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1.
Commun Chem ; 7(1): 91, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643239

RESUMO

Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (-)-diethyl D-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising ß-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 µM in recombinant human GCase activity in Gaucher cell lines.

2.
JACS Au ; 4(3): 908-918, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38559739

RESUMO

The use of pharmacological chaperones (PCs) to stabilize specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. Our previous study found that dibasic polyhydroxylated pyrrolidine 5 exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) compared with its monobasic parent molecule, 4. To further investigate the role of different C-2 moieties on the pH-selectivity and protecting effects of these compounds, we designed and synthesized a library of monobasic and dibasic iminosugars, screened them for α-Gal A-stabilizing activity using thermal shift and heat-induced denaturation assays, and characterized the mechanistic basis for this stabilization using X-ray crystallography and binding assays. We noted that the dibasic iminosugars 5 and 20 protect α-Gal A from denaturation and inactivation at lower concentrations than monobasic or other N-substituted derivatives; a finding attributed to the nitrogen on the C-2 methylene of 5 and 20, which forms the bifurcated salt bridges (BSBs) with two carboxyl residues, E203 and D231. Additionally, the formation of BSBs at pH 7.0 and the electrostatic repulsion between the vicinal ammonium cations of dibasic iminosugars at pH 4.5 are responsible for their pH-selective binding to α-Gal A. Moreover, compounds 5 and 20 demonstrated promising results in improving enzyme replacement therapy and exhibited significant chaperoning effects in Fabry cells. These findings suggest amino-iminosugars 5 and 20 as useful models to demonstrate how an additional exocyclic amino group can improve their pH-selectivity and protecting effects, providing new insights for the design of pH-selective PCs.

3.
Front Behav Neurosci ; 18: 1357453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562516

RESUMO

Introduction: Autism spectrum disorder (ASD) is a neurological condition that is marked by deficits in social interaction, difficulty expressing oneself, lack of enthusiasm, and stereotypical conduct. The TOMATIS training method is an effective music therapy for children with ASD for its individually developed programs to improve behavioral deficits. Methods: The research employed both longitudinal and crosssectional designs. Results: In the cross-sectional study, the experimental group showed significant improvement in symptoms after TOMATIS training compared to the control group of children with ASD. The results validated the effect of TOMATIS treatment for ASD-related deficits, including perceptual-motor, attentional, social, and emotional issues. Discussion: ASD's auditory hypersensitivity hampers social information processing, but TOMATIS enhances cochlear frequency selectivity, aiding in capturing relevant auditory stimuli. In addition, the longitudinal study confirmed these findings, which proved TOMATIS training effective in clinically treating ASD. This study focused on audiometric indicators and behavioural improvement, elucidating the mechanisms behind the training's success. Behavioral improvements might stem from TOMATIS' frequency selectivity, reshaping auditory organ-cortical feedback loops to filter interference and focus on valid information.

4.
Int J Nanomedicine ; 19: 3233-3257, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601346

RESUMO

Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Preparações de Ação Retardada , Comunicação Celular , Transdução de Sinais
5.
Int J Oral Sci ; 16(1): 32, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627388

RESUMO

Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.


Assuntos
Má Oclusão , Humanos , Criança , Consenso , Má Oclusão/epidemiologia , Assistência Odontológica , China
6.
Front Bioeng Biotechnol ; 12: 1339135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476968

RESUMO

Introduction: Bone tissue engineering is considered the ideal approach for bone repair. Mesoporous bioactive glass (MBG) possesses the characteristics of high drug-loading capacity and bioactivity. Low-intensity pulsed ultrasound contributes to promoting fracture healing and bone defect repair, and dimethyloxalyl glycine (DMOG) is a small molecular inhibitor that can suppress prolyl hydroxylase, reducing the degradation of hypoxia-inducible factor. Methods: In this study, we proposed to prepare DMOG-loaded MBG/poly(D,L-lactide) composite scaffolds (DMOG-MBG/PDLLA) for promoting bone repair. The effects of ultrasound stimulation and DMOG release on the cell responses of rat bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) and bone repair in vivo were investigated. Results and Discussion: The results showed that both ultrasound stimulation and DMOG release could promote the proliferation, adhesion and differentiation of BMSCs and HUVECs, respectively. After the implantation of scaffolds in rat cranial bone defect model for 8 weeks, the results indicated that the combined ultrasound stimulation and DMOG release contributed to the highest ability for promoting bone repair. Hence, the DMOG-MBG/PDLLA scaffolds with ultrasound stimulation are promising for application in bone repair.

7.
J Am Chem Soc ; 146(10): 6974-6982, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38417031

RESUMO

The two-dimensional (2D) perovskites have drawn intensive attention due to their unique stability and outstanding optoelectronic properties. However, the debate surrounding the spatial phase distribution and band alignment among different 2D phases in the quasi-2D perovskite has created complexities in understanding the carrier dynamics, hindering material and device development. In this study, we employed highly sensitive transient absorption spectroscopy to investigate the carrier dynamics of (BA)2(MA)n-1PbnI3n+1 quasi-2D Ruddlesden-Popper perovskite thin films, nominally prepared as n = 4. We observed the carrier-density-dependent electron and hole transfer dynamics between the 2D and three-dimensional (3D) phases. Under a low carrier density within the linear response range, we successfully resolved three ultrafast processes of both electron and hole transfers, spanning from hundreds of femtoseconds to several picoseconds, tens to hundreds of picoseconds, and hundreds of picoseconds to several nanoseconds, which can be attributed to lateral-epitaxial, partial-epitaxial, and disordered-interface heterostructures between 2D and 3D phases. By considering the interplay among the phase structure, band alignment, and carrier dynamics, we have proposed material synthesis strategies aimed at enhancing the carrier transport. Our results not only provide deep insights into an accurate intrinsic photophysics of quasi-2D perovskites but also inspire advancements in the practical application of these materials.

8.
Bioorg Chem ; 145: 107203, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38377817

RESUMO

Antimicrobial photodynamic therapy (PDT) is a promising alternative to antibiotics for eradicating pathogenic bacterial infections. It holds advantage of not inducing antimicrobial resistance but is limited for the treatment of gram-negative bacterial infection due to the lack of photosensitizer (PS) capable of targeted permeating the outer membrane (OM) of gram-negative bacteria. To facilitate the targeted permeability of PS, cyclic polymyxin b nonapeptide that can specifically bind to the lipopolysaccharide on OM, is conjugated to an FDA approved PS chlorin e6 via variable linkers. Based on structure to activity study, C6pCe6 with aminohexanoic linker and P2pCe6 with amino-3, 6-dioxaoctanoic linker are identified to preferentially image gram-negative bacteria. These two conjugates also exhibit improved aqueous dispersity and enhanced ROS generation, consequently enabled their selective bactericidal activities against gram-negative bacteria upon 660 nm light irradiation. The effective photobactericidal ability of P2pCe6 is further validated on P. aeruginosa infected G. mellonella. Moreover, it is demonstrated to effectively treat the P. aeruginosa infection and accelerate the healing process at the wound site of mouse. Owing to the light irradiation triggered targeted imaging and enhanced bactericidal capacities, P2pCe6 hold great potential to serve as a potent PS for mediating the phototheranostics of gram-negative bacterial infection.


Assuntos
Anti-Infecciosos , Infecções por Bactérias Gram-Negativas , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Fotoquimioterapia/métodos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas
9.
World J Clin Cases ; 12(2): 431-442, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313641

RESUMO

BACKGROUND: The relation between orthodontic treatment and temporomandibular disorders (TMDs) is under debate; the management of TMD during orthodontic treatment has always been a challenge. If TMD symptoms occur during orthodontic treatment, an immediate pause of orthodontic adjustments is recommended; the treatment can resume when the symptoms are managed and stabilized. CASE SUMMARY: This case report presents a patient (26-year-old, female) with angle class I, skeletal class II and TMDs. The treatment was a hybrid of clear aligners, fixed appliances and temporary anchorage devices (TADs). After 3 mo resting and treatment on her TMD, the patient's TMD symptom alleviated, but her anterior occlusion displayed deep overbite. Therefore, the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves. After the levelling, the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion. After careful examination of temporomandibular joints (TMJ) position, the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion. Eventually, the improved facial appearance and relatively stable occlusion were achieved. The 1-year follow-up records showed there was no obvious change in TMJ morphology, and her occlusion was stable. CONCLUSION: TMD screening and monitoring is of great clinical importance in the TMD susceptible patients. Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

10.
Sci Rep ; 14(1): 4966, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424179

RESUMO

To investigate and compare the facial asymmetry (hard and soft tissues) among skeletal Class I, II, and III patients. A total of 221 subjects, including skeletal Class I (n = 80), skeletal Class II (n = 75), and skeletal Class III (n = 66), were included in the study. CBCT, 22 skeletal landmarks, and 10 soft tissue landmarks were used for the measurements and the asymmetry index was calculated to assess the facial asymmetry. Statistical analyses included one-way ANOVA, Kruskal-Wallis test, and Spearman correlation analysis. The skeletal Class III patients presented greater asymmetry than Class II patients for 10 hard tissue landmarks and 3 soft tissue landmarks (p < 0.05). High correlation of asymmetry was found between four soft tissue landmarks and their corresponding skeletal landmarks (rs ≥ 0.71), as well as Me and ANS (r > 0.86). The ANS and Me in 21.3% patients deviated to contralateral sides. The skeletal Class III patients had more facial asymmetry than the Class II patients. Soft tissues showed similar asymmetry as the underlying hard tissues rather than a compensation of the hard tissue asymmetry. The inconsistency in the deviation of Me and ANS may exacerbate facial asymmetry.


Assuntos
Assimetria Facial , Mandíbula , Humanos , Cefalometria , Imageamento Tridimensional
11.
Nat Commun ; 15(1): 1548, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378784

RESUMO

Mitochondrial cytochrome c maturation (CCM) requires heme attachment via distinct pathways termed systems I and III. The mosaic distribution of these systems in Archaeplastida raises questions about the genetic mechanisms and evolutionary forces promoting repeated evolution. Here, we show a recurrent shift from ancestral system I to the eukaryotic-specific holocytochrome c synthase (HCCS) of system III in 11 archaeplastid lineages. Archaeplastid HCCS is sufficient to rescue mutants of yeast system III and Arabidopsis system I. Algal HCCS mutants exhibit impaired growth and respiration, and altered biochemical and metabolic profiles, likely resulting from deficient CCM and reduced cytochrome c-dependent respiratory activity. Our findings demonstrate that archaeplastid HCCS homologs function as system III components in the absence of system I. These results elucidate the evolutionary trajectory and functional divergence of CCM pathways in Archaeplastida, providing insight into the causes, mechanisms, and consequences of repeated cooption of an entire biological pathway.


Assuntos
Citocromos c , Mitocôndrias , Sequência de Aminoácidos , Citocromos c/genética , Citocromos c/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo
12.
Physiol Behav ; 277: 114461, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215863

RESUMO

Esketamine, the right-handed optical isomer of racemic ketamine, is a rapidly acting antidepressant approved by the FDA for treatment-resistant depression in 2019. However, few studies have investigated esketamine's role in learning and memory, particularly in the context of memory reconsolidation. Herein, we evaluated esketamine's role in memory reconsolidation in 7-week-old male Institute of Cancer Research mice subjected to the novel object recognition (NOR) memory task. The NOR reconsolidation procedure comprised three phases: sampling, reactivation, and testing. Esketamine-enhanced NOR memory performance when injected into mice 0 h after reactivation rather than following a 6 h delay. Conversely, administering esketamine 24 h after sampling without reactivation did not enhance NOR memory performance. Notably, esketamine exhibited no discernible effects on nonspecific responses, such as locomotor activity and exploratory behavior. Furthermore, the α-amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor antagonist NBQX effectively blocked the esketamine-induced enhancement of memory reconsolidation. In conclusion, esketamine treatment markedly improves memory reconsolidation in NOR tasks, and this effect is linked to AMPA receptor activity.


Assuntos
Ketamina , Masculino , Camundongos , Animais , Ketamina/farmacologia , Antidepressivos/farmacologia , Aprendizagem
13.
Sci Rep ; 14(1): 2519, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291067

RESUMO

This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.


Assuntos
Face , Má Oclusão Classe III de Angle , Adulto , Humanos , Face/diagnóstico por imagem , Face/anatomia & histologia , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Nariz , Maxila/diagnóstico por imagem , Maxila/cirurgia , Lábio , Cefalometria/métodos , Imageamento Tridimensional/métodos
14.
Angew Chem Int Ed Engl ; 63(17): e202319462, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38286750

RESUMO

Developing highly active oxygen evolution reaction (OER) catalysts in acidic conditions is a pressing demand for proton-exchange membrane water electrolysis. Manipulating proton character at the electrified interface, as the crux of all proton-coupled electrochemical reactions, is highly desirable but elusive. Herein we present a promising protocol, which reconstructs a connected hydrogen-bond network between the catalyst-electrolyte interface by coupling hydrophilic units to boost acidic OER activity. Modelling on N-doped-carbon-layer clothed Mn-doped-Co3O4 (Mn-Co3O4@CN), we unravel that the hydrogen-bond interaction between CN units and H2O molecule not only drags the free water to enrich the surface of Mn-Co3O4 but also serves as a channel to promote the dehydrogenation process. Meanwhile, the modulated local charge of the Co sites from CN units/Mn dopant lowers the OER barrier. Therefore, Mn-Co3O4@CN surpasses RuO2 at high current density (100 mA cm-2 @ ~538 mV).

15.
J Pept Sci ; : e3566, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38271799

RESUMO

Figainin 2 is a cationic, hydrophobic, α-helical host-defense peptide with 28 residues, which was isolated from the skin secretions of the Chaco tree frog. It shows potent inhibitory activity against both Gram-negative and Gram-positive pathogens and has garnered considerable interest in developing novel classes of natural antibacterial agents. However, as a linear peptide, conformational flexibility and poor proteolytic stability hindered its development as antibacterial agent. To alleviate its susceptibility to proteolytic degradation and improve its antibacterial activity, a series of hydrocarbon-stable analogs of Figainin 2 were synthesized and evaluated for their secondary structure, protease stability, antimicrobial, and hemolytic activities. Among them, F2-12 showed significant improvement in protease resistance and antimicrobial activity compared to that of the template peptide. This study provides a promising strategy for the development of antimicrobial drugs.

16.
China CDC Wkly ; 6(1): 12-22, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38223659

RESUMO

Objective: This study aims to provide a theoretical foundation for the development and practical application of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) prevention and control policy systems in China by scrutinizing, analyzing, and synthesizing the evolution of Chinese policies in this domain. Methods: Utilizing grounded theory, we employed NVivo12 software to perform text content analysis, mining, and coding classification, along with visualization techniques, on policy texts sourced from Chinese government platforms, including the official website of China's State Council. We considered four analytical dimensions - time, subject, type, and object. Results: The National Health Commission and the State Council emerged as the primary entities engaged in policymaking for HIV/AIDS in China. We identified four distinct stages in the evolution of these policies, culminating in a novel 'sun-shaped' HIV/AIDS prevention and control policy network model with an emphasis on 'knowledge, attitude, and practice' at its nucleus, which aligns with national conditions and societal progress. Furthermore, the focal groups of these policies have been dynamically refined and updated over time. Conclusions: Our findings introduce a 'sun-shaped' HIV/AIDS prevention and control policy network model specific to China. We observed a conceptual policy shift towards prioritizing overall human health rather than confining the focus to disease treatment. Additionally, in light of China's growing elderly population, the imperative to address HIV/AIDS prevention and control among older adults is an issue that warrants increased attention.

17.
BMC Cancer ; 24(1): 41, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183079

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing. METHODS: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas. RESULTS: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-ß signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma. CONCLUSIONS: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/genética , Transcriptoma , Processos Neoplásicos , Hipóxia/genética
18.
Fish Shellfish Immunol ; 144: 109218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37977543

RESUMO

Grouper is one of the most important and valuable mariculture fish in China, with a high economic value. As the production of grouper has increased, massive outbreaks of epidemic diseases have limited the development of the industry. Singapore grouper iridovirus (SGIV) is one of the most serious infectious viral pathogens and has caused huge economic losses to grouper farming worldwide due to its rapid spread and high lethality. To find new strategies for the effective prevention and control of SGIV, we constructed two chimeric DNA vaccines using Lysosome-associated membrane protein 1 (LAMP1) fused with major capsid proteins (MCP) against SGIV. In addition, we evaluated the immune protective effects of vaccines including pcDNA3.1-3HA, pcDNA3.1-MCP, pcDNA3.1-LAMP1, chimeric DNA vaccine pcDNA3.1-MLAMP and pcDNA3.1-LAMCP by intramuscular injection. Our results showed that compared with groups injected with PBS, pcDNA3.1-3HA, pcDNA3.1-LAMP1 or pcDNA3.1-MCP, the antibody titer significantly increased in the chimeric vaccine groups. Moreover, the mRNA levels of immune-related factors in groupers, including IRF3, MHC-I, TNF-α, and CD8, showed the same trend. However, MHC-II and CD4 were significantly increased only in the chimeric vaccine groups. After 28 days of vaccination, groupers were challenged with SGIV, and mortality was documented for each group within 14 days. The data showed that two chimeric DNA vaccines provided 87 % and 91 % immune protection for groupers which were significantly higher than the 52 % protection rate of pcDNA3.1-MCP group, indicating that both forms of LAMP1 chimeric vaccines possessed higher immune protection against SGIV, providing the theoretical foundation for the creation of novel DNA vaccines for fish.


Assuntos
Bass , Infecções por Vírus de DNA , Doenças dos Peixes , Iridovirus , Ranavirus , Vacinas de DNA , Animais , Singapura , Fatores de Transcrição , Infecções por Vírus de DNA/prevenção & controle , Infecções por Vírus de DNA/veterinária , Infecções por Vírus de DNA/genética , Proteínas de Peixes/genética
19.
Plants (Basel) ; 12(24)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38140429

RESUMO

Understory planting affects the growth environment of tea plants, regulating the tea plant growth and the formation of secondary metabolites, which in turn affects the flavor of Xiaobai white tea. The present research adopted biochemical composition determination, widely targeted volatilities (WTV) analysis, multivariate statistical analysis, and odor activity value (OAV) analysis to analyze the characteristics in the macro-composition and volatile compounds of understory white tea. The sensory evaluation results indicated that understory Xiaobai white tea (LWTs) was stronger than ordinary Xiaobai white tea (PWTs) in terms of the taste of smoothness, sweetness, and thickness as well as the aromas of the flower and sweet. Understory planting reduced light intensity and air temperature, increased air humidity, organic matter, total nitrogen, and available nitrogen contents, which improved the growth environment of tea plants. The phytochemical analysis showed that the water-extractable substances, caffeine, flavonoids, and soluble sugar contents of understory tea fresh-leaf (LF) were higher than those of ordinary fresh-leaf (PF). The phytochemical analysis showed that the free amino acids, theaflavins, thearubigins, water-extractable substances, and tea polyphenols contents of LWTs were significantly higher than those of PWTs, which may explain the higher smoothness, sweetness, and thickness scores of LWTs than those of PWTs. The 2-heptanol, 2-decane, damasone, and cedar alcohol contents were significantly higher in LWTs than in PWTs, which may result in stronger flowery and sweet aromas in LWTs than in PWTs. These results provide a firm experimental basis for the observed differences in the flavor of LWTs and PWTs.

20.
Opt Express ; 31(22): 36845-36858, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017826

RESUMO

For ultra-precision machining of convex blazed grating elements there are inevitable machining errors, surface defects, and surface roughness, all of which can have an impact on their diffraction efficiency. In this paper, we use PCGrate software based on the integration method to establish the machining error model, surface defect model, and surface roughness model of convex spherical blazed grating with a curvature radius of 41.104 mm, a substrate diameter of 14 mm, a grating density of 53.97 line/mm and a blazed angle of 3.86° as the basic specification. To investigate the effect of base curvature radius error, grating period error, blazed angle error, grating ridge and valley passivation radius, Poisson burr height, and blaze surface roughness on their -1 order diffraction efficiency in the 0.95-2.5 µm spectral range. The results show that when the curvature radius error of the spherical base is less than ±80µm, the influence on diffraction efficiency can be ignored. Among the three groups of grating microstructure parameters, the influence of blazed angle on grating diffraction efficiency is the largest, followed by a grating period, and the influence of grating apex angle is the smallest, among which when the error of blazed angle is less than ±0.1° and the error of grating period is less than ±0.1µm, the influence on diffraction efficiency can be ignored. The effect of the passivation radius of the grating valley on the diffraction efficiency is smaller than that of the passivation radius of the grating ridge, and the maximum reduction of diffraction efficiency is 0.096 and 0.144 when the grating ridge and valley passivation radius are 50nm∼650 nm, respectively. The diffraction efficiency decreases significantly in the wavelength range of 1.9-2.5 µm with the increase of Poisson burr height and blaze surface roughness, and its effect on the diffraction efficiency can be neglected when the Poisson burr height is less than 0.5 µm and the blaze surface roughness value is less than RMS 1 nm. The machining error, surface defect, and surface roughness models of the convex blazed grating are optimized to provide a comprehensive machining accuracy basis for ultra-precision cutting of convex grating components.

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