Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros












Base de dados
Intervalo de ano de publicação
1.
Nat Rev Chem ; 8(5): 359-375, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38671189

RESUMO

Halogen-powered static conversion batteries (HSCBs) thrive in energy storage applications. They fall into the category of secondary non-flow batteries and operate by reversibly changing the chemical valence of halogens in the electrodes or/and electrolytes to transfer electrons, distinguishing them from the classic rocking-chair batteries. The active halide chemicals developed for these purposes include organic halides, halide salts, halogenated inorganics, organic-inorganic halides and the most widely studied elemental halogens. Aside from this, various redox mechanisms have been discovered based on multi-electron transfer and effective reaction pathways, contributing to improved electrochemical performances and stabilities of HSCBs. In this Review, we discuss the status of HSCBs and their electrochemical mechanism-performance correlations. We first provide a detailed exposition of the fundamental redox mechanisms, thermodynamics, conversion and catalysis chemistry, and mass or electron transfer modes involved in HSCBs. We conclude with a perspective on the challenges faced by the community and opportunities towards practical applications of high-energy halogen cathodes in energy-storage devices.

2.
BMC Med Genomics ; 17(1): 57, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383389

RESUMO

BACKGROUND: Copy number variation (CNV) of X chromosome can lead to a variety of neonatal abnormalities, especially for male fetuses. In recent years, due to the high sensitivity and high specificity of NIPS, its application has gradually expanded from chromosome aneuploidy to CNV. Few prenatal cases involving the detection of Xq duplication and deletion by NIPS have been reported, but it is of great significance for genetic counseling. CASE PRESENTATION: A 36-year-old woman was referred for prenatal diagnosis and genetic counseling at 17 weeks of gestation because of abnormal result of noninvasive prenatal screening (NIPS). Multiple congenital malformations, hydrocephalus, and enlarged gallbladder were observed by prenatal ultrasound. Amniocentesis revealed the karyotype of the fetus as 46, XN, add(X) (p22.2) and the result of chromosomal microarray analysis was arr[hg19] Xq27.1q28(138,506,454-154896094) × 2 and arr[hg19] Xp22.33p22.32(168,551-5,616,964) × 1. CNV-seq showed that the mother shares a 16.42 Mb duplication in the Xq27.1-q28 region and a 2.97 Mb deletion in the Xp22.33-p22.32 region. After genetic counseling, the couple chose to terminate the pregnancy. CONCLUSION: The combination of NIPS and CMA would be of values in detection of subchromosomal duplications and/or deletions at fetal stage. The detection of X chromosome aberration in a male fetus should give suspicion of the possibility of maternal inheritance.


Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Gravidez , Feminino , Recém-Nascido , Humanos , Masculino , Adulto , Amniocentese , Cariotipagem , Aneuploidia
3.
Materials (Basel) ; 17(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276436

RESUMO

Manganese slag (MS) is a kind of chemical waste, which may pollute the environment if conventional handling methods (stacking and landfill) are applied. Ultra-high-performance concrete (UHPC)-with considerably high compactness and strength-can be used not only as a special concrete material, but also to solidify the toxic substances in solid waste. This study proposes the addition of MS to UHPC, where the mass ratio of MS varies from 0% to 40% in the total mass of MS and silica fume. The effects of MS on the fluidity, plastic viscosity, and yield shear stress are investigated, and the flexural strength, compressive strength, and dry shrinkage rate of UHPC with MS are measured. X-ray diffraction (XRD) spectrum and energy spectrum analysis (EDS) diagrams are obtained to analyze the performance mechanism of the UHPC. A rheological study confirms that the slump flow increases with the increasing rate of 0-14.3%, while the yield shear stress and plastic viscosity decrease with the rates of 0-29.6% and 0-22.2%, respectively. The initial setting time increases with the mass ratio of MS by 0-14.3%, and MS has a positive effect on the flexural and compressive strengths of UHPC. In the early curing stage (less than 14 days), the increasing rate in the specimens increases with the curing age; meanwhile, when the curing age reaches 14 days or higher, the increasing rate decreases with increasing curing age. The compactness of UHPC is increased by adding MS. Furthermore, MS can increase the elements of Al and decrease crystals of Ca(OH)2 and calcium silicate hydrate in UHPC.

4.
Nutr Rev ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287649

RESUMO

Dietary restriction and fasting have been recognized for their beneficial effects on health and lifespan and their potential application in managing chronic metabolic diseases. However, long-term adherence to strict dietary restrictions and prolonged fasting poses challenges for most individuals and may lead to unhealthy rebound eating habits, negatively affecting overall health. As a result, a periodic fasting-mimicking diet (PFMD), involving cycles of fasting for 2 or more days while ensuring basic nutritional needs are met within a restricted caloric intake, has gained widespread acceptance. Current research indicates that a PFMD can promote stem cell regeneration, suppress inflammation, extend the health span of rodents, and improve metabolic health, among other effects. In various disease populations such as patients with diabetes, cancer, multiple sclerosis, and Alzheimer's disease, a PFMD has shown efficacy in alleviating disease symptoms and improving relevant markers. After conducting an extensive analysis of available research on the PFMD, it is evident that its advantages and potential applications are comparable to other fasting methods. Consequently, it is proposed in this review that a PFMD has the potential to fully replace water-only or very-low-energy fasting regimens and holds promise for application across multiple diseases.

5.
Microbiol Res ; 281: 127597, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38266597

RESUMO

Pest feeding affects the rhizobacteria community. The rhizomicrobiota activates salicylic acid and jasmonic acid signaling pathways to help plants deal with pest infestation. However, whether plants can recruit special pesticidal microorganisms to deal with attack from herbivores is unclear. A system composed of peanuts and first-instar larvae of Holotrichia parallela were used to analyze whether peanuts truly enrich the insecticidal bacteria after feeding by larvae, and whether inoculation of the enriched bacteria promotes the resistance of plants to herbivore. In this study, high-throughput sequencing of 16 S rRNA gene amplicons was used to demonstrate that infestation of the subterranean pest H. parallela quickly changed the rhizosphere bacterial community structure within 24 h, and the abundance of Enterobacteriaceae, especially Enterobacter, was manifestly enriched. Root feeding induced rhizobacteria to form a more complex co-occurrence network than the control. Rhizosphere bacteria were isolated, and 4 isolates with high toxicity against H. parallela larvae were obtained by random forest analysis. In a back-inoculation experiment using a split-root system, green fluorescent protein (GFP)-labeled Enterobacter sp. IPPBiotE33 was observed to be enriched in uneaten peanut roots. Additionally, supplementation with IPPBiotE33 alleviated the adverse effects of H. parallela on peanuts. Our findings indicated that herbivore infestation could induce plants to assemble bacteria with specific larvicidal activity to address threats.


Assuntos
Besouros , Inseticidas , Animais , Herbivoria , Inseticidas/farmacologia , Inseticidas/metabolismo , Besouros/microbiologia , Larva , Bactérias/genética , Plantas , Raízes de Plantas/microbiologia
6.
Nutr J ; 22(1): 48, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37798712

RESUMO

BACKGROUND: The relationship between marine polyunsaturated fatty acid (PUFA) intake and cardiovascular disease and mortality in dyslipidemic patients is unclear. Men with dyslipidemia have a higher risk of cardiovascular disease than women, and PUFA supplementation may be more beneficial in men. OBJECTIVE: The purpose of this study was to assess the relationship between different types of marine polyunsaturated fatty acids intakes and cardiovascular disease, all-cause mortality, and cardiovascular mortality in adult U.S. males with dyslipidemia. METHODS: The study ultimately included 11,848 adult men with dyslipidemia who were screened from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2016. This was linked to the 2019 National Death Index (NDI) records to establish a prospective cohort. In the study, a logistic regression model was established to assess the relationship between PUFA intake and prevalent CVD, and a Cox proportional hazards regression model was established to assess the relationship between PUFA intake and death. RESULTS: In the fully adjusted models, compared with participants in the lowest tertile, participants with the highest DPA intake were associated with a lower risk of CVD (CVD: OR = 0.71, 95%CI: 0.55, 0.91; angina: OR = 0.54, 95%CI: 0.38, 0.79; stroke: OR = 0.62, 95%CI: 0.43, 0.89), but not with three subtypes of congestive heart failure, coronary heart disease, and myocardial infarction. And the highest tertile level of DPA intake can reduce all-cause mortality (HR = 0.77, 95%CI: 0.64, 0.91) and CVD mortality (HR = 0.68, 95%CI: 0.52, 0.90). CONCLUSIONS: Cardiovascular disease risk, all-cause mortality, and CVD mortality were inversely associated with dietary DPA intake but not EPA and DHA intakes in U.S. male participants with dyslipidemia.


Assuntos
Doenças Cardiovasculares , Doença das Coronárias , Humanos , Masculino , Adulto , Feminino , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Estudos Prospectivos , Risco
7.
Chem Biol Drug Des ; 102(6): 1643-1657, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37705131

RESUMO

Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti-cardiovascular and anti-diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti-diabetes anti-cardiovascular reagents.


Assuntos
Triterpenos , Solubilidade , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Ácido Ursólico
8.
Materials (Basel) ; 16(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569969

RESUMO

Secondary aluminum ash is a kind of common solid waste which will pollute the environment without any treatment. In this study, the influence of secondary aluminum ash on the rheological properties and the initial setting time of fresh reactive powder concrete (RPC) are researched. Meanwhile, the mechanical properties and the drying shrinkage rates of RPC with the secondary aluminum ash are determined. The electrical parameters of RPC with the secondary aluminum ash are measured. Scanning electron microscopy is obtained to reflect the internal structure of RPC. Results show that the addition of secondary aluminum ash can lead to decreasing the fluidity and increase the yield shear stress of fresh RPC paste by varying rates of 16.1% and 58.3%, respectively. The addition of secondary aluminum ash can decrease the flexural and compressive strengths of RPC cured for 1 day by the decreasing rates of 0~18.7% and 0~19.3%. When the curing age is 28 days, the flexural and compressive strengths of RPC are increased by 0~9.1% and 0~19.1% with adding the secondary aluminum ash. The secondary aluminum ash can promote the condensation of RPC. The addition of the secondary aluminum ash can decrease the electrical resistance of RPC by an order of magnitude. The relationship between the electrical resistance and the electrical reactance fits the quadratic function equation. The electrical resistance of the pore solution increases in the form of a quadratic function with the mass ratio of the secondary aluminum ash. The dry shrinkage rates of RPC cured for 1 day and 28 days are decreased by 0~36.4% and 0~41.3% with the increasing dosages of secondary aluminum ash. As obtained from the microscopic testing results, the secondary aluminum ash can improve the compactness of hydration products.

9.
Int J Bioprint ; 9(5): 769, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457935

RESUMO

Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.

10.
ACS Appl Mater Interfaces ; 15(12): 16266-16276, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36918536

RESUMO

Negatively charged surfaces and readily oxidizabile characteristics fundamentally restrict the use of MXene building blocks as anodes for anion intercalation. Herein, by embedding bacterial cellulose nanofibers with conformal polypyrrole coating (BC@PPy) and populating them between MXene (Ti3C2Tx) interlayers, we enable the fabricated MXene/BC@PPy (MBP) composite films to be highly efficient anodes for Cl--capturing in asymmetric capacitive deionization (CDI) systems. Performance gains are realized due to the surface electronegativity of MXene nanosheets becoming compensated by positively charged BC@PPy nanofibers, alleviating electrostatic repulsion, thus realizing reversible Cl- intercalation. More crucially, the anodization voltage of MBP is effectively enhanced as a result of the increase of the Ti valence state in MXene nanosheets with the addition of the BC@PPy spacer. Furthermore, BC@PPy nanopillars effectively enlarge the interlayer space for facile Cl- de-/intercalation, improve the vertical electron transfer between loosely deposited MXene nanosheets, and perform as additional active materials for Cl--capturing. Consequently, the MBP anode exhibits a promising desalination capacity of up to 17.56 mg g-1 at 1.2 V with a high capacity retention of 94.6% after 30 cycles in an asymmetric CDI system. This work offers a simple and effective strategy to unlock the application potential of MXene building blocks as anodes for Cl--capturing in electrochemical desalination.

11.
Expert Opin Biol Ther ; 23(8): 705-715, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36892190

RESUMO

BACKGROUND: MW031 is a biosimilar candidate of denosumab (Prolia®). This study aimed to compare the pharmacokinetics, pharmacodynamics, safety and immunogenicity of MW031 to denosumab in healthy Chinese participants. RESEARCH DESIGN AND METHODS: In this single-center, randomized, double-blind, parallel-controlled, single-dose trial, participants were given 60 mg MW031 (N = 58) or denosumab (N = 61) by subcutaneous injection and observed for 140 days. The primary endpoint was the bioequivalence of PK parameters (Cmax, AUC0-∞), and secondary endpoints including PD parameter, safety, and immunogenicity. RESULTS: A comparison of main PK parameters showed that the geometric mean ratios (GMR) (90% confidence intervals [CIs]) of AUC0-∞ and Cmax for MW031 over denosumab were 105.48% (98.96%, 112.43%) and 98.58% (92.78%, 104.75%), respectively. The inter-CV values of AUC0-∞ and Cmax for MW031 ranged from 19.9% to 23.1%. PD parameter (sCTX) in the MW031 and denosumab groups were similar, and the positivity rates of immunogenicity were 0% in both groups. This study also showed similar safety profiles in both groups, and there were no drug-related, high-incidence and previously unreported adverse reactions. CONCLUSION: This trial confirmed similar pharmacokinetic profiles of MW031 and denosumab in healthy male participants, and pharmacodynamic profile, immunogenicity and safety were comparable for both drugs. TRIAL REGISTRATION: NCT04798313; CTR20201149.


Assuntos
Anticorpos Monoclonais Humanizados , Medicamentos Biossimilares , Denosumab , Humanos , Masculino , Área Sob a Curva , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/metabolismo , Medicamentos Biossimilares/farmacocinética , Denosumab/efeitos adversos , Denosumab/imunologia , Denosumab/farmacocinética , Método Duplo-Cego , População do Leste Asiático , Voluntários Saudáveis , Equivalência Terapêutica , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacocinética , Ligante RANK/antagonistas & inibidores , Ligante RANK/imunologia , Injeções Subcutâneas
12.
J Colloid Interface Sci ; 630(Pt A): 34-45, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36215822

RESUMO

It is widely recognized that designing a special micro/nanostructure of microwave absorption materials for enhancing interface polarization benefits dielectric loss capability. In this work, a facile charge-driven self-assembly strategy is reported to prepare wrinkled reduced graphene oxide wrapped polymer-derived carbon (CS@rGO) microspheres. Noticeably, the unique three-dimensional (3D) multi-interface structure imparts CS@rGO microspheres with promoted microwave absorption capability. Adjusting the charge-driven self-assembly cycle times, the dielectric properties and impedance matching characteristics of the CS@rGO microspheres can be optimized. The minimum reflection loss (RLmin) of the sample can reach up to -55.24 dB at 13.75 GHz and the effective absorption bandwidth (RL ≤ -10 dB) is 4.30 GHz (11.55-15.85 GHz) at only a thickness of 1.85 mm. This research provides a pathway to explore the high-performance microwave absorber through the construction of the unique 3D multi-interface structure.


Assuntos
Carbono , Micro-Ondas , Microesferas , Polímeros
13.
Ecol Evol ; 12(11): e9542, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36447595

RESUMO

Riparian zones are biodiversity hotspots in montane ecosystems and are of critical conservation concern. However, studies on longitudinal diversity patterns and environmental drivers have been restricted to aquatic fauna, while the animals that rely on both river and riparian resources have been of much less concern. Here, we examined the multifaceted diversity distribution of riparian birds along longitudinal gradients and analyzed the importance of environmental factors in shaping these patterns in the Changbai Mountains. Hump-shaped relationships between elevation and taxonomic, phylogenetic, and functional diversity, as well as with the conservation value index, were evident along each of the classic submontane rivers. Forest cover, vegetation height variation, and land cover patches positively affected the taxonomic diversity indices. In addition to the species richness, fluvial geomorphology variables (river sinuosity and gravel bar) were significantly related to the phylogenetic diversity. However, there was no statistical evidence for a relationship between functional diversity and the environmental variables examined. This study emphasized the necessity of including multiple diversity measures beyond taxonomic diversity and demonstrated the importance of both terrestrial and aquatic components in shaping the multifaceted biodiversity pattern of riparian organisms living in riparian zones. The results suggested that conservation priority should be given to both rivers and banks in the middle reaches and that riparian birds could be good candidate indicators of environmental change in the submontane river-forest ecotone.

14.
Sensors (Basel) ; 22(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36146340

RESUMO

UAV-based object detection has recently attracted a lot of attention due to its diverse applications. Most of the existing convolution neural network based object detection models can perform well in common object detection cases. However, due to the fact that objects in UAV images are spatially distributed in a very dense manner, these methods have limited performance for UAV-based object detection. In this paper, we propose a novel transformer-based object detection model to improve the accuracy of object detection in UAV images. To detect dense objects competently, an advanced foreground enhancement attention Swin Transformer (FEA-Swin) framework is designed by integrating context information into the original backbone of a Swin Transformer. Moreover, to avoid the loss of information of small objects, an improved weighted bidirectional feature pyramid network (BiFPN) is presented by designing the skip connection operation. The proposed method aggregates feature maps from four stages and keeps abundant information of small objects. Specifically, to balance the detection accuracy and efficiency, we introduce an efficient neck of the BiFPN network by removing a redundant network layer. Experimental results on both public datasets and a self-made dataset demonstrate the performance of our method compared to the state-of-the-art methods in terms of detection accuracy.

15.
Med Chem ; 19(1): 64-74, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674304

RESUMO

BACKGROUND: Genistein has been limited in clinical application due to its low bioavailability, extremely poor liposolubility, and fast glycosylation rate, though it possesses anti-breast cancer activity. Therefore, the discovery of novel genistein derivatives is an urgency. OBJECTIVE: To enhance the anti-breast cancer activity of genistein, a series of novel fluorinated genistein derivatives were synthesized. METHODS: Their in vitro antitumor activity was investigated by the MTT assay against three cancer cell lines, via, MDA-MB-231, MCF-7, and MDA-MB-435, respectively. RESULTS: Analogs 1d, 2b, and 3b showed remarkable anticancer activities compared to tamoxifen, a clinical anti-breast cancer drug on the market. CONCLUSION: The activities against breast cancer of genistein were enhanced by introducing the 7- alkoxyl group and fluorine atom into the B-ring. Therefore, these compounds may be potential candidates for treating breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Genisteína/farmacologia , Genisteína/uso terapêutico , Neoplasias da Mama/patologia , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Linhagem Celular , Proliferação de Células , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
16.
Polymers (Basel) ; 14(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35406287

RESUMO

To obtain the influence of the Bi2O3 particle content of a PTFE/Al/Bi2O3 reactive material (later referred to as PAB) on its shock-induced chemical reaction (SICR) characteristics, five kinds of PAB with different Bi2O3 contents were prepared; the reaction process in a drop-hammer test, recorded using a high-speed camera, was analyzed. The ignition and reaction mechanisms of PAB under mechanical impact were analyzed based on the thermochemical reaction characteristics and the microstructure. The results show that with an increase in Bi2O3 content, the shock-induced chemical reaction duration and the sensitivity of PAB increase, and then decrease. When the Bi2O3 content is 9%, the impact sensitivity is the highest and the reaction duration is the longest. The heating at the crack tip is responsible for PAB ignition under long-pulse low-velocity impact. During ignition, PAB undergoes several physicochemical changes such as the melting of PTFE, a PTFE/Bi2O3 reaction, an Al/Bi2O3 reaction, pyrolysis of the melted PTFE, and a C2F4/Al reaction; moreover, the presence of Bi2O3 decreases the excitation threshold of the reactive material, which facilitates the propagation of the reaction and improves the degree of the reaction and overall energy release of the reactive material.

17.
Int Immunopharmacol ; 107: 108666, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35286913

RESUMO

OBJECTIVE: To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity between MW032 (denosumab biosimilar) and Xgeva® (denosumab) in healthy Chinese subjects. STUDY DESIGN: In this single-center, randomized, double-blind, single-dose, parallel-controlled design study, 120 healthy male subjects were randomized 1:1 to receive a single dose subcutaneous injection of 120 mg MW032 or Xgeva®, with an observation period of 161 days. The primary endpoint was the bioequivalence of PK parameters (Cmax, AUC0-t), and secondary endpoints including PD parameters, safety, and immunogenicity. RESULTS: One hundred and twelve subjects completed the study, including 56 subjects in each group. The geometric mean ratio and 90% CI for AUC0-t and Cmax were 1.117 (1.034, 1.205) and 1.060 (0.984, 1.142), respectively, which were both within the equivalence interval (0.8, 1.25). The inter-subject variation ranged from 21.37% to 27.37%. The PD parameters between MW032 and Xgeva® were similar. There was no statistically significant difference in the positive incidence of anti-drug antibody test between the two groups. Both MW032 and Xgeva® appeared to be well-tolerated and no Grade 3 or above serious adverse reactions occurred. The adverse reactions observed in the study were reported for denosumab generally. Moreover, there were no high-incidence or previously unreported adverse reactions. CONCLUSION: This study evidenced that the PK profiles of MW032, a denosumab biosimilar, and Xgeva® were bioequivalent. We also found that the PDs, safety, and immunogenicity were similar between the two drugs. Therefore, our results supported the next confirmatory studies for the development of MW032.


Assuntos
Medicamentos Biossimilares , Denosumab , Medicamentos Biossimilares/efeitos adversos , China , Denosumab/efeitos adversos , Denosumab/farmacocinética , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Masculino , Equivalência Terapêutica
18.
Plant Sci ; 315: 111146, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35067309

RESUMO

Ring rot disease, which is caused by Botryosphaeria dothidea (B. dothidea), is one of the most serious diseases affecting the pear industry. Currently, knowledge of the mechanism about pear-pathogen interactions is unclear. To explore the early response of pear leaves to B. dothidea infection, we compared the early transcriptome of pear leaves infected with B. dothidea. The results revealed 3248 differentially expressed genes (DEGs) and 4862 DEGs at D2 and D4, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation of DEGs showed that these genes were predominately involved in plant-pathogen interactions, hormone signal transduction and other biosynthesis-related metabolic processes, including glucosinolate accumulation and flavonoid pathway enhancement. However, many hormone- and disease resistance-related genes and transcription factors (TFs) were differentially expressed during B. dothidea infection. These results were consistent with the changes in the physiological characteristics of B. dothidea. In addition, the expression of PbrPUB29, an E3 ubiquitin ligase with a U-box domain, was significantly higher than it was at 0 dpi. PbrPUB29 silencing enhanced the sensitivity of pear leaves to B. dothidea, reflected by more severe symptoms and higher reactive oxygen species (ROS) content in the defective pear seedlings after inoculation, revealing that PbrPUB29 has a significant role in pear disease resistance. In brief, we explored the interaction between pear leaves and B. dothidea at the transcriptome level, implied the early response of pear leaves to pathogens, and identified a hub gene in a B. dothidea-infected pear. These results provide a basis and new strategy for exploring the molecular mechanisms underlying pear-pathogen interactions and disease resistance breeding.


Assuntos
Ascomicetos/patogenicidade , Resistência à Doença/genética , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/genética , Folhas de Planta/microbiologia , Pyrus/genética , Pyrus/microbiologia , Pyrus/fisiologia , China , Produtos Agrícolas/genética , Produtos Agrícolas/microbiologia , Produtos Agrícolas/fisiologia , Regulação Fúngica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Doenças das Plantas/microbiologia , Transcriptoma
19.
Phytopathology ; 112(6): 1335-1344, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34989595

RESUMO

Pear is an important fruit tree worldwide, but it is often infected by the pathogen Botryosphaeria dothidea, which causes pear ring rot disease. To explore the effect of exogenous melatonin on the disease resistance of pear, we treated inoculated pear fruits with different concentrations of melatonin. The results showed that 100 µΜ of melatonin had the most significant effect with resistance to B. dothidea. In addition, melatonin treatment significantly reduced the diameter of disease lesions and enhanced the endogenous melatonin content in pears inoculated with B. dothidea. Compared with the control treatment, melatonin treatment suppressed increases in reactive oxygen species (ROS) and activated ROS-scavenging enzymes. Treatment with exogenous melatonin maintained ascorbic acid-glutathione at more reductive status. The expression levels of core autophagic genes and autophagosome formation were elevated by melatonin treatment in pear fruits. Silencing of PbrATG5 in Pyrus pyrifolia conferred sensitivity to inoculation that was only slightly attenuated by melatonin treatment. After inoculation with B. dothidea, exogenous melatonin treatment led to higher levels of soluble sugars and organic acids in pear fruits than H2O treatment. Overall, our results demonstrate that melatonin enhances resistance to B. dothidea by increasing autophagic activity and soluble sugar/organic acid accumulation.


Assuntos
Melatonina , Pyrus , Ascomicetos , Melatonina/farmacologia , Doenças das Plantas/genética , Espécies Reativas de Oxigênio , Açúcares
20.
Bioact Mater ; 8: 140-152, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541392

RESUMO

Magnesium (Mg) alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants. However, the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes. In this study, we fabricated a porous 3D-printed Mg-Nd-Zn-Zr (denoted as JDBM) implant with suitable mechanical properties using selective laser melting technology. The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro. Furthermore, the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S. aureus (MRSA) and Escherichia coli, respectively. The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation, blood tests, and Mg2+ deposition detection. In addition, enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage. The high Mg2+ environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages (Tnf, iNOS, Ccl3, Ccl4, Ccl5, Cxcl10, and Cxcl2), and enhance the phagocytic ability of macrophages. The enhanced immunoregulatory effect generated by relatively fast Mg2+ release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant. Our findings indicate that 3D-printed porous JDBM implants, having both antibacterial property and osteoinductivity, hold potential for future orthopedic applications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...