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2.
Mater Today Bio ; 24: 100938, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38260033

RESUMO

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-ß1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-ß1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

3.
Faraday Discuss ; 250(0): 129-144, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37965707

RESUMO

Locally aromatic alkyl-N-substituted squarephaneic tetraimide (SqTI) conjugated macrocycles are four-electron reducible, owing to global aromaticity and presumed global Baird aromaticity of the dianion and tetraanion states, respectively. However, their good solubility inhibits their application as a battery electrode material. By applying sidechain removal as a strategy to reduce SqTI solubility, we report the development of its unsubstituted derivative SqTI-H, which was obtained directly from squarephaneic tetraanhydride by facile treatment with hexamethyldisilazane and MeOH. Compared to alkyl-N-substituted SqTI-Rs, SqTI-H exhibited further improved thermal stability and low neutral state solubility in most common organic solvents, owing to computationally demonstrated hydrogen-bonding capabilities emanating from each imide position on SqTI-H. Reversible solid state electrochemical reduction of SqTI-H to the globally aromatic dianion state was also observed at -1.25 V vs. Fc/Fc+, which could be further reduced in two stages. Preliminary testing of SqTI-H in composite electrodes for lithium-organic half cells uncovered imperfect cycling performance, which may be explained by persistent solubility of reduced states, necessitating further optimisation of electrode fabrication procedures to attain maximum performance.

4.
Macromolecules ; 56(15): 5825-5834, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37576475

RESUMO

Bisthienoazepinedione (BTA) has been reported for constructing high-performing p-type conjugated polymers in organic electronics, but the ring extended version of BTA is not well explored. In this work, we report a new synthesis of a key building block to the ring expanded electron-deficient pentacyclic azepinedione (BTTA). Three copolymers of BTAA with benzodithiophene substituted by different side chains are prepared. These polymers exhibit similar energy levels and optical absorption in solution and solid state, while significant differences are revealed in their film morphologies and behavior in transistor and photovoltaic devices. The best-performing polymers in transistor devices contained alkylthienyl side chains on the BDT unit (pBDT-BTTA-2 and pBDT-BTTA-3) and demonstrated maximum saturation hole mobilities of 0.027 and 0.017 cm2 V-1 s-1. Blends of these polymers with PC71BM exhibited a best photovoltaic efficiency of 6.78% for pBDT-BTTA-3-based devices. Changing to a low band gap non-fullerene acceptor (BTP-eC9) resulted in improved efficiency of up to 13.5%. Our results are among the best device performances for BTA and BTTA-based p-type polymers and highlight the versatile applications of this electron-deficient BTTA unit.

5.
Cell Death Dis ; 14(8): 493, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532692

RESUMO

An immunosuppressive microenvironment enriched with regulatory CD4+ T lymphocytes (Tregs) facilitates the progression of lung adenocarcinoma (LUAD). This study aims to investigate the cellular mechanism underlying the formation of the immunosuppressive microenvironment in LUAD. LUAD samples (n = 12) and normal lung samples (n = 3) were obtained from patients with different pathological stages of LUAD. Single-cell RNA sequencing was performed to classify cellular components and analyze the transcriptomes, including transcription factors/targets and chemokine ligands/receptors, followed by bioinformatics study such as pseudotime analysis. Myeloid cells and T cells were the most abundant cell types in tumors and normal lung tissues, while tumor-associated macrophage-folate receptor 2 (TAM-FOLR2) and CD4+ nuclear receptor subfamily 4 group A member 3 (NR4A3) exhibited sharp increases in invasive adenocarcinoma (IA). The enrichment of TAM-FOLR2 in IA might result from alveolar resident macrophage-resistin (ARM-RETN) transformation and recruitment of dendritic cells (DCs) and other TAMs, as evidenced by temporal trajectories and differential expression profiles of chemokine ligands/receptors versus those in the early stages of tumors. High expression of CCL17/19/22 was observed in IA as well as in DCs, along with the strong interaction of TAM-FOLR2 with DCs. The results of pseudotime analysis suggested that CD4+NR4A3 might potentially convert to CD4+FOXP3, further supported by the high expression of NR4A3 target genes in CD4+FOXP3 cells. This study provides a single-cell transcriptome atlas from preinvasive to invasive LUAD and reveals a potential ARM-RETN/TAM-FOLR2/DCs/CD4+NR4A3/CD4+FOXP3 trajectory in shaping the immune suppressive microenvironment along the pathogenesis of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Receptor 2 de Folato , Neoplasias Pulmonares , Humanos , Linfócitos T Reguladores , Ligantes , Macrófagos Associados a Tumor , Adenocarcinoma de Pulmão/genética , Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Quimiocinas/genética , Fatores de Transcrição Forkhead/genética , Microambiente Tumoral/genética
6.
Front Oncol ; 13: 1202650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427127

RESUMO

Background: Immediate breast reconstruction is widely accepted following oncologic mastectomy. This study aimed to build a novel nomogram predicting the survival outcome for Chinese patients undergoing immediate reconstruction following mastectomy for invasive breast cancer. Methods: A retrospective review of all patients undergoing immediate reconstruction following treatment for invasive breast cancer was performed from May 2001 to March 2016. Eligible patients were assigned to a training set or a validation set. Univariate and multivariate Cox proportional hazard regression models were used to select associate variables. Two nomograms were developed based on the training cohort for breast cancer-specific survival (BCSS) and disease-free survival (DFS). Internal and external validations were performed, and the C-index and calibration plots were generated to evaluate the performance (discrimination and accuracy) of the models. Results: The 10-year estimated BCSS and DFS were 90.80% (95% CI: 87.30%-94.40%) and 78.40% (95% CI: 72.50%-84.70%), respectively, in the training cohort. In the validation cohort, they were and 85.60% (95% CI, 75.90%-96.50%) and 84.10% (95% CI, 77.80%-90.90%), respectively. Ten independent factors were used to build a nomogram for prediction of 1-, 5- and 10-year BCSS, while nine were used for DFS. The C-index was 0.841 for BCSS and 0.737 for DFS in internal validation, and the C-index was 0.782 for BCSS and 0.700 for DFS in external validation. The calibration curve for both BCSS and DFS demonstrated acceptable agreement between the predicted and actual observation in the training and the validation cohorts. Conclusion: The nomograms provided valuable visualization of factors predicting BCSS and DFS in invasive breast cancer patients with immediate breast reconstruction. The nomograms may have tremendous potential in guiding individualized decision-making for physicians and patients in choosing the optimized treatment methods.

7.
Chem Mater ; 35(8): 3290-3299, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37123107

RESUMO

Emergent bioelectronic technologies are underpinned by the organic electrochemical transistor (OECT), which employs an electrolyte medium to modulate the conductivity of its organic semiconductor channel. Here we utilize postpolymerization modification (PPM) on a conjugated polymer backbone to directly introduce glycolated or anionic side chains via fluoride displacement. The resulting polymers demonstrated increased volumetric capacitances, with subdued swelling, compared to their parent polymer in p-type enhancement mode OECTs. This increase in capacitance was attributed to their modified side chain configurations enabling cationic charge compensation for thin film electrochemical oxidation, as deduced from electrochemical quartz crystal microbalance measurements. An overall improvement in OECT performance was recorded for the hybrid glycol/ionic polymer compared to the parent, owing to its low swelling and bimodal crystalline orientation as imaged by grazing-incidence wide-angle X-ray scattering, enabling its high charge mobility at 1.02 cm2·V-1·s-1. Compromised device performance was recorded for the fully glycolated derivative compared to the parent, which was linked to its limited face-on stacking, which hindered OECT charge mobility at 0.26 cm2·V-1·s-1, despite its high capacitance. These results highlight the effectiveness of anionic side chain attachment by PPM as a means of increasing the volumetric capacitance of p-type conjugated polymers for OECTs, while retaining solid-state macromolecular properties that facilitate hole transport.

8.
Mater Horiz ; 10(8): 3090-3100, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37218468

RESUMO

Functionalized polymeric mixed ionic-electronic conductors (PMIECs) are highly desired for the development of electrochemical applications, yet are hindered by the limited conventional synthesis techniques. Here, we propose a "graft-onto-polymer" synthesis strategy by post-polymerization functionalization (GOP-PPF) to prepare a family of PMIECs sharing the same backbone while functionalized with varying ethylene glycol (EG) compositions (two, four, and six EG repeating units). Unlike the typical procedure, GOP-PPF uses a nucleophilic aromatic substitution reaction for the facile and versatile attachment of functional units to a pre-synthesized conjugated-polymer precursor. Importantly, these redox-active PMIECs are investigated as a platform for energy storage devices and organic electrochemical transistors (OECTs) in aqueous media. The ion diffusivity, charge mobility and charge-storage capacity can be significantly improved by optimizing the EG composition. Specifically, g2T2-gBT6 containing the highest EG density gives the highest charge-storage capacity exceeding 180 F g-1 among the polymer series, resulting from the improved ion diffusivity. Moreover, g2T2-gBT4 with four EG repeating units exhibits a superior performance compared to its two analogues in OECTs, associated with a high µC* up to 359 F V-1 cm-1 s-1, owing to the optimal balance between ionic-electronic coupling and charge mobility. Through the GOP-PPF, PMIECs can be tailored to access desirable performance metrics at the molecular level.

9.
Am J Surg Pathol ; 47(4): 431-439, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36764678

RESUMO

To describe the histologic features of bronchiolar adenoma/ciliated muconodular papillary tumors (BA/CMPTs) and analyze the pitfalls in diagnosis from frozen sections. A total of 208 frozen and permanent sections of BA/CMPTs from Shanghai Chest Hospital from July 2018 to July 2021 were retrospectively analyzed. The median age of BA/CMPT patients was 65 years (15 to 79 y), and women accounted for 61.62% (122/198). The median size of BA/CMPTs was 0.6 cm (range 0.2 to 2 cm), of which 88.94% were small (≤1 cm, 185/208). In terms of location, the right lower lobe accounted for 44.23% (92/208), and the left lower lobe accounted for 33.65% (70/208). In 10 patients with 2 independent BA/CMPTs, 5 lesions were located in the left lower lobe and 4 in the right lower lobe. A total of 86.06% of the CT images of BA/CMPT showed solid/subsolid nodules (179/208). Among 208 tumors, 68.75% were distal type (143/208), and 31.25% were proximal type (65/208). The qualitative error rate of frozen sections was 21.33% (32/150), of which the distal type accounted for 75% (24/32); most of them were misdiagnosed as invasive adenocarcinoma during frozen diagnosis. The frozen diagnosis of BA/CMPTs might result in misdiagnosis as invasive adenocarcinoma. A careful search for characteristics of BA/CMPT, such as bilayer epithelial cells with basal cells and a lack of cellular atypia and invasive growth patterns, may be helpful for frozen diagnosis.


Assuntos
Adenocarcinoma Bronquioloalveolar , Neoplasias Pulmonares , Estudos Retrospectivos , Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adenocarcinoma Bronquioloalveolar/patologia , Neoplasias Pulmonares/patologia
10.
J Comput Chem ; 44(12): 1174-1188, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-36648254

RESUMO

Easy and effective usage of computational resources is crucial for scientific calculations, both from the perspectives of timeliness and economic efficiency. This work proposes a bi-level optimization framework to optimize the computational sequences. Machine-learning (ML) assisted static load-balancing, and different dynamic load-balancing algorithms can be integrated. Consequently, the computational and scheduling engine of the ParaEngine is developed to invoke optimized quantum chemical (QC) calculations. Illustrated benchmark calculations include high-throughput drug suit, solvent model, P38 protein, and SARS-CoV-2 systems. The results show that the usage rate of given computational resources for high throughput and large-scale fragmentation QC calculations can primarily profit, and faster accomplishing computational tasks can be expected when employing high-performance computing (HPC) clusters.

11.
Adv Mater ; 35(11): e2209800, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36565038

RESUMO

Narrowband photoresponsive molecules are highly coveted in high-resolution imaging, sensing, and monochromatic photodetection, especially those extending into the near-infrared (NIR) spectral range. Here, a new class of J-aggregating materials based on quinoidal indacenodithiophenes (IDTs) that exhibit an ultra-narrowband (full width half maxima of 22 nm) NIR absorption peak centered at 770 nm is reported. The spectral width is readily tuned by the length of the solubilizing alkyl group, with longer chains resulting in significant spectral narrowing. The J-aggregate behavior is confirmed by a combination of excited state lifetime measurements and single-crystal X-ray diffraction measurements. Their utility as electron-transporting materials is demonstrated in both transistor and phototransistor devices, with the latter demonstrating good response at NIR wavelengths (780 nm) over a range of intensities.

12.
J Cancer Res Clin Oncol ; 149(8): 4455-4463, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36121510

RESUMO

PURPOSE: SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown. METHODS: In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. RESULTS: Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months. CONCLUSION: Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.


Assuntos
Proteínas Tirosina Quinases , Neoplasias Torácicas , Humanos , Proteínas Proto-Oncogênicas , Neoplasias Torácicas/genética , Neoplasias Torácicas/cirurgia , Neoplasias Torácicas/patologia , Prognóstico , Receptores Proteína Tirosina Quinases , Biomarcadores Tumorais/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética
13.
Angew Chem Int Ed Engl ; 61(48): e202212623, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36178733

RESUMO

Aromatic carboxylic anhydrides are ubiquitous building blocks in organic materials chemistry and have received considerable attention in the synthesis of organic semiconductors, pigments, and battery electrode materials. Here we extend the family of aromatic carboxylic anhydrides with a unique new member, a conjugated cyclophane with four anhydride groups. The cyclophane is obtained in a three-step synthesis and can be functionalised efficiently, as shown by the conversion into tetraimides and an octacarboxylate. Crystal structures reveal the high degree of porosity achievable with the new building block. Excellent electrochemical properties and reversible reduction to the tetraanions are shown for the imides; NMR and EPR measurements confirm the global aromaticity of the dianions and evidence the global Baird aromaticity of the tetraanions. Considering the short synthesis and unique properties, we expect widespread use of the new building block in the development of organic materials.

14.
Oxid Med Cell Longev ; 2022: 9306614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915613

RESUMO

As a previously discovered target of DNA damage, Na+/H+ exchanger 1 (NHE1) plays a role in regulation of intracellular pH (pHi) through the extrusion of intracellular proton (H+) in exchange for extracellular sodium (Na+). Its abnormal expression and dysfunction have been reported in solid tumor and hematopoietic malignancies. Here, we reported that suppression of NHE1 in BCR-ABL+ hematopoietic malignancies' K562 cells treated with Etoposide was manipulated by miR-19 and c-MYC. Inhibition of miR-19 or c-MYC enhanced the expression of NHE1 and sensitized K562 cells to Etoposide in vitro. The in vivo nude mouse transplantation model was also performed to confirm the enhanced sensitivity of K562 cells to Etoposide by inhibiting the miR-19 or c-MYC pathway. TCGA analysis conferred a negative correlation between miR-19 level and leukemia patients' survival. Thus, our results provided a potential management by which the c-MYC-miRNA 19 pathway might have a crucial impact on sensitizing K562 cells to Etoposide in the therapeutic approaches.


Assuntos
Neoplasias Hematológicas , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , Trocador 1 de Sódio-Hidrogênio/metabolismo , Animais , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Regulação Leucêmica da Expressão Gênica , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Camundongos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Regulação para Cima
15.
BMC Med Genomics ; 15(1): 146, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778737

RESUMO

PURPOSE: To analyze the mutational landscape of pan-cancer patients with PIK3CA mutations in Chinese population in real-world. METHODS: We analyzed PIK3CA mutation status in sequencing data of cell-free DNA from plasma and genomic DNA from matched peripheral blood lymphocyte in 11,904 Chinese pan-cancer patients, and compared them with genomic data from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Besides, concomitant genomic aberrations in PIK3CA-mutated samples were detected to investigate cancer driver genes, as well as their enriched pathways. Meanwhile, the mutations of Alpelisib targeting genes were screened and their co-alterations were analyzed according to OncoKB definition to identify the potential actionable ones. RESULTS: The proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The most common PIK3CA mutation hotspots were found to be E545K, E542K and H1047R. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. Compared with COSMIC cohort, the mutation frequencies of Alpelisib-targeted genes in breast cancer were significantly reduced in the Chinese cohort. All PIK3CA-mutated patients had concomitant genomic aberrations. While the most common concomitant genomic alterations occurred in TP53, EGFR and FAT1, these co-mutated genes were mainly enriched in RTK/RAS pathway, PI3K pathway and P53 pathway. Moreover, 83.6% of patients carrying mutations in Alpelisib-targeted genes had at least one actionable concomitant alteration. Level 1 actionable alteration was identified in LUAD, BRCA, COAD, LUSC, READ, and STAD. CONCLUSION: Compared with the Western cohort, the mutation frequency of PIK3CA in breast cancer was reduced in the Chinese cohort. RTK/RAS pathway, PI3K pathway and P53 pathway were identified as the most common co-mutation pathways, suggesting that they may potentially serve as targets for possible Alpelisib-based combination therapy.


Assuntos
Neoplasias da Mama , Fosfatidilinositol 3-Quinases , Neoplasias da Mama/genética , China , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Humanos , Mutação , Fosfatidilinositol 3-Quinases/genética , Proteína Supressora de Tumor p53/genética
16.
Transl Cancer Res ; 11(6): 1844-1849, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35836509

RESUMO

Background: Primary pulmonary choriocarcinoma is an extremely rare malignant trophoblastic tumor with a poor prognosis. Most choriocarcinomas originated from gonads, such as the ovaries and testes. Review the previous literature, only 41 cases were reported. Case Description: We reported that a 65-year-old man found shadows in the lungs when undergoing the X-ray examination. Positron emission tomography (PET) was performed to exclude metastatic disease before surgery. The patient underwent three-dimension uniportal thoracoscopic left upper lung resection and lymph node dissection. The operation was uneventful, and he was discharged on the fourth day postoperatively. Postoperative pathology: malignant trophoblastic tumors (choriocarcinoma). After the operation, the patient has genetically tested, the mutations in tumor protein p53 (TP53), NRAS proto-oncogene (NRAS), and fibroblast growth factor receptor 1 (FGFR1) were found. Conclusions: Primary pulmonary choriocarcinoma is an extremely rare and highly malignant tumor difficult to detect in the early stage. By analyzing the previous literature, the patients with active treatment have more extended survival periods than the patients without treatment (P=0.0051). Patients, including surgery, had better survival than patients without surgery (P=0.027) depending on the different treatment regimens. Hence, once the diagnosis was confirmed, the comprehensive treatment of surgical resection combined with chemotherapy and radiotherapy is of great significance to improve the prognosis of patients.

17.
Math Biosci Eng ; 19(6): 5925-5956, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35603385

RESUMO

The closed-loop supply chain (CLSC) plays an important role in sustainable development and can help to increase the economic benefits of enterprises. The optimization for the CLSC network is a complicated problem, since it often has a large problem scale and involves multiple constraints. This paper proposes a general CLSC model to maximize the profits of enterprises by determining the transportation route and delivery volume. Due to the complexity of the multi-constrained and large-scale model, a genetic algorithm with two-step rank-based encoding (GA-TRE) is developed to solve the problem. Firstly, a two-step rank-based encoding is designed to handle the constraints and increase the algorithm efficiency, and the encoding scheme is also used to improve the genetic operators, including crossover and mutation. The first step of encoding is to plan the routes and predict their feasibility according to relevant constraints, and the second step is to set the delivery volume based on the feasible routes using a rank-based method to achieve greedy solutions. Besides, a new mutation operator and an adaptive population disturbance mechanism are designed to increase the diversity of the population. To validate the efficiency of the proposed algorithm, six heuristic algorithms are compared with GA-TRE by using different instances with three problem scales. The results show that GA-TRE can obtain better solutions than the competitors, especially on large-scale instances.


Assuntos
Algoritmos , Meios de Transporte
18.
Front Immunol ; 13: 844931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251045

RESUMO

TNF receptor 2 (TNFR2) has become one of the best potential immune checkpoints that might be targeted, mainly because of its vital role in tumor microenvironments (TMEs). Overexpression of TNFR2 in some tumor cells and essential function in immunosuppressive cells, especially regulatory T cells (Tregs), makes blocking TNFR2 an excellent strategy in cancer treatment; however, there is evidence showing that activating TNFR2 can also inhibit tumor progression in vivo. In this review, we will discuss drugs that block and activate TNFR2 under clinical trials or preclinical developments up till now. Meanwhile, we summarize and explore the possible mechanisms related to them.


Assuntos
Neoplasias , Receptores Tipo II do Fator de Necrose Tumoral , Humanos , Neoplasias/terapia , Cidade de Roma , Linfócitos T Reguladores , Microambiente Tumoral
19.
Math Biosci Eng ; 19(1): 271-286, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902991

RESUMO

Supply chain network is important for the enterprise to improve the operation and management, but has become more complicated to optimize in reality. With the consideration of multiple objectives and constraints, this paper proposes a constrained large-scale multi-objective supply chain network (CLMSCN) optimization model. This model is to minimize the total operation cost (including the costs of production, transportation, and inventory) and to maximize the customer satisfaction under the capacity constraints. Besides, a coevolutionary algorithm based on the auxiliary population (CAAP) is proposed, which uses two populations to solve the CLMSCN problem. One population is to solve the original complex problem, and the other population is to solve the problem without any constraints. If the infeasible solutions are generated in the first population, a linear repair operator will be used to improve the feasibility of these solutions. To validate the effectivity of the CAAP algorithm, the experiment is conducted on the randomly generated instances with three different problem scales. The results show that the CAAP algorithm can outperform other compared algorithms, especially on the large-scale instances.


Assuntos
Algoritmos , Meios de Transporte
20.
Adv Mater ; 34(7): e2107355, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34852181

RESUMO

Owing to their outstanding electrical/electrochemical performance, operational stability, mechanical flexibility, and decent biocompatibility, organic mixed ionic-electronic conductors have shown great potential as implantable electrodes for neural recording/stimulation and as active channels for signal switching/amplifying transistors. Nonetheless, no studies exist on a general design rule for high-performance electrochemical diodes, which are essential for highly functional circuit architectures. In this work, generalizable electrochemical diodes with a very high current density over 30 kA cm-2 are designed by introducing an asymmetric active layer based on organic mixed ionic-electronic conductors. The underlying mechanism on polarity-sensitive balanced ionic doping/dedoping is elucidated by numerical device analysis and in operando spectroelectrochemical potential mapping, while the general material requirements for electrochemical diode operation are deduced using various types of conjugated polymers. In parallel, analog signal rectification and digital logic processing circuits are successfully demonstrated to show the broad impact of circuits incorporating organic electrochemical diodes. It is expected that organic electrochemical diodes will play vital roles in realizing multifunctional soft bioelectronic circuitry in combination with organic electrochemical transistors.

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