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2.
Clin Appl Thromb Hemost ; 30: 10760296241250002, 2024.
Article En | MEDLINE | ID: mdl-38779806

Hypoxemia is a clinical characteristic of pulmonary embolism (PE). Hypoxemia is associated with variations in serum prostate-specific antigen (PSA) levels. Thus, the present study aimed to determine serum PSA levels in patients with PE, which may be helpful in improving clinical evaluation in screening for prostate diseases in those with PE. Clinical data from 61 consecutive male patients with PE and 113 age-matched healthy male controls were retrospectively analyzed. The pulmonary artery obstruction index (PAOI) was used to evaluate the pulmonary embolic burden. Compared with healthy controls, serum total PSA (tPSA) levels were significantly increased (P = .003), and free PSA (fPSA)/tPSA ratio was significantly decreased in patients with PE (P < .001). There was no significantly difference in serum fPSA levels between patients with PE and healthy controls (P = .253). A significant positive association was observed between serum tPSA levels and PAOI in patients with PE (ß = .270, P = .036). Multivariable linear regression analysis revealed that serum tPSA levels were independently associated with PAOI in patients with PE (ß = .347, P = .003). Serum tPSA levels were higher in male patients with PE than those in healthy controls, but fPSA was not affected. These findings highlight that PE may elevate serum tPSA levels, and that measures of tPSA should be interpreted with caution in screening for prostate diseases in patients with PE.


Prostate-Specific Antigen , Pulmonary Embolism , Humans , Male , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Prostate-Specific Antigen/blood , Middle Aged , Aged , Retrospective Studies , Case-Control Studies
3.
Sci Adv ; 10(16): eadi1782, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38630819

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.


Glutarates , Leukemia, Myeloid, Acute , Lysine , Humans , Necroptosis , Leukemia, Myeloid, Acute/drug therapy , Apoptosis , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
4.
Front Oncol ; 14: 1367907, 2024.
Article En | MEDLINE | ID: mdl-38665944

Purpose: To assess the utility of fat fraction quantification using quantitative multi-echo Dixon for evaluating tumor proliferation and microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: A total of 66 patients with resection and histopathologic confirmed HCC were enrolled. Preoperative MRI with proton density fat fraction and R2* mapping was analyzed. Intratumoral and peritumoral regions were delineated with manually placed regions of interest at the maximum level of intratumoral fat. Correlation analysis explored the relationship between fat fraction and Ki67. The fat fraction and R2* were compared between high Ki67(>30%) and low Ki67 nodules, and between MVI negative and positive groups. Receiver operating characteristic (ROC) analysis was used for further analysis if statistically different. Results: The median fat fraction of tumor (tFF) was higher than peritumor liver (5.24% vs 3.51%, P=0.012). The tFF was negatively correlated with Ki67 (r=-0.306, P=0.012), and tFF of high Ki67 nodules was lower than that of low Ki67 nodules (2.10% vs 4.90%, P=0.001). The tFF was a good estimator for low proliferation nodules (AUC 0.747, cut-off 3.39%, sensitivity 0.778, specificity 0.692). There was no significant difference in tFF and R2* between MVI positive and negative nodules (3.00% vs 2.90%, P=0.784; 55.80s-1 vs 49.15s-1, P=0.227). Conclusion: We infer that intratumor fat can be identified in HCC and fat fraction quantification using quantitative multi-echo Dixon can distinguish low proliferative HCCs.

5.
World Neurosurg ; 186: e662-e672, 2024 Jun.
Article En | MEDLINE | ID: mdl-38608808

OBJECTIVE: Due to the infiltrative nature and high local recurrence of gliomas, particularly high-grade gliomas, gross total resection (GTR) of a tumor is the first critical step in treatment. This study aimed to determine whether the integration of intraoperative contrast-enhanced ultrasound (CEUS) and fluorescein sodium can improve the identification of tumor boundaries and residuals, and increasethe extent of resection (EOR) to better protect neurological function. METHODS: We retrospectively analysed clinical data from 87 glioma surgeries and categorised the patients into 3 groups: CEUS plus fluorescein sodium, fluorescein sodium alone and microsurgery alone. RESULTS: In terms of EOR, GTR was achieved in 22 (91.7%) patients in the CEUS plus fluorescein sodium group, which was significantly higher than that in other groups. In the subgroup analysis of tumors with lobulated or satellite lesions and WHO grade III or IV gliomas, CEUS plus fluorescein sodium group showed the highest GTR (86.7% and 88.9% respectively) among the groups. Logistic regression analysis of factors that may affect the GTR of tumors showed that the functional areas involvement and the presence of lobulated or satellite lesions were risk factors, whereas CEUS plus fluorescein sodium group was a protective factor. However, CEUS plus fluorescein sodium group had the longest surgery time. CONCLUSIONS: Intraoperative CEUS with fluorescein sodium is a real-time, straightforward, safe, and effective approach to perform surgical resection of gliomas. This approach assists surgeons in identifying tumor boundaries, residual tumors, and normal brain parenchyma, which increases the EOR.


Brain Neoplasms , Contrast Media , Fluorescein , Glioma , Humans , Glioma/surgery , Glioma/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/diagnostic imaging , Female , Male , Middle Aged , Retrospective Studies , Adult , Aged , Ultrasonography/methods , Neurosurgical Procedures/methods , Monitoring, Intraoperative/methods , Young Adult
6.
J Agric Food Chem ; 72(17): 9994-10004, 2024 May 01.
Article En | MEDLINE | ID: mdl-38648468

Triterpenoid saponins, synthesized via the mevalonic acid (MVA) pathway in the cytoplasm, provide protection against pathogens and pests in plants and health benefits for humans. However, the mechanisms by which triterpenoid saponins are transported between cellular compartments remain uncharacterized. Here, we characterize a tonoplast localized multidrug and toxic compound extrusion transporter, GmMATE100 (encoded by Glyma.18G143700), from soybean (Glycine max L.). GmMATE100 is co-expressed with soyasaponin biosynthetic genes, and its expression was induced by MeJA treatment, which also led to soyasaponin accumulation in soybean roots. GmMATE100 efficiently transports multiple type-B soyasaponins as well as type-A soyasaponins with low affinity from the cytosol to the vacuole in a yeast system. The GmMATE100 loss-of-function mutant showed a significant decrease in type-A and type-B soyasaponin contents in soybean roots. This study not only characterized the first soybean triterpenoid saponin transporter but also provided new knowledge for the rational engineering of soyasaponin content and composition in soybean plants to modulate their levels within crop environments.


Glycine max , Plant Proteins , Saponins , Vacuoles , Glycine max/metabolism , Glycine max/chemistry , Glycine max/genetics , Saponins/metabolism , Vacuoles/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Biological Transport , Plant Roots/metabolism , Plant Roots/chemistry , Plant Roots/genetics , Gene Expression Regulation, Plant
7.
Int J Biol Macromol ; 266(Pt 2): 131277, 2024 May.
Article En | MEDLINE | ID: mdl-38565366

Bacteria-infected wound healing has attracted widespread attention in biomedical engineering. Wound dressing is a potential strategy for repairing infectious wounds. However, the development of wound dressing with appropriate physiochemical, antibacterial, and hemostatic properties, remains challenging. Hence, there is a motivation to develop new synthetic dressings to improve bacteria-infected wound healing. Here, we fabricate a biocompatible sponge through the covalent crosslinking of collagen (Col), quaternized chitosan (QCS), and graphene oxide (GO). The resulting Col-QCS-GO sponge shows an elastic modulus of 1.93-fold higher than Col sponge due to enhanced crosslinking degree by GO incorporation. Moreover, the fabricated Col-QCS-GO sponge shows favorable porosity (84.30 ± 3.12 %), water absorption / retention (2658.0 ± 113.4 % / 1114.0 ± 65.7 %), and hemostasis capacities (blood loss <50.0 mg). Furthermore, the antibacterial property of the Col-QCS-GO sponge under near-infrared (NIR) irradiation is significantly enhanced (the inhibition rates are 99.9 % for S. aureus and 99.9 % for E. coli) due to the inherent antibacterial properties of QCS and the photothermal antibacterial capabilities of GO. Finally, the Col-QCS-GO+NIR sponge exhibits the lowest percentage of wound area (9.05 ± 1.42 %) at day 14 compared to the control group (31.61 ± 1.76 %). This study provides new insights for developing innovative sponges for bacteria-infected wound healing.


Anti-Bacterial Agents , Chitosan , Graphite , Hemostatics , Wound Healing , Animals , Rats , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bandages , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Collagen/chemistry , Collagen/pharmacology , Escherichia coli/drug effects , Graphite/chemistry , Graphite/pharmacology , Hemostasis/drug effects , Hemostatics/pharmacology , Hemostatics/chemistry , Porosity , Staphylococcus aureus/drug effects , Wound Healing/drug effects
8.
J Colloid Interface Sci ; 668: 213-222, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38677210

Regarding carbon-based electrodes, simultaneously establishing a well-defined meso-porous architecture, introducing abundant hetero-atoms and improving the graphitization degree can effectively enhance their capacitive performance. However, it remains a significant challenge to achieve a good balance between defects and graphitization degree. In this study, the porous structure and composition of carbon materials are co-optimised through a 'dual-function' strategy. Briefly, K3Fe(C2O4)3 and H3BO3 were hybridised with a gelatin aqueous solution to form a homogeneous composite hydrogel, followed by lyophilisation and carbonisation. Owing to the dual functionality of raw materials, the graphitization, activation and hetero-atom doping processes can occur simultaneously during a one-step high-temperature treatment. The resultant carbon material exhibits a high graphitization degree (ID/IG = 0.9 ± 0.1), high hetero-atom content (N: 9.0 ± 0.3 at.%, B: 6.9 ± 0.5 at.%) and a large specific area (1754 ± 58 m2/g). The as-prepared electrode demonstrates a superior capacitance of 383 ± 1F g-1 at 1 A/g. Interestingly, the cyclic voltammetry (CV) curves exhibit a distinctive pair of broad redox peaks, which is uncommon in KOH electrolyte. Experiment data and density functional theory (DFT) simulation verify that N-5, B co-doping enhances the activity of the faradic reaction of carbon electrodes in KOH electrolyte. Furthermore, the fabricated Zn-ion hybrid supercapacitor (ZHSC) based on this carbon electrode delivers a high-energy density of 140.7 W h kg-1 at a power density of 840 W kg-1.

9.
J Transl Med ; 22(1): 224, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38429799

BACKGROUND: In recent years, natural bone extracellular matrix (ECM)-inspired materials have found widespread application as scaffolds for bone tissue engineering. However, the challenge of creating scaffolds that mimic natural bone ECM's mechanical strength and hierarchical nano-micro-macro structures remains. The purposes of this study were to introduce an innovative bone ECM-inspired scaffold that integrates a 3D-printed framework with hydroxyapatite (HAp) mineralized graphene oxide-collagen (GO-Col) microscaffolds and find its application in the repair of mandibular bone defects. METHODS: Initially, a 3D-printed polycaprolactone (PCL) scaffold was designed with cubic disks and square pores to mimic the macrostructure of bone ECM. Subsequently, we developed multi-layer mineralized GO-Col-HAp microscaffolds (MLM GCH) to simulate natural bone ECM's nano- and microstructural features. Systematic in vitro and in vivo experiments were introduced to evaluate the ECM-inspired structure of the scaffold and to explore its effect on cell proliferation and its ability to repair rat bone defects. RESULTS: The resultant MLM GCH/PCL composite scaffolds exhibited robust mechanical strength and ample assembly space. Moreover, the ECM-inspired MLM GCH microscaffolds displayed favorable attributes such as water absorption and retention and demonstrated promising cell adsorption, proliferation, and osteogenic differentiation in vitro. The MLM GCH/PCL composite scaffolds exhibited successful bone regeneration within mandibular bone defects in vivo. CONCLUSIONS: This study presents a well-conceived strategy for fabricating ECM-inspired scaffolds by integrating 3D-printed PCL frameworks with multilayer mineralized porous microscaffolds, enhancing cell proliferation, osteogenic differentiation, and bone regeneration. This construction approach holds the potential for extension to various other biomaterial types.


Durapatite , Graphite , Osteogenesis , Rats , Animals , Durapatite/analysis , Durapatite/metabolism , Durapatite/pharmacology , Tissue Scaffolds/chemistry , Bone Regeneration , Collagen/metabolism , Extracellular Matrix/metabolism , Tissue Engineering , Polyesters/chemistry , Mandible , Printing, Three-Dimensional
10.
Eur J Cancer ; 202: 113979, 2024 May.
Article En | MEDLINE | ID: mdl-38471289

BACKGROUND: The outcome of relapsed/refractory (R/R) acute myeloid leukemia (AML) remains extremely poor. Venetoclax (VEN)-based regimens have shown promise in treating R/R AML. OBJECTIVE: This phase 2 study aimed to systematically evaluate the efficacy and safety of the VAA regimen (VEN plus Cytarabine and Azacitidine) in R/R AML patients. METHODS: Thirty R/R AML patients were enrolled. The study adopted a stepwise ramp-up of VEN dosing, starting with 100 mg on day 1, escalating to 200 mg on day 2, and reaching 400 mg from day 3 to day 9. Cytarabine (10 mg/m2, q12h) was administered intravenously twice daily from days 1 to 10, and Azacitidine (75 mg/m2) was administered via subcutaneous injection once daily from days 1-7. The primary efficacy endpoint was the composite complete remission rate (CRc), including complete response (CR) and complete response with incomplete blood count recovery (CRi). Secondary endpoints included overall survival (OS), duration of response (DOR), and safety analysis. RESULTS: The CRc rate was 63.3% (19/30), with CR in 36.7% of patients and CRi in 26.7%. Notably, 14 (73.7%) of 19 patients achieving CRc showed undetectable measurable residual disease by flow cytometry. With a median follow-up of 10.7 months, the median OS had not been reached, and the median DOR was 18.3 months. The most common grade 3-4 adverse events (AEs) were neutropenia (100%), anemia (96.7%), thrombocytopenia (90.0%), and leukopenia (90.0%). Infections, with pneumonia being the most prevalent (43.3%), were observed, including one fatal case of Pseudomonas aeruginosa septicemia. There were no treatment-related deaths. CONCLUSION: The VAA regimen is an effective and safe option for patients with R/R AML, demonstrating a high CRc rate and manageable safety profile.


Leukemia, Myeloid, Acute , Leukopenia , Sulfonamides , Humans , Cytarabine/adverse effects , Azacitidine , Leukemia, Myeloid, Acute/drug therapy , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Pathologic Complete Response , Leukopenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects
11.
Int J Biol Macromol ; 263(Pt 2): 130386, 2024 Apr.
Article En | MEDLINE | ID: mdl-38395288

The management of diabetic wounds poses a substantial economic and medical burden for diabetic patients. Oxidative stress and persistent bacterial infections are considered to be the primary factors. Qiai essential oil (QEO) exhibits various pharmacological characteristics, including inflammatory-reducing, antibacterial, and antioxidant properties. Nevertheless, the hydrophobic nature and propensity for explosive release of this substance present constraints on its potential for future applications. Here, we developed a stimulus-responsive hydrogel to overcome the multiple limitations of QEO-based wound dressings. The QEO was encapsulated within graphene oxide (GO) through repeated extrusion using an extruder. Subsequently, QEO@GO nanoparticles were incorporated into a Gelatin-methacryloyl (GelMA) hydrogel. The QEO@GO-GelMA hydrogel demonstrated controlled release ablation, photothermal antibacterial effects, and contact ablation against two representative bacterial strains. It effectively reduced reactive oxygen species (ROS) generation, promoted angiogenesis, and decreased levels of the pro-inflammatory cytokine interleukin-6 (IL-6), thereby accelerating the healing process of diabetic wounds. In addition, in vitro and in vivo tests provided further evidence of the favorable biocompatibility of this multifunctional hydrogel dressing. Overall, the QEO@GO-GelMA hydrogel provides numerous benefits, encompassing antimicrobial properties, ROS-scavenging abilities, anti-inflammatory effects, and the capacity to expedite diabetic wound healing. These attributes make it an optimal choice for diabetic wound management.


Anti-Infective Agents , Diabetes Mellitus , Methacrylates , Humans , Reactive Oxygen Species , Gelatin , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents
13.
J Clin Invest ; 134(8)2024 Feb 22.
Article En | MEDLINE | ID: mdl-38386414

Chromosomal instability is a prominent biological feature of myelodysplastic syndromes (MDS), with over 50% of patients with MDS harboring chromosomal abnormalities or a complex karyotype (CK). Despite this observation, the mechanisms underlying mitotic and chromosomal defects in MDS remain elusive. In this study, we identified ectopic expression of the transcription factor ONECUT3, which is associated with CKs and poorer survival outcomes in MDS. ONECUT3-overexpressing cell models exhibited enrichment of several notable pathways, including signatures of sister chromosome exchange separation and mitotic nuclear division with the upregulation of INCENP and CDCA8 genes. Notably, dysregulation of chromosome passenger complex (CPC) accumulation, besides the cell equator and midbody, during mitotic phases consequently caused cytokinesis failure and defective chromosome segregation. Mechanistically, the homeobox (HOX) domain of ONECUT3, serving as the DNA binding domain, occupied the unique genomic regions of INCENP and CDCA8 and transcriptionally activated these 2 genes. We identified a lead compound, C5484617, that functionally targeted the HOX domain of ONECUT3, inhibiting its transcriptional activity on downstream genes, and synergistically resensitized MDS cells to hypomethylating agents. This study revealed that ONECUT3 promoted chromosomal instability by transcriptional activation of INCENP and CDCA8, suggesting potential prognostic and therapeutic roles for targeting high-risk MDS patients with a CK.


Myelodysplastic Syndromes , Transcription Factors , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , Ectopic Gene Expression , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , Chromosomal Instability , Karyotype
14.
BMC Cancer ; 24(1): 220, 2024 Feb 16.
Article En | MEDLINE | ID: mdl-38365636

BACKGROUND: Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. METHODS: The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. RESULTS: In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. CONCLUSION: In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.


Brain Neoplasms , Bromodomain Containing Proteins , Glioblastoma , Animals , Child , Humans , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Bromodomain Containing Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Prospective Studies , Syndecan-1/antagonists & inhibitors , Transcription Factors/genetics
15.
Plant Commun ; 5(5): 100830, 2024 May 13.
Article En | MEDLINE | ID: mdl-38297839

Neonicotinoids (NEOs), a large class of organic compounds, are a type of commonly used pesticide for crop protection. Their uptake and accumulation in plants are prerequisites for their intra- and intercellular movements, transformation, and function. Understanding the molecular mechanisms that underpin NEO uptake by plants is crucial for effective application, which remains elusive. Here, we demonstrate that NEOs enter plant cells primarily through the transmembrane symplastic pathway and accumulate mainly in the cytosol. Two plasma membrane intrinsic proteins discovered in Brassica rapa, BraPIP1;1 and BraPIP2;1, were found to encode aquaporins (AQPs) that are highly permeable to NEOs in different plant species and facilitate NEO subcellular diffusion and accumulation. Their conserved transport function was further demonstrated in Xenopus laevis oocyte and yeast assays. BraPIP1;1 and BraPIP2;1 gene knockouts and interaction assays suggested that their proteins can form functional heterotetramers. Assessment of the potential of mean force indicated a negative correlation between NEO uptake and the energy barrier of BraPIP1;1 channels. This study shows that AQPs transport organic compounds with greater osmolarity than previously thought, providing new insight into the molecular mechanisms of organic compound uptake and facilitating innovations in systemic pesticides.


Aquaporins , Aquaporins/metabolism , Aquaporins/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Biological Transport , Neonicotinoids/metabolism , Animals , Pesticides/metabolism , Xenopus laevis/metabolism , Brassica rapa/metabolism , Brassica rapa/genetics , Oocytes/metabolism , Insecticides/metabolism
16.
J Control Release ; 365: 889-904, 2024 Jan.
Article En | MEDLINE | ID: mdl-37952829

Immunoregulation mediated bone tissue engineering (BTE) has demonstrated huge potential in promoting repair of critical-size bone defects (CSBDs). The trade-off between stable immunoregulation function and extended immunoregulation period has posed a great challenge to this strategy. Here, we reported a 3D porous biodegradable Poly(HEMA-co-3APBA)/LUT scaffold, in which reversible boronic acid ester bond was formed between the 3APBA moiety and the catechol moiety of luteolin (LUT). The boronic acid ester bond not only protected the bioactivity of LUT but also extended the release period of LUT. The rationale behind the phenomenon of sustained LUT release was explained using a classical transition state theory. In vitro/in vivo assays proved the immunoregulation function of the scaffold in inducing M2 polarization of both M0 and M1 Mφ. The crosstalk between the scaffold treated Raw 264.7 and BMSCs were also investigated through the in vitro co-culture assay. The results demonstrated that the scaffold could induce immunoregulation mediated osteogenic differentiation of BMSCs. In addition, CSBDs model of SD rats was also applied, and the corresponding data proved that the scaffold could accelerate new bone formation, therefore promoting repair of CSBDs. The as-prepared scaffold might be a promising candidate for repair of CSBDs in the future.


Osteogenesis , Tissue Scaffolds , Rats , Animals , Tissue Scaffolds/chemistry , Luteolin/pharmacology , Rats, Sprague-Dawley , Tissue Engineering , Macrophages , Boronic Acids , Esters , Bone Regeneration
18.
Int J Nanomedicine ; 18: 6725-6741, 2023.
Article En | MEDLINE | ID: mdl-38026526

Introduction: The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs). Methods: In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats. Results: The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group. Discussion: Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.


Microgels , Rats , Animals , Biomimetics , Gelatin/chemistry , Apatites , Tissue Engineering/methods , Hydrogels , Tissue Scaffolds/chemistry
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(10): 1028-1033, 2023 Oct 15.
Article Zh | MEDLINE | ID: mdl-37905759

OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS: Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.


Autism Spectrum Disorder , Child , Humans , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/psychology , Diagnosis, Differential , Machine Learning , Social Behavior
20.
Environ Sci Technol ; 57(45): 17312-17323, 2023 11 14.
Article En | MEDLINE | ID: mdl-37907425

Plants have developed an adaptive strategy for coping with biotic or abiotic stress by recruiting specific microorganisms from the soil pool. Recent studies have shown that the foliar spraying of pesticides causes oxidative stress in plants and leads to changes in the rhizosphere microbiota, but the mechanisms by which these microbiota change and rebuild remain unclear. Herein, we provide for the first-time concrete evidence that rice plants respond to the stress of application of the insecticide chlorpyrifos (CP) by enhancing the release of amino acids, lipids, and nucleotides in root exudates, leading to a shift in rhizosphere bacterial community composition and a strong enrichment of the genus Sphingomonas sp. In order to investigate the underlying mechanisms, we isolated a Sphingomonas representative isolate and demonstrated that it is both attracted by and able to consume linolenic acid, one of the root exudates overproduced after pesticide application. We further show that this strain selectively colonizes roots of treated plants and alleviates pesticide stress by degrading CP and releasing plant-beneficial metabolites. These results indicate a feedback loop between plants and their associated microbiota allowing to respond to pesticide-induced stress.


Chlorpyrifos , Pesticides , Sphingomonas , Chlorpyrifos/metabolism , Sphingomonas/metabolism , Rhizosphere , Bacteria/metabolism , Plants/metabolism , Linolenic Acids/metabolism , Plant Roots/metabolism , Plant Roots/microbiology , Soil Microbiology
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