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1.
Nat Commun ; 15(1): 8298, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333067

RESUMEN

Wearable visual bionic devices, fueled by advancements in artificial intelligence, are making remarkable progress. However, traditional silicon vision chips often grapple with high energy losses and challenges in emulating complex biological behaviors. In this study, we constructed a van der Waals P3HT/GaAs nanowires P-N junction by carefully directing the arrangement of organic molecules. Combined with a Schottky junction, this facilitated multi-faceted birdlike visual enhancement, including broadband non-volatile storage, low-light perception, and a near-zero power consumption operating mode in both individual devices and 5 × 5 arrays on arbitrary substrates. Specifically, we realized over 5 bits of in-memory sensing and computing with both negative and positive photoconductivity. When paired with two imaging modes (visible and UV), our reservoir computing system demonstrated up to 94% accuracy for color recognition. It achieved motion and UV grayscale information extraction (displayed with sunscreen), leading to fusion visual imaging. This work provides a promising co-design of material and device for a broadband and highly biomimetic optoelectronic neuromorphic system.

2.
World J Diabetes ; 15(9): 1842-1846, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39280174

RESUMEN

The bidirectional relationship between periodontitis and type 2 diabetes mellitus has been well-established. However, the underlying molecular mechanisms remain unclear. Diabetic retinopathy (DR) is an important complication of diabetes, but there are few studies on the relationship between DR and periodontitis, especially on the intrinsic inflammatory pathway mechanism. This article reviews the latest clinical data on how diabetes promotes susceptibility to periodontitis from the epidemiological and molecular perspectives, with a special focus on the key roles of systemic inflammation and endothelial dysfunction in the interplay between DR and periodontitis. Comprehension of the intertwined pathogenesis of DR and periodontitis can better guide the development of comprehensive management strategies for glycemic control and periodontal health, with the aim of mitigating the progression of DR and enhancing overall well-being.

3.
Nat Commun ; 15(1): 7796, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39242635

RESUMEN

Epigenetic modifications are crucial for plant development. EFD (Exine Formation Defect) encodes a SAM-dependent methyltransferase that is essential for the pollen wall pattern formation and male fertility in Arabidopsis. In this study, we find that the expression of DRM2, a de novo DNA methyltransferase in plants, complements for the defects in efd, suggesting its potential de novo DNA methyltransferase activity. Genetic analysis indicates that EFD functions through HB21, as the knockout of HB21 fully restores fertility in efd mutants. DNA methylation and histone modification analyses reveal that EFD represses the transcription of HB21 through epigenetic mechanisms. Additionally, we demonstrate that HB21 directly represses the expression of genes crucial for pollen formation and anther dehiscence, including CalS5, RPG1/SWEET8, CYP703A2 and NST2. Collectively, our findings unveil a double negative regulatory cascade mediated by epigenetic modifications that coordinates anther development, offering insights into the epigenetic regulation of this process.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Metilación de ADN , Epigénesis Genética , Flores , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Polen/crecimiento & desarrollo , Polen/genética , Polen/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Mutación , Plantas Modificadas Genéticamente
4.
J Cancer ; 15(17): 5506-5514, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39308690

RESUMEN

Objective: To evaluate the efficacy, toxicity, and long-term outcomes of PD1 inhibitors plus chemotherapy versus re-irradiation/chemoradiotherapy in patients with unresectable locally recurrent T3-4 nasopharyngeal carcinoma (NPC). Methods: A retrospective analysis was conducted on 42 patients with recurrent nasopharyngeal cancer (NPC) after receiving immunochemotherapy or re-irradiation between February 2018 and May 2022 in Zhejiang Cancer Hospital. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were determined using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression. Results: With a median follow-up duration of 28.7 months (ranging from 7.2 to 63.9 months), the 3-year OS rate was 23.3% in the re-irradiotherapy (RI) group (N = 24) and 59.6% in the immunochemotherapy (IC) group (N = 18) (p = 0.042). The 3-year PFS, LRFS, and DMFS rates were not significantly different between the two groups (PFS: 45.3% vs. 62.6%, P = 0.482; LRFS: 54.4% vs. 62.6%, P =0.891; DMFS: 89.8% vs. 100.0%, P = 0.489). The univariate analysis revealed that regimen (HR: 0.354, 95% CI: 0.130-0.962, P = 0.042) was significantly correlated with OS. Multivariate analysis also showed that treatment regimen (HR: 0.329, 95% CI: 0.12-0.970, P =0.044) was the only significant prognostic factor associated with OS. The most common late toxicities in the RI group were xerostomia, deafness, and nasopharyngeal necrosis. Of these, nasopharyngeal necrosis was present in 16 patients (66.7%) and in 10 patients (41.7%) at a grade 3 or above. Nasopharyngeal necrosis is the main cause of death in the RI group. In contrast, in the IC group, grade 3 or higher immune-related adverse events or late adverse events were not observed. Conclusions: For unresectable locally recurrent NPC, re-irradiation is an effective treatment; nevertheless, the survival obtains are usually surpassed by serious late complications. For these individuals, chemotherapy in addition to an anti-PD-1 checkpoint inhibitor may be a helpful course of treatment.

5.
J Nanobiotechnology ; 22(1): 485, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138462

RESUMEN

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.


Asunto(s)
Fosfatasa Alcalina , Antibacterianos , Cobre , Desinfección , Escherichia coli , Profármacos , Especies Reactivas de Oxígeno , Cobre/química , Cobre/farmacología , Animales , Profármacos/farmacología , Profármacos/química , Fosfatasa Alcalina/metabolismo , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Desinfección/métodos , Ácido Ascórbico/farmacología , Ácido Ascórbico/química , Ácido Ascórbico/análogos & derivados , Nanopartículas del Metal/química , Ratas Sprague-Dawley , Masculino
6.
IEEE Trans Med Imaging ; PP2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088491

RESUMEN

Contrastive learning (CL) is a form of self-supervised learning and has been widely used for various tasks. Different from widely studied instance-level contrastive learning, pixel-wise contrastive learning mainly helps with pixel-wise dense prediction tasks. The counter-part to an instance in instance-level CL is a pixel, along with its neighboring context, in pixel-wise CL. Aiming to build better feature representation, there is a vast literature about designing instance augmentation strategies for instance-level CL; but there is little similar work on pixel augmentation for pixel-wise CL with a pixel granularity. In this paper, we attempt to bridge this gap. We first classify a pixel into three categories, namely low-, medium-, and high-informative, based on the information quantity the pixel contains. We then adaptively design separate augmentation strategies for each category in terms of augmentation intensity and sampling ratio. Extensive experiments validate that our information-guided pixel augmentation strategy succeeds in encoding more discriminative representations and surpassing other competitive approaches in unsupervised local feature matching. Furthermore, our pretrained model improves the performance of both one-shot and fully supervised models. To the best of our knowledge, we are the first to propose a pixel augmentation method with a pixel granularity for enhancing unsupervised pixel-wise contrastive learning. Code is available at https: //github.com/Curli-quan/IGU-Aug.

7.
Lung Cancer ; 195: 107933, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39191079

RESUMEN

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen. METHODS: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF. RESULTS: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups. CONCLUSIONS: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Exones , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Exones/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mutagénesis Insercional , Pronóstico
8.
Glob Chang Biol ; 30(7): e17428, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39021355

RESUMEN

Global hydroclimatic variability is increasing with more frequent extreme dry and wet years, severely destabilizing terrestrial ecosystem productivity. However, what regulates the consequence of precipitation extremes on productivity remains unclear. Based on a 9-year field manipulation experiment on the Qinghai-Tibetan Plateau, we found that the responses of gross primary productivity (GPP) to extreme drought and wetness were differentially regulated by nitrogen (N) deposition. Over increasing N deposition, extreme dry events reduced GPP more. Among the 12 biotic and abiotic factors examined, this was mostly explained by the increased plant canopy height and proportion of drought-sensitive species under N deposition, making photosynthesis more sensitive to hydraulic stress. While extreme wet events increased GPP, their effect did not shift over N deposition. These site observations were complemented by a global synthesis derived from the GOSIF GPP dataset, which showed that GPP sensitivity to extreme drought was larger in ecosystems with higher N deposition, but GPP sensitivity to extreme wetness did not change with N deposition. Our findings indicate that intensified hydroclimatic variability would lead to a greater loss of land carbon sinks in the context of increasing N deposition, due to that GPP losses during extreme dry years are more pronounced, yet without a synchronous increase in GPP gains during extreme wet years. The study implies that the conservation and management against climate extremes merit particular attention in ecosystems subject to N deposition.


Asunto(s)
Sequías , Nitrógeno , Nitrógeno/metabolismo , Nitrógeno/análisis , Ecosistema , Cambio Climático , Fotosíntesis , China , Tibet
9.
Chem Commun (Camb) ; 60(58): 7471-7474, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38938073

RESUMEN

Visible light-induced, transition metal-free oxidative dehydroxylation and C-H amidation of α-hydroxy ketones involving Ritter-type amidation has been developed, leading to the selective synthesis of α,α-diamido- and α-monoamido ketones with tunable selectivity as well as broad substrate tolerance.

10.
Nat Commun ; 15(1): 4440, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789422

RESUMEN

Inorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm2/(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 µs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill.

11.
Med Image Anal ; 96: 103200, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38801797

RESUMEN

The success of deep learning methodologies hinges upon the availability of meticulously labeled extensive datasets. However, when dealing with medical images, the annotation process for such abundant training data often necessitates the involvement of experienced radiologists, thereby consuming their limited time resources. In order to alleviate this burden, few-shot learning approaches have been developed, which manage to achieve competitive performance levels with only several labeled images. Nevertheless, a crucial yet previously overlooked problem in few-shot learning is about the selection of template images for annotation before learning, which affects the final performance. In this study, we propose a novel TEmplate Choosing Policy (TECP) that aims to identify and select "the most worthy" images for annotation, particularly within the context of multiple few-shot medical tasks, including landmark detection, anatomy detection, and anatomy segmentation. TECP is composed of four integral components: (1) Self-supervised training, which entails training a pre-existing deep model to extract salient features from radiological images; (2) Alternative proposals for localizing informative regions within the images; and (3) Representative Score Estimation, which involves the evaluation and identification of the most representative samples or templates. (4) Ranking, which rank all candidates and select one with highest representative score. The efficacy of the TECP approach is demonstrated through a series of comprehensive experiments conducted on multiple public datasets. Across all three medical tasks, the utilization of TECP yields noticeable improvements in model performance.


Asunto(s)
Aprendizaje Profundo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos
12.
Org Lett ; 26(22): 4678-4683, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38787784

RESUMEN

The radical 1,4-functionalizations of 1,3-enynes have emerged as a powerful strategy for the synthesis of multisubstituted allenes. However, the phosphorus-centered radical-initiated transformations remain largely elusive. Herein, visible-light photoredox catalytic regioselective radical hydrophosphinylation of 1,3-enynes with diaryl phosphine oxides as phosphinoyl radical precursors has been realized. This protocol features mild conditions, a wide substrate scope, and good functional group tolerance, producing a diverse range of phosphinoyl-substituted allenes in moderate to good yields with high atom economy. Detailed mechanistic experiments revealed a radical-polar crossover process in the reaction.

13.
Nat Plants ; 10(6): 890-900, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38755277

RESUMEN

Growing evidence indicates that plant community structure and traits have changed under climate warming, especially in cold or high-elevation regions. However, the impact of these warming-induced changes on ecosystem carbon sequestration remains unclear. Using a warming experiment on the high-elevation Qinghai-Tibetan Plateau, we found that warming not only increased plant species height but also altered species composition, collectively resulting in a taller plant community associated with increased net ecosystem productivity (NEP). Along a 1,500 km transect on the Plateau, taller plant community promoted NEP and soil carbon through associated chlorophyll content and other photosynthetic traits at the community level. Overall, plant community height as a dominant trait is associated with species composition and regulates ecosystem C sequestration in the high-elevation biome. This trait-based association provides new insights into predicting the direction, magnitude and sensitivity of ecosystem C fluxes in response to climate warming.


Asunto(s)
Secuestro de Carbono , Ecosistema , Calentamiento Global , Plantas/metabolismo , Fotosíntesis , Cambio Climático , Altitud , Tibet , Carbono/metabolismo , Suelo/química
14.
World J Diabetes ; 15(4): 591-597, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38680699

RESUMEN

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease (ESKD). Wide glycemic var-iations, such as hypoglycemia and hyperglycemia, are broadly found in diabetic patients with DKD and especially ESKD, as a result of impaired renal metabolism. It is essential to monitor glycemia for effective management of DKD. Hemoglobin A1c (HbA1c) has long been considered as the gold standard for monitoring glycemia for > 3 months. However, assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction. Continuous glucose monitoring (CGM) has provided new insights on glycemic assessment and management. CGM directly measures glucose level in interstitial fluid, reports real-time or retrospective glucose concentration, and provides multiple glycemic metrics. It avoids the pitfalls of HbA1c in some contexts, and may serve as a precise alternative to estimation of mean glucose and glycemic variability. Emerging studies have demonstrated the merits of CGM for precise monitoring, which allows fine-tuning of glycemic management in diabetic patients. Therefore, CGM technology has the potential for better glycemic monitoring in DKD patients. More research is needed to explore its application and management in different stages of DKD, including hemodialysis, peritoneal dialysis and kidney transplantation.

15.
Sci Total Environ ; 928: 172226, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38593880

RESUMEN

Corn is the third most cultivated food crop in the world, and climate change has important effects on corn production and food security. China is the top user of chemical fertilizer in the world, and analyzing how to effectively manage fertilizer application in such a developing country with resource constraints is crucial. We present empirical evidence from China to demonstrate the nonlinear impact of temperature on fertilizer usage in corn production based on a panel dataset that shows 2297 corn-growing counties during 1998-2016. Our findings indicate that fertilizer usage barely changes with increasing temperatures that are below 28 °C; however, exposure to temperatures above 28 °C leads to a sharp increase in fertilizer use. The increase in temperatures in the sample period implies that fertilizer usage per hectare for corn increased by 1.5 kg. Summer corn fertilizer application in the Yellow-Huai River Valley is more sensitive to warming than in the North region. Moreover, nitrogen, phosphorus, and potassium fertilizers have different temperature thresholds of 32 °C, 20 °C, and 20 °C, respectively, that cause significant changes.


Asunto(s)
Agricultura , Cambio Climático , Fertilizantes , Zea mays , Fertilizantes/análisis , Zea mays/crecimiento & desarrollo , China , Agricultura/métodos , Productos Agrícolas/crecimiento & desarrollo , Temperatura , Nitrógeno/análisis
16.
J Dent Sci ; 19(1): 58-63, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38303873

RESUMEN

Background/purpose: Excessive host immune response is thought to be an important cause of periodontal tissue damage during periodontitis. The potent chemotaxis produced by locally released chemokines is the key signal to trigger this response. Here, we aimed to investigate the expression of CXC chemokine receptor 1 (CXCR1), and chemokines interleukin-8 (IL-8) and pro-platelet basic protein (PPBP) in human inflammatory gingival tissues compared with healthy tissues. Materials and methods: A total of 54 human gingival tissues, 27 healthy and 27 inflammatory samples, were collected. Fifteen specimens of each group were employed for quantitative reverse transcription polymerase chain reaction to determine the mRNA levels of CXCR1, IL-8, and PPBP. Six samples of each group were used for Western blotting to investigate the protein expression of CXCR1 and for enzyme-linked immunosorbent assay to evaluate the protein levels of IL-8 and PPBP, respectively. Results: The mRNA levels of chemokine receptor CXCR1, chemokine IL-8, and PPBP in inflammatory gingival tissues were significantly higher than those in healthy controls (P < 0.05). The protein levels of CXCR1, IL-8, and PPBP in inflammatory gingival tissues were also significantly higher than those in healthy gingival tissues (P < 0.05). Conclusion: When compared to healthy gingival tissues, the expression of CXCR1, IL-8, and PPBP in inflammatory gingival tissues is higher.

17.
Org Biomol Chem ; 22(11): 2156-2174, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38385507

RESUMEN

Cascade reactions represent an efficient and economical synthetic approach, enabling the rapid synthesis of a wide array of structurally complex organic compounds. These compounds, previously inaccessible, can now be synthesized in a remarkably limited number of steps. Concurrently, the photochemical reactions of organic molecules have gained prominence as a potent strategy for accessing a diverse range of radical species and intermediates. This is achieved in a controlled manner under mild conditions. Owing to the relentless endeavors of chemists, significant strides have been made in the realm of photochemical cascade reactions. These advancements have facilitated the synthesis of novel molecular structures with high complexity, structures that are typically challenging to generate under thermal conditions. In this review, we comprehensively summarize and underscore the recent pivotal advancements in visible-light-induced cascade reactions. Our focus is on the elucidation of multiple photochemical catalytic cycles, emphasizing the catalytic activation modes and the types of reactions involved.

18.
BMC Cancer ; 24(1): 57, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200410

RESUMEN

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).


Asunto(s)
Adenocarcinoma , Neoplasias Encefálicas , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Neoplasias Pancreáticas , Neoplasias del Recto , Humanos , Canal Anal , Protocolos de Quimioterapia Combinada Antineoplásica , Irinotecán , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto
19.
Nat Commun ; 15(1): 728, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38272917

RESUMEN

High synthesis temperatures and specific growth substrates are typically required to obtain crystalline or oriented inorganic functional thin films, posing a significant challenge for their utilization in large-scale, low-cost (opto-)electronic applications on conventional flexible substrates. Here, we explore a pulse irradiation synthesis (PIS) to prepare thermoelectric metal chalcogenide (e.g., Bi2Se3, SnSe2, and Bi2Te3) films on multiple polymeric substrates. The self-propagating combustion process enables PIS to achieve a synthesis temperature as low as 150 °C, with an ultrafast reaction completed within one second. Beyond the photothermoelectric (PTE) property, the thermal coupling between polymeric substrates and bismuth selenide films is also examined to enhance the PTE performance, resulting in a responsivity of 71.9 V/W and a response time of less than 50 ms at 1550 nm, surpassing most of its counterparts. This PIS platform offers a promising route for realizing flexible PTE or thermoelectric devices in an energy-, time-, and cost-efficient manner.

20.
World J Oncol ; 15(1): 28-37, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38274726

RESUMEN

The dynamic changes between glycolysis and oxidative phosphorylation (OXPHOS) for adenosine triphosphate (ATP) output, along with glucose, glutamine, and fatty acid utilization, etc., lead to the maintenance and selection of growth advantageous to tumor cell subgroups in an environment of iron starvation and hypoxia. Iron plays an important role in the three major biochemical reactions in nature: photosynthesis, nitrogen fixation, and oxidative respiration, which all require the participation of iron-sulfur proteins, such as ferredoxin, cytochrome b, and the complex I, II, III in the electron transport chain, respectively. Abnormal iron-sulfur cluster synthesis process or hypoxia will directly affect the function of mitochondrial electron transfer and mitochondrial OXPHOS. More research results have indicated that iron metabolism, oxygen availability and hypoxia-inducible factor mutually regulate the shift between glycolysis and OXPHOS. In this article, we make a perspective review to provide novel opinions of the regulation of glycolysis and OXPHOS in tumor cells.

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