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1.
Infect Drug Resist ; 17: 1243-1249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560704

RESUMO

Background: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited. Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to "beauty needle" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with "metronidazole", and oral "cephalosporin" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient's facial symptoms were significantly improved, and no drug-related adverse reactions happened. Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.

2.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 232-236, 2024 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-38605628

RESUMO

In order to realize the diagnosis of slit lamp in cross-regional patients and improve the real-time and convenience of diagnosis, a remote slit lamp diagnosis platform based on Internet of Things (IoT) technology is designed. Firstly, the feasibility of remote slit lamp is analyzed. Secondly, the IoT platform architecture of doctor/server/facility (D/S/F) is proposed and a remote slit lamp is designed. Finally, the performance of the remote slit lamp diagnostic platform is tested. The platform solves the communication problem of distributed slit lamps and realizes respectively numerical control of multi-area slit lamp by multi-eye experts. The test results show that the remote control delay of the platform is less than 20 ms, which supports multiple experts to diagnose multiple patients separately.


Assuntos
Internet das Coisas , Lâmpada de Fenda , Humanos , Tecnologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38666303

RESUMO

The human vaginal epithelium is a crucial component of numerous reproductive processes and serves as a vital protective barrier against pathogenic invasion. Despite its significance, a comprehensive exploration of its molecular profiles, including molecular expression and distribution across its multiple layers, has not been performed. In this study, we perform a spatial transcriptomic analysis within the vaginal wall of human fetuses to fill this knowledge gap. We successfully categorize the vaginal epithelium into four distinct zones based on transcriptomic profiles and anatomical features. This approach reveals unique transcriptomic signatures within these regions, allowing us to identify differentially expressed genes and uncover novel markers for distinct regions of the vaginal epithelium. Additionally, our findings highlight the varied expressions of keratin ( KRT) genes across different zones of the vaginal epithelium, with a gradual shift in expression patterns observed from the basal layer to the surface/superficial layer. This suggests a potential differentiation trajectory of the human vaginal epithelium, shedding light on the dynamic nature of this tissue. Furthermore, abundant biological processes are found to be enriched in the basal zone by KEGG pathway analysis, indicating an active state of the basal zone cells. Subsequently, the expressions of latent stem cell markers in the basal zone are identified. In summary, our research provides a crucial understanding of human vaginal epithelial cells and the complex mechanisms of the vaginal mucosa, with potential applications in vaginal reconstruction and drug delivery, making this atlas a valuable tool for future research in women's health and reproductive medicine.

4.
Front Public Health ; 12: 1322426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304182

RESUMO

Objective: To investigate the positivity rates and drug resistance characteristics of Mycobacterium tuberculosis (MTB) among suspected tuberculosis (TB) patients in Shandong Province, the second-largest population province in China. Methods: A prospective, multi-center study was conducted from April 2022 to June 2023. Pathogen and drug resistance were identified using nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS). Results: Of 940 suspected TB patients included in this study, 552 cases were found to be infected with MTB giving an overall positivity rate of 58.72%. Total of 346 cases were resistant to arbitrary anti-TB drug (62.68%), with Zibo (76.47%), Liaocheng and Weihai (both 69.23%) ranking top three and TB treatment history might be a related factor. Monoresistance was the most common pattern (33.53%), with isoniazid the highest at 12.43%, followed by rifampicin at 9.54%. Further analysis of gene mutations conferring resistance revealed diverse types with high heteroresistance rate found in multiple anti-TB drugs. Conclusion: A relatively high rate of MTB positivity and drug resistance was found in Shandong Province during and after the COVID-19 pandemic, indicating the need for strengthening rapid identification of species and drug resistance among suspected TB patients to guide better medication and minimize the occurrence of drug resistance.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Antituberculosos/farmacologia , Mycobacterium tuberculosis/genética , Nucleotídeos , Pandemias , Estudos Prospectivos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tuberculose/epidemiologia
5.
Cell Death Dis ; 14(12): 846, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114473

RESUMO

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.


Assuntos
Neoplasias Esofágicas , Interleucina-6 , Humanos , Recidiva Local de Neoplasia , Tolerância a Radiação/fisiologia , Neoplasias Esofágicas/radioterapia
6.
Front Plant Sci ; 14: 1275464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37799557

RESUMO

Introduction: Seasonal droughts will become more severe and frequent under the context of global climate change, this would result in significant variations in the root distribution and water utilization patterns of plants. However, research on the determining factors of deep fine root and water utilization is limited. Methods: We measured the fine root biomass and water utilization of trees, shrubs and herbs, and soil properties, light transmission, and community structure parameters in subtropical pine plantations with seasonal droughts. Results and Discussion: We found that the proportion of deep fine roots (below 1 m depth) is only 0.2-5.1%, but that of deep soil water utilization can reach 20.9-38.6% during the dry season. Trees improve deep soil water capture capacity by enhancing their dominance in occupying deep soil volume, and enhance their deep resource foraging by increasing their branching capacity of absorptive roots. Shrubs and herbs showed different strategies for deep water competition: shrubs tend to exhibit a "conservative" strategy and tend to increase individual competitiveness, while herbs exhibited an "opportunistic" strategy and tend to increase variety and quantity to adapt to competitions. Conclusion: Our results improve our understanding of different deep fine root distribution and water use strategies between overstory trees and understory vegetations, and emphasize the importance of deep fine root in drought resistance as well as the roles of deep soil water utilization in shaping community assembly.

7.
Nat Commun ; 14(1): 5556, 2023 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689690

RESUMO

Chemicals or drugs can accumulate within biomolecular condensates formed through phase separation in cells. Here, we use super-resolution imaging to search for chemicals that induce phase transition within chromatin at the microscale. This microscopic screening approach reveals that adriamycin (doxorubicin) - a widely used anticancer drug that is known to interact with chromatin - specifically induces visible local condensation and global conformational change of chromatin in cancer and primary cells. Hi-C and ATAC-seq experiments systematically and quantitatively demonstrate that adriamycin-induced chromatin condensation is accompanied by weakened chromatin interaction within topologically associated domains, compartment A/B switching, lower chromatin accessibility, and corresponding transcriptomic changes. Mechanistically, adriamycin complexes with histone H1 and induces phase transition of H1, forming fibrous aggregates in vitro. These results reveal a phase separation-driven mechanism for a chemotherapeutic drug.


Assuntos
Condensados Biomoleculares , Cromatina , Sequenciamento de Cromatina por Imunoprecipitação , Doxorrubicina/farmacologia , Perfilação da Expressão Gênica
8.
Environ Res ; 237(Pt 1): 116895, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37586454

RESUMO

BACKGROUND: The cancer-testis protein melanoma antigen A3 (MAGE-A3) is highly expressed in a broad range of malignant tumor forms. It has been confirmed that affibody molecules, a novel family of small (∼6.5 kDa) targeting proteins, are useful agents for molecular imaging and targeted tumor treatment. As a novel agent for in vivo molecular imaging detection of MAGE-A3-positive tumors, the efficacy of affibody molecules was assessed in this research. METHODS: In this study, three cycles of phage display library screening resulted in the isolation of two new affibody molecules (ZMAGE-A3:172 and ZMAGE-A3:770) that attach to MAGE-A3. These molecules were then expressed in bacteria and purified. The affibody molecules with high affinity and specificity were evaluated using western blotting, immunohistochemistry, indirect immunofluorescence, surface plasmon resonance, and near-infrared optical imaging of tumor-bearing nude mice. RESULTS: The selected ZMAGE-A3 affibodies can precisely bind to the MAGE-A3 protein in living cells and display high-affinity binding to the MAGE-A3 protein at the molecular level. Furthermore, the accumulation of DyLight755-labeled ZMAGE-A3:172 or ZMAGE-A3:770 in MAGE-A3-positive tumors was achieved as early as 30 min and disappeared at 48 h post-injection. CONCLUSION: Our findings support the potential of the two MAGE-A3 protein-binding affibody molecules for their use as molecular imaging agents.

9.
Free Radic Biol Med ; 205: 151-162, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37302615

RESUMO

Intrauterine adhesions (IUA), characterized by endometrial fibrosis, is a challenging clinical issue in reproductive medicine. We previously demonstrated that epithelial-mesenchymal transition (EMT) and fibrosis of endometrial stromal cells (HESCs) played a vital role in the development of IUA, but the precise pathogenesis remains elucidated. Ferroptosis has now been recognized as a unique form of oxidative cell death, but whether it is involved in endometrial fibrosis remains unknown. In the present study, we performed an RNA-seq of the endometria from 4 severe IUA patients and 4 normal controls. Enrichment analysis and protein-protein interactions (PPIs) network analysis of differentially expressed genes (DEGs) were conducted. Immunohistochemistry was used to assess ferroptosis levels and cellular localization. The potential role of ferroptosis for IUA was investigated by in vitro and in vivo experiments. Here, we demonstrated that ferroptosis load is increased in IUA endometria. In vitro experiments showed that erastin-induced ferroptosis promoted EMT and fibrosis in endometrial epithelial cells (P < 0.05), but did not lead to pro-fibrotic differentiation in endometrial stromal cells (HESCs). Cell co-culture experiments showed that erastin-stimulated epithelial cell supernatants promoted fibrosis in HESCs (P < 0.05). In vivo experiments suggested that elevation of ferroptosis level in mice by erastin led to mild endometrial EMT and fibrosis. Meanwhile, the ferroptosis inhibitor Fer-1 significantly ameliorated endometrial fibrosis in a dual-injury IUA murine model. Overall, our findings revealed that ferroptosis may serve as a potential therapeutic target for endometrial fibrosis in IUA.


Assuntos
Ferroptose , Doenças Uterinas , Humanos , Feminino , Camundongos , Animais , Ferroptose/genética , Doenças Uterinas/genética , Doenças Uterinas/metabolismo , Doenças Uterinas/patologia , Endométrio/metabolismo , Células Estromais/metabolismo , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia , Aderências Teciduais/terapia , Fibrose
10.
Dalton Trans ; 52(24): 8294-8301, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37255020

RESUMO

A thermally tunable terahertz window based on the combination of a metamaterial and the phase change material VO2 is proposed. The window is composed of two vanadium oxide films with a SiO2 layer sandwiched between them. The thermochromic phase change properties of VO2 are the key to the functionality of the window. By controlling the temperature around the room temperature of 300 K, our material can be used as a smart window and it is able to regulate both the absorption and transmission of external terahertz waves in response to changes in temperature. The absorbance can be regulated by more than 90% and the transmittance by more than 80%. The switching characteristics of the window are explained by the insulator-metal transition that vanadium oxide undergoes during the heating process, while localized surface plasmon resonance explains the perfect absorption. In addition, the designed window is not only insensitive to polarised waves, but is thermally flexible and maintains excellent performance over a wide angular range of 0° to 40°. This design will have significant potential for applications in stealth technologies, thermal sensing and switching, and terahertz energy harvesting.

11.
BMC Cardiovasc Disord ; 23(1): 275, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37226099

RESUMO

OBJECTIVE: This study aims to investigate the association of lysine methyltransferase 2 C (MLL3) and transforming growth factor ß (TGF-ß) signaling-related gene polymorphisms with the susceptibility of Stanford type B aortic dissection (AD) and its clinical prognostic outcomes. The methods involved investigating the MLL3 (rs10244604, rs6963460, rs1137721), TGFß1 (rs1800469), TGFß2 (rs900), TGFR1 (rs1626340) and TGFR2 (rs4522809) gene polymorphisms. Logistic regression was performed to investigate the association between 7 single nucleotide gene polymorphisms (SNPs) and Stanford type B aortic dissection. The GMDR software was used to analyze gene-gene and gene-environment interactions. The odds ratio (OR) with a 95% confidence interval (CI) was employed to evaluate the association of genes and Stanford type B AD risk. RESULTS: Genotypes and allele distributions in the case and control groups showed significant differences (P < 0.05). Logistic regression has shown that the Stanford Type B AD risk was highest in individuals with the rs1137721 CT genotype (OR = 4.33, 95% CI = 1.51-12.40). Additionally, WBC, drinking, hypertension, triglycerides (TG), and low-density lipoprotein (LDL-C) were independent risk factors for Stanford Type B AD. Logistic regression showed that the Stanford Type B AD risk was highest in individuals with the MLL3 (rs1137721)-TT + CT and TGFß1 (rs4522809)-AA genotype (OR = 6.72, 95% CI = 1.56-29.84), and lowest in those with the MLL3 (rs1137721)-CC and TGFß1 (rs4522809)-AA + GG genotype (OR = 4.38, 95% CI = 0.92-20.83). However, the 55-month median long-term follow-up did not show statistical significance. CONCLUSION: Carriers of both TT + CT of MLL3 (rs1137721) and AA of TGFß1 (rs4522809) polymorphisms may be closely related to the development of Stanford type B AD. MLL3 (rs1137721), WBC, and TG/TC were found to be associated with the morbidity of Stanford type B AD. MLL3 (KMT2C) is associated with the TGF-ß signaling pathway protein. The risk of Stanford type B AD is related to the interactions of gene-gene and gene-environment.


Assuntos
Dissecção Aórtica , Proteínas de Ligação a DNA , Fator de Crescimento Transformador beta1 , Humanos , Dissecção Aórtica/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Transdução de Sinais , Proteínas de Ligação a DNA/genética , Fator de Crescimento Transformador beta1/genética
12.
J Magn Reson Imaging ; 58(6): 1703-1713, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37074789

RESUMO

BACKGROUND: Endometrial fibrosis may cause infertility. Accurate evaluation of endometrial fibrosis helps clinicians to schedule timely therapy. PURPOSE: To explore T2 mapping for assessing endometrial fibrosis. STUDY TYPE: Prospective. POPULATION: Ninety-seven women with severe endometrial fibrosis (SEF) and 21 patients with mild to moderate endometrial fibrosis (MMEF), diagnosed by hysteroscopy, and 37 healthy women. FIELD STRENGTH/SEQUENCE: 3T, T2-weighted turbo spin echo (T2-weighted imaging) and multi-echo turbo spin echo (T2 mapping) sequences. ASSESSMENT: Endometrial MRI parameters (T2, thickness [ET], area [EA], and volume [EV]) were measured by N.Z. and Q.H. (9- and 4-years' experience in pelvic MRI) and compared between the three subgroups. A multivariable model including MRI parameters and clinical variables (including age and body mass index [BMI]) was developed to predict endometrial fibrosis assessed by hysteroscopy. STATISTICAL TESTS: Kruskal-Wallis; ANOVA; Spearman's correlation coefficient (rho); area under the receiver operating characteristic curve (AUC); binary logistic regression; intraclass correlation coefficient (ICC). P value <0.05 for statistical significance. RESULTS: Endometrial T2, ET, EA, and EV of MMEF patients (185 msec, 8.2 mm, 168 mm2 , and 2181 mm3 ) and SEF patients (164 msec, 6.7 mm, 120 mm2 , and 1762 mm3 ) were significantly lower than those of healthy women (222 msec, 11.7 mm, 316 mm2 , and 3960 mm3 ). Endometrial T2 and ET of SEF patients were significantly lower than those of MMEF patients. Endometrial T2, ET, EA, and EV were significantly correlated to the degree of endometrial fibrosis (rho = -0.623, -0.695, -0.694, -0.595). There were significant strong correlations between ET, EA, and EV in healthy women and MMEF patients (rho = 0.850-0.908). Endometrial MRI parameters and the multivariable model accurately distinguished MMEF or SEF from normal endometrium (AUCs >0.800). Age, BMI, and MRI parameters in univariable analysis and age and T2 in multivariable analysis significantly predicted endometrial fibrosis. The reproducibility of MRI parameters was excellent (ICC, 0.859-0.980). DATA CONCLUSION: T2 mapping has potential to noninvasively and quantitatively evaluate the degree of endometrial fibrosis. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.


Assuntos
Imageamento por Ressonância Magnética , Humanos , Feminino , Pré-Escolar , Reprodutibilidade dos Testes , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Curva ROC , Fibrose
13.
Bioact Mater ; 27: 125-137, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37064803

RESUMO

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

14.
Bioeng Transl Med ; 8(2): e10448, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925694

RESUMO

Neural progenitor cell (NPC) transplantation is a promising approach for repairing spinal cord injury (SCI). However, cell survival, maturation and integration after transplantation are still major challenges. Here, we produced a novel centimeter-scale human spinal cord neural tissue (hscNT) construct with human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, to form a linearly ordered spinal cord-like structure consisting of mature neurons and glia cells. When transplanted into rats with SCI, the hscNT created a favorable microenvironment by inhibiting inflammation and glial scar formation, and promoted neural and vascular regeneration. Notably, the hscNT promoted neural circuit reconstruction and motor functional recovery. Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may therefore have potential in the treatment of SCI.

15.
Front Plant Sci ; 14: 1130477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36794217

RESUMO

Introduction: Soil salinity is known to affect plant performance and nutrient stoichiometry by altering their ecophysiology, and thus playing a crucial role in determining plant distribution patterns and nutrient cycles in salinized ecosystems. However, there was little consensus on the effects of salinity stress on plant C, N, and P stoichiometries. Moreover, determining the relationships between species relative species abundance and plant C, N, and P stoichiometries can help to understand the different adaptive strategies between the common and rare species as well as the community assembly process. Methods: We determined the plant C, N, P stoichiometries at the community and species levels and the relative abundance of species as well as the corresponding soil properties from five sampling sites along a soil salinity gradient in the Yellow River Delta, China. Results and Discussion: We found that the C concentration of belowground part increased with soil salinity. Meanwhile, plant community N concentration and C:N ratio tended to decrease with soil salinity, whereas the P concentration, C:P, and N:P ratios exhibited the opposite trends. This indicated that N use efficiency increased, while P use efficiency decreased with soil salinity. Moreover, the decreased N:P ratio indicated that N limitation was gradually aggravated along the soil salinity gradient. The soil C:P ratio and P concentration were the major factors of plant C, N, and P stoichiometries in the early growth stage, whereas the soil pH and P concentration were the major factors of plant C, N, and P stoichiometries in the late growth stage. Compared with that of the rare species, the C:N:P stoichiometry of the most common species was medium. Moreover, the intraspecific variations in the aboveground part N:P ratio and belowground part C concentration showed a significant correlation with species' relative abundance, which indicated that higher intraspecific trait variation might facilitate greater fitness and survival opportunities in environments with high heterogeneity. Conclusion: Our results revealed that the plant community C:N:P stoichiometry and its determining soil properties varied with plant tissues as well as sampling seasons, and emphasized the importance of intraspecific variation in determining the functional response of plant communities to salinity stress.

16.
Opt Lett ; 48(4): 1012-1015, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36790992

RESUMO

We report an all-fiber ultra-short pulse burst laser operating at around 1.98 µm that is obtained through a nonlinear wavelength converter and Tm-doped fiber amplifier. A mode-locked Er-doped fiber laser was first built and then amplified in subsequent amplifiers to an average power of 1.3 W. Ultra-short pulse burst output was achieved through a pulse multiplier and a fiber-pigtailed acousto-optic modulator. It was then injected into an all-fiber nonlinear wavelength converter constructed from P-doped fiber and Tm-doped fiber, obtaining an ultra-short pulse burst laser of 540 mW around 1.98 µm. Its average output power was then amplified to 4.33 W in a Tm-doped fiber amplifier with an intra-burst pulse repetition frequency of 0.9 GHz, a burst repetition frequency of 200 kHz, and a duty cycle of 2%, corresponding to about 200 pulses within each burst. This 1.98 µm pulse burst laser has enormous potential to be applied in bio-medical areas.

17.
Microbiol Spectr ; 11(1): e0356222, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36511681

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented public health disaster in human history, and its spike (S) protein is the major target for vaccines and antiviral drug development. Although widespread vaccination has been well established, the viral gene is prone to rapid mutation, resulting in multiple global spread waves. Therefore, specific antivirals are needed urgently, especially those against variants. In this study, the domain of the receptor binding motif (RBM) and fusion peptide (FP) (amino acids [aa] 436 to 829; denoted RBMFP) of the SARS-CoV-2 S protein was expressed as a recombinant RBMFP protein in Escherichia coli and identified as being immunogenic and antigenically active. Then, the RBMFP proteins were used for phage display to screen the novel affibody. After prokaryotic expression and selection, four novel affibody molecules (Z14, Z149, Z171, and Z327) were obtained. Through surface plasmon resonance (SPR) and pseudovirus neutralization assay, we showed that affibody molecules specifically bind to the RBMFP protein with high affinity and neutralize against SARS-CoV-2 pseudovirus infection. Especially, Z14 and Z171 displayed strong neutralizing activities against Delta and Omicron variants. Molecular docking predicted that affibody molecule interaction sites with RBM overlapped with ACE2. Thus, the novel affibody molecules could be further developed as specific neutralization agents against SARS-CoV-2 variants. IMPORTANCE SARS-CoV-2 and its variants are threatening the whole world. Although a full dose of vaccine injection showed great preventive effects and monoclonal antibody reagents have also been used for a specific treatment, the global pandemic persists. So, developing new vaccines and specific agents are needed urgently. In this work, we expressed the recombinant RBMFP protein as an antigen, identified its antigenicity, and used it as an antigen for affibody phage-display selection. After the prokaryotic expression, the specific affibody molecules were obtained and tested for pseudovirus neutralization. Results showed that the serum antibody induced by RBMFP neutralized Omicron variants. The screened affibody molecules specifically bound the RBMFP of SARS-CoV-2 with high affinity and neutralized the Delta and Omicron pseudovirus in vitro. So, the RBMFP induced serum provides neutralizing effects against pseudovirus in vitro, and the affibodies have the potential to be developed into specific prophylactic agents for SARS-CoV-2 and its variants.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Simulação de Acoplamento Molecular , Testes de Neutralização/métodos , Proteínas Recombinantes , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
18.
J Cardiovasc Pharmacol ; 80(1): 118-124, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35500095

RESUMO

ABSTRACT: We aim to investigate whether genetic variants of the Fibrillin-1 (FBN1) gene were associated with DeBakey type III aortic dissection (AD) and its clinical prognosis in Chinese Han population. Three single-nucleotide polymorphisms (SNPs) (rs145233125, rs11070646, rs201170905) in FBN1 were analyzed in patients with DeBakey type III AD (159) and healthy subjects (216). Gene-environment interactions were evaluated to use generalized multifactor dimensionality reduction. Haplotype analysis of the 3 SNPs in the FBN1 gene was performed by Haploview software. Patients were followed up for average 4 years. G carriers of rs11070646 and rs201170905 in FBN1 have an increased risk of DeBakey type III AD. The interaction of FBN1 and environmental factors facilitated to the increased risk of DeBakey type III AD (cross-validation consistency = 10/10, P = 0.001). One of the most common haplotypes revealed an increased risk of DeBakey type III AD (CGG, P = 0.009). Recessive models of rs145233125 CC genotype ( P < 0.05) and rs201170905 GG genotype ( P < 0.001) were associated with an increased risk of death and recurrent chest pain of DeBakey type III AD. In conclusions, FBN1 gene polymorphisms contribute to DeBakey type III AD susceptibility. The interactions of gene and environment are related with the risk of DeBakey type III AD. C carriers of rs145233125 and G carriers of rs201170905 may be the adverse prognostic indicators of death and recurrent chest pain in DeBakey type III AD.


Assuntos
Dissecção Aórtica , Fibrilina-1/genética , Predisposição Genética para Doença , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/genética , Estudos de Casos e Controles , Dor no Peito , China/epidemiologia , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Prognóstico
19.
BMC Med Genomics ; 15(1): 65, 2022 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-35307021

RESUMO

BACKGROUND: This study is aimed at investigating the association of Fibrillin-1 (FBN1) and transforming growth factor ß (TGF-ß) signaling-related gene polymorphisms with the susceptibility of Stanford type B aortic dissection (AD) and its clinical prognostic outcomes. METHODS: Five single-nucleotide polymorphism (SNPs) (FBN1rs 145233125, rs201170905, rs11070646, TGFB1rs1800469, and TGFB2rs900) were analyzed in patients with Stanford type B AD (164) and healthy controls (317). Gene-gene and gene-environment interactions were assessed by generalized multifactor dimensionality reduction. A 4-year follow-up was performed for all AD patients. RESULTS: G carriers of FBN1 rs201170905 and TGFB1 rs1800469 have an increased risk of Stanford type B AD. The interaction of FBN1, TGFB1, TGFB2 and environmental promoted to the increased risk of type B AD (cross-validation consistency = 10/10, P = 0.001). Dominant models of FBN1rs145233125 TC + CC genotype (P = 0.028), FBN1 rs201170905 AG + GG (P = 0.047) and TGFB1 rs1800469 AG + GG (P = 0.052) were associated with an increased risk of death of Stanford type B AD. The recessive model of FBN1 rs145233125 CC genotype (P < 0.001), FBN1rs201170905 GG (P < 0.001), TGFB1 rs1800469 AG + GG genotype (P = 0.011) was associated with an increased risk of recurrence of chest pain in Stanford type B AD. CONCLUSIONS: The interactions of gene-gene and gene-environment are related with the risk of Stanford type B AD. C carriers of rs145233125, G carriers of rs201170905 and G carriers of rs1800469 may be the poor clinical outcome indicators of mortality and recurrent chest pain in Stanford type B AD.


Assuntos
Dissecção Aórtica , Fator de Crescimento Transformador beta , Dissecção Aórtica/genética , Dor no Peito , Fibrilina-1/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Prognóstico , Fator de Crescimento Transformador beta/genética
20.
Abdom Radiol (NY) ; 47(4): 1448-1456, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35113173

RESUMO

PURPOSE: To investigate the feasibility of using diffusion kurtosis imaging (DKI) for the assessment of endometrial fibrosis. METHODS: 40 patients with hysteroscopy confirmed endometrial fibrosis and 30 healthy women underwent MR examination including the DKI sequence (b = 0, 500, 1000, 1500, and 2000 s/mm2). Endometrial thickness (ET), apparent diffusion coefficient (ADC), corrected ADC (D), and kurtosis of diffusion (K) were measured and compared, and the diagnostic performance of those parameters was evaluated using ROC curves analysis. RESULTS: Patients with endometrial fibrosis had a thinner endometrium than the healthy controls (P < 0.001). They also had significantly lower ADC and D values and significantly higher K values of the endometrium than the healthy controls (all P < 0.001). ADC, D, K, and ET all performed excellently in diagnosing endometrial fibrosis, with areas under the curve (AUCs) of 0.940, 0.879, 0.860, and 0.853, respectively. ADC showed the highest AUC, demonstrating better diagnostic accuracy than K (z = 2.307, P < 0.05). However, there were no differences in AUC between D, K, and ET, or ADC, D, and ET (all P > 0.05). The reproducibility of ADC, D, and K values in patients with endometrial fibrosis and healthy controls was excellent (ICC 0.951-0.991). CONCLUSION: DKI of the endometrium has promising potential for the noninvasive assessment of endometrial fibrosis.


Assuntos
Imagem de Tensor de Difusão , Doenças Uterinas , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Fibrose , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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