Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 135
Filtrar
1.
Sci Rep ; 14(1): 23879, 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39396096

RESUMEN

Hyperspectral image (HSI) data has a wide range of valuable spectral information for numerous tasks. HSI data encounters challenges such as small training samples, scarcity, and redundant information. Researchers have introduced various research works to address these challenges. Convolution Neural Network (CNN) has gained significant success in the field of HSI classification. CNN's primary focus is to extract low-level features from HSI data, and it has a limited ability to detect long-range dependencies due to the confined filter size. In contrast, vision transformers exhibit great success in the HSI classification field due to the use of attention mechanisms to learn the long-range dependencies. As mentioned earlier, the primary issue with these models is that they require sufficient labeled training data. To address this challenge, we proposed a spectral-spatial feature extractor group attention transformer that consists of a multiscale feature extractor to extract low-level or shallow features. For high-level semantic feature extraction, we proposed a group attention mechanism. Our proposed model is evaluated using four publicly available HSI datasets, which are Indian Pines, Pavia University, Salinas, and the KSC dataset. Our proposed approach achieved the best classification results in terms of overall accuracy (OA), average accuracy (AA), and Kappa coefficient. As mentioned earlier, the proposed approach utilized only 5%, 1%, 1%, and 10% of the training samples from the publicly available four datasets.

3.
Sci Rep ; 14(1): 26068, 2024 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-39478132

RESUMEN

Medical image machines serve as a valuable tool to monitor and diagnose a variety of diseases. However, manual and centralized interpretation are both error-prone and time-consuming due to malicious attacks. Numerous diagnostic algorithms have been developed to improve precision and prevent poisoning attacks by integrating symptoms, test methods, and imaging data. But in today's digital technology world, it is necessary to have a global cloud-based diagnostic artificial intelligence model that is efficient in diagnosis and preventing poisoning attacks and might be used for multiple purposes. We propose the Healthcare Federated Ensemble Internet of Learning Cloud Doctor System (FDEIoL) model, which integrates different Internet of Things (IoT) devices to provide precise and accurate interpretation without poisoning attack problems, thereby facilitating IoT-enabled remote patient monitoring for smart healthcare systems. Furthermore, the FDEIoL system model uses a federated ensemble learning strategy to provide an automatic, up-to-date global prediction model based on input local models from the medical specialist. This assures biomedical security by safeguarding patient data and preserving the integrity of diagnostic processes. The FDEIoL system model utilizes local model feature selection to discriminate between malicious and non-malicious local models, and ensemble strategies use positive and negative samples to optimize the performance of the test dataset, enhancing its capability for remote patient monitoring. The FDEIoL system model achieved an exceptional accuracy rate of 99.24% on the Chest X-ray dataset and 99.0% on the MRI dataset of brain tumors compared to centralized models, demonstrating its ability for precision diagnosis in IoT-enabled healthcare systems.


Asunto(s)
Nube Computacional , Internet de las Cosas , Humanos , Algoritmos , Aprendizaje Automático , Atención a la Salud , Monitoreo Fisiológico/métodos , Internet , Seguridad Computacional , Inteligencia Artificial
4.
J Am Chem Soc ; 146(32): 22180-22192, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39087925

RESUMEN

Metal nanoclusters (NCs) hold great promise for expressing multipeak emission based on their well-defined total structure with diverse luminescent centers. Herein, we report the surface motif-dictated triple phosphorescence of Au NCs with dynamic color turning. The deprotonation-triggered isomerization of terminal thiouracils can evolve into a mutual transformation among their hierarchical motifs, thus serving a multipeak-emission expression with good tailoring. More importantly, the underlying electron transfer is thoroughly identified by excluding the radiative and nonradiative energy transfer, where electrons flow from the first phosphorescent state to the last two ones. The findings shed light on finely tailing motifs at the molecular level to motivate studies on customizable luminescence characteristics of metal NCs.

5.
J Plant Physiol ; 302: 154317, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39068773

RESUMEN

Common vetch (Vicia sativa L.) is widely planted as forage, green manure and food. Phosphate (Pi) deficiency is an important constraint for legume crop production. In this study, P-deficiency tolerance in 40 common vetch collections was evaluated under hydroponic condition. The collections were clustered into three groups based on the tolerance level. Physiological responses to P-deficiency in two tolerant collections (418 and 426) in comparison with one sensitive collection (415) were investigated. Greater growth inhibition was observed in sensitive collection compared with two tolerant collections, although the inorganic phosphorus (P) content in sensitive collection was higher than those in tolerant collections. The internal and external purple acid phosphatase activity in plants showed no significant difference between 418 and 415 under low phosphate condition. Transcriptomic analysis in the tolerant collection 426 in response to Pi starvation showed that many common adaptive strategies were applied and PHOSPHATE STARVATION RESPONSE (PHR)-related Pi signaling and transporter genes were altered. VsPHT1.2 had the highest expression level in root among all VsPHT1s, and it was remarkably upregulated after short time of P-deficiency treatment in tolerant collections compared with sensitive collection. In conclusion, common vetch response to P starvation by altering the expressions of core genes involved in Pi transport and signaling, and the elevated expression of VsPHT1.2 gene might contribute to higher Pi acquisition efficiency in P-deficiency tolerant collections.


Asunto(s)
Adaptación Fisiológica , Fosfatos , Fosfatos/deficiencia , Fosfatos/metabolismo , Adaptación Fisiológica/genética , Regulación de la Expresión Génica de las Plantas , Fósforo/deficiencia , Fósforo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
6.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(4): 401-410, 2024 Aug 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39034143

RESUMEN

OBJECTIVES: To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds. METHODS: Clinical data of 38 patients with large limb surface wound (11 cm×39 cm-16 cm×65 cm) admitted to the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed. Eighteen patients were treated by anterolateral thigh perforator flap combined with superficial circumflex iliac artery flap (ALTP-SCIAP) with turbocharge technique (interregional flap group); while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps, combined with skin grafting if necessary (traditional anterolateral femoral flap group). The survival of skin flap, repair of donor area, complications and patient satisfaction were compared between the two groups. RESULTS: In interregional flap group, 18 flaps were harvested and transplanted, the flap width, length and the viable area were (9.9±2.0) cm, (44.2±3.5) cm and (343.2±79.9) cm2, respectively. In traditional anterolateral femoral flap group, 29 flaps were harvested and transplanted, the flap width, length and the viable area were (11.0±2.8) cm, (21.7±3.2) cm and (186.4±49.2) cm2, respectively. There were significant differences in the flap length and the viable area between the two groups (t=22.365 and 8.345, both P<0.05). In the interregional flap group, the donor site of flap was closed by direct suture in 11 flaps, by skin retractor assisted suture in 6 flaps, and by skin grafting in one flap. In traditional anterolateral femoral flap group, the donor site of flap was closed by direct suture in 12 flaps, by skin retractor assisted suture in 11 flaps, and by skin grafting in 6 flaps. The skin graft rates of the two groups were 5.6% (1/18) and 20.7% (6/29), respectively (χ2=2.007, P>0.05). The interregional flap group had lower postoperative complications rate (5.6% vs. 35.0%, χ2=4.942, P<0.05) and higher patient satisfaction rate (94.4% vs. 70.0%, χ2=4.448, P<0.05) than traditional anterolateral femoral flap group. CONCLUSIONS: Compared with the traditional anterolateral femoral flap, the anterolateral femoral interregional flap with turbocharge technique has a larger flap area, most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.


Asunto(s)
Colgajo Perforante , Procedimientos de Cirugía Plástica , Trasplante de Piel , Colgajos Quirúrgicos , Humanos , Estudios Retrospectivos , Trasplante de Piel/métodos , Procedimientos de Cirugía Plástica/métodos , Masculino , Femenino , Satisfacción del Paciente , Fémur/cirugía , Muslo/cirugía , Arteria Ilíaca/cirugía , Cicatrización de Heridas , Persona de Mediana Edad , Adulto
7.
Sci Bull (Beijing) ; 69(17): 2756-2764, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39054158

RESUMEN

Extreme drought events have increased, causing serious losses and damage to the social economy under current warming conditions. However, short-term meteorological data limit our understanding and projection of these extremes. With the accumulation of proxy data, especially tree-ring data, large-scale precipitation field reconstruction has provided opportunities to explore underlying mechanisms further. Using point-by-point regression, we reconstructed the April-September precipitation field in China for the past ∼530 years on the basis of 590 proxy records, including 470 tree-ring width chronologies and 120 drought/flood indices. Our regression models explained average 50% of the variance in precipitation. In the statistical test on calibration and verification, our models passed the significance level that assured reconstruction quality. The reconstruction data performed well, showing consistency and better quality than previously reported reconstructions. The first three leading modes of variability in the reconstruction revealed the main distribution modes of precipitation over China. Wet/drought and extremely wet/drought years accounted for 12.81%/10.92% (68 years/58 years) and 1.69%/3.20% (9 years/17 years) of the past ∼530 years in China, respectively. Major extreme drought events can be identified explicitly in our reconstruction. The detailed features of the Chongzhen Great Drought (1637-1643), the Wanli Great Drought (1585-1590), and the Ding-Wu Great Famine (1874-1879), indicated the existence of potentially different underlying mechanisms that need further exploration. Although further improvements can be made for remote uninhabited areas and large deserts, our gridded reconstruction of April-September precipitation in China over the past ∼530 years can provide a solid database for studies on the attribution of climate change and the mechanism of extreme drought events.

8.
J Control Release ; 370: 821-834, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38740092

RESUMEN

The poor outcome of glioblastoma multiforme (GBM) treated with immunotherapy is attributed to the profound immunosuppressive tumor microenvironment (TME) and the lack of effective delivery across the blood-brain barrier. Radiation therapy (RT) induces an immunogenic antitumor response that is counteracted by evasive mechanisms, among which transforming growth factor-ß (TGF-ß) activation is the most prominent factor. We report an extracellular vesicle (EV)-based nanotherapeutic that traps TGF-ß by expressing the extracellular domain of the TGF-ß type II receptor and targets GBM by decorating the EV surface with RGD peptide. We show that short-burst radiation dramatically enhanced the targeting efficiency of RGD peptide-conjugated EVs to GBM, while the displayed TGF-ß trap reversed radiation-stimulated TGF-ß activation in the TME, offering a synergistic effect in the murine GBM model. The combined therapy significantly increased CD8+ cytotoxic T cells infiltration and M1/M2 macrophage ratio, resulting in the regression of tumor growth and prolongation of overall survival. These results provide an EV-based therapeutic strategy for immune remodeling of the GBM TME and eradication of therapy-resistant tumors, further supporting its clinical translation.


Asunto(s)
Neoplasias Encefálicas , Vesículas Extracelulares , Glioblastoma , Factor de Crecimiento Transformador beta , Microambiente Tumoral , Glioblastoma/terapia , Animales , Humanos , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Oligopéptidos/química , Oligopéptidos/administración & dosificación , Ratones Endogámicos C57BL , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Ratones , Femenino
9.
Cancer Res Commun ; 4(5): 1363-1368, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38709066

RESUMEN

PURPOSE: Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously. EXPERIMENTAL DESIGN: We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA. RESULTS: Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of 18.3 months and overall survival not-yet-reached with median duration of follow-up of 40 months. These survival intervals were significantly longer relative to a clinically and molecularly matched synthetic control cohort treated with cytotoxic chemotherapy designed for colorectal cancer (PFS of 4.4 months, P = 0.041). CONCLUSIONS: In light of recent data demonstrating a lack of efficacy of 5-fluorouracil-based chemotherapy, Atezo+Bev is a promising treatment option for patients with low-grade unresectable AA; further study is warranted. SIGNIFICANCE: AA remains an orphan disease with limited systemic therapy options for patients who are not candidates for surgical resection. These data suggest activity from combined VEGF and PD-L1 inhibition that warrants further study.


Asunto(s)
Adenocarcinoma , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Apéndice , Bevacizumab , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/efectos adversos , Bevacizumab/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Anciano , Neoplasias del Apéndice/tratamiento farmacológico , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/mortalidad , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años
10.
Water Res ; 257: 121714, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38723357

RESUMEN

Membrane breakage can lead to filtration failure, which allows harmful substances to enter the effluent, posing potential hazards to human health and the environment. This study is an innovative combination of fluorescence and ultraviolet-visible (UV-Vis) spectroscopy to identify membrane breakage. It aims to unravel more comprehensive information, improve detection sensitivity and selectivity, and enable real-time monitoring capabilities. Fluorescence and UV-Vis data are extracted through variance partitioning analysis (VPA) and integrated through a decision tree algorithm to form a superior system with enhanced discrimination capabilities. VPA improves discrimination efficiency by extracting key information from spectral data and eliminating redundancy. The decision tree algorithm, on the other hand, can process large amounts of data simultaneously. In addition, the method has a wide range of applications and can be used in various scenarios accurately. The scenarios include domestic sewage, micropollutant water, aquaculture wastewater, and secondary treated sewage. The experimental results validate the application of machine learning classifiers in membrane breakage detection with an accuracy rate of 96.8 % to 97.4 %.


Asunto(s)
Aprendizaje Automático , Membranas Artificiales , Filtración , Espectrometría de Fluorescencia , Aguas Residuales , Aguas del Alcantarillado , Algoritmos , Espectrofotometría Ultravioleta , Contaminantes Químicos del Agua/análisis
11.
Int J Biometeorol ; 68(8): 1545-1558, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38656351

RESUMEN

The Hindu Kush high-altitude regions of Pakistan are currently experiencing severe consequences as a result of global warming. In this sense, increasing soil erosion and the quick melting of glaciers are two particularly evident effects. In such a scenario, understanding long-term temperature changes is crucial for making accurate forecasts about how the Hindu Kush region may experience regional temperature changes in the future. In this study, the climate tree-ring width (TRW) analysis designated a positive and significant correlation (r = 0.622, p < 0.001) between the TRW chronology and the June to September (summer) mean maximum temperature (MMT). Using the tree-ring width of Pinus wallichiana A. B. Jackson, we reconstructed summer temperatures in the Hindu Kush region from 1790 CE. Statistical analysis showed that the reconstruction model has explained 38.7% of the climate variance during the instrumental period of 1967 to 2018 CE. Five extremely warm summer periods (≥ 4 years; before the instrumental period 1967-2018 CE) of 1804-1830, 1839-1862, 1876-1879, 1905-1910, 1923-1935 CE, and six cold summer periods of 1790-1803, 1832-1838, 1863-1875, 1880-1904, 1911-1922, and 1936-1945 CE have been observed during the past 229 years. Individually, the year 1856 CE experienced severe warmth (31.85 °C), whereas 1794 CE was relatively cooler (29.60 °C). The spectral multi-taper method (MTM) shows significant (p < 0.05) cycles, which take place about every 9.3, 5.7, 4.2, and 3.6 years. In particular, the 9.3-year cycle, which closely aligns with the 11-year solar activity cycle, suggests a potential correlation between solar activity and local temperature fluctuations. Moreover, our reconstruction demonstrates a significant degree of consistency when compared to actual climate data and regional temperature reconstruction series, reporting a strong logic of trust in the reliability and accuracy of our findings. This evidence reaffirms that our reconstruction shows significant and dependable regional temperature signals, notably being representative for the Hindu Kush region.


Asunto(s)
Estaciones del Año , Temperatura , Árboles , Pakistán , Historia del Siglo XIX , Historia del Siglo XX , Pinus , Historia del Siglo XVIII
12.
Ecol Lett ; 27(4): e14403, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38577961

RESUMEN

Species interactions such as facilitation and competition play a crucial role in driving species range shifts. However, density dependence as a key feature of these processes has received little attention in both empirical and modelling studies. Herein, we used a novel, individual-based treeline model informed by rich in situ observations to quantify the contribution of density-dependent species interactions to alpine treeline dynamics, an iconic biome boundary recognized as an indicator of global warming. We found that competition and facilitation dominate in dense versus sparse vegetation scenarios respectively. The optimal balance between these two effects was identified at an intermediate vegetation thickness where the treeline elevation was the highest. Furthermore, treeline shift rates decreased sharply with vegetation thickness and the associated transition from positive to negative species interactions. We thus postulate that vegetation density must be considered when modelling species range dynamics to avoid inadequate predictions of its responses to climate warming.


Asunto(s)
Ecosistema , Árboles , Árboles/fisiología , Calentamiento Global , Cambio Climático , Clima
13.
Plant Physiol ; 194(1): 564-577, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37801609

RESUMEN

Zinc finger proteins (ZFPs) are transcription factors involved in multiple cellular functions. We identified a C2H2 type ZFP (MtZPT2-2) in Medicago truncatula and demonstrated that it localizes to the nucleus and inhibits the transcription of 2 genes encoding high-affinity potassium transporters (MtHKT1;1 and MtHKT1;2). MtZPT2-2 transcripts were detected in stem, leaf, flower, seeds and roots, with the highest level in the xylem and phloem of roots and stems. MtZPT2-2 transcription in leaves was reduced after salt stress. Compared with the wild-type (WT), transgenic lines overexpressing MtZPT2-2 had decreased salt tolerance, while MtZPT2-2-knockout mutants showed increased salt tolerance. MtHKT1;1 and MtHKT1;2 transcripts and Na+ accumulation in shoots and roots, as well as in the xylem of all genotypes of plants, were increased after salt treatment, with higher levels of MtHKT1;1 and MtHKT1;2 transcripts and Na+ accumulation in MtZPT2-2-knockout mutants and lower levels in MtZPT2-2-overexpressing lines compared with the WT. K+ levels showed no significant difference among plant genotypes under salt stress. Moreover, MtZPT2-2 was demonstrated to bind with the promoter of MtHKT1;1 and MtHKT1;2 to inhibit their expression. Antioxidant enzyme activities and the gene transcript levels were accordingly upregulated in response to salt, with higher levels in MtZPT2-2-knockout mutants and lower levels in MtZPT2-2-overexpressing lines compared with WT. The results suggest that MtZPT2-2 regulates salt tolerance negatively through downregulating MtHKT1;1 and MtHKT1;2 expression directly to reduce Na+ unloading from the xylem and regulates antioxidant defense indirectly.


Asunto(s)
Medicago truncatula , Tolerancia a la Sal , Tolerancia a la Sal/genética , Medicago truncatula/metabolismo , Antioxidantes/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/metabolismo , Dedos de Zinc , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo
14.
Natl Sci Rev ; 10(10): nwad182, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37671321

RESUMEN

Despite the importance of species interaction in modulating the range shifts of plants, little is known about the responses of coexisting life forms to a warmer climate. Here, we combine long-term monitoring of cambial phenology in sympatric trees and shrubs at two treelines of the Tibetan Plateau, with a meta-analysis of ring-width series from 344 shrubs and 575 trees paired across 11 alpine treelines in the Northern Hemisphere. Under a spring warming of +1°C, xylem resumption advances by 2-4 days in trees, but delays by 3-8 days in shrubs. The divergent phenological response to warming was due to shrubs being 3.2 times more sensitive than trees to chilling accumulation. Warmer winters increased the thermal requirement for cambial reactivation in shrubs, leading to a delayed response to warmer springs. Our meta-analysis confirmed such a mechanism across continental scales. The warming-induced phenological mismatch may give a competitive advantage to trees over shrubs, which would provide a new explanation for increasing alpine treeline shifts under the context of climate change.

15.
Molecules ; 28(18)2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37764450

RESUMEN

Unique nonlinear optical properties for converting low-energy incident light into high-energy radiation enable up-conversion materials to be employed in photocatalytic systems. An efficient near-infrared (NIR) response photocatalyst was successfully fabricated through a facile two-step method to load BiOBr on the Nd3+, Er3+@NaYF4 (NE@NYF) up-conversion material. The NE@NYF can transform NIR into visible and UV light and promote charge-energy transfer in the semiconductor. Consequently, the as-obtained photocatalysts exhibit excellent photodegradation performance for rhodamine B dye (RhB) and tetracycline (TC) organic pollutants. About 98.9% of the RhB was decomposed within 60 min with the 20% NE@NYF-B sample, outperforming the pristine BiOBr (61.9%). In addition, the 20% NE@NYF-B composite could decompose approximately 72.7% of the organic carbon during a 10 h reaction, which was almost two-fold more than that of BiOBr. Meanwhile, a possible charge transfer mechanism is proposed based on the recombination of electron-hole pairs and reactive oxygen species. This work provides a rational hybrid structure photocatalyst for improving photocatalytic performance in the broadband spectrum and provides a new strategy for NIR light utilization.

16.
Clin Cancer Res ; 29(19): 4002-4015, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37527013

RESUMEN

PURPOSE: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it. EXPERIMENTAL DESIGN: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC. RESULTS: ATR inhibition activated the cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory cytokines and immune checkpoints. Among the common RCC genotypes, SETD2 loss is associated with preferential ATR activation and sensitizes cells to ATR inhibition. SETD2 knockdown promoted the cytosolic DNA-sensing pathway in response to ATR inhibition. Treatment with the ATR inhibitor VE822 concurrently upregulated immune cell infiltration and immune checkpoint expression in Setd2 knockdown Renca tumors, providing a rationale for ATR inhibition plus ICB combination therapy. Setd2-deficient Renca tumors demonstrated greater vulnerability to ICB monotherapy or combination therapy with VE822 than Setd2-proficient tumors. Moreover, SETD2 mutations were associated with a higher response rate and prolonged overall survival in patients with ICB-treated RCC but not in patients with non-ICB-treated RCC. CONCLUSIONS: SETD2 loss and ATR inhibition synergize to promote cGAS signaling and enhance immune cell infiltration, providing a mechanistic rationale for the combination of ATR and checkpoint inhibition in patients with RCC with SETD2 mutations.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Daño del ADN , Línea Celular Tumoral , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Inmunoterapia , ADN , Proteínas de la Ataxia Telangiectasia Mutada , Microambiente Tumoral/genética
17.
Plant Physiol ; 193(2): 1621-1634, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37392433

RESUMEN

Allene oxide cyclase (AOC) is a key enzyme in the biosynthesis of jasmonic acid (JA), which is involved in plant growth and development as well as adaptation to environmental stresses. We identified the cold- and pathogen-responsive AOC2 gene from Medicago sativa subsp. falcata (MfAOC2) and its homolog MtAOC2 from Medicago truncatula. Heterologous expression of MfAOC2 in M. truncatula enhanced cold tolerance and resistance to the fungal pathogen Rhizoctonia solani, with greater accumulation of JA and higher transcript levels of JA downstream genes than in wild-type plants. In contrast, mutation of MtAOC2 reduced cold tolerance and pathogen resistance, with less accumulation of JA and lower transcript levels of JA downstream genes in the aoc2 mutant than in wild-type plants. The aoc2 phenotype and low levels of cold-responsive C-repeat-binding factor (CBF) transcripts could be rescued by expressing MfAOC2 in aoc2 plants or exogenous application of methyl jasmonate. Compared with wild-type plants, higher levels of CBF transcripts were observed in lines expressing MfAOC2 but lower levels of CBF transcripts were observed in the aoc2 mutant under cold conditions; superoxide dismutase, catalase, and ascorbate-peroxidase activities as well as proline concentrations were higher in MfAOC2-expressing lines but lower in the aoc2 mutant. These results suggest that expression of MfAOC2 or MtAOC2 promotes biosynthesis of JA, which positively regulates expression of CBF genes and antioxidant defense under cold conditions and expression of JA downstream genes after pathogen infection, leading to greater cold tolerance and pathogen resistance.


Asunto(s)
Ciclopentanos , Oxilipinas , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Oxidorreductasas Intramoleculares/genética , Oxidorreductasas Intramoleculares/metabolismo , Fenotipo , Regulación de la Expresión Génica de las Plantas
18.
ACS Appl Mater Interfaces ; 15(30): 36477-36488, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37477612

RESUMEN

Developing highly water-stable zeolitic imidazolate frameworks (ZIFs) for visible-light-driven photocatalytic hydrolysis is important and challenging. Herein, the Type II heterojunction catalyst Mn0.5Cd0.5S@ZIF-8 and its derivatives (including MCS@ZIF-8-Mn, MCS@ZIF-8-Br, and MCS@ZIF-8-MB) were successfully constructed using a facile strategy. Through dual postsynthetic ligand and cation exchange (PSE) treatments of Mn(Ac)2·4H2O and 4-bromo-1H-imidazole for ZIF-8, the hydrogen production efficiency of the MCS@ZIF-8-MB heterojunction catalyst can reach 5.450 mmol·g-1·h-1 and remain at 97.11% after 9 h of the stability test. Construction of heterojunctions can effectively improve the hydrogen production performance of Mn0.5Cd0.5S while maintaining excellent water stability. X-ray photoelectron spectroscopy results show that upon successful construction of the MCS@ZIF-8-MB heterojunction an interface forms between the surface of MCS and ZIF-8-MB, effectively weakening the photocorrosion of MCS. Density functional theory calculations also indicate that the induction of Mn can increase the electronic states of p and d orbitals near the Fermi level of ZIF-8, suggesting that Mn(II) attracts more electrons than Zn(II). This provides more powerful theoretical evidence for the electron cloud shift from the electron donor S2- to Mn2+.

19.
Front Microbiol ; 14: 1180319, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37143547

RESUMEN

Mycorrhizal helper bacteria (MHB) can promote mycorrhizal fungal colonization and form mycorrhizal symbiosis structures. To investigate the effect of interactions between mycorrhizal beneficial microorganisms on the growth of blueberry, 45 strains of bacteria isolated from the rhizosphere soil of Vaccinium uliginosum were screened for potential MHB strains using the dry-plate confrontation assay and the bacterial extracellular metabolite promotion method. The results showed that the growth rate of mycelium of Oidiodendron maius 143, an ericoid mycorrhizal fungal strain, was increased by 33.33 and 77.77% for bacterial strains L6 and LM3, respectively, compared with the control in the dry-plate confrontation assay. In addition, the extracellular metabolites of L6 and LM3 significantly promoted the growth of O. maius 143 mycelium with an average growth rate of 40.9 and 57.1%, respectively, the cell wall-degrading enzyme activities and genes of O. maius 143 was significantly increased. Therefore, L6 and LM3 were preliminarily identified as potential MHB strains. In addition, the co-inoculated treatments significantly increased blueberry growth; increased the nitrate reductase, glutamate dehydrogenase, glutamine synthetase, and glutamate synthase activities in the leaves; and promoted nutrient uptake in blueberry. Based on the physiological, and 16S rDNA gene molecular analyses, we initially identified strain L6 as Paenarthrobacter nicotinovorans and LM3 as Bacillus circulans. Metabolomic analysis revealed that mycelial exudates contain large amounts of sugars, organic acids and amino acids, which can be used as substrates to stimulate the growth of MHB. In conclusion, L6 and LM3 and O. maius 143 promote each other's growth, while co-inoculation of L6 and LM3 with O. maius 143 can promote the growth of blueberry seedlings, providing a theoretical basis for further studies on the mechanism of ericoid mycorrhizal fungi-MHB-blueberry interactions. It laid the technical foundation for the exploitation of biocontrol strain resources and the development of biological fertilizer.

20.
Plants (Basel) ; 12(9)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37176907

RESUMEN

The wall-associated kinases (WAKs) can perceive and transmit extracellular signals as one kind of unique receptor-like kinases (RLKs) involved in the regulation of cell expansion, pathogen resistance and abiotic stress tolerance. To understand their potential roles and screen some key candidates in Medicago truncatula (M. truncatula), genome-wide identification and characterization of MtWAKs were conducted in this study. A total of 54 MtWAK genes were identified and classified into four groups based on their protein domains. They were distributed on all chromosomes, while most of them were clustered on chromosome 1 and 3. The synteny analysis showed that 11 orthologous pairs were identified between M. truncatula and Arabidopsis thaliana (A. thaliana) and 31 pairs between M. truncatula and Glycine max (G. max). The phylogenetic analysis showed that WAK-RLKs were classified into five clades, and they exhibited a species-specific expansion. Most MtWAK-RLKs had similar exon-intron organization and motif distribution. Multiple cis-acting elements responsive to phytohormones, stresses, growth and development were observed in the promoter regions of MtWAK-RLKs. In addition, the expression patterns of MtWAK-RLKs varied with different plant tissues, developmental stages and biotic and abiotic stresses. Interestingly, plasm membrane localized MtWAK24 significantly inhibited Phytophthora infection in tobacco. The study provides valuable information for characterizing the molecular functions of MtWAKs in regulation of plant growth, development and stress tolerance in legume plants.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...