Targeting MCH Neuroendocrine Circuit in Lateral Hypothalamus to Protect Against Skeletal Senescence.

Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism and skeletal senescence is unelucidated. Here, a central neuroendocrine circuit is identified that directly controls osteogenesis. Using virus based tracing, this study is identified that melanin concentrating hormone (MCH) expressing neurons in the lateral hypothalamus (LH) are connected to the bone. Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis. Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs) and induces senescence. Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling, and activating MCHR1 by MCH agonists attenuate skeletal senescence in mice. By elucidating a brain-bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation and protect against skeletal senescence.

Composite Mineralized Collagen/Polycaprolactone Scaffold-Loaded Microsphere System with Dual Osteogenesis and Antibacterial Functions.

Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration.

Failure in a population: Tauopathy disrupts homeostatic set-points in emergent dynamics despite stability in the constituent neurons.

Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal pairwise interactions and criticality, a homeostatically controlled, ideal computational regime. Deviations in criticality correlated with symptoms, predicted underlying anatomical pathology, occurred in a sleep-wake-dependent manner, and could be used to reliably classify an animal's genotype. This work illustrates how neurodegeneration may disrupt the computational capacity of neurobiological systems.

Preoperative CT and Radiomics Nomograms for Distinguishing Bronchiolar Adenoma and Early-Stage Lung Adenocarcinoma.

RATIONALE AND OBJECTIVES: Evaluating the capability of CT nomograms and CT-based radiomics nomograms to differentiate between Bronchiolar Adenoma (BA) and Early-stage Lung Adenocarcinoma (LUAD). MATERIALS AND METHODS: In this retrospective study; we analyzed data from 226 patients who were treated at our institution and pathologically confirmed to have either BA or Early-stage LUAD. Patients were randomly divided into a training cohort (n=158) and a testing cohort (n=68). All CT images were independently analyzed and measured by two radiologists using conventional computed tomography. Clinical predictive factors were identified using logistic regression. Multivariable logistic regression analysis was used to construct differential diagnostic models for BA and early-stage LUAD, including traditional CT and radiomics models. The performance of the models was determined based on the area under the receiver operating characteristic curve, discrimination ability, and decision curve analysis (DCA). RESULTS: Lesion shape, tumor-lung interface, and pleural retraction signs were identified as independent clinical predictors. The areas under the curve for the CT nomogram, radiomic features, and radiomics nomogram were 0.854, 0.769, and 0.901, respectively. Both the CT nomogram and the radiomics nomogram demonstrated good generalizability in distinguishing between the two entities. DCA indicated that the nomograms achieved a higher net benefit compared to the use of radiomic features alone. CONCLUSION: The two preoperative nomograms hold significant value in differentiating between patients with BA and those with Early-stage LUAD, and they contribute to informed clinical treatment decision-making.

Abnormal suppression of thermal transport by long-range interactions in networks.

Heat and electricity are two fundamental forms of energy widely utilized in our daily lives. Recently, in the study of complex networks, there is growing evidence that they behave significantly different at the micro-nanoscale. Here, we use a small-world network model to investigate the effects of reconnection probability p and decay exponent α on thermal and electrical transport within the network. Our results demonstrate that the electrical transport efficiency increases by nearly one order of magnitude, while the thermal transport efficiency falls off a cliff by three to four orders of magnitude, breaking the traditional rule that shortcuts enhance energy transport in small-world networks. Furthermore, we elucidate that phonon localization is a crucial factor in the weakening of thermal transport efficiency in small-world networks by characterizing the density of states, phonon participation ratio, and nearest-neighbor spacing distribution. These insights will pave new ways for designing thermoelectric materials with high electrical conductance and low thermal conductance.

Expression and immune infiltration studies of IL-33-ST2-NF-κB signaling pathway in prostate cancer.

BACKGROUND: To analyze the expression of interleukin-33 (IL-33), growth-stimulated expression gene 2 (ST2), nuclear factor-kappaB (NF-κB) and immune cell infiltration in prostate cancer, this study aims to provide an experimental basis for the clinical prevention and treatment of prostate cancer. METHODS: The expression of IL-33 in PCa tissues was analyzed using TCGA, TIMER and HPA databases. Using the UALCAN database, the systematic exploration of the relationship between IL-33 and various clinicopathological parameters was conducted. The correlation between IL-33 expression and immune cell infiltration was investigated using TIMER, CIBERSORT and GEPIA databases. To verify these analyses, 22 cases of normal prostate (NP), 76 cases of benign prostatic hyperplasia (BPH), and 100 cases of PCa were recruited. Immunohistochemical staining was performed to examine the expression of IL-33, ST2, NF-κB, and the infiltration of immune cells. Correlations between these factors were then determined. RESULTS: The expression of IL-33, ST2 and NF-κB was significantly lower in PCa tissues compared with NP (p < 0.05). IL-33 was not associated with age in PCa but showed associations with race, molecular characteristics, lymph node metastatic status, TP53 mutation and tumor grade. Furthermore, IL-33 was associated with immune cell infiltration. Positive correlations were observed between IL-33 and ST2 expressions, as well as between IL-33 and CD68+ macrophages in BPH and PCa. CONCLUSIONS: IL-33, ST2 and NF-κB are lowly expressed in PCa tissues, their expression decreases with the increasing malignancy of cancer. IL-33, ST2 and NF-κB are factors associated with PCa immune infiltration. IL-33 has an inhibitory effect on prostate cancer through the IL-33/ST2/NF-κB signalling pathway.

Unveiling the multifaceted potential of Pseudomonas khavaziana strain SR9: a promising biocontrol agent for wheat crown rot.

Fusarium pseudograminearum, a soil-borne fungus, is the cause of the devastating wheat disease known as wheat crown rot (WCR). The persistence of this pathogen in the soil and crop residues contributes to the increased occurrence and severity of WCR. Therefore, developing effective strategies to prevent and manage WCR is of great importance. In this study, we isolated a bacterial strain, designated as SR9, from the stem of wheat, that exhibited potent antagonistic effects against F. pseudograminearum, as well as the biocontrol efficacy of SR9 on WCR was quantified at 83.99% ± 0.11%. We identified SR9 as Pseudomonas khavaziana and demonstrated its potential as a plant probiotic. SR9 displayed broad-spectrum antagonism against other fungal pathogens, including Neurospora dictyophora, Botrytis californica, and Botryosphaeria dothidea. Whole-genome sequencing analysis revealed that SR9 harbored genes encoding various cell wall-degrading enzymes, cellulases, and lipases, along with antifungal metabolites, which are responsible for its antagonistic activity. Gene knockout and quantitative PCR analyses reveal that phenazine is the essential factor for antagonism. SR9 possessed genes related to auxin synthesis, flagellar biosynthesis, biofilm adhesion, and the chemotaxis system, which play pivotal roles in plant colonization and growth promotion; we also evaluated the effects of SR9 on plant growth in wheat and Arabidopsis. Our findings strongly suggest that SR9 holds great promise as a biocontrol agent for WCR in sustainable agriculture.IMPORTANCEThe escalating prevalence of wheat crown rot, primarily attributed to Fusarium pseudograminearum, necessitates the development of cost-effective and eco-friendly biocontrol strategies. While plant endophytes are recognized for their biocontrol potential, reports on effective strains targeting wheat crown rot are sparse. This study introduces the Pseudomonas khavaziana SR9 strain as an efficacious antagonist to the wheat crown rot pathogen Fusarium pseudograminearum. Demonstrating a significant reduction in wheat crown rot incidence and notable plant growth promotion, SR9 emerges as a key contributor to plant health and agricultural sustainability. Our study outlines a biological approach to tackle wheat crown rot, establishing a groundwork for innovative sustainable agricultural practices.

Global disease burden attributable to kidney dysfunction, 1990-2019: A health inequality and trend analysis based on the global burden of disease study.

OBJECTIVE: This study aimed to evaluate the burden of kidney dysfunction (KD), assess socioeconomic inequalities, and project trends in the future. METHODS: Data on deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were from Global Burden of Disease Study 2019. The Joinpoint regression model was utilized to analyze the temporal trend by the annual percentage change (APC). The slope index and concentration index were employed to evaluate cross-country disparities. The future trend was predicted using an age-period-cohort analysis. RESULTS: In the past three decades, the death numbers of KD increased from 1,571,720 to 3,161,552, DALYs from 42,090,331 to 76,486,945, YLDs from 5,003,267 to 11,282,484, and YLLs from 37,087,065 to 65,204,461, respectively. The age-standardized rate (ASR) of deaths, DALYs, and YLLs exhibited a declining trend. The ASR of YLDs increased until 2017, then decreased. The slope index and concentration index for DALYs increased from 248.1 to 351.9 and from 40.70 to 57.8. In the future, the ASR of deaths, DALYs, YLDs, and YLLs will remain stable, while their numbers will continue to rise, except for YLLs. CONCLUSIONS: The disease burden of KD remained serious. Tailored interventions should be developed based on national contexts.

Dipole Orientation Engineering in Crosslinking Polymer Blends for High-Temperature Energy Storage Applications.

Polymer dielectrics that perform efficiently under harsh electrification conditions are critical elements of advanced electronic and power systems. However, developing polymer dielectrics capable of reliably withstanding harsh temperatures and electric fields remains a fundamental challenge, requiring a delicate balance in dielectric constant (K), breakdown strength (Eb), and thermal parameters. Here, amide crosslinking networks into cyano polymers is introduced, forming asymmetric dipole pairs with differing dipole moments. This strategy weakens the original electrostatic interactions between dipoles, thereby reducing the dipole orientation barriers of cyano groups, achieving dipole activation while suppressing polarization losses. The resulting styrene-acrylonitrile/crosslinking styrene-maleic anhydride (SAN/CSMA) blends exhibit a K of 4.35 and an Eb of 670 MV m-1 simultaneously at 120 °C, and ultrahigh discharged energy densities (Ue) with 90% efficiency of 8.6 and 7.4 J cm-3 at 120 and 150 °C are achieved, respectively, more than ten times that of the original dielectric at the same conditions. The SAN/CSMA blends show excellent cyclic stability in harsh conditions. Combining the results with SAN/CSMA and ABS (acrylonitrile-butadiene-styrene copolymer)/CSMA blends, it is demonstrated that this novel strategy can meet the demands of high-performing dielectric polymers at elevated temperatures.

Facile engineering of interactive double network hydrogels for heart valve regeneration.

Regenerative heart valve prostheses are essential for treating valvular heart disease, which requested interactive materials that can adapt to the tissue remodeling process. Such materials typically involves intricate designs with multiple active components, limiting their translational potential. This study introduces a facile method to engineer interactive materials for heart valve regeneration using 1,1'-thiocarbonyldiimidazole (TCDI) chemistry. TCDI crosslinking forms cleavable thiourea and thiocarbamate linkages which could gradually release H2S during degradation, therefore regulates the immune microenvironment and accelerates tissue remodeling. By employing this approach, a double network hydrogel was formed on decellularized heart valves (DHVs), showcasing robust anti-calcification and anti-thrombosis properties post fatigue testing. Post-implantation, the DHVs could adaptively degrade during recellularization, releasing H2S to further support tissue regeneration. Therefore, the comprehensive endothelial cell coverage and notable extracellular matrix remodeling could be clearly observed. This accessible and integrated strategy effectively overcomes various limitations of bioprosthetic valves, showing promise as an attractive approach for immune modulation of biomaterials.

The research landscape of ferroptosis in neurodegenerative disease: a bibliometric analysis.

Background: Ferroptosis, a newly proposed concept of programmed cell death, has garnered significant attention in research across different diseases in the last decade. Despite thorough citation analyses in neuroscience, there is a scarcity of information on ferroptosis research specifically related to neurodegenerative diseases. Method: The Web of Science Core Collection database retrieved relevant articles and reviews. Data on publications, countries, institutions, authors, journals, citations, and keywords in the included studies were systematically analyzed using Microsoft Excel 2019 and CiteSpace 6.2.R7 software. Result: A comprehensive analysis and visualization of 563 research papers on ferroptosis in neurodegenerative diseases from 2014 to 2023 revealed emerging research hotspots and trends. The number of annual publications in this field of study has displayed a pattern of stabilization in the early years of the decade, followed by a notable increase in the later years and peaking in 2023 with 196 publications. Regarding publication volume and total citations, notable research contributions were observed from countries, institutions, and authors in North America, Western Europe, and China. Current research endeavors primarily focus on understanding the intervention mechanisms of neurodegenerative diseases through the ferroptosis pathway and exploring and identifying potential therapeutic targets. Conclusion: The study highlights key areas of interest and emerging trends in ferroptosis research on neurodegenerative diseases, offering valuable insights for further exploration and potential directions for diagnosing and treating such conditions.

LncRNA SOX21-AS1 Promotes Activation of BV2 Cells via Epigenetical Silencing of SOCS3 and Aggravates Parkinson's Disease.

BACKGROUND: LncRNAs perform a crucial impact on microglia's activation in Parkinson's disease (PD). Here, our purpose was to probe the function and involved mechanism of lncRNA SOX21-AS1 on microglial activation in PD. METHODS: Mice were treated with MPTP, and BV2 cells were treated with LPS/ATP to build PD animal and cell models. Genes' expression was measured using RT-qPCR, immunoblotting, and IHC stain. ELISA was applied for testing inflammatory factors' levels. Cell viability and apoptosis were tested using kits. RIP and RNA pull-down assay were utilized for monitoring the bond of SOX21-AS1 to EZH2, and ChIP was applied for affirming the bond between EZH2 and SOCS3's promoter. RESULTS: The expression of SOX21-AS1 and SOCS3 was abnormal in PD cell and animal models. Inhibition of SOX21-AS1 repressed LPS/ATP-induced activation in BV2 cells and nerve damage caused by activated BV2 cells, alleviating the pathological features of PD mice. Further studies found that SOX21-AS1 epigenetically inhibited SOCS3 by recruiting EZH2 to SOCS3 promoter. SOX21-AS1 overexpression partially offset the repressive impact of SOCS3 enhancement on BV2 cell activation and the protective effect on nerve cells. CONCLUSION: SOX21-AS1 enhances LPS/ATP-induced activation of BV2 cells and nerve damage caused by activated BV2 cells though recruiting EZH2 to SOCS3's promoter, thereby alleviating PD progression. Our research supplies new potential target for curing PD.

Incidence rate and risk factors for suicide in patients with breast cancer in the USA: A surveillance, epidemiology, and end results analysis (SEER).

PURPOSE: To investigate suicide mortality and the related factors among female breast cancer patients in the United States. METHODS: The SEER database was used to identify 716,422 patients diagnosed with breast cancer between 2010 and 2018 to calculate a standardized mortality rate (SMR). An analysis of risk factors for suicide death was conducted using the univariate and multivariate Cox proportional risk model. An estimation of suicide probability was performed through a nomogram model. RESULTS: Compared with the expected suicide cases (n = 155) in the general population of the United States at the corresponding period (a suicide death rate of 5.71 per 100,000 person-years), the suicide rate among 716,422 breast cancer patients was followed during 2010-2018 and showed a relatively higher rate of 9.02 per 100,000 person-years. The SMR was 1.58 (95%CI: 1.39-1.79). White and other races were nine and seven times more likely to complete suicide than Black race, respectively (aHR = 9.013, 95%CI: 3.335-24.36, P < 0.001; aHR = 7.129, 95%CI: 2.317-21.931, P = 0.001); unmarried or single patients were at higher risk than married patients (aHR = 1.693, 95%CI: 1.206-2.377, P = 0.002). Patients receiving radiotherapy (aHR = 0.731, 95%CI: 0.545-0.980, P = 0.036) were less likely to complete suicide than those who did not. CONCLUSION: Female breast cancer patients in the United States have a higher suicide rate than the general public, and the risk factors consist of non-black ethnicity, being single or unmarried, and not being treated with radiotherapy. As a result of this study, clinicians may be able to identify female breast cancer patients who are at high risk of suicide, thus providing appropriate psychological support at the early stage.

Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation.

The mechanical stress environment in the temporomandibular joint (TMJ) is constantly changing due to daily mandibular movements. Therefore, TMJ tissues, such as condylar cartilage, the synovial membrane and discs, are influenced by different magnitudes of mechanical stimulation. Moderate mechanical stimulation is beneficial for maintaining homeostasis, whereas abnormal mechanical stimulation leads to degeneration and ultimately contributes to the development of temporomandibular joint osteoarthritis (TMJOA), which involves changes in critical signaling molecules. Under abnormal mechanical stimulation, compensatory molecules may prevent degenerative changes while decompensatory molecules aggravate. In this review, we summarize the critical signaling molecules that are stimulated by moderate or abnormal mechanical loading in TMJ tissues, mainly in condylar cartilage. Furthermore, we classify abnormal mechanical stimulation-induced molecules into compensatory or decompensatory molecules. Our aim is to understand the pathophysiological mechanism of TMJ dysfunction more deeply in the ever-changing mechanical environment, and then provide new ideas for discovering effective diagnostic and therapeutic targets in TMJOA.

Predicting histological grade in pediatric glioma using multiparametric radiomics and conventional MRI features.

Prediction of glioma is crucial to provide a precise treatment plan to optimize the prognosis of children with glioma. However, studies on the grading of pediatric gliomas using radiomics are limited. Meanwhile, existing methods are mainly based on only radiomics features, ignoring intuitive information about tumor morphology on traditional imaging features. This study aims to utilize multiparametric magnetic resonance imaging (MRI) to identify high-grade and low-grade gliomas in children and establish a classification model based on radiomics features and clinical features. A total of 85 children with gliomas underwent tumor resection, and part of the tumor tissue was examined pathologically. Patients were categorized into high-grade and low-grade groups according to World Health Organization guidelines. Preoperative multiparametric MRI data, including contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted images, and apparent diffusion coefficient sequences, were obtained and labeled by two radiologists. The images were preprocessed, and radiomics features were extracted for each MRI sequence. Feature selection methods were used to select radiomics features, and statistically significant clinical features were identified using t-tests. The selected radiomics features and conventional MRI features were used to train the AutoGluon models. The improved model, based on radiomics features and conventional MRI features, achieved a balanced classification accuracy of 66.59%. The cross-validated areas under the receiver operating characteristic curve for the classifier of AutoGluon frame were 0.8071 on the test dataset. The results indicate that the performance of AutoGluon models can be improved by incorporating conventional MRI features, highlighting the importance of the experience of radiologists in accurately grading pediatric gliomas. This method can help predict the grade of pediatric glioma before pathological examination and assist in determining the appropriate treatment plan, including radiotherapy, chemotherapy, drugs, and gene surgery.

The Global Burden of Disease Attributable to Child and Maternal Malnutrition: 1990-2019.

OBJECTIVE: With this study, we aimed to estimate the disease burden attributable to child and maternal malnutrition (CMM) throughout the world between 1990 and 2019. METHODS: The number, age-standardized rate, population attributable fraction of deaths, disability-adjusted life-years, years of life lost, and years lived with disability associated with CMM were estimated using the Global Burden of Disease Study 2019 by age, sex, year, location, and sociodemographic index at the global level. The slope index of inequality and concentration index were employed to measure socioeconomic-related health inequalities across countries. RESULTS: The number (million) of global deaths, disability-adjusted life-years, and years of life lost related to CMM were 2.9, 294.8, and 250.5 in 2019, showing decreases of 60.8, 57.4, and 60.7% since 1990. However, the number of years lived with CMM-related disability increased from 36.0 in 1990 to 44.3 in 2019. Additionally, the age-standardized rates of these 4 indicators showed varying degrees of decline. The global burden of CMM-related conditions differed with age and sex. The burden was the heaviest in western sub-Saharan Africa, especially in Chad. In terms of diseases, neonatal disorders represented the most significant burden attributed to CMM. Additionally, the CMM burden was more concentrated in regions with low sociodemographic indices, shown by the slope index of inequality and concentration index. CONCLUSIONS: The findings of this study highlight the ongoing global burden of CMM, particularly in terms of years lived with disability. Population-wide actions targeting the effective treatment and relief of CMM may reduce the CMM-related disease burden.

Deep learning-based method for defect detection in electroluminescent images of polycrystalline silicon solar cells.

To achieve defect detection in bare polycrystalline silicon solar cells under electroluminescence (EL) conditions, we have proposed ASDD-Net, a deep learning algorithm evaluated offline on EL images. The model integrates strategies such as downsampling adjustment, feature fusion optimization, and detection head improvement. The ASDD-Net utilizes the Space to Depth (SPD) module to effectively extract edge and fine-grained information. The proposed Enhanced Cross-Stage Partial Network Fusion (EC2f) and Hybrid Attention CSP Net (HAC3) modules are placed at different positions to enhance feature extraction capability and improve feature fusion effects, thereby enhancing the model's ability to perceive defects of different sizes and shapes. Furthermore, placing the MobileViT_CA module before the second detection head balances global and local information perception, further enhancing the performance of the detection heads. The experimental results show that the ASDD-Net model achieves a mAP value of 88.81% on the publicly available PVEL-AD dataset, and the detection performance is better than the current SOTA model. The experimental results on the ELPV and NEU-DET datasets verify that the model has some generalization ability. Moreover, the proposed model achieves a processing frame rate of 69 frames per second, meeting the real-time defect detection requirements for solar cell surface defects.

PSMD9 promotes the malignant progression of hepatocellular carcinoma by interacting with c-Cbl to activate EGFR signaling and recycling.

BACKGROUND: Mounting evidences shows that the ubiquitin‒proteasome pathway plays a pivotal role in tumor progression. The expression of 26S proteasome non-ATPase regulatory subunit 9 (PSMD9) is correlated with recurrence and radiotherapy resistance in several tumor types. However, the role and mechanism of PSMD9 in hepatocellular carcinoma (HCC) progression remain largely unclear. METHODS: PSMD9 was identified as a prognosis-related biomarker for HCC based on analysis of clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the JP Project of the International Cancer Genome Consortium (ICGC-LIRI-JP). PSMD9 expression was analyzed in cancer tissues and adjacent noncancerous tissues via immunohistochemistry and Western blotting. Multiple in vivo and in vitro experimental techniques (such as CCK-8, colony formation, EdU, and Transwell assays; flow cytometry; Western blotting; quantitative RT-PCR; Coimmunoprecipitation assay and immunofluorescence confocal imaging) were used to assess the functions of PSMD9 in the pathogenesis of HCC. RESULTS: We found that the expression of PSMD9 was upregulated and associated with a poor prognosis in HCC patients. PSMD9 promoted HCC cell proliferation, migration, invasion and metastasis. Knockdown of PSMD9 significantly inhibited HCC cell proliferation by inducing G1/S cell cycle arrest and apoptosis. Mechanistically, we demonstrated that PSMD9 promoted HCC cell proliferation and metastasis via direct interaction with the E3 ubiquitin ligase c-Cbl, suppresses EGFR ubiquitination, influenced EGFR endosomal trafficking and degradation and subsequently activated ERK1/2 and Akt signaling. In addition, we showed that PSMD9 knockdown sensitized HCC cells to the tyrosine kinase inhibitor erlotinib in vitro and in vivo. CONCLUSIONS: Collectively, our results indicate that PSMD9 drives HCC progression and erlotinib resistance by suppressing c-Cbl mediated EGFR ubiquitination and therefore can be a potential therapeutic target for HCC.

Regulation of phonon localization on thermal transport in complex networks.

The regulation of thermal transport is a challenging topic in complex networks. At present, the hidden physical mechanism behind thermal transport is poorly understood. This paper addresses this issue by proposing a complex network model that focuses on the thermal transport regulation through the manipulation of the network's degree distribution and clustering coefficient. Our findings indicate that increasing the degree distribution regulation parameter σ leads to reduced phonon localization and improved thermal transport efficiency. Conversely, increasing the clustering coefficient c results in enhanced phonon localization and reduced thermal transport efficiency. Meanwhile, by calculating the pseudodispersion relation of the network, we find that the maximum (or the second smallest) eigenfrequency decreases with increasing σ (or c). Finally, we elucidate that phonon localization plays a pivotal role in the thermal transport of the network, as demonstrated through density of states and the participation ratio.