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1.
Nature ; 630(8015): 222-229, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38657677

RESUMEN

Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology1-3. The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex2. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy4. Here we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes5,6, revealing two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ-TCRδ extracellular domain and connecting peptides. The length of the connecting peptides regulates the ligand association and T cell activation. A cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signalling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, whereby two protomers nestle back to back through the Vγ5 domains of the TCR extracellular domains. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the unique properties of γδ TCR and facilitating immunotherapeutic interventions.


Asunto(s)
Complejo CD3 , Receptores de Antígenos de Linfocitos T gamma-delta , Linfocitos T , Humanos , Complejo CD3/química , Complejo CD3/inmunología , Complejo CD3/metabolismo , Complejo CD3/ultraestructura , Colesterol/metabolismo , Colesterol/química , Microscopía por Crioelectrón , Ligandos , Activación de Linfocitos/inmunología , Modelos Moleculares , Dominios Proteicos , Multimerización de Proteína , Receptores de Antígenos de Linfocitos T gamma-delta/química , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/ultraestructura , Linfocitos T/química , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transducción de Señal , Membrana Celular/química , Membrana Celular/metabolismo
2.
J Nanobiotechnology ; 22(1): 150, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575923

RESUMEN

Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.


Asunto(s)
MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Células Endoteliales , Pulpa Dental , Células Madre , Diferenciación Celular , Regeneración , ADN/metabolismo , Proliferación Celular/fisiología
3.
Lipids Health Dis ; 23(1): 26, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263019

RESUMEN

Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets.


Asunto(s)
Dermatitis Atópica , Humanos , Calidad de Vida , Obesidad , Prurito , Adipoquinas
4.
Int J Biometeorol ; 68(6): 1123-1132, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38507092

RESUMEN

Multiple evidence has supported that air pollution exposure has detrimental effects on the cardiovascular and respiratory systems. However, most investigations focus on the general population, with limited research conducted on medically insured populations. To address this gap, the current research was designed to examine the acute effects of inhalable particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), ground-level ozone (O3), and sulfur dioxide (SO2) on the incidence of upper respiratory tract infections (URTI), utilizing medical insurance data in Wuhan, China. Data on URTI were collected from the China Medical Insurance Basic Database for Wuhan covering the period from 2014 to 2018, while air pollutant data was gathered from ten national monitoring stations situated in Wuhan city. Statistical analysis was performed using generalized additive models for quasi-Poisson distribution with a log link function. The analysis indicated that except for ozone, higher exposure to four other pollutants (NO2, SO2, PM2.5, and PM10) were significantly linked to an elevated risk of URTI, particularly during the previous 0-3 days and previous 0-4 days. Additionally, NO2 and SO2 were found to be positively linked with laryngitis. Furthermore, the effects of air pollutants on the risk of URTI were more pronounced during cold seasons than hot seasons. Notably, females and the employed population were more susceptible to infection than males and non-employed individuals. Our findings gave solid proof of the link between ambient air pollution exposure and the risk of URTI in medically insured populations.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Material Particulado , Infecciones del Sistema Respiratorio , Dióxido de Azufre , Humanos , China/epidemiología , Femenino , Masculino , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/efectos adversos , Persona de Mediana Edad , Material Particulado/análisis , Adulto , Infecciones del Sistema Respiratorio/epidemiología , Dióxido de Azufre/análisis , Anciano , Adolescente , Adulto Joven , Ozono/análisis , Ozono/efectos adversos , Niño , Preescolar , Seguro de Salud/estadística & datos numéricos , Dióxido de Nitrógeno/análisis , Lactante , Estaciones del Año , Recién Nacido , Incidencia , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/efectos adversos
5.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000180

RESUMEN

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 µg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.


Asunto(s)
Péptidos Antimicrobianos , Pruebas de Sensibilidad Microbiana , Animales , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/metabolismo , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Bacterias Gramnegativas/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/genética , Humanos
6.
Acta Derm Venereol ; 103: adv6226, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37606155

RESUMEN

Hypopigmented mycosis fungoides is a rare form of mycosis fungoides that is characterized by achromic lesions, early onset of disease, a predilection for darker skinned populations, and a predominance of CD8+ T cells. Due to the rarity and heterogeneous presentation of hypopigmented mycosis fungoides, there are no criteria that clearly define the clinical characteristics and treatment regimens for this condition. This retrospective study of 44 paediatric patients with hypopigmented mycosis fungoides aimed to summarize their epidemiological and clinical characteristics and assess the effectiveness and safety of different treatment regimens. Clinical manifestations were further classified into 3 morphological groups: hypopigmented lesions, papules overlying hypopigmented lesions, and erythematous plaques overlying hypopigmented lesions. In addition, the results of this study suggest that interferon alpha might be an effective and well-tolerated therapy that could shorten the treatment time to complete response compared with other treatments. Maintenance therapy and long-term follow-up reduced the recurrence rate.


Asunto(s)
Micosis Fungoide , Neoplasias Cutáneas , Humanos , Niño , Estudios Retrospectivos , Micosis Fungoide/tratamiento farmacológico , Linfocitos T CD8-positivos , Pacientes , Neoplasias Cutáneas/tratamiento farmacológico
7.
Oral Dis ; 2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38155397

RESUMEN

OBJECTIVES: Periodontal ligament stem cells (PDLSCs) are essential for the treatment of bone diseases because of its great potential to differentiate into osteoblasts. Remarkably, increasing long-non-coding RNAs (lncRNAs) have been reported to be involved in the osteogenic differentiation of PDLSCs. Maternally expressed 8, small nucleolar RNA host gene (MEG8) is implicated in multiple diseases. This study intended to unearth the potential role of MEG8 and unveil the mechanism in PDLSCs undergoing osteoblastic differentiation. MATERIALS AND METHODS: MEG8 expression was measured by quantitative real-time PCR (RT-qPCR) during osteogenic differentiation of PDLSCs into bone cells. Functional assays were used to uncover the biological function of MEG8. Besides, RNA pulldown, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assays were used to explore the molecular mechanism of MEG8. RESULTS: MEG8 was apparently overexpressed in osteogenically differentiated PDLSCs. Moreover, MEG8 deficiency suppressed the osteoblastic differentiation of PDLSCs. Furthermore, MEG8 modulated the expression of transcription factor 4 (TCF4) by scavenging microRNA-495-3p (miR-495-3p) and microRNA-485-3p (miR-485-3p) through the competing endogenous RNA (ceRNA) mechanism, further stimulating the Wnt/ß-catenin pathway. CONCLUSION: MEG8 stimulates the capacity of PDLSCs for osteogenic differentiation through a ceRNA mode.

8.
Oral Dis ; 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37357358

RESUMEN

OBJECTIVE: Obesity can affect periodontal tissues and exacerbate periodontitis. Pyroptosis, a newly identified type of inflammatory cell death, is involved in the development of periodontal inflammation. The saturated fatty acid palmitic acid (PA) is elevated in obese patients. The effect of PA on pyroptosis in periodontal ligament cells (PDLCs) and its underlying mechanisms remain unknown. MATERIALS AND METHODS: Human PDLCs were isolated from healthy individuals and cultured for experiments. The effects of PA on PDLC pyroptosis and the underlying mechanisms were examined by transmission electron microscopy, quantitative real-time PCR and western blotting. RESULTS: The morphology of PDLCs in the PA group indicated pyroptotic characteristics, including swollen cells, plasma membrane rupture and changes in subcellular organelles. PA induced inflammatory responses in PDLCs, as indicated by an increase in IL-1ß in the cell culture supernatant. Furthermore, we found that the pyroptosis-related proteins caspase-1, caspase-4 and GSDMD were involved in PA-induced cell death. GSDMD and caspase-4 inhibitors alleviated pyroptotic death of PDLCs. Moreover, PA promoted NF-κB P65 phosphorylation. A NF-κB inhibitor decreased IL-1ß expression and partly rescued cell death induced by PA. CONCLUSION: PA activated the NF-κB pathway and induced the inflammatory response in PDLCs. Caspase-4/GSDMD mediated PDLC pyroptosis induced by PA.

9.
Int J Environ Health Res ; 33(5): 452-463, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35333137

RESUMEN

Although evidence showed the adverse effects of air pollution on cardiovascular disease (CVDs), few studies were based on medically insured populations. We applied a generalized additive Poisson model (GAM) to estimate the short-term effects of ambient air pollution on a group of medically insured population in Wuhan, China. We extracted daily air pollution data, meteorological data, and daily hospital visits for CVDs. We found that the ambient air pollutants sulfur dioxide (SO2), nitrogen dioxide (NO2), ground-level ozone (O3) particulate matter (PM) with an aerodynamic diameter ≤10 µm (PM10), and those ≤2.5 µm (PM2.5) all increased the risk of daily hospital visits for CVDs. We also found that the effect of air pollution on daily hospital visits for CVDs is greater in the cold season than in the warm season. Our findings can be used as evidence that supports the formulation of policies for air pollution and CVDs.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Enfermedades Cardiovasculares , Seguro , Humanos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , China/epidemiología , Dióxido de Nitrógeno/análisis
10.
BMC Oral Health ; 23(1): 130, 2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36890501

RESUMEN

OBJECTIVES: This study aimed to determine the prevalence and independent risk factors of SDB, and explore its association with malocclusion among 6-11-year-old children in Shanghai, China. METHODS: A cluster sampling procedure was adopted in this cross-sectional study. Pediatric Sleep Questionnaire (PSQ) was applied to evaluate the presence of SDB. Questionnaires including PSQ, medical history, family history, and daily habits/environment were completed by parents under instruction, and oral examinations were implemented by well-trained orthodontists. Multivariable logistic regression was applied to identify independent risk factors for SDB. Chi-square tests and Spearman's Rank Correlation were used to estimate the relationship between SDB and malocclusion. RESULTS: A total of 3433 subjects (1788 males and 1645 females) were included in the study. The SDB prevalence was about 17.7%. Allergic rhinitis (OR 1.39, 95% CI 1.09-1.79), adenotonsillar hypertrophy (OR 2.39, 95% CI 1.82-3.19), paternal snoring (OR 1.97, 95% CI 1.53-2.53), and maternal snoring (OR 1.35, 95% CI 1.05-1.73) were independent risk factors for SDB. The SDB prevalence was higher in children with retrusive mandibles than in proper or excessive ones. No significant difference was observed in the correlation between SDB and lateral facial profile, mandible plane angle, constricted dental arch form, the severity of anterior overjet and overbite, degree of crowding and spacing, and the presence of crossbite and open bite. CONCLUSIONS: The prevalence of SDB in primary students in the Chinese urban population was high and highly associated with mandible retrusion. The independent risk factors included Allergic rhinitis, adenotonsillar hypertrophy, paternal snoring, and maternal snoring. More efforts should be made to enhance public education about SDB and related dental-maxillofacial abnormalities.


Asunto(s)
Maloclusión , Síndromes de la Apnea del Sueño , Masculino , Femenino , Humanos , Niño , Ronquido/complicaciones , Ronquido/epidemiología , Estudios Transversales , China/epidemiología , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/epidemiología , Maloclusión/complicaciones , Maloclusión/epidemiología , Factores de Riesgo , Hipertrofia/complicaciones , Encuestas y Cuestionarios
11.
J Environ Sci (China) ; 130: 75-84, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37032044

RESUMEN

Beijing-Tianjin-Hebei and its surrounding areas (hereinafter referred to as "2+26" cities) are one of the most severe air pollution areas in China. The fine particulate matter (PM2.5) and surface ozone (O3) pollution have aroused a significant concern on the national scale. In this study, we analyzed the pollution characteristics of PM2.5 and O3 in "2+26" cities, and then estimated the health burden and economic loss before and after the implementation of the joint PM2.5-O3 control policy. During 2017-2019, PM2.5 concentration reduced by 19% while the maximum daily 8 hr average (MDA8) O3 stayed stable in "2+26" cities. Spatially, PM2.5 pollution in the south-central area and O3 pollution in the central region were more severe than anywhere else. With the reduction in PM2.5 concentration, premature deaths from PM2.5 decreased by 18% from 2017 to 2019. In contrast, premature deaths from O3 increased by 5%. Noticeably, the huge potential health benefits can be gained after the implementation of a joint PM2.5-O3 control policy. The premature deaths attributed to PM2.5 and O3 would be reduced by 91.6% and 89.1%, and the avoidable economic loss would be 60.8 billion Chinese Yuan (CNY), and 68.4 billion CNY in 2035 compared with that in 2019, respectively. Therefore, it is of significance to implement the joint PM2.5-O3 control policy for improving public health and economic development.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Beijing , Contaminantes Atmosféricos/análisis , Mejoramiento de la Calidad , Monitoreo del Ambiente , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , Material Particulado/análisis , China , Ciudades , Políticas
12.
Angew Chem Int Ed Engl ; 62(16): e202300654, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36811228

RESUMEN

A series of vanadyl complexes bearing 3-t-butyl-5-bromo, 3-aryl-5-bromo, 3,5-dihalo-, and benzo-fused N-salicylidene-tert-leucinates was examined as catalysts for 1,2-alkoxy-phosphinoylation of 4-, 3-, 3,4-, and 3,5-substituted styrene derivatives (including Me/t-Bu, Ph, OR, Cl/Br, OAc, NO2 , C(O)Me, CO2 Me, CN, and benzo-fused) with HP(O)Ph2 in the presence of t-BuOOH (TBHP) in a given alcohol or cosolvent with MeOH. The best scenario involved the use of 5 mol % 3-(2,5-dimethylphenyl)-5-Br (i.e., 3-DMP-5-Br) catalyst at 0 °C in MeOH. The desired catalytic cross coupling reactions proceeded smoothly with enantioselectivities of up to 95 % ee of (R)-configuration as confirmed by X-ray crystallographic analysis of several recrystallized products. The origin of enantiocontrol and homolytic substitution of the benzylic intermediates by vanadyl-bound methoxide and radical type catalytic mechanism were proposed.

13.
Angew Chem Int Ed Engl ; 62(5): e202212011, 2023 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-36347780

RESUMEN

Synthetic single-stranded (ss) DNA is a cornerstone for life and materials science, yet the purity, quantity, length, and customizability of synthetic DNA are still limiting in various applications. Here, we present PECAN, paired-end cutting assisted by DNAzymes (DNA enzymes or deoxyribozymes), which enables mass production of ssDNA of arbitrary sequence (up to 7000 nucleotides, or nt) with single-base precision. At the core of PECAN technique are two newly identified classes of DNAzymes, each robustly self-hydrolyzing with minimal sequence requirement up- or down-stream of its cleavage site. Flanking the target ssDNA with a pair of such DNAzymes generates a precursor ssDNA amplifiable by pseudogene-recombinant bacteriophage, which subsequently releases the target ssDNA in large quantities after efficient auto-processing. PECAN produces ssDNA of virtually any terminal bases and compositions with >98.5 % purity at the milligram-to-gram scale. We demonstrate the feasibility of using PECAN ssDNA for RNA in situ detection, homology-directed genome editing, and DNA-based data storage.


Asunto(s)
ADN Catalítico , ADN de Cadena Simple , ADN Catalítico/metabolismo , ADN , ARN , Nucleótidos
14.
J Cell Mol Med ; 26(16): 4401-4415, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35775112

RESUMEN

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas Musculares/metabolismo , Factor de Transcripción Activador 2/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Transducción de Señal
15.
J Am Chem Soc ; 144(36): 16598-16603, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36040192

RESUMEN

The excellent programmability and modifiability of DNA has enabled chemists to reproduce a series of specific molecular interactions in self-assembled synthetic systems. Among diverse modifications, cholesterol conjugation can turn DNA into an amphiphilic molecule (cholesterol-DNA), driving the formation of DNA assemblies through the cholesterol-endowed hydrophobic interaction. However, precise control of such an assembly process remains difficult because of the unbiased accumulation of cholesterol. Here, we report the serendipitous discovery of the favored tetramerization of cholesterol in cholesterol-DNA copolymers that carry the cholesterol modification at the blunt end of DNA. The discovery expands the repertoire of controllable molecular interactions by DNA and provides an effective way to precisely control the hydrophobic stacking of cholesterol for programmed cholesterol-DNA assembly.


Asunto(s)
ADN , Polímeros , Colesterol/química , ADN/química , Interacciones Hidrofóbicas e Hidrofílicas , Polímeros/química
16.
Microb Cell Fact ; 21(1): 4, 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983528

RESUMEN

Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC-MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 µg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Antibacterianos/uso terapéutico , Bacillus/química , Bacillus/enzimología , Proteínas Bacterianas/química , Proteínas Bacterianas/aislamiento & purificación , China , Cromatografía Liquida , Farmacorresistencia Bacteriana Múltiple , Femenino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Espectrometría de Masas en Tándem
17.
Dermatol Ther ; 35(11): e15821, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36114601

RESUMEN

Vitiligo is a chronic treatment-resistant autoimmune disorder characterized by circumscribed depigmented maculae. This study was conducted to evaluate the efficacy and safety of tofacitinib combined with narrowband ultraviolet B (NB-UVB) phototherapy for refractory nonsegmental vitiligo. Fifteen patients with nonsegmental vitiligo resistant to conventional therapies were administered oral tofacitinib at 5 mg twice daily plus topical halometasone cream, tacrolimus 0.1% ointment, or pimecrolimus cream twice daily and NB-UVB three times per week for 16 weeks. The control group comprised 19 patients with nonsegmental vitiligo treated with topical drugs plus NB-UVB same as the combination group. Treatment efficacy was measured by the percentage of repigmentation of vitiligo lesions at 4th, 8th, 12th, and 16th week after beginning treatment. From 8th week, the repigmentation level was significantly higher in the combination group than in the controls. From fourth week, the response rate was significantly higher in the combination group than in the controls. Only one patient in the combination group reported mild pain in the hand and foot joints, but the pain subsided with cessation of therapy. No other severe adverse effects occurred. So, tofacitinib in combination with NB-UVB phototherapy may be an effective and safe alternative modality for refractory vitiligo.


Asunto(s)
Terapia Ultravioleta , Vitíligo , Humanos , Vitíligo/diagnóstico , Vitíligo/radioterapia , Estudios Prospectivos , Terapia Ultravioleta/efectos adversos , Resultado del Tratamiento , Emolientes/uso terapéutico , Enfermedad Crónica , Dolor/etiología , Terapia Combinada , Fototerapia/efectos adversos
18.
BMC Geriatr ; 22(1): 380, 2022 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-35488207

RESUMEN

BACKGROUND: Previous studies suggest that retirement, a major life event, affects overall healthcare utilization. We examine, the effects of retirement on inpatient healthcare utilization, including effect heterogeneity by gender, disease category, and type of health service. METHODS: We used routine health insurance claims data (N = 87,087) spanning the period 2021 - September 2013 from the Urban Employee Basic Medical Insurance (UEBMI), a mandatory social health insurance for working and retired employees in urban China. We applied a non-parametric fuzzy regression discontinuity design using the statutory retirement age in urban China as an exogenous instrument to measure the causal effect of retirement on six measures of inpatient healthcare utilization. RESULTS: Retirement reduced total hospital costs (-84.71 Chinese Yuan (CNY), 95% confidence interval (CI) -172.03 - 2.61), shortened length of hospital stays (-44.59, 95% CI -70.50 - -18.68), and increased hospital readmissions (0.06, 95% CI 0.00 - 0.12) and primary hospital visits (0.06, 95% CI 0.02 - 0.09) among women. Retirement did not significantly change inpatient healthcare utilization among men. The retirement effects among women varied by disease category. Specifically, retirement substantially increased hospitalizations for non-communicable diseases (NCDs), yet had only modest or no effect on hospitalizations for communicable diseases or injuries. Retirement effects among women also varied by the type of services. For relatively inexpensive services, such as nonoperative treatment, there were surges in the extensive margin (hospital readmission). For relatively expensive and invasive services, such as surgeries, retirement reduced the intensive margin (out-of-pocket expenditures and length of stay). CONCLUSIONS: Retirement decreases overall use of inpatient healthcare for women. The examination on the disease-related heterogeneous effects helps with the introduction and implementation of integrated healthcare delivery and appropriate incentive schemes to encourage better use of healthcare resources among older adults.


Asunto(s)
Pacientes Internos , Jubilación , Anciano , China/epidemiología , Atención a la Salud , Femenino , Humanos , Seguro de Salud , Masculino , Aceptación de la Atención de Salud
19.
Clin Oral Investig ; 26(5): 4137-4145, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35254527

RESUMEN

OBJECTIVES: The purpose of this study was to investigate the prevalence of alveolar bone dehiscence and fenestration of Class I individuals with normality patterns in the anterior region using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 4715 retrospective cases from January 2018 to December 2020 in the Orthodontic Department of xxx Hospital were screened. Sixty-one cases were Class I individuals with normality patterns in the anterior region. Their incidence of dehiscence and fenestration in the anterior teeth region was studied and statistically analyzed. RESULTS: Dehiscence was found in 27.46% of the evaluated anterior teeth and fenestration was found in 26.91% of anterior teeth. Severe dehiscences and fenestrations mainly occurred in mandibular canines and maxillary canines, respectively. Alveolar bone defects were present in 100% of patients, while one patient had alveolar bone defects in 91.67% of the anterior teeth. CONCLUSIONS: Dehiscence was found in 27.46% of the anterior teeth of Class I individuals with normality patterns, while fenestration was found in 26.91% of them. Alveolar bone defects were present in 100% of patients. CLINICAL RELEVANCE: Alveolar bone dehiscence and fenestration were normal and common in our sample, indicating that they are more likely to be physiological rather than pathological defects. Orthodontists should be aware of the presence and severity of these defects before treatment in order to avoid both possible complications and overtreatment.


Asunto(s)
Proceso Alveolar , Tomografía Computarizada de Haz Cónico Espiral , Tomografía Computarizada de Haz Cónico , Diente Canino/diagnóstico por imagen , Humanos , Maxilar , Estudios Retrospectivos
20.
Sensors (Basel) ; 22(9)2022 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-35590962

RESUMEN

The feeding behaviour of cows is an essential sign of their health in dairy farming. For the impression of cow health status, precise and quick assessment of cow feeding behaviour is critical. This research presents a method for monitoring dairy cow feeding behaviour utilizing edge computing and deep learning algorithms based on the characteristics of dairy cow feeding behaviour. Images of cow feeding behaviour were captured and processed in real time using an edge computing device. A DenseResNet-You Only Look Once (DRN-YOLO) deep learning method was presented to address the difficulties of existing cow feeding behaviour detection algorithms' low accuracy and sensitivity to the open farm environment. The deep learning and feature extraction enhancement of the model was improved by replacing the CSPDarknet backbone network with the self-designed DRNet backbone network based on the YOLOv4 algorithm using multiple feature scales and the Spatial Pyramid Pooling (SPP) structure to enrich the scale semantic feature interactions, finally achieving the recognition of cow feeding behaviour in the farm feeding environment. The experimental results showed that DRN-YOLO improved the accuracy, recall, and mAP by 1.70%, 1.82%, and 0.97%, respectively, compared to YOLOv4. The research results can effectively solve the problems of low recognition accuracy and insufficient feature extraction in the analysis of dairy cow feeding behaviour by traditional methods in complex breeding environments, and at the same time provide an important reference for the realization of intelligent animal husbandry and precision breeding.


Asunto(s)
Algoritmos , Conducta Alimentaria , Animales , Bovinos , Granjas , Femenino , Reconocimiento en Psicología , Semántica
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