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1.
Eur J Med Chem ; 275: 116610, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38896992

RESUMO

Mutations in IDH1 are commonly observed across various cancers, causing the conversion of α-KG to 2-HG. Elevated levels of 2-HG disrupt histone and DNA demethylation processes, promoting tumor development. Consequently, there is substantial interest in developing small molecule inhibitors targeting the mutant enzymes. Herein, we report a structure-based high-throughput virtual screening strategy using a natural products library, followed by hit-to-lead optimization. Through this process, we discover a potent compound, named 11s, which exhibited significant inhibition to IDH1 R132H and IDH1 R132C with IC50 values of 124.4 and 95.7 nM, respectively. Furthermore, 11s effectively reduced 2-HG formation, with EC50 values of 182 nM in U87 R132H cell, and 84 nM in HT-1080 cell. In addition, 11s significantly reduced U87 R132H and HT-1080 cell proliferation with GC50 values of 3.48 and 1.38 µM, respectively. PK-PD experiments further confirmed that compound 11s significantly decreased 2-HG formation in an HT-1080 xenograft mouse model, resulting in notable suppression of tumor growth without apparent loss in body weight.

2.
Neurol Sci ; 45(7): 3495-3501, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714597

RESUMO

BACKGROUND: Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. METHODS: In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failure from other factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. RESULTS: A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. CONCLUSION: This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.


Assuntos
Hidrocefalia , Derivação Ventriculoperitoneal , Humanos , Derivação Ventriculoperitoneal/efeitos adversos , Feminino , Masculino , Hidrocefalia/cirurgia , Hidrocefalia/líquido cefalorraquidiano , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Adulto , Falha de Equipamento
3.
J Med Chem ; 67(11): 9028-9053, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38787534

RESUMO

This work identified a class of cyanomethylquinolones (CQs) and their carboxyl analogues as potential multitargeting antibacterial candidates. Most of the prepared compounds showed high antibacterial activities against most of the tested bacteria, exhibiting lower MIC values (0.125-2 µg/mL) than those of clinical norfloxacin, ciprofloxacin, and clinafloxacin. The low hemolysis, drug resistance, and cytotoxicity, as well as good predictive pharmacokinetics of active CQs and carboxyl analogues revealed their development potential. Furthermore, they could eradicate the established biofilm, facilitating bacterial exposure to these antibacterial candidates. These active compounds could induce bacterial death through multitargeting effects, including intercalating into DNA, up-regulating reactive oxygen species, damaging membranes directly, and impeding metabolism. Moreover, the highly active cyclopropyl CQ 15 exhibited more effective in vivo anti-MRSA potency than ciprofloxacin. These findings highlight the potential of CQs and their carboxyl analogues as multitargeting broad-spectrum antibacterial candidates for treating intractable bacterial infections.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Quinolonas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/síntese química , Humanos , Relação Estrutura-Atividade , Biofilmes/efeitos dos fármacos , Camundongos , Hemólise/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Ciprofloxacina/análogos & derivados , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
4.
Front Neurorobot ; 18: 1401075, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774519

RESUMO

Introduction: In recent years, the perceptual capabilities of robots have been significantly enhanced. However, the task execution of the robots still lacks adaptive capabilities in unstructured and dynamic environments. Methods: In this paper, we propose an ontology based autonomous robot task processing framework (ARTProF), to improve the robot's adaptability within unstructured and dynamic environments. ARTProF unifies ontological knowledge representation, reasoning, and autonomous task planning and execution into a single framework. The interface between the knowledge base and neural network-based object detection is first introduced in ARTProF to improve the robot's perception capabilities. A knowledge-driven manipulation operator based on Robot Operating System (ROS) is then designed to facilitate the interaction between the knowledge base and the robot's primitive actions. Additionally, an operation similarity model is proposed to endow the robot with the ability to generalize to novel objects. Finally, a dynamic task planning algorithm, leveraging ontological knowledge, equips the robot with adaptability to execute tasks in unstructured and dynamic environments. Results: Experimental results on real-world scenarios and simulations demonstrate the effectiveness and efficiency of the proposed ARTProF framework. Discussion: In future work, we will focus on refining the ARTProF framework by integrating neurosymbolic inference.

5.
Eur J Med Chem ; 268: 116219, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368710

RESUMO

The emergence of drug-resistant microorganisms threatens human health, and it is usually exacerbated by the formation of biofilm, which forces the development of new antibacterial agents with antibiofilm activity. In this work, a novel category of aminothiazoximone-corbelled ethoxycarbonylpyrimidones (ACEs) was designed and synthesized, and some of the prepared ACEs showed potent bioactivity against the tested bacteria. In particular, imidazolyl ACE 6c showed better inhibitory activity towards Acinetobacter baumannii and Escherichia coli with MIC values both of 0.0066 mmol/L than norfloxacin. It was also revealed that imidazolyl ACE 6c not only possessed inconspicuous hemolytic rate and cytotoxicity, low drug resistance and no risk of penetrating the blood-brain barrier, but also exhibited obvious biofilm inhibition and eradication activities. The preliminary mechanism research suggested that imidazolyl ACE 6c could induce metabolic dysfunction by deactivating lactate dehydrogenase and promote the accumulation of reactive oxygen species to decrease the reduced glutathione and ultimately cause oxidative damage in bacteria. Furthermore, ACE 6c was also found that could insert into DNA to form the supramolecular complex of 6c-DNA and trigger cell death. The multidimensional effect might promote bacterial cell rupture, leading to the leakage of intracellular content. These findings manifested that novel imidazolyl ACE 6c as a potential multitargeting antibacterial agent with potent antibiofilm activity could provide new possibility for the treatment of refractory biofilm-intensified bacterial infections.


Assuntos
Antibacterianos , Norfloxacino , Humanos , Antibacterianos/farmacologia , Norfloxacino/farmacologia , Bactérias Gram-Negativas , Bactérias , Biofilmes , DNA/farmacologia , Testes de Sensibilidade Microbiana
6.
Eur J Med Chem ; 265: 116107, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38171147

RESUMO

Unique benzopyridone cyanoacetates (BCs) as new type of promising broad-spectrum antibacterial candidates were discovered with large potential to combat the lethal multidrug-resistant bacterial infections. Many prepared BCs showed broad antibacterial spectrum with low MIC values against the tested strains. Some highly active BCs exhibited rapid sterilization capacity, low resistant trend and good predictive pharmacokinetic properties. Furthermore, the highly active sodium BCs (NaBCs) displayed low hemolysis and cytotoxicity, and especially octyl NaBC 5g also showed in vivo potent anti-infective potential and appreciable pharmacokinetic profiles. A series of preliminary mechanistic explorations indicated that these active BCs could effectively eliminate bacterial biofilm and destroy membrane integrity, thus resulting in the leakage of bacterial cytoplasm. Moreover, their unique structures might further bind to intracellular DNA, DNA gyrase and topoisomerase IV through various direct noncovalent interactions to hinder bacterial reproduction. Meanwhile, the active BCs also induced bacterial oxidative stress and metabolic disturbance, thereby accelerating bacterial apoptosis. These results provided a bright hope for benzopyridone cyanoacetates as potential novel multitargeting broad-spectrum antibacterial candidates to conquer drug resistance.


Assuntos
Antibacterianos , Inibidores da Topoisomerase II , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , DNA Girase/metabolismo , DNA Topoisomerase IV , Testes de Sensibilidade Microbiana , Inibidores da Topoisomerase II/farmacologia , Piridonas/química , Piridonas/farmacologia , Nitrilas/química , Nitrilas/farmacologia
7.
Nat Commun ; 15(1): 764, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278943

RESUMO

The gate-type carbon nanotubes cathodes exhibit advantages in long-term stable emission owing to the uniformity of electrical field on the carbon nanotubes, but the gate inevitably reduces the transmittance of electron beam, posing challenges for system stabilities. In this work, we introduce electron beam focusing technique using the self-charging SiNx/Au/Si gate. The potential of SiNx is measured to be approximately -60 V quickly after the cathode turning on, the negative potential can be maintained as the emission goes on. The charged surface generates rebounding electrostatic forces on the following electrons, significantly focusing the electron beam on the center of gate hole and allowing them to pass through gate with minimal interceptions. An average transmittance of 96.17% is observed during 550 hours prototype test, the transmittance above 95% is recorded for the cathode current from 2.14 µA to 3.25 mA with the current density up to 17.54 mA cm-2.

8.
Eur J Med Chem ; 264: 116008, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056298

RESUMO

Proliferating cancer cells are characterized by the Warburg effect, a metabolic alteration in which ATP is generated from cytoplasmic glycolysis instead of oxidative phosphorylation. The pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (PDC/PDK) axis plays a crucial role in this effect and has been identified as a potential target for anticancer drug development. Herein, we present the discovery and pharmacological evaluation of potent PDK inhibitors targeting the PDK/PDC axis. We successfully identified 6 compounds from a small molecule library through a structure-based virtual screening campaign and evaluated their enzymatic inhibitory potencies for PDK1-4. Our results indicated that compound 1 exhibited submicromolar inhibitory activities against PDK1-3 (IC50 = 109.3, 135.8, and 458.7 nM, respectively), but is insensitive to PDK4 (IC50 = 8.67 µM). Furthermore, compound 1 inhibited the proliferation of A549 cells with an EC50 value of 10.7 µM. In addition, compound 1 induced cell apoptosis, arrested the cell cycle at the S phase, and reduced cell invasion and migration, while showing low in vivo toxicity at a high dose. Based on these observations, it can be concluded that compound 1 is a promising anti-PDK1-3 lead that merits further investigation.


Assuntos
Proteínas Serina-Treonina Quinases , Complexo Piruvato Desidrogenase , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Fosforilação Oxidativa , Divisão Celular
9.
J Neurosurg ; 140(4): 1019-1028, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856412

RESUMO

OBJECTIVE: The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs. METHODS: A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0-2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor-1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion. RESULTS: Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = -0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001). CONCLUSIONS: Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.


Assuntos
Acromegalia , Adenoma , Neoplasias Hipofisárias , Adulto , Masculino , Feminino , Humanos , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Receptores de Somatostatina/uso terapêutico , Acromegalia/cirurgia , Acromegalia/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Estudos Retrospectivos , Adenoma/patologia , Somatostatina/uso terapêutico , Neoplasias Hipofisárias/cirurgia , RNA Mensageiro/metabolismo
10.
Eur J Med Chem ; 264: 115973, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38096652

RESUMO

Infections caused by drug-resistant bacteria have become a new challenge in infection treatment, gravely endangering public health. Chloramphenicol (CL) is a well-known antibiotic which has lost its efficacy due to bacterial resistance. To address this issue, herein we report the design, synthesis and biological evaluations of novel triphenylphosphonium chloramphenicol conjugates (TPP+-CL). Study results indicated that compounds 39 and 42 possessed remarkable antibacterial effects against clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1 to 2 µg/mL, while CL was inactive to the tested MRSA strains. In addition, these conjugates exhibited rapid bactericidal properties and low toxicity, and did not readily induced bacterial resistance, obviously outperforming the parent drug CL. In a mouse model infected with a clinically isolated MRSA strain, compound 39 at a dose of 20 mg/kg exhibited a comparable or even better in vivo anti-MRSA efficacy than the golden standard drug vancomycin, while no toxicity was observed.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Camundongos , Cloranfenicol/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
11.
Mol Cell ; 83(19): 3485-3501.e11, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37802024

RESUMO

p62 is a well-characterized autophagy receptor that recognizes and sequesters specific cargoes into autophagosomes for degradation. p62 promotes the assembly and removal of ubiquitinated proteins by forming p62-liquid droplets. However, it remains unclear how autophagosomes efficiently sequester p62 droplets. Herein, we report that p62 undergoes reversible S-acylation in multiple human-, rat-, and mouse-derived cell lines, catalyzed by zinc-finger Asp-His-His-Cys S-acyltransferase 19 (ZDHHC19) and deacylated by acyl protein thioesterase 1 (APT1). S-acylation of p62 enhances the affinity of p62 for microtubule-associated protein 1 light chain 3 (LC3)-positive membranes and promotes autophagic membrane localization of p62 droplets, thereby leading to the production of small LC3-positive p62 droplets and efficient autophagic degradation of p62-cargo complexes. Specifically, increasing p62 acylation by upregulating ZDHHC19 or by genetic knockout of APT1 accelerates p62 degradation and p62-mediated autophagic clearance of ubiquitinated proteins. Thus, the protein S-acylation-deacylation cycle regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins.


Assuntos
Autofagossomos , Proteínas Ubiquitinadas , Camundongos , Ratos , Humanos , Animais , Autofagossomos/metabolismo , Proteínas Ubiquitinadas/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Autofagia/genética , Acilação , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mamíferos/metabolismo
12.
Nanomaterials (Basel) ; 13(19)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37836344

RESUMO

Perovskite nanocrystals (PeNCs) have emerged as a promising class of luminescent materials offering size and composition-tunable luminescence with high efficiency and color purity in the visible range. PeNCs doped with Yb3+ ions, known for their near-infrared (NIR) emission properties, have gained significant attention due to their potential applications. However, these materials still face challenges with weak NIR electroluminescence (EL) emission and low external quantum efficiency (EQE), primarily due to undesired resonance energy transfer (RET) occurring between the host and Yb3+ ions, which adversely affects their emission efficiency and device performance. Herein, we report the synergistic enhancement of NIR emission in a CsPbCl3 host through co-doping with Yb3+/Nd3+ ions for perovskite LEDs (PeLEDs). The co-doping of Yb3+/Nd3+ ions in a CsPbCl3 host resulted in enhanced NIR emission above 1000 nm, which is highly desirable for NIR optoelectronic applications. This cooperative energy transfer between Yb3+ and Nd3+ can enhance the overall efficiency of energy conversion. Furthermore, the PeLEDs incorporating the co-doped CsPbCl3/Yb3+/Nd3+ PeNCs as an emitting layer exhibited significantly enhanced NIR EL compared to the single doped PeLEDs. The optimized co-doped PeLEDs showed improved device performance, including increased EQE of 6.2% at 1035 nm wavelength and low turn-on voltage. Our findings highlight the potential of co-doping with Yb3+ and Nd3+ ions as a strategy for achieving synergistic enhancement of NIR emission in CsPbCl3 perovskite materials, which could pave the way for the development of highly efficient perovskite LEDs for NIR optoelectronic applications.

13.
FEBS J ; 290(19): 4792-4809, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37410361

RESUMO

Lung cancer cells often show elevated levels of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH). However, the connections between deregulated redox homeostasis in different subtypes of lung cancer and acquired drug resistance in lung cancer have not yet been fully established. Herein, we analyzed different subtypes of lung cancer data reported in the Cancer Cell Line Encyclopedia (CCLE) database, the Cancer Genome Atlas program (TCGA), and the sequencing data obtained from a gefitinib-resistant non-small-cell lung cancer (NSCLC) cell line (H1975GR). Using flux balance analysis (FBA) model integrated with multiomics data and gene expression profiles, we identified cytosolic malic enzyme 1 (ME1) and glucose-6-phosphate dehydrogenase as the major contributors to the significantly upregulated NADPH flux in NSCLC tissues as compared with normal lung tissues, and gefitinib-resistant NSCLC cell line as compared with the parental cell line. Silencing the gene expression of either of these two enzymes in two osimertinib-resistant NSCLC cell lines (H1975OR and HCC827OR) exhibited strong antiproliferative effects. Our findings not only underscored the pivotal roles of cytosolic ME1 and glucose-6-phosphate dehydrogenase in regulating redox states in NSCLC cells but also provided novel insights into their potential roles in drug-resistant NSCLC cells with disturbed redox states.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Gefitinibe/farmacologia , NADP/metabolismo , Glucosefosfato Desidrogenase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Oxirredução , Linhagem Celular Tumoral , Proliferação de Células
14.
J Med Chem ; 66(14): 9866-9880, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37428137

RESUMO

Molecular complexity plays an increasingly important role in the modern pharmaceutical industry. Setting up multiple stereogenic centers in privileged substructures may give rise to improved or even unprecedented bioactivities; however, this area remains largely unexplored due to the tremendous synthetic challenges. Herein, we report a series of multisubstituted pyrrolidines with four continuous stereogenic centers, including up to two aza-QSCs (quaternary stereogenic centers). Systematic evaluations, including phenotypic screening, molecular docking, molecular dynamics, bioinformatics, and bioactivity analysis, have been performed to screen entities with pharmacological properties of interest. Among them, compound 4m with two QSCs was identified to be a potent antiproliferation agent through disturbing mitosis exit, and the presence of QSCs was found to be crucial for anticancer efficacy. This work illustrates that the introduction of QSCs in privileged scaffolds not only helps to expand the unpatented chemical space but also provides new opportunities for the discovery of novel therapeutic agents.


Assuntos
Pirrolidinas , Pirrolidinas/farmacologia , Pirrolidinas/química , Estereoisomerismo , Simulação de Acoplamento Molecular
15.
Quant Imaging Med Surg ; 13(6): 3747-3759, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37284118

RESUMO

Background: The primary treatment goals in acromegaly patients are complete surgical removal of underlying pituitary tumors and biochemical remission. One of the challenges in developing countries is the difficulty in monitoring postoperative biochemical levels in acromegaly patients, particularly those who live in remote areas or regions with limited medical resources. Methods: In an attempt to overcome the abovementioned challenges, we conducted a retrospective study and established a mobile and low-cost method to predict biochemical remission in acromegaly patients after surgery, the efficacy of which was assessed retrospectively using the China Acromegaly Patient Association (CAPA) database. A total of 368 surgical patients from the CAPA database were successfully followed up to obtain their hand photographs. Demographics, baseline clinical characteristics, pituitary tumor features, and treatment details were collated. Postoperative outcome, defined as biochemical remission at the last follow-up timepoint, was assessed. Transfer learning with a new mobile tailored neurocomputing architecture, MobileNetv2, was used to explore the identical features that could be used as predictors of long-term biochemical remission after surgery. Results: As expected, the MobileNetv2-based transfer learning algorithm was shown to predict biochemical remission with statistical accuracies of 0.96 and 0.76 in the training cohort (n=803) and validation cohort (n=200), respectively, and the loss function value was 0.82. Conclusions: Our findings demonstrate the potential of the MobileNetv2-based transfer learning algorithm in predicting biochemical remission for postoperative patients who are at home or live far away from a pituitary or neuroendocrinological treatment center.

16.
Micromachines (Basel) ; 14(6)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37374696

RESUMO

This study conducted longitudinal ultrasonic-assisted milling (UAM) tests and optimized a combination of milling technological parameters to achieve high-quality machining of TC18 titanium alloy. The motion paths of the cutter under the coupled superposition states of longitudinal ultrasonic vibration and end milling were analyzed. Based on the orthogonal test, the cutting forces, cutting temperatures, residual stresses, and surface topographical patterns of TC18 specimens under different UAM conditions (cutting speeds, feeds per tooth, cutting depths, and ultrasonic vibration amplitudes) were examined. The differences between ordinary milling and UAM in terms of machining performance were compared. Using UAM, numerous characteristics (including variable cutting thickness in the cutting area, variable cutting front angles of the tool, and the lifting of the cuttings by the tool) were optimized, reducing the average cutting force in all directions, lowering the cutting temperature, increasing the surface residual compressive stress, and significantly improving the surface morphology. Finally, fish scale bionic microtextures with clear, uniform, and regular patterns were formed on the machined surface. High-frequency vibration can improve material removal convenience, thus reducing surface roughness. The introduction of longitudinal ultrasonic vibration to the end milling process can overcome the limitations of traditional processing. The optimal combination of UAM parameters for titanium alloy machining was determined through the end milling orthogonal test with compound ultrasonic vibration, which significantly improved the surface quality of TC18 workpieces. This study provides insightful reference data for subsequent machining process optimization.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37224363

RESUMO

Endowing the robot with tactile perception can effectively improve manipulation dexterity, along with various benefits of human-like touch. Using GelStereo (GS) tactile sensing, which gives high-resolution contact geometry information, including 2-D displacement field, and 3-D point cloud of the contact surface, we present a learning-based slip detection system in this study. The results reveal that the well-trained network achieves 95.79% accuracy on the never-seen testing dataset, which surpasses the current model-based and learning-based methods using visuotactile sensing. We also propose a general framework for slip feedback adaptive control for dexterous robot manipulation tasks. The experimental results show the effectiveness and efficiency of the proposed control framework using GS tactile feedback when deployed on real-world grasping and screwing manipulation tasks on various robot setups.

18.
RSC Adv ; 13(22): 15148-15156, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37213332

RESUMO

Hybrid organic switch-inorganic semiconductor systems have important applications in both photo-responsive intelligent surfaces and microfluidic devices. In this context, herein, we performed first-principles calculations to investigate a series of organic switches of trans/cis-azobenzene fluoride and pristine/oxidized trimethoxysilane adsorbed on low-index anatase slabs. The trends in the surface-adsorbate interplay were examined in terms of the electronic structures and potential distributions. Consequently, it was found that the cis-azobenzene fluoride (oxidized trimethoxysilane)-terminated anatase surface attains a lower ionization potential than the trans-azobenzene fluoride (pristine trimethoxysilane)-terminated anatase surface due to its smaller induced (larger intrinsic) dipole moment, whose direction points inwards (outwards) from the substrate, which originates from the electron charge redistribution at the interface (polarity of attached hydroxyl groups). By combining the induced polar interaction analysis and the experimental measurements in the literature, we demonstrate that the ionization potential is an important predictor of the surface wetting properties of adsorbed systems. The anisotropic absorbance spectra of anatase grafted with azobenzene fluoride and trimethoxysilane are also related to the photoisomerization and oxidization process under UV irradiation, respectively.

19.
Materials (Basel) ; 16(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37048893

RESUMO

Vibration procedures significantly affect the performances of cement-based materials. However, studies on the distribution of certain particles within cement-based materials are limited due to the complexity and difficulty of identifying each specific particle. This paper presents a new method for simulating and quantifying the movements of particles within cement paste through the use of "tagged materials". By separating the tagged particles from the cement paste after vibration, the distribution of the particles in the cement paste can be calculated statistically. The effect of the vibration time and frequency, fresh behavior, and powder characteristics of cement paste on particle motions are investigated. The results demonstrate that when the vibration exceeds 1800 s, it induces a significant uneven dispersion of microparticles. This effect is more pronounced at low viscosities (<1 Pa·s) of cement paste or high vibration frequencies (>200 Hz). Larger and denser particles exhibit greater dispersion. This method provides a valuable tool for investigating the theory of particle motion in cement paste, which is crucial for understanding the influence of vibration on the properties of cement-based materials.

20.
Nanotechnology ; 34(27)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37011606

RESUMO

Perovskite nanocrystals (NCs) feature adjustable bandgap, wide absorption range, and great color purity for robust perovskite optoelectronic applications. Nevertheless, the absence of lasting stability under continues energization, is still a major hurdle to the widespread use of NCs in commercial applications. In particular, the reactivity of red-emitting perovskites to environmental surroundings is more sensitive than that of their green counterparts. Here, we present a simple synthesis of ultrathin ZrO2coated, Sr2+doped CsPbBrI2NCs. Introducing divalent Sr2+may significantly eliminate Pb° surface traps, whereas ZrO2encapsulation greatly improves environmental stability. The photoluminescence quantum yield of the Sr2+-doped CsPbBrI2/ZrO2NCs was increased from 50.2% to 87.2% as a direct consequence of the efficient elimination of Pb° surface defects. Moreover, the thickness of the ZrO2thin coating gives remarkable heat resistance and improved water stability. Combining CsPbSr0.3BrI2/ZrO2NCs in a white light emitting diode (LED) with an excellent optical efficiency (100.08 lm W-1), high and a broad gamut 141% (NTSC) standard. This work offers a potential method to suppress Pb° traps by doping with Sr2+and improves the performance of perovskite NCs by ultrathin coating structured ZrO2, consequently enabling their applicability in commercial optical displays.

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