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1.
Int J Dev Disabil ; 68(4): 495-499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937175

RESUMO

Objective: This study intends to explore the effect of parent-training program on the rehabilitation intervention in children with autism spectrum disorder (ASD) in Chinese-speaking areas of China by offering parent skill training and psychology counseling. Methods: From January 2018 to June 2019, a total of 80 children diagnosed with ASD from the Department of Children Healthcare of Wuxi Children's Hospital were randomly grouped into the parent training groups and control groups. Parents in the training group received 12 weeks of skill training, including 8 group and 2 individual training sessions, as well as psychology counseling. This enabled them to give their children >2 h of intervention training daily in a natural environment. Children in the control group were placed on a rehabilitation waiting list or received general community training. Before grouping and after the intervention, all children underwent neuropsychological evaluations with Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Gesell Developmental Schedule (GDS). GDS covers five sectors, namely adaptive behavior, gross motor, fine motor, language, and personal-social behavior. Results: Statistically significant differences were not detected between the two groups in ABC, CARS, and GDS scoring at baseline evaluation. And significant differences were detected between the two groups in ABC, CARS, adaptive behavior, and personal-social behavior scoring at endpoint evaluation. Furthermore, the re-evaluation results of ABC scoring and CARS scoring of the children in the parent training group decreased significantly from the preliminary evaluation results when compared before and after the intervention. Moreover, the intragroup comparison of adaptive behavior scoring, language scoring, and personal-social behavior scoring of the experiment group increased significantly from the preliminary evaluation results, while the difference of the same of the children in the control group between re-evaluation and preliminary evaluation did not differ significantly. Conclusions: In China, the parent-training program enables parents to train ASD children in a natural environment, which would markedly improve behavioral problems, core symptoms, adaptability, language competence, and social development capability.

2.
Cell Prolif ; : e13318, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35932176

RESUMO

OBJECTIVES: Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1α modRNA. MATERIALS AND METHODS: The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed. RESULTS: The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro. CONCLUSIONS: This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.

5.
Soc Sci Med ; 307: 115120, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35792410

RESUMO

RATIONALE: Vaccination uptake is a major strategy to prevent infection with SARS-CoV-2 and curb the transmission of COVID-19. However, many people remain unwilling to receive the COVID-19 vaccine. OBJECTIVE: Using default nudges, the present study examines (a) whether opt-out policy and its improvements could increase intention and attitude to get vaccinated and (b) whether these default effects differ across diverse risk-perception groups. METHOD: An online experiment with 1926 unvaccinated Chinese respondents was conducted in February 2021. We measured willingness to be vaccinated after informing opt-in policy, standard opt-out policy, and its five improvements (opt-out education, opt-out opportunity, opt-out social norm, opt-out feedback, and opt-out opportunity). Risk perception of the pandemic of COVID-19 and vaccination were also measured. RESULTS: (a) Opt-out policy and its improvement (except the opt-out transparency) increased intentions to be vaccinated. Policies with a vaccination default did not weaken people's attitude toward policy and policymakers compared with the opt-in policy, but participants in the transparent improvement group reported lower freedom of choice than those in the opt-out group. (b) Further latent profile analysis revealed four classes underlying risk perception: risk exaggerators, risk deniers, disease-specific risk perceivers, and vaccine-specific risk perceivers. But there was no conclusive evidence that the effect of risk perception differs as a function of defaults. CONCLUSIONS: These findings provide new psychological evidence for formulating more targeted vaccination policies and highlight the importance of risk perception to understand vaccination intentions.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Humanos , Intenção , Políticas , SARS-CoV-2 , Vacinação/psicologia
6.
Front Oncol ; 12: 915871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875089

RESUMO

Introduction: The aim of this work was to determine the feasibility of using a deep learning approach to predict occult lymph node metastasis (OLM) based on preoperative FDG-PET/CT images in patients with clinical node-negative (cN0) lung adenocarcinoma. Materials and Methods: Dataset 1 (for training and internal validation) included 376 consecutive patients with cN0 lung adenocarcinoma from our hospital between May 2012 and May 2021. Dataset 2 (for prospective test) used 58 consecutive patients with cN0 lung adenocarcinoma from June 2021 to February 2022 at the same center. Three deep learning models: PET alone, CT alone, and combined model, were developed for the prediction of OLM. The performance of the models was evaluated on internal validation and prospective test in terms of accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curve (AUCs). Results: The combined model incorporating PET and CT showed the best performance, achieved an AUC of 0.81 [95% confidence interval (CI): 0.61, 1.00] in the prediction of OLM in internal validation set (n = 60) and an AUC of 0.87 (95% CI: 0.75, 0.99) in the prospective test set (n = 58). The model achieved 87.50% sensitivity, 80.00% specificity, and 81.00% accuracy in the internal validation set and achieved 75.00% sensitivity, 88.46% specificity, and 86.60% accuracy in the prospective test set. Conclusion: This study presented a deep learning approach to enable the prediction of occult nodal involvement based on the PET/CT images before surgery in cN0 lung adenocarcinoma, which would help clinicians select patients who would be suitable for sublobar resection.

7.
Proc Inst Mech Eng H ; : 9544119221114200, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35880904

RESUMO

Adolescent idiopathic scoliosis (AIS) is a three-dimensional curvature of spine. Children with AIS and low bone quality have higher chance to get curve progression leading to bigger spinal curvature. In addition, bone quality affects acoustic impedance of bone, thus influencing the reflection coefficient of ultrasound signal from the soft tissue-bone interface. This study aimed to estimate the bone quality of AIS patients based on the reflection coefficients to determine the correlation of the bone quality with curve severity. A simple bone model was used to develop an equation to calculate the reflection coefficient value. Experiments were conducted on five different phantoms. Acrylic was used to design a vertebral shape to study the effect of surface roughness and inclination, including: smooth flat surface (SFS), smooth curved surface (SCS), rough curved surface (RCS), and the rough curved inclined surface (RCIS). A clinical study with 37 AIS patients were recruited. The estimated reflection coefficient values of plate phantoms agreed well with the predicted values and the maximum error was 6.7%. The reflection coefficients measured from the acrylic-water interface for the SFS, SCS, RCS, RCIS (3° and 5°) were 0.37, 0.33, 0.28, (0.23 and 0.12), respectively. The surface roughness and inclination increased the reflection loss. From the clinical data, the average reflection coefficients for children with AIS were 0.11 and 0.07 for the mild curve group and the moderate curve group, respectively. A moderate linear correlation was found between the reflection coefficients and curve severity (r2 = 0.3). Patients with lower bone quality have observed to have larger spinal curvature.

8.
Neurosci Bull ; 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804219

RESUMO

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

9.
Reprod Biomed Online ; 2022 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-35821214

RESUMO

RESEARCH QUESTION: Testis-specific PRSS55 is a chymotrypsin-like serine protease that is highly conserved among mammalian species. The essential role of Prss55 in mouse male fertility has been established. What is the role of PRSS55 in human reproduction? DESIGN: Whole exome sequencing was used to identify the genetic cause in an infertile male with teratozoospermia. Papanicolaou staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to explore morphological defects in the patient's spermatozoa. Immunofluorescence staining and western blot analysis were conducted to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist the patient with fertilization. RESULTS: Sanger sequencing of the pedigree demonstrated that the infertile man carried a novel homozygous mutation in PRSS55 (c.575C>T [p.A192V]). Morphological defects in the sperm head, neck, midpiece and tail were demonstrated by Papanicolaou staining, SEM and TEM. Immunofluorescence staining and western blotting of the patient's spermatozoa showed that the point mutation changed the conformation of PRSS55 and caused a sharp decrease in the PRSS55 protein concentration. The expression and subcellular localization of PRSS55 in the testis and spermatozoa of mice and humans showed that PRSS55 was expressed in the head and flagella of spermatids and epididymal spermatozoa. Moreover, ICSI treatment for this kind of infertile patient was shown to be effective. CONCLUSIONS: These findings revealed a novel mutation in PRSS55 in an infertile patient, suggesting for the first time the crucial role of PRSS55 in human fertility. This study provides new insight into genetic counselling diagnoses and subsequent treatment for male infertility.

10.
Huan Jing Ke Xue ; 43(7): 3708-3717, 2022 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-35791554

RESUMO

This study was based on the pilot one-stage combined partial nitritation and ANAMMOX process (CPNA), using data mining and analysis of 16S rRNA high-throughput sequencing data of activated sludge in the process of sludge bulking and recovery, combined with PISCRUSt2. The function prediction analysis aimed to reveal the microbial community changes and the characteristics of nitrogen metabolism and carbon metabolism at different stages of sludge bulking and recovery of the one-stage CPNA process. The results of the study showed that the microbial α-diversity in the sludge bulking and recovery process first increased and then declined. The relative abundance of Nitrosomonas, Candidatus_Brocadia, and Thaurea decreased in the sludge-bulking stage from 12.36%, 11.86%, and 0.272% to 5.97%, 8.30%, and 0.061%, whereas the relative abundance of Candidatus Kuenenia remained stable. The relative abundance of Levilinea, Longilinea, and Turicibacter increased from 0.031%, 0.018%, and 0.009% to 0.055%, 0.025%, and 0.033%. The PICRUSt2 function prediction analysis results showed that there were a total of 47 functional enzyme genes involved in nitrogen metabolism, of which nitrification, denitrification, dissimilative nitrate reduction (DNRA), assimilation nitrate reduction (ANRA), and nitrogen fixation were relatively abundant. The degrees of each had changed. During the sludge-bulking stage, the relative abundance of the ammonia monooxygenase gene (pmoABC-amoABC) and the hydroxylamine dehydrogenase gene hao decreased, whereas the relative abundance of the nitrate-reducing gene increased at the initial stage and then showed a downward trend. Carbon metabolism analysis showed that sodium acetate had a promoting effect on the heterotrophic growth of the CPNA process, but the energy metabolism and glucose production of sodium acetate were not active.


Assuntos
Actinobacteria , Microbiota , Oxidação Anaeróbia da Amônia , Bactérias , Carbono/metabolismo , Microbiota/genética , Nitratos/metabolismo , Nitrogênio/metabolismo , RNA Ribossômico 16S/genética , Esgotos , Acetato de Sódio/metabolismo
11.
Brief Bioinform ; 23(4)2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35656709

RESUMO

In the previous study, we developed the generalized drug-induced liver injury (DILI) prediction model-ResNet18DNN to predict DILI based on multi-source combined DILI dataset and achieved better performance than that of previously published described DILI prediction models. Recently, we were honored to receive the invitation from the editor to response the Letter to Editor by Liu Zhichao, et al. We were glad that our research has attracted the attention of Liu's team and they has put forward their opinions on our research. In this response to Letter to the Editor, we will respond to these comments.


Assuntos
Inteligência Artificial , Doença Hepática Induzida por Substâncias e Drogas , Humanos
12.
Physiol Genomics ; 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35723222

RESUMO

Objective Troxerutin is known for its anti-inflammatory and antioxidative effects in nerve impairment. The purpose of this study is to investigate the effect of troxerutin and cerebroprotein hydrolysate injections (TCHis) on prenatal valproic acid (VPA)-exposed rats. Methods The VPA was administered to pregnant rats on gestational day 12.5 to induce a model of autism. The offsprings were given the treatment of TCHis on postnatal day (PND) 21-50. On PND 43-50, the behavioral analysis of offsprings was performed after the treatment of TCHis for 1 h. On PND 50, the offsprings were harvested and the brains were collected. The hippocampus and prefrontal cortex were isolated for relevant biochemical detections. Results The administration of TCHis increased the pain sensitivity and improved abnormal social behaviors in prenatal VPA-exposed rats. Prenatal expose of VPA induced neuronal loss and apoptosis, enhanced reactive oxygen species (ROS) production, and promoted oxidative stress in hippocampus and prefrontal cortex, while these effects were reversed by the postnatal treatment of TCHis. In addition, postnatal administration of TCHis ameliorated mitochondrial function in hippocampus and prefrontal cortex of prenatal VPA-exposed rats. Conclusion This study concluded that postnatal treatment of TCHis reduced oxidative stress and ameliorated abnormal behavior in a prenatal VPA-induced rat model of autism.

13.
Nanoscale ; 14(25): 9045-9052, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35703448

RESUMO

Due to the perfection of the nanofabrication in nanotechnology and nanoscience, ice lithography (IL) by patterning ice thin-films with a focused electron beam, as a significant derivative technology of electron beam lithography (EBL), is attracting growing attention, evoked by its advantages over traditional EBL with respects of in situ-fabrication, high efficiency, high accuracy, limited proximity effect, three-dimensional (3D) profiling capability, etc. However, theoretical modeling of ice lithography for replicated profiles on the ice resist (amorphous solid water, ASW) has rarely been reported so far. As the result, the development of ice lithography still stays at the experimental stage. The shortage of modeling methods limits our insight into the ice lithography capability, as well as theoretical anticipations for future developments of this emerging technique. In this work, an e-beam induced etching ice model based on the Monte Carlo algorithm for point/line spread functions is established to calculate the replicated profiles of the resist by ice lithography. To testify the fidelity of the modeling method, systematic simulations of the ice lithography property under the processing parameters of the resist thickness, electron accelerating voltage and actual patterns are performed. Theoretical comparisons between the IL on ASW and the conventional EBL on polymethyl methacrylate (PMMA) show superior properties of IL over EBL in terms of the minimum feature size, the highest aspect ratio, 3D nanostructure/devices, etc. The success in developing a modeling method for ice lithography, as reported in this paper, offers a powerful tool in characterizing ice lithography up to the theoretical level and down to molecular scales.

14.
J Med Genet ; 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35654582

RESUMO

BACKGROUND: Loss-of-function mutations in FSIP2 result in multiple morphological abnormalities of the flagella in humans and mice. Intriguingly, a recent study found that FSIP2 might regulate the expression of acrosomal proteins, indicating that Fsip2 might be involved in acrosome development in mice. However, whether FSIP2 also function in acrosome biogenesis in humans is largely unknown, and the underlying mechanism of which is unexplored. OBJECTIVE: Our objective was to reveal potential function of FSIP2 in regulating sperm acrosome formation. METHODS: We performed whole exome sequencing on four asthenoteratozoospermic patients. Western blot analysis and immunofluorescence staining were conducted to assess the protein expression of FSIP2. Proteomics approach, liquid chromatography-tandem mass spectrometry and co-immunoprecipitation were implemented to clarify the molecules in acrosome biogenesis regulated by FSIP2. RESULTS: Biallelic FSIP2 variants were identified in four asthenoteratozoospermic individuals. The protein expression of MUT-FSIP2 was sharply decreased or absent in vitro or in vivo. Interestingly, aside from the sperm flagellar defects, the acrosomal hypoplasia was detected in numerous sperm from the four patients. FSIP2 co-localised with peanut agglutinin in the acrosome during spermatogenesis. Moreover, FSIP2 interacted with proteins (DPY19L2, SPACA1, HSP90B1, KIAA1210, HSPA2 and CLTC) involved in acrosome biogenesis. In addition, spermatozoa from patients carrying FSIP2 mutations showed downregulated expression of DPY19L2, ZPBP, SPACA1, CCDC62, CCIN, SPINK2 and CSNK2A2. CONCLUSION: Our findings unveil that FSIP2 might involve in sperm acrosome development, and consequently, its mutations might contribute to globozoospermia or acrosomal aplasia. We meanwhile first uncover the potential molecular mechanism of FSIP2 regulating acrosome biogenesis.

15.
J Genet Genomics ; 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35691554

RESUMO

CRISPR/Cas9-mediated site-specific insertion of exogenous genes holds potential for clinical applications. However, it is still infeasible because homologous recombination (HR) is inefficient, especially for non-dividing cells. To overcome the challenge, we report that a homology-independent targeted integration (HITI) strategy is used for permanent integration of high-specificity-activity Factor IX variant (F9 Padua, R338L) at the albumin (Alb) locus in a novel haemophilia B (HB) rat model. The knock-in efficiency reaches 3.66%, as determined by droplet digital PCR (ddPCR). The clotting time is reduced to a normal level 4 weeks after treatment, and the circulating FIX level is gradually increased up to 52% of the normal level over 9 months even after partial hepatectomy, demonstrating the amelioration of haemophilia. Through primer-extension-mediated sequencing (PEM-seq), no significant off-target effect is detected. This study not only provides a novel model for haemophilia B but also identifies a promising therapeutic approach for rare inherited diseases.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35687281

RESUMO

The outdoor thermal environment is an important factor when measuring the livability of a city. Residents will avoid intense heat by reducing their outdoor activities, which decreases the vitality of a city and increases the energy consumed for air conditioning. Outdoor thermal comfort has a great impact on outdoor activities; therefore, we need to evaluate and design the urban outdoor thermal environments in cold regions to improve the outdoor thermal comfort level. In this study, we conducted a questionnaire survey to assess the outdoor thermal comfort and adaptive thermal comfort in four different urban forms in Xi'an during July 2019, and measuring meteorological parameters, such as the temperature, relative humidity, wind speed, and black bulb temperature. The results are showed as follows. (1) In the cold study area, urban residents generally perceived the outdoor climate as relatively hot during the summer. (2) The participants exhibited psychological and physical adaptations in terms of their thermal comfort. In particular, when the PET was 30 °C, the MTCV was about 1.25 points higher in the later summer period than the early summer period. (3) The neutral PET differs among regions, and it is affected by the climate zone and latitude. Comparisons of our results with thermal comfort studies in different regions such as Singapore and Umeå in north Sweden showed that the thermal comfort is correlated with the regional climate and latitude. The neutral PET is higher in tropical regions. Our findings support the theoretical understanding of adaptive thermal comfort in cold regions and they provide a reference for formulating policies related to adaptive thermal comfort.

17.
PLoS One ; 17(6): e0270021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35771800

RESUMO

Sexual dimorphism is seen in many dioecious plant and animal species, which may influence their trophic interactions. The differences in trophic interactions derived from sexual dimorphism in plants may influence herbivorous performance and population dynamics. Both silkworm (Bombyx mori L.) and mulberry (Morus alba L.) usually exhibit sexual dimorphism. However, few studies have been conducted on the effect of sex-related silkworm and mulberry pairings on cocoon and silk qualities, which are crucial in sericulture. Here, we compared the differences in cocoon and silk qualities under four feeding combinations (FS-FL: female silkworm fed with leaves from female mulberry trees; MS-FL: male silkworm fed with leaves from female mulberry trees; FS-ML: female silkworm fed with leaves from male mulberry trees; MS-ML: male silkworm fed with leaves from male mulberry trees). The results showed that silkworms exhibited male-biased herbivory with more male mulberry leaves digested. The FS-ML group had higher silk weight and silk ratio of fresh cocoons than the FS-FL group, and the MS-ML group had lower coarse points than the MS-FL group. Compared with groups FS-ML and FS-FL, both MS-FL and MS-ML had smaller cocoons with longer silk lengths and a higher silk ratio of the fresh cocoons. In addition, the Entropy Weight-TOPSIS method showed the cocoon quality rank as FS-ML > FS-FL > MS-FL > MS-ML, whereas silk quality rank was MS-ML > FS-FL > FS-ML > MS-FL. These results indicate that the quality of cocoon and silk is related to the interaction of silkworm and mulberry at the sex level. Furthermore, female silkworms fed with female and male tree leaves have a higher total yield in cocoon production, while male silkworms fed with male tree leaves produced higher silk quality.


Assuntos
Bombyx , Morus , Animais , Frutas , Folhas de Planta , Seda
18.
Prostaglandins Other Lipid Mediat ; 162: 106651, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35680078

RESUMO

Cystinuria is a genetic disorder of cystine transport, including defective protein b0,+AT (encoded by SLC7A9), and/or rBAT (encoded by SLC3A1). Patients present hyperexcretion of cystine in the urine, recurrent cystine lithiasis, and progressive decline in kidney function. Moreover, heterodimer transport is defective. To date, little omics data are accessible regarding this metabolic disease caused by membrane proteins. Since membrane function is closely related to changes in the lipidome, we decided to explore the changes in kidney tissue of a self-established cystinuria rat model by performing lipidomic analysis by LC-MS/MS. Our results demonstrated that Slc7a9 deficiency changed the lipid profile of the renal cortex and induced vital modifications in the lipidome, including major alterations in ChE, LPA, and PA. Among those alterations, this lipidomic study highlights the lipid changes that participate in inflammatory responses during cystinuria. As a result, lipid research, perhaps has great potential, for it may lead to the identification of novel therapeutic targets for the prevention and treatment of cystinuria.

19.
Cell Death Dis ; 13(6): 559, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729109

RESUMO

Primary cilia dyskinesia (PCD) is a rare genetic disease caused by ciliary structural or functional defects. It causes severe outcomes in patients, including recurrent upper and lower airway infections, progressive lung failure, and randomization of heterotaxy. To date, although 50 genes have been shown to be responsible for PCD, the etiology remains elusive. Meanwhile, owing to the lack of a model mimicking the pathogenesis that can be used as a drug screening platform, thereby slowing the development of related therapies. In the current study, we identified compound mutation of DNAH9 in a patient with PCD with the following clinical features: recurrent respiratory tract infections, low lung function, and ultrastructural defects of the outer dynein arms (ODAs). Bioinformatic analysis, structure simulation assay, and western blot analysis showed that the mutations affected the structure and expression of DNAH9 protein. Dnah9 knock-down (KD) mice recapitulated the patient phenotypes, including low lung function, mucin accumulation, and increased immune cell infiltration. Immunostaining, western blot, and co-immunoprecipitation analyses were performed to clarify that DNAH9 interacted with CCDC114/GAS8 and diminished their protein levels. Furthermore, we constructed an airway organoid of Dnah9 KD mice and discovered that it could mimic the key features of the PCD phenotypes. We then used organoid as a drug screening model to identify mitochondrial-targeting drugs that can partially elevate cilia beating in Dnah9 KD organoid. Collectively, our results demonstrated that Dnah9 KD mice and an organoid model can recapture the clinical features of patients with PCD and provide an excellent drug screening platform for human ciliopathies.


Assuntos
Dineínas do Axonema , Discinesias , Síndrome de Kartagener , Animais , Dineínas do Axonema/genética , Dineínas do Axonema/metabolismo , Cílios/metabolismo , Avaliação Pré-Clínica de Medicamentos , Dineínas/metabolismo , Discinesias/metabolismo , Discinesias/patologia , Humanos , Síndrome de Kartagener/genética , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/patologia , Camundongos , Mutação/genética , Organoides/metabolismo
20.
Front Vet Sci ; 9: 906973, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769322

RESUMO

Escherichia coli is a gram-negative bacterium that is distributed widely throughout the world; it is mainly found in contaminated food, the poultry industry, and animal feces. The emergence of antibiotic-resistant E. coli poses a threat to human and animal health, which has led to renewed interest in phage-based therapy. E. coli biofilm control and prevention are of great importance. In this study, the isolated phages Flora and KM18 were found to belong to the family Myoviridae; the optimal preservation buffer was pH = 6~7, and the phage genome sizes were 168,909 (Flora) and 168,903 (KM18) bp. Phage Flora had a broader lytic spectrum than KM18. Phage Flora had a better antibiofilm effect than kanamycin sulfate in high-concentration E. coli cultures. A combination of the phage Flora and kanamycin sulfate showed better antibiofilm effects than Flora or kanamycin sulfate alone in low-concentration E. coli cultures. These characteristics can serve as a guideline for the selection of effective candidates for phage therapy, in this case antibiotic-resistant E. coli control in the poultry industry.

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