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1.
Front Pharmacol ; 15: 1390615, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698811

RESUMO

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

2.
Org Lett ; 26(17): 3530-3535, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38656165

RESUMO

State-of-the-art strategies for alkene-hydroxyazidation, which yield a mixture of ß-azido alcohol and ß-azido peroxide, must rely on phosphine reagents to improve the chemoselectivity. To overcome the above problems, we present a photochemical hydroxyazidation of alkenes via Mn-mediated ligand-to-metal charge transfer (LMCT) in O2, which activates N3- to •N3 and incorporates O2 to be used as an oxygen source in the hydroxyazidation products. Broad alkene range and step-economy chemistry for the hydroxyazidation transformation were also demonstrated.

3.
Adv Mater ; 36(26): e2401271, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38549262

RESUMO

The advancement of aqueous micro-supercapacitors offers an enticing prospect for a broad spectrum of applications, spanning from wearable electronics to micro-robotics and sensors. Unfortunately, conventional micro-supercapacitors are characterized by low capacity and slopy voltage profiles, limiting their energy density capabilities. To enhance the performance of these devices, the use of 2D MXene-based compounds has recently been proposed. Apart from their capacitive contributions, these structures can be loaded with redox-active nanowires which increase their energy density and stabilize their operation voltage. However, introducing rigid nanowires into MXene films typically leads to a significant decline in their mechanical properties, particularly in terms of flexibility. To overcome this issue, super stretchable micro-pseudocapacitor electrodes composed of MXene nanosheets and in situ reconstructed Ag nanoparticles (Ag-NP-MXene) are herein demonstrated, delivering high energy density, stable operation voltage of ≈1 V, and fast charging capabilities. Careful experimental analysis and theoretical simulations of the charging mechanism of the Ag-NP-MXene electrodes reveal a dual nature charge storage mechanism involving ad(de)sorption of ions and conversion reaction of Ag nanoparticles. The superior mechanical properties of synthesized films obtained through in situ construction of Ag-NP-MXene structure show an ultra stretchability, allowing the devices to provide stable voltage and energy output even at 100% elongation.

4.
Biochem Biophys Rep ; 37: 101605, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38188362

RESUMO

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013505

RESUMO

@#Objective To summarize and analyze the clinical diagnosis, surgical treatment and prognosis of multiple pulmonary nodules (MPNs). Methods The clinical data of lung cancer patients who received surgical treatment in our hospital from 2018 to 2020 were collected. The short-term efficacy of surgical treatment for MPNs was analyzed. Results A total of 97 patients were enrolled, including 30 males and 67 females with an average age of 56.1±10.0 years at onset ill. There were 62 patients with double lesions, 22 patients with three lesions, 4 patients with four lesions, and 9 patients with more than four lesions. A total of 213 lesions were surgically treated, including 88 pure ground-glass nodules, 81 partially solid nodules, and 7 solid nodules. There were 87 simultaneous surgeries and 10 staged surgeries, with an average operation interval of 5.2 months. The pathological combination type included adenocarcinoma-adenocarcinoma in 96 (99.0%) patients, squamous cell carcinoma-squamous cell carcinoma in 1 (1.0%) patient, and no lymph node metastasis was found. The 2-year disease-free survival (DFS) rate was 92.1%, and the overall survival (OS) rate was 100.0%. Univariate analysis showed that high-risk lesion size>2 cm (P=0.316), residual lesions (P=0.782) and pathological combination type (P=0.913) had statistical effect on the 2-year DFS rate. Conclusion MPNs are mainly diagnosed with multiple primary lung cancers, and the pathological combination is mostly adenocarcinoma-adenocarcinoma combination. Imaging examination is of great help to the surgical approach selection, diagnosis and differential diagnosis of MPNs. During the operation, maximal preservation of lung function and complete resection of high-risk nodules should be taken as the principle, and the prognosis is satisfactory.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993070

RESUMO

Objective:To investigate the effect of radiofrequency radiation (RF) from 5G mobile phone communication frequency bands (3.5 GHz and 4.9 GHz) on the permeability of the blood-brain barrier (BBB) in mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into Sham, 3.5 GHz RF and 4.9 GHz RF groups, and 8 mice in each group. Mice in the RF groups were systemically exposed to 5G cell phone radiation for consecutive 35 d(1 h/d) with 50 W/m 2 power density. The BBB permeability of mice was detected by Evans Blue (EB) fluorescence experiment. The expression levels of the BBB tight junction-related proteins (ZO-1, occludin and claudin-11) and the gap junction-related protein Connexin 43 were determined by Western blot. Results:The number of spots, fluorescence intensity and comprehensive score of EB were significantly increased in 3.5 GHz RF group and 4.9 GHz RF group compared with the Sham group ( t=12.98, 17.82, P<0.001). Compared with the Sham group, the content of S100B in mouse serum was significantly increased in 3.5 GHz RF group and 4.9 GHz RF group ( t=19.34, 14.68, P<0.001). The BBB permeability was increased in the RF group. The expression level of occludin protein was significantly reduced in the 3.5 GHz RF group ( t=-3.13, P<0.05), and this decrease was much profound in the 4.9 GHz RF group ( t=-6.55, P<0.01). But the protein levels of ZO-1, Claudin-11 and Connexin 43 in the cerebral cortex of the RF groups had no significantly difference in comparison with the Sham group( P>0.05). Conclusions:The continuous exposure of mobile phone RF at 3.5 GHz or 4.9 GHz for 35 d (1 h/d) induces an increase of BBB permeability in the mouse cerebral cortex, perhaps by reducing the expression of occludin protein.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-990283

RESUMO

Objective:To explore the effect of emergency rescue ability training of operating room nurses based on video tracking method, and provide reference for improving emergency ability of operating room nurses.Methods:This study was a quasi-experimental study. In March 2021, 85 nurses working in the Department of Anesthesiology and Surgery of the Provincial Hospital Affiliated to Shandong First Medical University were selected by cluster sampling method. We implemented a training program of rescue emergency ability based on video tracking and adopted the inspection list of rescue emergency ability assessment and doctors′ satisfaction questionnaire of operating room nurses to evaluate the scores of each item in the nurses' rescue emergency ability list and doctors' satisfaction of rescue cooperation of operating room nurses.Results:The scores of the dimensions of recognition of fatal arrhythmias, fatal arrhythmia, several situations that can directly call help, writing of emergency state nursing records and handover of medical records, use of defibrillator, correct use and maintenance of negative pressure attraction, use and management of rescue vehicle and situation disposal in the inspection list of rescue ability after training were 9.80 ± 1.61, 26.06 ± 2.20, 17.34 ± 1.29, 13.00 ± 1.57, 7.35 ± 0.74, 10.24 ± 1.14, 33.89 ± 2.73, which were higher than before training 9.24 ± 1.18, 24.92 ± 2.15, 15.69 ± 1.92, 12.21 ± 1.66, 6.55 ± 0.92, 8.94 ± 1.32, 32.94 ± 2.20. The differences were statistically significant ( t values were -6.83 to -2.51, all P<0.05); after the training, in the questionnaire of doctors' satisfaction with nurses, surgical materials and instruments preparation, first aid skill operating level, attention to surgical progress, active and correct delivery, orderly and busy, coordination and communication ability, professional knowledge, evaluation ability and foresight, ability to deal with emergencies, clear division of labor and good cooperation, and responsibility scores were 4.22 ± 0.58, 4.52 ± 0.54, 4.53 ± 0.47, 4.43 ± 0.58, 4.44 ± 0.44, 4.37 ± 0. 59, 4.45 ± 0.51, 4.51 ± 0.53, 4.51 ± 0.57, 4.17 ± 0.63, which were higher than the pre-training 4.05 ± 0.58, 4.38 ± 0.56, 4.26 ± 0.76, 4.04 ± 0.67, 4.25 ± 0.62, 4.19 ± 0.74, 4.25 ± 0.74, 4.34 ± 0.67, 4.21 ± 0.84 and 3.56 ± 0.58. All differences were statistically significant ( t values were -8.22 to -2.10, all P<0.05). Conclusions:The training method based on video tracking method improved the emergency rescue ability of operating room nurses and the doctor's satisfaction with rescue cooperation, and provided a reference for the training of operating room nurses.

8.
China Tropical Medicine ; (12): 260-2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-979627

RESUMO

@#Abstract: Objective To investigate a poisoning incident caused by eating eight treasure congee, and establish liquid chromatography (LC)-mass spectrometry (MS)/MS screening method of 28 alkaloids to provide references for disposal of similar poisoning incidents. Methods LC-MS/MS was used for screening 28 alkaloids in the urine, eight treasure congee and food raw material, and the detected alkaloids were quantified. Samples were extracted with 0.4% formic acid aqueous solution and separated by a Acquity UPLC BEH C18 column (1.7 μm, 100 × 2.1 mm). Acetonitrile-0.2% formic acid aqueous solution was used as the mobile phase and gradient elution was adopted. The ionization mode was electrospray positive ionization mode, and the detection method was multi-reaction monitoring (MRM). Analytes were quantified with the external standard method. Results In the concentration range of 0-100 ng/mL, the linear correlation coefficient r were greater than 0.999 for 28 alkaloids. The recovery of 28 alkaloids in urine sample ranged from 63.0% to 105.0%, and the relative standard deviations (RSDs) were between 5.8% and 8.6%. The recovery of 28 alkaloids in eight treasure congee sample ranged from 72.0% to 109.0%, and the RSDs were between 6.3% and 9.7%. The recovery of 28 alkaloids in semen sesami nigrum sample ranged from 60.0% to 95.0%, and the RSDs were between 4.8% and 8.2%. Hyoscyamine (2 380.0 ng/mL), scopliamine (3.6 ng/mL) and rac-anisodamine (4.7 ng/mL) were detected in the patient's urine. Hyoscyamine (63.3 μg/g), scopliamine (5.7 μg/g) and rac-anisodamine (2.1 μg/g) were detected in eight treasure congee. Hyoscyamine (901.0 μg/g), scopliamine (80.0 μg/g) and rac-anisodamine (30.1 μg/g) were detected in the seed of Datura stramonium L. The ratio of scopliamine and hyoscyamine in the seed of D. stramonium was 1∶11, which complies with the characteristics of D. stramonium L. In urine sample, the proportion of scopliamine and rac-anisodamine was 0.15% and 0.20%, and hyoscyamine accounted for 99.65%. Conclusion Seed morphology, the content range and proportion of three alkaloids are all in accord with the characteristics of D. stramonium. Combined with the clinical symptoms of atropine poisoning, it can be deduced that this incident is a family food poisoning caused by accidental consumption of seed of D. stramonium L. The method can provide technical support for the clinical diagnosis and treatment of alkaloid poisoning patients, and also provide a basis for emergency detection and disposal of alkaloid poisoning events.

9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971668

RESUMO

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.


Assuntos
Humanos , Fosforilação Oxidativa , Berberina , Transporte de Elétrons , Mitocôndrias , Leucemia Mieloide Aguda , Isocitrato Desidrogenase
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985504

RESUMO

Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.


Assuntos
Pré-Escolar , Humanos , Lactente , Pequim/epidemiologia , Diarreia/epidemiologia , Fezes , Norovirus/genética , Filogenia , Rotavirus/genética , Viroses/epidemiologia , Vírus/genética
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-996999

RESUMO

@#Objective     To analyze the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis. Methods     Thymoma patients who received treatment in Sichuan Cancer Hospital from March 2015 to March 2021 were collected. Clinical data of the patients were analyzed using Kaplan-Meier and Cox regression analyses. Results     A total of 177 patients were included. There were 89 males and 88 females aged 17-88 (52.3±13.0) years, including 160 surgical patients and 17 non-surgical patients. There were 160 patients survived, 17 died of thymoma, and 5 had recurrence and metastasis. Overall, the 1-year, 3-year and 5-year progression-free survival rates were 94.4%, 88.7%, 88.1%, respectively; the 1-year, 3-year and 5-year overall survival rates were 94.9%, 91.5%, 91.0%, respectively. The Kaplan-Meier analysis showed that World Health Organization classification, clinical symptoms, Masaoka-Koga staging, treatment methods and surgery were statistically associated with progression-free survival; clinical symptoms, age, treatment methods and surgery were statistically associated with overall survival (P<0.05). Patients with younger age (P=0.018), without clinical symptoms (P=0.039), and with surgical treatment (P=0.004) had higher overall survival rates; those patients undergoing surgery had a higher progression-free survival rate (P=0.002). Conclusion     Age, clinical symptoms and surgical treatment are independent factors influencing the prognosis of patients with thymoma.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009091

RESUMO

OBJECTIVE@#To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects.@*METHODS@#The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively.@*RESULTS@#NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05).@*CONCLUSION@#NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.


Assuntos
Ratos , Animais , Osteogênese , Preparações de Ação Retardada/farmacologia , Microesferas , Berberina/farmacologia , Antibacterianos/farmacologia , Escherichia coli
13.
Bioorg Med Chem ; 57: 116647, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35121400

RESUMO

Neuraminidase (NA) is an important target in the development of anti-influenza virus drugs. Compounds containing 1,3, 4-oxadiazole heterocycles have good biological activity and have been proved to have wide applications in antibacterial and antiviral drugs. In this paper, a series of novel 1, 3, 4-oxadiazole neuraminidase inhibitors (6a-6l) were designed and synthesized and their inhibitory activities of NA was tested in vitro. The results displayed that compound 6d exerts the best inhibitory activity (IC50 = 0.027 µM), which was obviously lower than that of oseltamivir carboxylate (OSC) (IC50 = 0.082 µM). Molecular docking analysis showed that the 1, 3, 4-oxadiazole heterocycle plays crucial part in compound 6d, and it can interact with the key arginine triad (Arg118, Arg292 and Arg 371) at the NA S1 site. The good efficacy of 6d may also be attributed to the extension of the substituted aniline ring to the 150-cavitiy. The theoretical and experimental results may provide reference for development of new anti-influenza drugs.


Assuntos
Antivirais/farmacologia , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Neuraminidase/antagonistas & inibidores , Orthomyxoviridae/efeitos dos fármacos , Oxidiazóis/farmacologia , Antivirais/síntese química , Antivirais/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Neuraminidase/metabolismo , Oxidiazóis/síntese química , Oxidiazóis/química , Relação Estrutura-Atividade
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-932606

RESUMO

Objective:To investigate the effect of thoracic X-ray irradiation on the spermatogenesis of adult male mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into radiation group (Radiation) and sham-radiation group (Sham), 12 mice in each group. The area of thoracic irradiation was 1.5 cm× 2 cm, and the dose rate was 3.04 Gy/min, 8 Gy/d for 3 consecutive days, 24 Gy in total. At 7 d and 21 d after thoracic irradiation, the bilateral testes and epididymal tails were stripped and the testicular index was calculated. The morphology of testis was examined by haematoxylin-eosin (HE) staining, then the diameter of seminiferous tubules and the thickness of seminiferous epithelium were measured. The sperms were collected from the bilateral epididymal tails for sperm counting. The level of apoptosis in testis and levels of apoptosis-related proteins were detected by TUNEL and Western blot, respectively.Results:Compared with Sham group, the morphology of testis and epididymis was seriously damaged, the diameter of seminiferous tubules significantly decreased at 21 d after irradiation ( t = 8.93, P < 0.05), and the seminiferous epithelium significantly decreased at 7 d and 21 d after irradiation ( t = 4.24, 12.77, P < 0.05). In addition, the number of sperms significantly decreased ( t = 4.30, 2.98, P < 0.05). The number of TUNEL positive cells in the seminiferous epithelium significantly increased at 7 d and 21 d after irradiation ( t = -2.73, -3.74, P < 0.05). Meanwhile, the level of cleaved Caspase-3 protein significantly increased at 7 d and 21 d after irradiation ( t = -2.96, -2.46, P < 0.05). The concentrations of SCF and GDNF did not change at 7 d after irradiation, but were significantly increased at 21 d after irradiation ( t = -10.46, -5.42, P < 0.05). Conclusions:The thoracic X-ray irradiation could lead to spermatogenesis disorder in male adult mice, and the induction of spermatogenic cell apoptosis and the secretory dysfunction of sertoli cells may be involved.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-940575

RESUMO

Diabetic wound healing disorder,one of the common chronic complications of diabetes,seriously influences the quality of life of patients and even causes disability and death,bringing a heavy burden to the society. Chinese medicine,a unique and precious resource in China,is safe with definite effect. Oxidative stress plays an important role in the occurrence and development of diabetic wound and the disturbance of antioxidant defense mechanism is among the causes of the lingering diabetic wound. As a vital transcription factor for intracellular redox homeostasis,nuclear factor erythroid 2-related factor 2 (Nrf2) regulates oxidative/heterogenous stress and reduces inflammatory responses. Although it is unnecessary for common wound healing,it is of great importance for diabetic wound healing. Many Chinese medicinals and the active ingredients have been found to enhance diabetic wound healing by mechanisms related to activation of the Nrf2 signaling pathway. Targeted activation of Nrf2 by Chinese medicine can alleviate oxidative stress,inflammatory response,and apoptosis in diabetic wound,thereby delaying further exacerbation of symptoms. Therefore,Nrf2 is regarded as a potential target for drugs to boost diabetic wound healing. This study summarizes the relationship between the Nrf2 signaling pathway and diabetic wound and analyzes the mode of action and possible mechanisms of Chinese medicine and its active ingredients in promoting diabetic wound healing through modulating the Nrf2 pathway,which is expected to serve as a reference for developing drugs for diabetic wound based on this pathway.

16.
Chinese Journal of Burns ; (6): 256-265, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-936003

RESUMO

Objective: To investigate the effects and mechanism of hydrogen peroxide (HP) pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs). Methods: The experimental research methods were used. BMSCs were isolated and cultured from two 2-week-old male BALB/c mice by the whole bone marrow culture method. The 3rd-7th passages of cells in logarithmic growth phase were used for the experiments after identification. According to the random number table (the same grouping method below), the cells were divided into 0 μmol/L HP group (without HP, the same below), 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. The apoptosis rate was detected by flow cytometry (n=4) after 24 hours of culture. The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, and 100 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively. After 24 hours of culture, the protein expressions of B-lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) were detected by Western blotting, and the Bcl-2/Bax ratio was calculated (n=3). The cells were divided into 0 μmol/L HP group, 25 μmol/L HP group, 50 μmol/L HP group, 100 μmol/L HP group, 200 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. After 24 hours of culture, the protein expressions of glycogen synthase kinase-3β (GSK-3β) and phosphorylated GSK-3β (p-GSK-3β) were detected by Western blotting (n=3). The cells were divided into 0 μmol/L HP group, 50 μmol/L HP group, and 300 μmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively, and HP pretreatment group with 50 μmol/L HP being added in advance for 12 h and then 300 μmol/L HP being added. After 24 hours of culture, the morphology and growth of cells were observed by inverted fluorescence microscopy (non-fluorescent condition) and immunofluorescence method, the apoptosis rate was detected by flow cytometry, the protein expressions of Bcl-2, Bax, cysteine aspartic acid specific protease-3 (caspase-3), caspase-9, cleavage caspase-3, cleavage caspase-9, GSK-3β, and p-GSK-3β were detected by Western blotting, and the Bcl-2/Bax ratio was calculated, with all the number of samples being 3. Data were statistically analyzed with one-way analysis of variance and Bonferroni test. Results: After 24 hours of culture, compared with that in 0 μmol/L HP group, the apoptosis rate of cells did not change significantly in 25 μmol/L HP group, 50 μmol/L HP group, or 100 μmol/L HP group (P>0.05) but increased significantly in 150 μmol/L HP group, 200 μmol/L HP group, 250 μmol/L HP group, and 300 μmol/L HP group (P<0.01). After 24 hours of culture, compared with that in 0 μmol/L HP group, the Bcl-2/Bax ratio of cells increased significantly in 25 μmol/L HP group and 50 μmol/L HP group (P<0.05 or P<0.01) but decreased significantly in 100 µmol/L HP group (P<0.05). After 24 hours of culture, compared with those in 0 μmol/L HP group, the protein expression of GSK-3β in cells showed no significant change in 25 μmol/L HP group and 50 μmol/L HP group (P>0.05), the protein expressions of p-GSK-3β in cells significantly increased in 25 μmol/L HP group and 50 μmol/L HP group (P<0.01), the protein expressions of GSK-3β and p-GSK-3β in cells in 100 μmol/L HP group showed no significant change (P>0.05), the protein expressions of GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group were significantly increased (P<0.05). but the protein expression of p-GSK-3β in cells in 200 μmol/L HP group and 300 μmol/L HP group was significantly decreased (P<0.05). After 24 hours of culture, the morphology and growth of cells in 0 μmol/L HP group and 50 μmol/L HP group were similar and normal; in contrast, the cells in 300 µmol/L HP group became smaller and round, with the cell protrusions being shorter or disappeared, the nucleus being cavitated, and the cell abscission being increased significantly; the morphology of most cells in HP pretreatment group was normal, with the shedding of cells being less than that in 300 µmol/L HP group, and the morphology of nucleus being normal. After 24 hours of culture, the protein expression of caspase-9 was similar among the four groups (P>0.05). Compared with that in 0 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 50 μmol/L HP group showed no significant changes (P>0.05), the Bcl-2/Bax ratio of cells in 50 μmol/L HP group increased significantly (P<0.05), the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 300 μmol/L HP group were significantly increased (P<0.01), while the Bcl-2/Bax ratio of cells in 300 μmol/L HP group was significantly decreased (P<0.05). Compared with those in 300 μmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells were significantly decreased in HP pretreatment group (P<0.05 or P<0.01), while the Bcl-2/Bax ratio of cells was significantly increased in HP pretreatment group (P<0.01). After 24 hours of culture, the protein expressions of GSK-3β and p-GSK-3β of cells in 0 μmol/L HP group, 50 μmol/L HP group, 300 μmol/L HP group, and HP pretreatment group were 1.09±0.14, 0.62±0.17, 1.35±0.21, 0.74±0.34, 0.68±0.03, 0.85±0.08, 0.38±0.10, and 0.54±0.09, respectively. Compared with those in 0 μmol/L HP group, the protein expression of p-GSK-3β of cells was significantly increased in 50 μmol/L HP group (P<0.05) but significantly decreased in 300 μmol/L HP group (P<0.01), while the protein expression of GSK-3β of cells was significantly increased in 300 μmol/L HP group (P<0.05). Compared with those in 300 μmol/L HP group, the protein expression of GSK-3β of cells was significantly decreased in HP pretreatment group (P<0.01), while the protein expression of p-GSK-3β of cells was significantly increased in HP pretreatment group (P<0.01). Conclusions: The molarity of 50 μmol/L may be the optimal molarity of HP to pretreat mouse BMSCs, and 50 μmol/L HP pretreatment can antagonize mitochondrial pathway of oxidative stress induced apoptosis by inhibiting the activity of GSK-3β.


Assuntos
Animais , Masculino , Camundongos , Apoptose , Glicogênio Sintase Quinase 3 beta/farmacologia , Peróxido de Hidrogênio/farmacologia , Células-Tronco Mesenquimais , Estresse Oxidativo
17.
International Eye Science ; (12): 1191-1194, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-929505

RESUMO

AIM: To explore the application value of deep learning technology in automatic meibomian glands segmentation. METHODS:Infrared meibomian gland images were collected and 193 of them were picked out for establishing the database. The images were manually labeled by three clinicians. UNet++ network and automatic data expansion strategy were introduced to construct the automatic meibomian glands segmentation model. The feasibility and effectiveness of the proposed segmentation model were analyzed by precision, sensitivity, specificity, accuracy and intersection over union.RESULTS: Taking manual labeling as the gold standard, the presented method segment the glands effectively and steadily with accuracy, sensitivity and specificity of 94.31%, 82.15% and 96.13% respectively. On the average, only 0.11s was taken for glands segmentation of single image.CONCLUSIONS: In this paper, deep learning technology is introduced to realize automatic segmentation of meibomian glands, achieving high accuracy, good stability and efficiency. It would be quite useful for calculation of gland morphological parameters, the clinical diagnosis and screening of related diseases, improving the diagnostic efficiency.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-928010

RESUMO

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D_(eff)) and activation energy(E_a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D_(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E_a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.


Assuntos
Atractylodes , Medicamentos de Ervas Chinesas , Temperatura Alta , Cinética , Rizoma
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-927679

RESUMO

Objective@#The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases.@*Methods@#A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up.@*Results@#Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases.@*Conclusions@#Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.


Assuntos
Humanos , COVID-19/complicações , Seguimentos , Transtornos do Olfato/etiologia , Pandemias , Estudos Prospectivos , SARS-CoV-2
20.
PLoS One ; 16(7): e0255376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34324571

RESUMO

The development of information technology has produced massive amounts of data, which has brought severe challenges to information storage. Traditional electronic storage media cannot keep up with the ever-increasing demand for data storage, but in its place DNA has emerged as a feasible storage medium with high density, large storage capacity and strong durability. In DNA data storage, many different approaches can be used to encode data into codewords. DNA coding is a key step in DNA storage and can directly affect storage performance and data integrity. However, since errors are prone to occur in DNA synthesis and sequencing, and non-specific hybridization is prone to occur in the solution, how to effectively encode DNA has become an urgent problem to be solved. In this article, we propose a DNA storage coding method based on the equilibrium optimization random search (EORS) algorithm, which meets the Hamming distance, GC content and no-runlength constraints and can reduce the error rate in storage. Simulation experiments have shown that the size of the DNA storage code set constructed by the EORS algorithm that meets the combination constraints has increased by an average of 11% compared with previous work. The increase in the code set means that shorter DNA chains can be used to store more data.


Assuntos
Algoritmos , DNA , Composição de Bases , Replicação do DNA , Análise de Sequência de DNA
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