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1.
Int J Nanomedicine ; 19: 6427-6447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952675

RESUMO

Background: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. Purpose: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. Methods: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Results: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. Conclusion: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.


Assuntos
Antibacterianos , Materiais Revestidos Biocompatíveis , Escherichia coli , Osteogênese , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos Sprague-Dawley , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Osteogênese/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Próteses e Implantes , Ligas/farmacologia , Ligas/química , Ratos , Titânio/química , Titânio/farmacologia , Prata/química , Prata/farmacologia , Proliferação de Células/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Masculino , Microtomografia por Raio-X , Linhagem Celular , Nanopartículas Metálicas/química
2.
Cell Death Dis ; 15(7): 504, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009589

RESUMO

Abnormal epigenetic modifications are involved in the regulation of Warburg effect in tumor cells. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have critical functions in cellular responses. PRMTs are deregulated in a variety of cancers, but their precise roles in Warburg effect in cancer is largely unknown. Experiments from the current study showed that PRMT1 was highly expressed under conditions of glucose sufficiency. PRMT1 induced an increase in the PKM2/PKM1 ratio through upregulation of PTBP1, in turn, promoting aerobic glycolysis in non-small cell lung cancer (NSCLC). The PRMT1 level in p53-deficient and p53-mutated NSCLC remained relatively unchanged while the expression was reduced in p53 wild-type NSCLC under conditions of glucose insufficiency. Notably, p53 activation under glucose-deficient conditions could suppress USP7 and further accelerate the polyubiquitin-dependent degradation of PRMT1. Melatonin, a hormone that inhibits glucose intake, markedly suppressed cell proliferation of p53 wild-type NSCLC, while a combination of melatonin and the USP7 inhibitor P5091 enhanced the anticancer activity in p53-deficient NSCLC. Our collective findings support a role of PRMT1 in the regulation of Warburg effect in NSCLC. Moreover, combination treatment with melatonin and the USP7 inhibitor showed good efficacy, providing a rationale for the development of PRMT1-based therapy to improve p53-deficient NSCLC outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteínas de Membrana , Proteína-Arginina N-Metiltransferases , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos , Proteína Supressora de Tumor p53 , Efeito Warburg em Oncologia , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Efeito Warburg em Oncologia/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Hormônios Tireóideos/metabolismo , Linhagem Celular Tumoral , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proliferação de Células/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Peptidase 7 Específica de Ubiquitina/metabolismo , Peptidase 7 Específica de Ubiquitina/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Animais , Glicólise/efeitos dos fármacos , Camundongos Nus , Glucose/metabolismo , Camundongos , Regulação Neoplásica da Expressão Gênica , Células A549 , Proteína de Ligação a Regiões Ricas em Polipirimidinas
3.
Plant Commun ; : 101038, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38993115

RESUMO

Comparative metabolomics plays a crucial role in investigating gene function, exploring metabolite evolution, and accelerating crop genetic improvement. However, a systematic platform for comparing intra- and cross-species metabolites is currently lacking. Here, we report the Plant Comparative Metabolome Database (PCMD; http://yanglab.hzau.edu.cn/PCMD), a multilevel comparison database based on predicted metabolic profiles in 530 plant species. PCMD serves as a platform for comparing metabolite characteristics at various levels, including species, metabolites, pathways, and biological taxonomy. The database also provides a series of user-friendly online tools, such as Species-comparison, Metabolites-enrichment, and ID conversion, enabling users to perform comparisons and enrichment analyses of metabolites across different species. In addition, PCMD establishes a unified system based on existing metabolite-related databases by standardizing metabolite numbering. PCMD is the most species-rich comparative plant metabolomics database currently available, and a case study demonstrated its capability to provide new insights into understanding plant metabolic diversity.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38904566

RESUMO

INTRODUCTION: This study aimed to analyze the comprehensive maxillofacial features of patients with skeletal Class III malocclusion and facial asymmetry to develop a classification system for diagnosis and surgical planning. METHODS: A total of 161 adult patients were included, with 121 patients in the asymmetry group (menton deviation >2 mm) and 40 patients in the symmetry group (menton deviation ≤2 mm). Twenty-eight variables were determined, including transverse translation, roll and yaw of each facial unit, transverse width, mandibular morphology, and transverse dental compensation. Principal component (PC) analysis was conducted to extract PCs, and cluster analysis was performed using these components to classify the asymmetry group. A decision tree was constructed on the basis of the clustering results. RESULTS: Six PCs were extracted, explaining 80.622% of the data variability. The asymmetry group was classified into 4 subgroups: (1) atypical type (15.7%) showed an opposite roll direction of maxillary dentition than of menton deviation; (2) compound type (34.71%) demonstrated significant ramus height differences, maxillary roll, and mandibular roll and yaw; (3) mandibular yaw type (44.63%) showed slight mandibular yaw without mandibular morphology asymmetry; and (4) maxillary-shift type (4.96%) shared similarities with the compound type but showed significant maxillary translation. The classification and regression tree model achieved a prediction accuracy of up to 85.11%. CONCLUSIONS: This study identified 4 distinct phenotypes using cluster analysis and proposed tailored treatment recommendations on the basis of their specific characteristics. The classification results emphasized the importance of spatial displacement features, especially mandibular yaw, in diagnosing facial asymmetry. The established classification and regression tree model enables clinicians to identify patients conveniently.

5.
Sci Data ; 11(1): 488, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734729

RESUMO

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.


Assuntos
Herbivoria , Transcriptoma , Animais , Bovinos/genética , Feminino , Coelhos/genética , Bases de Dados Genéticas , Cervos/genética , Equidae/genética , Cabras/genética , Cavalos/genética , Ovinos/genética
6.
Front Cell Infect Microbiol ; 14: 1361326, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572322

RESUMO

Spinal tuberculosis is a common extrapulmonary type that is often secondary to pulmonary or systemic infections. Mycobacterium tuberculosis infection often leads to the balance of immune control and bacterial persistence. In this study, 64 patients were enrolled and the clinicopathological and immunological characteristics of different age groups were analyzed. Anatomically, spinal tuberculosis in each group mostly occurred in the thoracic and lumbar vertebrae. Imaging before preoperative anti-tuberculosis therapy showed that the proportion of abscesses in the older group was significantly lower than that in the younger and middle-aged groups. However, pathological examination of surgical specimens showed that the proportion of abscesses in the older group was significantly higher than that in the other groups, and there was no difference in the granulomatous inflammation, caseous necrosis, inflammatory necrosis, acute inflammation, exudation, granulation tissue formation, and fibrous tissue hyperplasia. B cell number was significantly lower in the middle-aged and older groups compared to the younger group, while the number of T cells, CD4+ T cells, CD8+ T cells, macrophages, lymphocytes, plasma cells, and NK cells did not differ. Meaningfully, we found that the proportion of IL-10 high expression and TGF-ß1 positive in the older group was significantly higher than that in the younger group. TNF-α, CD66b, IFN-γ, and IL-6 expressions were not different among the three groups. In conclusion, there are some differences in imaging, pathological, and immune features of spinal tuberculosis in different age groups. The high expression of IL-10 and TGF-ß1 in older patients may weaken their anti-tuberculosis immunity and treatment effectiveness.


Assuntos
Mycobacterium tuberculosis , Tuberculose da Coluna Vertebral , Pessoa de Meia-Idade , Humanos , Idoso , Interleucina-10/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Tuberculose da Coluna Vertebral/tratamento farmacológico , Tuberculose da Coluna Vertebral/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Abscesso/tratamento farmacológico , Abscesso/metabolismo , Antituberculosos/uso terapêutico , Necrose/tratamento farmacológico , Necrose/metabolismo , Linfócitos T CD4-Positivos , Citocinas/metabolismo
7.
Biomed Pharmacother ; 174: 116506, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554525

RESUMO

Combination therapy has become the most important treatment for advanced non-small cell lung cancer (NSCLC), which can significantly improve the prognosis of patients. However, poor targeting and adverse reactions limited its clinical application. Here, we constructed an AS1411 aptamer-programmed cell death ligand-1 (PD-L1) siRNA chimera/polyethylenimine/glutamine/ß-cyclodextrin/doxorubicin (Chimera/ PEI/Gln/ß-CD/DOX) nanoparticle for the combination therapy (chemotherapy combined with immunotherapy). Scanning electron microscopy showed that PEI/Gln/ß-CD/DOX nanoparticle was conical, with a diameter of about 250-500 nm. AS1411 aptamer-PD-L1 siRNA chimera can effectively bind NSCLC cells and inhibit PD-L1 expression, further activating T cells and CD8+T cells. Glutamine modification effectively promoted the doxorubicin uptake by cancer cells and induced their apoptosis. Animal experiments showed that our nanoparticles effectively treated the transplanted tumor, and the adverse reactions were reduced. Compared with the Aptamer/ß-CD/DOX group, the volume and ki-67 index of transplanted tumors in the Chimera/ß-CD/DOX group were significantly decreased, while the apoptosis ratio was increased. Immunohistochemical results showed that Compared with the Aptamer/ß-CD/DOX group, the number of T cells and CD8+T cells in the Chimera/ß-CD/DOX group was increased by 1.34 and 1.41 times. Glutamine modification enhanced the chemotherapeutic efficacy and anti-tumor immune response in vivo. Our study provided a new method for the combination therapy of lung squamous cell carcinoma.


Assuntos
Aptâmeros de Nucleotídeos , Doxorrubicina , Glutamina , Neoplasias Pulmonares , Nanopartículas , RNA Interferente Pequeno , beta-Ciclodextrinas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Aptâmeros de Nucleotídeos/farmacologia , Animais , Humanos , beta-Ciclodextrinas/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Nanopartículas/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Linhagem Celular Tumoral , Camundongos Nus , Camundongos Endogâmicos BALB C , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Camundongos , Terapia Combinada , Apoptose/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética
9.
Technol Health Care ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38073341

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. OBJECTIVE: To examine the role and effect of DKK1 in OSCC. METHODS: The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. RESULTS: The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4+ T cells were associated with improved 5-year survival rates. CONCLUSION: DKK1 is a prognostic biomarker for patients with OSCC.

10.
Materials (Basel) ; 16(22)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38005047

RESUMO

Although nondestructive ultrasonic technologies have been applied in laboratory and field tests in the field of heritage conservation, few studies have quantified the relationship among the real microstructures, micromechanical properties, and macroscopic acoustic responses of earthen-site soils. This paper develops a micromechanics-based multiscale model for quantitatively exploring the ultrasonic propagation characteristics of elastic waves in untreated and consolidated earthen-site soils. Scanning electron microscope images and image processing technology are integrated into the finite-element simulation. The effects of microstructure and wave features on the acoustic characteristics of soils are quantitatively investigated under pulsive loading. The simulation results of untreated and consolidated soils are efficiently compared to ultrasonic test data. It is demonstrated that the integration of microstructure image processing and multiscale modeling can predict the ultrasonic pulse velocity well, which improves the accuracy of laboratory testing and field monitoring and better serves the evaluation and implementation of engineering practice in the field of heritage conservation.

11.
Nat Prod Res ; : 1-7, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37690002

RESUMO

The phytochemical investigation on the rhizomes of Dryopteris crassirhizoma (Dryopteridaceae) resulted in the discovery of one novel compound, drycrassirhizomamide A (1), and one new natural product, drycrassirhizomamide B (2), as well as four known isolates, (S)-(-)-N-benzoylphenylalaninol (3), blumenol A (4), 8-C-glucosylnoreugenin (5), and dryopteroside (6). Their chemical structures were identified by NMR and mass spectroscopy. Compounds 1-2 were determined to be 1,19-diethyl 10-oxo-2,9,11,18-tetraazanonadecanedioate and C,C'-diethyl N,N'-1,6-hexanediylbis[carbamate]. The anti-inflammatory activities of these compounds were evaluated with LPS-stimulated RAW264.7 macrophage and BV2 microglia. The results showed that compounds 1-3 and 6 have inhibitory effects of NO production with IC50 values of 13.41, 30.36, 25.51, and 11.35 µM in LPS-stimulated RAW264.7 cells. Also, compounds 1 and 4-6 have abilities to inhibit NO production with the IC50 values of 40.11, 30.94, 15.76, and 16.79 µM in BV2 cells, which demonstrated that they may possess the potential anti-inflammatory activity.

12.
BMC Biol ; 21(1): 202, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37775748

RESUMO

BACKGROUND: Brassica napus is an important oilseed crop providing high-quality vegetable oils for human consumption and non-food applications. However, the regulation between embryo and seed coat for the synthesis of oil and phenylpropanoid compounds remains largely unclear. RESULTS: Here, we analyzed the transcriptomes in developing seeds at 2-day intervals from 14 days after flowering (DAF) to 64 DAF. The 26 high-resolution time-course transcriptomes are clearly clustered into five distinct groups from stage I to stage V. A total of 2217 genes including 136 transcription factors, are specifically expressed in the seed and show high temporal specificity by being expressed only at certain stages of seed development. Furthermore, we analyzed the co-expression networks during seed development, which mainly included master regulatory transcription factors, lipid, and phenylpropane metabolism genes. The results show that the phenylpropane pathway is prominent during seed development, and the key enzymes in the phenylpropane metabolic pathway, including TT5, BAN, and the transporter TT19, were directly or indirectly related to many key enzymes and transcription factors involved in oil accumulation. We identified candidate genes that may regulate seed oil content based on the co-expression network analysis combined with correlation analysis of the gene expression with seed oil content and seed coat content. CONCLUSIONS: Overall, these results reveal the transcriptional regulation between lipid and phenylpropane accumulation during B. napus seed development. The established co-expression networks and predicted key factors provide important resources for future studies to reveal the genetic control of oil accumulation in B. napus seeds.


Assuntos
Brassica napus , Transcriptoma , Humanos , Brassica napus/genética , Perfilação da Expressão Gênica , Óleos de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sementes/genética , Regulação da Expressão Gênica de Plantas
13.
Front Microbiol ; 14: 1230572, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645226

RESUMO

The special blood circulation, anatomy, and tissue structure of the spine may lead to significant differences in pathological features and drug resistance between spinal tuberculosis and pulmonary tuberculosis. Here, we collected 168 spinal tuberculosis cases and 207 pulmonary tuberculosis cases, and compared their clinical and pathological features as well as drug resistance. From the anatomical location, the highest incidence was of lumbar tuberculosis, followed by thoracic tuberculosis. PET-CT scans showed increased FDG uptake in the diseased vertebrae, discernible peripheral soft tissue shadow, visible internal capsular shadow, and an abnormal increase in FDG uptake. MRI showed infectious lesions in the diseased vertebral body, formation of paravertebral and bilateral psoas muscle abscess, and edema of surrounding soft tissues. As with control tuberculosis, the typical pathological features of spinal tuberculosis were chronic granulomatous inflammation with caseous necrosis. The incidence of granulomas was not statistically different between the groups. However, the proportions of caseous necrosis, acute inflammation, abscess, exudation, and granulation tissue formation in the spinal tuberculosis group were all significantly increased relative to the control tuberculosis group. Compared to the control tuberculosis group, the incidences of resistance to rifampicin (RFP) + isoniazid (INH) + streptomycin (STR) and INH + ethambutol (EMB) were lower in the spinal tuberculosis group, while the incidences of resistance to RFP + INH + EMB and RFP + EMB were higher. Moreover, we also found some differences in drug-resistance gene mutations. In conclusion, there are noticeable differences between spinal Mycobacterium tuberculosis and pulmonary tuberculosis in pathological characteristics, drug resistance, and drug resistance gene mutations.

14.
Cell Death Discov ; 9(1): 289, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37543653

RESUMO

Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevertheless, the senescence-associated secretion phenotype (SASP) promotes chronic inflammation of the cancer microenvironment and further accelerates the progression of tumors. Therefore, inducing the senescence of cancer cells and inhibiting the production of SASP factors during anticancer treatment have become effective therapeutic strategies to improve the anticancer effect of drugs. Here we reported that SCLC cells treated with an FDA-approved HDAC inhibitor SAHA underwent senescence and displayed remarkable SASP. In particular, SAHA promoted the formation of cytoplasmic chromatin fragments (CCFs) in SCLC cells. The increased CCFs in SAHA-treated SCLC cells were related to nuclear porin Tpr, which activated the cGAS-STING pathway, and promoted the secretion of SASP in cancer cells. Inhibition of EZH2 suppressed the increase of CCFs in SAHA-treated SCLC cells, weakened the production of SASP, and increased the antiproliferative effect of SAHA. Overall, our work affords new insight into the secretion of SASP in SCLC and establishes a foundation for constructing a new therapeutic strategy for SCLC patients.

15.
Neuroimage ; 278: 120282, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37468021

RESUMO

The posterior superior temporal gyrus (pSTG) has been implicated in the integration of auditory feedback and motor system for controlling vocal production. However, the question as to whether and how the pSTG is causally involved in vocal feedback control is currently unclear. To this end, the present study selectively stimulated the left or right pSTG with continuous theta burst stimulation (c-TBS) in healthy participants, then used event-related potentials to investigate neurobehavioral changes in response to altered auditory feedback during vocal pitch regulation. The results showed that, compared to control (vertex) stimulation, c-TBS over the right pSTG led to smaller vocal compensations for pitch perturbations accompanied by smaller cortical N1 and larger P2 responses. Enhanced P2 responses received contributions from the right-lateralized temporal and parietal regions as well as the insula, and were significantly correlated with suppressed vocal compensations. Surprisingly, these effects were not found when comparing c-TBS over the left pSTG with control stimulation. Our findings provide evidence, for the first time, that supports a causal relationship between right, but not left, pSTG and auditory-motor integration for vocal pitch regulation. This lends support to a right-lateralized contribution of the pSTG in not only the bottom-up detection of vocal feedback errors but also the involvement of driving motor commands for error correction in a top-down manner.


Assuntos
Fala , Voz , Humanos , Fala/fisiologia , Área de Wernicke , Retroalimentação , Percepção da Altura Sonora/fisiologia , Voz/fisiologia , Retroalimentação Sensorial/fisiologia , Estimulação Acústica/métodos
16.
PLoS One ; 18(6): e0287343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37319305

RESUMO

OBJECTIVE: To evaluate transverse maxillomandibular discrepancy and dental compensation in first molar areas in 7- to 9-year-old children with skeletal Class III malocclusion without posterior crossbite using cone-beam computed tomography (CBCT). METHODS: The sample of this retrospective study consisted of 60 children (7 to 9 years old), who were divided into the skeletal Class III malocclusion group (study group, skeletal Class III malocclusion without posterior crossbite, N = 31) and the Class I occlusion group (control group, Class I occlusion with one or two impacted teeth, N = 30). CBCT data were obtained from the database of the Department of Radiology of Hospital of Stomatology, Shandong University. For three-dimensional reconstruction of the head, the dental arch width, basal bone width, and buccolingual inclination angle were measured using MIMICS 21.0 software. Independent-sample t tests were used to compare the two groups. RESULTS: The mean age of the children was 8.18±0.83years. The width of the maxillary basal bone was significantly smaller in the skeletal Class III malocclusion group (59.75 ± 3.14 mm) than in the Class I occlusion group (62.39 ± 3.01 mm) (P < 0.01). The mandibular basal bone width was significantly larger in the skeletal Class III malocclusion group (60.00 ± 2.56 mm) than in the Class I occlusion group (58.19 ± 2.42 mm) (P < 0.01). The difference in the width of the maxillary and mandibular bases in the skeletal Class III malocclusion group (-0.25 ± 1.73 mm) was significantly different from that in the Class I occlusion group (4.20 ± 1.25 mm) (P < 0.01). However, there was no significant difference in the upper or lower dental arch width between the two groups (P > 0.05). The buccal inclination of the maxillary molars in the skeletal Class III malocclusion group (31.4° ± 8.9°) was significantly higher than that in the Class I occlusion group (17.64° ± 7.3°) (P < 0.01), as was the lingual inclination angle of mandibular molars (45.24° ± 8.3° vs. 37.96° ± 10.18°; P < 0.01). CONCLUSION: Transverse maxillary and mandibular discrepancies in the posterior area and transverse dental compensation were found in the early mixed dentition of patients with skeletal Class III malocclusion without posterior crossbite. This suggests that even in the absence of posterior crossbite, maxillary expansion can be attempted to correct the maxillomandibular transverse discrepancy.


Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Criança , Humanos , Dentição Mista , Estudos Retrospectivos , Má Oclusão/diagnóstico por imagem , Má Oclusão Classe III de Angle/diagnóstico por imagem , Mandíbula/diagnóstico por imagem , Maxila/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Cefalometria/métodos
17.
Nat Commun ; 14(1): 3243, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277343

RESUMO

Insertions are one of the major types of structural variations and are defined as the addition of 50 nucleotides or more into a DNA sequence. Several methods exist to detect insertions from next-generation sequencing short read data, but they generally have low sensitivity. Our contribution is two-fold. First, we introduce INSurVeyor, a fast, sensitive and precise method that detects insertions from next-generation sequencing paired-end data. Using publicly available benchmark datasets (both human and non-human), we show that INSurVeyor is not only more sensitive than any individual caller we tested, but also more sensitive than all of them combined. Furthermore, for most types of insertions, INSurVeyor is almost as sensitive as long reads callers. Second, we provide state-of-the-art catalogues of insertions for 1047 Arabidopsis Thaliana genomes from the 1001 Genomes Project and 3202 human genomes from the 1000 Genomes Project, both generated with INSurVeyor. We show that they are more complete and precise than existing resources, and important insertions are missed by existing methods.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos
18.
Biology (Basel) ; 12(5)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37237509

RESUMO

Breast cancer is now the most common cancer worldwide, and it is also the main cause of cancer-related death in women. Survival rates for female breast cancer have significantly improved due to early diagnosis and better treatment. Nevertheless, for patients with advanced or metastatic breast cancer, the survival rate is still low, reflecting a need for the development of new therapies. Mechanistic insights into metastatic breast cancer have provided excellent opportunities for developing novel therapeutic strategies. Although high-throughput approaches have identified several therapeutic targets in metastatic disease, some subtypes such as triple-negative breast cancer do not yet have an apparent tumor-specific receptor or pathway to target. Therefore, exploring new druggable targets in metastatic disease is a high clinical priority. In this review, we summarize the emerging intrinsic therapeutic targets for metastatic breast cancer, including cyclin D-dependent kinases CDK4 and CDK6, the PI3K/AKT/mTOR pathway, the insulin/IGF1R pathway, the EGFR/HER family, the JAK/STAT pathway, poly(ADP-ribose) polymerases (PARP), TROP-2, Src kinases, histone modification enzymes, activated growth factor receptors, androgen receptors, breast cancer stem cells, matrix metalloproteinases, and immune checkpoint proteins. We also review the latest development in breast cancer immunotherapy. Drugs that target these molecules/pathways are either already FDA-approved or currently being tested in clinical trials.

19.
BMC Oral Health ; 23(1): 295, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37189105

RESUMO

BACKGROUND: The purpose of this study was to assess morphological changes of the upper anterior alveolus after retraction of a maxillary incisor by applying three-dimensional (3D) superimposition of pretreatment (T1) and posttreatment (T2) cone-beam computed tomography (CBCT) data. METHODS: The study group was comprised of 28 patients with skeletal Class II malocclusion who underwent incisor retraction. CBCT data were acquired before (T1) and after (T2) orthodontic treatment. Labial and palatal alveolar thickness were assessed at the crestal, midroot and apical levels of the retracted incisors. Following three-dimensional (3D) cranial base superimposition, we performed surface modeling and inner remodeling of the labial and palatal alveolar cortex of the maxillary incisors. Paired t-tests were used to compare T0 and T1 bone thickness and volume measurements. Comparisons between labial and palatal surface modeling, inner remodeling and outer surface modeling were performed with paired t-tests in SPSS 20.0 version. RESULTS: We observed controlled tipping retraction of the upper incisor. After treatment, the alveolar thickness on the labial sides increased and the palatal alveolar thickness decreased. The labial cortex showed a wider range of modeling area with a larger bending height and a smaller bending angle than the palatal side. The extent of inner remodeling was more prominent than the outer surface on both the labial and palatal sides. CONCLUSIONS: Adaptive alveolar surface modeling occurred in response to incisor tipping retraction on both the lingual and labial sides although these changes occurred in an uncoordinated manner. Tipping retraction of the maxillary incisors led to a reduction in alveolar volume.


Assuntos
Incisivo , Má Oclusão Classe II de Angle , Humanos , Incisivo/diagnóstico por imagem , Técnicas de Movimentação Dentária/métodos , Cefalometria/métodos , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/terapia , Maxila/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico
20.
Plant Biotechnol J ; 21(8): 1611-1627, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154465

RESUMO

Plant hormones are the intrinsic factors that control plant development. The integration of different phytohormone pathways in a complex network of synergistic, antagonistic and additive interactions has been elucidated in model plants. However, the systemic level of transcriptional responses to hormone crosstalk in Brassica napus is largely unknown. Here, we present an in-depth temporal-resolution study of the transcriptomes of the seven hormones in B. napus seedlings. Differentially expressed gene analysis revealed few common target genes that co-regulated (up- and down-regulated) by seven hormones; instead, different hormones appear to regulate distinct members of protein families. We then constructed the regulatory networks between the seven hormones side by side, which allowed us to identify key genes and transcription factors that regulate the hormone crosstalk in B. napus. Using this dataset, we uncovered a novel crosstalk between gibberellin and cytokinin in which cytokinin homeostasis was mediated by RGA-related CKXs expression. Moreover, the modulation of gibberellin metabolism by the identified key transcription factors was confirmed in B. napus. Furthermore, all data were available online from http://yanglab.hzau.edu.cn/BnTIR/hormone. Our study reveals an integrated hormone crosstalk network in Brassica napus, which also provides a versatile resource for future hormone studies in plant species.


Assuntos
Brassica napus , Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Brassica napus/metabolismo , Giberelinas/metabolismo , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Hormônios/metabolismo , Citocininas/metabolismo
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