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1.
Plant Cell Environ ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132878

RESUMO

Reactive oxygen species (ROS) play a crucial role in regulating numerous functions in organisms. Among the key regulators of ROS production are NADPH oxidases, primarily referred to as respiratory burst oxidase homologues (RBOHs). However, our understanding of whether and how pathogens directly target RBOHs has been limited. In this study, we revealed that the effector protein RipBJ, originating from the phytopathogenic bacterium Ralstonia solanacearum, was present in low- to medium-virulence strains but absent in high-virulence strains. Functional genetic assays demonstrated that the expression of ripBJ led to a reduction in bacterial infection. In the plant, RipBJ expression triggered plant cell death and the accumulation of H2O2, while also enhancing host defence against R. solanacearum by modulating multiple defence signalling pathways. Through protein interaction and functional studies, we demonstrated that RipBJ was associated with the plant's plasma membrane and interacted with the tomato RBOH known as SlWfi1, which contributed positively to RipBJ's effects on plants. Importantly, SlWfi1 expression was induced during the early stages following R. solanacearum infection and played a key role in defence against this bacterium. This research uncovers the plant RBOH as an interacting target of a pathogen's effector, providing valuable insights into the mechanisms of plant defence.

2.
BMC Cancer ; 24(1): 411, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566028

RESUMO

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.


Assuntos
Proteína BRCA1 , Neoplasias da Mama , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Proteína BRCA1/genética , Mutação em Linhagem Germinativa , Proteína BRCA2/genética , Predisposição Genética para Doença , Detecção Precoce de Câncer , China/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Mutação
3.
Analyst ; 149(6): 1907-1920, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38372525

RESUMO

Arachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer (CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using a liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin (PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that the expression level of PGE2 synthases, the key protein of PGE2 biosynthesis, was upregulated in CRC and positively correlated with the CD68+ macrophage density and CRC development. Our study indicates that the PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.


Assuntos
Neoplasias Colorretais , Dinoprostona , Humanos , Dinoprostona/metabolismo , Ácido Araquidônico , Metaboloma , Metabolômica , Neoplasias Colorretais/metabolismo
4.
J Nanobiotechnology ; 22(1): 240, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735931

RESUMO

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.


Assuntos
Ouro , Grafite , Estresse Oxidativo , Pontos Quânticos , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas , Óxido de Zinco , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Ouro/química , Grafite/química , Óxido de Zinco/química , Animais , Pontos Quânticos/química , Camundongos , Nanopartículas Metálicas/química , Apoptose/efeitos dos fármacos , Ácido Hialurônico/química , Elétrons
5.
Mikrochim Acta ; 191(8): 444, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38955823

RESUMO

Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10-8 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.


Assuntos
Técnicas Biossensoriais , Ácidos Borônicos , Ouro , Análise Espectral Raman , Ácidos Borônicos/química , Técnicas Biossensoriais/métodos , Ouro/química , Humanos , Análise Espectral Raman/métodos , Prata/química , Nanopartículas Metálicas/química , Limite de Detecção , Transferrina/análise , Transferrina/química , Impressão Molecular , Polímeros Molecularmente Impressos/química , Glicoproteínas/sangue , Glicoproteínas/química , Materiais Biomiméticos/química , Dopamina/sangue , Dopamina/análise , Compostos de Sulfidrila
6.
Artigo em Inglês | MEDLINE | ID: mdl-38199909

RESUMO

BACKGROUND: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). METHODS: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. RESULTS: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. CONCLUSIONS: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

7.
Artigo em Zh | MEDLINE | ID: mdl-39118519

RESUMO

In recent years, a large number of studies have demonstrated that obstructive sleep apnea (OSA) can lead to the abnormal development of maxillofacial region in pediatric patients, which may result in a 'vicious circle' aggravating OSA, therefore adversely affecting quality of life. Understanding the effect and mechanism of OSA on children's maxillofacial development is helpful to better prevent and treat OSA and maxillofacial dysplasia in children.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/etiologia , Criança , Desenvolvimento Maxilofacial , Qualidade de Vida , Anormalidades Maxilofaciais
8.
Neural Regen Res ; 19(9): 2050-2056, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38227535

RESUMO

JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic effects, can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury; however, its effect on spinal cord injury is still unclear. In this study, a rat model of spinal cord injury was established using the heavy object impact method, and the rats were then treated with Biochanin A (40 mg/kg) via intraperitoneal injection for 14 consecutive days. The results showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal cord tissue injury, reduced inflammation and oxidative stress in spinal cord neurons, and reduced apoptosis and pyroptosis. In addition, Biochanin A inhibited the expression of inflammasome-related proteins (ASC, NLRP3, and GSDMD) and the Toll-like receptor 4/nuclear factor-κB pathway, activated the Nrf2/heme oxygenase 1 signaling pathway, and increased the expression of the autophagy markers LC3 II, Beclin-1, and P62. Moreover, the therapeutic effects of Biochanin A on early post-spinal cord injury were similar to those of methylprednisolone. These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways. These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

9.
Front Immunol ; 15: 1339914, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304432

RESUMO

Background: The diagnosis of lung adenocarcinoma (LUAD) leptomeningeal metastasis (LM) remains a clinical challenge. Human epididymis protein 4 (HE4) functions as a novel tumor biomarker for cancers. This study aimed to assess the diagnostic value of cerebrospinal fluid (CSF) HE4, and combined with CEACAM6, for LUAD LM. Methods: The CSF HE4 protein level was measured in two independent cohorts by electrochemiluminescence. Test cohort included 58 LUAD LM patients, 22 LUAD patients without LM (Wiot-LM), and 68 normal controls. Validation cohort enrolled 50 LUAD LM patients and 40 normal controls, in parallel with Wiot-LM patients without brain metastases (19 Wiot-LM/BrM patients) or with BrM (26 BrM patients). The CSF level of CEA, CA125, CA153, CA199, CA724, NSE and ProGRP of these samples was measured by electrochemiluminescence, whereas the CSF CEACAM6 level was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the serum level of these biomarkers was detected by same method as CSF. Results: The level of HE4 or CEACAM6 in CSF samples from LUAD LM patients was significantly higher than those from normal controls and Wiot-LM patients. The HE4 or CEACAM6 level in CSF was higher than that in serum of LM patient. The CSF HE4 or CEACAM6 level for distinguished LM from Wiot-LM showed good performance by receiver-operating characteristic analysis. The better discriminative power for LM was achieved when HE4 was combined with CEACAM6. In addition, the CSF HE4 and CEACAM6 level showed little or no difference between Wiot-LM/BrM and BrM patients, the BrM would not significantly influence the HE4 or CEACAM6 level in CSF. The diagnostic power of CSF CA125, CA153, CA199, CA724, NSE and ProGRP for LUAD LM were not ideal. Conclusion: The combination with HE4 and CEACAM6 has the promising application for the diagnosis of LUAD LM.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais , Curva ROC , Neoplasias Pulmonares/patologia
10.
Clin Chim Acta ; 561: 119827, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38909978

RESUMO

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare malignant lymphoproliferative tumor. Our study aimed to investigate the mutational profile of VRL distinguishing from uveitis using next-generation sequencing (NGS) analysis on small amounts of vitreous fluid. METHODS: Vitreous samples from twenty-six eyes of twenty VRL patients and six eyes of five uveitis patients were enrolled. All vitreous samples underwent cytology, immunocytochemistry for B-cell markers, cytokines analysis of IL-10 and IL-6, and flow cytometry. NGS was performed in vitreous specimens from the 25 patients using 82 DLBCL-targeted mutation panels. Vitreous fluids from 8 cases were performed paired NGS-based mutation analysis on both cell-free DNA (cfDNA) and genomic DNA. RESULTS: The sensitivity and accuracy rates for vitreous cytology were 70 % and 76 %, and for cytokine analysis (IL-10/IL-6 > 1) were 65 % and 72 %, respectively. Overall, the common mutations in VRL were PIM1 (88.5 %), IGLL5 (88.5 %), KMT2C (73 %), MYD88 (77 %), CD79B (50 %) and TBL1XR1 (46.2 %). In addition, the genetic mutation in cfDNA was consistent with that in genomic DNA in eight VRL cases. CONCLUSIONS: The mutation analysis of 82 DLBCL-targeted spectrum mutation panels by NGS on the vitreous samples is a sensitive and specific tool for distinguishing VRL from uveitis. Utilizing cfDNA for NGS analysis may serve as a liquid biopsy to aid in the diagnosis of VRL, particularly when using small-volume aspirate.


Assuntos
População do Leste Asiático , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias da Retina , Corpo Vítreo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , População do Leste Asiático/genética , Linfoma/genética , Linfoma/diagnóstico , Neoplasias da Retina/genética , Neoplasias da Retina/diagnóstico , Corpo Vítreo/patologia , Corpo Vítreo/metabolismo
11.
Bioinspir Biomim ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146962

RESUMO

In this paper, the innovative design of a robotic hand with soft jointed structure is carried out and a tendon-driven mechanism, a master-slave motor coordinated drive mechanism, a thumb coupling transmission mechanism and a thumb steering mechanism are proposed. These innovative designs allow for more effective actuation in each finger, enhancing the load capacity of the robotic hand while maintaining key performance indicators such as dexterity and adaptability. A mechanical model of the robotic finger was made to determine the application limitations and load capacity. The robotic hand was then prototyped for a set of experiments. The experimental results showed that the proposed theoretical model were reliable. Also, the fingertip force of the robotic finger could reach up to 10.3N, and the load force could reach up to 72.8N. When grasping target objects of different sizes and shapes, the robotic hand was able to perform the various power grasping and precision grasping in the Cutkosky taxonomy. Moreover, the robotic hand had good flexibility and adaptability by means of adjusting the envelope state autonomously. .

12.
Ann Clin Lab Sci ; 54(3): 402-407, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39048161

RESUMO

OBJECTIVE: We conducted this study to determine the impact of serum glycosaminoglycan hyaluronan (HA) on the prognosis of coronavirus disease 2019 (COVID-19). METHODS: A total of 497 hospitalized patients with COVID-19 were included. Patients were divided into two subgroups based on the severity of infection: mild (n=344) and severe (n=153). The levels of HA, lymphocyte count, C-reactive protein (CRP), ferritin, interleukin 6 (IL-6), and D-dimer were measured and the correlation of these parameters with the prognosis of COVID-19 was assessed. RESULTS: The mean HA level of the severe group was significantly higher than that of the mild group (204.4 ng/mL versus 850.6 ng/mL, P<0.01). In receiver operating characteristic curve analysis, an HA level ≥607.8 ng/mL predicted severe COVID-19 with a sensitivity of 62.3% and specificity of 88.6%. Multivariate regression analysis demonstrated that serum HA level was a significant predictor of disease severity (odds ratio=60.56, P<0.01). CONCLUSION: Our findings show that higher serum HA concentrations are associated with severe COVID-19 disease. Early analysis of HA level in patients with COVID-19 might effectively predict disease severity.


Assuntos
COVID-19 , Ácido Hialurônico , Índice de Gravidade de Doença , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Ácido Hialurônico/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Prognóstico , Estudos Retrospectivos , Curva ROC
13.
Microbiol Spectr ; : e0058324, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869308

RESUMO

Malaria infection remains a serious threat to human health worldwide. Rapid and accurate detection technology is crucial for preventing malaria transmission and minimizing damage. We aimed to establish and validate a new rapid molecular detection method for malaria, called EasyNAT Malaria Assay, targeting Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, and Plasmodium malariae. The analytical performance of EasyNAT Malaria Assay was determined using positive materials. We identified 42 clinical samples as malaria positive and 95 negative samples. Each sample was examined by four methods: light microscopy, rapid diagnostic test, EasyNAT Malaria Assay, and digital PCR. Diagnostic accuracy and clinical performance were evaluated. The limit of detection (LOD)95% of EasyNAT Malaria was consistently 40 parasites/mL. It specifically amplified Plasmodium and performed with reliable repeatability and reproducibility. In 137 clinical samples, EasyNAT Malaria detected four more positive samples than microscopic examination and two more positive samples than rapid diagnostic test (RDT). One clinical sample was positive only under digital PCR. However, no significant differences statistically in sensitivity or specificity were observed. Compared with microscopy, the total, positive, and negative concordance rates of EasyNAT were 97.08%, 100%, and 95.79%, respectively. Enhanced diagnostic accuracy of EasyNAT Malaria in patients who had taken anti-malarial medication before their clinical appointment was observed. The EasyNAT Malaria Assay has good detection efficiency for clinical samples, presents a promising molecular detection tool in clinical practice, and is particularly suitable for rapid screening of high-risk populations in the emergency room. IMPORTANCE: This study established and validated EasyNAT Malaria Assay as a promising molecular detection tool for malaria screening of high-risk populations in clinical practice. This novel isothermal amplification method may effectively facilitate the rapid diagnosis of malaria and prevent its transmission.

14.
ACS Omega ; 9(4): 4974-4985, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38313474

RESUMO

Infectious wounds pose a significant challenge in the field of wound healing primarily due to persistent inflammation and the emergence of antibiotic-resistant bacteria. To combat these issues, the development of an effective wound dressing that can prevent infection and promote healing is of the utmost importance. Photodynamic therapy (PDT) has emerged as a promising noninvasive treatment strategy for tackling antibiotic-resistant bacteria. A biodegradable photosensitizer called hematoporphyrin monomethyl ether (HMME) has shown potential in generating reactive oxygen species (ROS) upon laser activation to combat bacteria. However, the insolubility of HMME limits its antibacterial efficacy and its ability to facilitate skin healing. To overcome these limitations, we have synthesized a compound hydrogel by combining carbomer, HMME, and Cu2O nanoparticles. This compound hydrogel exhibits enhanced antimicrobial ability and excellent biocompatibility and promotes angiogenesis, which is crucial for the healing of skin defects. By integrating the benefits of HMME, Cu2O nanoparticles, and the gel-forming properties of carbomer, this compound hydrogel shows great potential as an effective wound dressing material. In summary, the compound hydrogel developed in this study offers a promising solution for infectious wounds by addressing the challenges of infection prevention and promoting skin healing. This innovative approach utilizing PDT and the unique properties of the compound hydrogel could significantly improve the outcomes of wound healing in clinical settings.

15.
Adv Mater ; 36(16): e2311855, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38164817

RESUMO

The onset of implant-associated infection (IAI) triggers a cascade of immune responses, which are initially dominated by neutrophils. Bacterial aggregate formation and hypoxic microenvironment, which occur shortly after implantation, may be two major risk factors that impair neutrophil function and lead to IAI. Here, the implant surface with phytic acid-Zn2+ coordinated TiO2 nanopillar arrays (PA-Zn@TiNPs) and oxygen self-supporting CaO2 nanoparticles, named as CPZTs, is mechanochemically reprogrammed. The engineered CPZTs interface integrates multiple properties to inhibit the formation of nascent biofilm, encompassing antibacterial adhesion, mechanobactericidal effect, and chemobiocidal effect. Meanwhile, continuous oxygenation fuels the neutrophils with reactive oxygen species (ROS) for efficient bacterial elimination on the implant surface and inside the neutrophils. Furthermore, this surface modulation strategy accelerates neutrophil apoptosis and promotes M2 macrophage-mediated osteogenesis both in vitro and in a rat model of IAI. In conclusion, targeting neutrophils for immunomodulation is a practical and effective strategy to prevent IAI and promote bone-implant integration.


Assuntos
Apoptose , Neutrófilos , Ratos , Animais , Antibacterianos/farmacologia , Macrófagos , Próteses e Implantes
16.
Eur J Med Chem ; 271: 116410, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38615409

RESUMO

With the increasing reports of antibiotic resistance in this species, Pseudomonas aeruginosa is a common human pathogen with important implications for public health. Bacterial quorum sensing (QS) systems are potentially broad and versatile targets for developing new antimicrobial compounds. While previous reports have demonstrated that certain amide compounds can inhibit bacterial growth, there are few reports on the specific inhibitory effects of these compounds on bacterial quorum sensing systems. In this study, thirty-one amide derivatives were synthesized. The results of the biological activity assessment indicated that A9 and B6 could significantly inhibit the expression of lasB, rhlA, and pqsA, effectively reducing several virulence factors regulated by the QS systems of PAO1. Additionally, compound A9 attenuated the pathogenicity of PAO1 to Galleria mellonella larvae. Meanwhile, RT-qPCR, SPR, and molecular docking studies were conducted to explore the mechanism of these compounds, which suggests that compound A9 inhibited the QS systems by binding with LasR and PqsR, especially PqsR. In conclusion, amide derivatives A9 and B6 exhibit promising potential for further development as novel QS inhibitors in P. aeruginosa.


Assuntos
Amidas , Antibacterianos , Descoberta de Drogas , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa , Percepção de Quorum , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Amidas/farmacologia , Amidas/química , Amidas/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Testes de Sensibilidade Microbiana , Relação Dose-Resposta a Droga , Animais
17.
Clin Chim Acta ; 562: 119879, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39029646

RESUMO

BACKGROUND: The diagnostic utility of cerebrospinal fluid (CSF) cytology encounters impediments stemming from variability in cell collection techniques and pathologists' morphological acumen, resulting in wide-ranging CSF positivity rates for primary central nervous system lymphomas (PCNSL). Such disparity impacts patient evaluation, treatment stratagem, and prognostication. Thus, this study endeavors to explore liquid biomarkers complementary to CSF cytology or immunophenotype analysis in the diagnosis of CSF involvement. METHODS: 398 newly diagnosed PCNSL patients were categorized into CSF involvement and non-involvement groups based on CSF cytology and immunophenotype analysis. Binary logistic regression analysis was performed on 338 patients to investigate factors predicting CSF involvement and to develop a joint prediction model. An additional cohort of 60 PCNSL patients was recruited for model validation. Statistical analyses included the Mann-Whitney U test for comparing various CSF parameters between two groups. ROC curve analyses were performed for each biomarker to identify PCNSL CSF involvement. RESULTS: The cytokine IL-10 level in CSF has emerged as the most promising biomarker for CSF evaluation, boasting an ROC AUC of 0.922. C-TNFα and soluble C-IL2R demonstrate efficacy in quantifying tumor burden within the CSF. Logistic regression identified C-IL10lg (OR = 30.103, P < 0.001), C-TNC (OR = 1.126, P < 0.001), C-IL2Rlg (OR = 3.743, P = 0.029) as independent predictors for CSF involvement, contributing to a joint predictive model with an AUC of 0.935, sensitivity of 74.1 %, and specificity of 93.0 %. Validation of the model in an independent cohort confirmed its effectiveness, achieving an AUC of 0.9713. CONCLUSIONS: The identification of these feasible biomarkers and the development of an accurate prediction model may facilitate the precise evaluation of CSF status in PCNSL, offering significant advancements in patient management.


Assuntos
Neoplasias do Sistema Nervoso Central , Citocinas , Linfoma , Humanos , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Modelos Logísticos , Citocinas/líquido cefalorraquidiano , Linfoma/líquido cefalorraquidiano , Linfoma/diagnóstico , Idoso , Adulto , Biomarcadores Tumorais/líquido cefalorraquidiano
18.
Artigo em Inglês | MEDLINE | ID: mdl-38451772

RESUMO

In this paper, we present a novel multi-modal attention guidance method designed to address the challenges of turn-taking dynamics in meetings and enhance group conversations within virtual reality (VR) environments. Recognizing the difficulties posed by a confined field of view and the absence of detailed gesture tracking in VR, our proposed method aims to mitigate the challenges of noticing new speakers attempting to join the conversation. This approach tailors attention guidance, providing a nuanced experience for highly engaged participants while offering subtler cues for those less engaged, thereby enriching the overall meeting dynamics. Through group interview studies, we gathered insights to guide our design, resulting in a prototype that employs light as a diegetic guidance mechanism, complemented by spatial audio. The combination creates an intuitive and immersive meeting environment, effectively directing users' attention to new speakers. An evaluation study, comparing our method to state-of-the-art attention guidance approaches, demonstrated significantly faster response times (p < 0.001), heightened perceived conversation satisfaction (p < 0.001), and preference (p < 0.001) for our method. Our findings contribute to the understanding of design implications for VR social attention guidance, opening avenues for future research and development.

19.
IEEE Trans Image Process ; 33: 3765-3777, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38857134

RESUMO

Reshaping, a point operation that alters the characteristics of signals, has been shown capable of improving the compression ratio in video coding practices. Out-of-loop reshaping that directly modifies the input video signal was first adopted as the supplemental enhancement information (SEI) for the HEVC/H.265 without the need to alter the core design of the video codec. VVC/H.266 further improves the coding efficiency by adopting in-loop reshaping that modifies the residual signal being processed in the hybrid coding loop. In this paper, we theoretically analyze the rate-distortion performance of the in-loop reshaping and use experiments to verify the theoretical result. We prove that the in-loop reshaping can improve coding efficiency when the entropy coder adopted in the coding pipeline is suboptimal, which is in line with the practical scenarios that video codecs operate in. We derive the PSNR gain in a closed form and show that the theoretically predicted gain is consistent with that measured from experiments using standard testing video sequences.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38980775

RESUMO

Marker-based motion capture (mocap) is a conventional method used in biomechanics research to precisely analyze human movement. However, the time-consuming marker placement process and extensive post-processing limit its wider adoption. Therefore, markerless mocap systems that use deep learning to estimate 2D keypoint from images have emerged as a promising alternative, but annotation errors in training datasets used by deep learning models can affect estimation accuracy. To improve the precision of 2D keypoint annotation, we present a method that uses anatomical landmarks based on marker-based mocap. Specifically, we use multiple RGB cameras synchronized and calibrated with a marker-based mocap system to create a high-quality dataset (RRIS40) of images annotated with surface anatomical landmarks. A deep neural network is then trained to estimate these 2D anatomical landmarks and a ray-distance-based triangulation is used to calculate the 3D marker positions. We conducted extensive evaluations on our RRIS40 test set, which consists of 10 subjects performing various movements. Compared against a marker-based system, our method achieves a mean Euclidean error of 13.23 mm in 3D marker position, which is comparable to the precision of marker placement itself. By learning directly to predict anatomical keypoints from images, our method outperforms OpenCap's augmentation of 3D anatomical landmarks from triangulated wild keypoints. This highlights the potential of facilitating wider integration of markerless mocap into biomechanics research. The RRIS40 test set is made publicly available for research purposes at koonyook.github.io/rris40.

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