ABSTRACT
In eukaryotes, RNA N6-methyladenosine (m6A) modification and microRNA (miRNA)-mediated RNA silencing represent two critical epigenetic regulatory mechanisms. The m6A methyltransferase complex (MTC) and the microprocessor complex both undergo liquid-liquid phase separation to form nuclear membraneless organelles. Although m6A methyltransferase has been shown to positively regulate miRNA biogenesis, a mechanism of reciprocal regulation between the MTC and the microprocessor complex has remained elusive. Here, we demonstrate that the MTC and the microprocessor complex associate with each other through the METHYLTRANSFERASE B (MTB)-SERRATE (SE) interacting module. Knockdown of MTB impaired miRNA biogenesis by diminishing microprocessor complex binding to primary miRNAs (pri-miRNAs) and their respective MIRNA loci. Additionally, loss of SE function led to disruptions in transcriptome-wide m6A modification. Further biochemical assays and fluorescence recovery after photobleaching (FRAP) assay indicated that SE enhances the liquid-liquid phase separation and solubility of the MTC. Moreover, the MTC exhibited enhanced retention on chromatin and diminished binding to its RNA substrates in the se mutant background. Collectively, our results reveal the substantial regulatory interplay between RNA m6A modification and miRNA biogenesis.
ABSTRACT
Nano-TiO2 photocatalysis technology has attracted wide attention because of its safety, nontoxicity and long-lasting performance. However, traditional nano-TiO2 has been greatly limited in its application because its wide band gap can only be activated by ultraviolet light (λ < 387 nm). In this paper, nano-TiO2 was prepared by self-doping method. The synthesized nano-TiO2 was a single anatase crystal type with a particle size of 10 nm and uniform size. In addition, nano-TiO2 has high stability and good dispersion. More importantly, nano-TiO2 exhibits excellent visible light (400-780 nm) activity due to the decrease of bandgap from 3.20 eV to 1.80 eV (less than 2.0 eV) and the presence of a large number of hydroxyl groups on the surface of the nanoparticles. In the antibacterial test, the antibacterial rate of both E.coli and S.aureus was close to 100 % under the irradiation of household low-power LED lamps, showing excellent antibacterial performance, indicating that the prepared nano-TiO2 has broad application prospects in the field of bactericidal and bacteriostatic.
ABSTRACT
Abscisic acid (ABA) signaling is crucial for plant responses to various abiotic stresses. The Arabidopsis (Arabidopsis thaliana) transcription factor ABA INSENSITIVE 5 (ABI5) is a central regulator of ABA signaling. ABI5 BINDING PROTEIN 1 (AFP1) interacts with ABI5 and facilitates its 26S-proteasome-mediated degradation, although the detailed mechanism has remained unclear. Here, we report that an ABA-responsive U-box E3 ubiquitin ligase, PLANT U-BOX 35 (PUB35), physically interacts with AFP1 and ABI5. PUB35 directly ubiquitinated ABI5 in a bacterially reconstituted ubiquitination system and promoted ABI5 protein degradation in vivo. ABI5 degradation was enhanced by AFP1 in response to ABA treatment. Phosphorylation of the T201 and T206 residues in ABI5 disrupted the ABI5-AFP1 interaction and affected the ABI5-PUB35 interaction and PUB35-mediated degradation of ABI5 in vivo. Genetic analysis of seed germination and seedling growth showed that pub35 mutants were hypersensitive to ABA as well as to salinity and osmotic stresses, whereas PUB35 overexpression lines were hyposensitive. Moreover, abi5 was epistatic to pub35, whereas the pub35-2 afp1-1 double mutant showed a similar ABA response to the two single mutants. Together, our results reveal a PUB35-AFP1 module involved in fine-tuning ABA signaling through ubiquitination and 26S-proteasome-mediated degradation of ABI5 during seed germination and seedling growth.
Subject(s)
Abscisic Acid , Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Signal Transduction , Ubiquitin-Protein Ligases , Ubiquitination , Abscisic Acid/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Basic-Leucine Zipper Transcription Factors/metabolism , Basic-Leucine Zipper Transcription Factors/genetics , Proteolysis , Germination/genetics , Phosphorylation , Plants, Genetically Modified , Proteasome Endopeptidase Complex/metabolism , Protein Binding , Mutation/geneticsABSTRACT
Immunodeficient murine models are usually used as the preclinical models of osteosarcoma. Such models do not effectively simulate the process of tumorigenesis and metastasis. Establishing a suitable animal model for understanding the mechanism of osteosarcoma and the clinical translation is indispensable. The UMR-106 cell suspension was injected into the marrow cavity of Balb/C nude mice. Tumor masses were harvested from nude mice and sectioned. The tumor fragments were transplanted into the marrow cavities of SD rats immunosuppressed with cyclosporine A. Through muti-rounds selection in SD rats, we constructed orthotopic osteosarcoma animal models using rats with intact immune systems. The primary tumor cells were cultured in-vitro to obtain the immune-tolerant cell line. VX2 tumor fragments were transplanted into the distal femur and parosteal radius of New Zealand white rabbit to construct orthotopic osteosarcoma animal models in rabbits. The rate of tumor formation in SD rats (P1 generation) was 30%. After four rounds of selection and six rounds of acclimatization in SD rats with intact immune systems, we obtained immune-tolerant cell lines and established the orthotopic osteosarcoma model of the distal femur in SD rats. Micro-CT images confirmed tumor-driven osteolysis and the bone destruction process. Moreover, the orthotopic model was also established in New Zealand white rabbits by implanting VX2 tumor fragments into rabbit radii and femurs. We constructed orthotopic osteosarcoma animal models in rats with intact immune systems through muti-rounds in-vivo selection and the rabbit osteosarcoma model.
Subject(s)
Bone Neoplasms , Disease Models, Animal , Osteosarcoma , Animals , Osteosarcoma/pathology , Osteosarcoma/immunology , Rabbits , Rats , Bone Neoplasms/pathology , Bone Neoplasms/immunology , Cell Line, Tumor , Mice , Mice, Nude , Rats, Sprague-Dawley , X-Ray Microtomography , Mice, Inbred BALB C , Immunocompetence , Humans , Neoplasm Transplantation , Femur/pathology , Femur/diagnostic imaging , MaleABSTRACT
Vascular transplantation is a common treatment for Cardiovascular disease (CVD). However, the mismatch of mechanical, structural, or microenvironmental properties of materials limits the clinical application. Therefore, the functional construction of artificial vessels or other blood contact materials remains an urgent challenge. In this paper, the composite nanofibers of polycaprolactone (PCL) with dopamine and polyethylenimine (PEI) coating are first prepared, which are further self-assembled by anticoagulant hirudin (rH) and antimicrobial peptide (AMP) of HHC36 through layer-by-layer (LBL) method. The results of FTIR and XPS analysis show that hirudin and AMP are successfully loaded on PEI-PDA/PCL nanofibers and the hydrophilicity is improved. They also show good mechanical properties that the ultimate tensile strength and elongation at break are better than natural blood vessels. The antibacterial results show that the antibacterial effect is still 93% against E. coli on the fifth day because of the stable and continuous release of HHC36 and rH. The performance of anticoagulant activity also exhibited the same results, which APTT is even 9.7s longer in the experimental group than the control group on the fifth day. The novel materials would be effectively solve the formation of thrombosis around artificial blood vessel grafts and the treatment of inflammation.
Subject(s)
Anti-Bacterial Agents , Anticoagulants , Escherichia coli , Nanofibers , Polyesters , Anticoagulants/pharmacology , Anticoagulants/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Polyesters/chemistry , Polyesters/pharmacology , Nanofibers/chemistry , Humans , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Hirudins/pharmacology , Hirudins/chemistry , Dopamine/pharmacology , Dopamine/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Tensile StrengthABSTRACT
One of the fundamental objectives in ecology is to investigate the ecological processes and associated factors governing the abundance and spatial distribution patterns of biodiversity. However, the reaction of biological communities to environmental degradation remains relatively unknown, even for ecologically crucial communities like macroinvertebrates in aquatic ecosystems. Here, we sampled 117 locations to quantify relative contributions of geographical and environmental factors, including water quality, land use, climate, and hydrological factors, to determine the absolute and relative compositions of macroinvertebrate communities and their spatial distribution in the Yellow River Basin (YRB), the sixth-longest river system on Earth. We assessed relative roles of species sorting and dispersal in determining macroinvertebrate community structure along YRB. Our results demonstrated that alpha and beta diversity indices showed an increase from the up- to low-reaches of YRB. The middle and low-reaches exhibited elevated species diversity and both regions exhibited relatively stable community compositions. The biodiversity of macroinvertebrates was influenced by a combination of geographical factors and environmental variables, with environmental factors predominantly serving as the principal determinants. Results of multiple linear regression and variance decomposition showed that the effect of environmental factors was approximately three times greater than that of spatial factors. These findings provide support for the hypothesis that species sorting, driven by environmental gradients, plays a significant role in shaping the community structure of macroinvertebrates in running water ecosystems at the basin scales. Moreover, the factors contributing to substantial shifts in biodiversity across different segments of YRB indicate that distinct river sections have been influenced by varying stressors, with downstream areas being more susceptible to the impacts of water pollution and urbanization resulting from human activities.
Subject(s)
Biodiversity , Invertebrates , Rivers , Rivers/chemistry , Animals , Invertebrates/classification , Invertebrates/physiology , China , Ecosystem , Environmental Monitoring , Water QualityABSTRACT
OBJECTIVE: To analyze and summarize the medical security situation of the snowmobile, sled, and steel frame snowmobile tracks at the National Sliding Centre, and to provide experience for future event hosting and medical security work for mass ice and snow sports. METHODS: Retrospective analysis of injuries and treatment of athletes participating in the International Training Week and World Cup for Ski, Sled, and Steel Frame Ski from October to November 2021(hereinafter referred to as "International Training Week"), as well as the Ski, Sled, and Steel Frame Ski events at the Beijing Winter Olympics in February 2022 (hereinafter referred to as the "Beijing Winter Olympics"). We referred to and drew on the "Medical Security Standards for Winter Snow Sports" to develop specific classification standards for analyzing injured areas, types of injuries, and accident locations. RESULTS: A total of 743 athletes participated in the International Training Week and the Beijing Winter Olympics. During the competition, there were 58 incidents of overturning, prying, and collision, of which 28 (28 athletes) were injured, accounting for 48.3% of the total accidents and 3.8% of the total number of athletes. Among them, there were 9 males (32.1%) and 19 females (67.9%), with an average age of (26.3 ± 4.7) years. Among the 28 injured athletes, 20 cases (71.4%) received on-site treatment for Class â injuries, while 8 cases (28.6%) had more severe injuries, including Class â ¡ injuries (7 cases) and Class â ¢ injuries (1 case), which were referred to designated hospitals for further treatment. Among the 28 injured athletes, 3 cases (10.7%) experienced multiple injuries, including 2 cases of 2 injuries and 1 case of 3 injuries. The most common injuries were in the ankle and toes (10/32, 31.3%). Out of 28 injured athletes, one (3.6%) experienced two types of injuries simultaneously, with joint and/or ligament injuries being the most common (11/29, 37.9%). The most accident prone point on the track was the ninth curve (18/58, 31.0%). CONCLUSION: Through the analysis and summary of medical security work, it can provide better experience and reference for the future development of snowmobile, sled, and steel frame snowmobile sports in China, making the National Snowy and Ski Center truly a sustainable Olympic heritage.
Subject(s)
Athletic Injuries , Skiing , Male , Female , Humans , Young Adult , Adult , Athletic Injuries/epidemiology , Athletic Injuries/therapy , Beijing/epidemiology , Retrospective Studies , SteelABSTRACT
In the clinic, inactivation of osteosarcoma using microwave ablation would damage the periosteum, resulting in frequent postoperative complications. Therefore, the development of an artificial periosteum is crucial for postoperative healing. In this study, we prepared an artificial periosteum using silk fibroin (SF) loaded with stromal cell-derived factor-1α (SDF-1α) and calcitonin gene-related peptide (CGRP) to accelerate bone remodeling after the microwave ablation of osteosarcoma. The prepared artificial periosteum showed a sustained release of SDF-1α and CGRP after 14 days of immersion. In vitro culture of rat periosteal stem cells (rPDSCs) demonstrated that the artificial periosteum is favorable for cell recruitment, the activity of alkaline phosphatase, and bone-related gene expression. Furthermore, the artificial periosteum improved the tube formation and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs). In an animal study, the periosteum in the femur of a rabbit was inactivated through microwave ablation and then removed. The damaged periosteum was replaced with the as-prepared artificial periosteum and favored bone regeneration. In all, the designed dual-factor-loaded artificial periosteum is a promising strategy to replace the damaged periosteum in the therapy of osteosarcoma for a better bone-rebuilding process.
Subject(s)
Osteosarcoma , Periosteum , Rats , Humans , Animals , Rabbits , Chemokine CXCL12/genetics , Chemokine CXCL12/pharmacology , Calcitonin Gene-Related Peptide , Endothelial Cells , Bone RegenerationABSTRACT
Polar lipids have biosynthetic pathways which intersect and overlap with triacylglycerol biosynthesis; however, polar lipids have not been well characterized in the developing endosperms of oat with high oil accumulation. The polar lipids in endosperms of oat and wheat varieties having different oil contents were analyzed and compared at different developmental stages. Our study shows that the relative contents of polar lipid by mass were decreased more slowly in wheat than in oat. Phosphatidylcholine and phosphatidylethanolamine were the major phospholipids, which showed similar abundance and gradual decreases during endosperm development in oat and wheat, while lysophospholipids were noticeably higher in oat. Monogalactosyldiacylglycerol showed a gradual increase in wheat and a decrease in oat during endosperm development. The relative contents of some polar lipid species and their unsaturation index were significantly different in their endosperms. These characteristics of polar lipids might indicate an adaption of oat to accommodate oil accumulation.
Subject(s)
Avena , Endosperm , Endosperm/metabolism , Avena/metabolism , Triticum , Lipidomics , Phosphatidylcholines/metabolismABSTRACT
The discovery of co-suppression in plants has greatly boosted the study of gene silencing mechanisms, but its triggering mechanism has remained a mystery. In this study, we explored its possible trigger mechanism by using Fatty acid desaturase 2 (FAD2) and Fatty acid elongase 1 (FAE1) strong co-suppression systems. Analysis of small RNAs in FAD2 co-suppression lines showed that siRNAs distributed throughout the coding region of FAD2 with an accumulated peak. However, mutations of the peak siRNA-matched site and siRNA derived site had not alleviated the co-suppression of its transgenic lines. Synthetic FAD2 (AtFAD2sm), which has synonymous mutations in the entire coding region, failed to trigger any co-suppression. Furthermore, 5' and 3' portions of AtFAD2 and AtFAD2sm were swapped to form two hybrid genes, AtFAD2-3sm and AtFAD2-5sm. 80 % and 92 % of their transgenic lines exhibited co-suppression, respectively. Finally, FAE1s with different degrees of the continuous sequence identity compared with AtFAE1 were tested in their Arabidopsis transgenic lines, and the results showed the co-suppression frequency was reduced as their continuous sequence identity stepped down. This work suggests that contiguous identity between the entire coding regions of transgenic and native genes rather than a special region is essential for a strong co-suppression.
Subject(s)
Arabidopsis , Fatty Acid Desaturases , RNA Interference , Fatty Acid Desaturases/genetics , Fatty Acid Desaturases/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Genes, Plant/genetics , RNA, Small InterferingABSTRACT
Regulating the wound microenvironment to promote proliferation, vascularization, and wound healing is challenging for hemostats and wound dressings. Herein, polypeptide composite hydrogels have been simply fabricated by mixing a smaller amount of metal ion-coordinated nanoparticles into dopamine-modified poly(L-glutamic acid) (PGA), which had a microporous size of 10-16 µm, photothermal conversion ability, good biocompatibility, and multiple biological activities. In vitro scratch healing of fibroblast L929 cells and the tube formation of HUVECs provide evidence that the PGA composite hydrogels could promote cell proliferation, migration, and angiogenesis with the assistance of mild photothermia. Moreover, these composite hydrogels plus mild photothermia could effectively eliminate reactive oxygen species (ROS), alleviate inflammation, and polarize the pro-inflammatory M1 macrophage phenotype into the pro-healing M2 phenotype to accelerate wound healing, as assessed by means of fluorescent microscopy, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, a rat liver bleeding model illustrates that the composite hydrogels reduced the blood loss ratio to about 10% and shortened the hemostasis time to about 25 s better than commercial chitosan-based hemostats. Furthermore, the full-thickness rat skin defect models showcase that the composite hydrogels plus mild photothermia could proheal wounds completely with a fast healing rate, optimal neovascularization, and collagen deposition. Therefore, the biodegradable polypeptide PGA composite hydrogels are promising as potent wound hemostats and dressings.
Subject(s)
Glutamic Acid , Nanoparticles , Rats , Animals , Glutamic Acid/pharmacology , Hydrogels/pharmacology , Wound Healing , Hemostasis , Peptides/pharmacology , Anti-Bacterial Agents/pharmacologyABSTRACT
Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8+ T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8+ T cells and contributes to antitumor immunity. CD8+ T cells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8+ T cells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification.
Subject(s)
CD8-Positive T-Lymphocytes , Serotonin , CD8-Positive T-Lymphocytes/metabolism , Serotonin/metabolism , Serotonin/pharmacology , Protein Processing, Post-Translational , Signal TransductionABSTRACT
Despite the intense progress of photodynamic and chemotherapy, however, they cannot prevent solid tumor invasion, metastasis, and relapse, along with inferior efficacy and severe side effects. The hypoxia-responsive nanoprodrugs integrating photodynamic functions are highly sought to address the above-mentioned problems and overcome the tumor hypoxia-reduced efficacy. Herein, a hypoxia-responsive tetrameric supramolecular polypeptide nanoprodrug (SPN-TAPP-PCB4) is constructed from the self-assembly of tetrameric porphyrin-central poly(l-lysine-azobenzene-chlorambucil) (TAPP-(PLL-Azo-CB)4) and an anionic water-soluble [2]biphenyl-extended-pillar[6]arene (AWBpP6) via the synergy of hydrophobic, π-π stacking, and host-guest interactions. Upon laser irradiation, the central TAPP can convert oxygen to generate single oxygen (1 O2 ) to kill tumor cells. Furthermore, under the acidic and PDT-aggravated hypoxia tumor cell microenvironment, SPN-TAPP-PCB4 is rapidly disassembled, and then efficiently releases activated CB through the hypoxic-responsive cleavage of azobenzene linkages. Both in vitro and in vivo biological studies showcase synergistic cancer-killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia-responsive nanoprodrug for a potential combo PDT-CT transition.
Subject(s)
Hypoxia , Oxygen , Humans , Azo Compounds , PeptidesABSTRACT
The frequency and extent of transgene-mediated cosuppression varies substantially among plant genes. However, the underlying mechanisms leading to strong cosuppression have received little attention. In previous studies, we showed that the expression of FAD2 in the seeds of Arabidopsis results in strong RDR6-mediated cosuppression, where both endogenous and transgenic FAD2 were silenced. Here, the FAD2 strong cosuppression system was quantitatively investigated to identify the genetic factors by the expression of FAD2 in their mutants. The involvement of DCL2, DCL4, AGO1, and EIN5 was first confirmed in FAD2 cosuppression. SKI2, a remover of 3' end aberrant RNAs, was newly identified as being involved in the cosuppression, while DCL3 was identified as antagonistic to DCL2 and DCL3. FAD2 cosuppression was markedly reduced in dcl2, dcl4, and ago1. The existence of an RDR6-independent cosuppression was revealed for the first time, which was demonstrated by weak gene silencing in rdr6 ein5 ski2. Further investigation of FAD2 cosuppression may unveil unknown genetic factor(s).
Subject(s)
Arabidopsis Proteins , Arabidopsis , RNA Interference , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , RNA, Small Interfering/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Gene Silencing , RNA-Dependent RNA Polymerase/metabolism , Ribonuclease III/metabolismABSTRACT
BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.
Subject(s)
Radiation Injuries , Thrombocytopenia , Thrombosis , Humans , Animals , Mice , Megakaryocytes/metabolism , Megakaryocytes/pathology , Thrombocytopenia/etiology , Apoptosis , Nucleotidyltransferases/metabolism , Thrombosis/metabolismABSTRACT
Background: The combination of computed tomography angiography (CTA) and computed tomography perfusion (CTP) evaluation of cerebral perfusion status and vascular conditions can improve the diagnostic accuracy of infarction, ischemia, and vascular occlusion in stroke patients, as well as a comprehensive assessment of cerebral edema, collateral circulation, and blood perfusion in the lesion area. However, the consequent radiation safety and contrast agent nephropathy have aroused increasing concern. The purpose of this study was to assess the image quality and diagnostic accuracy of CTA images derived from CTP data, and to explore the feasibility of replacing conventional CTA. Methods: A total of 31 consecutive patients with suspected acute ischemic stroke were retrospectively analyzed. All patients underwent head and neck CTA and brain CTP examinations. All the CTP images were transmitted to the ShuKun artificial intelligence system, which reconstructs CTA derived from CTP (CTA-DF-CTP). The images were divided into 2 groups, including CTA-DF-CTP (Group A) and conventional CTA (Group B). The CT attenuation values, subjective image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), image quality, CT volume dose index (CTDIvol), dose length product (DLP), and effective radiation dose (ED) were compared between the 2 groups. Moreover, the consistency of vascular stenosis and stenosis degree between the 2 groups were measured and evaluated. Results: There were no significant differences in image noise, SNR, or CNR between Groups A and B (P>0.05). The CT attenuation values of the arteries were higher in Group A than in B [internal carotid artery (ICA) =548±112 vs. 454±85 Hounsfield units (HU), middle cerebral artery (MCA) =453±118 vs. 388±70 HU, and basilar artery (BA) =431±99 vs. 360±83 HU] (P<0.01). The image quality of the 2 groups met the requirement of clinical diagnosis (4.97±0.18 vs. 4.94±0.25). No significant difference was found in subjective evaluation (P>0.05). In Group A compared with Group B, the following reductions were observed: CTDIvol (10.7%; 100.8 vs. 112.9 mGy), DLP (23.0%; 1,613±0 vs. 2,093±88 mGy·cm), and ED (23.0%; 5.00±0.00 vs. 6.49±0.27 mSv). Conclusions: CTA-DF-CTP data provide diagnostic accuracy and image quality similar to those of conventional CTA of head and neck CTA.
ABSTRACT
The simultaneous removal of toxic, carcinogenic organic dyes and metal ions from water by one material offers significant advantages when fast, facile, and robust water purification is required. Ionic covalent organic frameworks (ICOFs) have the combined properties of COFs and ion exchange resins and are expected to achieve simultaneous capture of heavy metal ions and organic dyes from water. Herein, a novel guanidinium-based ICOF was synthesized using a solvothermal method. Benefitting from the cationic character, porosity and nanoscale pore size of ICOFs, the adsorbent exhibited high simultaneous adsorption capacities of 290 mg g-1 and 158 mg g-1 for methyl orange (MO) and Cr(vi), respectively, and retained more than 90% adsorption capacity after six adsorption-desorption cycles. In addition, based on dual control of size-exclusion and charge-selection, precisely selective adsorption is achieved towards diverse mixed anionic and cationic pollutants. This strategy offers a practical solution for COFs to confront environmental pollution issues.
ABSTRACT
BACKGROUND: The tumor microenvironment contains chemokines that play a crucial role in various processes, such as tumorigenesis, inflammation, and therapy resistance, in different types of cancer. CXCL5 is a significant chemokine that has been shown to promote tumor proliferation, invasion, angiogenesis, and therapy resistance when overexpressed in various types of cancer. This research aims to investigate the impact of CXCL5 on the biological functions of glioblastoma (GBM). METHODS: The TCGA GBM and GEO databases were utilized to perform transcriptome microarray analysis and oncogenic signaling pathway analysis of CXCL5 in GBM. Validation of CXCL5 expression was performed using RT-qPCR and Western Blot. The impact of CXCL5 on cell proliferation, tumorigenesis, and angiogenesis in GBM was assessed through various methods, including cell proliferation assay, cloning assay, intracranial xenograft tumor models, and tube formation assay. Clinical prognosis was evaluated in 59 samples of gliomas with varying degrees of malignancy (grades 2, 3, and 4) and the TCGA GBM database, based on CXCL5 expression levels. The activities of the JAK-STAT and NF-κB signaling pathways were detected using Western Blot. RESULTS: The expression of CXCL5 was highly enriched in GBM. Moreover, the inhibition of CXCL5 showed a significant efficacy in suppressing cellular proliferation and angiogenesis, resulting in extended survival rates in xenograft mouse models in comparison to the control group. Notably, pretreatment with dapsone exhibited a reversal of the impact of CXCL5 on the formation of colonies and tubes in GBM cells. Elevated expression of CXCL5 was correlated with poor outcomes in GBM patients. Furthermore, the overexpression of CXCL5 has been associated with the activation of JAK-STAT and NF-κB signaling pathways. CONCLUSIONS: CXCL5 plays an important role in tumorigenesis and angiogenesis, indicating the potential for novel therapies targeting CXCL5 in GBM.
Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Animals , Mice , NF-kappa B/metabolism , Glioblastoma/metabolism , Signal Transduction , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Tumor Microenvironment , Chemokine CXCL5/genetics , Chemokine CXCL5/metabolismABSTRACT
OBJECTIVE: This study aimed to investigate the clinical value of combined serum matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) for the prognosis of perianal fistula patients. METHODS: Patients diagnosed and treated for perianal fistula by minimally invasive surgery (MIS) were enrolled. The concentrations of serum MMP-2, MMP-9 and TIMP-1 were measured at 24â h after surgery. Different levels of wound secretion, growth of granulation tissue and wound pain were used as criteria to evaluate surgical incision healing. The receiver operating characteristic curve was used to analyze the predicted assessment value. RESULTS: The concentrations of serum MMP-2 and MMP-9 were significantly higher, while the concentrations of serum TIMP-1 at 24â h after surgery were significantly lower in the poor healing group than in the good healing group. It was further found that high levels of serum MMP-2 and MMP-9 were risk factors for poor healing, while high concentrations of serum TIMP-1 at 24â h after surgery were protective factors for poor healing. CONCLUSION: High concentrations of serum MMP-2 and MMP-9 and low concentrations of serum TIMP at 24â h after surgery are risk factors for poor healing in perianal fistula patients who receive MIS, and the combined test has a higher predictive value.
Subject(s)
Fistula , Tissue Inhibitor of Metalloproteinase-1 , Humans , Matrix Metalloproteinase 9 , Matrix Metalloproteinase 2 , Prognosis , Minimally Invasive Surgical ProceduresABSTRACT
Moderate oxygen (O2) supply and uneven distribution of oxygen at the tumor site usually hinder the therapeutic efficacy of hypoxia-activated prodrugs. In this report, we designed a ferrocene-containing supramolecular nanomedicine (PFC/GOD-TPZ) with the PEG corona and disulfide-bond cross-linked core to co-encapsulate 4-di-N-oxide tirapazamine (TPZ) and glucose oxidase (GOD). The PEG corona of PFC/GOD-TPZ could be weakly acidic tumor pH-responsively detached for an enhanced cellular internalization, while the disulfide-bond cross-linked core could be cleavaged by intracellular glutathione (GSH) to present a GSH-triggered drug-release behavior. Subsequently, the cascade reactions, including catalytic reactions among the released GOD, glucose, and O2 to generate H2O2 and the subsequent Fenton reaction between ferrocene and H2O2, occurred. With the depletion of O2, the non-toxic TPZ was activated and converted into the cytotoxic therapeutic agent benzotriazinyl (BTZ) radical under the exacerbated hypoxic microenvironment. Collectively, the PFC/GOD-TPZ provides a promising strategy for effective combination therapy of GOD-mediated starvation therapy, chemodynamic therapy (CDT), and hypoxia-activated chemotherapy (CT).