Double-Phase-Networking Polyimide Hybrid Aerogel with Exceptional Dimensional Stability for Superior Thermal Protection System.

Polyimide aerogels have been extensively used in thermal protection domain because they possess a combination of intrinsic characteristics of aerogels and unique features of polyimide. However, polyimide aerogels still suffer significant thermally induced shrinkage at temperatures above 200 °C, restricting their application at high temperature. Here, a novel "double-phase-networking" strategy is proposed for fabricating a lightweight and mechanically robust polyimide hybrid aerogel by forming silica-zirconia-phase networking skeletons, which possess exceptional dimensional stability in high-temperature environments and superior thermal insulation. The rational mechanism responsible for the formation of double-phase-networking aerogel is further explained, generally attributing to chemical crosslinking reactions and supramolecular hydrogen bond interactions derived from the main chains of polyimide and silane/zirconia precursor/sol. The as-prepared aerogels exhibit excellent high-temperature (270 °C) dimensional stability (5.09% ± 0.16%), anti-thermal-shock properties, and low thermal conductivity. Moreover, the hydrophobic treatment provides aerogels high water resistance with water contact angle of 136.9°, further suggestive of low moisture content of 3.6% after exposure to 70 °C and 85% relative humidity for 64 h. The proposed solution for significantly enhancing high-temperature dimensional stability and thermal insulation provides a great supporting foundation for fabricating high-performance organic aerogels as thermal protection materials in aerospace.

Screening of active components of Ganoderma lucidum and decipher its molecular mechanism to improve learning and memory disorders.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a "main active ingredient-target" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

Harnessing Bacterial Membrane Components for Tumor Vaccines: Strategies and Perspectives.

Tumor vaccines stand at the vanguard of tumor immunotherapy, demonstrating significant potential and promise in recent years. While tumor vaccines have achieved breakthroughs in the treatment of cancer, they still encounter numerous challenges, including improving the immunogenicity of vaccines and expanding the scope of vaccine application. As natural immune activators, bacterial components offer inherent advantages in tumor vaccines. Bacterial membrane components, with their safer profile, easy extraction, purification, and engineering, along with their diverse array of immune components, activate the immune system and improve tumor vaccine efficacy. This review systematically summarizes the mechanism of action and therapeutic effects of bacterial membrane and its derivatives (including bacterial membrane vesicles and hybrid membrane biomaterials) in tumor vaccines. Subsequently, we delve into the preparation and advantages of tumor vaccines based on bacterial membranes and hybrid membrane biomaterials. Following this, the immune effects of tumor vaccines based on bacterial outer membrane vesicles (OMVs) are elucidated, and their mechanisms are explained. Moreover, their advantages in tumor combination therapy are analyzed. Lastly, the challenges and trends in this field are discussed. Our comprehensive analysis aims to offer a more informed reference and scientific foundation for the design and implementation of bacterial membrane-based tumor vaccines. This article is protected by copyright. All rights reserved.

Screening of drug targets for tuberculosis on the basis of transcription factor regulatory network and mRNA sequencing technology.

Background: Tuberculosis is a worldwide epidemic disease, posing a serious threat to human health. To find effective drug action targets for Mycobacterium tuberculosis, differentially expressed genes in tuberculosis patients and healthy people were screened by mRNA sequencing in this study. A total of 556 differentially expressed genes in tuberculosis patients and healthy people were screened out by mRNA sequencing technology. 26 transcription factors and 66 corresponding target genes were screened out in the AnimalTFDB 3.0 database, and a transcription factor regulatory network was constructed. Results: Three key transcription factors (TP53, KLF5 and GATA2) and one key gene (AKT1) were screened as new potential drug targets and diagnostic targets for tuberculosis by MCODE cluster analysis, and the key genes and key transcription factors were verified by RT-PCR. Finally, we constructed the and a key factor and KEGG signaling pathway regulatory network to clarify the possible molecular pathogenesis of tuberculosis. Conclusion: This study suggested M. tuberculosis may activate the AKT1 gene expression by regulating transcription factors TP53, KLF5, and GATA2, thus activating the B cell receptor signaling pathway to induce the infection and invasion of M. tuberculosis. AKT1, TP53, KLF5, and GATA2 can be used as new potential drug targets for tuberculosis.

Study of hub nodes of transcription factor-target gene regulatory network and immune mechanism for type 2 diabetes based on chip analysis of GEO database.

Identification of novel therapeutic targets for type 2 diabetes is a key area of contemporary research. In this study, we screened differentially expressed genes in type 2 diabetes through the GEO database and sought to identify the key virulence factors for type 2 diabetes through a transcription factor regulatory network. Our findings may help identify new therapeutic targets for type 2 diabetes. Data pertaining to the humoral (whole blood) gene expression profile of diabetic patients were obtained from the NCBI's GEO Datasets database and gene sets with differential expression were identified. Subsequently, the TRED transcriptional regulatory element database was integrated to build a gene regulatory network for type 2 diabetes. Functional analysis (GO-Analysis) and Pathway-analysis of differentially expressed genes were performed using the DAVID database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Finally, gene-disease correlation analysis was performed using the DAVID online annotation tool. A total of 236 pathogenic genes, four transcription factors related to the pathogenic genes, and 261 corresponding target genes were identified. A transcription factor-target gene regulatory network for type 2 diabetes was constructed. Most of the key factors of the transcription factor-target gene regulatory network for type 2 diabetes were found closely related to the immune metabolic system and the functions of cell proliferation and transformation.

Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission.

BACKGROUND: Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped. MATERIALS AND METHODS: In vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically. RESULTS: We found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes. CONCLUSION: Collectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration.

ROS-Responsive Injectable Hydrogel Loaded with SLC7A11-modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats.

Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, low back pain imposes a significant global economic burden. However, the effectiveness of treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective IVDD treatments by focusing on oxidative stress as a starting point. In this study, an injectable reactive oxygen species-responsive hydrogel (PVA-tsPBA@SLC7A11 modRNA) is developed, designed to achieve rapid loading and selective release of chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA is specifically used to upregulate the expression of the ferroptosis marker SLC7A11. The local injection of PVA-tsPBA@SLC7A11 modRNA into the degenerated intervertebral disc (IVD) results in the cleavage of PVA-tsPBA, leading to the release of enclosed SLC7A11 modRNA. The extent of SLC7A11 modRNA release is directly proportional to the severity of IVDD, ultimately ameliorating IVDD by inhibiting ferroptosis in nucleus pulposus cells (NPCs). This study proposes an innovative system of PVA-tsPBA hydrogel-encapsulated modRNA, representing a potential novel treatment strategy for patients with early-stage IVDD.

HIF-1α-induced expression of the m6A reader YTHDF1 inhibits the ferroptosis of nucleus pulposus cells by promoting SLC7A11 translation.

The nucleus pulposus is in a hypoxic environment in the human body, and when intervertebral disc degeneration (IVDD) occurs, the hypoxic environment is disrupted. Nucleus pulposus cell (NPC) ferroptosis is one of the causes of IVDD. N6-methyladenosine (m6A) and its reader protein YTHDF1 regulate cellular activities by affecting RNA metabolism. However, the regulation of ferroptosis in NPCs by m6A-modified RNAs under hypoxic conditions has not been as well studied. In this study, through in vitro and in vivo experiments, we explored the underlying mechanism of HIF-1α and YTHDF1 in regulating ferroptosis in NPCs. The results indicated that the overexpression of HIF-1α or YTHDF1 suppressed NPC ferroptosis; conversely, the knockdown of HIF-1α or YTHDF1 increased ferroptosis levels in NPCs. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region. Polysome profiling results showed that YTHDF1 promoted the translation of SLC7A11 and consequently the expression of the anti-ferroptosis protein GPX4 by binding to m6A-modified SLC7A11 mRNA. In conclusion, HIF-1α-induced YTHDF1 expression reduces NPC ferroptosis and delays IVDD by promoting SLC7A11 translation in a m6A-dependent manner.

RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response.

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1ß-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.

Evaluation of the modified MRI vertebral bone quality score for bone quality in lumbar degenerative disorders.

OBJECTIVE: The traditional VBQ scoring method may lead to overestimation due to the concentration of intravertebral fat and vascular structures in the posterior half of vertebral bodies, potentially resulting in false-positive outcomes. This study aims to modify the measurement method of VBQ score (Modified-VBQ) and evaluate its effectiveness in evaluating bone quality of lumbar degenerative diseases. METHODS: Retrospective analysis was conducted on clinical data from patients undergoing lumbar surgery for degenerative diseases between September 2022 and September 2023. Preoperative lumbar t1-weighted Magnetic resonance imaging was used for both modified and traditional VBQ scoring. Computed tomography (CT) images and dual-energy X-ray absorptiometry (DEXA) data were collected through the picture archiving and communication system. The effectiveness of the modified VBQ score was evaluated, considering P < 0.05 as statistically significant. RESULTS: The study included 212 patients, revealing a significant difference between the modified VBQ and VBQ scores (P < 0.0001). Notably, patients with a history of hyperlipidemia exhibited a significant difference between the two scores (P = 0.0037). The area under the ROC curve (AUC) for the modified VBQ was 0.86, surpassing the VBQ score (AUC = 0.74). Linear regression analysis demonstrated a moderate to strong correlation between the modified VBQ and DEXA T-score (r = - 0.49, P < 0.0001) and a high correlation with CT Hounsfield units (HU) values (r = - 0.60, P < 0.0001). CONCLUSION: The modified VBQ score provides a simple, effective, and relatively accurate means of assessing bone quality in lumbar degenerative diseases. Preoperative implementation of the modified VBQ score facilitates rapid screening for patients with abnormal bone quality.

GEO dataset mining analysis reveals novel Staphylococcus aureus virulence gene regulatory networks and diagnostic targets in mice.

Staphylococcus (S.) aureus infection is a serious, worldwide health concern, particularly in many communities and hospitals. Understanding the S. aureus pathogenetic regulatory network will provide significant insights into diagnostic target screening to improve clinical treatment of diseases caused by S. aureus. We screened differentially expressed genes between normal mice and S. aureus-infected mice. We used the Gene Expression Omnibus (GEO) DataSets database for functional analysis (GO-analysis) and the DAVID and KEGG databases for signaling pathway analyses. We next integrated the gene and pathway analyses with Transcriptional Regulatory Element Database (TRED) to build an antimicrobial resistance gene regulatory network of S. aureus. We performed association analysis of network genes and diseases using DAVID online annotation tools. We identified a total of 437 virulence genes and 15 transcription factors (TFs), as well as 444 corresponding target genes, in the S. aureus TF regulatory network. We screened seven key network nodes (Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl), four key transcription factors (Jun, C3, Spil, and Il6) and an important signaling pathway (TNF). We hypothesized that the cytokine activity and growth factor activity of S. aureus are combinatorically cross-regulated by Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl genes, the TFs Jun, C3, Spi1, and Il6, as well as the immune response, cellular response to lipopolysaccharide, and inflammatory response. Our study provides information and reference values for the molecular understanding of the S. aureus pathogenetic gene regulatory network.

A Study on Interobserver and Intraobserver Reliability of the Huashan Radiologic Classification System for Cervical Spinal Cord Injury Without Fracture and Dislocation.

STUDY DESIGN: Observational study. OBJECTIVE: To assess the reproducibility and reliability of the system. BACKGROUND: The Huashan radiologic classification system for cervical spinal cord injury without fracture and dislocation (CSCIWFD) was recently proposed and found useful for clinical practice. PATIENTS AND METHODS: Patients diagnosed with CSCIWFD between 2015 and 2021 were recruited. Six spine surgeons from different institutions, three experienced and other inexperienced respectively, were trained as observers of the system, and these surgeons classified the recruited patients using the system. Then, 8 weeks later, they repeated the classification on the same patients in a different order. The interobserver and intraobserver agreement between the results was analyzed using percentage agreement, weighted kappa, and Cohen kappa (κ) statistics. RESULTS: A total of 60 patients were included in the analysis. Type I was the most frequent type (29 cases, 48.3%), followed by type II (13 cases, 21.7%), type III (12 cases, 20%), and type IV (6 cases, 10%). For all the observers, experienced observers, and inexperienced observers, the overall agreement percentages were 77.6% (κ = 0.78), 84.4% (κ = 0.84), and 72.8% (κ = 0.74), respectively, indicating substantial to nearly perfect interobserver reproducibility. A higher level of agreement was found for differentiating type I from other types, with the percentage agreement ranging from 87.8% to 94.4% (κ= 0.74-0.88). For distinguishing compression on the spinal cord (types I and II vs types III and IV) among the different groups of observers, the percentage agreement was 97.8% (κ = 0.94), indicating nearly perfect reproducibility. As for intraobserver agreement, the percentage agreement ranged from 86.7% to 96.7% (κ = 0.78-0.95), indicating at least substantial reliability. CONCLUSIONS: The Huashan radiologic classification system for CSCIWFD was easy to learn and apply in a clinical environment, showing excellent reproducibility and reliability. Therefore, it would be promising to apply and promote this system for the precise evaluation and personalized treatment strategy.

Targeting pyroptosis to treat ischemic stroke: From molecular pathways to treatment strategy.

Ischemic stroke is the primary reason for human disability and death, but the available treatment options are limited. Hence, it is imperative to explore novel and efficient therapies. In recent years, pyroptosis (a pro-inflammatory cell death characterized by inflammation) has emerged as an important pathological mechanism in ischemic stroke that can cause cell death through plasma membrane rupture and release of inflammatory cytokines. Pyroptosis is closely associated with inflammation, which exacerbates the inflammatory response in ischemic stroke. The level of inflammasomes, GSDMD, Caspases, and inflammatory factors is increased after ischemic stroke, exacerbating brain injury by mediating pyroptosis. Hence, inhibition of pyroptosis can be a therapeutic strategy for ischemic stroke. In this review, we have summarized the relationship between pyroptosis and ischemic stroke, as well as a series of treatments to attenuate pyroptosis, intending to provide insights for new therapeutic targets on ischemic stroke.

Design, synthesis, and biological evaluation of selective covalent inhibitors of FGFR4.

Aberrant signaling via fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) has been identified as a driver of tumorigenesis and the development of many solid tumors, making FGFR4 is a promising target for anticancer therapy. Herein, we designed and synthesized a series of bis-acrylamide covalent FGFR4 inhibitors and evaluated their inhibitory activity against FGFRs, FGFR4 mutants, and their antitumor activity. CXF-007, verified by mass spectrometry and crystal structures to form covalent bonds with Cys552 of FGFR4 and Cys488 of FGFR1, exhibited stronger selectivity and potent inhibitory activity for FGFR4 and FGFR4 cysteine mutants. Moreover, CXF-007 exhibited significant antitumor activity in hepatocellular carcinoma cell lines and breast cancer cell lines through sustained inhibition of the FGFR4 signaling pathway. In summary, our study highlights a novel covalent FGFR4 inhibitor, CXF-007, which has the potential to overcome drug-induced FGFR4 mutations and might provide a new strategy for future anticancer drug discovery.

Cellulose Diacetate Aerogels with Low Drying Shrinkage, High-Efficient Thermal Insulation, and Superior Mechanical Strength.

The inherent characteristics of cellulose-derived aerogels, such as their natural abundance and environmental friendliness, make them highly interesting. However, its significant shrinkage before and after the supercritical drying procedure and low mechanical strength limit its potential application. Here, we propose a strategy to prepare cellulose diacetate aerogels (CDAAs) with low drying shrinkage, exceptional thermal insulation, and superior mechanical strength. The low drying shrinkage (radial drying shrinkage of 1.4%) of CDAAs is attributed to their relative strong networking skeletons, which are greatly formed by tert-butanol solvent exchange in exerting the interaction of reducing the surface tension force. In this case, CDAAs are eventually endowed with the low bulk density of 0.069 g cm-3 as well. Additionally, as-prepared CDAAs possess an abundant three-dimensional networking structure whose pore size is concentrated in the diameter range of ~50 nm, and the result above is beneficial for improving the thermal insulation performance (thermal conductivity of 0.021 W m-1 K-1 at ambient environmental and pressure conditions). On the other hand, the optimal compressive stresses of CDAAs at 3% and 5% strain are 0.22 and 0.27 MPa respectively, indicating a mechanically well robustness. The above evidence demonstrates indeed the exceptional thermal insulation and superior compressive properties of CDAAs. This work may provide a new solution for developing a kind of high-performance cellulose-derived aerogel in the future.

Subsurface acoustic ducts in the Northern California current system.

This study investigates the subsurface sound channel or acoustic duct that appears seasonally along the U.S. Pacific Northwest coast below the surface mixed layer. The duct has a significant impact on sound propagation at mid-frequencies by trapping sound energy and reducing transmission loss within the channel. A survey of the sound-speed profiles obtained from archived mooring and glider observations reveals that the duct is more prevalent in summer to fall than in winter to spring and offshore of the shelf break than over the shelf. The occurrence of the subsurface duct is typically associated with the presence of a strong halocline and a reduced thermocline or temperature inversion. Furthermore, the duct observed over the shelf slope corresponds to a vertically sheared along-slope velocity profile, characterized by equatorward near-surface flow overlaying poleward subsurface flow. Two potential duct formation mechanisms are examined in this study, which are seasonal surface heat exchange and baroclinic advection of distinct water masses. The former mechanism regulates the formation of a downward-refracting sound-speed gradient that caps the duct near the sea surface, while the latter contributes to the formation of an upward-refracting sound-speed gradient that defines the duct's lower boundary.

Ginkgo biloba extract alleviates CCl4-induced acute liver injury by regulating PI3K/AKT signaling pathway.

Acute liver injury (ALI) is a global health problem associated with high mortality and has attracted clinical attention. Ginkgo biloba extract (GBE) is an extract from dried Ginkgo leaves that has many pharmacological effects because of its various ingredients and has been shown to be hepatoprotective. We investigated the hepatoprotective effect of GBE on carbon tetrachloride (CCl4)-induced acute liver injury in vitro. The components of Ginkgo biloba extract are analyzed by LC-MS, and the key targets of "liver injury-Ginkgo biloba" are identified based on bioinformatics analysis. The signaling pathways such as PI3K/AKT are mainly enriched with high correlation in KEGG. The results of in vitro experiments showed that compared with the Model group, except that the ALT activity level and MDA content in EGB-L group were not significantly decreased (P > 0.05), the activity of ALT, AST and MDA content in other EGB groups were significantly decreased (P < 0.05), and the activities of SOD and CAT were significantly increased (P < 0.05). The expression of inflammatory factors IL-1ß, IL-6 and TNF-α were also detected. The results showed that compared with the Model group, the contents of IL-6 in EGB-L group were not significantly decreased (P > 0.05), while the contents of IL-1ß, IL-6 and TNF-α in other EGB groups were significantly decreased (P < 0.05), indicating that EGB could reduce the level of cell inflammation. Western blot assay detected the protein expression levels of GF, RTK, PI3K, AKT and p-AKT in cells. The results showed that compared with the Model group, the protein expression levels of GF, RTK, PI3K, AKT and P-AKT were significantly increased after EGB treatment (P < 0.05), and the protein expression level of the EGB-H group was higher than the EGB-L group. Ginkgo biloba extract can inhibit the expression of downstream related genes by activating PI3K/AKT signaling pathway, and at the same time alleviate the inflammatory response of cells, reduce the level of inflammation, and protect the cell damage caused by CCl4.

Inflammation-Responsive Cell Membrane-Camouflaged Nanoparticles against Liver Fibrosis via Regulating Endoplasmic Reticulum Stress and Oxidative Stress.

Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, and the production of fibers in the liver exceeds their degradation. Oxidative stress (OS) resulting from tissue injury and endoplasmic reticulum stress (ERS) triggered by the overproduction of proteins are pivotal factors in liver fibrosis. Melatonin demonstrates the capability to neutralize free radicals, shielding cells from oxidative harm. It is also a specific inhibitor of the ERS receptor transcription activating factor 6 (ATF6), indicating its great potential in ameliorating liver fibrosis. However, its limited water solubility and oral bioavailability of under 15% present hurdles in achieving therapeutic blood concentrations for treating liver fibrosis. The PLGA@Melatonin is constructed by loading melatonin with poly (lactic-co-glycolic acid) (PLGA). Platelet membranes (PM) and activated hepatic stellate cell membranes (HSCM) with high expression of the platelet-derived growth factor receptor (PDGFR) are extracted to successfully construct PM@PLGA@Melatonin and HSCM@PLGA@Melatonin, which are subsequently utilized to treat mice with liver fibrosis. The results illustrated the remarkable therapeutic effects of the two nanoparticles on liver fibrosis, along with their excellent targeting and biosafety properties.

Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study.

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.