RESUMO
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
Assuntos
RNA Mensageiro/genética , RNA Viral/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Vacinas contra COVID-19 , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Feminino , Células HEK293 , Células HeLa , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas/química , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Th1/imunologia , Potência de Vacina , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/genéticaRESUMO
The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.
Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Imunidade Humoral , Pneumonia Viral/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19 , Convalescença , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Lithium niobate (LiNbO3) is viewed as a promising material for optical communications and quantum photonic chips1,2. Recent breakthroughs in LiNbO3 nanophotonics have considerably boosted the development of high-speed electro-optic modulators3-5, frequency combs6,7 and broadband spectrometers8. However, the traditional method of electrical poling for ferroelectric domain engineering in optic9-13, acoustic14-17 and electronic applications18,19 is limited to two-dimensional space and micrometre-scale resolution. Here we demonstrate a non-reciprocal near-infrared laser-writing technique for reconfigurable three-dimensional ferroelectric domain engineering in LiNbO3 with nanoscale resolution. The proposed method is based on a laser-induced electric field that can either write or erase domain structures in the crystal, depending on the laser-writing direction. This approach offers a pathway for controllable nanoscale domain engineering in LiNbO3 and other transparent ferroelectric crystals, which has potential applications in high-efficiency frequency mixing20,21, high-frequency acoustic resonators14-17 and high-capacity non-volatile ferroelectric memory19,22.
RESUMO
BACKGROUND: Congenital myopathies are a clinical, histopathological and genetic heterogeneous group of inherited muscle disorders that are defined on peculiar architectural abnormalities in the muscle fibres. Although there have been at least 33 different genetic causes of the disease, a significant percentage of congenital myopathies remain genetically unresolved. The present study aimed to report a novel TUBA4A variant in two unrelated Chinese patients with sporadic congenital myopathy. METHODS: A comprehensive strategy combining laser capture microdissection, proteomics and whole-exome sequencing was performed to identify the candidate genes. In addition, the available clinical data, myopathological changes, the findings of electrophysiological examinations and thigh muscle MRIs were also reviewed. A cellular model was established to assess the pathogenicity of the TUBA4A variant. RESULTS: We identified a recurrent novel heterozygous de novo c.679C>T (p.L227F) variant in the TUBA4A (NM_006000), encoding tubulin alpha-4A, in two unrelated patients with clinicopathologically diagnosed sporadic congenital myopathy. The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiquitin-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of the L227F mutant TUBA4A resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model. CONCLUSION: Our findings expanded the phenotypic and genetic manifestations of TUBA4A as well as tubulinopathies, and added a new type of congenital myopathy to be taken into consideration in the differential diagnosis.
Assuntos
Miopatias Congênitas Estruturais , Tubulina (Proteína) , Adulto , Feminino , Humanos , Masculino , Sequenciamento do Exoma , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Mutação , Miofibrilas/patologia , Miofibrilas/genética , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/patologia , Miotonia Congênita/genética , Miotonia Congênita/patologia , Linhagem , Tubulina (Proteína)/genéticaRESUMO
A nonlinear holographic technique is capable of processing optical information in the newly generated optical frequencies, enabling fascinating functions in laser display, security storage, and image recognition. One popular nonlinear hologram is based on a periodically poled lithium niobate (LN) crystal. However, due to the limitations of traditional fabrication techniques, the pixel size of the LN hologram is typically several micrometers, resulting in a limited field-of-voew (FOV) of several degrees. Here, we experimentally demonstrate an ultra-high-resolution LN hologram by using the laser poling technique. The minimal pixel size reaches 200 nm, and the FOV is extended above 120° in our experiments. The image distortions at large view angles are effectively suppressed through the Fourier transform. The FOV is further improved by combining multiple diffraction orders of SH fields. The ultimate FOV under our configuration is decided by a Fresnel transmission. Our results pave the way for expanding the applications of nonlinear holography to wide-view imaging and display.
RESUMO
Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.
RESUMO
BACKGROUND: While NTRK fusion-positive cancers can be exquisitely sensitive to first-generation TRK inhibitors, resistance inevitably occurs, mediated in many cases by acquired NTRK mutations. Next-generation inhibitors (e.g., selitrectinib, repotrectinib) maintain activity against these TRK mutant tumors; however, there are no next-generation TRK inhibitors approved by the FDA and select trials have stopped treating patients. Thus, the identification of novel, potent and specific next-generation TRK inhibitors is a high priority. METHODS: In silico modeling and in vitro kinase assays were performed on TRK wild type (WT) and TRK mutant kinases. Cell viability and clonogenic assays as well as western blots were performed on human primary and murine engineered NTRK fusion-positive TRK WT and mutant cell models. Finally, zurletrectinib was tested in vivo in human xenografts and murine orthotopic glioma models harboring TRK-resistant mutations. RESULTS: In vitro kinase and in cell-based assays showed that zurletrectinib, while displaying similar potency against TRKA, TRKB, and TRKC WT kinases, was more active than other FDA approved or clinically tested 1st- (larotrectinib) and next-generation (selitrectinib and repotrectinib) TRK inhibitors against most TRK inhibitor resistance mutations (13 out of 18). Similarly, zurletrectinib inhibited tumor growth in vivo in sub-cute xenograft models derived from NTRK fusion-positive cells at a dose 30 times lower when compared to selitrectinib. Computational modeling suggests this stronger activity to be the consequence of augmented binding affinity of zurletrectinib for TRK kinases. When compared to selitrectinib and repotrectinib, zurletrectinib showed increased brain penetration in rats 0.5 and 2 h following a single oral administration. Consistently, zurletrectinib significantly improved the survival of mice harboring orthotopic NTRK fusion-positive, TRK-mutant gliomas (median survival = 41.5, 66.5, and 104 days for selitrectinib, repotrectinib, and zurletrectinib respectively; P < 0.05). CONCLUSION: Our data identifies zurletrectinib as a novel, highly potent next-generation TRK inhibitor with stronger in vivo brain penetration and intracranial activity than other next-generation agents.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases , Receptor trkA , Receptor trkB , Receptor trkC , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Animais , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Receptor trkA/genética , Receptor trkA/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptor trkB/antagonistas & inibidores , Receptor trkB/genética , Receptor trkC/genética , Receptor trkC/antagonistas & inibidores , Linhagem Celular Tumoral , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Ratos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pirazóis/farmacologia , Glioma/tratamento farmacológico , Glioma/genética , Glioma/patologia , Pirimidinas/farmacologia , Mutação , Feminino , Glicoproteínas de MembranaRESUMO
BACKGROUND: Microglia is the major contributor of post-stroke neuroinflammation cascade and the crucial cellular target for the treatment of ischemic stroke. Currently, the endogenous mechanism underlying microglial activation following ischemic stroke remains elusive. Serglycin (SRGN) is a proteoglycan expressed in immune cells. Up to now, the role of SRGN on microglial activation and ischemic stroke is largely unexplored. METHODS: Srgn knockout (KO), Cd44-KO and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO) to mimic ischemic stroke. Exogenous SRGN supplementation was achieved by stereotactic injection of recombinant mouse SRGN (rSRGN). Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological functions were evaluated by the modified neurological severity score (mNSS) and grip strength. Microglial activation was detected by Iba1 immunostaining, morphological analysis and cytokines' production. Neuronal death was examined by MAP2 immunostaining and FJB staining. RESULTS: The expression of SRGN and its receptor CD44 was significantly elevated in the ischemic mouse brains, especially in microglia. In addition, lipopolysaccharide (LPS) induced SRGN upregulation in microglia in vitro. rSRGN worsened ischemic brain injury in mice and amplified post-stroke neuroinflammation, while gene knockout of Srgn exerted reverse impacts. rSRGN promoted microglial proinflammatory activation both in vivo and in vitro, whereas Srgn-deficiency alleviated microglia-mediated inflammatory response. Moreover, the genetic deletion of Cd44 partially rescued rSRGN-induced excessed neuroinflammation and ischemic brain injury in mice. Mechanistically, SRGN boosted the activation of NF-κB signal, and increased glycolysis in microglia. CONCLUSION: SRGN acts as a novel therapeutic target in microglia-boosted proinflammatory response following ischemic stroke.
Assuntos
Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Proteínas de Transporte Vesicular , Animais , Camundongos , Microglia/metabolismo , Isquemia Encefálica/metabolismo , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/metabolismo , Proteoglicanas/metabolismo , AVC Isquêmico/metabolismo , Lesões Encefálicas/metabolismoRESUMO
Transparent nano-polycrystalline diamond (t-NPD) possesses superior mechanical properties compared to single and traditional polycrystalline diamonds. However, the harsh synthetic conditions significantly limit its synthesis and applications. In this study, a synthesis routine is presented for t-NPD under low pressure and low temperature conditions, 10 GPa, 1600 °C and 15 GPa, 1350 °C similar with the synthesis condition of organic precursor. Self-catalyzed hydrogenated carbon nano-onions (HCNOs) from the combustion of naphthalene enable synthesis under nearly industrial conditions, which are like organic precursor and much lower than that of graphite and other carbon allotropes. This is made possible thanks to the significant impact of hydrogen on the thermodynamics, as it chemically facilitates phase transition. Ubiquitous nanotwinned structures are observed throughout t-NPD due to the high concentration of puckered layers and stacking faults of HCNOs, which impart a Vickers hardness about 140 GPa. This high hardness and optical transparency can be attributed to the nanocrystalline grain size, thin intergranular films, absence of secondary phase and pore-free features. The facile and industrial-scale synthesis of the HCNOs precursor, and mild synthesis conditions make t-NPD suitable for a wide range of potential applications.
RESUMO
0D organic-inorganic metal halides (OIMHs) provide unprecedented versatility in structures and photoluminescence properties. Here, a series of bluish-white emissive 0D OIMHs, (TPE-TPP)2Sb2BrxCl8-x (x = 1.16 to 8), are prepared by assembling the 1-triphenylphosphonium-4-(1,2,2-triphenylethenyl)benzene cation (TPE-TPP)+ with antimony halides anions. Based on experimental characterizations and theoretical calculations, the emission of the 0D OIMHs are attributed to the fluorescence of the organic cations with aggregation-induced emission (AIE) properties. The 0D structure minimized the molecular motion and intermolecular interactions between (TPE-TPP)+ cations, effectively suppressing the non-radiative recombination processes. Consequently, the photoluminescence quantum efficiency (PLQE) of (TPE-TPP)2Sb2Br1.16Cl6.84 is significantly enhanced to 55.4% as compared to the organic salt (TPE-TPP)Br (20.5%). The PLQE of (TPE-TPP)2Sb2BrxCl8-x can also be readily manipulated by halide substitution, due to the competitive processes between non-radiative recombination on the inorganic moiety and the energy transfer from inorganic to organic. In addition, electrically driven light-emitting diodes (LEDs) are fabricated based on (TPE-TPP)2Sb2Br1.16Cl6.84 emitter, which exhibited bluish-white emission with a maximum external quantum efficiency (EQE) of 1.1% and luminance of 335 cd m-2. This is the first report of electrically driven LED based on 0D OIMH with bluish-white emission.
RESUMO
OBJECTIVES: Total-body PET/CT scanners with long axial fields of view have enabled unprecedented image quality and quantitative accuracy. However, the ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Therefore, we attempted to generate CT-free attenuation-corrected (CTF-AC) total-body PET images through deep learning. METHODS: Based on total-body PET data from 122 subjects (29 females and 93 males), a well-established cycle-consistent generative adversarial network (Cycle-GAN) was employed to generate CTF-AC total-body PET images directly while introducing site structures as prior information. Statistical analyses, including Pearson correlation coefficient (PCC) and t-tests, were utilized for the correlation measurements. RESULTS: The generated CTF-AC total-body PET images closely resembled real AC PET images, showing reduced noise and good contrast in different tissue structures. The obtained peak signal-to-noise ratio and structural similarity index measure values were 36.92 ± 5.49 dB (p < 0.01) and 0.980 ± 0.041 (p < 0.01), respectively. Furthermore, the standardized uptake value (SUV) distribution was consistent with that of real AC PET images. CONCLUSION: Our approach could directly generate CTF-AC total-body PET images, greatly reducing the radiation risk to patients from redundant anatomical examinations. Moreover, the model was validated based on a multidose-level NAC-AC PET dataset, demonstrating the potential of our method for low-dose PET attenuation correction. In future work, we will attempt to validate the proposed method with total-body PET/CT systems in more clinical practices. CLINICAL RELEVANCE STATEMENT: The ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Our CT-free PET attenuation correction method would be beneficial for a wide range of patient populations, especially for pediatric examinations and patients who need multiple scans or who require long-term follow-up. KEY POINTS: ⢠CT is the main source of radiation in PET/CT imaging, especially for total-body PET/CT devices, and reduced radiopharmaceutical doses make the radiation burden from CT more obvious. ⢠The CT-free PET attenuation correction method would be beneficial for patients who need multiple scans or long-term follow-up by reducing additional radiation from redundant anatomical examinations. ⢠The proposed method could directly generate CT-free attenuation-corrected (CTF-AC) total-body PET images, which is beneficial for PET/MRI or PET-only devices lacking CT image poses.
RESUMO
Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N-oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N-oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N-oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.
RESUMO
A visible-light-induced radical relay cyclization/C-C bond formation of quinoxalin-2(1H)-ones with allyloxy-tethered aryl iodides using polysulfide anions as a photocatalyst is described. This protocol allows efficient access to a variety of complicated molecules bearing both quinoxalin-2(1H)-one and 2,3-dihydrobenzofuran motifs in high yields under mild reaction conditions with a broad range of substrates.
RESUMO
Advanced sensor technology is widely applied in human motion monitoring and research. However, it often encounters problems such as scratches, fractures, and aging, which affect its lifespan and reliability. To address these challenges, we draw inspiration from the inherent self-healing properties of organic biological entities in nature to endow our sensors with self-healing capability. In this work, we constructed a reversible multi-hydrogen-bonded physical crosslinking network and introduced aromatic disulfide bonds into the polyurethane backbone. This design not only achieves a very high mechanical strength of the material, but also efficient self-healing properties. At 80 °C, the tensile strength of the WPU-U2D1 material reached 28.88 MPa, with a fracture elongation of 748.64%, and a self-healing efficiency as high as 99.24%. Based on this material, we successfully prepared a flexible conductive composite film (WPU@AgNW) and applied it to flexible strain sensors. The sensor demonstrated excellent sensitivity and reliability in human motion monitoring (electrical conductivity of 2.66 S cm-1), which provides a new idea for realising the breakthrough of high-performance flexible sensors. These outstanding properties makes it have great potential for application in flexible wearable devices, human-computer interaction, bionic electronic devices and other fields.
RESUMO
This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.
RESUMO
KEY MESSAGE: HanMYB1 was found to play positive roles in the modulation of anthocyanins metabolism based on the integrative analysis of different color cultivars and the related molecular genetic analyses. As a high value ornamental and edible crop with various colors, sunflowers (Helianthus annuus L.) provide an ideal system to understand the formation of flower color. Anthocyanins are major pigments in higher plants, which is associated with development of flower colors and ability of oxidation resistance. Here, we performed an integrative analysis of the transcriptome and flavonoid metabolome in five sunflower cultivars with different flower colors. According to differentially expressed genes and differentially accumulated flavonoids, these cultivars could be grouped into yellow and red. The results showed that more anthocyanins were accumulated in the red group flowers, especially the chrysanthemin. Some anthocyanins biosynthesis-related genes like UFGT (UDP-glycose flavonoid glycosyltransferase) also expressed more in the red group flowers. A MYB transcriptional factor, HanMYB1, was found to play vital positive roles in the modulation of anthocyanins metabolism by the integrative analysis. Overexpressed HanMYB1 in tobacco could deepen the flower color, increase the accumulation of anthocyanins and directly active the express of UFGT genes. Our findings indicated that the MYB transcriptional factors provide new insight into the dynamic regulation of the anthocyanin biosynthesis in facilitating sunflower color formation and anthocyanin accumulation.
Assuntos
Antocianinas , Helianthus , Antocianinas/metabolismo , Transcriptoma/genética , Helianthus/genética , Helianthus/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Flavonoides/metabolismo , Metaboloma , Flores , Regulação da Expressão Gênica de Plantas , Cor , Pigmentação/genética , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.
Assuntos
Celulose , Dissulfetos , Molibdênio , Regeneração Nervosa , Células de Schwann , Alicerces Teciduais , Regeneração Nervosa/efeitos dos fármacos , Animais , Ratos , Alicerces Teciduais/química , Dissulfetos/química , Dissulfetos/farmacologia , Células de Schwann/efeitos dos fármacos , Molibdênio/química , Molibdênio/farmacologia , Celulose/química , Celulose/farmacologia , Celulose/análogos & derivados , Ratos Sprague-Dawley , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Proliferação de Células/efeitos dos fármacos , Engenharia Tecidual/métodos , Masculino , Traumatismos dos Nervos Periféricos , EstereoisomerismoRESUMO
BACKGROUND: Nasal reconstruction after conventional surgical excision (CSE) of nonmelanoma skin cancer (NMSC) can be challenging. After excision and before the pathologic report, a simple reconstruction is favored. Yet, little is known about patient satisfaction after primary closure and second intention healing. OBJECTIVE: Patient satisfaction after nasal defect reconstruction with primary closure or second intention healing, using the FACE-Q Skin Cancer. METHODS: All patients who underwent CSE of nasal NMSC with immediate primary closure or second intention healing between March 2018 and March 2020 at Máxima Medisch Centrum Veldhoven were identified and asked to complete the FACE-Q Skin Cancer. RESULTS: Of 183 patients, 140 patients completed the questionnaire. Fifty-five defects were closed by primary closure (38.5%) and 88 by second intention healing (61.5%). Thirty-one complications were reported (16.7%), of which 87.1% ( n = 27) after second intention healing ( p = .004). Both groups experienced high facial and scar satisfaction, low appearance-related distress, and no to minimal adverse effects. Second intention healing had 2.7 higher odds of achieving the maximum scar satisfaction score ( p = .02). CONCLUSION: This study shows high satisfaction on facial and scar appraisal, low appearance-related distress, and no to minimal adverse effects for second intention healing and primary closure after CSE of nasal NMSC.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Faciais , Neoplasias Nasais , Neoplasias Cutâneas , Humanos , Satisfação do Paciente , Cicatriz/etiologia , Estudos Transversais , Intenção , Neoplasias Cutâneas/cirurgia , Neoplasias Nasais/cirurgia , Neoplasias Faciais/cirurgia , Estudos de CoortesRESUMO
INTRODUCTION: Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients. METHODS: Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot. RESULTS: GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1,390-1,556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles. CONCLUSION: The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases.
RESUMO
BACKGROUND: Lumbar degenerative conditions are a major cause of back pain and disability in individuals aged 45 and above. Gait analysis utilizes sensor technology to collect movement data, aiding in the evaluation of various gait aspects like spatiotemporal parameters, joint angles, neuromuscular activity, and joint forces. It is widely used in conditions such as cerebral palsy and knee osteoarthritis. This research aims to assess the effectiveness of 3D gait analysis in evaluating surgical outcomes and postoperative rehabilitation for lumbar degenerative disorders. METHODS: A prospective self-controlled before-after study (n = 85) carried out at our Hospital (Sep 2018 - Dec 2021) utilized a 3D motion analysis system to analyze gait in patients with lumbar degenerative diseases. The study focused on the multifidus muscle, a crucial spinal muscle, during a minimally invasive lumbar interbody fusion surgery conducted by Shandong Weigao Pharmaceutical Co., Ltd. Pre- and postoperative assessments included time-distance parameters (gait speed, stride frequency, stride length, stance phase), hip flexion angle, and stride angle. Changes in 3D gait parameters post-surgery and during rehabilitation were examined. Pearson correlation coefficient was employed to assess relationships with the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) scores. Patient sagittal alignment was evaluated using "Surgimap" software from two types of lateral radiographs to obtain parameters like pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), intervertebral space height (DH), posterior height of the intervertebral space (PDH) at the operative segment, and anterior height of the intervertebral space (ADH). RESULTS: By the 6th week post-operation, significant improvements were observed in the VAS score, JOA score, and ODI score of the patients compared to preoperative values (P < 0.05), along with notable enhancements in 3D gait quantification parameters (P < 0.05). Pearson correlation analysis revealed a significant positive correlation between improvements in 3D gait quantification parameters and VAS score, JOA score, and ODI value (all P < 0.001). CONCLUSION: 3D gait analysis is a valuable tool for evaluating the efficacy of surgery and rehabilitation training in patients.