution, its HCOOH selectivity can reach up to 92.2% at -16.8 mA cm-2, which is more efficient than In2O3.

20.
J Colloid Interface Sci ; 587: 121-130, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33360884

ABSTRACT

Due to the p-π conjugative effect between the nitrogen atom of the amide and the carbonyl, the amide carbonyl has much low reactivity and the Schiff base reaction between the amide and amine usually did not take place, but after the amide was polymerized, it's quite different. Herein, benzene-1,3,5-triyltris((9H-carbazol-9-yl) methanone) (HTCZ) is not able to have the Schiff base reaction with melamine. Surprisingly, after HTCZ was polymerized according to the Friedel-Crafts reaction, the resultant polymer PHTCZ-1 performed the Schiff base reaction with melamine successfully, and a kind of novel N-rich porous organic polymers, namely, PHTCZ-1-MA was successfully synthesized. Moreover, PHTCZ-1-MA owned much higher Brunauer-Emmett-Teller surface area (613 m2·g-1) and pore volume (0.57 cm3·g-1) with very high nitrogen content (42.39 wt%). The theoretical calculation showed that the positive charge of the carbonyl carbon increased by 18% after the polymerization, which greatly improved the reactivity of the carbonyl. Because of this amazing change, PHTCZ-1-MA was proven to be an excellent adsorbent for CO2 capture (180 mg·g-1 at 273 K and 1.0 bar) and mercury(II) adsorption (335 mg·g-1 at 273 K). This study makes the impossibility possible and provides a unique synthesis strategy for the fabrication of a kind of N-rich porous organic polymers.

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