Hot air treatment alleviates chilling injury of sweet potato tuberous roots by regulating osmoregulatory substances and inducing antioxidant defense system.

Sweet potato tuberous roots are susceptible to chilling injury (CI) when stored below 10 °C. In this study, we investigated the mitigating effects of hot air (HA) treatment on CI. Results showed that HA45°C-3h treatment delayed the CI and internal browning during cold storage. After HA45°C-3h treatment, the cells' structural integrity was maintained, malondialdehyde accumulation and ion leakage were inhibited. Additionally, the osmoregulatory substances, such as total soluble solids, proline were maintained, and soluble protein was enhanced. Higher activity of antioxidant enzymes including superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, and the antioxidant substances including ascorbic acid, glutathione, total phenols, and flavonoids were observed in sweet potato tuberous roots treated by HA45°C-3h than untreated group. Our study suggested that HA45°C-3h treatment could reduce CI and maintain a better quality of sweet potato tuberous roots following cold storage.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery.

BACKGROUND: Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM: To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS: This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein ß (S-100ß) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS: There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P > 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P < 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P < 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P < 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P < 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P < 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P < 0.05). Marked elevations in serum levels of VEGF, TGF-ß1, TNF-α, and S-100ß were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P < 0.05). CONCLUSION: TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-ß1, TNF-α, and S-100ß levels. This scheme also reduced POCD and had a high safety profile.

Study on the Occurrence Characteristics of the Remaining Oil in Sandstone Reservoirs with Different Permeability after Polymer Flooding.

After polymer flooding, the heterogeneity between different layers intensifies, forming intricate seepage channels and fluid diversions, which results in decreased circulation efficiency and lower recovery rates, leaving a significant amount of residual oil trapped within the reservoir. Understanding the characteristics of residual oil occurrence is crucial for enhancing oil recovery post-polymer flooding. This study focused on sandstone reservoirs with varying permeability in the Saertu block of the Daqing oilfield. Using cryosectioning and laser scanning confocal microscopy, the occurrence characteristics of the residual oil in these sandstone reservoirs post-polymer flooding were investigated. Additionally, micro-CT and scanning electron microscopy were employed to analyze the impact of the pore structure on the distribution characteristics of the residual oil. The results indicate that laser scanning confocal images reveal that post-polymer flooding, the residual oil in high- and low-permeability sandstone reservoirs predominantly exists in a bound state (average > 47%), mostly as particle-adsorbed oil. In contrast, the residual oil in medium-permeability reservoirs is primarily in a free state (average > 49%), mostly as intergranular-adsorbed oil. In high-permeability sandstone reservoirs, heavy oil components are mainly in a particle-adsorbed form; in medium-permeability sandstone reservoirs, residual oil predominantly consists of heavy components, with most light components occurring in a clustered form; in low-permeability sandstone reservoirs, clustered residual oil exists in a balanced coexistence of light and heavy components, while the heavy components primarily exist in a particle-adsorbed form. Post-polymer flooding, the large pore-throat structure in high-permeability sandstone reservoirs results in effective displacement and less free residual oil; medium-permeability sandstone reservoirs, with medium-large pores and throats, have preferential channels and fine particles blocking the throats, leading to some unswept pores and more free residual oil; low-permeability sandstone reservoirs, with small pores and throats, exhibit weak displacement forces and poor mobility, resulting in more bound residual oil. The distribution and content of clay particles and clay minerals, along with the complex microscopic pore structure, are the main factors causing the differences in the residual oil occurrence states in sandstones with varying permeability.

miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization.

BACKGROUND: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. METHODS: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. RESULTS: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. CONCLUSION: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM.

Breast tumor segmentation via deep correlation analysis of multi-sequence MRI.

Precise segmentation of breast tumors from MRI is crucial for breast cancer diagnosis, as it allows for detailed calculation of tumor characteristics such as shape, size, and edges. Current segmentation methodologies face significant challenges in accurately modeling the complex interrelationships inherent in multi-sequence MRI data. This paper presents a hybrid deep network framework with three interconnected modules, aimed at efficiently integrating and exploiting the spatial-temporal features among multiple MRI sequences for breast tumor segmentation. The first module involves an advanced multi-sequence encoder with a densely connected architecture, separating the encoding pathway into multiple streams for individual MRI sequences. To harness the intricate correlations between different sequence features, we propose a sequence-awareness and temporal-awareness method that adeptly fuses spatial-temporal features of MRI in the second multi-scale feature embedding module. Finally, the decoder module engages in the upsampling of feature maps, meticulously refining the resolution to achieve highly precise segmentation of breast tumors. In contrast to other popular methods, the proposed method learns the interrelationships inherent in multi-sequence MRI. We justify the proposed method through extensive experiments. It achieves notable improvements in segmentation performance, with Dice Similarity Coefficient (DSC), Intersection over Union (IoU), and Positive Predictive Value (PPV) scores of 80.57%, 74.08%, and 84.74% respectively.

Clinical use of quantitative computed tomography to evaluate the effect of less paraspinal muscle damage on bone mineral density changes after lumbar interbody fusion.

STUDY DESIGN: A retrospective cohort study. PURPOSE: This study aimed to assess the reliability of quantitative computed tomography (QCT) in measuring bone mineral density (BMD) of instrumented vertebrae and investigate the effect of less paraspinal muscle damage on BMD changes after lumbar interbody fusion. OVERVIEW OF LITERATURE: Patients always experience a decrease in vertebral BMD after lumbar interbody fusion. However, to the best of our knowledge, no study has analyzed the effect of paraspinal muscles on BMD changes. METHODS: This retrospective analysis included a total of 155 patients who underwent single-level lumbar fusion, with 81 patients in the traditional group and 74 patients in the Wiltse group (less paraspinal muscle damage). QCT was used to measure the volumetric BMD (vBMD), Hounsfield unit value, and cross-sectional area of the paraspinal muscles at the upper instrumented vertebrae (UIV), vertebrae one segment above the UIV (UIV+1), and the vertebrae one segment above the UIV+1 (UIV+2). Statistical analyses were performed. RESULTS: No significant differences in general data were observed between the two groups (p>0.05). Strong correlations were noted between the preoperative and 1-week postoperative vBMD of each segment (p<0.01), with no significant difference between the two time points in both groups (p>0.05). Vertebral BMD loss was significantly higher in UIV+1 and UIV+2 in the traditional group than in the Wiltse group (-13.6%±19.1% vs. -4.2%±16.5%, -10.8%±20.3% vs. -0.9%±37.0%; p<0.05). However, no statistically significant difference was observed in the percent vBMD changes in the UIV segment between the two groups (37.7%±70.1% vs. 36.1%±78.7%, p>0.05). CONCLUSIONS: QCT can reliably determine BMD in the instrumented spine after lumbar interbody fusion. With QCT, we found that reducing paraspinal muscle destruction through the Wiltse approach during surgery can help preserve the adjacent vertebral BMD; however, it does not help increase the BMD in the instrumented vertebrae.

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Vaccarin Ameliorates Doxorubicin-Induced Cardiotoxicity via Inhibition of p38 MAPK Mediated Mitochondrial Dysfunction.

Doxorubicin is a frequently used chemotherapeutic agent for treating various malignancies. However, it leads to severe cardiotoxic side effects, such as heart failure, and elevates the risk of sudden cardiac death among cancer patients. While oxidative stress has been identified as the primary cause of doxorubicin-induced cardiotoxicity, therapeutic antioxidant approaches have yielded unsatisfactory outcomes. The aim of this study is to explore the therapeutic potential of vaccarin, an active flavonoid glycoside extracted from traditional Chinese herbal agent Semen Vaccariae, in doxorubicin-induced cardiotoxicity. We observed that vaccarin significantly ameliorates doxorubicin-induced heart dysfunction in mouse model and suppresses oxidative stress mediated cell apoptosis via specifically inhibiting the activation of p38 MAPK pathway. In vitro, we observed that vaccarin alleviates doxorubicin-induced mitochondrial membrane depolarization and ROS generation in H9c2 cell, but the p38 MAPK agonist anisomycin reverses these effects. Our findings provide a promising natural antioxidant to protect against DOX-induced cardiotoxicity.

Case report: a case report of excision of giant lipoma in the posterior neck.

Lipomas, benign tumors originating from the anomalous proliferation of adipocytes, predominantly emerge in regions rich in adipose tissue. However, their presence in the head and neck areas remains rare, constituting approximately 13% of all diagnosed lipoma cases. This study presents a case involving a substantial subcutaneous lipoma located at the posterior neck, measuring about 20 cm × 19 cm × 10 cm. The patient presented with swelling and pain in the back of the neck. And the considerable dimensions of this lipoma significantly impacted the patient's quality of life and aesthetic appearance. Concurrently, the patient exhibited symptoms indicative of degenerative cervical spine disease and cervical disc herniation. After admission, a comprehensive examination, including ultrasound, CT scan, and MRI, was conducted. Given the clinical complexity, the decision for surgical intervention was deemed essential. The surgical strategy entailed a meticulous total excision of the tumor through an incision made in the posterior cross-neck, coupled with the strategic removal of excess skin. To facilitate wound healing, postoperative management included the use of negative pressure drainage. Pathological examination conclusively identified the mass as a lipoma. Postoperative follow-ups indicated successful recovery, as evidenced by the restoration of the neck's aesthetic contour and the complete resolution of the previously observed restrictions in sagittal neck movement.

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways.

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays.

Epithelial-mesenchymal transition (EMT) is critical for tumor invasion and many other cell-relevant processes. While much progress has been made about EMT, no report concerns the EMT of cells on topological biomaterial interfaces with significant nuclear deformation. Herein, we prepared a poly(lactide-co-glycolide) micropillar array with an appropriate dimension to enable significant deformation of cell nuclei and examined EMT of a human lung cancer epithelial cell (A549). We show that A549 cells undergo serious nuclear deformation on the micropillar array. The cells express more E-cadherin and less vimentin on the micropillar array than on the smooth surface. After transforming growth factor-ß1 (TGF-ß1) treatment, the expression of E-cadherin as an indicator of the epithelial phenotype is decreased and the expression of vimentin as an indicator of the mesenchymal phenotype is increased for the cells both on smooth surfaces and on micropillar arrays, indicating that EMT occurs even when the cell nuclei are deformed and the culture on the micropillar array more enhances the expression of vimentin. Expression of myosin phosphatase targeting subunit 1 is reduced in the cells on the micropillar array, possibly affecting the turnover of myosin light chain phosphorylation and actin assembly; this makes cells on the micropillar array prefer the epithelial-like phenotype and more sensitive to TGF-ß1. Overall, the micropillar array exhibits a promoting effect on the EMT.

Targeting macrophagic RasGRP1 with catechin hydrate ameliorates sepsis-induced multiorgan dysfunction.

BACKGROUND: The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new regulatory targets for macrophage homeostasis and devising effective treatment strategies remains a significant challenge in contemporary research. PURPOSE: This study aims to identify new regulatory targets for macrophage homeostasis and develop effective strategies for treating sepsis. STUDY DESIGN AND METHODS: Macrophage infiltration in septic patients and in lungs, kidneys, and brains of caecum ligation and puncture (CLP)-induced septic mice was observed using CIBERSORT and immunofluorescence (IF). Upon integrating the MSigDB database and GSE65682 dataset, differently expressed macrophage-associated genes (DEMAGs) were identified. Critical DEMAGs were confirmed through machine learning. The protein level of the critical DEMAG was detected in PBMCs of septic patients, RAW264.7 cells, and mice lungs, kidneys, and brains using ELISA, western blot, immunohistochemistry, and IF. siRNA was applied to investigate the effect of the critical DEMAG in RAW264.7 cells. A natural product library was screened to find a compound targeting the critical DEMAG protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis. The therapeutic efficacy of the compounds against sepsis was then evaluated through in vitro and in vivo experiments. RESULTS: Macrophage infiltration was inversely correlated with survival in septic patients. The critical differentially expressed molecule RasGRP1 was frequently observed in the PBMCs of septic patients, LPS-induced RAW264.7 cells, and the lungs, kidneys, and brains of septic mice. Silencing RasGRP1 alleviated proinflammatory response and oxidative stress in LPS-treated RAW264.7 cells. Catechin Hydrate (CH) was identified as an inhibitor of RasGRP1, capable of maintaining macrophage homeostasis and mitigating lung, kidney, and brain damage during sepsis. CONCLUSION: This study demonstrates that RasGRP1, a novel activator of macrophage proinflammatory responses, plays a crucial role in the excessive inflammation and oxidative stress associated with sepsis. CH shows potential for treating sepsis by inhibiting RasGRP1.

The mechanism of extracellular CypB promotes glioblastoma adaptation to glutamine deprivation microenvironment.

Glioblastoma, previously known as glioblastoma multiform (GBM), is a type of glioma with a high degree of malignancy and rapid growth rate. It is highly dependent on glutamine (Gln) metabolism during proliferation and lags in neoangiogenesis, leading to extensive Gln depletion in the core region of GBM. Gln-derived glutamate is used to synthesize the antioxidant Glutathione (GSH). We demonstrated that GSH levels are also reduced in Gln deficiency, leading to increased reactive oxygen species (ROS) levels. The ROS production induces endoplasmic reticulum (ER) stress, and the proteins in the ER are secreted into the extracellular medium. We collected GBM cell supernatants cultured with or without Gln medium; the core and peripheral regions of human GBM tumor tissues. Proteomic analysis was used to screen out the target-secreted protein CypB. We demonstrated that the extracellular CypB expression is associated with Gln deprivation. Then, we verified that GBM can promote the glycolytic pathway by activating HIF-1α to upregulate the expression of GLUT1 and LDHA expressions. Meanwhile, the DRP1 was activated, increasing mitochondrial fission, thus inhibiting mitochondrial function. To explore the specific mechanism of its regulation, we constructed a si-CD147 knockout model and added human recombinant CypB protein to verify that extracellular CypB influenced the expression of downstream p-AKT through its cell membrane receptor CD147 binding. Moreover, we confirmed that p-AKT could upregulate HIF-1α and DRP1. Finally, we observed that extracellular CypB can bind to the CD147 receptor, activate p-AKT, and upregulate HIF-1α and DRP1 in order to promote glycolysis while inhibiting mitochondrial function to adapt to the Gln-deprived microenvironment.

The characteristics of arterial risk factors and ankle-brachial index in patients with lower extremity chronic venous diseases: results from the BEST study.

BACKGROUND: The aim of our study was to explore the characteristics of the arterial risk factors and ankle-brachial index (ABI) in patients with lower extremity chronic venous disease (LECVD). METHODS: A total of 2642 subjects were employed in our study. The lifestyle and clinical data were collected. The history of vascular diseases contained coronary artery disease, stroke, hypertension, and diabetes. ABI low than 0.9 was considered as lower extremity artery disease (LEAD). A series of blood indicators were measured. RESULTS: Patients with ABI low than 0.9 belonged to the group of LEAD. Age, smoking, drinking, hypertension, diabetes mellitus, lipid-lowering drug, antidiabetic, total protein, total protein, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin and homocysteine were the common risk factors shared by LEAD and LECVD (P<0.05). The prevalence of LEAD in patients with LECVD was higher than those without LECVD (P<0.05). In Pearson correlation analysis, LECVD was related to LEAD (P<0.05). Before and after adjusted shared factors, as the performance of the logistic regression models, LEAD was an independent risk factor for the prevalence of LECVD (OR=2.937, 95% CI: [1.956, 4.411], P<0.001). CONCLUSIONS: Our study demonstrated that an ABI lower than 0.9 is an independent risk factor for LECVD.

Bisphenol A: Unveiling Its Role in Glioma Progression and Tumor Growth.

Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial-mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology.

Conductive and Enhanced Mechanical Strength of Mo2Ti2C3 MXene-Based Hydrogel Promotes Neurogenesis and Bone Regeneration in Bone Defect Repair.

Bone defects are common with increasing high-energy fractures, tumor bone invasion, and implantation revision surgery. Bone is an electroactive tissue that has electromechanical interaction with collogen, osteoblasts, and osteoclasts. Hydrogel provides morphological plasticity and extracellular matrix (ECM) 3D structures for cell survival, and is widely used as a bone engineering material. However, the hydrogels have poor mechanical intensity and lack of cell adhesion, slow gelation time, and limited conductivity. MXenes are novel nanomaterials with hydrophilic groups that sense cell electrophysiology and improve hydrogel electric conductivity. Herein, gelatin had multiple active groups (NH2, OH, and COOH) and an accelerated gelation time. Acrylamide has Schiff base bonds to cross-link with gelatin and absorb metal ions. Deacetylated chitosan improved cell adhesion and active groups to connect MXene and acrylamide. We constructed Mo2Ti2C3 MXene hydrogel with improved elastic modulus and viscosity, chemical cross-linking structure, electric conductivity, and good compatibility. Mo2Ti2C3 MXene hydrogel exhibits outstanding osteogenesis in vitro. Mo2Ti2C3 MXene hydrogel promotes osteogenesis via alkaline phosphatase (ALP) and alizarin red S (ARS) staining, improving osteogenic marker genes and protein expressions in vitro. Mo2Ti2C3 MXene hydrogel aids new bone formation in the in vivo calvarial bone defect model via micro-CT and histology. Mo2Ti2C3 MXene hydrogel facilitates neurogenesis factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression, and aids newly born neuron marker Tuj-1 and sensory neuron marker serotonin (5-HT) and osteogenesis pathway proteins, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), SMAD family member 4 (SMAD4), and bone morphogenetic protein-2 (BMP2) in the bone defect repair process. Mo2Ti2C3 MXene hydrogel promotes osteogenesis and neurogenesis, which extends its biomedical application in bone defect reconstruction.

A novel mitochondrial unfolded protein response-related risk signature to predict prognosis, immunotherapy and sorafenib sensitivity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cause of cancer-associated death worldwide. The mitochondrial unfolded protein response (UPRmt) not only maintains mitochondrial integrity but also regulates cancer progression and drug resistance. However, no study has used the UPRmt to construct a prognostic signature for HCC. This work aimed to establish a novel signature for predicting patient prognosis, immune cell infiltration, immunotherapy, and chemotherapy response based on UPRmt-related genes (MRGs). Transcriptional profiles and clinical information were obtained from the TCGA and ICGC databases. Cox regression and LASSO regression analyses were applied to select prognostic genes and develop a risk model. The TIMER algorithm was used to investigate immunocytic infiltration in the high- and low-risk subgroups. Here, two distinct clusters were identified with different prognoses, immune cell infiltration statuses, drug sensitivities, and response to immunotherapy. A risk score consisting of seven MRGs (HSPD1, LONP1, SSBP1, MRPS5, YME1L1, HDAC1 and HDAC2) was developed to accurately and independently predict the prognosis of HCC patients. Additionally, the expression of core MRGs was confirmed by immunohistochemistry (IHC) staining, single-cell RNA sequencing, and spatial transcriptome analyses. Notably, the expression of prognostic MRGs was significantly correlated with sorafenib sensitivity in HCC and markedly downregulated in sorafenib-treated HepG2 and Huh7 cells. Furthermore, the knockdown of LONP1 decreased the proliferation, invasion, and migration of HepG2 cells, suggesting that upregulated LONP1 expression contributed to the malignant behaviors of HCC cells. To our knowledge, this is the first study to investigate the consensus clustering algorithm, prognostic potential, immune microenvironment infiltration and drug sensitivity based on the expression of MRGs in HCC. In summary, the UPRmt-related classification and prognostic signature could assist in determining the prognosis and personalized therapy of HCC patients from the perspectives of predictive, preventative and personalized medicine.