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1.
Food Chem ; 455: 139850, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38850984

ABSTRACT

Direct, rapid and highly sensitive detection of heavy metals in rice is essential to ensure food safety. In this research, a combination of laser ablation and microwave plasma torch optical emission spectrometry (LA-MPT-OES) was proposed. Based on the optimal observation positions, a high sensitivity and direct determination of Cd, Hg, Pb and Cr in rice were realized. The limits of detection (LOD) were 0.97, 0.12, 0.61 and 0.15 µg/kg, respectively, which were reduced by one order of magnitude compared to the optimal observation height. In addition, the LOD was reduced by one to two orders of magnitude compared with the techniques that require sample pre-treatment. Moreover, the results of the Certified Reference Materials and real samples were in agreement with the reference values with a relative error in the range of 0.28% âˆ¼ 14.16%. The results demonstrated that LA-MPT-OES could be a promising tool to detect heavy metals in rice.

2.
Biomed Pharmacother ; 177: 116972, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38906024

ABSTRACT

Breast cancer is one of the most prevalent malignancies affecting women worldwide, underscoring the urgent need for more effective and specific treatments. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy to develop new lead compounds by selectively targeting oncoproteins for degradation. In this study, we designed, synthesized and evaluated a CRBN-based PROTAC, L055, which targets CDK9. Our findings demonstrate that L055 effectively inhibits the proliferation, induces cell cycle arrest, and decreases the survival of ERα-positive breast cancer cells in vitro. L055 specifically binds to CDK9, facilitating its degradation via the CRBN-dependent proteasomal pathway. Additionally, L055 suppressed the growth of organoids and tumors derived from T47D and MCF7 cells in nude mice. Thus, L055 represents a potential novel therapeutic agent for ERα-positive breast cancer and potentially other malignancies.

3.
Huan Jing Ke Xue ; 45(6): 3329-3340, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897755

ABSTRACT

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

4.
Article in English | MEDLINE | ID: mdl-38934271

ABSTRACT

Infection and oxidative stress seriously hinder the healing of diabetic wounds, resulting in various serious health and clinical problems. Herein, a sustainable biological hydrogen (H2)-producing hyaluronic acid-based hydrogel patch (HAP-Chl) was constructed by loading an imidazolium-based poly(ionic liquid) (PIL) flocculated live Chlorella as a diabetic wound dressing. The PIL can flocculate Chlorella through electrostatic interactions between PIL and Chlorella to form Chlorella agglomerates, endowing the Chlorella in the central agglomerates with the ability to continuously produce H2 for 24 h under mild conditions. Combining the membrane disruption-related bactericidal mechanism of PIL and the antioxidant properties of the produced H2, HAP-Chl was determined to be antibacterial and antioxidant. In addition to exhibiting biocompatible and nontoxic activities, subsequent Staphylococcus aureus-infected chronic wound studies revealed that HAP-Chl is capable of promoting the healing of chronic wounds by effectively killing bacteria, reducing extensive ROS, relieving inflammation, and promoting the deposition of mature collagen and angiogenesis. This study provides a new strategy for constructing an in situ sustainable H2-producing hydrogel, enabling the formation of novel antibacterial and antioxidant material platforms with potential for wound dressing applications.

5.
Food Res Int ; 183: 114202, 2024 May.
Article in English | MEDLINE | ID: mdl-38760133

ABSTRACT

Pixian broad bean paste is a renowned fermented seasoning. The fermentation of broad bean is the most important process of Pixian broad bean paste. To enhance the flavor of tank-fermented broad bean paste, salt-tolerant Bacillus amyloliquefaciens strain was inoculated, resulting in an increase in total amount of volatile compounds, potentially leading to different flavor characteristics. To investigate the fermentation mechanism, monoculture simulated fermentation systems were designed. Metabolomics and transcriptomics were used to explore Bacillus amyloliquefaciens' transcriptional response to salt stress and potential aroma production mechanisms. The results highlighted different metabolite profiles under salt stress, and the crucial roles of energy metabolism, amino acid metabolism, reaction system, transportation system in Bacillus amyloliquefaciens' hypersaline stress response. This study provides a scientific basis for the industrial application of Bacillus amyloliquefaciens and new insights into addressing the challenges of poor flavor quality in tank fermentation products.


Subject(s)
Bacillus amyloliquefaciens , Fermentation , Metabolomics , Bacillus amyloliquefaciens/metabolism , Bacillus amyloliquefaciens/genetics , Transcriptome , Food Microbiology , Fermented Foods/microbiology , Volatile Organic Compounds/analysis , Volatile Organic Compounds/metabolism , Gene Expression Profiling , Taste , Fabaceae/microbiology
6.
Anim Reprod ; 21(2): e20240010, 2024.
Article in English | MEDLINE | ID: mdl-38756621

ABSTRACT

As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating lipid metabolism, and stimulating energy expenditure. However, the t10c12-CLA products are mostly mixtures, making it difficult to obtain accurate results. Studies are needed to investigate the effects of pure t10c12-CLA on animals and humans. In this study, we used the biallelic transgenic (tg) mice, which could produce t10c12-CLA itself, to investigate the effects of pure t10c12-CLA on female reproductive ability. The results showed that the body and relative ovary weights had no significant difference between tg and wild-type (wt) littermates at ages 3 or 10 weeks. While the fecundity test found that tg mice had a significantly longer first litter time (32.0 ± 4.70 days vs. 21.3 ± 2.31 days, P<0.05), and a significantly lower number of litters (4.75 ± 2.75 vs. 6.67 ± 0.57, P<0.05) when compared with wt mice during continuous mating within seven months. Hormone profiles showed that serum estradiol levels did not change in tg mice; however, significantly (P<0.05) decreased progesterone and increased prostaglandin E2 levels were observed in tg mice compared with those of wt mice. Hematoxylin-eosin staining showed no pathological characteristics in tg ovaries, except for the increased atresia follicles (P<0.05). Moreover, the tg mice had a significantly more extended diestrus period than the wt mice (48.4 ± 6.38% vs. 39.6 ± 3.81%, P<0.05). In summary, t10c12-CLA could affect serum progesterone and prostaglandin E2 levels, lead to a disordered estrus cycle, and impact the reproductive performance of female mice. This study provided theoretical and biosafety recommendations for applying t10c12-CLA in female mammals.

7.
Int J Ophthalmol ; 17(3): 420-434, 2024.
Article in English | MEDLINE | ID: mdl-38721513

ABSTRACT

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

8.
ACS Appl Mater Interfaces ; 16(19): 24723-24733, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38695440

ABSTRACT

We demonstrated the use of hydrated calcium vanadate (CaV6O16·3H2O, denoted as CaVO-2) as a cathode for aqueous zinc-ion batteries (AZIBs). Nanoribbons of hydrated calcium vanadate facilitated shortening of the Zn2+ transport distance and accelerated zinc-ion insertion. The introduction of interlayer structure water increased the interlayer spacing of calcium vanadate and as a "lubricant". Ca2+ insertion also expanded the interlayer spacing and further stabilized the interlayer structure of vanadium-based oxide. The density functional theory results showed that the introduction of Ca2+ and structured water could effectively improve the diffusion kinetics, resulting in the rapid transport of zinc ions. As a result, AZIBs based on the CaVO-2 cathode offered high specific capacity (329.6 mAh g-1 at 200 mA g-1) and fast charge/discharge capability (147 mAh g-1 at 10 A g-1). Impressively, quasi-solid-state zinc-ion batteries based on the CaVO-2 cathode and polyacrylamide-cellulose nanofiber hydrogel electrolytes maintained an outstanding specific capacity and long cycle life (162 mAh g-1 over 10 000 cycles at 5 A g-1). This study provided a reliable strategy for metal-ion insertion and the structural water introduction of oxides to produce a high-quality cathode for ZIBs. Meanwhile, it provides ideas for the combination of vanadium-based materials and gel electrolytes to construct solid-state zinc-ion batteries.

9.
ACS Appl Mater Interfaces ; 16(21): 27785-27793, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38757309

ABSTRACT

Flexible nanocomposite dielectrics with inorganic nanofillers exhibit great potential for energy storage devices in advanced microelectronics applications. However, high loading of inorganic nanofillers in the matrix results in an inhomogeneous electric field distribution, thereby hindering the improvement of the energy storage density (Ue) of the dielectrics. Herein, we proposed a strategy that utilized (00l)-oriented barium titanate (BT) single-crystal platelets to fabricate trilayered nanocomposite dielectrics for energy storage applications. The trilayered nanocomposites consisted of two high-permittivity layers of (Ta2O5, Al2O3) codoped TiO2 nanoparticles (Ta-Al@TiO2 nps) dispersed in a poly(vinylidene fluoride) (PVDF) matrix to facilitate large electric displacement and a middle layer of (00l)-oriented BT single-crystal platelets to provide high breakdown strength. Hence, the trilayered PVDF/Ta-Al@TiO2 nps/BT single-crystal platelet nanocomposite film attains an outstanding Ue of 16.9 J cm-3 at 370 kV mm-1, which is ∼625% higher than that of the single-layer PVDF/Ta-Al@TiO2 nps film. Finite element simulation further clarified that the successive inner layer of highly (00l)-oriented BT single-crystal platelets could effectively restrain the propagation of electrical treeing in trilayered nanocomposites. This research offers an effective approach for developing flexible dielectric capacitors with an excellent energy storage performance.

10.
Sci Rep ; 14(1): 12430, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38816541

ABSTRACT

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.


Subject(s)
Corticosterone , Dinoprostone , Epinephrine , Fibroblast Growth Factors , Glucagon , Linoleic Acids, Conjugated , Mice, Transgenic , Animals , Female , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/genetics , Mice , Linoleic Acids, Conjugated/pharmacology , Linoleic Acids, Conjugated/metabolism , Corticosterone/metabolism , Dinoprostone/metabolism , Glucagon/metabolism , Epinephrine/metabolism , Thermogenesis/drug effects , Thermogenesis/genetics , Male , Lipid Metabolism/drug effects , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/drug effects , Fatty Liver/metabolism , Fatty Liver/genetics , Lipolysis/drug effects , Hypertriglyceridemia/metabolism , Hypertriglyceridemia/genetics , Adiposity/drug effects
11.
Adv Sci (Weinh) ; 11(25): e2308186, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38664976

ABSTRACT

Natural products, while valuable for drug discovery, encounter limitations like uncertainty in targets and toxicity. As an important active ingredient in traditional Chinese medicine, celastrol exhibits a wide range of biological activities, yet its mechanism remains unclear. In this study, they introduced an innovative "Degradation-based protein profiling (DBPP)" strategy, which combined PROteolysis TArgeting Chimeras (PROTAC) technology with quantitative proteomics and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques, to identify multiple targets of natural products using a toolbox of degraders. Taking celastrol as an example, they successfully identified its known targets, including inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα), and cellular inhibitor of PP2A (CIP2A), as well as potential new targets such as checkpoint kinase 1 (CHK1), O-GlcNAcase (OGA), and DNA excision repair protein ERCC-6-like (ERCC6L). Furthermore, the first glycosidase degrader is developed in this work. Finally, by employing a mixed PROTAC toolbox in quantitative proteomics, they also achieved multi-target identification of celastrol, significantly reducing costs while improving efficiency. Taken together, they believe that the DBPP strategy can complement existing target identification strategies, thereby facilitating the rapid advancement of the pharmaceutical field.


Subject(s)
Pentacyclic Triterpenes , Proteomics , Triterpenes , Proteomics/methods , Humans , Triterpenes/pharmacology , Triterpenes/metabolism , Proteolysis/drug effects , Mass Spectrometry/methods , Immunoprecipitation/methods
12.
Sci Bull (Beijing) ; 69(11): 1776-1797, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38614856

ABSTRACT

Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted, but are of great clinical significance. According to statistics, over 80% of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods. In recent years, with the advancement of basic research and new technologies, the development of various new technologies and mechanisms has brought new perspectives to overcome challenging drug targets. Among them, targeted protein degradation technology is a breakthrough drug development strategy for challenging drug targets. This technology can specifically identify target proteins and directly degrade pathogenic target proteins by utilizing the inherent protein degradation pathways within cells. This new form of drug development includes various types such as proteolysis targeting chimera (PROTAC), molecular glue, lysosome-targeting Chimaera (LYTAC), autophagosome-tethering compound (ATTEC), autophagy-targeting chimera (AUTAC), autophagy-targeting chimera (AUTOTAC), degrader-antibody conjugate (DAC). This article systematically summarizes the application of targeted protein degradation technology in the development of degraders for challenging drug targets. Finally, the article looks forward to the future development direction and application prospects of targeted protein degradation technology.


Subject(s)
Autophagy , Proteolysis , Proteolysis/drug effects , Humans , Autophagy/drug effects , Proteins/metabolism , Lysosomes/metabolism , Drug Development/methods , Molecular Targeted Therapy/methods , Animals
13.
J Am Chem Soc ; 146(18): 12587-12594, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38685488

ABSTRACT

Triphenylphosphine (PPh3) is a ubiquitous ligand in organometallic chemistry that has been shown to give enhanced 31P NMR signals at high magnetic field via a scalar-dominated Overhauser effect dynamic nuclear polarization (OE DNP). However, PPh3 can only be polarized via DNP in the free form, while the coordinated form is DNP-inactive. Here, we demonstrate the possibility of enhancing the 31P NMR signals of coordinated PPh3 in metal complexes in solution at room temperature by combining Overhauser effect DNP and chemical exchange between the free and coordinated PPh3 forms. With this method, we successfully obtain 31P DNP enhancements of up to 2 orders of magnitude for the PPh3 ligands in Rh(I), Ru(II), Pd(II), and Pt(II) complexes, and we show that the DNP enhancements can be used to determine the activation energy of the ligand exchange reaction.

14.
Angew Chem Int Ed Engl ; 63(24): e202402853, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38598262

ABSTRACT

In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro-adjuvants grafted with copolymers of 2-(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal-free surface-initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer-sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non-metabolized nanoparticles. Additionally, the adjuvants exhibit a "micro-ligand-mediated maturation enhancement" effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod-like and spherical micro-adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo-carrying "micro-shuttles", releasing antigens upon binding to DCs to facilitate efficient antigen delivery.


Subject(s)
Adjuvants, Immunologic , Dendritic Cells , Polymerization , Dendritic Cells/metabolism , Dendritic Cells/immunology , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemical synthesis , Vaccines/chemistry , Vaccines/immunology , Particle Size , Mice , Animals , Polymers/chemistry , Polymers/pharmacology , Polymers/chemical synthesis
15.
Adv Mater ; 36(15): e2307585, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38307004

ABSTRACT

Hypoxia and infection are urgent clinical problems in chronic diabetic wounds. Herein, living Chlorella-loaded poly(ionic liquid)-based microneedles (PILMN-Chl) are constructed for microacupuncture oxygen and antibacterial therapy against methicillin-resistant Staphylococcus aureus (MRSA)-infected chronic diabetic wounds. The PILMN-Chl can stably and continuously produce oxygen for more than 30 h due to the photosynthesis of the loaded self-supported Chlorella. By combining the barrier penetration capabilities of microneedles, the continuous and sufficient oxygen supply of Chlorella, and the sterilization activities of PIL, the PILMN-Chl can accelerate chronic diabetic wounds in vivo by topical targeted sterilization and hypoxia relief in deep parts of wounds. Thus, the self-oxygen produced microneedles modality may provide a promising and facile therapeutic strategy for treating chronic, hypoxic, and infected diabetic wounds.


Subject(s)
Chlorella , Diabetes Mellitus , Methicillin-Resistant Staphylococcus aureus , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria , Oxygen , Hypoxia/therapy
16.
Angew Chem Int Ed Engl ; 63(9): e202317337, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38193258

ABSTRACT

We evaluate the overall sensitivity gains provided by a series of eighteen nitroxide biradicals for dynamic nuclear polarization (DNP) solid-state NMR at 9.4 T and 100 K, including eight new biradicals. We find that in the best performing group the factors contributing to the overall sensitivity gains, namely the DNP enhancement, the build-up time, and the contribution factor, often compete with each other leading to very similar overall sensitivity across a range of biradicals. NaphPol and HydroPol are found to provide the best overall sensitivity factors, in organic and aqueous solvents respectively. One of the new biradicals, AMUPolCbm, provides high sensitivity for all three solvent formulations measured here, and can be considered to be a "universal" polarizing agent.

17.
Biomacromolecules ; 25(1): 89-103, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38056946

ABSTRACT

Antimicrobial peptide mimics have been used to kill bacteria and construct antibacterial materials. Precise design and construction of chemical structure are essential for easy access to highly effective antimicrobial peptide mimics. Herein, cationic guanidinium-based polymers (PGXs) with varying hydrophobic structures were synthesized to explore the structure and antibacterial activity relationship of antimicrobial peptide mimics and to construct antibacterial implants. The effect of the hydrophobic chemical structure, including carbon chain length and configuration, on the antimicrobial activities against both Escherichia coli and Staphylococcus aureus was investigated. The antibacterial activities of PGXs improved with increasing alkyl chain length, and PGXs with a straight-chain hydrophobic structure exhibited better bactericidal activities than those with cyclic alkane and aromatic hydrocarbon. Furthermore, PGXs grafted with poly(dimethylsiloxane) (PDMS-PGXs) showed a similar bactericidal change tendency of PGXs in solution. Additionally, the PDMS-PGXs showed potent antibiofilm performance in vitro, which can inhibit bacterial infection in vivo as subcutaneous implants. This study may propose a basis for the precise design and construction of antibacterial materials and provide a promising way of designing biomedical devices and implants with bacterial infection-combating activities.


Subject(s)
Polymers , Staphylococcal Infections , Humans , Polymers/pharmacology , Polymers/chemistry , Guanidine/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antimicrobial Peptides , Escherichia coli , Microbial Sensitivity Tests
18.
Front Med ; 17(5): 823-854, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37935945

ABSTRACT

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.


Subject(s)
Cyclin-Dependent Kinases , Cyclins , Humans , Cell Cycle/physiology , Cell Division , Cyclin-Dependent Kinases/genetics , Cyclin-Dependent Kinases/metabolism , Cyclins/genetics , Cyclins/metabolism
19.
ACS Appl Mater Interfaces ; 15(48): 55734-55744, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37985366

ABSTRACT

Molybdenum sulfide has been widely investigated as a prospective anode material for Li+/Na+ storage because of its unique layered structure and high theoretical capacity. However, the enormous volume variation and poor conductivity limit the development of molybdenum sulfide. The rational design of a heterogeneous interface is of great importance to improve the structure stability and electrical conductivity of electrode materials. Herein, a high-temperature mixing method is implemented in the hydrothermal process to synthesize the hybrid structure of MoS2/V2O3@carbon-graphene (MoS2/V2O3@C-rGO). The MoS2/V2O3@C-rGO composites exhibit superior Li+/Na+ storage performance due to the construction of the interface between the MoS2 and V2O3 components and the introduction of carbon materials, delivering a prominent reversible capacity of 564 mAh g-1 at 1 A g-1 after 600 cycles for lithium-ion batteries and 376.3 mAh g-1 at 1 A g-1 after 450 cycles for sodium-ion batteries. Theoretical calculations confirm that the construction of the interface between the MoS2 and V2O3 components can accelerate the reaction kinetics and enhance the charge-ionic transport of molybdenum sulfide. The results illustrate that interfacial engineering may be an effective guide to obtain high-performance electrode materials for Li+/Na+ storage.

20.
Sci Rep ; 13(1): 18230, 2023 10 25.
Article in English | MEDLINE | ID: mdl-37880296

ABSTRACT

To assess whether Roberts' age-adjusted warfarin loading protocol is effective in Chinese patients and whether the SAMeTT2R2 score can predict international normalized ratio (INR) control. Roberts' protocol for warfarin titration was applied to patients with non-valvular atrial fibrillation (NVAF) complicated with ischemic stroke at the Department of Neurology between 2014 and 2019. Clinical and sociodemographic variables were recorded. A minimum of 1-year follow-up was used to calculate the time in therapeutic range (TTR) of the INR. A total of 94 acute ischemic stroke patients with NVAF were included in the study. Seventy-seven (81.9%) of the patients had attained stable INR (2.0-3.0) at the fifth dose, and 90.0% of the patients had achieved stable INR on the ninth day. Seventeen (18.1%) of the patients had an INR > 4 during dose-adjustment period. Patients with INR > 4 had significantly lower body weight (53.8 vs. 63.1 kg, P = 0.014), lower rate of achievement of stable INR (35.3% vs. 92.2%, P = 0.000), and lower rate of TTR ≥ 65% (23.5% vs. 70.1%, P = 0.001), but with no significant increase in bleeding risk. A total of 89 patients underwent long-term INR follow-up, of which 58 (65.2%) patients achieved TTR ≥ 65%. Patients with poor TTR had significantly lower body weight (56.3 vs. 63.7 kg, P = 0.020) and lower rate of stable INR achievement (64.5% vs. 89.7%, P = 0.002). All 94 patients had SAMeTT2R2 score ≥ 2. There was no linear association between SAMeTT2R2 score and the rate of TTR ≥ 65% (Ptrend = 0.095). Chinese ischemic stroke patients with NVAF on warfarin can safely and quickly achieve therapeutic INR using Roberts' age-adjusted protocol and can obtain a good TTR. Lower body weight may be a predictor of poor TTR and INR > 4. Patients who have not attained stable INR after adjusting the dose five times are at high risk for poor TTR. SAMeTT2R2 score may not predict TTR in Chinese ischemic stroke patients with NVAF.


Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , Humans , Warfarin/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/chemically induced , International Normalized Ratio , Anticoagulants/therapeutic use , Ischemic Stroke/drug therapy , East Asian People , Treatment Outcome , Retrospective Studies , Stroke/etiology , Stroke/complications , Body Weight
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