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1.
Int J Pharm ; 658: 124204, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38710297

ABSTRACT

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.

2.
Drug Des Devel Ther ; 18: 1531-1546, 2024.
Article in English | MEDLINE | ID: mdl-38737331

ABSTRACT

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Down-Regulation , Drug Screening Assays, Antitumor , Lung Neoplasms , Pyrazines , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Pyrazines/pharmacology , Pyrazines/chemistry , Cell Proliferation/drug effects , Animals , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Down-Regulation/drug effects , Chalcone/pharmacology , Chalcone/chemistry , Molecular Structure , Dose-Response Relationship, Drug , Structure-Activity Relationship , Molecular Docking Simulation , Mice, Nude , Mice, Inbred BALB C , A549 Cells , Cell Movement/drug effects , Chalcones/pharmacology , Chalcones/chemistry , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Tumor Cells, Cultured
3.
Virol Sin ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38677713

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. In this study, we detected accessory protein-specific antibodies in COVID-19 patients' sera using various techniques, including Luciferase Immunoprecipitation System (LIPS), Immunofluorescence assay (IFA), and Western blot (WB). Proteins 3a, 3b, 7b, 8 and 9c specific antibodies can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. And antibodies against protein 3a and 7b only detected in ICU patients, which may serve as a marker for predicting the disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for the protein detection assays and their role in pathogenesis.

4.
Front Microbiol ; 15: 1332458, 2024.
Article in English | MEDLINE | ID: mdl-38601926

ABSTRACT

Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

5.
Nanoscale Adv ; 6(8): 2002-2012, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38633054

ABSTRACT

Copper (Cu) has a soft-plastic nature, which makes it susceptible to damages from scratching or abrasive machining, such as lapping and polishing. It is a challenge to control these damages as the damage mechanism is elusive. Nonetheless, controlling damages is essential, especially on the atomic surfaces of Cu. To interpret the damage mechanism, in situ transmission electron microscopy (TEM) nanoindentation was performed using a cube-corner indenter with a radius of 57 nm at a loading speed of 5 nm s-1. Experimental results showed that damages originate from dislocations, evolve to stack faults, and then form broken crystallites. When the indentation depth was 45 nm at a load of 20 µN, damages comprised dislocations and stacking faults. After increasing the depth to 67 nm and load to 30 µN, the formation of broken crystallites initiated; and the critical depth was 67 nm. To validate the damage mechanism, fixed-abrasive lapping, mechanical polishing, and chemical mechanical polishing (CMP) were conducted. Firstly, a novel green CMP slurry containing silica, hydrogen peroxide, and aspartic acid was developed. After CMP, a surface roughness Ra of 0.2 nm was achieved with a scanning area of 50 µm × 50 µm; and the thickness of the damaged layer was 3.1 nm, which included a few micro-stacking faults. Lapping and mechanical polishing were carried out using a silicon carbide plate and cerium slurry, with surface roughness Ra values of 16.42 and 1.74 nm, respectively. The damaged layer of the former with a thickness of 300 nm comprised broken crystallites, dislocations, and stacking faults and that of the latter with a thickness of 33 nm involved several stacking faults. This verifies that the damage mechanism derived from in situ TEM nanoindentation is in agreement with lapping and polishing. These outcomes propose new insights into understanding the origin of damages and controlling them, as well as obtaining atomic surfaces using a novel green CMP technique for soft-plastic metals.

6.
ACS Omega ; 9(11): 13469-13480, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38524438

ABSTRACT

Hydraulic fracturing technology is the main method to develop low-permeability reservoirs. Fracture conductivity is not only the basis of fracture optimization design but also one of the key parameters to determine the effect of hydraulic fracturing. However, current methods of calculating fracture conductivity require a lot of time and labor cost. This research proposes a fracture conductivity prediction model based on machine learning. The main controlling factors of fracture conductivity are determined using the Pearson coefficient method and gray correlation analysis. Example application shows that the R2 values of the BP neural network model based on a genetic algorithm for predicting the fracture conductivity of block A and block B are 0.981 and 0.975, respectively, indicating that the machine learning model can accurately predict fracture conductivity.

7.
Appl Opt ; 63(5): 1394-1401, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38437320

ABSTRACT

Broadband antireflection (AR) is highly significant in a wide range of optical applications, and using a gold (Au) micropattern presents a viable method for controlling the behavior of light propagation. This study investigates a novel, to the best of our knowledge, methodology to achieve broadband AR properties in Au micropatterns. It employed the three-dimensional finite-difference time-domain (FDTD) method to simulate and optimize the design of micropatterns. In contrast, the fabrication of Au micropatterns was carried out using two-beam laser interference lithography (LIL). The fabricated Au micropatterns were characterized by a scanning electron microscope (SEM) and spectroscope to validate their antireflection and transmission properties and evaluate their performance at various wavelengths. The optimized Au micropatterns had a high transmittance rating of 96.2%. In addition, the device exhibits a broad-spectrum antireflective property, covering wavelengths ranging from 400 to 1100 nm. The simulation data and experimentally derived results show comparable patterns. These structures can potentially be employed in many optical devices, such as solar cells and photodetectors, whereby achieving optimal device performance reduced reflection and enhanced light absorption.

8.
Crit Rev Eukaryot Gene Expr ; 34(4): 13-23, 2024.
Article in English | MEDLINE | ID: mdl-38505869

ABSTRACT

Lung adenocarcinoma (LUAD) severely affects human health, and cisplatin (DDP) resistance is the main obstacle in LUAD treatment, the mechanism of which is unknown. Bioinformatics methods were utilized to predict expression and related pathways of AURKB in LUAD tissues, as well as the upstream regulated microRNAs. qRT-PCR assayed expression of AURKB and microRNA-486-5p. RIP and dual-luciferase experiments verified the binding and interaction between the two genes. CCK-8 was used to detect cell proliferation ability and IC50 values. Flow cytometry was utilized to assess the cell cycle. Comet assay and western blot tested DNA damage and γ-H2AX protein expression, respectively. In LUAD, AURKB was upregulated, but microRNA-486-5p was downregulated. The targeted relationship between the two was confirmed by RIP and dual-luciferase experiments. Cell experiments showed that AURKB knock-down inhibited cell proliferation, reduced IC50 values, induced cell cycle arrest, and caused DNA damage. The rescue experiment presented that high expression of microRNA-486-5p could weaken the impact of AURKB overexpression on LUAD cell behavior and DDP resistance. microRNA-486-5p regulated DNA damage to inhibit DDP resistance in LUAD by targeting AURKB, implying that microRNA-486-5p/AURKB axis may be a possible therapeutic target for DDP resistance in LUAD patients.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , MicroRNAs , Humans , Cisplatin/pharmacology , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , DNA Damage , MicroRNAs/genetics , Cell Proliferation , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Luciferases , Cell Line, Tumor , Aurora Kinase B
9.
Anal Chem ; 96(12): 5056-5064, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38497564

ABSTRACT

Aptamer-based detection targeting glycoconjugates has attracted significant attention for its remarkable potential in identifying structural changes in saccharides in different stages of various diseases. However, the challenges in screening aptamers for small carbohydrates or glycoconjugates, which contain highly flexible and diverse glycosidic bonds, have hindered their application and commercialization. In this study, we investigated the binding conformations between three glycosidic bond-containing small molecules (GlySMs; glucose, N-acetylneuraminic acid, and neomycin) and their corresponding aptamers in silico, and analyzed factors contributing to their binding affinities. Based on the findings, a novel binding mechanism was proposed, highlighting the central role of the stem structure of the aptamer in binding and recognizing GlySMs and the auxiliary role of the mismatched bases in the adjacent loop. Guided by this binding mechanism, an aptamer with a higher 6'-sialyllactose binding affinity was designed, achieving a KD value of 4.54 ± 0.64 µM in vitro through a single shear and one mutation. The binding mechanism offers crucial guidance for designing high-affinity aptamers, enhancing the virtual screening efficiency for GlySMs. This streamlined workflow filters out ineffective binding sites, accelerating aptamer development and providing novel insights into glycan-nucleic acid interactions.


Subject(s)
Aptamers, Nucleotide , Glycosides , Aptamers, Nucleotide/chemistry , DNA, Single-Stranded , Binding Sites , Glycoconjugates , SELEX Aptamer Technique
10.
Stroke Vasc Neurol ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38336369

ABSTRACT

BACKGROUND: Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation. METHODS: Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction. RESULTS: Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/). CONCLUSIONS: The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT.

11.
J Colloid Interface Sci ; 661: 930-942, 2024 May.
Article in English | MEDLINE | ID: mdl-38330665

ABSTRACT

Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi2Se3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi2Se3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi2Se3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi2Se3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi2Se3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi2Se3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT.


Subject(s)
Glioma , Hyperthermia, Induced , Nanoparticles , Neoplasms , Photochemotherapy , Humans , Phototherapy/methods , Neoplasms/drug therapy , Glioma/drug therapy , Hyperthermia, Induced/methods , Cell Line, Tumor
12.
Adv Sci (Weinh) ; 11(12): e2306499, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38229201

ABSTRACT

EZH2 is the catalytic subunit of the histone methyltransferase Polycomb Repressive Complex 2 (PRC2), and its somatic activating mutations drive lymphoma, particularly the germinal center B-cell type. Although PRC2 inhibitors, such as tazemetostat, have demonstrated anti-lymphoma activity in patients, the clinical efficacy is not limited to EZH2-mutant lymphoma. In this study, Activin A Receptor Type 1 (ACVR1), a type I Bone Morphogenetic Protein (BMP) receptor, is identified as critical for the anti-lymphoma efficacy of PRC2 inhibitors through a whole-genome CRISPR screen. BMP6, BMP7, and ACVR1 are repressed by PRC2-mediated H3K27me3, and PRC2 inhibition upregulates their expression and signaling in cell and patient-derived xenograft models. Through BMP-ACVR1 signaling, PRC2 inhibitors robustly induced cell cycle arrest and B cell lineage differentiation in vivo. Remarkably, blocking ACVR1 signaling using an inhibitor or genetic depletion significantly compromised the in vitro and in vivo efficacy of PRC2 inhibitors. Furthermore, high levels of BMP6 and BMP7, along with ACVR1, are associated with longer survival in lymphoma patients, underscoring the clinical relevance of this study. Altogether, BMP-ACVR1 exhibits anti-lymphoma function and represents a critical PRC2-repressed pathway contributing to the efficacy of PRC2 inhibitors.


Subject(s)
Lymphoma, B-Cell , Lymphoma , Humans , Polycomb Repressive Complex 2/genetics , Polycomb Repressive Complex 2/metabolism , Signal Transduction/physiology , Activin Receptors, Type I/genetics , Activin Receptors, Type I/metabolism
13.
Adv Healthc Mater ; 13(9): e2303394, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38288911

ABSTRACT

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.


Subject(s)
Glioma , Proto-Oncogene Proteins c-akt , Animals , Humans , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Cell Proliferation , Glioma/genetics , Glioma/radiotherapy , Glioma/metabolism , Signal Transduction , Tumor Microenvironment
14.
Phys Chem Chem Phys ; 26(4): 3415-3423, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38205513

ABSTRACT

Currently, it remains a challenge to make comprehensive improvements to overcome the disadvantages of volume expansion, Li2O irreversibility and low conductivity of SnO2. Heterostructure construction has been investigated as an effective strategy to promote electron transfer and surface reaction kinetics, leading to high electrochemical performance. Herein, NiO/SnO2 heterojunction modified nitrogen doped graphene (NiO/SnO2@NG) anode materials were prepared using hydrothermal and carbonization techniques. Based on the excellent structural advantages, sufficiently small NiO/SnO2 heterojunction nanoparticles increase the interfacial density to promote Li2O decomposition, and the built-in electric field accelerates the charge transport rate to improve the conductivity. The three-dimensional porous graphene framework effectively mitigates volume expansion during cycling and stabilizes the reactive interface of electrode materials. The results show that the NiO/SnO2@NG mixture has high reversible specific capacity (938.8 mA h g-1 after 450 cycles at 0.1 A g-1), superior multiplicity performance (374.5 mA h g-1 at 3.0 A g-1) and long cycle life (685.3 mA h g-1 after 1000 cycles at 0.5 A g-1). Thus, this design of introducing NiO to form heterostructures with SnO2 is directly related to enhancing the electrochemical performance of lithium-ion batteries (LIBs).

15.
J Am Chem Soc ; 146(3): 2275-2285, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38215226

ABSTRACT

The construction of structurally well-defined supramolecular hosts to accommodate catalytically active species within a cavity is a promising way to address catalyst deactivation. The resulting supramolecular catalysts can significantly improve the utilization of catalytic sites, thereby achieving a highly efficient chemical conversion. In this study, the Co-metalated phthalocyanine (Pc-Co) was successfully confined within a tetragonal prismatic metallacage, leading to the formation of a distinctive type of supramolecular photocatalyst (Pc-Co@Cage). The host-guest architecture of Pc-Co@Cage was unambiguously elucidated by single-crystal X-ray diffraction (SCXRD), NMR, and ESI-TOF-MS, revealing that the single cobalt active site can be thoroughly isolated within the space-restricted microenvironment. In addition, we found that Pc-Co@Cage can serve as a homogeneous supramolecular photocatalyst that displays high CO2 to CO conversion in aqueous media under visible light irradiation. This supramolecular photocatalyst exhibits an obvious improvement in activity (TONCO = 4175) and selectivity (SelCO = 92%) relative to the nonconfined Pc-Co catalyst (TONCO = 500, SelCO = 54%). The present strategy provided a rare example for the construction of a highly active, selective, and stable photocatalyst for CO2 reduction through a cavity-confined molecular catalyst within a discrete metallacage.

16.
PeerJ ; 12: e16594, 2024.
Article in English | MEDLINE | ID: mdl-38188143

ABSTRACT

Background: Gastric cancer (GC) is one of the most common malignant tumours in the digestive system. Serine hydroxymethyltransferase 2 (SHMT2) is one of the key enzymes associated with serine metabolism. However, the prognostic role of SHMT2 in GC carcinogenesis has yet to be studied. Methods: The expression of SHMT2 in human tumors and normal tissues was detected by the Assistant for Clinical Bioinformatics and Immunohistochemistry (IHC). The relationship of the expression of SHMT2 with clinical characteristics and survival data was analysed by the chi-square test, survival analysis and online databases. Finally, the correlation between SHMT2 expression and associated signalling channels, and molecules was analysed by online databases. Results: SHMT2 was strongly expressed in numerous human cancers. The expression rate of SHMT2 was 56.44% in GC (P = 0.018). The survival analysis indicated that patients with high expression of SHMT2 had the worse overall survival (OS; log-rank P = 0.007). The expression of SHMT2 was correlated with tumour size (P = 0.034) and, TNM stage (P = 0.042). In particular, SHMT2, vessel invasion and M stage were independent factors for OS in GC (P = 0.044, P < 0.001, P < 0.001). The SHMT2 gene was substantially correlated with cell signalling pathways. Conclusions: SHMT2 is highly expressed in GC and is associated with a poor prognosis. The exploration of its mechanism may be related to tumour proliferation, DNA repair and replication. SHMT2 is an independent prognostic risk factor and a potential biomarker for the diagnosis and treatment of GC.


Subject(s)
Stomach Neoplasms , Humans , Carcinogenesis , Cell Division , Clinical Relevance , Computational Biology , Stomach Neoplasms/genetics
17.
ACS Nano ; 18(4): 3023-3042, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38241477

ABSTRACT

Antibiotic resistance is a pressing public health threat. Despite rising resistance, antibiotic development, especially for Gram-negative bacteria, has stagnated. As the traditional antibiotic research and development pipeline struggles to address this growing concern, alternative solutions become imperative. Synthetic molecular nanomachines (MNMs) are molecular structures that rotate unidirectionally in a controlled manner in response to a stimulus, such as light, resulting in a mechanical action that can propel molecules to drill into cell membranes, causing rapid cell death. Due to their broad destructive capabilities, clinical translation of MNMs remains challenging. Hence, here, we explore the ability of nonlethal visible-light-activated MNMs to potentiate conventional antibiotics against Gram-negative bacteria. Nonlethal MNMs enhanced the antibacterial activity of various classes of conventional antibiotics against Gram-negative bacteria, including those typically effective only against Gram-positive strains, reducing the antibiotic concentration required for bactericidal action. Our study also revealed that MNMs bind to the negatively charged phospholipids of the bacterial inner membrane, leading to permeabilization of the cell envelope and impairment of efflux pump activity following light activation of MNMs. The combined effects of MNMs on membrane permeability and efflux pumps resulted in increased antibiotic accumulation inside the cell, reversing antibiotic resistance and attenuating its development. These results identify nonlethal MNMs as pleiotropic antibiotic enhancers or adjuvants. The combination of MNMs with traditional antibiotics is a promising strategy against multidrug-resistant Gram-negative infections. This approach can reduce the amount of antibiotics needed and slow down antibiotic resistance development, thereby preserving the effectiveness of our current antibiotics.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Anti-Bacterial Agents/metabolism , Gram-Negative Bacteria , Biological Transport , Permeability
18.
Chemistry ; 30(19): e202302865, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-37833823

ABSTRACT

Recently, it has become imperative to develop high energy density as well as high safety lithium-ion batteries (LIBS) to meet the growing energy demand. Among the anode materials used in LIBs, the currently used commercial graphite has low capacity and is a safety hazard due to the formation of lithium dendrites during the reaction. Among the transition metal oxide (TMO) anode materials, TMO based on the intercalation reaction mechanism has a more stable structure and is less prone to volume expansion than TMO based on the conversion reaction mechanism, especially the niobium-based oxide in it has attracted much attention. Niobium-based oxides have a high operating potential to inhibit the formation of lithium dendrites and lithium deposits to ensure safety, and have stable and fast lithium ion transport channels with excellent multiplicative performance. This review summarizes the recent developments of niobium-based oxides as anode materials for lithium-ion batteries, discusses the special structure and electrochemical reaction mechanism of the materials, the synthesis methods and morphology of nanostructures, deficiencies and improvement strategies, and looks into the future developments and challenges of niobium-based oxide anode materials.

19.
Pest Manag Sci ; 80(2): 544-553, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37735842

ABSTRACT

BACKGROUND: To discover and develop novel acaricidal compounds, a series of 2-fluoro-4-methyl/chlorine-5-((2,2,2-trifluoroethyl)thio)aniline/phenol compounds containing N/O-benzyl moieties were synthesized based on lead compound LZ-1. RESULTS: The activity of these compounds against carmine spider mites (Tetranychus cinnabarinus) was determined using the leaf-spray method. Bioassays indicated that most of the designed target compounds possessed moderate to excellent acaricidal activity against adult T. cinnabarinus. The median lethal concentrations of 25b and 26b were 0.683 and 2.448 mg L-1 against adult mites, respectively; exceeding those of bifenazate (7.519 mg L-1 ) and lead compound LZ-1(3.658 mg L-1 ). Compound 25b exhibited 100% mortality in T. cinnabarinus larvae at 10 mg L-1 . CONCLUSION: Continuing the study of these compounds in field trials, we compared the efficacy of mite killing by compound 25b with the commercial pesticide spirodiclofen and showed that mite control achieved 95.9% and 83.0% lethality at 10 and 22 days post-treatment. In comparison, spirodiclofen showed 92.7% lethality at 10 days and 77.2% lethality at 22 days post-treatment at a concentration of 100 mg L-1 . Results showed that 25b produced more facile and long-lasting control against T. cinnabarinus than the commercial acaricide spirodiclofen. Density functional theory analysis and electrostatic potential calculations of various molecular substitutions suggested some useful models to achieve other highly active miticidal compounds. © 2023 Society of Chemical Industry.


Subject(s)
4-Butyrolactone/analogs & derivatives , Acaricides , Spiro Compounds , Tetranychidae , Animals , Sulfides/pharmacology , Structure-Activity Relationship
20.
Int J Biol Macromol ; 254(Pt 2): 127851, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37924920

ABSTRACT

Electromagnetic waves have an irreplaceable role as information carriers in civil and radar stealth fields, but they also lead to electromagnetic pollution and electromagnetic leakage. Therefore, electromagnetic wave absorbing materials that can reduce electromagnetic radiation have come into being. Especially, SnO2 has made a wave among many wave-absorbing materials as an easily tunable dielectric material, but it hardly has both broadband and powerful absorption properties. Here, the nested porous C/SnO2 composites derived from nitrogen-doped chitosan is obtained by freeze-drying and supplemented with carbonization treatment. The chitosan creates a nested cross-linked conductive network that can make part of the contribution to conduction loss. The amino groups contained in the molecule either help promote in situ nitrogen doping and trigger dipole polarization. The multiphase dissimilar interface between the nested carbon layer and the inner clad SnO2 formation is the major inducer of interfacial polarization. It reached intense absorption of -48.8 dB and bandwidth of 5.2 GHz at 3.46 mm. The interfacial polarization is confirmed to be the main force of dielectric loss by simulating the electromagnetic field distribution. In addition, the RCS simulation data assure the prospect of enticing applications of C/SnO2 composites in the field of radar stealth.


Subject(s)
Chitosan , Microwaves , Porosity , Carbon , Nitrogen
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