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1.
J Am Chem Soc ; 146(3): 1825-1831, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38226869

RESUMO

We report a convergent and efficient total synthesis of the C-nor D-homo steroidal alkaloid (+)-heilonine with a hexacyclic ring system, nine stereocenters, and a trans-hydrindane moiety. Our synthesis features four selective C-H functionalizations to form key C-C bonds and stereocenters, a Stille carbonylative cross-coupling to connect the AB ring system with the DEF ring system, and a Nazarov cyclization to construct the five-membered C ring. These enabling transformations significantly reduced functional group manipulations and delivered (+)-heilonine in 11 or 13 longest linear sequence (LLS) steps.

2.
Anal Chem ; 96(33): 13379-13388, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39105793

RESUMO

Highly sensitive detection of low-frequency EGFR-L858R mutation is particularly important in guiding targeted therapy of nonsmall-cell lung carcinoma (NSCLC). To this end, a ligase chain reaction (LCR)-based electrochemical biosensor (e-LCR) with an inverted sandwich-type architecture was provided by combining a cooperation of lambda exonuclease-RecJf exonuclease (λ-RecJf exo). In this work, by designing a knife-like DNA substrate (an overhang ssDNA part referred to the "knife arm") and introducing the λ-RecJf exo, the unreacted DNA probes in the LCR were specially degraded while only the ligated products were preserved, after which the ligated knife-like DNA products were hybridized with capture probes on the gold electrode surface through the "knife arms", forming the inverted sandwich-type DNA structure and bringing the methylene blue-label close to the electrode surface to engender the electrical signal. Finally, the sensitivity of the e-LCR could be improved by 3 orders of magnitude with the help of the λ-RecJf exo, and due to the mutation recognizing in the ligation site of the employed ligase, this method could detect EGFR-L858R mutation down to 0.01%, along with a linear range of 1 fM-10 pM and a limit detection of 0.8 fM. Further, the developed method could distinguish between L858R positive and negative mutations in cultured cell samples, tumor tissue samples, and plasma samples, whose accuracy was verified by the droplet digital PCR, holding a huge potential in liquid biopsy for precisely guiding individualized-treatment of NSCLC patients with advantages of high sensitivity, low cost, and adaptability to point-of-care testing.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Técnicas Eletroquímicas , Receptores ErbB , Exodesoxirribonucleases , Neoplasias Pulmonares , Mutação , Receptores ErbB/genética , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Exodesoxirribonucleases/química , Exodesoxirribonucleases/metabolismo , Exodesoxirribonucleases/genética , Técnicas Biossensoriais , Reação em Cadeia da Ligase , Limite de Detecção , Proteínas Virais
3.
Biochem Biophys Res Commun ; 707: 149513, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38508051

RESUMO

Cancer is a significant global health concern, and finding effective methods to treat it has been a focus of scientific research. It has been discovered that the growth, invasion, and metastasis of tumors are closely related to the environment in which they exist, known as the tumor microenvironment (TME). The immune response interacting with the tumor occurring within the TME constitutes the tumor immune microenvironment, and the immune response can lead to anti-tumor and pro-tumor outcomes and has shown tremendous potential in immunotherapy. A channel called the P2X7 receptor (P2X7R) has been identified within the TME. It is an ion channel present in various immune cells and tumor cells, and its activation can lead to inflammation, immune responses, angiogenesis, immunogenic cell death, and promotion of tumor development. This article provides an overview of the structure, function, and pharmacological characteristics of P2X7R. We described the concept and components of tumor immune microenvironment and the influence immune components has on tumors. We also outlined the impact of P2X7R regulation and how it affects the development of tumors and summarized the effects of drugs targeting P2X7R on tumor progression, both past and current, assisting researchers in treating tumors using P2X7R as a target.


Assuntos
Neoplasias , Receptores Purinérgicos P2X7 , Microambiente Tumoral , Humanos , Neoplasias/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Animais
4.
Respir Res ; 25(1): 203, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730430

RESUMO

BACKGROUND: Although electronic nose (eNose) has been intensively investigated for diagnosing lung cancer, cross-site validation remains a major obstacle to be overcome and no studies have yet been performed. METHODS: Patients with lung cancer, as well as healthy control and diseased control groups, were prospectively recruited from two referral centers between 2019 and 2022. Deep learning models for detecting lung cancer with eNose breathprint were developed using training cohort from one site and then tested on cohort from the other site. Semi-Supervised Domain-Generalized (Semi-DG) Augmentation (SDA) and Noise-Shift Augmentation (NSA) methods with or without fine-tuning was applied to improve performance. RESULTS: In this study, 231 participants were enrolled, comprising a training/validation cohort of 168 individuals (90 with lung cancer, 16 healthy controls, and 62 diseased controls) and a test cohort of 63 individuals (28 with lung cancer, 10 healthy controls, and 25 diseased controls). The model has satisfactory results in the validation cohort from the same hospital while directly applying the trained model to the test cohort yielded suboptimal results (AUC, 0.61, 95% CI: 0.47─0.76). The performance improved after applying data augmentation methods in the training cohort (SDA, AUC: 0.89 [0.81─0.97]; NSA, AUC:0.90 [0.89─1.00]). Additionally, after applying fine-tuning methods, the performance further improved (SDA plus fine-tuning, AUC:0.95 [0.89─1.00]; NSA plus fine-tuning, AUC:0.95 [0.90─1.00]). CONCLUSION: Our study revealed that deep learning models developed for eNose breathprint can achieve cross-site validation with data augmentation and fine-tuning. Accordingly, eNose breathprints emerge as a convenient, non-invasive, and potentially generalizable solution for lung cancer detection. CLINICAL TRIAL REGISTRATION: This study is not a clinical trial and was therefore not registered.


Assuntos
Aprendizado Profundo , Nariz Eletrônico , Neoplasias Pulmonares , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Respiratórios/métodos , Neoplasias Pulmonares/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes
5.
Anal Biochem ; 694: 115605, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38992485

RESUMO

Sepsis is a life-threatening condition characterized by organ dysfunction resulting from a dysregulated host response to infection. Dysregulated tryptophan (TRP) metabolites serve as significant indicators for endogenous immune turnovers and abnormal metabolism in the intestinal microbiota during sepsis. Therefore, a high coverage determination of TRP and its metabolites in sepsis is beneficial for the diagnosis and prognosis of sepsis, as well as for understanding the underlying mechanism of sepsis development. However, similar structures in TRP metabolites make it challenging for separation and metabolite identification. Here, high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) was developed to determine TRP metabolites in rat serum. The first-order derivative spectrophotometry of targeted metabolites in the serum was investigated and proved to be promising for chromatographic peak annotation across different columns and systems. The established method separating the targeted metabolites was optimized and validated to be sensitive and accurate. Application of the method revealed dysregulated TRP metabolites, associated with immune disorders and NAD + metabolism in both the host and gut flora in septic rats. Our findings indicate that the derivative spectrophotometry-assisted method enhances metabolite identifications for the chromatographic systems based on DAD detectors and holds promise for precision medicine in sepsis.


Assuntos
Microbioma Gastrointestinal , Sepse , Triptofano , Triptofano/metabolismo , Animais , Sepse/microbiologia , Sepse/metabolismo , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Ratos Sprague-Dawley , Espectrofotometria
6.
BMC Infect Dis ; 24(1): 314, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486143

RESUMO

BACKGROUND: Lassa fever is a hemorrhagic disease caused by Lassa virus (LASV), which has been classified by the World Health Organization as one of the top infectious diseases requiring prioritized research. Previous studies have provided insights into the classification and geographic characteristics of LASV lineages. However, the factor of the distribution and evolution characteristics and phylodynamics of the virus was still limited. METHODS: To enhance comprehensive understanding of LASV, we employed phylogenetic analysis, reassortment and recombination detection, and variation evaluation utilizing publicly available viral genome sequences. RESULTS: The results showed the estimated the root of time of the most recent common ancestor (TMRCA) for large (L) segment was approximately 634 (95% HPD: [385879]), whereas the TMRCA for small (S) segment was around 1224 (95% HPD: [10301401]). LASV primarily spread from east to west in West Africa through two routes, and in route 2, the virus independently spread to surrounding countries through Liberia, resulting in a wider spread of LASV. From 1969 to 2018, the effective population size experienced two significant increased, indicating the enhanced genetic diversity of LASV. We also found the evolution rate of L segment was faster than S segment, further results showed zinc-binding protein had the fastest evolution rate. Reassortment events were detected in multiple lineages including sub-lineage IIg, while recombination events were observed within lineage V. Significant amino acid changes in the glycoprotein precursor of LASV were identified, demonstrating sequence diversity among lineages in LASV. CONCLUSION: This study comprehensively elucidated the transmission and evolution of LASV in West Africa, providing detailed insights into reassortment events, recombination events, and amino acid variations.


Assuntos
Febre Lassa , Vírus Lassa , Humanos , Vírus Lassa/genética , Filogenia , Febre Lassa/epidemiologia , Aminoácidos , Libéria
7.
J Appl Microbiol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39108092

RESUMO

AIMS: To identify efficient, broad-spectrum, and non-toxic preservatives for natural agricultural products, eight essential oils were screened for high inhibitory and antioxidant activities against spoilage microbes. METHODS AND RESULTS: The zone of inhibition test and minimum inhibitory concentration (MIC) assay were performed to assess the antimicrobial activity of eight essential oils against B. subtilis, S. aureus, Penicillium, Saccharomyces, and E. coli. Among the eight essential oils, garlic and rose essential oils exhibited the best inhibitory effects, their MICs against the spoilage microbes were 40-640 µL/L and 10-320 µL/L, respectively. In addition, the antioxidant activities of eight essential oils were compared using the DPPH and ABTS radical-scavenging assays and the reducing power assay. eight essential oils had antioxidant capacity, among which rosemary, thyme, rose, and tea tree essential oils performed best. Moreover, the combination of thyme and rose exerted stronger antioxidant activity. Therefore, the concentrations of rose and garlic, and thyme essential oils were optimized using response surface methodology to obtain the optimal composite ratios, which were 1254 µL/L, 640 µL/L, and 1228 µL/L for rose, garlic, and thyme, respectively. The DPPH free radical-scavenging rate detected using this formulation was 50.2%, basically consistent with the prediction. Zone of inhibition diameters with the compound essential oil, against five spoilage microbes, were all greater than 45 mm. CONCLUSIONS: The essential oil combination had high antimicrobial, against agricultural product spoilage microbes, and antioxidant activities.

8.
Ecotoxicol Environ Saf ; 277: 116330, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636406

RESUMO

PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and multiple diseases in humans. Previously, 5 toxicity pathways were proposed from hundreds of toxicological studies that underlie BaP-induced lung injuries, and a "Bottom-up" approach was established to identify small non-coding RNAs that drive BaP-induced pulmonary effects by investigating the activation of these pathways in vitro, and the expression of the candidate microRNAs were validated in tissues of patients with lung diseases from publications. Here in this study, we employed the "Bottom-up" approach to identifying the roles of piRNAs and further validated the mechanisms in vivo using mouse acute lung injury model. Specifically, by non-coding RNA profiling in in vitro BaP exposure, a total of 3 suppressed piRNAs that regulate 5 toxicity pathways were proposed, including piR-004153 targeting CYP1A1, FGFR1, ITGA5, IL6R, NGRF, and SDHA, piR-020326 targeting CDK6, and piR-020388 targeting RASD1. Animal experiments demonstrated that tail vein injection of respective formulated agomir-piRNAs prior to BaP exposure could all alleviate acute lung injury that was shown by histopathological and biochemical evidences. Immunohistochemical evaluation focusing on NF-kB and Bcl-2 levels showed that exogenous piRNAs protect against BaP-induced inflammation and apoptosis, which further support that the inhibition of the 3 piRNAs had an important impact on BaP-induced lung injuries. This mechanism-driven, endpoint-supported result once again confirmed the plausibility and efficiency of the approach integrating in silico, in vitro, and in vivo evidences for the purpose of identifying key molecules.


Assuntos
Lesão Pulmonar Aguda , Benzo(a)pireno , RNA de Interação com Piwi , Animais , Masculino , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Benzo(a)pireno/toxicidade , Camundongos Endogâmicos C57BL
9.
J Formos Med Assoc ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971711

RESUMO

BACKGROUNDPURPOSE: Immunotherapy is a new treatment option for patients with Lung Cancer (LC). However, relatively limited research has explored about patients' perception of hope and its associated factors during the process. This study aimed to examine level of perceived hope and the factors related to hope, with a particular focus on treatment and physically related factors, in LC patients receiving immunotherapy. METHODS: A cross-sectional study was conducted and patients who had already received at least one immunotherapy cycle were recruited from two hospitals in northern Taiwan. The questionnaire included a background information form, the Herth's Hope Index, and the Symptom Severity Scale. Stepwise regression was applied to identify the most robust factors related to level of hope in the participants. RESULTS: A total of 130 patients were recruited. Overall, patients reported moderate to high levels of hope and mild symptoms. Fatigue, weakness, appearance changes, pruritus, and shortness of breath were identified as the most severe symptoms. Further regression analysis showed that patients with poor performance status, less immunotherapy cycles, higher level of fatigue, and more severe pruritus reported to have lower level of hope which explained 47% of the variances. CONCLUSIONS: This study revealed that lung cancer patients undergoing immunotherapy had moderate level of hope. Patients' performance status, selected symptoms and times of receiving immunotherapy were the robust factors related to hope. Systematic assessment of patients' symptoms and the development of appropriate interventions to reduce distress and enhance hope are strongly recommended for both clinical care and research.

10.
J Formos Med Assoc ; 123(8): 875-881, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38195317

RESUMO

BACKGROUND: Lorlatinib is a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-positive metastatic non-small cell lung cancer (NSCLC). In a global phase II study, patients who experience disease progression despite prior treatment with ALK tyrosine kinase inhibitors (TKIs) was assessed. Herein, we report real-world clinical outcomes of lorlatinib-treated patients with ALK-positive advanced NSCLC who were heavily pretreated and progressed on first- and second-generation ALK-TKIs, in a Taiwanese population under the lorlatinib expanded access program (EAP). METHODS: This multicenter observational study examined the effectiveness and safety of ALK-positive advanced NSCLC patients that progressed from previous second-generation ALK-TKI therapy and received lorlatinib treatment subsequently. Patients who received lorlatinib treatment under EAP between Jul 2017 and Sep 2019 were eligible. Patients were followed for at least one year from the first lorlatinib treatment until study completion. RESULTS: Sixty-three patients were eligible for safety analysis (male: 46.0 %; median age: 52.8 [27.5-78.3] years; brain metastases: 81.0 %). Fifty-four patients with more than one-month lorlatinib treatment were included in the effectiveness analysis. Prior to lorlatinib treatment, 10 patients (18.5 %) received one ALK-TKI, 27 (50.0 %) received two ALK-TKIs, and 17 (31.5 %) received three or more ALK-TKIs. The overall median rwPFS was 9.2 months (95 % confidence interval: 5.3-21.1). The best overall response rate (n = 51) was 13.7 %, with a disease control rate of 80.4 %. CONCLUSION: Lorlatinib exhibits substantial activity and tolerability when used clinically in a later-line setting in a Taiwanese population with ALK-positive advanced NSCLC.


Assuntos
Aminopiridinas , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas , Lactamas Macrocíclicas , Lactamas , Neoplasias Pulmonares , Pirazóis , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Idoso , Taiwan , Aminopiridinas/uso terapêutico , Lactamas/uso terapêutico , Adulto , Pirazóis/uso terapêutico , Lactamas Macrocíclicas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico
11.
J Formos Med Assoc ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39152072

RESUMO

INTRODUCTION: EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant subsequent treatment. For this study, we aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) among advanced EGFR-mutant NSCLC patients receiving platinum-pemetrexed after progression on EGFR-TKIs. Our analysis specifically focuses on 1st-line treatments limited to 1st- or 2nd-generation EGFR-TKIs, while not restricting later-line treatments involving osimertinib prior to chemotherapy. MATERIALS AND METHODS: From 2012 to 2017, 363 patients who received first-line treatment with first- or second-generation EGFR-TKIs, including gefitinib, erlotinib, and afatinib were enrolled. Some patients received different EGFR-TKIs, including osimertinib, as later-line treatment before platinum-pemetrexed. RESULTS: Median OS from the initiation of platinum-pemetrexed was 22.0 months and median PFS with platinum-pemetrexed was 6.2 months. In the multivariate Cox model, we identified three independent prognostic factors for better OS: postoperative recurrence (HR: 0.34, p = 0.004), first-line EGFR-TKI PFS ≥12 months (HR: 0.54, p = 0.002), and osimertinib treatment after platinum-pemetrexed (HR: 0.56, p = 0.005) while BMI <18.5 indicated poor prognosis (HR:1.76, p = 0.049). No statistically significant independent prognostic factors for PFS were found. Receiving osimertinib before platinum-pemetrexed treatment did not impact PFS with platinum-pemetrexed treatment (HR: 1.11, p = 0.64). CONCLUSION: Postoperative recurrence, first-line EGFR-TKI PFS ≥12 months and osimertinib treatment after platinum-pemetrexed predicted better OS, while BMI <18.5 predicted worse OS. Osimertinib treatment before platinum-pemetrexed treatment did not affect the efficacy of platinum-pemetrexed.

12.
Sensors (Basel) ; 24(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39001102

RESUMO

Visible light communication (VLC) is a promising complementary technology to its radio frequency (RF) counterpart to satisfy the high quality-of-service (QoS) requirements of intelligent vehicular communications by reusing LED street lights. In this paper, a hybrid handover scheme for vehicular VLC/RF communication networks is proposed to balance QoS and handover costs by considering the vertical handover and horizontal handover together judging from the mobile state of the vehicle. A Markov decision process (MDP) is formulated to describe this hybrid handover problem, with a cost function balancing the handover consumption, delay, and reliability. A value iteration algorithm was applied to solve the optimal handover policy. The simulation results demonstrated the performance of the proposed hybrid handover scheme in comparison to other benchmark schemes.

13.
Water Sci Technol ; 90(1): 1-17, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007303

RESUMO

Reverse osmosis (RO) membrane fouling and biological contamination problems faced by seawater desalination systems are microbiologically related. We used full-length 16S rRNA gene sequencing to assess the bacterial community structure and chlorine-resistant bacteria (CRB) associated with biofilm growth in different treatment processes under the winter mode of a chlorinated seawater desalination system in China. At the outset of the winter mode, certain CRB, such as Acinetobacter, Pseudomonas, and Bacillus held sway over the bacterial community structure, playing a pivotal role in biofouling. At the mode's end, Deinococcus and Paracoccus predominated, with Pseudomonas and Roseovarius following suit, while certain CRB genera still maintained their dominance. RO and chlorination are pivotal factors in shaping the bacterial community structure and diversity, and increases in total heterotrophic bacterial counts and community diversity in safety filters may adversely affect the effectiveness of subsequent RO systems. Besides, the bacterial diversity and culturable biomass in the water produced by the RO system remain high, and some conditionally pathogenic CRBs pose a certain microbial risk as a source of drinking water. Targeted removal of these CRBs will be an important area of research for advancing control over membrane clogging and ensuring water quality safety in the future.


Assuntos
Bactérias , Incrustação Biológica , Halogenação , Centrais Nucleares , RNA Ribossômico 16S , Purificação da Água , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Purificação da Água/métodos , Água do Mar/microbiologia , Cloro/química
14.
Clin Psychol Psychother ; 31(4): e3023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978207

RESUMO

OBJECTIVE: This study aims to assess the clinical effectiveness of combining mindfulness-based stress reduction (MBSR) with exercise intervention in improving anxiety, depression, sleep quality and mood regulation in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 60 patients with NSCLC who had not received surgical treatment were selected using convenience sampling and divided into an intervention group and control group, with 30 patients in each group. The control group received conventional psychological nursing care, whereas the intervention group received a combination of MBwSR and exercise therapy. Before the intervention, a questionnaire was completed to collect the basic data of the two groups. Further questionnaires were administered at 6 and 8 weeks after treatment to assess anxiety, depression, sleep quality and other items included in the five-item Brief Symptom Rating Scale (BSRS-5). RESULTS: No significant differences between the intervention and control groups were identified in terms of personal and clinical characteristics (p > 0.05). No significant differences were determined in the BSRS-5, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) or Pittsburgh Sleep Quality Index (PSQI) scores between the intervention and control groups before the intervention. However, 6 and 8 weeks after the intervention, scores were significantly lower in both groups (p < 0.001). Significant differences in the BSRS-5, SAS, SDS and PSQI scores were identified between the two groups at different time points (p < 0.001). CONCLUSION: The combination of MBSR and exercise intervention demonstrated improvements in anxiety, depression, sleep quality and BSRS-5 scores in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Terapia por Exercício , Neoplasias Pulmonares , Atenção Plena , Estresse Psicológico , Humanos , Atenção Plena/métodos , Feminino , Masculino , Carcinoma Pulmonar de Células não Pequenas/psicologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Pessoa de Meia-Idade , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Terapia por Exercício/métodos , Terapia por Exercício/psicologia , Estresse Psicológico/terapia , Estresse Psicológico/psicologia , Resultado do Tratamento , Idoso , Inquéritos e Questionários , Adulto , Qualidade do Sono , Terapia Combinada , Bem-Estar Psicológico
16.
Polymers (Basel) ; 16(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38475393

RESUMO

Triply periodic minimal surfaces (TPMSs) have demonstrated significant potential in lattice structure design and have been successfully applied across multiple industrial fields. In this work, a novel lattice structure with tunable anisotropic properties is proposed based on two typical TPMS types, and their mechanical performances are studied both experimentally and numerically after being fabricated using a polymer 3D printing process. Initially, adjustments are made to the original TPMS lattice structures to obtain honeycomb lattice structures, which are found to possess significant anisotropy, by utilizing numerical homogenization methods. Based on this, a continuous self-twisting deformation is proposed to change the topology of the honeycomb lattice structures to largely tune the mechanical properties. Quasi-static compression experiments are conducted with different twisting angles, and the results indicate that self-twisting can affect the mechanical properties in specific directions of the structure, and also enhance the energy absorption capacity. Additionally, it mitigates the risk of structural collapse and failure during compression while diminishing structural anisotropy. The proposed self-twisting strategy, based on honeycomb lattice structures, has been proven valuable in advancing the investigation of lattice structures with largely tunable mechanical properties.

17.
Int J Biol Macromol ; 265(Pt 1): 130789, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479668

RESUMO

In this study, the feasibility of shellac nanofibers as carrier system for colonic delivery of quercetin was evaluated. Firstly, the nanofibers without and with different amounts (2.5 %, 5.0 %, and 7.5 %) of quercetin were fabricated using pure shellac as a carrier by electrospinning. The morphology of nanofibers was bead-shape confirmed by SEM. FTIR, XRD, and DSC analysis showed that quercetin was encapsulated into shellac nanofibers, forming an amorphous complex. The molecular docking simulation indicated quercetin bound well to shellac through hydrogen bonding and van der Waals forces. These nanofibers had higher thermal stability than pure quercetin, and their surface wettability exhibited a pH-responsive behavior. The loading capacity of quercetin varied from 2.25 % to 6.84 % with the increased amount of quercetin, and it affected the stability of nanofibers in food simulants by measuring the release profiles of quercetin. The shellac nanofibers had high gastrointestinal stability, with a minimum quercetin release of 16.87 % in simulated digestive fluids, while the remaining quercetin was delivered to the colon and was released gradually. Moreover, the nanofibers exerted enhanced anticancer activity against HCT-116 cells by arresting cell cycle in G0/G1 phase and inducing cell apoptosis. Overall, shellac nanofibers are promising materials for colon-targeted delivery of active compounds.


Assuntos
Nanofibras , Quercetina , Resinas Vegetais , Quercetina/farmacologia , Quercetina/metabolismo , Simulação de Acoplamento Molecular , Colo
18.
Heliyon ; 10(11): e32103, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38867972

RESUMO

Continuous gain and loss of genes are the primary driving forces of bacterial evolution and environmental adaptation. Studying bacterial evolution in terms of protein domain, which is the fundamental function and evolutionary unit of proteins, can provide a more comprehensive understanding of bacterial differentiation and phenotypic adaptation processes. Therefore, we proposed a phylogenetic tree-based method for detecting genetic gain and loss events in terms of protein domains. Specifically, the method focuses on a single domain to trace its evolution process or on multiple domains to investigate their co-evolution principles. This novel method was validated using 122 Shigella isolates. We found that the loss of a significant number of domains was likely the main driving force behind the evolution of Shigella, which could reduce energy expenditure and preserve only the most essential functions. Additionally, we observed that simultaneously gained and lost domains were often functionally related, which can facilitate and accelerate phenotypic evolutionary adaptation to the environment. All results obtained using our method agree with those of previous studies, which validates our proposed method.

19.
Med Image Anal ; 95: 103199, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759258

RESUMO

The accurate diagnosis on pathological subtypes for lung cancer is of significant importance for the follow-up treatments and prognosis managements. In this paper, we propose self-generating hybrid feature network (SGHF-Net) for accurately classifying lung cancer subtypes on computed tomography (CT) images. Inspired by studies stating that cross-scale associations exist in the image patterns between the same case's CT images and its pathological images, we innovatively developed a pathological feature synthetic module (PFSM), which quantitatively maps cross-modality associations through deep neural networks, to derive the "gold standard" information contained in the corresponding pathological images from CT images. Additionally, we designed a radiological feature extraction module (RFEM) to directly acquire CT image information and integrated it with the pathological priors under an effective feature fusion framework, enabling the entire classification model to generate more indicative and specific pathologically related features and eventually output more accurate predictions. The superiority of the proposed model lies in its ability to self-generate hybrid features that contain multi-modality image information based on a single-modality input. To evaluate the effectiveness, adaptability, and generalization ability of our model, we performed extensive experiments on a large-scale multi-center dataset (i.e., 829 cases from three hospitals) to compare our model and a series of state-of-the-art (SOTA) classification models. The experimental results demonstrated the superiority of our model for lung cancer subtypes classification with significant accuracy improvements in terms of accuracy (ACC), area under the curve (AUC), positive predictive value (PPV) and F1-score.


Assuntos
Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/classificação , Tomografia Computadorizada por Raios X/métodos , Redes Neurais de Computação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Algoritmos
20.
Micromachines (Basel) ; 15(1)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38258226

RESUMO

SiCp/Al composite materials are widely used in various industries such as the aerospace and the electronics industries, primarily due to their excellent material properties. However, their machinability is significantly weakened due to their unique characteristics. Consequently, efficient and precise machining technology for SiCp/Al composite materials has become a crucial research area. By conducting a comprehensive analysis of the relevant research literature from both domestic and international sources, this study examines the processing mechanism, as well as the turning, milling, drilling, grinding, special machining, and hybrid machining characteristics, of SiCp/Al composite materials. Moreover, it summarizes the latest research progress in composite material processing while identifying the existing problems and shortcomings in this area. The aim of this review is to enhance the machinability of SiCp/Al composite materials and promote high-quality and efficient processing methods.

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