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1.
Nat Rev Mol Cell Biol ; 23(4): 286-301, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34815573

RESUMO

Double-stranded RNA (dsRNA) is associated with most viral infections - it either constitutes the viral genome (in the case of dsRNA viruses) or is generated in host cells during viral replication. Hence, nearly all organisms have the capability of recognizing dsRNA and mounting a response, the primary aim of which is to mitigate the potential infection. In vertebrates, a set of innate immune receptors for dsRNA induce a multitude of cell-intrinsic and cell-extrinsic immune responses upon dsRNA recognition. Notably, recent studies showed that vertebrate cells can accumulate self-derived dsRNAs or dsRNA-like species upon dysregulation of several cellular processes, activating the very same immune pathways as in infected cells. On the one hand, such aberrant immune activation in the absence of infection can lead to pathogenesis of immune disorders, such as Aicardi-Goutières syndrome. On the other hand, the same innate immune reaction can be induced in a controlled setting for a therapeutic benefit, as occurs in immunotherapies. In this Review, we describe mechanisms by which immunostimulatory dsRNAs are generated in mammalian cells, either by viruses or by the host cells, and how cells respond to them, with the focus on recent developments regarding the role of cellular dsRNAs in immune modulation.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Malformações do Sistema Nervoso , Viroses , Animais , Imunidade Inata , Mamíferos , RNA de Cadeia Dupla , Viroses/genética , Replicação Viral
2.
Pol J Vet Sci ; 25(1): 61-65, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35575992

RESUMO

Information regarding the correct pedigree of and relationship between animals is useful for managing dairy breeding, reducing inbreeding, estimating breeding value, and establishing correct breeding programs. Additionally, the successful implementation of progeny testing is crucial for improving the genetics of dairy cattle, which depends on the availability of correct pedigree information. Incorrect pedigree information leads to bias in bull evaluation. In this study, Neogen GeneSeek Genomic Profiler (GGP) 50K SNP chips were used to identify and verify the sire of Taiwanese Holstein dairy cattle and analyze the reasons that lead to incorrect sire records. Samples were collected from 2,059 cows of 36 dairy farms, and the pedigree information was provided by breeders. The results of sire verification can be divided into three categories: submitted unconfirmed sire, submitted confirmed sire, and incorrectly submitted verified sire. Data on the sires of 1,323 (64.25%) and 572 (27.78%) dairy cows were verified and discovered, respectively. Sires of 1,895 (92.03%) dairy cattle were identified, which showed that the paternal pedigree of dairy cattle could be discovered and verified through genetic testing. An error-like analysis revealed that the data of 37 sires were incorrectly recorded because the bull's NAAB code number was incorrectly entered into the insemination records: for 19 sires, the wrong bull was recorded because the frozen semen of a bull placed in the wrong storage tank was used, 6 had no sire records, and for 12 sires, the NAAB code of the correct bull was recorded but with a wrong stud code, marketing code, or unique number for the stud or breed. To reduce recorded sire error rates by at least 27.78%, automated identification of the mated bull must be adopted to reduce human error and improve dairy breeding management on dairy farms.

3.
Water Sci Technol ; 85(9): 2463-2478, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35576248

RESUMO

To obtain an efficient and low-cost adsorbent for the Sb(V) removal in Sb(V)-contaminated water, a novel composite manganese oxide/oxyhydroxide (CMO) was synthesized by a simple hydrothermal synthesis method. The synthesized adsorbent was characterized via scanning electron microscopy, X-ray diffraction, transmission electron microscopy, Brunauer-Emmett-Teller surface area, Fourier transform infrared, and X-ray photoelectron spectroscopy analyses. The results revealed that the as-prepared CMO adsorbent possessed a porous structure consisting of Mn3O4 nanoparticles and MnOOH nanorods. Batch experiments showed that the adsorption behaviours were well fitted by the Langmuir isotherm and the pseudo-second-order kinetic model, reaching the maximum adsorption capacity of 119.63 mg/g at 25 °C. The application of CMO adsorbent showed that the Sb(V) removal efficiency in 6.24 L Sb(V)-containing water with a concentration of 3.6 mg/L was more than 90%. The reusability of CMO adsorbent demonstrated that the Sb(V) removal efficiency was still more than 80% even after five times of regeneration. The adsorption mechanism for Sb(V) can be described as ligand exchange between hydroxyl groups on the adsorbent surface and hydroxyl groups in Sb(OH)6- molecules by forming inner-sphere complexes. Those results suggested that the CMO adsorbent can be considered as a potential adsorbent to remove Sb(V) from contaminated water.

4.
Artigo em Chinês | MEDLINE | ID: mdl-35527437

RESUMO

Objective: Functional near-infrared spectroscopy (fNIRS) was used to study the effect of aging on the neuroimaging characteristics of cerebral cortex in the process of speech perception. Method: Thirty-four adults with normal hearing were recruited from March 2021 to June 2021, including 17 in the young group, with 6 males, 11 females, age (32.1±5.0) years, age range 20-39 years. and 17 in the elderly group, with 6 males, 11 females, age (63.2±2.8) years, age range 60-70 years. The test material was the sentence table of the Mandarin Hearing Test in Noise (MHINT). The task state block experiment design was adopted, and the temporal lobe, Broca's area, Wernicke's area, motor cortex were used as regions of interest. Objective brain imaging technology (fNIRS) combined with subjective psychophysical testing method was used to analyze the activation area and degree of cerebral cortex related to auditory speech perception in the elderly and young people under different listening conditions (quiet, signal-to-noise ratio of 10 dB, 5 dB, 0 dB, -5 dB). SPSS 23 software was used for statistical analysis. Result: The activation area and degree of activation in the elderly group were lower than those in the young group under each task condition; The number of activation channels in the young group were significantly more than those in the old group, and the number of activation channels in the left hemisphere were more than those in the right hemisphere, but there was no difference in the number of activation channels. There were more channels affected by age in the left hemisphere than in the right hemisphere. The activation degree of the young group when the signal-to-noise ratio was 0 dB was significantly higher than that of other signal-to-noise ratio conditions (P<0.05), but there was no significant difference in the old group under the five conditions (P>0.05). The speech recognition score of the young group was higher than that of the old group under all conditions. When the quiet and signal-to-noise ratio was 10 dB, the correct score of the two groups was equal or close to 100%. With the gradual decrease of signal-to-noise ratio, there was a significant difference between the two groups when the signal-to-noise ratio was 5 dB. The speech recognition accuracy of the young group decreased significantly when the signal-to-noise ratio was 0 dB, while that of the old group decreased significantly when the signal-to-noise ratio was 5 dB. Conclusions: With the increase of age, the speech perception in noisy environment and the activity of cerebral cortex gradually deteriorate, and the speech dominance hemisphere (left hemisphere) will be significantly affected by aging. The overall activation area and activation degree of the elderly under different speech tasks are lower than those of the young.


Assuntos
Córtex Auditivo , Percepção da Fala , Estimulação Acústica/métodos , Adolescente , Adulto , Idoso , Córtex Auditivo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Luz Próxima ao Infravermelho , Percepção da Fala/fisiologia , Tecnologia , Adulto Jovem
5.
Artigo em Chinês | MEDLINE | ID: mdl-35527440

RESUMO

Objective: To investigate the sensitization characteristics of Juniperus chinensis pollen in patients with allergic rhinitis and/or allergic asthma in Beijing area, and to explore the characteristics of Juniper chinensis pollen sensitized population. Methods: Patients with suspected allergic rhinitis and/or asthma from January 2017 to December 2019 in the outpatient department of Allergy Department of Beijing Shijitan Hospital were selected in this study. Skin prick test (SPT) was performed with Juniper chinensis pollen allergen reagent to compare different age and disease allergen distribution, and to observe the sensitization characteristics of its population. All of the analyses were performed using SAS software version 9.4. Results: A total of 8 380 patients were enrolled in the end. The total positive rate of Juniper chinensis pollen SPT reached 49.92% (4 183/8 380). The positive rate of Juniper chinensis pollen SPT was highest in the 10-14 age group, reaching 60.99% (283/464). Compared with other age groups, there was a statistical difference (χ²=266.77, P<0.01). The SPT positive rate of patients aged less than 10 years increased with the increase of age, while the SPT positive rate of patients aged over 40 years decreased with the increase of age. Single Juniper chinensis pollen was less allergenic, accounting for about 25.05% (1 048/4 183), and the patients' age was (35.21±12.39) years. Regardless of single Juniper chinensis pollen or other pollen allergies, allergic rhinitis was the main disease. Among the patients with SPT positive Juniper chinensis pollen combined with other inhaled pollen allergens, willow pollen accounted for the first (74.99%). The positive rate of Juniper chinensis pollen was the highest in patients with single allergic rhinitis, accounting for 52.05% (3 797/7 295), and the rate in patients with single allergic asthma was the lowest, accounting for 17.49% (53/303), with statistically difference (χ²=138.99, P<0.01). Conclusions: Juniper chinensis pollen is highly sensitized in patients with allergic rhinitis and/or allergic asthma in Beijing . The positive rate of SPT is highest among 10-14 age group, most of which showed strong positive reaction, and allergic rhinitis is more common in Juniper chinensis pollen sensitization diseases.


Assuntos
Asma , Juniperus , Rinite Alérgica , Adolescente , Adulto , Alérgenos , Criança , Humanos , Pólen , Testes Cutâneos
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(5): 493-497, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35527464

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology, which was characterized by irreversible lung function decrease and high mortality. Up till now, only two drugs, i.e. Pirfenidone and Nintedanib,have been approved by Food and Drug Administration (FDA) for therapy of IPF, and the treatment is less effective. Therefore, it is urgent to develop new therapeutic drugs. In recent years, studies had paid attention to lipid metabolism in IPF. In this review, we discussed recent major advances of lipid metabolism, biomarkers and clinical trials in IPF.


Assuntos
Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Metabolismo dos Lipídeos , Pulmão , Piridonas/uso terapêutico
7.
Front Oncol ; 12: 822469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530342

RESUMO

Primary pulmonary EWS/PNET(PPES) is extremely rare and is associated with a poor prognosis. Tumor angiogenesis plays an important role in tumor, so it has become a hot topic in molecular targeted therapy. Anlotinib is a new oral small molecular multi-targeted receptor tyrosine kinase (RTK) inhibitor. This report describes a 20 year-old man with PPES. After 4 neoadjuvant chemotherapy cycles (VACwith alternating IE) combined with anlotinib, the left total pneumonectomy was performed. Then maintenance anlotinib monotherapy was continued, no sign of recurrence to date as an outcome. To our knowledge, this is the first demonstration of anlotinib combined with neoadjuvant chemotherapy efficacy in PPES.

8.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(4): 584-590, 2022 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-35527495

RESUMO

OBJECTIVE: To explore the effect of inhibiting polyribonucleotide nucleotidyl-transferase 1 (PNPT1) on oxygen-glucose deprivation (OGD)-induced apoptosis of mouse atrial myocytes. METHODS: Cultured mouse atrial myocytes (HL-1 cells) with or without OGD were transfected with PNPT1-siRNA or a negative control siRNA (NC-siRNA group), and the cell survival rate was detected using CCK-8 assay. The expression levels of ACTB and TUBA mRNA were detected with qPCR, and the protein expression of PNPT1 was detected with Western blotting. The apoptosis rate of the treated cells was determined with flow cytometry, the mitochondrial membrane potential was detected using JC-1 kit, and the mitochondrial morphology was observed using transmission electron microscope. RESULTS: With the extension of OGD time, the protein expression levels of PNPT1 increased progressively in the cytoplasm of HL-1 cells (P < 0.05). Transfection with PNPT1-siRNA significantly reduced PNPT1 expression in HL-1 cells (P < 0.05). Exposure to OGD significantly enhanced degradation of ACTB and TUBA mRNA (P < 0.05) and markedly increased the apoptosis rate of HL-1 cells (P < 0.05), and these changes were significantly inhibited by transfection with PNPT1-siRNA (P < 0.05), which obviously increased mitochondrial membrane potential and improved mitochondrial morphology of HL-1 cells exposed to OGD. CONCLUSION: Inhibition of PNPT1 improves mitochondrial damage and reduces degradation of apoptotic-associated mRNAs to alleviate OGD-induced apoptosis of mouse atrial myocyte.


Assuntos
Glucose , Oxigênio , Animais , Apoptose , Sobrevivência Celular , Glucose/farmacologia , Camundongos , Miócitos Cardíacos , Oxigênio/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
9.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 34(2): 122-127, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35537833

RESUMO

OBJECTIVE: To analyze the trends of human schistosomiasis prevalence in Hubei Province from 2004 to 2018, so as to provide the evidence for formulating the schistosomiasis elimination strategy in the province. METHODS: All data pertaining to human schistosomiasis prevalence in Hubei Province were collected from 2004 to 2018, and the trends for changes in seroprevalence, egg-positive rate and prevalence of human Schistosoma japonicum infection were analyzed using a Joinpoint regression model. RESULTS: Both of the numbers of residents seropositive and egg-positive for S. japonicum infections appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the prevalence of human S. japonicum infections reduced from 6.85% in 2004 to 0 in 2018. Joinpoint regression analysis showed that the prevalence of human S. japonicum infections appeared an overall tendency towards a reduction in Hubei Province from 2004 to 2018 [average annual percent change (AAPC) = -24.1%, P < 0.01], and the trends for the reduction were both significant during the period from 2004 to 2006 [annual percent change (APC) = -35.1%, P < 0.01] and from 2006 to 2018 (APC = -22.1%, P < 0.01). The prevalence of human S. japonicum infections appeared a tendency towards a decline in islet (AAPC = -25.1%, P < 0.01), inner embankment (AAPC = -26.4%, P < 0.01) and hilly subtypes of schistosomiasis-endemic areas (AAPC = -32.5%, P < 0.01) of Hubei Province from 2004 to 2018, and the prevalence all appeared a tendency towards a decline during the infection control stage (from 2004 to 2008), the transmission control stage (from 2009 to 2013) and the transmission interruption stage (from 2014 to 2018) (AAPC = -28.0%, -24.4% and -63.8%, all P values < 0.01). The seroprevalence of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = -14.5%, P < 0.01), and the trends for the reduction were both significant during the period from 2004 to 2012 (APC = -8.4%, P < 0.01) and from 2012 to 2018 (APC = -22.1%, P < 0.01). In addition, the egg-positive rate of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = -30.6%, P < 0.05), and the trend for the reduction was significant during the period from 2007 to 2014 (APC = -15.5%, P < 0.01). CONCLUSIONS: The prevalence of human schistosomiasis appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the islet and inner embankment subtypes of endemic areas are a high priority for schistosomiasis control during the stage moving towards elimination in Hubei Province.


Assuntos
Esquistossomose Japônica , Esquistossomose , Animais , China/epidemiologia , Humanos , Prevalência , Análise de Regressão , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose Japônica/epidemiologia , Estudos Soroepidemiológicos , Caramujos
10.
Ann Oncol ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35513244

RESUMO

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on down staging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov (KS) test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n=72) and corresponding controls (n=282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n=947) were used as validation sets to assess the performance of TES. We compared TES to KS, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with permutation test. RESULTS: In the validation set, TES identified arms with higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if pCR rate improved. The correlation between TES and survival was higher than the correlation between pCR rate difference and survival. CONCLUSION: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

11.
Opt Lett ; 47(10): 2518-2521, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561390

RESUMO

Lissajous structured beams emerging from a spherical laser cavity subject to the birefringent effect of the laser crystal are quantitatively analyzed. The analysis reveals that the birefringent effect leads to numerous frequency degeneracies at the cavity lengths near an ideal degenerate cavity. By using a diode-pumped Nd:GdVO4 laser, the emergence of Lissajous structured modes relevant to frequency degeneracies is precisely quantified by comparing experimental results with numerical analyses. The present quantitative analysis provides an important guideline for the generation of structured transverse modes related to the ray-wave correspondence.

12.
Zhonghua Yi Shi Za Zhi ; 52(1): 48-57, 2022 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-35570357

RESUMO

Tongji Medical College began its "education Long March" after the Battle of Shanghai in 1937, with six westward migrations across almost 10,000 kilometers over eight years. It first moved to the city of Shanghai because Tongji Medical College had to rent space in Shanghai, then moved to Jinhua in Zhejiang Province soon afterwards. After that it migrated to Ganzhou and Jian in Jiangxi Province, then He County in Guangxi Province and Kunming in Yunnan Province, ultimately locating in Li Village in Sichuan Province. Tongji Medical College was operated by Chinese and implemented high-level administration and teaching under the difficult conditions during the Anti-Japanese War. As a result, Tongji Medical College made advances in the medical field, such those by Professor Wu Mengchao. It also made advancements in research and treatment, such as identifying pathogenesis of a local epidemic and offering some treatment methods, and popularised medical knowledge for local people by exhibitions and news paper columns. It also established the Number One and the Number Five UMC Trauma Centre, participating in battlefield treatment. The German teachers of Tongji Medical College, who did not move to the west, established a German Medical School in Shanghai. Tongji Medical College returned back to Shanghai, incorporating the German Medical School in Shanghai after the Anti-Japanese War.

13.
Aust Vet J ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35560033

RESUMO

AIMS: To investigate the relative differences in the perceptions and awareness of outbreaks of photosensitisation in Australian livestock stakeholders, including veterinarians, livestock traders and producers. METHODS: A questionnaire was developed and circulated to livestock veterinarians, producers and traders in Australia via email addresses obtained from public access sources. The questionnaire was designed to evaluate participants' awareness and perception of health, welfare, and production issues associated with outbreaks of photosensitisation and towards the incidence and importance of photosensitisation in livestock. RESULTS: One hundred and twenty-eight online responses were received in total. Nearly half of the respondents (49.0%) indicated they would encounter 1-3 outbreaks annually. The majority of veterinarian and livestock producers stated that outbreaks of photosensitisation were common and economically important, with cattle and sheep being equally considered as susceptible species to this condition, and secondary (hepatogeneous) photosensitisation is the most common type. CONCLUSION: This survey confirms the anecdotal evidence that photosensitisation in livestock in Australia is commonly encountered by veterinarians and livestock producers. However, there is no industry-wide common acceptance of the issue, broader opinions should be canvassed when considering impacts on stakeholders regarding photosensitisation outbreaks in livestock in Australia or abroad in the future.

15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(3): 270-279, 2022 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-35381647

RESUMO

Objective: To investigate the influence and critical windows of prenatal exposure to pyrethroid pesticides (PYRs) on neurodevelopment of 2-year-old children. Methods: The subjects of this study were derived from the Xuanwei Birth Cohort. A total of 482 pregnant women who participated in the rural district of Xuanwei birth cohort from January 2016 to December 2018 were included. Maternal urinary concentrations of PYRs metabolites during 8-12 gestational weeks, 20-23 gestational weeks and 32-35 gestational weeks were measured with ultra high performance liquid chromatography system coupled with a tandem mass spectrometry detector. Child neurodevelopment was evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Multivariate linear regression models and binary logistic regression models were used to assess the association between PYRs exposure during pregnancy and children's neurodevelopment. Results: A total of 360 mother-child pairs had complete data on maternal urinary PYRs metabolites detection and children's neurodevelopment assessment. The detection rate of any one PYRs metabolites during the first, second and third trimester were 93.6% (337/360), 90.8% (327/360) and 94.2% (339/360), respectively. The neurodevelopmental scores of Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior of 2-year-old children were (102.3±18.9), (100.2±16.3), (102.0±20.3), (107.8±23.3) and (85.8±18.6) points, respectively. After controlling for confounding factors, 4-fluoro-3-phenoxybenzoic acid (4F3PBA, one of PYRs metabolites) exposure in the first trimester reduced Motor (ß=-5.02, 95%CI: -9.08, -0.97) and Adaptive Behavior (ß=-4.12, 95%CI:-7.92, -0.32) scores of 2-year-old children, and increased risk of developmental delay of adaptive behavior (OR=2.07, 95%CI:1.13-3.82). Conclusion: PYRs exposure during the first trimester of pregnancy may affect neurodevelopment of 2-year-old children, and the first trimester may be the critical window.


Assuntos
Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Piretrinas , Desenvolvimento Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Exposição Materna/efeitos adversos , Praguicidas/efeitos adversos , Gravidez , Terceiro Trimestre da Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Piretrinas/efeitos adversos , Piretrinas/metabolismo
16.
J Dent Res ; : 220345221085186, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35394372

RESUMO

Limited therapeutic options are available for treating deep caries. Those materials with potential of a dual effect to remineralize hard tissue and regenerate defective dentin tissues could be used as a new strategy for deep caries treatment. However, the application of the single component remains a challenge mainly because they lack calcium and phosphorus, are easily degraded, and are difficult to retain in the intricate body fluid environment. Considering the abundant source of calcium and phosphorus as well as the delivery performance of mesoporous bioactive glass (MBG), an amelogenin-derived peptide (QP5), which has a significant role in hard tissue remineralization, was loaded to fabricate a novel composite. After the synthesis of highly ordered MBG using a sol-gel method, the QP5 peptide was loaded increasingly by its extensive porous structure and enhanced electrostatic absorption. When used in an acidic environment, the MBG/QP5 composite presented pH-responsiveness, releasing therapeutic ions and functional peptides in a sequential cascade, and eventually adjusted the pH to a neutral state. The composite was internalized by dental pulp cells through a clathrin-mediated pathway and influenced by cell membrane lipid raft regulation. It could be also transported through the macro-pinocytotic pathway. Compared to the single treatment of peptide QP5 in 48 h, the composite facilitated a higher level of retention of the intracellular peptides. The composite further promoted migration and odontogenesis of dental pulp cells, including the improved activity of alkaline phosphatase, increased formation of mineralized nodules, and upregulated expression of mineralization-related genes compared to using MBG or QP5 alone. The composite further induced the dentin-like layer in a rat pulp capping model. The results suggested that this intelligent material with pH-responsiveness provides a promising alternative treatment method for biomimetic restoration of deep caries.

17.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(3): 321-329, 2022 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-35426794

RESUMO

OBJECTIVE: To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism. METHODS: Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq). RESULTS: Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level. CONCLUSION: LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.


Assuntos
Lipopolissacarídeos , Fator de Necrose Tumoral alfa , Acetilação , Animais , Mediadores da Inflamação , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Fator de Necrose Tumoral alfa/metabolismo
18.
Stem Cells ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429397

RESUMO

Lung maturation is not limited to proper structural development, but also includes differentiation and functionality of various highly specialized alveolar cell types. Alveolar type 1 cells (AT1s) occupy nearly 95% of the alveolar surface and are critical for establishing efficient gas exchange in the mature lung. AT1 cells arise from progenitors specified during the embryonic stage as well as alveolar epithelial progenitors expressing surfactant protein C (Sftpc pos cells) during postnatal and adult stages. Previously, we found that Wnt5a, a non-canonical Wnt ligand, is required for differentiation of AT1 cells during the saccular phase of lung development. To further investigate the role of Wnt5a in AT1 cell differentiation, we generated and characterized a conditional Wnt5a gain-of-function mouse model. Neonatal Wnt5a gain-of-function disrupted alveologenesis through inhibition of cell proliferation. In this setting Wnt5a downregulated beta-catenin-dependent canonical Wnt signaling, repressed AT2 (anti-AT2) and promoted AT1 (pro-AT1) lineage-specific gene expression. In addition, we identified two subpopulations of Sftpc high and Sftpc low alveolar epithelial cells. In Sftpc low cells, Wnt5a exhibits pro-AT1 and anti-AT2 effects, concurrent with inhibition of canonical Wnt signaling. Interestingly, in the Sftpc high subpopulation, although increasing AT1 lineage-specific gene expression, Wnt5a gain-of-function did not change AT2 gene expression, nor inhibit canonical Wnt signaling. Using primary epithelial cells isolated from human fetal lungs we demonstrate that this property of Wnt5a is evolutionarily conserved. Wnt5a therefore serves as a selective regulator that ensures proper AT1/AT2 balance in the developing lung.

19.
Phys Rev Lett ; 128(14): 142001, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35476477

RESUMO

The singly Cabibbo-suppressed decay Λ_{c}^{+}→nπ^{+} is observed for the first time with a statistical significance of 7.3σ by using 3.9 fb^{-1} of e^{+}e^{-} collision data collected at center-of-mass energies between 4.612 and 4.699 GeV with the BESIII detector at BEPCII. The branching fraction of Λ_{c}^{+}→nπ^{+} is measured to be (6.6±1.2_{stat}±0.4_{syst})×10^{-4}. By taking the upper limit of branching fractions of Λ_{c}^{+}→pπ^{0} from the Belle experiment, the ratio of branching fractions between Λ_{c}^{+}→nπ^{+} and Λ_{c}^{+}→pπ^{0} is calculated to be larger than 7.2 at the 90% confidence level, which disagrees with most predictions of the available phenomenological models. In addition, the branching fractions of the Cabibbo-favored decays Λ_{c}^{+}→Λπ^{+} and Λ_{c}^{+}→Σ^{0}π^{+} are measured to be (1.31±0.08_{stat}±0.05_{syst})×10^{-2} and (1.22±0.08_{stat}±0.07_{syst})×10^{-2}, respectively, which are consistent with previous results.

20.
Phys Rev Lett ; 128(14): 142005, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35476485

RESUMO

The measurement of two-particle angular correlation functions in high-multiplicity e^{+}e^{-} collisions at sqrt[s]=10.52 GeV is reported. In this study, the 89.5 fb^{-1} of hadronic e^{+}e^{-} annihilation data collected by the Belle detector at KEKB are used. Two-particle angular correlation functions are measured in the full relative azimuthal angle (Δϕ) and three units of pseudorapidity (Δη), defined by either the electron beam axis or the event-shape thrust axis, and are studied as a function of charged-particle multiplicity. The measurement in the thrust axis analysis, with mostly outgoing quark pairs determining the reference axis, is sensitive to the region of additional soft gluon emissions. No significant anisotropic collective behavior is observed with either coordinate analyses. Near-side jet correlations appear to be absent in the thrust axis analysis. The measurements are compared to predictions from various event generators and are expected to provide new constraints to the phenomenological models in the low-energy regime.

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