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1.
Luminescence ; 39(4): e4749, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38658767

ABSTRACT

Lipid droplet, an intracellular lipid reservoir, is vital for energy metabolism and signal transmission in cells. The viscosity directly affects the metabolism of lipid droplets, and the abnormal viscosity is associated with the occurrence and development of various diseases. Therefore, it is indispensable to develop techniques that can detect viscosity changes in intracellular lipid droplets. Based on twisted intramolecular charge transfer (TICT) mechanism, a novel small-molecule lipid droplet-targeted viscosity fluorescence probe PPF-1 was designed. The probe was easy to synthesize, it had a large Stokes shift, stable optical properties, and low bio-toxicity. Compared to being in methanol solution, the fluorescence intensity of PPF-1 in glycerol solution was increased 26.7-fold, and PPF-1 showed excellent ability to target lipid droplets. Thus, the probe PPF-1 could provide an effective means of detecting viscosity changes of lipid droplets and was of great value for physiological diagnosis of related diseases, pathological analysis, and medical research.


Subject(s)
Fluorescent Dyes , Lipid Droplets , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Viscosity , Lipid Droplets/chemistry , Humans , Molecular Structure , Optical Imaging , Spectrometry, Fluorescence
2.
Plant Physiol Biochem ; 207: 108426, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38340689

ABSTRACT

In nature, light intensity usually fluctuates and a sudden shade-sun transition can induce photodamage to photosystem I (PSI) in many angiosperms. Photosynthetic regulation in fluctuating light (FL) has been studied extensively in C3 plants; however, little is known about how C4 plants cope FL to prevent PSI photoinhibition. We here compared photosynthetic responses to FL between maize (Zea mays, C4) and tomato (Solanum lycopersicum, C3) grown under full sunlight. Maize leaves had significantly higher cyclic electron flow (CEF) activity and lower photorespiration activity than tomato. Upon a sudden shade-sun transition, maize showed a significant stronger transient PSI over-reduction than tomato, resulting in a significant greater PSI photoinhibition in maize after FL treatment. During the first seconds upon shade-sun transition, CEF was stimulated in maize at a much higher extent than tomato, favoring the rapid formation of trans-thylakoid proton gradient (ΔpH), which was helped by a transient down-regulation of chloroplast ATP synthase activity. Therefore, modulation of ΔpH by regulation of CEF and chloroplast ATP synthase adjusted PSI redox state at donor side, which partially compensated for the deficiency of photorespiration. We propose that C4 plants use different photosynthetic strategies for coping with FL as compared with C3 plants.


Subject(s)
Photosystem I Protein Complex , Zea mays , Photosystem I Protein Complex/metabolism , Zea mays/metabolism , Chloroplast Proton-Translocating ATPases , Photosynthesis/physiology , Light , Electron Transport , Photosystem II Protein Complex/metabolism , Plant Leaves/metabolism
3.
Technol Health Care ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38339943

ABSTRACT

BACKGROUND: The term 'dementia' covers a range of progressive brain diseases from which many elderly people suffer. Traditional cognitive and pathological tests are currently used to detect dementia, however, applications using Artificial Intelligence (AI) methods have recently shown improved results from improved detection accuracy and efficiency. OBJECTIVE: This research paper investigates the efficacy of one type of data analytics called supervised learning to detect Alzheimer's disease (AD) - a common dementia condition. METHODS: The aim is to evaluate cognitive tests and common biological markers (biomarkers) such as cerebrospinal fluid (CSF) to develop predictive classification systems for dementia detection. RESULTS: A data analytics process has been proposed, implemented, and tested against real data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) repository. CONCLUSION: The models showed good power in predicting AD levels, notably from specified cognitive tests' scores and tauopathy related features.

4.
ACS Energy Lett ; 9(1): 201-208, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38230374

ABSTRACT

Aqueous zinc-ion batteries (ZIBs) employing zinc metal anodes are gaining traction as batteries for moderate to long duration energy storage at scale. However, corrosion of the zinc metal anode through reaction with water limits battery efficiency. Much research in the past few years has focused on additives that decrease hydrogen evolution, but the precise mechanisms by which this takes place are often understudied and remain unclear. In this work, we study the role of an acetonitrile antisolvent additive in improving the performance of aqueous ZnSO4 electrolytes using experimental and computational techniques. We demonstrate that acetonitrile actively modifies the interfacial chemistry during Zn metal plating, which results in improved performance of acetonitrile-containing electrolytes. Collectively, this work demonstrates the effectiveness of solvent additive systems in battery performance and durability and provides a new framework for future efforts to optimize ion transport and performance in ZIBs.

5.
Eur J Med Chem ; 264: 115934, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38007911

ABSTRACT

Breast cancer is one of the most common malignant tumors in women worldwide, with the majority of cases showing expression of estrogen receptors (ERs). Although drugs targeting ER have significantly improved survival rates in ER-positive patients, drug resistance remains an unmet clinical need. Fulvestrant, which overcomes selective estrogen receptor modulator (SERM) and AI (aromatase inhibitor) resistance, is currently the only long-acting selective estrogen receptor degrader (SERD) approved for both first and second-line settings. However, it fails to achieve satisfactory efficacy due to its poor solubility. Therefore, we designed and synthesized a series of novel scaffold (THC) derivatives, identifying their activities as ER antagonists and degraders. G-5b, the optimal compound, exhibited binding, antagonistic, degradation or anti-proliferative activities comparable to fulvestrant in ER+ wild type and mutants breast cancer cells. Notably, G-5b showed considerably improved stability and solubility. Research into the underlying mechanism indicated that G-5b engaged the proteasome pathway to degrade ER, subsequently inhibiting the ER signaling pathway and leading to the induction of apoptosis and cell cycle arrest events. Furthermore, G-5b displayed superior in vivo pharmacokinetics and pharmacodynamics properties, coupled with a favorable safety profile in the MCF-7 tamoxifen-resistant (MCF-7/TR) tumor xenograft model. Collectively, G-5b has emerged as a highly promising lead compound, offering potent antagonistic and degradation activities, positioning it as a novel long-acting SERD worthy of further refinement and optimization.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Estrogen Receptor Antagonists , Fulvestrant , Estrogen Antagonists/pharmacology , Tamoxifen/pharmacology , Selective Estrogen Receptor Modulators/pharmacology , Estrogen Receptor alpha/metabolism
6.
Anal Methods ; 16(2): 293-300, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38115761

ABSTRACT

Viscosity, an essential parameter of the cellular microenvironment, has the ability to indicate the condition of living cells. It is closely linked to numerous diseases like Alzheimer's disease, diabetes, and cardiovascular disorders. Therefore, it is necessary to design tools to effectively monitor viscosity changes, which could provide promising avenues for therapeutic interventions in these diseases. Herein, we report a novel mitochondria-targeting fluorescent probe GX-VS which was suitable for the detection of viscosity changes in vivo and in vitro. The probe GX-VS had many advantages such as long emission wavelength (650 nm), large Stokes shift (105 nm), significant fluorescence enhancement (59-fold), high sensitivity, good biocompatibility and so on. Biological experiments showed that the probe could target mitochondria and detect viscosity alterations in HeLa cells. Moreover, it has been successfully utilized to monitor viscosity changes induced by lipopolysaccharides (LPS) in inflammatory zebrafishes and living mice, which further underscored the capacity of GX-VS to explore fluctuations in viscosity within living organisms.


Subject(s)
Fluorescent Dyes , Zebrafish , Humans , Mice , Animals , HeLa Cells , Viscosity , Mitochondria
7.
ACS Appl Mater Interfaces ; 15(41): 48072-48084, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37805993

ABSTRACT

Predictive understanding of the molecular interaction of electrolyte ions and solvent molecules and their chemical reactivity on electrodes has been a major challenge but is essential for addressing instabilities and surface passivation that occur at the electrode-electrolyte interface of multivalent magnesium batteries. In this work, the isolated intrinsic reactivities of prominent chemical species present in magnesium bis(trifluoromethanesulfonimide) (Mg(TFSI)2) in diglyme (G2) electrolytes, including ionic (TFSI-, [Mg(TFSI)]+, [Mg(TFSI):G2]+, and [Mg(TFSI):2G2]+) as well as neutral molecules (G2) on a well-defined magnesium vanadate cathode (MgV2O4) surface, have been studied using a combination of first-principles calculations and multimodal spectroscopy analysis. Our calculations show that nonsolvated [Mg(TFSI)]+ is the strongest adsorbing species on the MgV2O4 surface compared with all other ions while partially solvated [Mg(TFSI):G2]+ is the most reactive species. The cleavage of C-S bonds in TFSI- to form CF3- is predicted to be the most desired pathway for all ionic species, which is followed by the cleavage of C-O bonds of G2 to yield CH3+ or OCH3- species. The strong stabilization and electron transfer between ionic electrolyte species and MgV2O4 is found to significantly favor these decomposition reactions on the surface compared with intrinsic gas-phase dissociation. Experimentally, we used state-of-the-art ion soft landing to selectively deposit mass-selected TFSI-, [Mg(TFSI):G2]+, and [Mg(TFSI):2G2]+ on a MgV2O4 thin film to form a well-defined electrolyte-MgV2O4 interface. Analysis of the soft-landed interface using X-ray photoelectron, X-ray absorption near-edge structure, electron energy-loss spectroscopies, as well as transmission electron microscopy confirmed the presence of decomposition species (e.g., MgFx, carbonates) and the higher amount of MgFx with [Mg(TFSI):G2]+ formed in the interfacial region, which corroborates the theoretical observation. Overall, these results indicate that Mg2+ desolvation results in electrolyte decomposition facilitated by surface adsorption, charge transfer, and the formation of passivating fluorides on the MgV2O4 cathode surface. This work provides the first evidence of the primary mechanisms leading to electrolyte decomposition at high-voltage oxide surfaces in multivalent batteries and suggests that the design of new, anodically stable electrolytes must target systems that facilitate cation desolvation.

8.
BMC Geriatr ; 23(1): 568, 2023 09 16.
Article in English | MEDLINE | ID: mdl-37716937

ABSTRACT

BACKGROUND: Accurately predicting the future development trend of population aging is conducive to accelerating the development of the elderly care industry. This study constructed a combined optimization grey prediction model to predict the structure and density of elderly population. METHODS: In this paper, a GT-FGM model is proposed, which combines Theta residual optimization with fractional-order accumulation operator. Fractional-order accumulation can effectively weaken the randomness of the original data sequence. Meanwhile, Theta residual optimization can adjust parameter by minimizing the mean absolute error. And the population statistics of Shanghai city from 2006 to 2020 were selected for prediction analysis. By comparing with the other traditional grey prediction methods, three representative error indexes (MAE, MAPE, RMSE) were conducting for error analysis. RESULTS: Compared with the FGM model, GM (1,1) model, Verhulst model, Logistic model, SES and other classical prediction methods, the GT-FGM model shows significant forecasting advantages, and its multi-step rolling prediction accuracy is superior to other prediction methods. The results show that the elderly population density in nine districts in Shanghai will exceed 0.5 by 2030, among which Huangpu District has the highest elderly population density, reaching 0.6825. There has been a steady increase in the elderly population over the age of 60. CONCLUSIONS: The GT-FGM model can improve the prediction accuracy effectively. The elderly population in Shanghai shows a steady growth trend on the whole, and the differences between districts are obvious. The government should build a modern pension industry system according to the aging degree of the population in each region, and promote the balanced development of each region.


Subject(s)
Aging , Pensions , Humans , Aged , China/epidemiology , Logistic Models
10.
JAMA Oncol ; 9(9): 1230-1237, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37440217

ABSTRACT

Importance: The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. Objective: To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Interventions: Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/µL [to convert to ×109/µL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Main Outcomes and Measurements: The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. Results: A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. Conclusion and Relevance: This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03709316.


Subject(s)
Ovarian Neoplasms , Humans , Female , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Carcinoma, Ovarian Epithelial/drug therapy , Progression-Free Survival , Indazoles/adverse effects , Double-Blind Method , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
12.
Sci Total Environ ; 899: 165648, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37482363

ABSTRACT

In the context of dual carbon targets, a reliable prediction of China's carbon dioxide emissions is of great significance to the design and formulation of emission reduction policies by Chinese government. To this end, a novel grey Verhulst model with four parameters is proposed in this paper according to the evolution law and the data characteristics of China's carbon dioxide emissions. The new model solves the defect of poor structural adaptability of the traditional grey Verhulst model by introducing a nonlinear correction term. Besides, the range of values for the order of the grey generation operator of the new model is expanded from a positive real number to any real number (r ∈ R+ â†’ r ∈ R) by expanding the value range of the Gamma function. The new model is used to simulate China's carbon dioxide emissions, and its comprehensive mean relative percentage error is only 0.65 %, which is better than that of the other three grey models (2.39 %, 2.34 %, 2.35 % respectively). It shows that the proposed new model has better modeling ability. Finally, the new model is applied to predict China's carbon dioxide emissions, and the results show that it will still increase year by year, reaching 13,687 million tons by 2028 (only 11,420 million tons in 2021). Therefore, some countermeasures and suggestions are proposed to control China's carbon dioxide emissions in this paper.

13.
Plant Physiol ; 193(1): 855-873, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37279567

ABSTRACT

Banana (Musa spp.) fruits, as typical tropical fruits, are cold sensitive, and lower temperatures can disrupt cellular compartmentalization and lead to severe browning. How tropical fruits respond to low temperature compared to the cold response mechanisms of model plants remains unknown. Here, we systematically characterized the changes in chromatin accessibility, histone modifications, distal cis-regulatory elements, transcription factor binding, and gene expression levels in banana peels in response to low temperature. Dynamic patterns of cold-induced transcripts were generally accompanied by concordant chromatin accessibility and histone modification changes. These upregulated genes were enriched for WRKY binding sites in their promoters and/or active enhancers. Compared to banana peel at room temperature, large amounts of banana WRKYs were specifically induced by cold and mediated enhancer-promoter interactions regulating critical browning pathways, including phospholipid degradation, oxidation, and cold tolerance. This hypothesis was supported by DNA affinity purification sequencing, luciferase reporter assays, and transient expression assay. Together, our findings highlight widespread transcriptional reprogramming via WRKYs during banana peel browning at low temperature and provide an extensive resource for studying gene regulation in tropical plants in response to cold stress, as well as potential targets for improving cold tolerance and shelf life of tropical fruits.


Subject(s)
Food Preservation , Fruit , Musa , Musa/genetics , Musa/physiology , Fruit/physiology , Cold Temperature , Histones/metabolism , Chromatin , Plant Proteins/metabolism , Enhancer Elements, Genetic , Histone Code , Transcription Factors/metabolism , Membrane Lipids/metabolism
14.
Luminescence ; 38(9): 1618-1623, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37376960

ABSTRACT

As a fundamental physical parameter, viscosity influences the diffusion in biological processes. The changes in intracellular viscosity led to the occurrence of relevant diseases. Monitoring changes in cellular viscosity is important for distinguishing abnormal cells in cell biology and oncologic pathology. Here, we devised and synthesized a viscosity-sensitive fluorescent probe LBX-1. LBX-1 showed high sensitivity, providing a large Stokes shift as well as an enhancement in fluorescent intensity (16.1-fold) from methanol solution to glycerol solution. Furthermore, the probe LBX-1 could localize in mitochondria because of the ability of the probe to penetrate the cell membrane and accumulate in mitochondria. These results suggested that the probe could be utilized in monitoring the changes in mitochondrial viscosity in complex biological systems.


Subject(s)
Fluorescent Dyes , Mitochondria , Humans , Fluorescent Dyes/metabolism , HeLa Cells , Viscosity , Mitochondria/metabolism , Cell Membrane/metabolism
15.
BMC Geriatr ; 23(1): 237, 2023 04 20.
Article in English | MEDLINE | ID: mdl-37081383

ABSTRACT

BACKGROUND: To meet the needs of diversified pension services and the construction of aged care institutions is one of the urgent livelihood issues in China. Under the major national needs of pension and care for the elderly, it is necessary to optimize the allocation of pension and care for the elderly resources, and formulate operational coping strategies and optimization plans. It is of great significance to deal with the urgent problem of population aging in a timely and scientific way. METHODS: The economic benefits and social costs of aged care institutions are regarded as objective functions. To satisfy the economic benefits, it is necessary to reduce the social costs, and its construction quantity can only be an integer. The multi-objective genetic algorithm is improved with integer programming, and the global optimal solution is achieved after several times of searching. Under the multi-objective optimization model, the improved genetic algorithm was combined with the superior and inferior solution distance method to solve the genetic algorithm, and the corresponding objective function value was obtained after rounding. Finally, Pareto optimal solution set is selected by multi-objective decision, and the result of construction planning is obtained. RESULTS: Based on multi-attribute decision analysis and taking three years as the construction cycle, the planning scheme of aged care institutions construction in each district of Nanjing in the next 15 years was proposed. In addition, considering the intelligent trend of future pension, the proportion of home-based pension is increasing year by year, and the model is promoted to meet the needs of diversified pension services. With the gradual increase of the elderly population in Nanjing, the proportion of intelligent home-based care has been increasing year by year since 2027, and the construction demand of aged care institutions has also increased. The number of construction at all levels rises gradually in each cycle, and the increase is more obvious after 2027. CONCLUSIONS: The layout and planning of aged care institutions proposed in this paper not only considers economic and environmental benefits, but also combines the current situation of aged care institutions in various districts of Nanjing. The model is reasonable and effective, and has practical application value. It will help China optimize the allocation of elderly care resources under the target of active aging, and scientifically and comprehensively deal with the problem of population aging.


Subject(s)
Disabled Persons , Home Care Services , Aged , Humans , Aging , China/epidemiology , Pensions
16.
Small ; 19(19): e2207623, 2023 May.
Article in English | MEDLINE | ID: mdl-36759953

ABSTRACT

Photocatalyst with excellent semiconductor properties is the key point to realize the efficient photocatalytic hydrogen evolution (PHE). As a representative binary metal sulfide (BMS) semiconductor, cadmium sulfide (CdS) possesses suitable bandgap of 2.4 eV and negative conduction band potential, which has a great potential to realize efficient visible-light PHE performance. In this work, CdS with unique cubic/hexagonal phase junction is facilely synthesized through a sulfur-rich butyldithiocarbamate acid (BDCA) solution process. The results illustrate that the phase junction can efficiently enhance the separation and transfer of photogenerated electron-hole pairs, resulting in an excellent PHE performance. In addition, the sulfur-rich property of BDCA solution leads to the absence of additional sulfur sources during the synthesis of CdS photocatalyst, which greatly simplifies the fabrication process. The optimal PHE rate of the BDCA-synthesized phase junction CdS photocatalyst is 7.294 mmol g-1  h-1 and exhibits a favorable photostability. Moreover, density function theory calculations indicated that the apparent redistribution of charge density in the cubic/hexagonal phase junction regions gives a suitable hydrogen adsorption capacity, which is responsible for the enhanced PHE activity.

17.
Front Plant Sci ; 14: 1105521, 2023.
Article in English | MEDLINE | ID: mdl-36824194

ABSTRACT

The quality of seedlings is an important factor for development of the pear industry. A strong seedling with few branches and suitable internodes is ideal material as a rootstock for grafting and breeding. Several branching mutants of pear rootstocks were identified previously. In the present study, 'QAU-D03' (Pyrus communis L.) and it's mutants were used to explore the mechanism that affects branch formation by conducting phenotypic trait assessment, hormone content analysis, and transcriptome analysis. The mutant plant (MP) showed fewer branches, shorter 1-year-old shoots, and longer petiole length, compared to original plants (OP), i.e., wild type. Endogenous hormone analysis revealed that auxin, cytokinin, and jasmonic acid contents in the stem tips of MP were significantly higher than those of the original plants. In particular, the jasmonic acid content of the MP was 1.8 times higher than that of the original plants. Transcriptome analysis revealed that PcCOI1, which is a transcriptional regulatory gene downstream of the jasmonic acid signaling pathway, was expressed more highly in the MP than in the original plants, whereas the expression levels of PcJAZ and PcMYC were reduced in the MP compared with that of the original plants. In response to treatment with exogenous methyl jasmonate, the original plants phenotype was consistent with that of the MP in developing less branches. These results indicate that jasmonic acid negatively regulates branch growth of pear trees and that jasmonic acid downstream regulatory genes play a crucial role in regulating branching.

18.
Front Microbiol ; 14: 1023036, 2023.
Article in English | MEDLINE | ID: mdl-36846790

ABSTRACT

Objective: The widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA infection. Methods: The structure of Fe3O4 NPs with limited antibacterial activity was optimized, and the Fe2+ ↔ Fe3+ electronic coupling was eliminated by replacing 1/2 Fe2+ with Cu2+. A new type of copper-containing ferrite nanoparticles (hereinafter referred to as Cu@Fe NPs) that fully retained oxidation-reduction activity was synthesized. First, the ultrastructure of Cu@Fe NPs was examined. Then, antibacterial activity was determined by testing the minimum inhibitory concentration (MIC) and safety for use as an antibiotic agent. Next, the mechanisms underlying the antibacterial effects of Cu@Fe NPs were investigated. Finally, mice models of systemic and localized MRSA infections was established for in vivo validation. Results: It was found that Cu@Fe NPs exhibited excellent antibacterial activity against MRSA with MIC of 1 µg/mL. It effectively inhibited the development of MRSA resistance and disrupted the bacterial biofilms. More importantly, the cell membranes of MRSA exposed to Cu@Fe NPs underwent significant rupture and leakage of the cell contents. Cu@Fe NPs also significantly reduced the iron ions required for bacterial growth and contributed to excessive intracellular accumulation of exogenous reactive oxygen species (ROS). Therefore, these findings may important for its antibacterial effect. Furthermore, Cu@Fe NPs treatment led to a significant reduction in colony forming units within intra-abdominal organs, such as the liver, spleen, kidney, and lung, in mice with systemic MRSA infection, but not for damaged skin in those with localized MRSA infection. Conclusion: The synthesized nanoparticles has an excellent drug safety profile, confers high resistant to MRSA, and can effectively inhibit the progression of drug resistance. It also has the potential to exert anti-MRSA infection effects systemically in vivo. In addition, our study revealed a unique multifaceted antibacterial mode of Cu@Fe NPs: (1) an increase in cell membrane permeability, (2) depletion of Fe ions in cells, (3) generation of ROS in cells. Overall, Cu@Fe NPs may be potential therapeutic agents for MRSA infections.

19.
Curr Pharm Biotechnol ; 24(1): 50-60, 2023.
Article in English | MEDLINE | ID: mdl-35619298

ABSTRACT

Nucleic acids (DNA and RNA) hold great potential for the advancement of future medicine but suffer from unsatisfactory clinical success due to the challenges accompanied with their delivery. Nucleic acid-mediated nanomaterials have riveted the researchers from the past two decades and exhilarating tasks have prevailed. Nucleic acid nanotechnology offers unique control over the shape, size, time, mechanics and anisotropy. It can transfect numerous types of tissues and cells without any toxic effect, minimize the induced immune response, and penetrate most of the biological barriers and hence it reveals itself as a versatile tool for multidisciplinary research field and for various therapeutic purposes. Nucleic acid combines with other nanoscale objects also by altering the chemical functional groups and reproducing the varied array of nanomaterials. Interestingly, nucleic acidderived nanomaterials are characterized easily at atomic level accuracy. However, this advent of nanoscience has vital issues which must be addressed, such as the high cost of nucleic acids, their self-assembly nature, etc. Hence, the aim of this review is to highlight the systematic advances and methodology of nucleic acid-mediated synthesis of nanomaterials and their therapeutic applications.


Subject(s)
Nanostructures , Nucleic Acids , Nucleic Acids/therapeutic use , DNA/chemistry , Nanotechnology/methods , Nanostructures/therapeutic use , Nanostructures/chemistry , Pharmaceutical Preparations
20.
BMC Womens Health ; 22(1): 534, 2022 12 19.
Article in English | MEDLINE | ID: mdl-36536343

ABSTRACT

Cervical cancer is one of the most common gynecological malignancies. Due to the high heterogeneity of cervical cancer accelerating cancer progression, it is necessary to identify new prognostic markers and treatment regimens for cervical cancer to improve patients' survival rates. We purpose to construct and verify a risk prediction model for cervical cancer patients. Based on the analysis of data from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), differences of genes in normal and cancer samples were analyzed and then used analysis of WGCNA along with consistent clustering to construct single-factor + multi-factor risk models. After regression analysis, the target genes were obtained as prognostic genes and prognostic risk models were constructed, and the validity of the risk model was confirmed using the receiver operating characteristic curve (ROC) and Kaplan-Meier curve. Subsequently, the above model was verified on the GSE44001 data validation followed by independent prognostic analysis. Enrichment analysis was conducted by grouping the high and low risks of the model. In addition, differences in immune analysis (immune infiltration, immunotherapy), drug sensitivity, and other levels were counted by the high and low risks groups. In our study, three prognostic genes including APOD, APOC1, and SQLE were obtained, and a risk model was constructed along with validation based on the above-mentioned analysis. According to the model, immune correlation and immunotherapy analyses were carried out, which will provide a theoretical basis and reference value for the exploration and treatment of cervical cancer.


Subject(s)
Gynecology , Uterine Cervical Neoplasms , Female , Humans , Prognosis , Cluster Analysis , Databases, Factual
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