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1.
J Colloid Interface Sci ; 675: 646-659, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38991279

RESUMO

HYPOTHESIS: Poor storage stability and oxidative deterioration are the common drawbacks of edible oils rich in polyunsaturated fatty acids (PUFAs). We hypothesized that the natural zein/tannic acid self-assembly nanoparticles (ZT NPs) could be employed as stabilizers to anchor at the oil-water interface, thus constructing Pickering emulsion gel (PKEG) system for three types of PUFA-rich oils, soybean oil (SO), fish oil (FO) and cod liver oil (CLO), to improve the storage and oxidation stability. EXPERIMENTS: ZT NPs were prepared by the anti-solvent coprecipitation method, and the three-phase contact angle, FT-IR, and XRD were mainly characterized. To observe the shell-core structure and oil-water interface details of SO/FO/CLO PKEGs by confocal laser scanning microscope and cryo-scanning electron microscope. Accelerated oxidation of FO was performed to assess the protective effect of PKEG on lipids. FINDINGS: The SO, FO, and CLO PKEGs stabilized by 2 % ZT NPs, with oil fraction (φ = 0.5-0.6), were obtained. PKEGs show high viscoelasticity, clear shell-core structure spatial network structure, and ideal storage stability. Under accelerated oxidation, the degree of oxidative rancidity of FO PKEG was obviously lower than that of free FO. Overall, this work opens up new possibilities for using natural PKEG to prevent oxidative deterioration and prolong the shelf-life of PUFA-rich oils.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39046129

RESUMO

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

3.
World J Gastroenterol ; 30(25): 3155-3165, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39006389

RESUMO

BACKGROUND: Due to similar clinical manifestations and imaging signs, differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical practice. AIM: To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD. METHODS: We collected contrast-enhanced computed tomography (CECT) and clinical data from 120 patients form center 1. A total of 944 features were extracted single-phase images of CECT scans. Using the last absolute shrinkage and selection operator model, the best predictive radiographic features and clinical indications were screened. Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model. The area under the receiver operating characteristic curve, accuracy, sensitivity and specificity were used for evaluation. RESULTS: A total of five machine learning models were built to distinguish PIL from CD. Based on the results from the test group, most models performed well with a large area under the curve (AUC) (> 0.850) and high accuracy (> 0.900). The combined clinical and radiomics model (AUC = 1.000, accuracy = 1.000) was the best model among all models. CONCLUSION: Based on machine learning, a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.


Assuntos
Doença de Crohn , Neoplasias Intestinais , Aprendizado de Máquina , Curva ROC , Tomografia Computadorizada por Raios X , Humanos , Doença de Crohn/diagnóstico por imagem , Feminino , Diagnóstico Diferencial , Masculino , Pessoa de Meia-Idade , Adulto , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/patologia , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Idoso , Sensibilidade e Especificidade , Meios de Contraste/administração & dosagem , Adulto Jovem , Radiômica
4.
Nanoscale ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034677

RESUMO

This study reports a fluorescent nanoprobe operated in fluorescence turn-on mode for simultaneously sensing and imaging intracellular GSH and ATP. By using maleimide-derivatives as the ligand, the bimetallic nanoscale metal-organic framework (NMOF) Cu-Mi-UiO-66 has been synthesized for the first time using a straightforward one-step solvothermal approach, serving as a GSH recognition moiety. Subsequently, a Cy5-labeled ATP aptamer was assembled onto Cu-Mi-UiO-66 via strong coordination between phosphate and zirconium, π-π stacking and electrostatic adsorption to develop the dual-responsive fluorescence nanoprobe Cu-Mi-UiO-66/aptamer. Due to the photoinduced electron transfer (PET) effect between maleimide groups and the benzene ring of the ligand and the charge transfer between Cy5 and the Zr(IV)/Cu(II) bimetal center of the NMOF, the Cu-Mi-UiO-66/aptamer exhibits a fluorescence turn-off status. The Michael addition reaction between the thiol group of GSH and the maleimide on the NMOF skeleton results in turning on of the blue fluorescence of Cu-Mi-UiO-66. Meanwhile, upon specific interaction with ATP, the aptamer changes into internal loop structures and detaches from Cu-Mi-UiO-66, resulting in turning on of the red fluorescence of Cy5. The nanoprobe demonstrated an excellent sensing performance with a good linear range (GSH, 5.0-450.0 µM; ATP, 1.0-50.0 µM) and a low detection limit (GSH, 2.17 µM; ATP, 0.635 µM). More importantly, the Cu-Mi-UiO-66/aptamer exhibits good performance for tracing intracellular concentration variations of GSH and ATP in living HepG2 cells under different stimulations. This study highlights the potential of NMOFs for multiplexed analysis and provides a valuable tool for tumor microenvironment research and early cancer diagnosis.

5.
Appl Environ Microbiol ; : e0099524, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023266

RESUMO

Surveillance for animal plague was conducted in the Marmota himalayana plague focus of the Qinghai-Tibet Plateau from 2020 to 2023. A 22.89% positive rate of serum F1 antibody was detected in live-caught marmots, alongside a 43.40% incidence of Yersinia pestis isolation from marmot carcasses. Marmot carcasses infected with plague exhibited a significantly higher spleen-somatic index (P < 0.05). Twenty-one Y. pestis-specific phages were isolated, among which one Y. pestis lytic phage (AKS2022HT87GU_phi) was isolated from the bone marrow of a marmot carcass (no. AKS2022HT87) and was found to be symbiotic with Y. pestis. Microscopy revealed the coexistence of lysed and non-lysed colonies of Y. pestis AKS2022HT87. Genome-wide analysis showed that certain strains of the Y. pestis AKS2022HT87 carried phage DNA fragments consistent with phage AKS2022HT87GU_phi. The rare symbiotic relationship between a lytic phage and Y. pestis observed in vitro was highlighted in this study, laying the basis for further exploring the relationship between Y. pestis and its bacteriophages.IMPORTANCEBacteriophages and host bacteria commonly coexist in vivo or in soil environments through complex and interdependent microbial interactions. However, recapitulating this symbiotic state remains challenging in vitro due to limited medium nutrients. In this work, the natural symbiosis between Yersinia pestis and specific phages has been discovered in a Marmota himalayana specimen. Epidemiological analysis presented the characteristics of the Y. pestis and specific phages in the area with a strong plague epidemic. Crucially, comparative genomics has been conducted to analyze the genetic changes in both the Y. pestis and phages over different periods, revealing the dynamic and evolving nature of their symbiosis. These are the critical steps to study the mechanism of the symbiosis.

6.
BMC Public Health ; 24(1): 1928, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026227

RESUMO

BACKGROUND: The association between sarcopenia and cardiovascular disease (CVD) is well known. However, the clinical diagnosis of sarcopenia is complex and not suitable for early clinical identification and prevention of CVD. Relative muscle strength (RMS) is a relatively quantitative and straightforward indicator, but its association with CVD remains unclear. Hence, the objective of this research was to investigate the correlation between RMS and CVD incidence. METHODS: This was a cross-sectional study, using data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011. CVD events were assessed through self-reported physician diagnoses. The RMS was determined by dividing the maximum grip strength by the appendicular skeletal muscle mass (ASM). This study used multivariate logistic regression and restricted cubic spline (RCS) curves to explore the correlation between RMS and CVD incidence. Additionally, we conducted subgroup analyses to provide additional evidence supporting the association between the two variables. RESULTS: A total of 8,733 people were included in our study, with 1,152 (13.19%) CVD patients and 7,581 (86.81%) non-CVD patients. When the data were grouped according to quartiles (Q) of RMS, the inverse association between CVD and RMS remained statistically significant even after controlling for all potential confounding factors. Compared with participants in Q1 of RMS, the ORs (95% CIs) of CVD among those in Q2-Q4 were 0.99 (0.83, 1.17), 0.81 (0.67, 0.98), and 0.70 (0.57, 0.85), respectively. Moreover, the RCS results showed a negative linear correlation between the RMS and CVD incidence (P for nonlinearity = 0.555). Subgroup analysis revealed no significant interaction in any of the groups except for the sex group (P for interaction = 0.046). CONCLUSION: Our study indicated a stable negative correlation between RMS and CVD incidence. RMS is helpful for the early identification and prevention of CVD.


Assuntos
Doenças Cardiovasculares , Força Muscular , Humanos , China/epidemiologia , Doenças Cardiovasculares/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Força Muscular/fisiologia , Incidência , Estudos Longitudinais , Sarcopenia/epidemiologia
7.
Angew Chem Int Ed Engl ; : e202409436, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016543

RESUMO

The appearance of disordered lithium dendrites and fragile solid electrolyte interfaces (SEI) significantly hinder the serviceability of lithium metal batteries. Herein, guided by theoretical predictions, a multi-component covalent triazine framework with partially electronegative channels (4C-TA0.5TF0.5-CTF) is incorporated as a protective layer to modulate the interface stability of the lithium metal batteries. Notably, the 4C-TA0.5TF0.5-CTF with optimized electronic structure at the molecular level by fine-tuning the local acceptor-donor functionalities not only enhances the intermolecular interaction thereby providing larger dipole moment and improved crystallinity and mechanical stress, but also facilitates the beneficial effect of lithiophilic sites (C-F bonds, triazine cores, C=N linkages and aromatic rings) to further regulate the migration of Li+ and achieve a uniform lithium deposition behavior as determined by various in-depth in/ex situ characterizations. Due to the synergistic effect of multi-component organic functionalities, the 4C-TA0.5TF0.5-CTF modified full cells perform significantly better than the common two/three-component 2C-TA-CTF and 3C-TF-CTF electrodes, delivering an excellent capacity of 116.3 mAh g-1 (capacity retention ratio: 86.8%) after 1000 cycles at 5 C and improved rate capability. This work lays a platform for the prospective molecular design of improved organic framework relative artificial SEI for highly stable lithium metal batteries.

8.
Front Oncol ; 14: 1396439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887237

RESUMO

Objective: This study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment. Methods: This retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model. Results: The PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4+LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92). Conclusion: NICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies.

9.
Nat Microbiol ; 9(7): 1686-1699, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898217

RESUMO

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.


Assuntos
Antifúngicos , Mutagênese , Animais , Camundongos , Humanos , Virulência/genética , Antifúngicos/farmacologia , China , Temperatura Corporal , Modelos Animais de Doenças , Ascomicetos/genética , Ascomicetos/patogenicidade , Ascomicetos/efeitos dos fármacos , Caspofungina/farmacologia , Testes de Sensibilidade Microbiana , Fluconazol/farmacologia , Micoses/microbiologia , Farmacorresistência Fúngica Múltipla/genética , Farmacorresistência Fúngica/genética
10.
Acta Derm Venereol ; 104: adv24050, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38932592

RESUMO

To examine the prevalence of comorbidities in Chinese urticaria patients and assess medication use patterns across different ages (6-11 years, 12-17 years, above 18 years), a retrospective cohort study was performed in 192,647 urticaria patients within the Health Database. After 1:1 propensity score matching, 166,921 people were divided into the urticaria group and the control group, and the follow-up data were collected within 2 years. During the 12-month and 24-month follow-up period, significant comorbidities identified included allergic rhinitis and asthma, with distinct patterns observed across age groups. Chronic urticaria patients often have complications, such as allergic rhinitis, upper respiratory infection, oropharyngeal infection, and dental caries. The study underscores the need for age-specific treatment strategies in urticaria management.


Assuntos
Urticária Crônica , Comorbidade , Humanos , Estudos Retrospectivos , Criança , Masculino , Adolescente , Feminino , China/epidemiologia , Prevalência , Fatores Etários , Adulto Jovem , Urticária Crônica/epidemiologia , Urticária Crônica/tratamento farmacológico , Adulto , Rinite Alérgica/epidemiologia , Fatores de Tempo , Urticária/epidemiologia , Urticária/diagnóstico , Fatores de Risco , Pontuação de Propensão , Pessoa de Meia-Idade , Bases de Dados Factuais , Asma/epidemiologia , Asma/tratamento farmacológico , Asma/diagnóstico , População do Leste Asiático
11.
Cell Death Dis ; 15(6): 416, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879600

RESUMO

Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function. The reduced expression of HNF1α is a critical event in the development of HCC, but the underlying mechanism for its degradation remains elusive. In this study, we discovered that the expression of TRIM8 was upregulated in HCC tissues, and was positively correlated with aggressive tumor behavior of HCC and shorter survival of HCC patients. Overexpression of TRIM8 promoted the proliferation, colony formation, invasion, and migration of HCC cells, while TRIM8 knockdown or knockout exerted the opposite effects. RNA sequencing revealed that TRIM8 knockout suppresses several cancer-related pathways, including Wnt/ß-catenin and TGF-ß signaling in HepG2 cells. TRIM8 directly interacts with HNF1α, promoting its degradation by catalyzing polyubiquitination on lysine 197 in HCC cells. Moreover, the cancer-promoting effects of TRIM8 in HCC were abolished by the HNF1α-K197R mutant in vitro and in vivo. These data demonstrated that TRIM8 plays an oncogenic role in HCC progression through mediating the ubiquitination of HNF1α and promoting its protein degradation, and suggests targeting TRIM8-HNF1α may provide a promising therapeutic strategy of HCC.


Assuntos
Carcinoma Hepatocelular , Progressão da Doença , Fator 1-alfa Nuclear de Hepatócito , Neoplasias Hepáticas , Ubiquitinação , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética
12.
Ergonomics ; : 1-16, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912844

RESUMO

Based on multimodal measurement methods of NASA task load index (NASA-TLX), task performance, surface electromyography (sEMG), heart rate (HR), and functional near-infrared spectroscopy (fNIRS), this study conducted experimental measurements and analyses under 16 different load levels of physical fatigue and mental fatigue combination conditions. This study observed the interaction between physical fatigue and mental fatigue at different levels, and at the subjective level, the effect of physical fatigue on mental fatigue was greater than that of mental fatigue on physical fatigue. Secondly, the results of fNIRS analysis showed that the premotor cortex is affected by physical fatigue, and the dorsolateral prefrontal cortex is affected by mental fatigue. Finally, this study constructed a fatigue classification model with an accuracy of 95.3%, which takes multimodal physiological data as input and 16 fatigue states as output. The research results will provide a basis for fatigue analysis, evaluation, and improvement in complex working situations.


Based on multimodal measurement methods of NASA-TLX, task performance, sEMG, HR, and fNIRS, this study illustrated the relationship between physical fatigue and mental fatigue, and proposed a classification method for different fatigue situations.

13.
Opt Express ; 32(12): 21497-21505, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859502

RESUMO

Tamm plasmon polaritons (TPPs), localized near the boundary of a dielectric Bragg reflector (DBR) and a thin metal film, have attracted much attention for the lower ohm loss and flexible excitation. However, the radiation loss resulting from the direct coupling to the surroundings hinders their applications. Here, we propose and experimentally demonstrate a new type of hybrid plasmonic quasi-bound state in the continuum (BIC) in a Tamm-surface plasmon polariton system to suppress the radiation loss. Leveraging the scattering of the periodic metal array, the TPP interacts with the surface plasmon polariton (SPP) mode and form a Friedrich-Wintgen type quasi-BIC state that originated from the interference of two surface waves with different natures. Through angle resolved reflectance spectrum measurement, the hybrid plasmonic quasi-BIC was observed in the experiment. Our work proposes a new method to design a high Q mode in plasmonic systems, and thus holds promise for applications in the field of light matter interactions.

14.
Environ Res ; 258: 119402, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866314

RESUMO

Antibiotic residues, such as tetracycline (TET), in aquatic environments have become a global concern. The liver and gut are important for immunity and metabolism in aquatic organisms. In this study, juvenile groupers were subjected to 1 and 100 µg/L TET for 14 days, and the physiological changes of these fish were evaluated from the perspective of gut-liver axis. After TET exposure, the liver showed histopathology, lipid accumulation, and the elevated ALT activity. An oxidative stress response was induced in the liver and the metabolic pattern was disturbed, especially pyrimidine metabolism. Further, intestinal health was also affected, including the damaged intestinal mucosa, the decreased mRNA expression levels of tight junction proteins (ZO-1, Occludin, and Claudin-3), along with the increased gene expression levels of inflammation (IL-1ß, IL-8, TNF-α) and apoptosis (Casp-3 and p53). The diversity of intestinal microbes increased and the community composition was altered, and several beneficial bacteria (Lactobacillus, Bacteroidales S24-7 group, and Romboutsia) and harmful (Aeromonas, Flavobacterium, and Nautella) exhibited notable correlations with hepatic physiological indicators and metabolites. These results suggested that TET exposure can adversely affect the physiological homeostasis of groupers through the gut-liver axis.

15.
Anal Chem ; 96(25): 10451-10458, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38860917

RESUMO

Rapid and sensitive RNA detection is of great value in diverse areas, ranging from biomedical research to clinical diagnostics. Existing methods for RNA detection often rely on reverse transcription (RT) and DNA amplification or involve a time-consuming procedure and poor sensitivity. Herein, we proposed a CRISPR/Cas12a-enabled amplification-free assay for rapid, specific, and sensitive RNA diagnostics. This assay, which we termed T7/G4-CRISPR, involved the use of a T7-powered nucleic acid circuit to convert a single RNA target into numerous DNA activators via toehold-mediated strand displacement reaction and T7 exonuclease-mediated target recycling amplification, followed by activating Cas12a trans-cleavage of the linker strands inhibiting split G-Quadruplex (G4) assembly, thereby inducing fluorescence attenuation proportion to the input RNA target. We first performed step-by-step validation of the entire assay process and optimized the reaction parameters. Using the optimal conditions, T7/G4-CRISPR was capable of detecting as low as 3.6 pM target RNA, obtaining ∼100-fold improvement in sensitivity compared with the most direct Cas12a assays. Meanwhile, its excellent specificity could discriminate single nucleotide variants adjacent to the toehold region and allow species-specific pathogen identification. Furthermore, we applied it for analyzing bacterial 16S rRNA in 40 clinical urine samples, exhibiting a sensitivity of 90% and a specificity of 100% when validated by RT-quantitative PCR. Therefore, we envision that T7/G4-CRISPR will serve as a promising RNA sensing approach to expand the toolbox of CRISPR-based diagnostics.


Assuntos
Sistemas CRISPR-Cas , Quadruplex G , Sistemas CRISPR-Cas/genética , Humanos , Exodesoxirribonucleases/metabolismo , Exodesoxirribonucleases/química , RNA/análise , RNA/metabolismo , Técnicas de Amplificação de Ácido Nucleico , Proteínas Associadas a CRISPR/metabolismo , Proteínas de Bactérias , Endodesoxirribonucleases
16.
NPJ Biofilms Microbiomes ; 10(1): 51, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902226

RESUMO

Bacteria induced metamorphosis observed in nearly all marine invertebrates. However, the mechanism of bacteria regulating the larvae-juvenile metamorphosis remains unknown. Here, we test the hypothesis that c-di-GMP, a ubiquitous bacterial second-messenger molecule, directly triggers the mollusc Mytilus coruscus larval metamorphosis via the stimulator of interferon genes (STING) receptor. We determined that the deletion of c-di-GMP synthesis genes resulted in reduced c-di-GMP levels and biofilm-inducing activity on larval metamorphosis, accompanied by alterations in extracellular polymeric substances. Additionally, c-di-GMP extracted from tested varying marine bacteria all exhibited inducing activity on larval metamorphosis. Simultaneously, through pharmacological and molecular experiments, we demonstrated that M. coruscus STING (McSTING) participates in larval metamorphosis by binding with c-di-GMP. Our findings reveal that new role of bacterial c-di-GMP that triggers mussel larval metamorphosis transition, and extend knowledge in the interaction of bacteria and host development in marine ecosystems.


Assuntos
Biofilmes , GMP Cíclico , Larva , Metamorfose Biológica , Mytilus , Animais , Larva/microbiologia , Larva/crescimento & desenvolvimento , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Biofilmes/crescimento & desenvolvimento , Mytilus/microbiologia , Mytilus/crescimento & desenvolvimento , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
17.
J Dig Dis ; 25(4): 255-265, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38837552

RESUMO

OBJECTIVES: In this study we aimed to assess the impact of acetylation of hepatocyte nuclear factor 4α (HNF4α) on lysine 458 on the differentiation therapy of hepatocellular carcinoma (HCC). METHODS: Periodic acid-Schiff (PAS) staining, Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake, and senescence-associated ß-galactosidase (SA-ß-gal) activity analysis were performed to assess the differentiation of HCC cells. HNF4α protein was detected by western blot and immunohistochemistry (IHC). The effects of HNF4α-K458 acetylation on HCC malignancy were evaluated in HCC cell lines, a Huh-7 xenograft mouse model, and an orthotopic model. The differential expression genes in Huh-7 xenograft tumors were screened by RNA-sequencing analysis. RESULTS: K458R significantly enhanced the inhibitory effect of HNF4α on the malignancy of HCC cells, whereas K458Q reduced the inhibitory effects of HNF4α. Moreover, K458R promoted, while K458Q decreased, HNF4α-induced HCC cell differentiation. K458R stabilized HNF4α, while K458Q accelerated the degradation of HNF4α via the ubiquitin proteasome system. K458R also enhanced the ability of HNF4α to inhibit cell growth of HCC in the Huh-7 xenograft mouse model and the orthotopic model. RNA-sequencing analysis revealed that inhibiting K458 acetylation enhanced the transcriptional activity of HNF4α without altering the transcriptome induced by HNF4α in HCC. CONCLUSION: Our data revealed that inhibiting K458 acetylation of HNF4α might provide a more promising candidate for differential therapy of HCC.


Assuntos
Carcinoma Hepatocelular , Diferenciação Celular , Fator 4 Nuclear de Hepatócito , Neoplasias Hepáticas , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Acetilação , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Lisina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1122-1127, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856426

RESUMO

Synthetic dimensions have drawn intense recent attention in investigating higher-dimensional topological physics and offering additional degrees of freedom for manipulating light. It has been demonstrated that synthetic dimensions can help to concentrate light with different frequencies at different locations. Here, we show that synthetic dimensions can also route light from different incident directions. Our system consists of an interface formed by two different photonic crystals. A synthetic dimension ξ is introduced by shifting the termination position of the photonic crystal on the right-hand side of the interface. We identify a correspondence between ξ and the interface state such that light incident from a specific direction can be collected. Thus, routing incident light from different directions is achieved by designing an interface with a proper distribution of ξ. Traditionally, this goal is achieved with a standard 4f optical system using a convex lens, and our approach offers the possibility for such a capability within a few lattice sites of photonic crystals. Such an approach reduces the size of the system, making it easier for integration. Our work provides, to our knowledge, a new direction for routing light with different momentums and possibly contributes to applications such as lidar.

19.
Front Immunol ; 15: 1402862, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863706

RESUMO

Ovarian cancer, ranking as the seventh most prevalent malignancy among women globally, faces significant challenges in diagnosis and therapeutic intervention. The difficulties in early detection are amplified by the limitations and inefficacies inherent in current screening methodologies, highlighting a pressing need for more efficacious diagnostic and treatment strategies. Phage display technology emerges as a pivotal innovation in this context, utilizing extensive phage-peptide libraries to identify ligands with specificity for cancer cell markers, thus enabling precision-targeted therapeutic strategies. This technology promises a paradigm shift in ovarian cancer management, concentrating on targeted drug delivery systems to improve treatment accuracy and efficacy while minimizing adverse effects. Through a meticulous review, this paper evaluates the revolutionary potential of phage display in enhancing ovarian cancer therapy, representing a significant advancement in combating this challenging disease. Phage display technology is heralded as an essential instrument for developing effective immunodiagnostic and therapeutic approaches in ovarian cancer, facilitating early detection, precision-targeted medication, and the implementation of customized treatment plans.


Assuntos
Técnicas de Visualização da Superfície Celular , Neoplasias Ovarianas , Biblioteca de Peptídeos , Feminino , Humanos , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/imunologia , Biomarcadores Tumorais , Animais , Imunoterapia/métodos
20.
Int J Obes (Lond) ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926462

RESUMO

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

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