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1.
J Am Soc Nephrol ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39466275

RESUMO

BACKGROUND: Predicting the risk of AKI-CKD transition remains a major challenge in management of acute decompensated heart failure and AKI. This study investigated the clinical utility of urinary cytokeratin 20 (CK20), a novel biomarker reflecting severity of histological acute tubular injury, for identifying patients at risk of AKI-CKD progression. METHODS: This prospective cohort study included a Test set comprising 279 consecutive hospitalized patients with acute decompensated heart failure and AKI in 5 centers and a Validation set enrolling 206 similar patients at an external center. Urinary CK20 and seven reported renal tubular injury biomarkers at the time of AKI diagnosis were measured. The primary outcome was a composite of AKI-CKD transition 90 days after AKI or all-cause death within 90 days. The secondary outcome was AKI-CKD progression 90 days after AKI. RESULTS: In the Test set, 115 (41%) patients reached the primary endpoint. Concentrations of urinary CK20 peaked on the day of AKI diagnosis and remained elevated 14 days after AKI. After multivariable adjustment, the highest tertile of urinary CK20 was associated with 21-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and the secondary outcomes, urinary CK20 at the time of AKI diagnosis had area under the receiver-operating characteristic curves (AUC) of 0.82 (95% confidence interval [CI], 0.77-0.87) and 0.81 (95% CI, 0.75-0.87), and outperformed other reported biomarkers reflecting acute tubular injury and the risk of CKD. Adding urinary CK20 to the clinical variables improved the ability for predicting the primary outcome with an AUC of 0.90 (95% CI, 0.85-0.94), and largely improved the risk reclassification. The ability of urinary CK20 in predicting AKI-CKD transition was further confirmed in the Validation set. CONCLUSIONS: Urinary CK20 improved prediction of the risk for transition from AKI to CKD in patients with acute decompensated heart failure and AKI.

2.
Mar Drugs ; 22(9)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39330273

RESUMO

A chemical investigation of the extracts from the soft coral Litophyton brassicum led to the isolation and identification of four new meroterpenes, brassihydroxybenzoquinone A and B (1 and 2) and brassinaphthoquinone A and B (3 and 4), along with two known related meroterpenes (5 and 6). Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR) spectroscopy, and a comparison with the literature data. All compounds were evaluated for antibacterial activity against six pathogenic bacterial strains and for cytotoxic activity against three cancer cell lines. In the cytotoxic assay, all compounds were inactive at 10 µM against the A549, HeLa, and MDA-MB-231 cell lines. In the antibacterial assay, compounds 1 and 2 exhibited moderate inhibitory activity with minimum inhibitory concentrations (MIC) ranging from 8 to 64 µg/mL.


Assuntos
Antozoários , Antibacterianos , Testes de Sensibilidade Microbiana , Terpenos , Antozoários/química , Animais , Humanos , Linhagem Celular Tumoral , Terpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , China , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Células HeLa , Espectrometria de Massas por Ionização por Electrospray , Estrutura Molecular
3.
BioTech (Basel) ; 13(3)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39189210

RESUMO

The black soldier fly is a valuable resource insect capable of transforming organic waste while producing antimicrobial peptides (AMPs). The inhibition zone assay (IZA) is a method used to demonstrate the antimicrobial activity of AMPs. This study aimed to examine the experimental principles and establish a standardized IZA method. Results indicated that the AMPs extract consisted of proteins ranging in molecular weights from 0 to 40 kDa. The AMPs diffused radially on an agar plate through an Oxford cup. The diffusion radius was influenced by the concentration and volume of the AMPs but ultimately determined by the mass of the AMPs. The swabbing method was found to be effective for inoculating bacteria on the agar plate. Among the conditions tested, the plate nutrient concentration was the most sensitive factor for the IZA, followed by bacterial concentration and incubation time. Optimal conditions for the IZA included a nutrient plate of 0.5× TSA, a bacterial concentration of 106 CFU/mL, and an incubation time of 12 h, with oxytetracycline (OTC) at 0.01 mg/mL serving as the positive control. The antimicrobial-specific activity of AMPs could be standardized by the ratio of inhibition zone diameters between AMPs and OTC. These findings contribute to the standardization of the IZA method for profiling the antimicrobial activity of AMPs.

4.
Talanta ; 276: 126277, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761658

RESUMO

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet-triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with kcat/Km as 2.18 × 104 M-1 s-1. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.


Assuntos
Lisossomos , Nitrorredutases , Fotoquimioterapia , Fármacos Fotossensibilizantes , Nitrorredutases/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Lisossomos/metabolismo , Lisossomos/química , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Imagem Óptica , Estilbenos/química , Estilbenos/farmacologia , Células HeLa , Teoria da Densidade Funcional , Fluorescência , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo
5.
JCI Insight ; 9(13)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805402

RESUMO

BACKGROUNDIdentifying patients with acute kidney injury (AKI) at high risk of chronic kidney disease (CKD) progression remains a challenge.METHODSKidney transcriptome sequencing was applied to identify the top upregulated genes in mice with AKI. The product of the top-ranking gene was identified in tubular cells and urine in mouse and human AKI. Two cohorts of patients with prehospitalization estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 who survived over 90 days after AKI were used to derive and validate the predictive models. AKI-CKD progression was defined as eGFR < 60 mL/min/1.73 m2 and with minimum 25% reduction from baseline 90 days after AKI in patients with prehospitalization eGFR ≥ 60 mL/min/1.73 m2. AKI-advanced CKD was defined as eGFR < 30 mL/min/1.73 m2 90 days after AKI in those with prehospitalization eGFR 45-59 mL/min/1.73 m2.RESULTSKidney cytokeratin 20 (CK20) was upregulated in injured proximal tubular cells and detectable in urine within 7 days after AKI. High concentrations of urinary CK20 (uCK20) were independently associated with the severity of histological AKI and the risk of AKI-CKD progression. In the Test set, the AUC of uCK20 for predicting AKI-CKD was 0.80, outperforming reported biomarkers for predicting AKI. Adding uCK20 to clinical variables improved the ability to predict AKI-CKD progression, with an AUC of 0.90, and improved the risk reclassification.CONCLUSIONThese findings highlight uCK20 as a useful predictor for AKI-CKD progression and may provide a tool to identify patients at high risk of CKD following AKI.FUNDINGNational Natural Science Foundation of China, National Key R&D Program of China, 111 Plan, Guangdong Key R&D Program.


Assuntos
Injúria Renal Aguda , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/etiologia , Humanos , Animais , Insuficiência Renal Crônica/urina , Insuficiência Renal Crônica/metabolismo , Camundongos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/urina , Idoso , Progressão da Doença , Modelos Animais de Doenças
6.
Mar Drugs ; 22(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38667774

RESUMO

Five new biflorane-type diterpenoids, biofloranates E-I (1-5), and two new bicyclic diterpene glycosides, lemnaboursides H-I (6-7), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei. Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 µM.


Assuntos
Antozoários , Antibacterianos , Bacillus subtilis , Diterpenos , Glicosídeos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Antozoários/química , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Animais , Glicosídeos/farmacologia , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Staphylococcus aureus/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Células HeLa , Linhagem Celular Tumoral , Células Hep G2 , Estrutura Molecular , Células A549 , China
7.
J Am Chem Soc ; 146(17): 11906-11923, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629727

RESUMO

The complex and dynamic compositions of biofilms, along with their sophisticated structural assembly mechanisms, endow them with exceptional capabilities to thrive in diverse conditions that are typically unfavorable for individual cells. Characterizing biofilms in their native state is significantly challenging due to their intrinsic complexities and the limited availability of noninvasive techniques. Here, we utilized solid-state nuclear magnetic resonance (NMR) spectroscopy to analyze Bacillus subtilis biofilms in-depth. Our data uncover a dynamically distinct organization within the biofilm: a dominant, hydrophilic, and mobile framework interspersed with minor, rigid cores of limited water accessibility. In these heterogeneous rigid cores, the major components are largely self-assembled. TasA fibers, the most robust elements, further provide a degree of mechanical support for the cell aggregates and some lipid vesicles. Notably, rigid cell aggregates can persist even without the major extracellular polymeric substance (EPS) polymers, although this leads to slight variations in their rigidity and water accessibility. Exopolysaccharides are exclusively present in the mobile domain, playing a pivotal role in its water retention property. Specifically, all water molecules are tightly bound within the biofilm matrix. These findings reveal a dual-layered defensive strategy within the biofilm: a diffusion barrier through limited water mobility in the mobile phase and a physical barrier posed by limited water accessibility in the rigid phase. Complementing these discoveries, our comprehensive, in situ compositional analysis is not only essential for delineating the sophisticated biofilm architecture but also reveals the presence of alternative genetic mechanisms for synthesizing exopolysaccharides beyond the known pathway.


Assuntos
Bacillus subtilis , Biofilmes , Espectroscopia de Ressonância Magnética , Bacillus subtilis/química , Bacillus subtilis/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo
8.
Phytochemistry ; 223: 114097, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641142

RESUMO

A chemical investigation of the dichloromethane extract from the Xisha sponge Diacarnus sp. revealed seven undescribed norterpene cyclic peroxides, named diacarperoxides T-Z, and five unreported related norterpenes, named diacarnoids E-I, and eleven previously reported compounds. The structures of these isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, Snatzke's method, [Rh2(OCOCF3)4]-induced ECD spectra, and modified Mosher's method. Bioassays were performed to assess the antibacterial activity against six pathogenic bacteria, cytotoxicities toward three cancer cell lines, and antimalarial activity against Plasmodium parasites. Most of the cyclic peroxides exhibited substantial antibacterial activity (MIC 1-8 µg/mL). Diacarperoxide W and nuapapuin A showed substantial antimalarial activity with IC50 values of 0.98 and 2.83 µM. Moreover, many compounds exhibited <50% cell survival rates, and IC50 values of 0.22-6.33 µM. The apoptosis assay showed that nuapapuin A induced cancer cell apoptosis in a dose-dependent manner.


Assuntos
Antibacterianos , Antimaláricos , Peróxidos , Poríferos , Antimaláricos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Poríferos/química , Peróxidos/farmacologia , Peróxidos/química , Peróxidos/isolamento & purificação , Humanos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Estrutura Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade , Testes de Sensibilidade Microbiana , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
9.
ACS Sens ; 9(3): 1301-1309, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38373043

RESUMO

Continuous pulse wave detection can be used for monitoring and diagnosing cardiovascular diseases, and research on pulse sensing based on piezoelectric thin films is one of the hot spots. Usually, piezoelectric thin films do not come into direct contact with the skin and need to be connected through a layer of an elastic medium. Most views think that the main function of this layer of elastic medium is to increase the adhesion between the sensor component and the skin, but there is little discussion about the impact of the elastic medium on pulse vibration transmission. Here, we conducted a detailed study on the effects of Young's modulus and the thickness of elastic media on pulse sensing signals. The results show that the waveform amplitude of the piezoelectric sensing signal decreases with the increase of Young's modulus and thickness of the elastic medium. Then, we constructed a theoretical model of the influence of elastic media on pulse wave propagation. The amplitude of the pulse wave signal detected by the optimized sensor was increased to 480%. Our research shows that by regulating Young's modulus and thickness of elastic media, pulse wave signals can undergo a similar amplification effect, which has an important theoretical reference value for achieving ambulatory blood pressure monitoring based on high-quality pulse waves.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Elastômeros , Razão Sinal-Ruído , Módulo de Elasticidade , Modelos Teóricos
10.
Sci Adv ; 10(1): eadi6799, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181077

RESUMO

Electrical stimulation can effectively accelerate bone healing. However, the substantial size and weight of electrical stimulation devices result in reduced patient benefits and compliance. It remains a challenge to establish a flexible and lightweight implantable microelectronic stimulator for bone regeneration. Here, we use self-powered technology to develop an electric pulse stimulator without circuits and batteries, which removes the problems of weight, volume, and necessary rigid packaging. The fully implantable bone defect electrical stimulation (BD-ES) system combines a hybrid tribo/piezoelectric nanogenerator to provide biphasic electric pulses in response to rehabilitation exercise with a conductive bioactive hydrogel. BD-ES can enhance multiple osteogenesis-related biological processes, including calcium ion import and osteogenic differentiation. In a rat model of critical-sized femoral defects, the bone defect was reversed by electrical stimulation therapy with BD-ES and subsequent bone mineralization, and the femur completely healed within 6 weeks. This work is expected to advance the development of symbiotic electrical stimulation therapy devices without batteries and circuits.


Assuntos
Regeneração Óssea , Osteogênese , Humanos , Animais , Ratos , Terapia por Exercício , Calcificação Fisiológica , Estimulação Elétrica
11.
Mater Horiz ; 11(4): 1032-1045, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38073476

RESUMO

Peripheral nerve injury (PNI) is a common clinical challenge, requiring timely and orderly initiation of synergistic anti-inflammatory and reparative therapy. Although the existing cascade drug delivery system can realize sequential drug release through regulation of the chemical structure of drug carriers, it is difficult to adjust the release kinetics of each drug based on the patient's condition. Therefore, there is an urgent need to develop a cascade drug delivery system that can dynamically adjust drug release and realize personalized treatment. Herein, we developed a responsive cascade drug delivery scaffold (RCDDS) which can adapt to the therapeutic time window, in which Vitamin B12 is used in early controllable release to suppress inflammation and nerve growth factor promotes regeneration by cascade loading. The RCDDS exhibited the ability to modulate the drug release kinetics by hierarchically opening polymer chains triggered by ultrasound, enabling real-time adjustment of the anti-inflammatory and neuroregenerative therapeutic time window depending on the patient's status. In the rat sciatic nerve injury model, the RCDDS group was able to achieve neural repair effects comparable to the autograft group in terms of tissue structure and motor function recovery. The development of the RCDDS provides a useful route toward an intelligent cascade drug delivery system for personalized therapy.


Assuntos
Traumatismos dos Nervos Periféricos , Ratos , Humanos , Animais , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/farmacologia , Portadores de Fármacos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
12.
Int J Mol Sci ; 24(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37833866

RESUMO

The infection of implanted biomaterial scaffolds presents a major challenge. Existing therapeutic solutions, such as antibiotic treatment and silver nanoparticle-containing scaffolds are becoming increasingly impractical because of the growth of antibiotic resistance and the toxicity of silver nanoparticles. We present here a novel concept to overcome these limitations, an electrospun polycaprolactone (PCL) scaffold functionalised with zinc oxide nanowires (ZnO NWs). This study assessed the antibacterial capabilities and biocompatibility of PCL/ZnO scaffolds. The fabricated scaffolds were characterised by SEM and EDX, which showed that the ZnO NWs were successfully incorporated and distributed in the electrospun PCL scaffolds. The antibacterial properties were investigated by co-culturing PCL/ZnO scaffolds with Staphylococcus aureus. Bacterial colonisation was reduced to 51.3% compared to a PCL-only scaffold. The biocompatibility of the PCL/ZnO scaffolds was assessed by culturing them with HaCaT cells. The PCL scaffolds exhibited no changes in cell metabolic activity with the addition of the ZnO nanowires. The antibacterial and biocompatibility properties make PCL/ZnO a good choice for implanted scaffolds, and this work lays a foundation for ZnO NWs-infused PCL scaffolds in the potential clinical application of tissue engineering.


Assuntos
Nanopartículas Metálicas , Nanofios , Óxido de Zinco , Alicerces Teciduais , Óxido de Zinco/farmacologia , Prata , Engenharia Tecidual , Antibacterianos/farmacologia , Poliésteres
13.
Phytochemistry ; 209: 113616, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36828101

RESUMO

Sinulatones A and B, presented as the unusual carbon skeleton with bicyclo[4.5.0] system, two undescribed sesquiterpenoids, namely sinulalides A and B, along with eight known terpenoids, were isolated from the South China Sea soft coral Sinularia scabra. The structures and stereochemistry of these compounds were determined based on extensive spectroscopic data analyses, and computer-assisted methods, including the quantum mechanical-nuclear magnetic resonance (QM-NMR) and TDDFT-ECD calculations. In bioassay, sinulatones A and B showed inhibitory activity against osteoclast precursor cells, with IC50 values of 16.8 and 5.8 µM, respectively.


Assuntos
Antozoários , Diterpenos , Sesquiterpenos , Animais , Terpenos/farmacologia , Estrutura Molecular , Antozoários/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Espectroscopia de Ressonância Magnética , China , Diterpenos/farmacologia , Diterpenos/química
14.
BMC Cancer ; 23(1): 88, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698118

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It's important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL. METHODS: Patients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI. RESULTS: The 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients. CONCLUSIONS: The NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.


Assuntos
Linfoma Extranodal de Células T-NK , Linfoma de Células T , Humanos , Prognóstico , Imageamento por Ressonância Magnética/métodos , Nomogramas , Medição de Risco , Estudos Retrospectivos , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/patologia
15.
Chem Biodivers ; 20(1): e202200966, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36445809

RESUMO

Chemical investigation of the Xisha soft coral Sarcophyton sp. has led to the isolation of eight cembrane-type diterpenoids, including three new compounds, namely sarcophynoids A-C (1-3), and five known analog compounds (4-8). Their structures were clarified based on spectroscopic analysis, and computer-assisted methods including TDDFT-ECD calculation and the quantum mechanical-nuclear magnetic resonance (QM-NMR) method. All the above compounds were tested for their antibacterial activities. Among them, compounds 4-7 and 8 exhibited antibacterial activities against S. aureus, B. subtilis, and P. aeruginosa, with MIC of 4-64 µg/mL.


Assuntos
Antozoários , Diterpenos , Animais , Estrutura Molecular , Antozoários/química , Staphylococcus aureus , Espectroscopia de Ressonância Magnética , Diterpenos/química
16.
Sci Bull (Beijing) ; 67(12): 1284-1294, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-36546158

RESUMO

Atrial fibrillation is an "invisible killer" of human health. It often induces high-risk diseases, such as myocardial infarction, stroke, and heart failure. Fortunately, atrial fibrillation can be diagnosed and treated early. Low-level vagus nerve stimulation (LL-VNS) is a promising therapeutic method for atrial fibrillation. However, some fundamental challenges still need to be overcome in terms of flexibility, miniaturization, and long-term service of bioelectric stimulation devices. Here, we designed a closed-loop self-powered LL-VNS system that can monitor the patient's pulse wave status in real time and conduct stimulation impulses automatically during the development of atrial fibrillation. The implant is a hybrid nanogenerator (H-NG), which is flexible, light weight, and simple, even without electronic circuits, components, and batteries. The maximum output of the H-NG was 14.8 V and 17.8 µA (peak to peak). In the in vivo effect verification study, the atrial fibrillation duration significantly decreased by 90% after LL-VNS therapy, and myocardial fibrosis and atrial connexin levels were effectively improved. Notably, the anti-inflammatory effect triggered by mediating the NF-κB and AP-1 pathways in our therapeutic system is observed. Overall, this implantable bioelectronic device is expected to be used for self-powerability, intelligentization, portability for management, and therapy of chronic diseases.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Estimulação do Nervo Vago , Humanos , Fibrilação Atrial/terapia , Estimulação do Nervo Vago/métodos , Nervo Vago/fisiologia , Átrios do Coração
17.
Phytochemistry ; 204: 113438, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36154825

RESUMO

Five undescribed biscembranoids, bistrochelides H-L, along with four known biscembranoids, glaucumolides A-B and bistrochelides A-B, were isolated from the soft coral Sarcophyton serenei collected off the Xisha Island in the South China Sea. The structures of these compounds were elucidated by HRESIMS (high-resolution electrospray ionization mass spectroscopy) spectrometry, NMR (nuclear magnetic resonance) spectroscopy, X-ray diffraction analysis, electronic circular dichroism (ECD), and the comparison of their spectroscopic data with those reported in the literature. In bioassay, some compounds showed a strong inhibitory effect on osteoclast precursor cells at the concentration of 10 µM. Additionally, all compounds exhibited weakly antimicrobial activity against Vibrio harveyi.

18.
BMC Med Imaging ; 22(1): 139, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941559

RESUMO

BACKGROUND: To assess the value of whole-lesion apparent diffusion coefficient (ADC) histogram analysis in differentiating stage IA endometrial carcinoma (EC) from benign endometrial lesions (BELs) and characterizing histopathologic features of stage IA EC preoperatively. METHODS: One hundred and six BEL and 126 stage IA EC patients were retrospectively enrolled. Eighteen volumetric histogram parameters were extracted from the ADC map of each lesion. The Mann-Whitney U or Student's t-test was used to compare the differences between the two groups. Models based on clinical parameters and histogram features were established using multivariate logistic regression. Receiver operating characteristic (ROC) analysis and calibration curves were used to assess the models. RESULTS: Stage IA EC showed lower ADC10th, ADC90th, ADCmin, ADCmax, ADCmean, ADCmedian, interquartile range, mean absolute deviation, robust mean absolute deviation (rMAD), root mean squared, energy, total energy, entropy, variance, and higher skewness, kurtosis and uniformity than BELs (all p < 0.05). ADCmedian yielded the highest area under the ROC curve (AUC) of 0.928 (95% confidence interval [CI] 0.895-0.960; cut-off value = 1.161 × 10-3 mm2/s) for differentiating stage IA EC from BELs. Moreover, multivariate analysis demonstrated that ADC-score (ADC10th + skewness + rMAD + total energy) was the only significant independent predictor (OR = 2.641, 95% CI 2.045-3.411; p < 0.001) for stage IA EC when considering clinical parameters. This ADC histogram model (ADC-score) achieved an AUC of 0.941 and a bias-corrected AUC of 0.937 after bootstrap resampling. The model performed well for both premenopausal (accuracy = 0.871) and postmenopausal (accuracy = 0.905) patients. Besides, ADCmin and ADC10th were significantly lower in Grade 3 than in Grade 1/2 stage IA EC (p = 0.022 and 0.047). At the same time, no correlation was found between ADC histogram parameters and the expression of Ki-67 in stage IA EC (all p > 0.05). CONCLUSIONS: Whole-lesion ADC histogram analysis could serve as an imaging biomarker for differentiating stage IA EC from BELs and assisting in tumor grading of stage IA EC, thus facilitating personalized clinical management for premenopausal and postmenopausal patients.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias do Endométrio , Biomarcadores , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Curva ROC , Estudos Retrospectivos
19.
Contrast Media Mol Imaging ; 2022: 9579145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35854769

RESUMO

Objective: To compare the effects of 1.5 T and 3.0 T upper abdominal magnetic resonance diffusion-weighted imaging (DWI) under three acquisition techniques of breath holding, breath triggering, and free breathing, so as to provide a reference for the usage of upper abdominal DWI scanning. Methods: Twenty-one healthy subjects were selected from social volunteers and underwent routine magnetic resonance imaging (MRI) and DWI on 1.5 T and 3.0 T, respectively. DWI included three acquisition methods: breath triggering, breath holding, and free breathing, and b values were 100 and 800. The DWI image artifacts, image quality, apparent diffusion coefficient (ADC), and the signal-to-noise ratio (SNR) obtained through the three acquisition methods were compared. Results: The 1.5 T free-breathing DWI image quality was the best, while the 3.0 T had the best breath-triggered DWI image quality. The 3.0 T breath-triggered DWI image quality was better than the 1.5 T free-breathing DWI image (P=0.012), and the SNR of free-breathing DWI was the highest. Between the two field intensities, the SNR of the liver in the 3.0 T group was much lower than that in the 1.5 T group, and obvious differences were not observed in ADC values of normal liver, gallbladder, kidney, spleen, and pancreas. Conclusion: 3.0 T respiratory-triggered acquisition can obtain higher quality DWI images. But in the case of only 1.5 T field strength, free-breathing acquisition of DWI images should be selected.


Assuntos
Artefatos , Imagem de Difusão por Ressonância Magnética , Abdome/diagnóstico por imagem , Suspensão da Respiração , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Reprodutibilidade dos Testes , Razão Sinal-Ruído
20.
BMC Nephrol ; 23(1): 234, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778681

RESUMO

BACKGROUND: The all-cause mortality of patients undergoing hemodialysis (HD) is higher than in the general population. The first 6 months after dialysis are important for new patients. The aim of this study was to develop and validate a nomogram for predicting the 6-month survival rate of HD patients. METHODS: A prediction model was constructed using a training cohort of 679 HD patients. Multivariate Cox regression analyses were performed to identify predictive factors. The identified factors were used to establish a nomogram. The performance of the nomogram was assessed using the C-index and calibration plots. The nomogram was validated by performing discrimination and calibration tests on an additional cohort of 173 HD patients. RESULTS: During a follow-up period of six months, 47 and 16 deaths occurred in the training cohort and validation cohort, respectively, representing a mortality rate of 7.3% and 9.2%, respectively. The nomogram comprised five commonly available predictors: age, temporary dialysis catheter, intradialytic hypotension, use of ACEi or ARB, and use of loop diuretics. The nomogram showed good discrimination in the training cohort [C-index 0.775(0.693-0.857)] and validation cohort [C-index 0.758(0.677-0.836)], as well as good calibration, indicating that the performance of the nomogram was good. The total score point was then divided into two risk classifications: low risk (0-90 points) and high risk (≥ 91 points). Further analysis showed that all-cause mortality was significantly different between the high-risk group and the low-risk group. CONCLUSIONS: The constructed nomogram accurately predicted the 6-month survival rate of HD patients, and thus it can be used in clinical decision-making.


Assuntos
Antagonistas de Receptores de Angiotensina , Nomogramas , Inibidores da Enzima Conversora de Angiotensina , Humanos , Diálise Renal , Taxa de Sobrevida
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