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There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27â14.3 ng/g) and OPFRs (6.30â310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.
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Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , China , Medición de Riesgo , Hidrocarburos Policíclicos Aromáticos/análisis , Humanos , Suelo/química , Interacciones Hidrofóbicas e Hidrofílicas , Retardadores de Llama/análisis , Hidrocarburos Clorados/análisisRESUMEN
BACKGROUND: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). METHODS: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. RESULTS: The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P < 0.05) was significantly lower in the OFA group than in the OBA group. Moreover, the severity of PONV was less severe in the OFA group than in the OBA group in PACU (post-anesthesia care unit) (0 [0, 0] vs. 0 [0, 3], P<0.05 ) and in the ward 24 h postoperatively ( 0 [0, 0] vs. 0 [0, 2.25], P<0.05). Additionally, the OFA group experienced a significantly shorter length of stay in the PACU compared to the OBA group (39.4 ± 6.76 min vs. 48.7 ± 7.90 min, P < 0.001). CONCLUSIONS: Compared to the OBA with propofol-remifentanil, the OFA with esketamine- dexmedetomidine proved to be feasible for shoulder arthroscopy, resulting in a reduced incidence of PONV and a shorter duration of stay in the PACU. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (No: ChiCTR2100047355), 12/06/2021.
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Analgésicos Opioides , Anestésicos Intravenosos , Artroscopía , Dexmedetomidina , Ketamina , Náusea y Vómito Posoperatorios , Propofol , Remifentanilo , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Dexmedetomidina/administración & dosificación , Masculino , Remifentanilo/administración & dosificación , Propofol/administración & dosificación , Femenino , Artroscopía/métodos , Persona de Mediana Edad , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Adulto , Náusea y Vómito Posoperatorios/prevención & control , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/etiología , Anestésicos Intravenosos/administración & dosificación , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Anestesia Intravenosa/métodos , Bloqueo del Plexo Braquial/métodosRESUMEN
Global microplastic pollution has garnered widespread attention from researchers both domestically and internationally. However, compared to other regions worldwide, little is known about microplastic pollution in the marine ecosystems of the Antarctic region. This study investigated the abundance and characteristics of microplastics (MPs) in the gills and intestines of 15 species of Antarctic fish and Antarctic krill (Euphausia superba). The results indicate that the abundance of MPs in Antarctic fish and E. superba ranged from 0.625 to 2.0 items/individual and 0.17 to 0.27 items/individual, with mean abundances of 0.93 ± 0.96 items/individual and 0.23 ± 0.44 items/individual, respectively. Antarctic fish ingested significantly more MPs than E. superba. There was no significant difference in the abundance of MPs between the gills and intestines of Antarctic fish. However, the quantity of pellet-shaped MPs in the gills was significantly higher than in the intestines. The depth of fish habitat influenced the quantity and size of MPs in their bodies, with benthic fish ingesting significantly fewer MPs than pelagic fish. Pelagic fish ingested significantly more MPs sized 1-5 mm than benthic fish. Additionally, analysis of the characteristics of MPs revealed that fiber-shaped MPs were predominant in shape, with sizes generally smaller than 0.25 mm and 0.25-0.5 mm. The predominant colors of MPs were transparent, red, and black, while the main materials were polypropylene (PP), polystyrene (PS), polyamide (PA), and polyvinyl chloride (PVC). Compared to organisms from other regions, the levels of MPs in Antarctic fish and E. superba were relatively low. This study contributes to a better understanding of the extent of MP pollution in Antarctic fish and E. superba, aiding human efforts to mitigate its impact on the environment.
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Polyoxometalates (POMs) with various coordination fashions are versatile ligands for constructing single-ion magnets (SIMs), but enforcing POM-SIMs with a specific geometry remains a synthetic challenge. Herein, we synthesized a POM-cocrystallized DyIII-SIM [Dy(OPPh3)4(H2O)3][PW12O40]·4EtOH (1Dy) and a POM-ligated DyIII-SIM [{Dy(OPPh3)3(H2O)3}{PW12O40}]·Ph3PO·H2O (2Dy) with pentagonal bipyramidal local coordination geometry. Magnetic measurements indicate that 1Dy displays field-induced single-molecule magnet (SMM) behavior and the relaxation is dominated by under-barrier processes. 2Dy exhibits spin-lattice relaxation at a broader temperature region with a reversal barrier over 300 K. Magneto-structural analysis reveals that the enhancement of SMM behavior originated from the equatorial replacement of Ph3PO by POM, which strengthens the axial anisotropy in 2Dy. Luminescent experiments indicate that the characteristic DyIII emissions of 1Dy are covered up by the strong π-π* emission of Ph3PO at low-temperature regions. As for 2Dy, partial DyIII emission persists thanks to the antenna effect between DyIII and POM.
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Background and objective: To investigate the use of high-resolution magnetic resonance imaging (HR-MRI) to identify the characteristics of culprit plaques in intracranial arteries, and to evaluate the predictive value of the characteristics of culprit plaques combined with the modified Essen score for the recurrence risk of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) patients. Methods: A retrospective analysis was conducted on 180 patients with HR-NICE at the First Affiliated Hospital of Xinxiang Medical University, including 128 patients with no recurrence (non-recurrence group) and 52 patients with recurrence (recurrence group). A total of 65 patients with HR-NICE were collected from the Sixth Affiliated Hospital of Shanghai Jiaotong University as a validation group, and their modified Essen scores, high-resolution magnetic resonance vessel wall images, and clinical data were collected. The culprit plaques were analyzed using VesselExplorer2 software. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for recurrence, and a nomogram was constructed using R software to evaluate the discrimination of the model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to evaluate the model performance. Calibration curves and Decision Curve Analysis (DCA) were used to evaluate the model efficacy. Results: Intra-plaque hemorrhage (OR = 3.592, 95% CI = 1.474-9.104, p = 0.006), homocysteine (OR = 1.098, 95% CI = 1.025-1.179, p = 0.007), and normalized wall index (OR = 1.114, 95% CI = 1.027-1.222, p = 0.015) were significantly higher in the recurrent stroke group than in the non-recurrent stroke group, and were independent risk factors for recurrent stroke. The performance of the nomogram model (AUC = 0.830, 95% CI: 0.769-0.891; PR-AUC = 0.628) was better than that of the modified Essen scoring model (AUC = 0.660, 95% CI: 0.583-0.738) and the independent risk factor combination model (AUC = 0.827, 95% CI: 0.765-0.889). The nomogram model still had good model performance in the validation group (AUC = 0.785, 95% CI: 0.671-0.899), with a well-fitting calibration curve and a DCA curve indicating good net benefit efficacy for patients. Conclusion: High-resolution vessel wall imaging combined with a modified Essen score can effectively assess the recurrence risk of HR-NICE patients, and the nomogram model can provide a reference for identifying high-risk populations with good clinical application prospects.
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In recent years, osteoarthritis of the knee, a common degenerative joint disease, often occurs in the elderly population. This disease has a significant impact on the quality of life of patients. For treating knee osteoarthritis, physical therapy is highly regarded as a very effective treatment method. This article delves deeply into commonly used physical therapy methods and analyzes their therapeutic effects, cost-effectiveness, and applicability, aiming to find treatments with broader applicability and better cost-effectiveness. The goal is to help a large number of patients effectively alleviate the discomfort caused by knee osteoarthritis, enhance the clinical therapeutic effects, and introduce home treatment methods to reduce financial burdens. The article also compares various physical therapy methods and finds that moxibustion and electrotherapy are more suitable for home use. Other treatment methods provide a reliable scientific basis for patient treatment.
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Osteoartritis de la Rodilla , Modalidades de Fisioterapia , Humanos , Osteoartritis de la Rodilla/terapia , Análisis Costo-Beneficio , Calidad de Vida , Moxibustión/métodos , Terapia por Estimulación Eléctrica/métodosRESUMEN
Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.
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Lesiones Encefálicas , Ferroptosis , Fosfatidilinositol 3-Quinasas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Hemorragia Subaracnoidea , Serina-Treonina Quinasas TOR , Animales , Masculino , Ratones , Ratas , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/etiología , Cromonas/farmacología , Modelos Animales de Enfermedad , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Peroxidación de Lípido/efectos de los fármacos , Morfolinas/farmacología , Neuronas/metabolismo , Neuronas/patología , Neuronas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Stepped spin crossover (SCO) complexes with three or more spin states have promising applications in high-order data storage, multi-switches and multi-sensors. Further synergy with other functionalities, such as luminescence and dielectric properties, will provide a good chance to develop novel multifunctional SCO materials. Here, a bent pillar ligand and luminescent pyrene guest are integrated into a three-dimensional (3D) Hofmann-type metal-organic framework (MOF) [Fe(dpoda){Au(CN)2}2]·pyrene (dpoda = 2,5-di-(pyridyl)-1,3,4-oxadiazole). The magnetic data show an incomplete and two-step SCO behavior with the sequence of 1 â 1/2 â 1/4. The rare bi-directional light-induced excited spin-state trapping (LIESST) effect and light-induced stepped thermal relaxation after LIESST are observed. The pyrene guests interact with dpoda ligands via offset face-to-face πâ¯π interactions to form intermolecular exciplex emissions. The competition between thermal quenching and stepped SCO properties results in a complicated and stepped exciplex fluorescence. Moreover, the stepped dielectric property with higher dielectric permittivity at lower temperature may be related to the more frustrated octahedral distortion parameters in the intermediate spin states. Hence, a 3D Hofmann-type MOF with bent pillar ligands and fluorescent guests illustrates an effective way for the development of multifunctional switching materials.
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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.
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Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4) â 4H2O (H2quinha=quinaldichydroxamic acid, HClsal=5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4) â 3H2O (HClsaldt=4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S=0 to high-spin S=1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57â cm-1 to 423â cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2â K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.
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Phase transitions in molecular solids involve synergistic changes in chemical and electronic structures, leading to diversification in physical and chemical properties. Despite the pivotal role of hydrogen bonds (H-bonds) in many phase-transition materials, it is rare and challenging to chemically regulate the dynamics and to elucidate the structure-property relationship. Here, four high-spin CoII compounds were isolated and systematically investigated by modifying the ligand terminal groups (X=S, Se) and substituents (Y=Cl, Br). S-Cl and Se-Br undergo a reversible structural phase transition near room temperature, triggering the rotation of 15-crown-5 guests and the swing between syn- and anti-conformation of NCX- ligands, accompanied by switchable magnetism. Conversely, S-Br and Se-Cl retain stability in ordered and disordered phases, respectively. H-bonds geometric analysis and ab initio calculations reveal that the electronegativity of X and Y affects the strength of NY-ap-Hâ â â X interactions. Entropy-driven structural phase transitions occur when the H-bond strength is appropriate; otherwise, the phase stays unchanged if it is too strong or weak. This work highlights a phase transition driven by H-bond strength complementarity - pairing strong acceptor with weak donor and vice versa, which offers a straightforward and effective approach for designing phase-transition molecular solids from a chemical perspective.
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Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.
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Antivirales , Artocarpus , Flavonoides , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Artocarpus/química , Antivirales/química , Antivirales/farmacología , Antivirales/aislamiento & purificación , Estructura Molecular , Herpesvirus Humano 1/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Virus Sincitiales Respiratorios/efectos de los fármacos , Hojas de la Planta/química , Relación Estructura-Actividad , Modelos MolecularesRESUMEN
A series of two-dimensional (2D) spin-crossover coordination polymers (SCO-CPs) [FeII(TPE)(NCX)2]·solv (1: X = BH3, solv = H2O·2CH3OH·DMF; 2: X = Se, solv = H2O·2CH3OH·0.5DMF; 3: X = S, solv = H2O·2CH3OH·0.5DMF) were synthesized by employing 1,1,2,2-tetra(pyridin-4-yl)ethene (TPE) and pseudohalide (NCX-) coligands. Magnetic measurements indicated that complexes 1-3 exhibited SCO behaviors with diminishing thermal hysteresis (7/4/0 K) upon decreasing the ligand-field strength. The critical temperatures (Tc) during spin transition were found to be inversely proportional to the coordination ability parameters (a™) with a linear correlation. The guest effect was also investigated in the solvent-exchanged phases 1-SE/2-SE/3-SE wherein the DMF molecules were replaced by methanol molecules. Compared with 1-3, 1-SE/2-SE/3-SE displayed more abrupt and complete single-step SCO behaviors but narrower thermal hysteretic loops. The results reported here demonstrate that the Tc values of these two families were dominated by the ligand-field strength of the NCX- anions (NCBH3 > NCSe > NCS), whereas the guest effect only modulated the kinetic factor of the SCO nature in this system.
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OBJECTIVE: Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ. METHODS: Sensitive and TMZ-resistant glioma cells were subjected to either a normoxic or hypoxic environment, and the growth patterns and enzymatic activity of glycolysis enzymes were subsequently measured. From these cells, exosomal PKM2 was isolated and the subsequent effect on TMZ resistance was examined and characterized, with a particular focus on understanding the relevant mechanisms. Furthermore, the intercellular communication between hypoxic resistant cells and tumor-associated macrophages (TAMs) via exosomal PKM2 was also assessed. RESULTS: The adverse impact of hypoxic microenvironments on TMZ resistance in glioma cells was identified and characterized. Among the three glycolysis enzymes that were examined, PKM2 was found to be a critical mediator in hypoxia-triggered TMZ resistance. Upregulation of PKM2 was found to exacerbate the hypoxia-mediated TMZ resistance. Exosomal PKM2 were identified and isolated from hypoxic TMZ-resistant glioma cells, and were found to be responsible for transmitting TMZ resistance to sensitive glioma cells. The exosomal PKM2 also contributed towards mitigating TMZ-induced apoptosis in sensitive glioma cells, while also causing intracellular ROS accumulation. Additionally, hypoxic resistant cells also released exosomal PKM2, which facilitated TMZ resistance in tumor-associated macrophages. CONCLUSION: In the hypoxic microenvironment, glioma cells become resistant to TMZ due to the delivery of PKM2 by exosomes. Targeted modulation of exosomal PKM2 may be a promising strategy for overcoming TMZ resistance in glioma.
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BACKGROUND: Lung cancer (LC) is the leading cause of malignancy-related deaths worldwide. The most common sites of metastasis include the nervous system, bone, liver, respiratory system, and adrenal glands. LC metastasis in the parotid gland is very rare, and its diagnosis presents a challenge. Here, we report a case of parotid metastasis in primary LC. CASE SUMMARY: The patient was a 74-year-old male who was discovered to have bilateral facial asymmetry inadvertently two years ago. The right earlobe was slightly swollen and without pain or numbness. Computed tomography (CT) examination showed bilateral lung space-occupying lesions. Pulmonary biopsy was performed and revealed adenocarcinoma (right-upper-lung nodule tissue). Positron emission tomography-CT examination showed: (1) Two hypermetabolic nodules in the right upper lobe of the lung, enlarged hypermetabolic lymph nodes in the right hilar and mediastinum, and malignant space-occupying lesion in the right upper lobe of the lung and possible metastasis to the right hilar and mediastinal lymph nodes; and (2) multiple hypermetabolic nodules in bilateral parotid glands. Parotid puncture biopsy was performed considering lung adenocarcinoma metastasis. Gene detection of lung biopsy specimens revealed an EGFR gene 21 exon L858R mutation. CONCLUSION: This case report highlights the challenging diagnosis of parotid metastasis in LC given its rare nature. Such lesions should be differentiated from primary tumors of the parotid gland. Simple radiological imaging is unreliable, and puncture biopsy is needed for final diagnosis of this condition.
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In this study, we successfully synthesize cationic/neutral/anionic inverse-Hofmann-type spin crossover (SCO) frameworks with 1,1,2,2-tetrakis(4-(pyridine-4-yl)phenyl)-ethene ligand by means of cyanometallic charge engineering strategy. The cationic and neutral frameworks exhibit single-step thermally induced spin transition behaviors, while the SCO capability of anionic framework can be aroused by partial desolvation. This strategy provides a new idea to construct ionic SCO frameworks and extends the toolkit for SCO materials.
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BACKGROUND: Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. METHODS: In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization. RESULTS: In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells. CONCLUSIONS: CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Ratones , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Células Endoteliales/metabolismo , Neoplasias de la Boca/patología , Receptores CCR7/genética , Análisis de Secuencia de ARN , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral/genéticaRESUMEN
Lysosomal acid lipase (LAL) is a key enzyme in the metabolic pathway of neutral lipids, whose deficiency (LAL-D) induces the differentiation of myeloid lineage cells into myeloid-derived suppressor cells (MDSCs), which promotes tumor growth and metastasis. This protocol provides detailed procedures for assessment of various LAL biochemical and physiological activities in Ly6G+ and CD11c+ MDSCs, including isolation of Ly6G+ and CD11c+ cells from the bone marrow and blood of mice, assays of LAL-D-induced cellular metabolic and mitochondrial activities, assessment of LAL-D-induced pathogenic immunosuppressive activity and tumor stimulatory activity. Pharmacological inhibition of the LAL activity was also described in both murine myeloid cells and human white blood cells.
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Células Supresoras de Origen Mieloide , Neoplasias , Ratones , Humanos , Animales , Esterol Esterasa/metabolismo , Células Supresoras de Origen Mieloide/metabolismo , Ratones Noqueados , Células Mieloides/metabolismo , Células Mieloides/patología , Neoplasias/metabolismoRESUMEN
BACKGROUND: Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7. The Cancer Genome Atlas data suggests CCR7 has elevated expression in oral cancer. Specifically, CCR7 expression in tumor microenvironment (TME) may regulate the ability of some immune cells to engage in anti-tumor immune responses. Since CD8+ T cells have become a key immunotherapeutic target, the role of CCR7 in antitumor immune response of naïve CD8+ T cells in TME has not been thoroughly investigated. METHODS: A CCR7 knockout mouse model was constructed, and the mechanism of ccr7 on the regulation of tumor microenvironment by naïve CD8+ T cells was verified under the guidance of single-cell RNA sequencing combined with in vivo animal experiments and in vitro cell experiments. RESULTS: CCR7 is knocked out with impaired tumor growth and altered CD8+ T cell profiles, revealing the importance of this protein in OSCC. CONCLUSIONS: Inhibition of CCR7 enhances CD8+ T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.
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Backgrounds: Observational studies have shown that cigarette smoking is inversely associated with risk of rosacea, However, it remains uncertain whether this association is causal or it is a result of reverse causation, and whether this association is affected by drinking behaviors. Methods: This study utilized the summary-level data from the largest genome-wide association study (GWAS) for smoking, alcohol consumption, and rosacea. The objective was to investigate the effect of genetically predicted exposures to smoking and alcohol consumption on the risk of developing rosacea. Two-sample bidirectional Mendelian randomization (MR) was applied, accompanied by sensitive analyses to validate the robustness of findings. Furthermore, multivariable MR was conducted to evaluate the direct impact of smoking on rosacea. Results: A decreased risk of rosacea was observed in individuals with genetically predicted lifetime smoking [odds ratio (OR)MR - IVW = 0.53; 95% confidence interval (CI), 0.318-0.897; P = 0.017], and number of cigarettes per day (ORMR - IVW = 0.55; 95% CI, 0.358-0.845; P = 0.006). However, no significant associations were found between initiation of regular smoking, smoking cessation, smoking initiation, alcohol consumption and rosacea. Reverse MR analysis did not show any associations between genetic liability toward rosacea and smoking or alcohol drinking. Importantly, the effect of lifetime smoking and the number of cigarettes per day on rosacea remained significant even after adjusting for alcohol consumption in multivariable MR analysis. Conclusion: Smoking was causally related to a lower risk of rosacea, while alcohol consumption does not appear to be associated with risk of rosacea.