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1.
Nano Lett ; 24(11): 3548-3556, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38457277

RESUMEN

After spinal cord injury (SCI), successive systemic administration of microtubule-stabilizing agents has been shown to promote axon regeneration. However, this approach is limited by poor drug bioavailability, especially given the rapid restoration of the blood-spinal cord barrier. There is a pressing need for long-acting formulations of microtubule-stabilizing agents in treating SCI. Here, we conjugated the antioxidant idebenone with microtubule-stabilizing paclitaxel to create a heterodimeric paclitaxel-idebenone prodrug via an acid-activatable, self-immolative ketal linker and then fabricated it into chondroitin sulfate proteoglycan-binding nanomedicine, enabling drug retention within the spinal cord for at least 2 weeks and notable enhancement in hindlimb motor function and axon regeneration after a single intraspinal administration. Additional investigations uncovered that idebenone can suppress the activation of microglia and neuronal ferroptosis, thereby amplifying the therapeutic effect of paclitaxel. This prodrug-based nanomedicine simultaneously accomplishes neuroprotection and axon regeneration, offering a promising therapeutic strategy for SCI.


Asunto(s)
Axones , Traumatismos de la Médula Espinal , Ubiquinona/análogos & derivados , Animales , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Excipientes/farmacología , Excipientes/uso terapéutico , Nanomedicina , Regeneración Nerviosa , Traumatismos de la Médula Espinal/terapia
2.
Small ; 20(21): e2308403, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38098457

RESUMEN

Keratitis, an inflammation of the cornea caused by bacterial or fungal infections, is one of the leading causes of severe visual disability and blindness. Keratitis treatment requires both the prevention of infection and the reduction of inflammation. However, owing to their limited therapeutic functions, in addition to the ocular barrier, existing conventional medications are characterized by poor efficacy and low bioavailability, requiring high dosages or frequent topical treatment, which represents a burden on patients and increases the risk of side effects. In this study, manganese oxide nanocluster-decorated graphdiyne nanosheets (MnOx/GDY) are developed as multienzyme-like nanozymes for the treatment of infectious keratitis and loaded into hyaluronic acid and polymethyl methacrylate-based ocular microneedles (MGMN). MGMN not only exhibits antimicrobial and anti-inflammatory effects owing to its multienzyme-like activities, including oxidase, peroxidase, catalase, and superoxide dismutase mimics but also crosses the ocular barrier and shows increased bioavailability via the microneedle system. Moreover, MGMN is demonstrated to eliminate pathogens, prevent biofilm formation, reduce inflammation, alleviate ocular hypoxia, and promote the repair of corneal epithelial damage in in vitro, ex vivo, and in vivo experiments, thus providing a better therapeutic effect than commercial ophthalmic voriconazole, with no obvious microbial resistance or cytotoxicity.


Asunto(s)
Queratitis , Agujas , Queratitis/tratamiento farmacológico , Animales , Ratones , Enzimas/metabolismo , Biopelículas/efectos de los fármacos , Humanos , Óxidos , Compuestos de Manganeso
3.
J Transl Med ; 22(1): 580, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898490

RESUMEN

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Neutrófilos , Proteínas de Unión al ARN , Humanos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Animales , Proteínas de Unión al ARN/metabolismo , Línea Celular Tumoral , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Microambiente Tumoral/inmunología , Femenino , Antígeno B7-H1/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/inmunología , Masculino , Ratones , Resistencia a Antineoplásicos , Movimiento Celular , Tolerancia Inmunológica , Terapia de Inmunosupresión , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica , Ratones Desnudos , Inmunoterapia , Persona de Mediana Edad
4.
Opt Express ; 32(2): 1207-1217, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38297677

RESUMEN

The investigation into the spectral properties and refractive index (RI) sensitivities at low RI region of helical intermedium-period fiber gratings (HIPFGs) with varied periods ranging from 10-48 µm is presented in detail for the first time. The structure of HIPFG is optimized for RI sensing in the RI range of 1.3-1.33 by comparing the optical properties of HIPFGs with different grating periods. The HIPFG with optimized structure is demonstrated to have a high average sensitivity of 302.5 nm/RIU in the RI ranging from 1.3 to 1.33, which is two orders more elevated than the traditional long-period fiber gratings. The improved HIPFG is also experimentally applied to breath monitoring in different states. Normal breath, slow breath, fast breath, and unhealthy breath are distinguished based on breathing rate, intensity, and time of exhalation and inhalation. The fastest response time is determined to be 10 ms. The results demonstrate that the optical fiber's sensitivity in the low RI region can be increased by shortening its period, offering a special strategy for improving detection performance of HIPFGs. By verifying its performance in breathing monitoring, it is proved that the optimized HIPFG sensor has the great potential to expand medical applications.

5.
Opt Lett ; 49(5): 1233-1236, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426981

RESUMEN

We demonstrate a novel, to the best of our knowledge, high-temperature pressure sensor based on a highly birefringent fiber Bragg grating (Hi-Bi FBG) fabricated in a dual side-hole fiber (DSHF). The Hi-Bi FBG is generated by a femtosecond laser directly written sawtooth structure in the DSHF cladding along the fiber core through the slow axis (i.e., the direction perpendicular to the dual-hole axis). The sawtooth structure serves as an in-fiber stressor and also generates Bragg resonance due to its periodicity. The DSHF was etched by hydrofluoric acid to increase its pressure sensitivity, and the diameter of two air holes was enlarged from 38.2 to 49.6 µm. A Hi-Bi FBG with a birefringence of up to 1.8 × 10-3 was successfully created in the etched DSHF. Two distinct reflection peaks could be observed by using a commercial FBG interrogator. Moreover, pressure measurement from 0 to 3 MPa at a high temperature of 700°C was conducted by monitoring the birefringence-induced peak splits and achieved a high-pressure sensitivity of -21.2 pm/MPa. The discrimination of the temperature and pressure could be realized by simultaneously measuring the Bragg wavelength shifts and peak splits. Furthermore, a wavelength-division-multiplexed (WDM) Hi-Bi FBG array was also constructed in the DSHF and was used for quasi-distributed high-pressure sensing up to 3 MPa. As such, the proposed femtosecond laser-inscribed Hi-Bi FBG is a promising tool for high-temperature pressure sensing in harsh environments, such as aerospace vehicles, nuclear reactors, and petrochemical industries.

6.
Neurol Sci ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733435

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

7.
BMC Surg ; 24(1): 85, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475759

RESUMEN

BACKGROUND: The efficacy of palliative primary tumor resection (PTR) in improving prognosis for patients with unresectable metastatic colorectal neuroendocrine neoplasms (NENs) has not been fully explored. METHODS: We performed one retrospective cohort study and recruited 68 patients with unresectable metastatic colorectal NENs from two Chinese medical centers between 2000 and 2022. All patients were assigned to PTR group and no PTR group. The clinicopathological manifestation data were carefully collected, and the survival outcomes were compared between the two groups using Kaplan-Meier methods. Propensity score matching (PSM) was conducted to minimize confounding bias. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: A total of 32 patients received PTR, and the other 36 patients did not. The median progression-free survival (PFS) and overall survival (OS) times were 4 and 22 months in the whole cohort, respectively. For patients who received no PTR, the median OS was 16 months, and the 1-year OS rate and 3-year OS rate were 56.4% and 39.6%, respectively. For patients who received PTR, the median OS was 24 months, and the 1-year OS rate and 3-year OS rate were 67.9% and 34.1%, respectively. However, the Kaplan-Meier survival curves and log-rank test demonstrated no significant survival difference between the two groups (P = 0.963). Moreover, palliative PTR was also not confirmed as a prognostic factor in subsequent univariable and multivariable Cox proportional hazards regression analyses in both the original and matched cohorts. Only histological differentiation was identified as an independent prognostic factor affecting PFS [hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.02-3.41, P = 0.043] and OS [HR = 3.70, 95% CI: 1.09-12.48, P = 0.035] in the original cohort. CONCLUSIONS: Palliative PTR may not offer survival benefits for patients with unresectable metastatic colorectal NENs.


Asunto(s)
Neoplasias Colorrectales , Humanos , Estudios Retrospectivos , Neoplasias Colorrectales/cirugía , Pronóstico , Modelos de Riesgos Proporcionales , Supervivencia sin Progresión
8.
Sensors (Basel) ; 24(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38894474

RESUMEN

A highly sensitivity balloon-like fiber interferometer based on ethanol coating is presented in this paper. The Mach-Zehnder interferometer is formed by bending a single-mode fiber to a balloon-like structure and nested in the Teflon tube. Then, an ethanol solution was filled into the tube of the balloon-like fiber interferometer by the capillary effect. Due to the high sensitivity of the refractive index (RI) of ethanol solutions to temperature, when the external temperature varies, the optical path difference changes. The change in temperature can be detected by the shift in the interference spectrum. Limited by the size of the balloon-like structure, three kinds of these structures with different sensitive lengths were prepared to select the best parameters. The sensitive lengths were 10, 15 and 20 mm, respectively, and the RI detection performance of each structure in 10~26% NaCl solutions was investigated experimentally. The results show that when the sensitive length is 20 mm, the RI sensitivity of the sensor is the highest, which is 212.88 nm/RIU. Ultimately, the sensitive length filled with ethanol is 20 mm. The experimental results show that the temperature sensitivity of the structure is 1.145 nm/°C in the range of 28.1 °C~35 °C, which is 10.3 times higher than that of an unfilled balloon-like structure (0.111 nm/°C). The system has the advantages of low cost and easy fabrication, which can potentially be used in high-precision temperature monitoring processes.

9.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338769

RESUMEN

Stalk rot is a prevalent disease of maize (Zea mays L.) that severely affects maize yield and quality worldwide. The ascomycete fungus Fusarium spp. is the most common pathogen of maize stalk rot. At present, the molecular mechanism of Fusarium proliferation during the maize stalk infection that causes maize stalk rot has rarely been reported. In this study, we investigated the response of maize to F. proliferatum infestation by analyzing the phenotypic, transcriptomic, and metabolomic data of inbred lines ZC17 (resistant) and CH72 (susceptible) with different levels of resistance to stalk rot. Physiological and phenotypic results showed that the infection CH72 was significantly more severe than ZC17 after inoculation. Transcriptome analysis showed that after inoculation, the number of differentially expressed genes (DEGs) was higher in CH72 than in ZC17. Nearly half of these DEGs showed the same expression trend in the two inbred lines. Functional annotation and enrichment analyses indicated that the major pathways enriched for DEGs and DEMs included the biosynthesis of plant secondary metabolites, phenylalanine metabolism, biosynthesis of plant hormones, and plant-pathogen interactions. The comprehensive analysis of transcriptome and metabolome data indicated that phenylalanine metabolism and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways played a crucial role in maize resistance to F. proliferatum infection. In addition, a transcription factor (TF) analysis of the DEGs showed that several TF families, including MYB, bHLH, NAC, and WRKY, were significantly activated after inoculation, suggesting that these TFs play important roles in the molecular regulatory network of maize disease resistance. The findings of this study provide valuable insights into the molecular basis of the response of maize to Fusarium proliferatum infection and highlight the importance of combining multiple approaches, such as phenotyping, transcriptomics, and metabolomics, to gain a comprehensive understanding of plant-pathogen interactions.


Asunto(s)
Fusarium , Humanos , Fusarium/genética , Transcriptoma , Zea mays/genética , Zea mays/microbiología , Perfilación de la Expresión Génica , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 693-698, 2024 May 20.
Artículo en Zh | MEDLINE | ID: mdl-38948292

RESUMEN

Objective: To investigate the effects of intraoperative intravenous administration of dexmedetomidine (DEX) on the recovery quality of donors undergoing pure laparoscopic donor hepatectomy. Methods: A total of 56 liver donors who were going to undergo scheduled pure laparoscopic donor hepatectomy were enrolled and randomly assigned to two groups, a DEX group ( n=28) and a control group ( n=28). Donors in the DEX group received DEX infusion at a dose of 1 µg/kg over 15 minutes through a continuous pump, which was followed by DEX at 0.4 µg/(kg·h) until the disconnection of the portal branch. Donors in the control group were given an equal volume of 0.9% normal saline at the same infusion rate and over the same period of time as those of the dex infusion in the DEX group. The primary outcome was the incidence of emergence agitation (EA). The Aono's Four-point Scale (AFPS) score was used to assess EA. The secondary observation indicators included intraoperative anesthesia and surgery conditions, spontaneous respiration recovery time, recovery time, extubation time, scores for the Ramsay Sedation Scale, the incidence of chills, numeric rating scale (NRS) score for pain, and blood pressure and heart rate after extubation. Results: The incidence of EA was 10.7% and 39.3% in the DEX group and the control group, respectively, and the incidence of EA was significantly lower in the DEX group than that in the control group ( P=0.014). The APFS scores after extubation in the DEX group were lower than those in the control group (1 [1, 1] vs. 2 [1, 3], P=0.005). Compared to the control group, the dosages of intraoperative propofol and remifentanil were significantly reduced in the DEX group ( P<0.05). During the recovery period, the number of donors requiring additional boluses of analgesia, the blood pressure, and the heart rate were all lower in the DEX group than those in the control group ( P<0.05). No significant differences between the two groups were observed in the spontaneous respiration recovery time, recovery time, extubation time, the incidence of chills, NRS score, scores for the Ramsay Sedation Scale, and the length-of-stay in postanesthesia care unit (PACU) ( P>0.05). Conclusion: DEX can reduce the incidence of EA after pure laparoscopic donor hepatectomy and improve the quality of recovery without prolonging postoperative recovery time or extubation time.


Asunto(s)
Dexmedetomidina , Hepatectomía , Laparoscopía , Dexmedetomidina/administración & dosificación , Humanos , Hepatectomía/métodos , Masculino , Femenino , Adulto , Donadores Vivos , Trasplante de Hígado , Hipnóticos y Sedantes/administración & dosificación , Periodo de Recuperación de la Anestesia
11.
Osteoarthritis Cartilage ; 31(9): 1242-1248, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37209993

RESUMEN

PURPOSE: To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies. MATERIALS AND METHODS: This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance. RESULTS: In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1. CONCLUSION: The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues.


Asunto(s)
Enfermedades de los Cartílagos , Aprendizaje Profundo , Osteoartritis de la Rodilla , Humanos , Estudios Retrospectivos , Benchmarking , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Enfermedades de los Cartílagos/patología
12.
Plant Cell Environ ; 46(10): 3072-3089, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36207806

RESUMEN

Insect herbivory challenges plant survival, and coordination of the interactions between growth, herbivore resistance/tolerance is a key problem faced by plants. Based on field experiments into resistance to the Asian corn borer (ACB, Ostrinia furnacalis), we selected 10 inbred maize lines, of which five were resistant and five were susceptible to ACB. We conducted ACB larval bioassays, analysed defensive chemicals, phytohormones, and relative gene expression using RNA-seq and qPCR as well as agronomic traits, and found resistant lines had weaker inducibility, but were more resistant after ACB attack than susceptible lines. Resistance was related to high levels of major benzoxazinoids, but was not related to induced levels of JA or JA-Ile. Following combination analyses of transcriptome, metabolome and larval performance data, we discovered three benzoxazinoids biosynthesis-related transcription factors, NAC60, WRKY1 and WRKY46. Protoplast transformation analysis suggested that these may regulate maize defence-growth trade-offs by increasing levels of benzoxazinoids, JA and SA but decreasing IAA. Moreover, the resistance/tolerance-growth trade-offs were not observed in the 10 lines, and genotype-specific metabolic and genetic features probably eliminated the trade-offs. This study highlights the possibility of breeding maize varieties simultaneously with improved defences and higher yield under complex field conditions.


Asunto(s)
Mariposas Nocturnas , Zea mays , Animales , Zea mays/genética , Zea mays/metabolismo , Benzoxazinas/metabolismo , Mariposas Nocturnas/fisiología , Larva , Genotipo , Herbivoria
13.
Opt Express ; 31(11): 18693-18701, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37381576

RESUMEN

The paper presents a novel fiber-optic vector magnetic field sensor using a Fabry-Perot interferometer, which consists of an optical fiber end face and a graphene/Au membrane suspended on the ceramic ferrule end face. A pair of gold electrodes are fabricated on the ceramic ferrule by femtosecond laser to transmit electrical current to the membrane. Ampere force is generated when an electrical current flows through the membrane in a perpendicular magnetic field. The change in Ampere force causes a shift in the resonance wavelength in the spectrum. In the magnetic field intensity range of 0 ∼ 180 mT and 0 ∼ -180 mT, the as-fabricated sensor exhibits magnetic field sensitivity of 5.71 pm/mT and 8.07 pm/mT. The proposed sensor has great potential application in weak magnetic field measurements due to its compact structure, cost-effectiveness, ease to manufacture, and good sensing performance.

14.
Opt Express ; 31(7): 11053-11066, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37155749

RESUMEN

In this paper, we investigate the nonparaxial propagation dynamics of the chirped circular Airy derivative beams (CCADBs) based on vector angular spectrum method. In the case of nonparaxial propagation, the CCADBs still maintains excellent autofocusing performances. Derivative order and chirp factor are two important physical quantities of the CCADBs to regulate the nonparaxial propagation characteristics, such as focal length, focal depth and K-value. In the nonparaxial propagation model, the radiation force on a Rayleigh microsphere induced the CCADBs are also analyzed and discussed in detail. The results demonstrate that not all derivative order CCADBs can achieve stable microsphere trapping effect. The derivative order and chirp factor of the beam can be used to coarse and fine tune the capture effect of Rayleigh microsphere, respectively. This work will contribute to the more precise and flexible use of circular Airy derivative beams in optical manipulation, biomedical treatment and so on.

15.
Opt Lett ; 48(7): 1922-1925, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37221800

RESUMEN

A microbubble-probe whispering gallery mode resonator with high displacement resolution and spatial resolution for displacement sensing is proposed. The resonator consists of an air bubble and a probe. The probe has a diameter of ∼5 µm that grants micron-level spatial resolution. Fabricated by a CO2 laser machining platform, a universal quality factor of over 106 is achieved. In displacement sensing, the sensor exhibits a displacement resolution of 74.83 pm and an estimated measurement span of 29.44 µm. As the first microbubble probe resonator for displacement measurement, the component shows advantages in performance, and exhibits a potential in sensing with high precision.

16.
Pharmacol Res ; 188: 106644, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36603607

RESUMEN

poorly cohesive (PC) gastric cancer (GC) (PC-GC) is a distinct histological subtype of GC and is defined as a tumor consisting of isolated or small clusters of tumor cells with poorly differentiated and metastatic characteristics. According to multiple studies, PC-GC is intrinsically heterogeneous, with mesenchymal variants being the most aggressive. However, to date, the molecular mechanisms associated with PC-GC are still not fully understood. This study investigated the role of the USP51/ZEB1/ACTA2 axis in promoting GC metastasis. Single-cell sequencing revealed that E-box binding homeobox 1 (ZEB1) expression was significantly increased in a subpopulation of low-adherent cells and was an independent prognostic factor in GC patients. Furthermore, the bulk transcriptome analysis revealed a significant positive correlation between Ubiquitin Specific Peptidase 51 (USP51), ZEB1, and Actin Alpha 2 (ACTA2), and our data further confirmed that all three were highly co-localized in PC-GC tissues. According to the findings of in vitro and in vivo experiments, USP51 was able to maintain ZEB1 expression to promote ACTA2 transcription, thereby activating the mesenchymal phenotype of GC cells and promoting tumor metastasis. Moreover, USP51 could recruit and activate stromal cells, including M2-like macrophages and fibroblasts, through cancer cells. Clinical data suggested that overexpression of USP51 predicts that patients have difficulty benefiting from immunotherapy and is associated with immune-exclusion tumor characteristics. Collectively, the findings of this study shed light on a key mechanism by which elevated USP51 expression induces Epithelial-mesenchymal transition (EMT) in GC cells, hence facilitating GC cell proliferation, survival, and dissemination. In this view, USP51/ZEB1/ACTA2 may serve as a candidate therapeutic target against GC metastasis.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Actinas/metabolismo , Línea Celular Tumoral , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismo
17.
Plant Dis ; 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37931060

RESUMEN

Pineapple (Ananas comosus) is an economically important tropical fruit in Guangdong Province, China. The plants were seriously infected with a year-round leaf spot disease. During September to November 2022, the leaf spot disease of pineapple was found in Xuwen city and Zhanjiang city of Guangdong Province. A disease survey of 1 ha revealed that pineapple was affected at an incidence ranging from 30% to 50%. The disease caused economic loss to control plant diseases with chemicals. The initial symptoms were observed after 1 month of planting in October and included yellow spot and developed brown necrotic lesions. The leaves of pineapples showed symptoms of Large brown necrotic lesions appear on leaves especially on the tip of basal leaves. The diseased leaves were collected and surface-disinfested in 1% NaClO for 2-3 m, rinsed with sterilized water, air dried, placed on potato dextrose agar (PDA) medium, and incubated for 3 to 5 days at 28°C. Two isolates (PLF1 and PLF2) were collected and purified using the single-spore method. Colonies developing on PDA were in a circle with abundant white, densely fluffy aerial mycelium, pale to colorless after 3 d and pale orange 5-15 d later. Cultures of the isolates produced macroconidia which were falcate, 1-3-septate, hyaline, 18.2-43.4×4.8-6.8 µm(n=50). Cultures of the isolate also produced large amount of conidia which were hyaline, oblong, no septate, 5.2-10.6×2.7-5.2 µm (n=50). These characteristics were consistent with the description of Fusarium sp. (Chitrampalam et al. 2018). For molecular identification, the genomic DNA of the 2 isolates was extracted. The fragments of internal transcribed spacer (ITS), translation elongation factor 1α (EF1α) and ß-tubulin were amplified and sequened using the primer pairs of ITS4/ITS5, EF1/EF2 (O'Donnell et al. 2008) and T1/T2 (O'Donnell et al. 1997). These sequences were deposited in GenBank (OR501466, OR501467 for the ITS; OR499874, OR499875 for elongation factor; OR499876, OR499877 for ß-tubulin). Phylogenetic trees were constructed in MAGA 11 using the Maximum likelihood (ML) method based on the concatenated sequences of ITS, EF1α, and Tublin (Figure 1). The 2 isolates were grouped with F. solani A01-1 (GCA_027945525.1) with a bootstrap value of 100 in the phylogenetic tree. The morphology and multi-gene phylogenetic analysis indicated that the new isolates are F. solani. The 2 isolates were selected for pathogenicity tests to fulfill Koch's postulates. Six plants at seven- to ten-leaf stage were inoculated with each isolate separately. Three sites of each leaf were wounded with a sterile needle and covered with a piece of cotton drenched with 200 µl spore suspension (107 spores/ml) from each isolate cultured in PD medium. Leaves inoculated with PD medium served as negative controls. Inoculated plants were placed in an incubator at 28°C, and 80% humidity under a 12-h light/dark cycle for 7 days. After 7 days of incubation, necrotic spots were observed in all the inoculated plants except the negative control. The pathogenicity tests were conducted three times with similar results. The strains were then reisolated from the lesions and found to be Fusarium solani as those of the inoculum. F.ananatum, F. guttiforme and F. subglutinans have been reported to infect all parts of pineapplefusariosis disease (Jacobs et al. 2010; Stepien et al. 2013; Ventura et al. 1993). To our knowledge, this is the first report of fusariosis on Pineapple caused by F. solani. Identification of F. solani as a disease agent on pineapple will assist in disease management for this important fruit tree.

18.
Knee Surg Sports Traumatol Arthrosc ; 31(1): 86-93, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36242615

RESUMEN

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of the endoscopic-assisted locking block modified Krackow technique with a V-Y flap. The hypothesis was that the minimally invasive technique can reduce wound complications and facilitate early recovery. METHODS: In total, 29 men with chronic Achilles tendon rupture who underwent either minimally invasive technique (n = 13) or open repair (n = 16) at our department between 2013 and 2019 were retrospectively analyzed. The rate of complications, time to return to moderate-intensity exercise, American Orthopedic Foot and Ankle Society ankle hindfoot score, Achilles tendon Total Rupture Score, heel-rise repetitions in 1 min, heel-rise height, and bilateral calf circumference at 6 months, 1 year, and 2 years postoperatively were recorded. RESULTS: All incisions healed primarily in the minimally invasive technique group; however, three patients in the open repair group experienced wound complications. The time to return to moderate-intensity exercise, American Orthopedic Foot and Ankle Society score, Achilles tendon Total Rupture Score, heel-rise repetition ratio, and heel-rise height ratio at 6 months postoperatively in the minimally invasive technique group were significantly better than those in the open repair group. However, it was not significantly different between both groups at 2 years postoperatively. CONCLUSION: Endoscopy allowed scar tissue and adhesions to be removed, allowing the tendon ends to be mobilized out of the small proximal and distal incisions. Minimally invasive technique may result in a lower wound complication incidence and provide better early functional recovery and return to moderate-intensity exercise time than the conventional open procedure in treating chronic Achilles tendon ruptures. CLINICAL TRIAL REGISTRATION: Wuxi Ninth People's Hospital Medical Ethical Committee, LW2021026. LEVEL OF EVIDENCE: III.


Asunto(s)
Tendón Calcáneo , Traumatismos del Tobillo , Procedimientos Ortopédicos , Traumatismos de los Tendones , Masculino , Humanos , Resultado del Tratamiento , Tendón Calcáneo/cirugía , Estudios Retrospectivos , Procedimientos Ortopédicos/métodos , Rotura/cirugía , Técnicas de Sutura , Endoscopía , Traumatismos de los Tendones/cirugía , Traumatismos del Tobillo/cirugía , Enfermedad Crónica
19.
Angew Chem Int Ed Engl ; 62(19): e202300529, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-36892571

RESUMEN

Nowadays numerous thermally activated delayed fluorescence (TADF) polymers have been developed for PLEDs to realize high device performance and tunable emission colors. However, they often possess a strong concentration dependence on their luminescence including aggregation-caused quenching (ACQ) and aggregation-induced emission (AIE). Herein, we first report a nearly concentration-independent TADF polymer based on the strategy of polymerized TADF small molecules. It is found that when a donor-acceptor-donor (D-A-D) type TADF small molecule is polymerized through its long-axis direction, the triplet state is distributed along the polymeric backbone to effectively suppress the unwanted concentration quenching. Unlike the short-axis one with an ACQ effect, the photoluminescent quantum yield (PLQY) of the resultant long-axis polymer remains almost unchanged with the increasing doping concentration. Accordingly, a promising external quantum efficiency (EQE) up to 20 % is successfully achieved in a whole doping control window of 5-100 wt. %.

20.
Stroke ; 53(1): 7-16, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34915738

RESUMEN

BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82-1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62-1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77-1.64) for M1 occlusions, and 1.22 (95% CI, 0.53-2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03469206.


Asunto(s)
Trastornos Cerebrovasculares/terapia , Procedimientos Endovasculares/métodos , Fibrinolíticos/administración & dosificación , Trombectomía/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Administración Intravenosa , Anciano , Trastornos Cerebrovasculares/diagnóstico por imagen , Procedimientos Endovasculares/tendencias , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Trombectomía/tendencias , Resultado del Tratamiento
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