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1.
Bioinformatics ; 40(1)2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38175759

RESUMEN

MOTIVATION: Binding of peptides to major histocompatibility complex (MHC) molecules plays a crucial role in triggering T cell recognition mechanisms essential for immune response. Accurate prediction of MHC-peptide binding is vital for the development of cancer therapeutic vaccines. While recent deep learning-based methods have achieved significant performance in predicting MHC-peptide binding affinity, most of them separately encode MHC molecules and peptides as inputs, potentially overlooking critical interaction information between the two. RESULTS: In this work, we propose RPEMHC, a new deep learning approach based on residue-residue pair encoding to predict the binding affinity between peptides and MHC, which encode an MHC molecule and a peptide as a residue-residue pair map. We evaluate the performance of RPEMHC on various MHC-II-related datasets for MHC-peptide binding prediction, demonstrating that RPEMHC achieves better or comparable performance against other state-of-the-art baselines. Moreover, we further construct experiments on MHC-I-related datasets, and experimental results demonstrate that our method can work on both two MHC classes. These extensive validations have manifested that RPEMHC is an effective tool for studying MHC-peptide interactions and can potentially facilitate the vaccine development. AVAILABILITY: The source code of the method along with trained models is freely available at https://github.com/lennylv/RPEMHC.


Asunto(s)
Aprendizaje Profundo , Unión Proteica , Péptidos/química , Complejo Mayor de Histocompatibilidad , Antígenos de Histocompatibilidad Clase I/metabolismo
2.
Plant Physiol ; 195(1): 479-501, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38227428

RESUMEN

Flowering is an essential process in fruit trees. Flower number and timing have a substantial impact on the yield and maturity of fruit. Ethylene and gibberellin (GA) play vital roles in flowering, but the mechanism of coordinated regulation of flowering in woody plants by GA and ethylene is still unclear. In this study, a lemon (Citrus limon L. Burm) 1-aminocyclopropane-1-carboxylic acid synthase gene (CiACS4) was overexpressed in Nicotiana tabacum and resulted in late flowering and increased flower number. Further transformation of citrus revealed that ethylene and starch content increased, and soluble sugar content decreased in 35S:CiACS4 lemon. Inhibition of CiACS4 in lemon resulted in effects opposite to that of 35S:CiACS4 in transgenic plants. Overexpression of the CiACS4-interacting protein ETHYLENE RESPONSE FACTOR3 (CiERF3) in N. tabacum resulted in delayed flowering and more flowers. Further experiments revealed that the CiACS4-CiERF3 complex can bind the promoters of FLOWERING LOCUS T (CiFT) and GOLDEN2-LIKE (CiFE) and suppress their expression. Moreover, overexpression of CiFE in N. tabacum led to early flowering and decreased flowers, and ethylene, starch, and soluble sugar contents were opposite to those in 35S:CiACS4 transgenic plants. Interestingly, CiFE also bound the promoter of CiFT. Additionally, GA3 and 1-aminocyclopropanecarboxylic acid (ACC) treatments delayed flowering in adult citrus, and treatment with GA and ethylene inhibitors increased flower number. ACC treatment also inhibited the expression of CiFT and CiFE. This study provides a theoretical basis for the application of ethylene to regulate flower number and mitigate the impacts of extreme weather on citrus yield due to delayed flowering.


Asunto(s)
Citrus , Etilenos , Flores , Regulación de la Expresión Génica de las Plantas , Giberelinas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Giberelinas/metabolismo , Citrus/genética , Citrus/fisiología , Citrus/crecimiento & desarrollo , Flores/genética , Flores/fisiología , Flores/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Etilenos/metabolismo , Nicotiana/genética , Nicotiana/fisiología , Nicotiana/crecimiento & desarrollo , Liasas/metabolismo , Liasas/genética
3.
Nano Lett ; 24(1): 402-410, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38153842

RESUMEN

The ability of drugs to cross the blood-brain barrier (BBB) is crucial for treating central nervous system (CNS) disorders. Inspired by natural viruses, here we report a glucose and polydopamine (GPDA) coating method for the construction of delivery platforms for efficient BBB crossing. Such platforms are composed of nanoparticles (NPs) as the inner core and surface functionalized with glucose-poly(ethylene glycol) (Glu-PEG) and polydopamine (PDA) coating. Glu-PEG provides selective targeting of the NPs to brain capillary endothelial cells (BCECs), while PDA enhances the transcytosis of the NPs. This strategy is applicable to gold NPs (AuNPs), silica, and polymeric NPs, which achieves as high as 1.87% of the injected dose/g of brain in healthy brain tissues. In addition, the GPDA coating manages to deliver NPs into the tumor tissue in the orthotopic glioblastoma model. Our study may provide a universal strategy for the construction of delivery platforms for efficient BBB crossing and brain drug delivery.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Células Endoteliales , Oro/farmacología , Encéfalo , Sistemas de Liberación de Medicamentos/métodos
4.
J Am Chem Soc ; 146(36): 25016-25027, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39213506

RESUMEN

Developing the topochemical polymerization of metal-organic frameworks (MOFs) is of pronounced significance for expanding their functionalities but is still a challenge on third-order nonlinear optics (NLO). Here, we report diacetylene MOF (CAS-1-3) films prepared using a stepwise deposition method and film structural transformation approach, featuring dynamic structural diversity. The MOF structures were determined by the three-dimensional electron diffraction (3D ED) method from nanocrystals collected from the films, which provides a reliable strategy for determining the precise structure of unknown MOF films. We demonstrate the well-aligned diacetylene groups in the MOFs can promote topological polymerization to produce a highly conjugated system under thermal stimulation. As a result, the three MOF films have distinct NLO properties: the CAS-1 film exhibits saturable absorption (SA) while CAS-2 and CAS-3 films exhibit reverse saturable absorption (RSA). Interestingly, due to the topochemical polymerization of the MOF films, a transition from SA to RSA response was observed with increasing temperatures, and the optical limiting effect was significantly enhanced (∼46 times). This study provides a new strategy for preparing NLO materials and thermally regulation of nonlinear optics.

5.
J Am Chem Soc ; 146(23): 16213-16221, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38814730

RESUMEN

Combining metal-organic frameworks (MOFs) with liquid crystals to construct liquid crystalline MOFs (LCMOF) offers the advantage of endowing and enhancing their functionality, yet it remains a challenging task. Herein, we report chiral liquid crystalline MOF (CLCMOF) thin films by cross-linking the chiral liquid crystals (CLC) with MOF thin films to realize highly circular polarization luminescence (CPL) performance with photo and thermal switching. By layer by layer cross-linking stilbene-containing CLC with stilbene-based MOF (CLC/MOF) thin film, the CLCMOF thin films were successfully obtained after UV irradiation due to the abundant [2 + 2] photocycloaddition. The resulted CLCMOF thin films have strong chirality, obvious photochromic fluorescent, and strong CPL performance (the asymmetry factor reaches to 0.4). Furthermore, due to the photochromic fluorescent MOF and thermotropic CLC, the CPL can be reversed and red-shifted after heating and UV irradiation treatment, showing photo- and thermal CPL switching. Such MOF-based CPL thin films with photo/thermal CPL switching were prepared to patterns and codes for the demonstration of potential application in advanced information anticounterfeit and encryption. This study not only opens a strategy for developing chiral thin films combining MOFs and liquid crystals but also offers a new route to achieve CPL switching in optical applications.

6.
J Am Chem Soc ; 146(7): 4652-4664, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38265705

RESUMEN

Since sodium-ion batteries (SIBs) have become increasingly commercialized in recent years, Na3V2(PO4)2O2F (NVPOF) offers promising economic potential as a cathode for SIBs because of its high operating voltage and energy density. According to reports, NVPOF performs poorly in normal commercial poly(vinylidene fluoride) (PVDF) binder systems and performs best in combination with aqueous binder. Although in line with the concept of green and sustainable development for future electrode preparation, aqueous binders are challenging to achieve high active material loadings at the electrode level, and their relatively high surface tension tends to cause the active material on the electrode sheet to crack or even peel off from the collector. Herein, a cross-linkable and easily commercial hybrid binder constructed by intermolecular hydrogen bonding (named HPP) has been developed and utilized in an NVPOF system, which enables the generation of a stable cathode electrolyte interphase on the surface of active materials. According to theoretical simulations, the HPP binder enhances electronic/ionic conductivity, which greatly lowers the energy barrier for Na+ migration. Additionally, the strong hydrogen-bond interactions between the HPP binder and NVPOF effectively prevent electrolyte corrosion and transition-metal dissolution, lessen the lattice volume effect, and ensure structural stability during cycling. The HPP-based NVPOF offers considerably improved rate capability and cycling performance, benefiting from these benefits. This comprehensive binder can be extended to the development of next-generation energy storage technologies with superior performance.

7.
J Am Chem Soc ; 146(32): 22335-22347, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39092859

RESUMEN

Searching for high energy-density electrode materials for sodium ion batteries has revealed Na-deficient intercalation compounds with lattice oxygen redox as promising high-capacity cathodes. However, anionic redox reactions commonly encountered poor electrochemical reversibility and unfavorable structural transformations during dynamic (de)sodiation processes. To address this issue, we employed lithium orbital hybridization chemistry to create Na-O-Li configuration in a prototype P2-layered Na43/60Li1/20Mg7/60Cu1/6Mn2/3O2 (P2-NaLMCM') cathode material. That Li+ ions, having low electronegativity, reside in the transition metal slabs serves to stimulate unhybridized O 2p orbitals to facilitate the stable capacity contribution of oxygen redox at high state of charge. The prismatic-type structure evolving to an intergrowth structure of the Z phase at high charging state could be simultaneously alleviated by reducing the electrostatic repulsion of O-O layers. As a consequence, P2-NaLMCM' delivers a high specific capacity of 183.8 mAh g-1 at 0.05 C and good cycling stability with a capacity retention of 80.2% over 200 cycles within the voltage range of 2.0-4.5 V. Our findings provide new insights into both tailoring oxygen redox chemistry and stabilizing dynamic structural evolution for high-energy battery cathode materials.

8.
Breast Cancer Res ; 26(1): 27, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347651

RESUMEN

BACKGROUND: A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. METHODS: In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. RESULTS: The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. CONCLUSIONS: CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Ultrasonografía Mamaria , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Biopsia con Aguja Gruesa
9.
Bioinformatics ; 39(2)2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36688724

RESUMEN

MOTIVATION: Accurate and rapid prediction of protein-ligand binding affinity is a great challenge currently encountered in drug discovery. Recent advances have manifested a promising alternative in applying deep learning-based computational approaches for accurately quantifying binding affinity. The structure complementarity between protein-binding pocket and ligand has a great effect on the binding strength between a protein and a ligand, but most of existing deep learning approaches usually extracted the features of pocket and ligand by these two detached modules. RESULTS: In this work, a new deep learning approach based on the cross-attention mechanism named CAPLA was developed for improved prediction of protein-ligand binding affinity by learning features from sequence-level information of both protein and ligand. Specifically, CAPLA employs the cross-attention mechanism to capture the mutual effect of protein-binding pocket and ligand. We evaluated the performance of our proposed CAPLA on comprehensive benchmarking experiments on binding affinity prediction, demonstrating the superior performance of CAPLA over state-of-the-art baseline approaches. Moreover, we provided the interpretability for CAPLA to uncover critical functional residues that contribute most to the binding affinity through the analysis of the attention scores generated by the cross-attention mechanism. Consequently, these results indicate that CAPLA is an effective approach for binding affinity prediction and may contribute to useful help for further consequent applications. AVAILABILITY AND IMPLEMENTATION: The source code of the method along with trained models is freely available at https://github.com/lennylv/CAPLA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Aprendizaje Profundo , Ligandos , Proteínas/química , Unión Proteica , Programas Informáticos
10.
Plant Physiol ; 192(3): 1947-1968, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-36913259

RESUMEN

Dwarfism is an agronomic trait that has substantial effects on crop yield, lodging resistance, planting density, and a high harvest index. Ethylene plays an important role in plant growth and development, including the determination of plant height. However, the mechanism by which ethylene regulates plant height, especially in woody plants, remains unclear. In this study, a 1-aminocyclopropane-1-carboxylic acid synthase (ACC) gene (ACS), which is involved in ethylene biosynthesis, was isolated from lemon (Citrus limon L. Burm) and named CiACS4. Overexpression of CiACS4 resulted in a dwarf phenotype in Nicotiana tabacum and lemon and increased ethylene release and decreased gibberellin (GA) content in transgenic plants. Inhibition of CiACS4 expression in transgenic citrus significantly increased plant height compared with the controls. Yeast two-hybrid assays revealed that CiACS4 interacted with an ethylene response factor (ERF), CiERF3. Further experiments revealed that the CiACS4-CiERF3 complex can bind to the promoters of 2 citrus GA20-oxidase genes, CiGA20ox1 and CiGA20ox2, and suppress their expression. In addition, another ERF transcription factor, CiERF023, identified using yeast one-hybrid assays, promoted CiACS4 expression by binding to its promoter. Overexpression of CiERF023 in N. tabacum caused a dwarfing phenotype. CiACS4, CiERF3, and CiERF023 expression was inhibited and induced by GA3 and ACC treatments, respectively. These results suggest that the CiACS4-CiERF3 complex may be involved in the regulation of plant height by regulating CiGA20ox1 and CiGA20ox2 expression levels in citrus.


Asunto(s)
Citrus , Giberelinas , Giberelinas/farmacología , Giberelinas/metabolismo , Citrus/genética , Citrus/metabolismo , Etilenos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
11.
Nitric Oxide ; 145: 33-40, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38382866

RESUMEN

OBJECTIVE: Hydrogen sulfide (H2S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H2S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function. METHODS: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H2S and Hcy, and data were correlated to determine their potential as plasma biomarkers. RESULTS: Cross-sectional analyses revealed PSDs to have a low plasma H2S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H2S and Hcy in PSDs. Plasma levels of H2S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H2S and Hcy and expression of the TNF gene (i.e., H2S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents. CONCLUSION: Plasma levels of H2S and Hcy reflect changes in psychopathology and cognitive function in depression and H2S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.


Asunto(s)
Sulfuro de Hidrógeno , Humanos , Sulfuro de Hidrógeno/metabolismo , Estudios Transversales , Homocisteína
12.
J Org Chem ; 89(18): 12924-12934, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39197148

RESUMEN

The asymmetric cycloaddition between N-2,2,2-trifluoroethylisatin ketimines and unsymmetrical dicarbonyl-activated alkenes catalyzed by a bifunctional squaramide has been discovered. The present study demonstrates an efficient approach for the regio-, diastereo-, and enantioselective synthesis of densely functionalized 5'-trifluoromethylated 3,2'-pyrrolidinyl spirooxindoles featuring three different types of carbonyl groups.

13.
Inorg Chem ; 63(2): 1499-1506, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38175964

RESUMEN

Three hydrophobic porphyrin titanium-based metal-organic frameworks (MOFs) (HPA/DGIST-1, DPA/DGIST-1, and OPA/DGIST-1) were synthesized through a postsynthetic coordination reaction by using alkylphosphonic acid of different lengths (HPA, hexylphosphonic acid; DPA, dodecylphosphonic acid; OPA, octadecylphosphonic acid). Compared with the hydrophilic DGIST-1, modified DGIST-1 exhibits excellent hydrophobicity and presents good stability in humid atmospheres. Due to the introduction of porphyrin ligands, HPA/DGIST-1, DPA/DGIST-1, and OPA/DGIST-1 showed good visible-light absorption (380-700 nm) and sensitive photogenerated charge responses. When acted as catalysts, these hydrophobic Ti-MOFs can selectively reduce CO2 to HCOO- under visible-light irradiation with average reaction rates of 150.9, 178.5, and 228.3 µmol·h-1·g-1, where these values are 1.3-2.0 times higher than the system mediated by the initial porphyrin Ti-MOF catalyst. 13C NMR spectroscopy demonstrates that the catalytic product HCOO- anion originates from the reactant CO2. The photocatalytic experiments, electron paramagnetic resonance, and photoluminescence spectra tests showed that porphyrin ligands and Ti-O units can act as catalytic activity centers to realize the conversion of CO2 to HCOO-. This work demonstrated that the combination of porphyrin titanium-based MOF and alkyl hydrophobic groups is an effective way to enhance the stability of titanium-based MOFs and maintain their high photocatalytic performance.

14.
Int J Colorectal Dis ; 39(1): 140, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39266810

RESUMEN

BACKGROUND: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD). METHODS: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients. RESULTS: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor. CONCLUSION: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Trastornos del Sueño-Vigilia , Humanos , Masculino , Femenino , Factores de Riesgo , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/complicaciones , Prevalencia , Estudios Transversales , Adulto , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Persona de Mediana Edad , Estudios de Casos y Controles , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Análisis Multivariante , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Calidad del Sueño
15.
Future Oncol ; : 1-6, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39378048

RESUMEN

Large type 3 and type 4 gastric cancers (GC) have a significantly poor prognosis, primarily due to their high predisposition for peritoneal dissemination. The application of intraperitoneal chemotherapy has emerged as a viable therapeutic strategy for managing GC patients with peritoneal metastasis. This study is planned to enroll 37 resectable large type 3 or type 4 GC patients. These patients are scheduled to undergo a treatment comprising preoperative chemotherapy with paclitaxel, oxaliplatin and S-1, followed by D2 gastrectomy, and concluding with postoperative treatments that include prophylactic intraperitoneal chemotherapy. The study's primary objective is to evaluate the 3-year peritoneal recurrence rate. Secondary objectives are to assess the 3-year disease-free survival, 3-year overall survival and to monitor the adverse events.Clinical trial registration number: ChiCTR2400083253 (https://www.chictr.org.cn).


Gastric cancer (GC), specifically the large type 3 and type 4 kinds, is a serious health condition that often leads to a very poor chance of survival. This is mainly because these types of cancer easily spread to the lining of the abdomen, a process known as peritoneal dissemination. One way to tackle this issue is through a treatment known as intraperitoneal chemotherapy, which directly targets the abdominal lining to kill cancer cells. In our study, 37 resectable large type 3 and type 4 GC patients will receive a combination of chemotherapy drugs before undergoing surgery to remove the cancer. After surgery, they will receive additional treatment that combines chemotherapy into the abdomen with standard chemotherapy. The main goal of our study is to see if this treatment approach can reduce the chance of cancer returning to the abdominal lining within 3 years. We are also looking at how long patients remain free from cancer, their overall survival after 3 years, and any side effects they may experience from the treatment. This study aims to provide a clearer understanding of how effective this combined treatment is for patients with these aggressive types of GC, with the hope of improving their chances of survival and quality of life.

16.
Acta Pharmacol Sin ; 45(1): 166-179, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37605050

RESUMEN

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.


Asunto(s)
Neovascularización de la Córnea , Síndromes de Ojo Seco , Ratas , Humanos , Ratones , Animales , Femenino , Neovascularización de la Córnea/tratamiento farmacológico , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Roedores/metabolismo , Células Endoteliales/metabolismo , Angiogénesis , Inflamación/tratamiento farmacológico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/inducido químicamente , Factor de Transcripción STAT3/metabolismo
17.
Plant Dis ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320370

RESUMEN

Pantoea ananatis is a bacterium commonly found in various agronomic crops and agricultural pests. In this study, we present findings on a genome-reduced strain of P. ananatis, known as Lstr, which was initially isolated from Laodelphax striatellus (small brown rice planthopper, SBPH). We identified Lstr as a plant pathogen causing disease in rice using Koch's postulates. The pathogenicity of Lstr on rice is comparable to that of Xanthomonas oryzae pv. oryzae, the main causative agent of rice bacterial blight. Through a series of experiments involving live insects, molecular investigations, and microscopy, we find that Lstr can accumulate within SBPH. Subsequently, Lstr can be transmitted from SBPH to rice plants, resulting in leaf blight, and can also be transmitted to other SBPH individuals. Collectively, our results suggest that SBPH serves as a vector for P. ananatis Lstr in rice plants. P. ananatis may encounter susceptible insect populations and become endemic through horizontal transmission from these insects. This could also be valuable for predicting future occurrences of bacterial leaf blight in rice and other crops caused by P. ananatis.

18.
Nano Lett ; 23(5): 1904-1913, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36801829

RESUMEN

Cancer vaccines have received tremendous attention in cancer immunotherapy due to their capability to induce a tumor-specific immune response. However, their effectiveness is compromised by the insufficient spatiotemporal delivery of antigens and adjuvants in the subcellular level to induce a robust CD8+ T cell response. Herein, a cancer nanovaccine G5-pBA/OVA@Mn is prepared through multiple interactions of manganese ions (Mn2+), benzoic acid (BA)-modified fifth generation polyamidoamine (G5-PAMAM) dendrimer, and the model protein antigen ovalbumin (OVA). In the nanovaccine, Mn2+ not only exerts a structural function to assist OVA loading as well as its endosomal escape, but works as an adjuvant of stimulator of interferon genes (STING) pathway. These collaboratively facilitate the orchestrated codelivery of OVA antigen and Mn2+ into cell cytoplasm. Vaccination with G5-pBA/OVA@Mn not only shows a prophylactic effect, but also significantly inhibits growth against B16-OVA tumors, indicating its great potential for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Humanos , Animales , Ratones , Manganeso , Antígenos , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias/terapia , Inmunoterapia , Ratones Endogámicos C57BL , Nanopartículas/química , Células Dendríticas
19.
Molecules ; 29(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38931000

RESUMEN

Microbial fuel cells (MFCs) have the potential to directly convert the chemical energy in organic matter into electrical energy, making them a promising technology for achieving sustainable energy production alongside wastewater treatment. However, the low extracellular electron transfer (EET) rates and limited bacteria loading capacity of MFCs anode materials present challenges in achieving high power output. In this study, three-dimensionally heteroatom-doped carbonized grape (CG) monoliths with a macroporous structure were successfully fabricated using a facile and low-cost route and employed as independent anodes in MFCs for treating brewery wastewater. The CG obtained at 900 °C (CG-900) exhibited excellent biocompatibility. When integrated into MFCs, these units initiated electricity generation a mere 1.8 days after inoculation and swiftly reached a peak output voltage of 658 mV, demonstrating an exceptional areal power density of 3.71 W m-2. The porous structure of the CG-900 anode facilitated efficient ion transport and microbial community succession, ensuring sustained operational excellence. Remarkably, even when nutrition was interrupted for 30 days, the voltage swiftly returned to its original level. Moreover, the CG-900 anode exhibited a superior capacity for accommodating electricigens, boasting a notably higher abundance of Geobacter spp. (87.1%) compared to carbon cloth (CC, 63.0%). Most notably, when treating brewery wastewater, the CG-900 anode achieved a maximum power density of 3.52 W m-2, accompanied by remarkable treatment efficiency, with a COD removal rate of 85.5%. This study provides a facile and low-cost synthesis technique for fabricating high-performance MFC anodes for use in microbial energy harvesting.


Asunto(s)
Fuentes de Energía Bioeléctrica , Electrodos , Vitis , Aguas Residuales , Fuentes de Energía Bioeléctrica/microbiología , Aguas Residuales/química , Aguas Residuales/microbiología , Vitis/química , Purificación del Agua/métodos , Porosidad , Electricidad
20.
J Sci Food Agric ; 104(7): 4015-4027, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38294304

RESUMEN

BACKGROUND: The bacteriocins, particularly derived from lactic acid bacteria, currently exhibit potential as a promising food preservative owing to their low toxicity and potent antimicrobial activity. This study aimed to evaluate the efficacy of lactocin 63, produced by Lactobacillus coryniformis, in inhibiting the deterioration of Lateolabrax japonicas during chilled storage, while also investigating its underlying inhibitory mechanism. The measurement of total viable count, biogenic amines, and volatile organic compounds were conducted, along with high-throughput sequencing and sensory evaluation. RESULTS: The findings demonstrated that treatment with lactocin 63 resulted in a notable retardation of bacterial growth in L. japonicas fish fillet during refrigerated storage compared with the water-treated and nisin-treated groups. Moreover, lactocin 63 effectively maintained the microbial flora balance in the fish fillet and inhibited the proliferation and metabolic activity of specific spoilage microorganisms, particularly Shewanella, Pseudomonas, and Acinetobacter. Furthermore, the production of unacceptable volatile organic compounds (e.g. 1-octen-3-ol, hexanal, nonanal), as well as the biogenic amines derived from the bacterial metabolism, could be hindered, thus preventing the degradation in the quality of fish fillets and sustaining relatively high sensory quality. CONCLUSION: The results of this study provide valuable theoretical support for the development and application of lactocin 63, or other bacteriocins derived from lactic acid bacteria, as potential bio-preservatives in aquatic food. © 2024 Society of Chemical Industry.


Asunto(s)
Bacteriocinas , Compuestos Orgánicos Volátiles , Animales , Compuestos Orgánicos Volátiles/farmacología , Bacteriocinas/farmacología , Conservantes de Alimentos/farmacología , Conservantes de Alimentos/química , Peces , Aminas Biogénicas/análisis , Almacenamiento de Alimentos/métodos , Conservación de Alimentos/métodos , Microbiología de Alimentos
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