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1.
Colloids Surf B Biointerfaces ; 238: 113923, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692173

RESUMO

The rapid advancement of photodynamic therapy (PDT) antibacterial materials has led to promising alternatives to antibiotics for treating bacterial infections. However, antibacterial drugs have poor light absorption and utilization rates, which limits their practical application. Constructing two-dimensional (2D) heterojunctions from materials with matching photophysical properties has emerged as a highly effective strategy for achieving high-efficiency photo-antibacterial performance. Here, we designed and prepared an atom co-sharing Bi/Bi4O5Br2 nanosheet heterojunction by a simple in situ reduction. This heterojunction material combines outstanding biocompatibility with excellent bactericidal efficiency, which exceeded 90 % against Escherichia coli (a Gram-negative bacterium) and Staphylococcus aureus (a Gram-positive bacterium) under visible light irradiation, around nine-fold higher than that with pure Bi4O5Br2 nanosheets. The results suggest that localized surface plasmon resonance (LSPR) of shared Bi atoms on the Bi4O5Br2 nanosheets promotes light utilization and the separation and transfer of photo-generated charges, thus producing more abundant reactive oxygen species (ROS), which can partake in the PDT antibacterial effect. Our study underscores the potential utility of LSPR-enhanced Bi-based nanosheet heterojunctions for safe and efficient PDT to combat bacterial infections.


Assuntos
Antibacterianos , Bismuto , Escherichia coli , Luz , Nanoestruturas , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Nanoestruturas/química , Bismuto/química , Bismuto/farmacologia , Catálise , Testes de Sensibilidade Microbiana , Processos Fotoquímicos , Espécies Reativas de Oxigênio/metabolismo , Ressonância de Plasmônio de Superfície , Fotoquimioterapia , Tamanho da Partícula
3.
Health Qual Life Outcomes ; 22(1): 34, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637793

RESUMO

PURPOSE: This study aimed to assess the health-related quality of life (HRQoL) of the Chinese population by using the Chinese medicine quality of life-11 dimensions (CQ-11D) questionnaire and to identify factors associated with HRQoL. METHODS: The data was derived from a survey conducted by the Institute of Pharmacoeconomics Evaluation at Beijing University of Chinese Medicine on the quality of life of the Chinese population. The sex and age of respondents were considered through quota sampling. Demographic, socioeconomic, and health indicators were collected using the structured questionnaire. We performed bivariate analyses first to examine the associations between the above factors and the HRQoL of respondents measured by the CQ-11D. Multivariate linear regression and ordinal logistic regression models were established to analyze the factors (demographic, socioeconomic, and health indicators) differences in HRQoL, as well as the risk of each group reporting problems across the 11 dimensions of CQ-11D. RESULTS: From February 2021 to November 2022, a total of 7,604 respondents were involved and 7,498 respondents were included. The sample approximated the general adult Chinese population in terms of age, sex, and district of residence, and each geographic distribution ranged from 9.71 to 25.54%. Of the respondents, 45.84% were male, and 89.82% were Han ethnicity. The mean utility score ranged from 0.796 to 0.921 as age increased. According to the respondents, most health problems were identified in the PL (fatigue) (70.16%) and SM (quality of sleep) (63.63%) dimensions. The CQ-11D index scores varied with the demographic and socioeconomic characteristics of respondents, except for ethnicity (p > 0.05) and income (p > 0.05). The multivariate analysis revealed significant negative associations between health utility scores and various factors. These factors include sex (female), age over 65, belonging to ethnic minorities, rural household registration, being widowed or divorced, having a primary school education or below, being a student or unemployed, having a low income of 0-1,300, engaging in smoking or drinking, limited participation in physical activities, experiencing changes in self-perceived health status compared to the previous year, and having chronic diseases. The odds of respondents reporting problems in 11 dimensions varied among different socio-demographic groups. CONCLUSIONS: This study reports the first Chinese population norms for the CQ-11D derived using a representative sample of the Chinese general population. Self-reported health status measured by the CQ-11D varies among different socio-economic groups. In addition to participation a physical activity and the presence of chronic disease, smoking and drinking also significantly influence HRQoL.


Assuntos
Nível de Saúde , Qualidade de Vida , Adulto , Humanos , Masculino , Feminino , Fatores Socioeconômicos , Inquéritos e Questionários , Habitação , China/epidemiologia
4.
Z Gastroenterol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657616

RESUMO

RATIONALE: The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to health complications beyond respiratory symptoms, revealing multi-organ involvement, including potential gastrointestinal implications. PATIENT CONCERNS: We present a case of a 40-year-old female without any history of achalasia who developed symptoms of the condition following a confirmed SARS-CoV-2 infection. Unusually, multiple esophageal ulcers were identified, which are not typically associated with achalasia. DIAGNOSIS: Achalasia and esophageal ulcers were confirmed through a series of examinations, including barium swallow, CT scan, and upper endoscopy. Furthermore, immunohistochemical staining of esophageal biopsy specimens revealed the presence of the SARS-CoV-2 spike protein, suggesting direct viral involvement. INTERVENTIONS: The patient was treated with calcium channel blockers and proton pump inhibitors and later underwent a peroral endoscopic myotomy (POEM) procedure following the resolution of her COVID-19 infection. OUTCOME: After the POEM procedure, the patient made a good recovery. LESSONS: This case underscores the potential for SARS-CoV-2 to trigger gastrointestinal complications and emphasizes the need for ongoing patient management and further research into the long-term implications of COVID-19. Despite the single-case nature of this report, it contributes to the expanding understanding of the diverse and multi-systemic impact of COVID-19.

5.
Langmuir ; 40(19): 10250-10260, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38688029

RESUMO

Corrosion is an unavoidable issue that steel encounters during service; however, the generic methods employed for corrosion prevention often need high cost or preparation conditions. In this study, a facile chemical replacement deposition method was proposed to realize an anticorrosion superhydrophobic coating on a X80 steel surface. The growth mechanism of the rough structure and its impact on the wettability of the superhydrophobic coating were analyzed. The superhydrophobic coating, deposited for 50 s and modified for 30 min, achieved optimal electrochemical properties and a maximum water contact angle. The immersion test, in the saturated CO2 oilfield produced water, demonstrated the better corrosion resistance of superhydrophobic coating than X80 steel. Correspondingly, a kinetic corrosion model was established to analyze the anticorrosion mechanism. In summary, this method significantly improves the corrosion resistance of X80 steel and is attractive for other industrial fields.

6.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38492559

RESUMO

OBJECTIVES: Severe pulmonary complications such as postoperative respiratory failure can occur after minimally invasive oesophagectomy. However, the risk factors have not been well identified. The goal of this study was to develop a predictive model for the occurrence of postoperative respiratory failure with a large sample. METHODS: We collected data from patients with oesophageal cancer who had a minimally invasive oesophagectomy at Shanghai Chest Hospital from 2019 to 2022. Univariable and backward stepwise logistic regression analysis of 19 pre- and intra-operative factors was used before model fitting, and its performance was evaluated with the receiver operating characteristic curve. Internal validation was assessed with a calibration plot, decision curve analysis and area under the curve with 95% confidence intervals, obtained from 1000 resamples set by the bootstrap method. RESULTS: This study enrolled 2,386 patients, 57 (2.4%) of whom developed postoperative respiratory failure. Backward stepwise logistic regression analysis revealed that age, body mass index, cardiovascular disease, diabetes, diffusion capacity of the lungs for carbon monoxide, tumour location and duration of chest surgery ≥101.5 min were predictive factors. A predictive model was constructed and showed acceptable performance (area under the curve: 0.755). The internal validation with the bootstrap method proves the good agreement for prediction and reality. CONCLUSIONS: Obesity, severe diffusion dysfunction and upper segment oesophageal cancer were strong predictive factors. The established predictive model has acceptable predictive validity for postoperative respiratory failure after minimally invasive oesophagectomy, which may improve the identification of high-risk patients and enable health-care professionals to perform risk assessment for postoperative respiratory failure at the initial consultation.


Assuntos
Neoplasias Esofágicas , Insuficiência Respiratória , Humanos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , China/epidemiologia , Neoplasias Esofágicas/complicações , Fatores de Risco , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
7.
Discov Oncol ; 15(1): 71, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466483

RESUMO

BACKGROUND: Programmed cell death (PCD) functions critically in cancers and PCD-related genes are associated with tumor microenvironment (TME), prognosis and therapeutic responses of cancer patients. This study stratified hepatocellular carcinoma (HCC) patients and develop a prognostic model for predicting prognosis and therapeutic responses. METHODS: Consensus clustering analysis was performed to subtype HCC patients in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) among the subtypes were filtered and subjected to the least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox regression analysis to filter prognostic genes. A PCD-related prognostic gene signature in TCGA was constructed and validated in ICGC-LIRI-JP and GSE14520 datasets. TME was analyzed using CIBERSORT, MCP-counter, TIMER and EPIC algorithms. Drug sensitivity was predicted by oncoPredict package. Spearman analysis was used to detect correlation. RESULTS: Four molecular subtypes were categorized based on PCD-related genes. Subtype C1 showed the poorest prognosis, the most infiltration of Fibroblasts, dentritic cell (DC) and cancer-associated fibroblasts (CAFs), and the highest TIDE score. C4 had a better prognosis survival outcome, and lowest immune cell infiltration. The survival outcomes of C2 and C3 were intermediate. Next, a total of 69 co-DEGs were screened among the four subtypes and subsequently we identified five prognostic genes (MCM2, SPP1, S100A9, MSC and EPO) for developing the prognostic model. High-risk patients not only had unfavorable prognosis, higher clinical stage and grade, and more inflammatory pathway enrichment, but also possessed higher possibility of immune escape and were more sensitive to Cisplatin and 5. Fluorouracil. The robustness of the prognostic model was validated in external datasets. CONCLUSION: This study provides new insights into clinical subtyping and the PCD-related prognostic signature may serve as a useful tool to predict prognosis and guide treatments for patients with HCC.

8.
Bioorg Chem ; 146: 107305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537335

RESUMO

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.


Assuntos
Corantes Fluorescentes , Sulfitos , Humanos , Células HeLa , Dióxido de Enxofre , Inflamação/induzido quimicamente , Inflamação/diagnóstico por imagem
9.
Chemosphere ; 355: 141727, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499076

RESUMO

Growing focus has been drawn to the continuous detection of high estrogens levels in the soil environment. Additionally, microplastics (MPs) are also of growing concern worldwide, which may affect the environmental behavior of estrogens. However, little is known about effects of MPs occurrence on estrogens degradation in soil. In this study, polyethylene microplastics (PE-MPs) were chosen to examine the influence on six common estrogens (estrone (E1), 17α-estradiol (17α-E2), 17ß-estradiol (17ß-E2), estriol (E3), diethylstilbestrol (DES), and 17α-ethinylestradiol (17α-EE2)) degradation. The results indicated that PE-MPs had little effect on the degradation of E3 and DES, and slightly affected the degradation of 17α-E2, however, significantly inhibited the degradation of E1, 17α-EE2, and 17ß-E2. It was explained that (i) obvious oxidation reaction occurred on the surface of PE-MPs, indicating that PE-MPs might compete with estrogens for oxidation sites, such as redox and biological oxidation; (ii) PE-MPs significantly changed the bacterial community in soil, resulting in a decline in the abundance of some bacterial communities that biodegraded estrogens. Moreover, the rough surface of PE-MPs facilitated the estrogen-degrading bacterial species (especially for E1, E2, and EE2) to adhere, which decreased their reaction to estrogens. These findings are expected to deepen the understanding of the environmental behavior of typical estrogens in the coexisting system of MPs.


Assuntos
Microplásticos , Plásticos , Polietileno , Solo , Estradiol/metabolismo , Estrogênios , Estrona/metabolismo , Etinilestradiol/metabolismo
10.
Poult Sci ; 103(5): 103622, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513550

RESUMO

Ammonia (NH3) is a toxic gas that in intensive poultry houses, damages the poultry health and induces various diseases. This study investigated the effects of NH3 exposure (0, 15, 30, and 45 ppm) on growth performance, serum biochemical indexes, antioxidative indicators, tracheal and lung impairments in Pekin ducks. A total of 288 one-day-old Pekin male ducks were randomly allocated to 4 groups with 6 replicates and slaughtered after the 21-d test period. Our results showed that 45 ppm NH3 significantly reduced the average daily feed intake (ADFI) of Pekin ducks. Ammonia exposure significantly reduced liver, lung, kidney, and heart indexes, and lowered the relative weight of the ileum. With the increasing of in-house NH3, serum NH3 and uric acid (UA) concentrations of ducks were significantly increased, as well as liver malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX-Px) contents. High NH3 also induced trachea and lung injury, thereby increasing levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) in the lung, and decreasing the mRNA expressions of zonula occludens 1 (ZO-1) and claudin 3 (CLDN3) in the lung. In conclusion, in-house NH3 decrease the growth performance in ducks, induce trachea and lung injuries and meanwhile increase the compensatory antioxidant activity for host protection.


Assuntos
Amônia , Patos , Estresse Oxidativo , Doenças das Aves Domésticas , Animais , Patos/fisiologia , Patos/crescimento & desenvolvimento , Amônia/toxicidade , Amônia/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Doenças das Aves Domésticas/induzido quimicamente , Doenças das Aves Domésticas/metabolismo , Distribuição Aleatória , Abrigo para Animais , Relação Dose-Resposta a Droga
11.
Opt Express ; 32(4): 5149-5160, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439248

RESUMO

Putrescine and cadaverine are significant volatile indicators used to assess the degree of food spoilage. Herein, we propose a micro-nano multi cavity structure for surface-enhanced Raman spectroscopy (SERS) to analyze the volatile gas putrescine and cadaverine in decomposing food. The MoS2 nano-flowers are inserted into a PVDF micro-cavity through in-situ growth, followed by vacuum evaporation technology of Ag nanoparticles to form an Ag/MoS2 nano-flower cavity/PVDF micron-bowl cavity (FIB) substrate. The micro-nano multi cavity structure can improve the capture capacity of both light and gas, thereby exhibiting high sensitivity (EF = 7.71 × 107) and excellent capability for gas detection of 2-naphthalenethiol. The SERS detections of the putrescine and cadaverine are achieved in the spoiled pork samples with the FIB substrate. Therefore, this substrate can provide an efficient, accurate, and feasible method for the specific and quantitative detection in the food safety field.

12.
Mol Genet Genomic Med ; 12(3): e2405, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444283

RESUMO

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.


Assuntos
Disostose Mandibulofacial , Infecções Respiratórias , Feminino , Humanos , China , Perda Auditiva Condutiva , Disostose Mandibulofacial/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Estudos Retrospectivos
13.
Biomater Sci ; 12(6): 1449-1453, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38390765

RESUMO

The aggregation of amyloid-ß (Aß) is one of the important pathological markers of Alzheimer's disease. Ruthenium(II) complexes have good stability, low cytotoxicity, a high fluorescence quantum yield, and a good Stokes shift as fluorescent probes. Based on this, we constructed a fluorescent probe for in vivo real-time imaging and inhibition of Aß-fibril formation using a complex of Ru polypyridine with organic fluorophores (N,N-dimethylaniline) and hydrophobic peptides (KLVFF). DLS and TEM studies have shown that Ru-YH has an inhibitory effect on the fibrotic aggregation of Aß. Both in vivo and in vitro studies have shown that Ru-WJ and Ru-YH can quickly cross the blood-brain barrier and successfully detect Aß in early (2.5-month old) transgenic mouse models. In summary, we have explored the potential of Ru complex based biological probes for early diagnosis and inhibition of AD.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Barreira Hematoencefálica/patologia
14.
BMC Oral Health ; 24(1): 172, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308269

RESUMO

BACKGROUND: The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. METHODS: Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin-eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. RESULTS: The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40-3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53-4.61 mm. CONCLUSIONS: CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sensibilidade e Especificidade , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética , Neoplasias de Cabeça e Pescoço/patologia
15.
J Fluoresc ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329605

RESUMO

In this study, a novel dinuclear lanthanide complex, denoted as [Ho2(L)2(acac)2(CH3OH)2]·CH3OH (1) (where H2L is 2-[((4-methyl)-2-(carboxyl)-imino)]methyl]-8-hydroxyquinoline, and Hacac is acetylacetonate), was successfully synthesized and characterized using single-crystal and elemental analysis, with the auxiliary ligand ß-diketonate and the 8-hydroxyquinoline Schiff base derivative serving as the foundation. Through ligand-to-metal charge transfer, Compound 1 demonstrated remarkable green fluorescence properties, showcasing potential applications in green fluorescence materials and fluorescence sensing. Additionally, Hyaluronic Acid (HA)/Carboxymethyl Chitosan (CMCS) hydrogels were synthesized through a chemical method. Utilizing captopril as a drug model, a novel metal gel granule of captopril was developed and assessed for its inhibitory activity against glioma cells. Molecular docking simulations revealed that only the methanol group in the Ho complex could contribute a polar atom for the formation of binding interactions.

16.
FASEB J ; 38(4): e23477, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38334424

RESUMO

Liver transplantation (LT) is the only effective method to treat end-stage liver disease. Hepatic ischemia-reperfusion injury (IRI) continues to limit the prognosis of patients receiving LT. Histone deacetylase 6 (HDAC6) is a unique HDAC member involved in inflammation and apoptosis. However, its role and mechanism in hepatic IRI have not yet been reported. We examined HDAC6 levels in liver tissue from LT patients, mice challenged with liver IRI, and hepatocytes subjected to hypoxia/reoxygenation (H/R). In addition, HDAC6 global-knockout (HDAC6-KO) mice, adeno-associated virus-mediated liver-specific HDAC6 overexpressing (HDAC6-LTG) mice, and their corresponding controls were used to construct hepatic IRI models. Hepatic histology, inflammatory responses, and apoptosis were detected to assess liver injury. The molecular mechanisms of HDAC6 in hepatic IRI were explored in vivo and in vitro. Moreover, the HDAC6-selective inhibitor tubastatin A was used to detect the therapeutic effect of HDAC6 on liver IRI. Together, our results showed that HDAC6 expression was significantly upregulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Compared with control mice, HDAC6 deficiency mitigated liver IRI by inhibiting inflammatory responses and apoptosis, whereas HDAC6-LTG mice displayed the opposite phenotype. Further molecular experiments show that HDAC6 bound to and deacetylated AKT and HDAC6 deficiency improved liver IRI by activating PI3K/AKT/mTOR signaling. In conclusion, HDAC6 is a key mediator of hepatic IRI that functions to promote inflammation and apoptosis via PI3K/AKT/mTOR signaling. Targeting hepatic HDAC6 inhibition may be a promising approach to attenuate liver IRI.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Apoptose , Desacetilase 6 de Histona/metabolismo , Hipóxia/metabolismo , Inflamação/metabolismo , Isquemia/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/metabolismo , Serina-Treonina Quinases TOR/metabolismo
17.
Adv Sci (Weinh) ; 11(12): e2304342, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38229183

RESUMO

Immunotherapy targeting PD-L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine-threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8+ T and NK cells. Mechanistically, STK24 in tumor cells associates with and directly phosphorylates AKT at Thr21, which promotes AKT activation and subsequent PD-L1 induction. Deletion or inhibition of STK24, by contrast, blocks IFN-γ-mediated PD-L1 expression. Various murine models indicate that in vivo silencing of STK24 can significantly enhance the efficacy of the anti-PD-1 blockade strategy. Elevated STK24 levels are observed in patient specimens in multiple tumor types and inversely correlated with intratumoral infiltration of cytotoxic CD8+ T cells and with patient survival. The study collectively identifies STK24 as a critical modulator of antitumor immunity, which engages in AKT and PD-L1/PD-1 signaling and is a promising target for combined immunotherapy.


Assuntos
Antígeno B7-H1 , Linfócitos T CD8-Positivos , Humanos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Evasão Tumoral , Linhagem Celular Tumoral
18.
Clin Transl Oncol ; 26(6): 1438-1445, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38194018

RESUMO

BACKGROUND: Lung adenocarcinoma is a common cause of cancer-related deaths worldwide, and accurate EGFR genotyping is crucial for optimal treatment outcomes. Conventional methods for identifying the EGFR genotype have several limitations. Therefore, we proposed a deep learning model using non-invasive CT images to predict EGFR mutation status with robustness and generalizability. METHODS: A total of 525 patients were enrolled at the local hospital to serve as the internal data set for model training and validation. In addition, a cohort of 30 patients from the publicly available Cancer Imaging Archive Data Set was selected for external testing. All patients underwent plain chest CT, and their EGFR mutation status labels were categorized as either mutant or wild type. The CT images were analyzed using a self-attention-based ViT-B/16 model to predict the EGFR mutation status, and the model's performance was evaluated. To produce an attention map indicating the suspicious locations of EGFR mutations, Grad-CAM was utilized. RESULTS: The ViT deep learning model achieved impressive results, with an accuracy of 0.848, an AUC of 0.868, a sensitivity of 0.924, and a specificity of 0.718 on the validation cohort. Furthermore, in the external test cohort, the model achieved comparable performances, with an accuracy of 0.833, an AUC of 0.885, a sensitivity of 0.900, and a specificity of 0.800. CONCLUSIONS: The ViT model demonstrates a high level of accuracy in predicting the EGFR mutation status of lung adenocarcinoma patients. Moreover, with the aid of attention maps, the model can assist clinicians in making informed clinical decisions.


Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Receptores ErbB , Neoplasias Pulmonares , Mutação , Tomografia Computadorizada por Raios X , Humanos , Receptores ErbB/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto
19.
Comput Methods Programs Biomed ; 244: 107998, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176330

RESUMO

BACKGROUND AND OBJECTIVE: Estimating the three-dimensional (3D) deformation of the lung is important for accurate dose delivery in radiotherapy and precise surgical guidance in lung surgery navigation. Additional 4D-CT information is often required to eliminate the effect of individual variations and obtain a more accurate estimation of lung deformation. However, this results in increased radiation dose. Therefore, we propose a novel method that estimates lung tissue deformation from depth maps and two CT phases per patient. METHODS: The method models the 3D motion of each voxel as a linear displacement along a direction vector, with a variable amplitude and phase that depend on the voxel location. The direction vector and amplitude are derived from the registration of the CT images at the end-of-exhale (EOE) and the end-of-inhale (EOI) phases. The voxel phase is estimated by a neural network. Coordinate convolution (CoordConv) is used to fuse multimodal data and embed absolute position information. The network takes the front and side views as well as the previous phase views as inputs to enhance accuracy. RESULTS: We evaluate the proposed method on two datasets: DIR-Lab and 4D-Lung, and obtain average errors of 2.11 mm and 1.36 mm, respectively. The method achieves real-time performance of less than 7 ms per frame on a NVIDIA GeForce 2080Ti GPU. CONCLUSION: Compared with previous methods, our method achieves comparable or even better accuracy with less CT phases.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Pulmão/diagnóstico por imagem , Tomografia Computadorizada Quadridimensional/métodos , Redes Neurais de Computação , Tórax , Respiração
20.
Heliyon ; 10(1): e23720, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38226247

RESUMO

Background: Acral melanoma (AM), an aggressive subtype of melanoma with poor prognosis, has been increasingly studied. The present study aims to discuss the current status, hotspots and future directions of AM studies through visualized analysis with bibliometrics and knowledge graph. Method: Publications related to acral melanoma from January 1999 to May 2023 were searched and retrieved from the Web of Science. Data extraction and visualization of the top 10 publications by year of publication, journal, country and core author were performed using R Studio (Version 4.3.0) and Scimago Graphica (Version 1.0.34). Co-reference graphs regarding country/region, organization, author, and keywords, as well as reference collaborative network, co-occurrence network, and references were plotted using VOSviewer (Version 1.6.19) and CiteSpace (Version 6.2.R3). Results: A total of 1387 articles related to AM published in English from 1999 to 2023 were included in the present study. A total of 7499 authors were from 2092 organizations in 50 countries. The articles were published in 356 journals, involving 4131 keywords and 28,200 references. The 1387 articles related to AM had been cited a total of 10,014 times by the time of this study. The result showed that Journal of the American Academy of Dermatology had the largest number of citations and citation rate, with a total of 60 publications having been cited 2191 times. Having the top three productivity institutions in the world, the US is the most productive country in this field, with a total of 361 publications. The authors with the highest number of publications were Guo Jun (n = 43) and Si Lu (n = 38) from Peking University. The keyword burstiness test found that "ipilimumab", "open label", "efficacy" and "nivolumab" appeared most frequently in recent years. The co-cited reference timeline graph showed that the clustering of "advanced melanoma" and "melanocytic lesion" has been a hotspot since 2016. Conclusions: The number of AM-related studies has been increasing. The clinical characteristics and immunotherapy of AM are still key research directions, with the US playing a leading role in this field. This bibliometric analysis found up to 1387 publications, which not only comprehensively and quantitatively reflected the research trends and hotspots, but also provided a theoretical basis for future studies of AM. Researchers can benefit from choosing the right journals and finding potential collaborators or partner institutions.

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