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1.
Front Public Health ; 12: 1332346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322122

RESUMO

Purpose: To explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping. Methods: A total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc. Results: VAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05). Conclusions: In this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Composição Corporal , Imageamento por Ressonância Magnética/métodos
2.
Small ; : e2309863, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368256

RESUMO

Research on flexible thermoelectric (TE) materials has typically focused on conducting polymers and conducting polymer-based composites. However, achieving TE properties comparable in magnitude to those exhibited by their inorganic counterparts remains a formidable challenge. This study focuses on the synthesis of silver selenide (Ag2 Se) nanomaterials using solvothermal methods and demonstrates a significant enhancement in their TE properties through the synergistic dual doping of sulfur and copper. Flexible TE thin films demonstrating excellent flexibility are successfully fabricated using vacuum filtration and hot-pressing techniques. The resulting thin films also exhibited outstanding TE performance, with a high Seebeck coefficient (S = -138.5 µV K-1 ) and electrical conductivity (σ = 1.19 × 105  S m-1 ). The record power factor of 2296.8 µW m-1  K-2 at room temperature is primarily attributed to enhanced carrier transport and interfacial energy filtration effects in the composite material. Capitalizing on these excellent TE properties, the maximum power output of flexible TE devices reached 1.13 µW with a temperature difference of 28.6 K. This study demonstrates the potential of Ag2 Se-based TE materials for flexible and efficient energy-harvesting applications.

3.
Open Biol ; 14(2): 230278, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38378139

RESUMO

Neuroparasitism concerns the hostile take-over of a host's nervous system by a foreign invader, in order to alter the behaviour of the host in favour of the parasite. One of the most remarkable cases of parasite-induced host behavioural manipulation comprises the changes baculoviruses induce in their caterpillar hosts. Baculoviruses may manipulate caterpillar behaviour in two ways: hyperactivity (increased movement in the horizontal plane) and/or tree-top disease (movement to elevated levels in the vertical plane). Those behavioural changes are followed by liquefaction and death of the caterpillar. In Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected Spodoptera exigua caterpillars, an enzymatic active form of the virally encoded protein tyrosine phosphatase (PTP) is needed for the expression of hyperactivity from 3 days post infection (dpi). Using eGFP-expressing recombinant AcMNPV strains, we show that infection of the caterpillar's central nervous system (CNS) can be observed primarily from 3 dpi onwards. In addition, we demonstrate that the structural and enzymatic function of PTP does not play a role in infection of the CNS. Instead we show that the virus entered the CNS via the trachea, progressing caudally to frontally through the CNS and that the infection progressed from the outermost cell layers towards the inner cell layers of the CNS, in a PTP independent manner. These findings help to further understand parasitic manipulation and the mechanisms by which neuroparasites infect the host nervous system to manipulate host behaviour.


Assuntos
Baculoviridae , Sistema Nervoso Central , Nucleopoliedrovírus , Animais , Baculoviridae/genética , Baculoviridae/metabolismo , Spodoptera/metabolismo , Sistema Nervoso Central/metabolismo , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/metabolismo
4.
Evol Bioinform Online ; 20: 11769343241227331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38314309

RESUMO

Aims: Autophagy plays a significant role in the development of acute myocardial infarction (AMI), and cardiomyocyte autophagy is of major importance in maintaining cardiac function. We aimed to identify key genes associated with autophagy in AMI through bioinformatics analysis and verify them through clinical validation. Materials and Methods: We downloaded an AMI expression profile dataset GSE166780 from Gene Expression Omnibus (GEO). Autophagy-associated genes potentially differentially expressed in AMI were screened using R software. Then, to identify key autophagy-related genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) analysis, Receiver Operating Characteristic (ROC) curve analysis, and correlation analysis were performed on the differentially expressed autophagy-related genes in AMI. Finally, we used quantificational real-time polymerase chain reaction (qRT-PCR) to verify the RNA expression of the screened key genes. Results: TSC2, HSPA8, and HIF1A were screened out as key autophagy-related genes. qRT-PCR results showed that the expression levels of HSPA8 and TSC2 in AMI blood samples were lower, while the expression level of HIF1A was higher than that in the healthy controls. Conclusions: TSC2, HSPA8, and HIF1A were identified as key autophagy-related genes in this study. They may influence the development of AMI through autophagy. These findings may help deepen our understanding of AMI and may be useful for the treatment of AMI.

6.
Adv Sci (Weinh) ; : e2307812, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243646

RESUMO

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.

7.
Virulence ; 15(1): 2301246, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38170683

RESUMO

Streptococcus suis (S. suis), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome, meningitis, septicaemia, and abrupt fatality. The multifaceted roles of complement components C5a and C3a extend to orchestrating inflammatory cells recruitment, oxidative burst induction, and cytokines release. Despite the pivotal role of subtilisin-like serine proteases in S. suis pathogenicity, their involvement in immune evasion remains underexplored. In the present study, we identify two cell wall-anchored subtilisin-like serine proteases in S. suis, SspA-1 and SspA-2, as binding partners for C3a and C5a. Through Co-Immunoprecipitation, Enzyme-Linked Immunosorbent and Far-Western Blotting Assays, we validate their interactions with the aforementioned components. However, SspA-1 and SspA-2 have no cleavage activity against complement C3a and C5a performed by Cleavage assay. Chemotaxis assays reveal that recombinant SspA-1 and SspA-2 effectively attenuate monocyte chemotaxis towards C3a and C5a. Notably, the ΔsspA-1, ΔsspA-1, and ΔsspA-1/2 mutant strains exhibit compromised survival in blood, and resistance of opsonophagocytosis, alongside impaired survival in blood and in vivo colonization compared to the parental strain SC-19. Critical insights from the murine and Galleria mellonella larva infection models further underscore the significance of sspA-1 in altering mortality rates. Collectively, our findings indicate that SspA-1 and SspA-2 are novel binding proteins for C3a and C5a, thereby shedding light on their pivotal roles in S. suis immune evasion and the pathogenesis.


Assuntos
Infecções Estreptocócicas , Streptococcus suis , Animais , Humanos , Suínos , Camundongos , Evasão da Resposta Imune , Complemento C3a , Streptococcus suis/metabolismo , Citocinas , Subtilisinas/metabolismo , Infecções Estreptocócicas/microbiologia
8.
Adv Sci (Weinh) ; : e2306563, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168905

RESUMO

Vogt-Koyanagi-Harada (VKH) disease is a severe autoimmune disease. Herein, whole-exome sequencing (WES) study are performed on 2,573 controls and 229 VKH patients with follow-up next-generation sequencing (NGS) in a collection of 2,380 controls and 2,278 VKH patients. A rare c.188T>C (p Val63Ala) variant in the olfactory receptor 11H1 (OR11H1) gene is found to be significantly associated with VKH disease (rs71235604, Pcombined = 7.83 × 10-30 , odds ratio = 3.12). Functional study showes that OR11H1-A63 significantly increased inflammatory factors production and exacerbated barrier function damage. Further studies using RNA-sequencing find that OR11H1-A63 markedly increased growth arrest and DNA-damage-inducible gamma (GADD45G) expression. Moreover, OR11H1-A63 activates the MAPK and NF-κB pathways, and accelerates inflammatory cascades. In addition, inhibiting GADD45G alleviates inflammatory factor secretion, likely due to the regulatory effect of GADD45G on the MAPK and NF-κB pathways. Collectively, this study suggests that the OR11H1-A63 missense mutation may increase susceptibility to VKH disease in a GADD45G-dependent manner.

9.
Sci Rep ; 14(1): 1665, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238423

RESUMO

The first step in any dietary monitoring system is the automatic detection of eating episodes. To detect eating episodes, either sensor data or images can be used, and either method can result in false-positive detection. This study aims to reduce the number of false positives in the detection of eating episodes by a wearable sensor, Automatic Ingestion Monitor v2 (AIM-2). Thirty participants wore the AIM-2 for two days each (pseudo-free-living and free-living). The eating episodes were detected by three methods: (1) recognition of solid foods and beverages in images captured by AIM-2; (2) recognition of chewing from the AIM-2 accelerometer sensor; and (3) hierarchical classification to combine confidence scores from image and accelerometer classifiers. The integration of image- and sensor-based methods achieved 94.59% sensitivity, 70.47% precision, and 80.77% F1-score in the free-living environment, which is significantly better than either of the original methods (8% higher sensitivity). The proposed method successfully reduces the number of false positives in the detection of eating episodes.


Assuntos
Dieta , Mastigação , Humanos , Monitorização Fisiológica , Reconhecimento Psicológico , Processos Mentais
10.
Nano Lett ; 24(4): 1114-1121, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38252877

RESUMO

To avoid the epitaxy dilemma in various thin films, such as complex oxide, silicon, organic, metal/alloy, etc., their stacking at an atomic level and secondary growth are highly desired to maximize the functionality of a promising electronic device. The ceramic nature of complex oxides and the demand for accurate and long-range-ordered stoichiometry face severe challenges. Here, the transport and magnetic properties of the La0.7Ca0.3MnO3 (LCMO) secondary growth on single-crystal freestanding SrTiO3 (STO) membranes are demonstrated. It has been experimentally found that on an only 10 nm thick STO membrane, the LCMO can offer a bulk-like Curie temperature (TC) of 253 K and negative magnetoresistance of -64%, with a weak dependence on the thickness. The resurrected conductivity and ferromagnetism in LCMO confirm the advantages of secondary growth, which benefits from the excellent flexibility and transferability. Additionally, this study explores the integration strategy of complex oxides with other functional materials.

11.
Acta Biomater ; 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38253302

RESUMO

Zinc (Zn) and some of its alloys are recognized as promising biodegradable implant materials due to their acceptable biocompatibility, facile processability, and moderate degradation rate. Nevertheless, the limited mechanical properties and stability of as-cast Zn alloys hinder their clinical application. In this work, hot-rolled (HR) and hot-extruded (HE) Zn-5 wt.% gadolinium (Zn-5Gd) samples were prepared by casting and respectively combining with hot rolling and hot extrusion for bone-implant applications. Their microstructure evolution, mechanical properties, corrosion behavior, cytotoxicity, antibacterial ability, and in vitro and in vivo osteogenesis were systematically evaluated. The HR and HE Zn-5Gd exhibited significantly improved mechanical properties compared with those of their pure Zn counterparts and the HR Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%, all of which are greater than the mechanical properties required for bone-implant materials. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution and the HE Zn-5Gd had the lowest corrosion rate of 155 µm/y measured by electrochemical corrosion and degradation rate of 26.9 µm/y measured by immersion testing. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, high antibacterial effects against S. aureus, and better in vitro osteogenic activity than their pure Zn counterparts. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion behaviors, cytocompatibility, antibacterial ability, in vitro and in vivo osteogenesis of biodegradable Zn-Gd alloy for bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, good antibacterial effects against S. aureus, and better in vitro osteogenic activity. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti.

12.
Stem Cell Res Ther ; 15(1): 24, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38282037

RESUMO

BACKGROUND: Elderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe. METHODS: Our retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests. RESULTS: The median age of the cohort was 57 years (range: 55-75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043). CONCLUSION: The choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante , China , Síndromes Mielodisplásicas/terapia
13.
Med Teach ; : 1-9, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38295767

RESUMO

BACKGROUND: Advanced nursing practice and education with a Master's degree as the necessary preparation, is viewed as a major strategy to cultivate senior nursing talents. Competencies are central to advanced nursing practice and education, but how can competencies be measured? Entrustable professional activities (EPAs) have been used widely in medicine as a practical approach for bridging the gaps between competency and clinical practice. Considering the paucity of research in EPAs for nursing graduates in China, it is needed to develop EPAs specifically for Chinese Master of Nursing Specialist (MNS) graduates to improve patient safety and quality patient care. OBJECTIVES: To develop and evaluate a core competency-based EPAs framework for Chinese MNS graduates. METHODS: A four-stage approach was adopted for the EPAs development, including: (1) forming a research team, (2) drafting an initial EPAs framework, (3) reviewing EPAs framework, and (4) conducting EPAs consensus assessment. RESULTS: A framework containing twelve EPAs was developed, including: 1) perform health assessments, 2) identify and prioritize nursing diagnoses, 3) formulate and implement care plan, 4) perform basic and specialized care operations, 5) recognize and manage medication needs of patients, 6) assess and manage patients with mental health problems, 7) recognize and assist in rescuing critically ill patients, 8) perform transition and handover, 9) participate in multidisciplinary team collaborative care, 10) provide health education and nursing consultation, 11) formulate and implement discharge plans, and 12) instruct nursing students in a clinical setting. The I-CVI score for the two rounds of Delphi ranged from 0.92 ∼ 1.00 and 0.96 ∼ 1.00, respectively. The mean of Equal's score for the three domains ranged from 4.20 ∼ 4.47, 4.25 ∼ 4.51, and 4.23 ∼ 4.37, respectively. CONCLUSION: The developed EPAs framework in this study is a reliable tool to assess the core competencies of Chinese MNS graduates in clinical practice and assist with their curricula design.

14.
J Neurosci Methods ; 403: 110049, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151187

RESUMO

BACKGROUND: Dynamic spatial functional network connectivity (dsFNC) has shown advantages in detecting functional alterations impacted by mental disorders using magnitude-only fMRI data. However, complete fMRI data are complex-valued with unique and useful phase information. METHODS: We propose dsFNC of spatial source phase (SSP) maps, derived from complex-valued fMRI data (named SSP-dsFNC), to capture the dynamics elicited by the phase. We compute mutual information for connectivity quantification, employ statistical analysis and Markov chains to assess dynamics, ultimately classifying schizophrenia patients (SZs) and healthy controls (HCs) based on connectivity variance and Markov chain state transitions across windows. RESULTS: SSP-dsFNC yielded greater dynamics and more significant HC-SZ differences, due to the use of complete brain information from complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with magnitude-dsFNC, SSP-dsFNC detected additional and meaningful connections across windows (e.g., for right frontal parietal) and achieved 14.6% higher accuracy for classifying HCs and SZs. CONCLUSIONS: This work provides new evidence about how SSP-dsFNC could be impacted by schizophrenia, and this information could be used to identify potential imaging biomarkers for psychotic diagnosis.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Cadeias de Markov
15.
Environ Pollut ; 343: 123197, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38128710

RESUMO

The diversity of colloidal types and the differences in the composite ratios in porous media are important factors governing the migration and biological risk of pathogenic microorganisms in the subsurface environment. In this study, E. coli O157:H7 was subjected to co-migration experiments with different compositions of the composite colloid montmorillonite (MMT)-Fe2O3, and the biomolecular response of E. coli under the action of colloids was analyzed by Raman spectroscopy to quantify the risk of E. coli under the action of composite colloids based on both. The results showed that Fe2O3 colloids inhibited E. coli migration mainly by electrostatic adsorption and reduced E. coli metabolism. MMT colloid inhibited E. coli migration mainly by blockage, and E. coli metabolism increased, and surface macromolecules decreased to reduce E. coli adhesion. MMT-Fe2O3 complex colloids inhibited migration through electrostatic attraction between the two and formation of cohesive colloids, with reduced E. coli metabolism and insignificant biomolecular response. It was briefly assessed that the composite colloids reduced E. coli risk less strongly than single colloids, stemming from the difference in the mechanism of influence and the actual need to consider colloid interactions. This conclusion can inform the management and control of pathogen risk in porous media environments.


Assuntos
Bentonita , Escherichia coli , Porosidade , Bentonita/química , Coloides/química , Adsorção
16.
Dermatol Ther (Heidelb) ; 14(1): 233-249, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38100073

RESUMO

BACKGROUND: The excellent efficacy is mitigated by the limited safety profile of microfocused ultrasound procedures. OBJECTIVE: We sought to assess the safety and tightening efficacy of a novel microfocused ultrasound. METHODS: The randomized middle and lower face and submental region of the participants were treated with the novel device using the following transducers: M4.5, D4.5, M3.0, and D3.0. Improvement in paired comparison of pretreatment and posttreatment photographs, three-dimensional (3D) volumetric assessments, skin thickness measured by B-ultrasonography, and skin photoaging parameters were evaluated. Adverse events and patient satisfaction were also recorded. RESULTS: A total of 20 participants (20 female) were enrolled. Fourteen of 20 participants (70%) were judged to show clinically significant facial tightening during 3-month follow-up (P < 0.05). The mean volumetric change in the lower face, as quantitatively assessed after 3 months was -0.29 mL compared with +0.42 mL on the control side (P < 0.05). The VAS pain score was 3.00 ± 1.19 without any oral or intramuscular anesthesia. CONCLUSIONS: A small sample size, lack of clinical scales, and impersonalized treatment parameters. The novel microfocused ultrasound appears to be a safe and effective modality for lower-face tightening. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR 2200064666.

17.
Emerg Microbes Infect ; : 2294857, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085548

RESUMO

AbstractCampylobacter upsaliensis was the most common Campylobacter species in pets' gastrointestinal tracts and has been isolated from patients with bacteremia, hemolytic-uremic syndrome, spontaneous abortion, and Guillain-Barré syndrome. However, the genetic characteristics and the full extent of its significance as a human pathogen remain to be fully understood. This study involved an investigation for genomic analysis of 154 strains from different sources and additional antimicrobial resistance profiles of 26 strains for this species. The genomes contained 1,558-1,971 CDS and the genome sizes were estimated to vary from 1.53 Mb to 1.86 Mb, with an average GC content of 34.71%. The entire analyzed genomes could be divided into three clades (A, B, and C) based on ANI and phylogenomic analysis. Significantly, nearly all strains in Clade B were isolated from patient samples, and the virulence-related sequences FlgD, GmhA, and CdtC might serve as determining factors for the classification of Clade B. Half of the tested isolates had MIC values over 64 µg mL-1 for nalidixic acid, gentamicin, and streptomycin. Isolates from pets in China carried more resistant elements in the genomes. This study both provided a comprehensive profile of C. upsaliensis for its genomic features and suggested some pathogenic agents for human infection with this species.

18.
BMC Complement Med Ther ; 23(1): 459, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102654

RESUMO

OBJECTIVE: The aim of the present study was to investigate the therapeutic effect of ammidin on hypoxia/reoxygenation (H/R) injury in primary neonatal rat cardiomyocytes by observing the role of ferroptosis in the process of H/R injury, and to verify its target and regulatory signaling pathways. METHODS: The network pharmacology analysis was used to predict the biological processes, core targets and related signaling pathways of Angelica dahurica in the treatment of ferroptosis. Cell viability was assessed using live cell imaging and cell counting kit-8. Lactate dehydrogenase (LDH), reactive oxygen species (ROS) production, and malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) content were determined to assess the level of ferroptosis. Western blotting was performed to measure protein expression. RESULTS: Network pharmacology predicted that Acyl-CoA synthetase long chain family member 4 (ACSL4) was highly associated with myocardial H/R injury in the intersection of Angelica dahurica and ferroptosis. The top three active components of Angelica dahurica were found to be mandenol, alloisoimperatorin and ammidin, among which ammidin was found to have the strongest binding to the target proteins of the ACSL4/AMPK/mTOR pathway. H/R reduced the viability of cardiomyocytes, while the inhibition of ferroptosis by ferrostatin-1 alleviated the H/R-induced inhibition of cardiomyocyte viability. This was evidenced by the increased cell viability, SOD release, MMP level and glutathione peroxidase 4 (GPX4) protein expression, as well as the decreased LDH and MDA release and ROS production and ACSL4 protein expression (P < 0.05). To verify the existence of ferroptosis in myocardial hypoxia/reoxygenation injury. In addition, ammidin increased cell viability and GPX4 protein expression (P < 0.05), decreased ROS generation, and MDA and MTT expression (P < 0.05), then inhibited ferroptosis, and finally alleviated myocardial H/R injury by regulating the ACSL4/AMPK signaling pathway. CONCLUSIONS: Network pharmacology was used to predict the correlation between ammidin and ferroptosis following myocardial H/R injury. It was demonstrated that ammidin may regulate ferroptosis by inhibiting the ACSL4/AMPK/mTOR signaling pathway and reduce H/R injury in cardiomyocytes.


Assuntos
Ferroptose , Isquemia Miocárdica , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Hipóxia/metabolismo , Superóxido Dismutase/metabolismo
19.
bioRxiv ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38105964

RESUMO

Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a novel kinesin-based mechanism for polarized transport of vesicles to dendrites. Significance: Our findings suggest that at least one type of vesicles, those containing transferrin receptor, travel exclusively to dendrites and are excluded from axons because the kinase MARK2 phosphorylates the kinesin KIF13A to promote its separation from vesicles at the proximal axon, preventing vesicle transport into axons, such that they travel only to dendrites. Future studies should explore how this mechanism of polarized vesicle transport supports neuronal function.

20.
J Biomol Struct Dyn ; : 1-12, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38109076

RESUMO

To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and ß-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97 ± 1.41 kcal/mol and -21.15 ± 3.17 kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.

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