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1.
MycoKeys ; 106: 117-132, 2024.
Article in English | MEDLINE | ID: mdl-38948914

ABSTRACT

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T.meilingensis and T.yunjushanensis, as well as a new record of T.effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

2.
J Control Release ; 371: 588-602, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38866245

ABSTRACT

Immunosuppressive microenvironment and poor immunogenicity are two stumbling blocks in anti-tumor immune activation. Tumor associated macrophages (TAMs) play crucial roles in immunosuppressive microenvironment, while immunogenic cell death (ICD) is a typical strategy to boost immunogenicity. Herein, we developed a coordinative modular assembly-based self-reinforced nanoparticle, (CaO2/TA)-(Fe3+/BSA) which integrated CaO2, Fe3+-tannic acid coordinated networks and albumin under the instruction of molecular dynamics simulation. (CaO2/TA)-(Fe3+/BSA) could significantly enhance Fenton reaction through Fe3+ self-reduction and H2O2 self-sufficiency, and simultaneously increased intracellular accumulation of Ca2+. The self-augmented Fenton reaction with sufficient reactive oxygen species effectively repolarized TAMs and elicited ICD with Ca2+ overload. Besides, (CaO2/TA)-(Fe3+/BSA) was confirmed to self-reinforce deep tumor drug delivery by "treatment-delivery" positive feedback based on gp60-mediated transcytosis and M2-like macrophages repolarization-mediated perfusion promotion. Resultantly, (CaO2/TA)-(Fe3+/BSA) effectively alleviated immunosuppression, provoked local and systemic immune response and potentiated anti-PD-1 antibody therapy. Our strategy highlights a facile and controllable approach to construct penetrated effective antitumor nano-immunotherapeutic agent.


Subject(s)
Antineoplastic Agents , Nanoparticles , Tumor Microenvironment , Animals , Nanoparticles/chemistry , Mice , Tumor Microenvironment/drug effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Oxides/chemistry , Oxides/administration & dosage , Calcium Compounds/chemistry , Female , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/therapy , Tumor-Associated Macrophages/drug effects , Tumor-Associated Macrophages/immunology , Mice, Inbred BALB C , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/administration & dosage , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Humans , Calcium/metabolism , Immunogenic Cell Death/drug effects , Drug Delivery Systems , Immunotherapy/methods
3.
Adv Sci (Weinh) ; : e2309314, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38923275

ABSTRACT

Hypervascularized glioblastoma is naturally sensitive to anti-angiogenesis but suffers from low efficacy of transient vasculature normalization. In this study, a lipid-polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep-2 decoration for blood-brain barrier (BBB) penetration. The lipid-polymer nanoparticles can reach glioblastoma within 2 h post intravenous administration, and hypoxia in tumor cells triggers charge-elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding ≈50% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin-6 (IL-6) and interleukin-10 (IL-10) reduction to develop anti-glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9/sgRNA delivery provides a potential solution in glioblastoma therapy.

4.
Langmuir ; 40(26): 13515-13526, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38887887

ABSTRACT

Carbon nanotubes (CNTs) can be regarded as a potential platform for transmembrane drug delivery as many experimental works have demonstrated their capability to effectively transport bioactive molecules into living cells. Within this framework, the loading of a peptide drug onto either the interior or exterior of CNTs has gained considerable interest. This study aims to conduct a comprehensive comparison of these two loading methods. To this end, we performed molecular dynamics simulations and the umbrella sampling technique to investigate the interaction energy, conformational changes, and free energy changes of a model peptide drug containing α-helical structure interacting with the inner or outer walls of a 14.7-nm-long (20,20) CNT. Our finding reveals that, for a tube of such dimensions, it is thermodynamically more favorable for the peptide to be loaded onto the inner tube wall than the outer tube wall, primarily due to a larger free energy change for the former strategy. Conversely, unloading the drug from the tube interior poses greater challenges. Moreover, the tube's curvature plays an essential role in influencing the conformation of the adsorbed peptide. Despite the relatively weaker van der Waals interaction between the CNT exterior and the peptide, loading the peptide onto the exterior may induce significant conformational changes, particularly affecting the peptide's α-helix structure. In contrast, loading of the peptide on the CNT interior could maintain most of the α-helical content. CNTs do not typically attract specific peptide residues, with adsorbed groups primarily determined by the peptide's configurations and orientations. Finally, we offer a guideline for selecting an optimal loading strategy for CNT-based drug delivery.


Subject(s)
Molecular Dynamics Simulation , Nanotubes, Carbon , Peptides , Nanotubes, Carbon/chemistry , Peptides/chemistry , Thermodynamics , Drug Carriers/chemistry
5.
J Cell Mol Med ; 28(11): e18472, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38842129

ABSTRACT

Excessive load on the temporomandibular joint (TMJ) is a significant factor in the development of TMJ osteoarthritis, contributing to cartilage degeneration. The specific mechanism through which excessive load induces TMJ osteoarthritis is not fully understood; however, mechanically-activated (MA) ion channels play a crucial role. Among these channels, Piezo1 has been identified as a mediator of chondrocyte catabolic responses and is markedly increased in osteoarthritis. Our observations indicate that, under excessive load conditions, endoplasmic reticulum stress in chondrocytes results in apoptosis of the TMJ chondrocytes. Importantly, using the Piezo1 inhibitor GsMTx4 demonstrates its potential to alleviate this condition. Furthermore, Piezo1 mediates endoplasmic reticulum stress in chondrocytes by inducing calcium ion influx. Our research substantiates the role of Piezo1 as a pivotal ion channel in mediating chondrocyte overload. It elucidates the link between excessive load, cell apoptosis, and calcium ion influx through Piezo1. The findings underscore Piezo1 as a key player in the pathogenesis of TMJ osteoarthritis, shedding light on potential therapeutic interventions for this condition.


Subject(s)
Apoptosis , Calcium , Chondrocytes , Endoplasmic Reticulum Stress , Ion Channels , Osteoarthritis , Temporomandibular Joint , Chondrocytes/metabolism , Chondrocytes/pathology , Ion Channels/metabolism , Ion Channels/genetics , Animals , Temporomandibular Joint/metabolism , Temporomandibular Joint/pathology , Calcium/metabolism , Osteoarthritis/metabolism , Osteoarthritis/pathology , Humans , Mice , Signal Transduction , Spider Venoms , Intercellular Signaling Peptides and Proteins
6.
Front Endocrinol (Lausanne) ; 15: 1366219, 2024.
Article in English | MEDLINE | ID: mdl-38887267

ABSTRACT

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.


Subject(s)
Lymphatic Metastasis , Nomograms , Thymidine Kinase , Thyroid Cancer, Papillary , Thyroid Neoplasms , Ultrasonography , Humans , Male , Female , Thymidine Kinase/blood , Middle Aged , Adult , Thyroid Cancer, Papillary/blood , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/diagnostic imaging , Thyroid Neoplasms/blood , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroid Neoplasms/diagnostic imaging , Ultrasonography/methods , Biomarkers, Tumor/blood , Risk Factors , ROC Curve , Prognosis , Aged , Young Adult , Lymph Nodes/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery
7.
Polymers (Basel) ; 16(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38891544

ABSTRACT

Plant-derived PA10T is regarded as one of the most promising semi-aromatic polyamides; however, shortcomings, including low dimensional accuracy, high moisture absorption, and relatively high dielectric constant and loss, have impeded its extensive utilization. Polymer blending is a versatile and cost-effective method to fabricate new polymeric materials with excellent comprehensive performance. In this study, various ratios of PA10T/PPO blends were fabricated via melt blending with the addition of a SEBS-g-MAH compatibilizer. Molau test and scanning electron microscopy (SEM) were employed to study the influence of SEBS-g-MAH on the compatibility of PA10T and PPO. These studies indicated that SEBS-g-MAH effectively refines the domain size of the dispersed PPO phase and improves the dispersion stability of PPO particles within a hexafluoroisopropanol solvent. This result was attributed to the in situ formation of the SEBS-g-PA10T copolymer, which serves as a compatibilizer. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) results showed that the melting-crystallization behavior and thermal stability of blends closely resembled that of pure PA10T. Dynamic mechanical analysis (DMA) revealed that as the PPO content increased, there was a decrease in the glass transition temperature and storage modulus of PA10T. The water absorption rate, injection molding shrinkage, dielectric properties, and mechanical strength of blends were also systematically investigated. As the PPO content increased from 10% to 40%, the dielectric loss at 2.5 GHz decreased significantly from 0.00866 to 0.00572, while the notched Izod impact strength increased from 7.9 kJ/m2 to 13.7 kJ/m2.

8.
Int J Mol Sci ; 25(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38892264

ABSTRACT

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.


Subject(s)
Anticonvulsants , Drug Discovery , Epilepsy , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Humans , Animals , Drug Discovery/methods , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Inflammasomes/metabolism , Inflammasomes/antagonists & inhibitors , Drug Development
11.
ACS Omega ; 9(18): 20410-20424, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38737081

ABSTRACT

The droplet-to-iron electrochemical reaction is common in nature and industrial production, and it causes damage to the economy, safety, and the environment. The electrochemical reaction of droplet-to-iron is a coupling process of wetting and corrosion. Presently, investigations into electrochemical reactions mainly focus on the corrosions caused by a solution, and wetting is rarely considered. However, for the droplet-to-iron electrochemical reaction, the mechanism of charge transfer in the process is still unclear. In this paper, a reactive molecular dynamics simulation model for the droplet-to-iron electrochemical reaction is developed for the first time. The electrochemical reaction of droplet-to-iron is studied, and the interaction between droplet wetting and corrosion on iron is investigated. The effects of temperature, electric field strength, and salt concentration on the electrochemical reaction are explored. Results show that droplet wetting on the iron surface and the formation of a single-molecular-layer ordered structure are prerequisites for corrosion. The hydroxyl radicals that penetrate the ordered structure acquire electrons from iron atoms on the substrate surface under the action of Coulomb forces and form iron-containing oxides with these iron atoms. The corrosion products and craters lead to a reduced droplet height, which promotes droplet wetting on iron and further intensifies the droplet-to-iron electrochemical reaction.

12.
Cancer Cell Int ; 24(1): 163, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725047

ABSTRACT

It is commonly assumed that gastrointestinal cancer is the most common form of cancer across the globe and is the leading contributor to cancer-related death. The intricate mechanisms underlying the growth of GI cancers have been identified. It is worth mentioning that both non-coding RNAs (ncRNAs) and certain types of RNA, such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), can have considerable impact on the development of gastrointestinal (GI) cancers. As a tumour suppressor, in the group of short non-coding regulatory RNAs is miR-34a. miR-34a silences multiple proto-oncogenes at the post-transcriptional stage by targeting them, which inhibits all physiologically relevant cell proliferation pathways. However, it has been discovered that deregulation of miR-34a plays important roles in the growth of tumors and the development of cancer, including invasion, metastasis, and the tumor-associated epithelial-mesenchymal transition (EMT). Further understanding of miR-34a's molecular pathways in cancer is also necessary for the development of precise diagnoses and effective treatments. We outlined the most recent research on miR-34a functions in GI cancers in this review. Additionally, we emphasize the significance of exosomal miR-34 in gastrointestinal cancers.

13.
Front Cell Infect Microbiol ; 14: 1230650, 2024.
Article in English | MEDLINE | ID: mdl-38638824

ABSTRACT

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.


Subject(s)
Nanopore Sequencing , Respiratory Tract Infections , Humans , Retrospective Studies , China , Respiratory Tract Infections/diagnosis , Anti-Bacterial Agents , Bronchoalveolar Lavage Fluid , Metagenomics , High-Throughput Nucleotide Sequencing , Sensitivity and Specificity
14.
Cancer Cell Int ; 24(1): 146, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654238

ABSTRACT

BACKGROUND: Colon cancer ranks third among global tumours and second in cancer-related mortality, prompting an urgent need to explore new therapeutic targets. C6orf15 is a novel gene that has been reported only in Sjogren's syndrome and systemic lupus erythematosus patients. We found a close correlation between increased C6orf15 expression and the occurrence of colon cancer. The aim of this study was to explore the potential of C6orf15 as a therapeutic target for colorectal cancer. METHOD: RNA-seq differential expression analysis of the TCGA database was performed using the R package 'limma.' The correlation between target genes and survival as well as tumour analysis was analysed using GEPIA. Western blot and PCR were used to assess C6orf15 expression in colorectal cancer tissue samples. Immunofluorescence and immunohistochemistry were used to assess C6orf15 subcellular localization and tissue expression. The role of C6orf15 in liver metastasis progression was investigated via a mouse spleen infection liver metastasis model. The association of C6orf15 with signalling pathways was assessed using the GSEA-Hallmark database. Immunohistochemistry (IHC), qPCR and western blotting were performed to assess the expression of related mRNAs or proteins. Biological characteristics were evaluated through cell migration assays, MTT assays, and Seahorse XF96 analysis to monitor fatty acid metabolism. RESULTS: C6orf15 was significantly associated with liver metastasis and survival in CRC patients as determined by the bioinformatic analysis and further verified by immunohistochemistry (IHC), qPCR and western blot results. The upregulation of C6orf15 expression in CRC cells can promote the nuclear translocation of ß-catenin and cause an increase in downstream transcription. This leads to changes in the epithelial-mesenchymal transition (EMT) and alterations in fatty acid metabolism, which together promote liver metastasis of CRC. CONCLUSION: Our study identified C6orf15 as a marker of liver metastasis in CRC. C6orf15 can activate the WNT/ß-catenin signalling pathway to promote EMT and fatty acid metabolism in CRC.

15.
Orthod Craniofac Res ; 27(4): 635-644, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38512245

ABSTRACT

OBJECTIVE: To investigate the effects of congenital unilateral first permanent molar occlusal loss (CUMOL) on the morphology and position of temporomandibular joint (TMJ). MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) images of 37 patients with CUMOL (18 males and 19 females, mean age: 13.60 ± 4.38 years) were divided into two subgroups according to the status of second molar (G1: the second molar not erupted, n = 18, G2: second molar erupted, n = 19). The control group consisted of 33 normal occlusion patients (9 males and 24 females, mean age: 16.15 ± 5.44 years) and was divided into 2 subgroups accordingly (G3: the second molar had not erupted, n = 18, G4: the second molar had erupted and made contact with the opposing tooth, n = 15). Linear and angular measurements were used to determine the characteristics of TMJ. RESULTS: In G1, the condyle on the side of the CUMOL shifts posteriorly, with significant side differences observed in Anterior space (AS, P < .05) and Posterior space (PS, P < .05). However, with the eruption of the second permanent molars, in G2, the condyle on the CUMOL side moves posteriorly and inferiorly. This results in significant lateral differences in the AS (P < .05), PS (P < .05), and Superior space (SS, P < .05). Additionally, there is an increase in the thickness of the roof of the glenoid fossa (TRF) on the CUMOL side (P < .05), and a decrease in the inclination of the bilateral articular eminences (P < .05). CONCLUSIONS: CUMOL can affect the position and the morphology of the condyle and was associated with the eruption of the second permanent molars. Before the eruption of the second permanent molars, CUMOL primarily affects the position of the condyle. After the emergence of the second permanent molars, CUMOL leads to changes in both the condyle's position and the morphology of the glenoid fossa.


Subject(s)
Cone-Beam Computed Tomography , Molar , Temporomandibular Joint , Humans , Cone-Beam Computed Tomography/methods , Female , Male , Retrospective Studies , Molar/diagnostic imaging , Adolescent , Temporomandibular Joint/diagnostic imaging , Temporomandibular Joint/pathology , Child , Mandibular Condyle/diagnostic imaging , Mandibular Condyle/pathology , Mandibular Condyle/abnormalities , Temporal Bone/diagnostic imaging , Temporal Bone/pathology , Young Adult
16.
Cancer Cell Int ; 24(1): 90, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429738

ABSTRACT

BACKGROUND: Patients with colorectal cancer (CRC) with liver metastasis or drug resistance have a poor prognosis. Previous research has demonstrated that PPP2R1B inactivation results in the development of CRC. However, the role of PPP2R1B in CRC metastasis and drug resistance is unclear. METHODS: Venny 2.1 was used to determine the intersection between survival-related differentially expressed genes (DEGs) and liver metastasis-related DEGs according to RNA-seq data from The Cancer Genome Atlas (TCGA) and the GEO database (GSE179979). LC‒MS/MS and coimmunoprecipitation were performed to predict and verify the substrate protein of PPP2R1B. Gene Set Variation Analysis (GSVA) was subsequently utilized to assess pathway enrichment levels. The predictive performance of PPP2R1B was assessed by regression analysis, Kaplan-Meier (KM) survival analysis and drug sensitivity analysis. Immunohistochemistry (IHC), qRT-PCR and western blotting were performed to measure the expression levels of related mRNAs or proteins. Biological features were evaluated by wound healing, cell migration and invasion assays and CCK-8 assays. A mouse spleen infection liver metastasis model was generated to confirm the role of PPP2R1B in the progression of liver metastasis in vivo. RESULTS: According to bioinformatics analysis, PPP2R1B is significantly associated with liver metastasis and survival in CRC patients, and these findings were further verified via immunohistochemistry (IHC), qPCR and Western blotting. Pathway enrichment and LC‒MS/MS analysis revealed that PPP2R1B is negatively associated with the MAPK/ERK signalling pathway. Additionally, PD98059, a MAPK/ERK pathway inhibitor, inhibited EMT in vitro by reversing the changes in key proteins involved in EMT signalling (ZEB1, E-cadherin and Snail) and ERK/MAPK signalling (p-ERK) mediated by PPP2R1B. Oxaliplatin sensitivity prediction and validation revealed that PPP2R1B silencing decreased Oxaliplatin chemosensitivity, and these effects were reversed by PD98059 treatment. Moreover, PPP2R1B was coimmunoprecipitated with p-ERK in vitro. A negative correlation between PPP2R1B and p-ERK expression was also observed in clinical CRC samples, and the low PPP2R1B/high p-ERK coexpression pattern indicated a poor prognosis in CRC patients. In vivo, PPP2R1B silencing significantly promoted liver metastasis. CONCLUSIONS: This study revealed that PPP2R1B induces dephosphorylation of the p-ERK protein, inhibits liver metastasis and increases Oxaliplatin sensitivity in CRC patients and could be a potential candidate for therapeutic application in CRC.

17.
Int J Pharm X ; 7: 100238, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38511068

ABSTRACT

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

18.
Arch Microbiol ; 206(2): 63, 2024 Jan 13.
Article in English | MEDLINE | ID: mdl-38217700

ABSTRACT

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.


Subject(s)
Agaricales , Basidiomycota , Phylogeny , DNA, Fungal/genetics , China
19.
Environ Sci Pollut Res Int ; 31(7): 11178-11191, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38217805

ABSTRACT

As logistics carbon emission efficiency is an essential industry linking regions, investigating this issue from a spatial correlation perspective is practically significant. Utilizing data from 282 prefecture-level cities spanning 2006 to 2019, we used a super slacks-based measure model, a modified gravity model, motif analysis, the Infomap algorithm, and an exponential random graph model to analyze the spatial correlation patterns and influencing factors of logistics carbon emission efficiency. The following conclusions were drawn. (1) The spatial correlation of logistics carbon emission efficiency during the study period exhibited a core-edge pattern, with the central region emerging as a high-correlation hub. (2) The scale of the spatial association network community of carbon emission efficiency in the logistics industry changed constantly, and the stability of the network community structure gradually increased. From a microstructural perspective, the dispersed-mode structure was a pivotal element in the formation of the spatial correlation network of logistics carbon emission efficiency. (3) Node interaction tendencies were a critical force driving network formation. Financial investment, government concern, international openness, population density, and innovation ability were conducive to the formation of spatial correlations of logistics carbon emission efficiency.


Subject(s)
Algorithms , Carbon , China , Cities , Government , Economic Development
20.
J Therm Biol ; 119: 103752, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38194751

ABSTRACT

Heat stress can lead to hormonal imbalances, weakened immune system, increased metabolic pressure on the liver, and ultimately higher animal mortality rates. This not only seriously impairs the welfare status of animals, but also causes significant economic losses to the livestock industry. Due to its rich residual bioactive components and good safety characteristics, traditional Chinese medicine (TCM) residue is expected to become a high-quality feed additive with anti-oxidative stress alleviating function. This study focuses on the potential of Shengxuebao mixture herbal residue (SXBR) as an anti-heat stress feed additive. Through the UPLC (ultra performance liquid chromatography) technology, the average residue rate of main active ingredients from SXBR were found to be 25.39%. SXBR were then added into the basal diet of heat stressed New Zealand rabbits at the rates of 5% (SXBRl), 10% (SXBRm) and 20% (SXBRh). Heat stress significantly decreased the weight gain, as well as increased neck and ear temperature, drip loss in meat, inflammation and oxidative stress. Also, the hormone levels were disrupted, with a significant increase in serum levels of CA, COR and INS. After the consumption of SXBR in the basal diet for 3 weeks, the weight of New Zealand rabbits increased significantly, and the SXBRh group restored the redness value of the meat to a similar level as the control group. Furthermore, the serum levels T3 thyroid hormone in the SXBRh group and T4 thyroid hormone in the SXBRm group increased significantly, the SXBRh group showed a significant restoration in inflammation markers (IL-1ß, IL-6, and TNF-α) and oxidative stress markers (total antioxidant capacity, HSP-70, MDA, and ROS) levels. Moreover, the real-time fluorescence quantitative PCR analysis found that, the expression levels of antioxidant genes such as Nrf2, HO-1, NQO1, and GPX1 were significantly upregulated in the SXBRh group, and the expression level of the Keap1 gene was significantly downregulated. Additionally, the SXBRm group showed significant upregulation in the expression levels of HO-1 and NQO1 genes. Western blot experiments further confirmed the up-regulation of Nrf2, Ho-1 and NQO1 proteins. This study provides a strategy for the utilization of SXBR and is of great significance for the green recycling of the TCM residues, improving the development of animal husbandry and animal welfare.


Subject(s)
Antioxidants , Heat Stress Disorders , Rabbits , Animals , Antioxidants/metabolism , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1 , Oxidative Stress , Heat-Shock Response , Inflammation , Heat Stress Disorders/veterinary
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