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1.
Adv Mater ; : e2404330, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38723269

ABSTRACT

The pursuit of constructing humanoid robots to replicate the anatomical structures and capabilities of human beings has been a long-standing significant undertaking and especially garnered tremendous attention in recent years. However, despite the progress made over recent decades, humanoid robots have predominantly been confined to those rigid metallic structures, which however starkly contrast with the inherent flexibility observed in biological systems. To better innovate this area, the present article systematically explores the value and potential of liquid metals and their derivatives in facilitating a crucial transition towards soft humanoid robots. Through a comprehensive interpretation of bionics, we present an overview of liquid metals' multifaceted roles as essential components in constructing advanced humanoid robots - functioning as soft actuators, sensors, power sources, logical devices, circuit systems, and even transformable skeletal structures. We conceived that the integration of these components with flexible structures, facilitated by the unique properties of liquid metals, can create unexpected versatile functionalities and behaviors to better fulfill human needs. Finally, we envision a revolution in humanoid robots, transitioning from metallic frameworks to hybrid soft-rigid structures resembling that of biological tissues. This article is expected to provide fundamental guidance for the coming research, thereby advancing the area. This article is protected by copyright. All rights reserved.

2.
Ther Adv Respir Dis ; 18: 17534666241246637, 2024.
Article in English | MEDLINE | ID: mdl-38659187

ABSTRACT

BACKGROUND: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate. OBJECTIVE: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy. DESIGN: Prospective, randomized, and controlled study. METHODS: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively. RESULTS: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate. CONCLUSION: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy. REGISTRATION: NCT05298319 at ClinicalTrials.gov.


High-flow nasal cannula oxygenation during bronchoscopyMany patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that's causing trouble to find out what's wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there's a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren't sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levels­like slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.


Subject(s)
Bronchoscopy , Cannula , Oxygen Inhalation Therapy , Propofol , Humans , Bronchoscopy/adverse effects , Male , Prospective Studies , Female , Middle Aged , Oxygen Inhalation Therapy/methods , Aged , Propofol/administration & dosage , Propofol/adverse effects , Oxygen/administration & dosage , Hypnotics and Sedatives/administration & dosage , Conscious Sedation , Treatment Outcome , Adult
3.
Brain Sci ; 13(11)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-38002469

ABSTRACT

Ruptured dissecting aneurysms in posterior intracranial circulation present significant clinical challenges and often cause poor prognoses. Our cohort used overlapping stents as the primary treatment. We analyzed the medical records of 27 patients (18 men/nine women) with ruptured posterior circulation dissecting aneurysms (PCDAs). Their average age was 52 years. We selected 11 patients who used Enterprise (EP) and LVIS stents overlappingly and matched them 1:1 with counterparts who received either EP or LVIS stents individually. Overlapping stents was a feasible treatment in all 27 cases. We successfully followed up 26 patients for ≥6 months. Regrettably, one patient died from intracranial hypertension on Day 7 post-procedure. Immediate post-procedure angiographies indicated Raymond grade I, II, and III occlusions of PCDAs in 16 (59.3%), 7 (25.9%), and 4 (14.8%) cases, respectively. At an average follow-up duration of 16.2 months, 25 patients (96.2%) had modified Rankin Scale scores of 0-2, signifying positive outcomes. One patient (3.8%) had a score of 3-4. Recurrence rates for the EP and LVIS stent groups were higher than those of the overlapping stent group (45.45% vs. 9.09%, p = 0.15 and 27.27% vs. 9.09%, p = 0.59, respectively). No significant difference in recurrence rates existed between the overlapping and single-stent groups. Similarly, follow-up outcomes were consistent between the two groups. Overlapping stents could be an efficient method for treating ruptured PCDAs.

4.
Nat Mater ; 22(10): 1189-1195, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37550568

ABSTRACT

Glasses, unlike crystals, are intrinsically brittle due to the absence of microstructure-controlled toughening, creating fundamental constraints for their technological applications. Consequently, strategies for toughening glasses without compromising their other advantageous properties have been long sought after but elusive. Here we report exceptional toughening in oxide glasses via paracrystallization, using aluminosilicate glass as an example. By combining experiments and computational modelling, we demonstrate the uniform formation of crystal-like medium-range order clusters pervading the glass structure as a result of paracrystallization under high-pressure and high-temperature conditions. The paracrystalline oxide glasses display superior toughness, reaching up to 1.99 ± 0.06 MPa m1/2, surpassing any other reported bulk oxide glasses, to the best of our knowledge. We attribute this exceptional toughening to the excitation of multiple shear bands caused by a stress-induced inverse transformation from the paracrystalline to amorphous states, revealing plastic deformation characteristics. This discovery presents a potent strategy for designing highly damage-tolerant glass materials and emphasizes the substantial influence of atomic-level structural variation on the properties of oxide glasses.

5.
Environ Sci Pollut Res Int ; 30(36): 86352-86364, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37402917

ABSTRACT

Arsenic contamination in drinking water causes a global public health problem. Emerging evidence suggests that arsenic may act as an environmental risk factor for anxiety disorders. However, the exact mechanism underlying the adverse effects has not been fully elucidated. This study aimed to evaluate the anxiety-like behaviors of mice exposed to arsenic trioxide (As2O3), to observe the neuropathological changes, and to explore the link between the GABAergic system and behavioral manifestations. For this purpose, male C57BL/6 mice were exposed to various doses of As2O3 (0, 0.15, 1.5, and 15 mg/L) through drinking water for 12 weeks. Anxiety-like behaviors were assessed using the open field test (OFT), light/dark choice test, and elevated zero maze (EZM). Neuronal injuries in the cerebral cortex and hippocampus were assessed by light microscopy with H&E and Nissl staining. Ultrastructural alteration in the cerebral cortex was assessed by transmission electron microscope (TEM). The expression levels of GABAergic system-related molecules (i.e., glutamate decarboxylase, GABA transporter, and GABAB receptor subunits) in the prefrontal cortex (PFC) were determined by qRT-PCR and western blotting. Arsenic exposure showed a striking anxiogenic effect on mice, especially in the group exposed to 15 mg/L As2O3. Light microscopy showed neuron necrosis and reduced cell counts. TEM revealed marked ultrastructural changes, including the vacuolated mitochondria, disrupted Nissl bodies, an indentation in the nucleus membrane, and delamination of myelin sheath in the cortex. In addition, As2O3 influenced the GABAergic system in the PFC by decreasing the expression of the glutamate decarboxylase 1 (GAD1) and the GABAB2 receptor subunit, but not the GABAB1 receptor subunit. To sum up, sub-chronic exposure to As2O3 is associated with increased anxiety-like behaviors, which may be mediated by altered GABAergic signaling in the PFC. These findings shed light on the mechanisms responsible for the neurotoxic effects of arsenic and therefore more cautions should be taken.


Subject(s)
Arsenic , Drinking Water , Male , Mice , Animals , Arsenic/toxicity , Mice, Inbred C57BL , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Anxiety/chemically induced , gamma-Aminobutyric Acid/metabolism
6.
Plant Sci ; 334: 111774, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37331633

ABSTRACT

Leaf senescence is an integral step in the final stages of plant development, as nutrient remobilization from leaves to sink organs is accomplished during this process. NACs compose a large superfamily of plant-specific TFs involved in multiple plant development processes. Here, we identified a maize NAC TF, ZmNAC132, involved in leaf senescence and male fertility. ZmNAC132 expression was tightly linked to leaf senescence in an age-dependent manner. Knockout of ZmNAC132 led to delays in chlorophyll degradation and leaf senescence, whereas overexpression of ZmNAC132 had the opposite effects. ZmNAC132 could bind to and transactivate the promoter of ZmNYE1, a major chlorophyll catabolic gene, to accelerate chlorophyll degradation during leaf senescence. Moreover, ZmNAC132 affected male fertility through the upregulation of ZmEXPB1, an expansin-encoding gene associated with sexual reproduction and other related genes. Together, the results show that ZmNAC132 participates in the regulation of leaf senescence and male fertility through the targeting of different downstream genes in maize.


Subject(s)
Transcription Factors , Zea mays , Transcription Factors/genetics , Transcription Factors/metabolism , Zea mays/genetics , Zea mays/metabolism , Plant Senescence , Gene Expression Regulation, Plant , Chlorophyll/metabolism , Fertility/genetics , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism
7.
Aging (Albany NY) ; 15(11): 5144-5163, 2023 06 12.
Article in English | MEDLINE | ID: mdl-37310405

ABSTRACT

Increasing incidence of skin aging has highlighted the importance of identifying effective drugs with repurposed opportunities for skin aging. We aimed to identify pharmaco-active compounds with drug-repurposing opportunities for skin aging from Angelica acutiloba (Siebold & Zucc.) Kitag. (AAK). The proximity of network medicine framework (NMF) firstly identified 8 key AAK compounds with repurposed opportunities for skin aging, which may exert by regulating 29 differentially expressed genes (DGEs) of skin aging, including 13 up-regulated targets and 16 down-regulated targets. Connectivity MAP (cMAP) analysis revealed 8 key compounds were involved in regulating the process of cell proliferation and apoptosis, mitochondrial energy metabolism and oxidative stress of skin aging. Molecular docking analysis showed that 8 key compounds had a high docked ability with AR, BCHE, HPGD and PI3, which were identified as specific biomarker for the diagnosis of skin aging. Finally, the mechanisms of these key compounds were predicted to be involved in inhibiting autophagy pathway and activating Phospholipase D signaling pathway. In conclusion, this study firstly elucidated the drug-repurposing opportunities of AAK compounds for skin aging, providing a theoretical reference for identifying repurposing drugs from Chinese medicine and new insights for our future research.


Subject(s)
Angelica , Skin Aging , Angelica/metabolism , Drug Repositioning , Molecular Docking Simulation , Signal Transduction
8.
Front Immunol ; 14: 1123231, 2023.
Article in English | MEDLINE | ID: mdl-37153542

ABSTRACT

Background: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear. Methods: We investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram. Results: A total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients' characteristics and risk scores. Conclusion: CRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.


Subject(s)
Apoptosis , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Biomarkers , Carcinoma, Hepatocellular/genetics , Copper , Genes, Regulator , Liver Neoplasms/genetics , Tumor Microenvironment/genetics
10.
RSC Adv ; 13(16): 10914-10922, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37033443

ABSTRACT

Phloretin (Phl) is a natural flavonoid compound with wide range of biological activities but demonstrates poor water solubility and limited pharmacological effects. In this study, one cocrystal of phloretin-isoniazid (Phl-Inz) was prepared successfully using the solvent evaporation method. The physical properties of cocrystal were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG), powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR) and single crystal X-ray diffraction (SCXRD). The Hirshfeld surface analysis explained further interactions in the cocrystal. The solubility test showed that the solubility of the cocrystal was increased at pH 1.2 and pH 6.8 compared to that of the pure drug. The test in vitro simulated gastrointestinal digestion showed that the release of phloretin in the cocrystal was better than that in the pure phloretin. The results of the DPPH and ABTS scavenging activity showed that the in vitro antioxidant activity of the cocrystal was improved. The anticancer assay exhibited improved cytotoxicity in the Phl-Inz cocrystal as compared with the pure Phl.

11.
Front Immunol ; 14: 1114572, 2023.
Article in English | MEDLINE | ID: mdl-37063922

ABSTRACT

Background: Phosphoinositide 3-kinases (PI3Ks) are lipid enzymes that regulate a wide range of intracellular functions. In contrast to Class I and Class III PI3K, which have more detailed descriptions, Class II PI3K has only recently become the focus of functional research. PIK3C2A is a classical member of the PI3Ks class II. However, the role of PIK3C2A in cancer prognosis and progression remains unknown. Methods: The expression pattern and prognostic significance of PIK3C2A in human malignancies were investigated using multiple datasets and scRNA-seq data. The PIK3C2A expression in renal clear cell carcinoma (KIRC) was then validated utilizing Western blot. The functional role of PIK3C2A in KIRC was assessed using combined function loss experiments with in vitro experiments. Furthermore, the correlation of PIK3C2A expression with tumor immunity was investigated in KIRC. The TCGA database was employed to investigate PIK3C2A functional networks. Results: Significant decrease in PIK3C2A expression in KIRC, demonstrated that it potentially influences the prognosis of diverse tumors, particularly KIRC. In addition, PIK3C2A was significantly correlated with the T stage, M stage, pathologic stage, and histologic grade of KIRC. Nomogram models were constructed and used to predict patient survival based on the results of multivariate Cox regression analysis. PIK3C2A knockdown resulted in significantly increased KIRC cell proliferation. Of note, PIK3C2A expression demonstrated a significant correlation with the infiltrating levels of primary immune cells in KIRC. Conclusion: These findings support the hypothesis that PIK3C2A is a novel biomarker for tumor progression and indicates dynamic shifts in immune infiltration in KIRC. Furthermore, aberrant PIK3C2A expression can influence the biological activity of cancer cells.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Prognosis , Carcinoma, Renal Cell/genetics , Blotting, Western , Kidney Neoplasms/genetics , Kidney , Phosphatidylinositol 3-Kinases/genetics
12.
J Dent Sci ; 18(1): 135-144, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36643246

ABSTRACT

Background/purpose: Over-dependence on existing synthetic scaffolds and insufficient osteoinductive and vasculogenic growth factors have limited the development of bone regeneration. The study aimed to assess the feasibility of using marrow-derived mesenchymal stem cells (BMSCs) cell sheets co-expressing bone morphogenetic proteins 2 (BMP2) and vascular endothelial growth factor (VEGF) for repairing critical-sized calvarial defects. Materials and methods: BMSCs cell sheets were genetically engineered to express BMP2/VEGF alone or together. Alterations in osteogenic markers were examined by quantitative real-time PCR (qRT-PCR) and western blotting. A critical-sized calvarial bone defect model was used to investigate the osteogenesis effects of BMP2/VEGF cell sheets alone or in combination. The efficacy was assessed with micro-computed tomography (micro-CT) and histology. Results: In vitro, the expression of BMP2 and VEGF through lentiviral transduction was confirmed by qRT-PCR and western blotting against BMP2 and VEGF. Lentiviral delivery of BMP2 and VEGF resulted in the upregulation of osteogenic markers. In vivo, in a critical-sized calvarial bone defect model, 3D-reconstructed micro-CT images revealed that treatment of the calvarial defects with the BMP2/VEGF cell sheet resulted in significantly greater amounts of newly formed bone at 8 weeks after surgery than treatment with cell sheets with single gene transduction or vehicle controls. The results were confirmed by histological assessment by H&E staining and Masson staining. Conclusion: This study demonstrates that BMP2/VEGF co-expressing BMSCs sheets promote bone regeneration in critical-sized calvarial bone defects. The BMP2/VEGF cell sheets provide a functional bioactive scaffold for critical-size bone reconstruction.

13.
Head Neck ; 45(1): 103-114, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36226586

ABSTRACT

BACKGROUND: The current neck management for early oral squamous cell carcinoma (OSCC) has always been a controversial issue. A comprehensive model is necessary for predicting an individual's metastasis risk and appropriate patient counseling. METHODS: A nomogram for predicting 2-year LNM in patients with cT1-2N0 OSCC was developed and validated using clinicopathological data from 642 patients from 2000 to 2018 in four hospitals, China. RESULTS: Three variables (pathology grade, depth of invasion, tumor-infiltrating lymphocytes) were included in nomogram. C-indices were 0.826 (95% CI: 0.786-0.866) and 0.726 (95% CI: 0.653-0.780) in the internal and external validation. Kaplan-Meier method found the 2-year LNM rate of high-risk group (35.8%) was much higher than that of the low-risk group (14.5%). The nomogram model has an advantage over the 8th AJCC TNM stage in predicting the individual 2-year LNM probability for early OSCC. CONCLUSION: Patients with low-risk nomogram score may receive neck observation; those with high-risk score should receive END.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Lymphatic Metastasis , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/surgery , Nomograms , Risk Factors
14.
Oral Dis ; 29(2): 628-638, 2023 Mar.
Article in English | MEDLINE | ID: mdl-34455659

ABSTRACT

OBJECTIVE: The objectives of this study were to estimate the prognostic value of the tumour-stroma ratio (TSR) and tumour budding (TB) in oral tongue squamous cell carcinoma (OTSCC) and to establish a reliable model to predict the outcome of OTSCC patients. METHODS: A total of 103 patients surgically treated at our hospital were enrolled in this study. Chi-square tests, Kaplan-Meier analyses and Cox proportional hazards regression models were performed for statistical analysis. RESULTS: Fifty-six patients were categorized as stroma-rich, and 47 patients were categorized as stroma-poor. Only pathological grade was associated with the TSR (p = 0.017). Kaplan-Meier analysis showed that stroma-rich, high-intensity budding and high risk groups were associated with worse prognosis. The Cox regression model showed that the TSR was an independent risk factor for OTSCC patients prognosis, and the high risk group was also related to poor prognosis (p < 0.05). TB was significantly associated with poor prognosis but was not an independent risk factor. CONCLUSIONS: We found that patients in the stroma-rich group had a worse long-term prognosis. The TSR is an independent risk factor for OTSCC patients' outcome. In addition, a risk model that combined the TSR and TB proved to be valuable for predicting OTSCC patients' outcome.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Tongue Neoplasms , Humans , Prognosis , Squamous Cell Carcinoma of Head and Neck/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Tongue Neoplasms/surgery , Tongue Neoplasms/pathology , Retrospective Studies , Head and Neck Neoplasms/pathology , Neoplasm Staging
15.
Sensors (Basel) ; 22(12)2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35746373

ABSTRACT

To improve the ability of remote sensing technology in recognizing black-odorous water bodies in Hangzhou, this study analyzed the typical spectral characteristics of black-odorous water in Hangzhou based on measured spectral data and water quality parameters, including the transparency, dissolved oxygen, oxidation reduction potential, and ammonia nitrogen. The single-band threshold method, the normalized difference black-odorous water index (NDBWI) model, the black-odorous water index (BOI) model, and the color purity on a Commission Internationale de L'Eclairage (CIE) model were compared to analyze the spatial and temporal distribution characteristics of the black-odorous water in Hangzhou. The results showed that: (1) The remote sensing reflectance of black-odorous water was lower than that of ordinary water, the spectral curve was gentle, and the wave peak shifted toward the near-infrared direction in the wavelength range of 650-850 nm; (2) Among the aforementioned models, the normalized and improved normalized black-odorous water index methods had a higher accuracy, reaching 87.5%, and the threshold values for black-odorous water identification were 0.14 and 0.1, respectively; (3) From 2015 to 2018, the quantity of black-odorous water in the main urban area of Hangzhou showed a decreasing trend, and black-odorous water was mainly distributed in the Gongshu District and tended to appear in narrow rivers, densely populated areas, and factory construction sites. This study is expected to be of great practical value for the rapid tracking and monitoring of urban black-odorous water by using remote sensing technology for future work.


Subject(s)
Environmental Monitoring , Remote Sensing Technology , Odorants , Remote Sensing Technology/methods , Rivers , Water Quality
16.
Front Pharmacol ; 13: 868680, 2022.
Article in English | MEDLINE | ID: mdl-35677443

ABSTRACT

Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation-reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.

17.
Article in English | MEDLINE | ID: mdl-35463065

ABSTRACT

Objective: To explore a novel Immune-associated gene signature for overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). Methods: Expression profiles of genes and corresponding clinical materials of OSCC patients were obtained through the TCGA database. With a LASSO Cox regression model, a multigene signature was established to predict the OS of OSCC patients. Some molecular experiments including RNA interference, MTT, and Transwell assay were applied to verify the role of the risk gene FGF9 in OSCC. Results: 43 immune-related prognostic DEGs were identified in OSCC. A 17-gene signature was established to assign the patients to either a high-risk group (HG) or a low-risk group (LG). The HG presented a shorter OS than the LG (P < 0.05). According to multivariate Cox regression analyses, the risk score was considered an independent factor for OS prediction (training set: HR = 3.485, 95% CI = 2.037-5.961, P < 0.001; test set: HR = 4.531, 95% CI = 2.120-9.682, P < 0.001). ROC curve-based analysis revealed the signature's ability for prediction. According to functional analysis, the immune cell expression and immune function of the HG were significantly inhibited. After knocking down the high-risk gene FGF9, the migration, proliferation, and invasion capabilities of OSCC cells HSC6 were significantly suppressed (P < 0.05). Conclusion: A novel immune-associated gene signature was identified for predicting the prognosis of OSCC. These risk genes show great potential as targets for OSCC treatment.

18.
Free Radic Res ; 56(2): 209-221, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35468014

ABSTRACT

Cardiovascular complications are a well-documented limitation of cancer chemotherapy. Cisplatin-induced cardiotoxicity threatens the health and life of patients, and limits the application of cisplatin. Oxidative stress is the main mechanism underlying cisplatin-induced cardiac toxicity. Luteolin (Lut) has been reported to possess cardioprotective properties by activating nuclear factor-E2-related factor 2 (Nrf2) -mediated antioxidant response. However, the effect of Lut on cisplatin-induced cardiac damage remains unclear. In this study, we revealed that Lut exerted a protective effect against cisplatin-induced cardiac dysfunction and injury in vivo. In HL-1 cells, Lut was observed to dramatically reduce cisplatin-induced apoptosis and oxidative stress by modulating the Kelch-like epichlorohydrin-associated protein 1 (Keap1)/Nrf2 pathway. Altogether, these findings suggested that Lut showed promise in attenuating cisplatin-induced cardiac injury and might be considered a protective drug candidate for chemotherapy-associated cardiovascular complications.


Subject(s)
Heart Diseases , Kelch-Like ECH-Associated Protein 1 , Luteolin , NF-E2-Related Factor 2 , Oxidative Stress , Animals , Apoptosis , Cisplatin/adverse effects , Heart Diseases/chemically induced , Heart Diseases/drug therapy , Kelch-Like ECH-Associated Protein 1/metabolism , Luteolin/pharmacology , Mice , NF-E2-Related Factor 2/metabolism , Signal Transduction
19.
Phys Chem Chem Phys ; 24(17): 10561-10566, 2022 May 04.
Article in English | MEDLINE | ID: mdl-35445232

ABSTRACT

Pressure-induced sp2-to-sp3 transitions in graphite have been studied for decades by experiments and simulations. In general, pressures of 15-18 GPa are needed to initiate structural transitions in graphite at room temperature, and the high-pressure phases are usually unquenchable, as evidenced by in situ resistivity and optical transmittance measurements, X-ray diffraction (XRD), and inelastic X-ray scattering (IXS). However, our in situ Raman results show that the onset transition pressure can be as low as 9.7 GPa when using the methanol-ethanol-water (MEW) mixture as the pressure-transmitting medium (PTM), indicated by an additional GD Raman peak caused by the sp3 bonding between adjacent graphite layers. Moreover, using a combination of XRD, Raman, X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HRTEM), we show that a small amount of sp3 bonds associated with a unique feature of cross stacking are present in the recovered samples. Our findings will be useful to understand the intricate structural transitions in graphite-like materials under compression.

20.
FASEB J ; 36(3): e22179, 2022 03.
Article in English | MEDLINE | ID: mdl-35182399

ABSTRACT

The value of plasma fibronectin (pFN) in the diagnosis and prognosis of sepsis has not been fully established. Previous studies finding that pFN is significantly reduced in sepsis, however, whether reduced pFn affects the prognosis of sepsis has not been clarified. Here, we detected and analyzed pFN and other conventional inflammatory markers in advanced sepsis patients and performed correlation analysis with SOFA score. We also used Fn gene conditional knockout mice which were performed by cecum ligation and puncture (CLP) to investigate the effect of FN deficiency on sepsis prognosis. We found, compared with procalcitonin, c-reactive protein, and interleukin-6, pFN was more correlated with SOFA score in advanced sepsis patients (r -.720, p < .001). In animal experiments, Fn gene knockout mice showed significantly greater mortality after CLP compared with the control group because of inhibited phagocytosis and bacterial clearance ability of macrophages, with double cytokine storm. Furthermore, FN can regulate macrophages through the integrin α5ß1/Fak/Src signaling pathway. Overall, we found pFN can more accurately reflect the severity and prognosis of advanced sepsis. The absence of FN altered the cytokine storm and phagocytic function of macrophages, suggesting that FN could be a potential therapeutic target in sepsis.


Subject(s)
Cytokines/metabolism , Fibronectins/metabolism , Macrophages/metabolism , Sepsis/metabolism , Animals , Cells, Cultured , Fibronectins/blood , Fibronectins/genetics , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Humans , Integrin alpha5beta1/metabolism , Mice , Mice, Inbred C57BL , Sepsis/blood , src-Family Kinases/metabolism
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