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1.
Plant Cell ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963884

RESUMO

As an essential intrinsic component of photosystem II (PSII) in all oxygenic photosynthetic organisms, heme-bridged heterodimer cytochrome b559 (Cyt b559) plays critical roles in protection and assembly of PSII. However, the underlying mechanisms of Cyt b559 assembly are largely unclear. Here, we characterized the Arabidopsis (Arabidopsis thaliana) rph1 (resistance to Phytophthora1) mutant, which was previously shown to be susceptible to the oomycete pathogen Phytophthora brassicae. Loss of RPH1 leads to a drastic reduction in PSII accumulation, which can be primarily attributed to the defective formation of Cyt b559. Spectroscopic analyses showed that the heme level in PSII supercomplexes isolated from rph1 is significantly reduced, suggesting that RPH1 facilitates proper heme assembly in Cyt b559. Due to the loss of RPH1-mediated processes, a covalently bound PsbE-PsbF heterodimer is formed during the biogenesis of PSII. In addition, rph1 is highly photosensitive and accumulates elevated levels of ROS under photoinhibitory light conditions. RPH1 is a conserved intrinsic thylakoid protein present in green algae and terrestrial plants, but absent in Synechocystis, and it directly interacts with the subunits of Cyt b559. Thus, our data demonstrate that RPH1 represents a chloroplast acquisition specifically promoting the efficient assembly of Cyt b559, probably by mediating proper heme insertion into the apo-Cyt b559 during the initial phase of PSII biogenesis.

2.
Small ; : e2402890, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982951

RESUMO

Development of luminescent segmented heterostructures featuring multiple spatial-responsive blocks is important to achieve miniaturized photonic barcodes toward anti-counterfeit applications. Unfortunately, dynamic manipulation of the spatial color at micro/nanoscale still remains a formidable challenge. Here, a straightforward strategy is proposed to construct spatially varied heterostructures through amplifying the conformation-driven response in flexible lanthanide-metal-organic frameworks (Ln-MOFs), where the thermally induced minor conformational changes in organic donors dramatically modulate the photoluminescence of Ln acceptors. Notably, compositionally and structurally distinct heterostructures (1D and 2D) are further constructed through epitaxial growth of multiple responsive MOF blocks benefiting from the isomorphous Ln-MOF structures. The thermally controlled emissive colors with distinguishable spectra carry the fingerprint information of a specific heterostructure, thus allowing for the effective construction of smart photonic barcodes with spatially responsive characteristics. The results will deepen the understanding of the conformation-driven responsive mechanism and also provide guidance to fabricate complex stimuli-responsive hierarchical microstructures for advanced optical recording and high-security labels.

3.
Nat Methods ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025969

RESUMO

Studies of molecular and cellular functions of small-molecule inhibitors in cancer treatment, eliciting effects by targeting genome and epigenome associated proteins, requires measurement of drug-target engagement in single-cell resolution. Here we present EpiChem for in situ single-cell joint mapping of small molecules and multimodal epigenomic landscape. We demonstrate single-cell co-assays of three small molecules together with histone modifications, chromatin accessibility or target proteins in human colorectal cancer (CRC) organoids. Integrated multimodal analysis reveals diverse drug interactions in the context of chromatin states within heterogeneous CRC organoids. We further reveal drug genomic binding dynamics and adaptive epigenome across cell types after small-molecule drug treatment in CRC organoids. This method provides a unique tool to exploit the mechanisms of cell type-specific drug actions.

4.
J Am Chem Soc ; 146(23): 16281-16294, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38812457

RESUMO

Interfacial water on a metal surface acts as an active layer through the reorientation of water, thereby facilitating the energy transfer and chemical reaction across the metal surface in various physicochemical and industrial processes. However, how this active interfacial water collectively behaves on flat noble metal substrates remains largely unknown due to the experimental limitation in capturing librational vibrational motion of interfacial water and prohibitive computational costs at the first-principles level. Herein, by implementing a machine-learning approach to train neural network potentials, we enable performing advanced molecular dynamics simulations with ab initio accuracy at a nanosecond scale to map the distinct rotational motion of water molecules on a metal surface at room temperature. The vibrational density of states of the interfacial water with two-layer profiles reveals that the rotation and vibration of water within the strong adsorption layer on the metal surface behave as if the water molecules in the bulk ice, wherein the O-H stretching frequency is well consistent with the experimental results. Unexpectedly, the water molecules within the adjacent weak adsorption layer exhibit superdiffusive rotation, contrary to the conventional diffusive rotation of bulk water, while the vibrational motion maintains the characteristic of bulk water. The mechanism underlying this abnormal superdiffusive rotation is attributed to the translation-rotation decoupling of water, in which the translation is restrained by the strong hydrogen bonding within the bilayer interfacial water, whereas the rotation is accelerated freely by the asymmetric water environment. This superdiffusive rotation dynamics may elucidate the experimentally observed large fluctuation of the potential of zero charge on Pt and thereby the conventional Helmholtz layer model revised by including the contribution of interfacial water orientation. The surprising superdiffusive rotation of vicinal water next to noble metals will shed new light on the physicochemical processes and the activity of water molecules near metal electrodes or catalysts.

5.
J Org Chem ; 89(9): 6428-6443, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38608000

RESUMO

A highly efficient and straightforward one-pot synthesis of diversely substituted 3,4-dihydroquinazolines and quinazolin-4(3H)-ones has been achieved through a domino three-component assembly reaction of arenediazonium salts, nitriles, and bifunctional aniline derivatives. This new protocol involves three C-N bond formations through the initial formation of N-arylnitrilium intermediates from arenediazonium salts and nitriles, followed by the sequential nucleophilic addition and cyclization reactions with bifunctional anilines, leading to such N-heterocyclic compounds of biological and pharmacological importance. This method offers a simple, expedient, and robust approach with the use of amenable and easily accessible reactants/reagents under metal-free mild conditions, good functional group tolerance, and high efficiency. The synthetic applications were also demonstrated by derivatization of the products obtained from these processes and syntheses of a diverse range of valuable polycyclic N-heterocycles.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38425244

RESUMO

The recently discovered gene TRMT13 encodes a type of RNA methylase and is a member of the CCDC family (also called CCDC76). Here, we delineate its role in papillary thyroid cancer (PTC). Bioinformatics analysis shows significant TRMT13 and ANAPC4 downregulation in PTC and reveals that the expression levels of both genes are linearly correlated. Subsequent analyses confirm that both TRMT13 and ANAPC4 expressions are downregulated in PTC tissues and that this change in expression has a significant impact on cancer diagnosis. We conduct assays on PTC cells subjected to TRMT13 and ANAPC4 silencing or overexpression to assess the biological effects of these genes. We also perform rescue experiments to validate the regulatory effects of TRMT13 on ANAPC4. A nude mouse tumor model is used to evaluate the effects of TRMT13 and ANAPC4 on PTC tumorigenesis. TRMT13 expression is decreased in PTC tissues and cell lines and is positively correlated with that of ANAPC4. Cell assays reveal that TRMT13/ANAPC4 attenuates the malignancy of PTC cells by restraining cell proliferation, migration and invasion, while rescue experiments corroborate that ANAPC4 is a downstream target of TRMT13. In the nude mouse xenograft model, both TRMT13 and ANAPC4 inhibit tumor growth, and TRMT13 and ANAPC4 expression levels are significantly associated with survival. Taken together, these findings lead to the conclusion that TRMT13 inhibits PTC growth via ANAPC4, indicating a new role of TRMT13 and providing insights into the tRNA methyltransferase and coiled-coil domain-containing protein families.

7.
Sci Rep ; 14(1): 6601, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503814

RESUMO

Tooth wear and pain are the primary concerns of patients undergoing periodontal scaling. The aims of this study were to compare the effects of a new magnetostrictive ultrasonic scaler and a traditional piezoelectric ultrasonic scaler on tooth surface roughness and calculus removal and to determine their impacts on patient discomfort during supragingival cleaning. This article had two parts: an in vitro study and a clinical study. In the in vitro study, thirty teeth with subgingival calculus were randomly assigned to two scaling treatment groups: magnetostrictive scalers (n = 15) and piezoelectric scalers (n = 15). Surface roughness measurements were taken at baseline and after scaling, and the root samples were visualised by SEM after scaling. Additionally, a single-centre randomised split-mouth clinical trial was conducted. Eighty-five participants diagnosed with chronic gingivitis or periodontitis were randomly assigned to receive supragingival scaling. The magnetostrictive scaler was used in half of the mouths (n = 85), and the piezoelectric scaler was used in the other half of the mouths (n = 85). Data on pain, noise, and vibration were collected using a VAS questionnaire, and the operating time was recorded. In both in vitro and clinical studies, magnetostrictive scalers were reported to be more effective than piezoelectric scalers in removing dental deposits (P < 0.05). Additionally, the root surface after scaling with the magnetostrictive scaler was smoother than that after scaling with the piezoelectric scaler in the in vitro study (P = 0.02). SEM examination also revealed that fewer dental materials were lost after instrumentation with the magnetostrictive scaler than after instrumentation with the piezoelectric scaler. Piezoelectric scalers caused less discomfort to patients in terms of pain, noise, and vibration than magnetostrictive scalers (P < 0.05). According to this clinical study, the magnetostrictive scaler caused more discomfort during supragingival scaling than the piezoelectric scaler. Moreover, the magnetostrictive scaler was also more efficient and produced a smoother root surface with less material loss after scaling than the piezoelectric scaler, as demonstrated in the in vitro study.


Assuntos
Cálculos , Dente , Terapia por Ultrassom , Humanos , Ultrassom , Raiz Dentária , Dor
8.
Nat Commun ; 15(1): 1891, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424084

RESUMO

Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction.


Assuntos
Benzeno , Nanoestruturas , Feminino , Animais , Camundongos , Benzeno/química , Nanoestruturas/química , Fosfolipídeos
9.
Aging (Albany NY) ; 15(23): 13888-13900, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38070140

RESUMO

BACKGROUND: Heart failure is a prevalent and life-threatening medical condition characterized by abnormal atrial electrical activity, contributing to a higher risk of ischemic stroke. Atrial remodelling, driven by oxidative stress and structural changes, plays a central role in heart failure progression. Recent studies suggest that HACE1, a regulatory gene, may be involved in cardiac protection against heart failure. METHODS: Clinical data analysis involved heart failure patients, while an animal model utilized C57BL/6J mice. RT-PCR, microarray analysis, histological examination, ELISA, and Western blot assays were employed to assess gene and protein expression, oxidative stress, and cardiac function. Cell transfection and culture of mouse atrial fibroblasts were performed for in-vitro experiments. RESULTS: HACE1 expression was reduced in heart failure patients and correlated negatively with collagen levels. In mouse models, HACE1 up-regulation reduced oxidative stress, mitigated fibrosis, and improved cardiac function. Conversely, HACE1 knockdown exacerbated oxidative stress, fibrosis, and cardiac dysfunction. HACE1 also protected against ferroptosis and mitochondrial damage. NRF2, a transcription factor implicated in oxidative stress, was identified as a target of HACE1, with HACE1 promoting NRF2 activity through ubiquitination. CONCLUSIONS: HACE1 emerges as a potential therapeutic target and diagnostic marker for heart failure. It regulates oxidative stress, mitigates cardiac fibrosis, and protects against ferroptosis and mitochondrial damage. The study reveals that HACE1 achieves these effects, at least in part, through NRF2 activation via ubiquitination, offering insights into novel mechanisms for heart failure pathogenesis and potential interventions.


Assuntos
Ferroptose , Insuficiência Cardíaca , Animais , Humanos , Camundongos , Fibrose , Átrios do Coração/patologia , Insuficiência Cardíaca/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
11.
Nat Commun ; 14(1): 5873, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735469

RESUMO

Cubic materials host high crystal symmetry and hence are not expected to support anisotropy in transport phenomena. In contrast to this common expectation, here we report an anomalous anisotropy of spin current can emerge in the (001) film of Mn3Pt, a noncollinear antiferromagnetic spin source with face-centered cubic structure. Such spin current anisotropy originates from the intertwined time reversal-odd ([Formula: see text]-odd) and time reversal-even ([Formula: see text]-even) spin Hall effects. Based on symmetry analyses and experimental characterizations of the current-induced spin torques in Mn3Pt-based heterostructures, we find that the spin current generated by Mn3Pt (001) exhibits exotic dependences on the current direction for all the spin components, deviating from that in conventional cubic systems. We also demonstrate that such an anisotropic spin current can be used to realize low-power spintronic applications such as the efficient field-free switching of the perpendicular magnetizations.

12.
Low Urin Tract Symptoms ; 15(6): 256-264, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37649457

RESUMO

OBJECTIVES: A lot of ion channels participate in the regulation of bladder function. TACAN, a new mechanosensitive ion channel, was first discovered in 2020. TACAN has been found to be expressed in many tissues, such as the dorsal root ganglia (DRG) and adipose tissue. However, it is unclear whether or not TACAN is expressed in the bladder. In this work, we decided to study the expression and distribution of TACAN in human and rat bladders. Meanwhile, the expression of TACAN in the rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) was studied. METHODS: Human bladder tissues were obtained from female patients. Cyclophosphamide (CYP) was used to build the rat model of IC/BPS. Real-time polymerase chain reaction, agarose gel electrophoresis, and western blotting were used to assess the expression of TACAN in human and rat bladders. Immunohistochemistry and immunofluorescence were used to observe the distribution of TACAN in human and rat bladders. Hematoxylin-eosin stain, withdrawal threshold, and micturition interval were used to evaluate animal models. RESULTS: The results of agarose gel electrophoresis and western blotting suggested that TACAN was expressed in human and rat bladders. Immunohistochemical results suggested that TACAN showed positive immunoreaction in the urothelial and detrusor layers. The immunofluorescence results indicated that TACAN was co-stained with UPKIII, α-SMA, and PGP9.5. The IC/BPS model was successfully established with CYP. The mRNA and protein expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. CONCLUSIONS: TACAN was found in human and rat bladders. TACAN was mainly distributed in the urothelial and detrusor layers and bladder nerves. The expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. This new discovery will provide a theoretical basis for future research on the function of TACAN in the bladder and a potential therapeutic target for IC/BPS.


Assuntos
Cistite Intersticial , Bexiga Urinária , Humanos , Feminino , Ratos , Animais , Cistite Intersticial/tratamento farmacológico , Micção , Imuno-Histoquímica , Imunofluorescência
13.
Pract Lab Med ; 36: e00321, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37649538

RESUMO

Background: sST2 has emerged as a potential disease biomarker of cardiac and inflammatory diseases in pediatrics. This study aimed to evaluate the performance of the new Pylon sST2 assay and establish the reference intervals of sST2 in children and adolescence in China. Methods: The experiments on precision, linearity, effects of interferents and sample stability were carried out to evaluate the analytical performances. A total of 240 healthy participants, aged from 2 to 17 years were enrolled. The nonparametric method was used to calculate the age- and sex-specified reference intervals. sST2 levels were measured in children with different diseases to evaluate the assay's diagnostic performance. Results: The repeatability and within-laboratory imprecision CVs of the assay were 6.0% and 7.6% at 19.5 ng/ml, and 3.1% and 5.9% at 289.8 ng/ml, respectively. The method showed linearity between 2.5 and 918.5 ng/ml. It was also noteworthy that the sST2 level was not affected in the presence of hemoglobin (2 mg/ml), triglyceride (30 mg/ml), bilirubin (0.3 mg/ml) and cholesterol (5 mg/ml). sST2 was found stable for 5 days at 4 °C in serum sample. The reference interval was determined as 2.1-21.0 ng/ml in general. No significant variation was observed by sex. However, sST2 increased constantly with age, especially in male. Increased sST2 was found in patients of systemic lupus erythematosus, sepsis, Crohn's diseases, respiratory failure and post cardiac surgery. Conclusions: The Pylon sST2 assay showed good analytical performances. The reference intervals were established in children and adolescence and sST2 showed potential clinical values in several diseases in pediatrics.

14.
Angew Chem Int Ed Engl ; 62(46): e202310263, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37604784

RESUMO

Whispering-gallery-mode (WGM) microcavities featuring distinguishable sharp peaks in a broadband exhibit enormous advantages in the field of miniaturized photonic barcodes. However, such kind of barcodes developed hitherto are primarily based on microcavities wherein multiple gain medias were blended into a single matrix, thus resulting in the limited and indistinguishable coding elements. Here, a surface tension assisted heterogeneous assembly strategy is proposed to construct the spatially resolved WGM hetero-microrings with multiple spatial colors along its circular direction. Through precisely regulating the charge-transfer (CT) strength, full-color microrings covering the entire visible range were effectively acquired, which exhibit a series of sharp and recognizable peaks and allow for the effective construction of high-quality photonic barcodes. Notably, the spatially resolved WGM hetero-microrings with multiple coding elements were finally acquired through heterogeneous nucleation and growth controlled by the directional diffusion between the hetero-emulsion droplets, thus remarkably promoting the security strength and coding capacity of the barcodes. The results would be useful to fabricate new types of organic hierarchical hybrid WGM heterostructures for optical information recording and security labels.

15.
Opt Express ; 31(15): 24914-24925, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37475307

RESUMO

Ceramic phosphors are widely considered the next-generation phosphor material for white LED/LD lighting, and a wide spectrum is a key factor in improving the CRI of lighting sources. In this paper, a novel, to our knowledge, barcode-structured YAG:Ce/YAG:Ce,Mn ceramic phosphor was designed and fabricated. The lighting sources with the CRI value of 73.5 and 68.9 were obtained under the excitation of blue LEDs and blue LDs, respectively. Simultaneously, thanks to the effective supplementary emission from a red LD, the CRI of the ceramic-based lighting source reached 81.8 under blue LD excitation. Specifically, the microstructure and luminescent property of ceramic phosphors with different thicknesses and ion doping concentrations were systematically studied. Besides, by changing the blue power from 0.52 W to 2.60 W, the CCT of the laser lighting source with the encapsulation of optimized YAG:Ce/YAG:Ce,Mn ceramic phosphors ranged from 3928 K to 5895 K, while the CRI always maintained above 80. The above results indicate that barcode-structured Ce:YAG/Ce,MnYAG ceramic phosphor is a candidate to achieve a high CRI and ican be applied to various lighting occasions.

16.
Medicine (Baltimore) ; 102(29): e34260, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478232

RESUMO

RATIONALE: Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of plasma cells, which usually occurs in middle-aged and elderly male patients. Bisphosphonates (BP) are commonly used for the treatment of MM bone disease. Long-time use of BP may cause medication-related osteonecrosis of the jaw (MRONJ). MRONJ occurs in jaw exclusively, and Multiple myeloma can also invade the jaw. The 2 diseases have similar clinical manifestations and imaging findings. This report present a case of MM identified in surgical specimen at the site that had been previously pathologically diagnosed as MRONJ in a patient with MM. PATIENT CONCERNS: A 57-years-old male patient visited our clinic on October 16, 2020 because of gingival swelling and pain in the right mandible for 1 month after extraction of the lower right premolar. The patient had a long-time illness history of multiple myeloma, and received intravenous zoledronic acid treatment. DIAGNOSES: Based on the clinical characteristics, imaging, and pathological findings of sequestrum formation and high inflammatory cell infiltration, the patient was diagnosed with MRONJ. After 1 year, a mandibular osteotomy was performed and pathological analysis showed the presence of necrotic bone and a large number of abnormal plasma cell infiltration, suggesting the presence of MM in the mandible. INTERVENTIONS: The patient was treated with a series of conservative treatments including antibiotic treatment, saline irrigation and laser irradiation, as well as superficial sequestration was. One year later, a mandibular osteotomy was performed. OUTCOMES: For the patient, the symptoms of gingival swelling, pain and discharge disappeared after surgery. LESSONS: These findings suggested MRONJ and MM could occur simultaneously at same site, so patients with MM presenting with symptoms of MRONJ should be screened for concurrent or disease relapse of multiple myeloma to prevent misdiagnosis or inadequate management. Meanwhile, this also suggests long-term inflammatory may lead to invasion of multiple myeloma.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Mieloma Múltiplo , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos , Mandíbula/cirurgia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/complicações , Recidiva Local de Neoplasia/tratamento farmacológico , Dor/tratamento farmacológico
17.
J Child Neurol ; 38(6-7): 454-465, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37431191

RESUMO

In this study, we reviewed the safety and efficacy of botulinum toxin type A (BoNT-A) injection with respect to motor development in children with spastic cerebral palsy aged <2 years. Randomized controlled trials of BoNT-A published between July 1993 and May 2021 were searched in PubMed, WANFANG, CNKI (Chinese National Knowledge Infrastructure), and Cochrane Library Central Register of Controlled Trials using keywords "Botulinum Toxin," "cerebral palsy," "nao xing tan huan," "nao tan," and "rou du du su." The 11-item PEDro Scale was used to rate the quality of all the identified studies. Twelve studies, involving 656 subjects, met the inclusion criteria, and of these, 2 involved patients aged <2 years. Treatment safety was assessed based on adverse event (AE) number and frequency, and efficacy was assessed based on spasticity, range of movement, and motor development. We observed that 3 self-limiting adverse events that were frequently reported included weakness, dysesthesia of the skin, and pain at the injection site. Moreover, there was a significant decrease in the incidence of spasticity and a notable improvement in the range of movement of BoNT-A-treated patients. Therefore, BoNT-A injection shows great safety and efficacy in the treatment of children with cerebral palsy aged <2 years.


Assuntos
Toxinas Botulínicas Tipo A , Paralisia Cerebral , Fármacos Neuromusculares , Criança , Humanos , Toxinas Botulínicas Tipo A/efeitos adversos , Paralisia Cerebral/complicações , Fármacos Neuromusculares/efeitos adversos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Dor , Resultado do Tratamento
18.
Sci Adv ; 9(30): eade3470, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37494438

RESUMO

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Animais , Humanos , Anticorpos Antivirais , Testes de Neutralização , Vacina BNT162 , Anticorpos Monoclonais/química , Microscopia Crioeletrônica , COVID-19/prevenção & controle , SARS-CoV-2
19.
J Phys Condens Matter ; 35(41)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37406638

RESUMO

This study investigates a T-type field-free spin-orbit torque device with an in-plane magnetic layer coupled to a perpendicular magnetic layer via a non-magnetic spacer. The device utilizes a Co/Ta/CoTb structure, in which the in-plane Co layer and the perpendicular CoTb layer are ferromagnetically (FM) coupled through the Ta spacer. 'T-type' refers to the magnetization arrangement in the FM/spacer/FIM structure, where the magnetization in FM is in-plane, while in FIM, it is out-of-plane. This configuration forms a T-shaped arrangement for the magnetization of the two magnetic layers. Additionally, 'interlayer exchange coupling (IEC)' denotes the interaction between the two magnetic layers, which is achieved by adjusting the material and thickness of the spacer. Our results show that an in-plane effective field from the IEC enables deterministic current-induced magnetization switching of the CoTb layer. The field-driven and the current-driven asymmetric domain wall motion are observed and characterized by magneto-optic Kerr effect measurements. The functionality of multistate synaptic plasticity is demonstrated by understanding the relationship between the anomalous Hall resistance and the applied current pulses, indicating the potential for the device in spintronic memory and neuromorphic computing.

20.
Fitoterapia ; 168: 105562, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37295756

RESUMO

Ganodermasides E-H (1-4), four new ergosterol derivatives and two known ones (5 and 6) were isolated from the fermentation of the endophytic fungus Epicoccum poae DJ-F in the stems of Euphorbia royleana Boiss. Their structures were elucidated by spectroscopic analysis, including extensive 1D NMR, 2D NMR, and HRESIMS techniques. All the isolated compounds were tested for their vitro antibacterial activity. Compounds 1-6 showed weak inhibitory effects on Staphylococcus epidermidis, Pseudomonas syringae, and Ralstonia solanacearum with MIC values ranging from 0.4 to 3.6 mM.


Assuntos
Ascomicetos , Euphorbia , Estrutura Molecular , Ergosterol , Ascomicetos/química , Antibacterianos
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