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1.
Nat Commun ; 15(1): 5542, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956040

RESUMEN

Efficiently fabricating a cavity that can achieve strong interactions between terahertz waves and matter would allow researchers to exploit the intrinsic properties due to the long wavelength in the terahertz waveband. Here we show a terahertz detector embedded in a Tamm cavity with a record Q value of 1017 and a bandwidth of only 469 MHz for direct detection. The Tamm-cavity detector is formed by embedding a substrate with an Nb5N6 microbolometer detector between an Si/air distributed Bragg reflector (DBR) and a metal reflector. The resonant frequency can be controlled by adjusting the thickness of the substrate layer. The detector and DBR are fabricated separately, and a large pixel-array detector can be realized by a very simple assembly process. This versatile cavity structure can be used as a platform for preparing high-performance terahertz devices and opening up the study of the strong interactions between terahertz waves and matter.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38966874

RESUMEN

Personal thermal management technology, which adjusts the heat exchange between the human body and the environment, can passively heat or cool the body to maintain a comfortable core temperature, thereby enhancing comfort and reducing energy consumption. However, most existing personal thermal management materials have static properties, such as fixed solar reflectance and infrared emissivity, which do not support real-time dynamic temperature regulation. Moreover, sweat accumulation on the skin surface, while contributing to temperature regulation, can significantly reduce comfort. This study constructs a unidirectional moisture-permeable intelligent thermal management fabric system to achieve superior thermal and moisture comfort in complex environments. The fabric incorporates thermochromic microcapsules into PAN nanofibers by using electrospinning technology for intelligent thermal management. Subsequent hydrophobic treatment of the fiber film surface imparts the fabric with unidirectional wetting properties. The nanofibrous structure provides intrinsic elasticity and breathability. In heating mode, the fabric's average sunlight reflectance is 42.1%, which increases to 82.2% in cooling mode, resulting in a reflectance difference of approximately 40%. The hydrophobic treatment endows the fabric with excellent moisture absorption and perspiration properties, demonstrated by a unidirectional moisture transport index of 696.63 and a perspiration evaporation rate of 5.88 mg/min. When the fabric temperature matches the ambient temperature, the photothermal conversion power difference of the Janus metafabric in two modes reaches 248.37 W m-2. Additionally, Janus metafabrics show the potential for temperature-responsive design and repeated writing applications. The outstanding wearability and dynamic spectral properties of these metafabrics open new pathways for sustainable energy, smart textiles, and thermal-moisture comfort applications.

3.
Chemistry ; : e202401456, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738505

RESUMEN

The effective transition metal-free photoredox/bismuth dual catalytic reductive dialkylation of nitroarenes with benzaldehydes has been reported. The nitroarene redution through visible light-driven photoredox catalysis was integrated with subsequent reductive dialkylation of anilines under bismuth catalysis to enable the cascade reductive alkylation of nitroarenes with carbonyls. Salient features of this relay catalysis system include mild reaction conditions, no requirement for transition metal catalysts, easy handling, step-economy, and high selectivity.

4.
CNS Neurosci Ther ; 30(5): e14780, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38790106

RESUMEN

OBJECTIVE: Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody-positive NMOSD, but high-quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control. METHODS: Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded. RESULTS: Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50-8.38 vs. 5.00-8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30-0.84 vs. 0.95-1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation. DISCUSSION: After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile.


Asunto(s)
Acuaporina 4 , Eliminación de Componentes Sanguíneos , Neuromielitis Óptica , Puntaje de Propensión , Humanos , Femenino , Masculino , Neuromielitis Óptica/terapia , Neuromielitis Óptica/inmunología , Persona de Mediana Edad , Adulto , Acuaporina 4/inmunología , Estudios de Cohortes , Eliminación de Componentes Sanguíneos/métodos , Eliminación de Componentes Sanguíneos/efectos adversos , Resultado del Tratamiento , Intercambio Plasmático/métodos , Intercambio Plasmático/efectos adversos , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Autoanticuerpos/sangre , Estudios Prospectivos
5.
Nat Commun ; 15(1): 4009, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740761

RESUMEN

Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

6.
Ren Fail ; 46(1): 2332492, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38584135

RESUMEN

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.


Asunto(s)
Lesión Renal Aguda , Daño por Reperfusión , Animales , Humanos , Ratas , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Apoptosis , Hipoxia/metabolismo , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Isquemia , Riñón/patología , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales , Mitofagia , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Transducción de Señal
7.
Ann Neurol ; 96(1): 194-203, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38661030

RESUMEN

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). METHODS: This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. RESULTS: We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. INTERPRETATION: The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024;96:194-203.


Asunto(s)
Imagen por Resonancia Magnética , Vasculitis del Sistema Nervioso Central , Humanos , Masculino , Femenino , Vasculitis del Sistema Nervioso Central/diagnóstico por imagen , Vasculitis del Sistema Nervioso Central/patología , Vasculitis del Sistema Nervioso Central/complicaciones , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Adulto Joven , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Estudios de Cohortes , Adolescente
8.
Clin Chim Acta ; 558: 119669, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38599541

RESUMEN

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of central nervous system (CNS). Tryptophan indole catabolites have been reported to associate with the inflammatory diseases of the CNS. However, the roles of tryptophan indole catabolites have been rarely elucidated in MOGAD. METHODS: This cross-sectional study enrolled forty MOGAD patients, twenty patients with other non-inflammatory neurological diseases (OND) and thirty-five healthy participants. Serum and cerebrospinal fluid (CSF) samples of MOGAD and OND subjects during clinical attacks, serum samples of healthy participants were obtained. The concentrations of tryptophan, indoleacetic acid (IAA), indoleacrylic acid (IA) and indole-3-carboxylic acid (I-3-CA) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The correlations between tryptophan indole catabolites and maintenance immunotherapy, disease duration, overall numbers of attacks, short-term outcome in MOGAD patients were investigated. RESULTS: Levels of serum tryptophan, IAA, IA and CSF tryptophan in MOGAD patients were significantly decreased, while levels of serum I-3-CA and CSF IA were markedly increased compared with OND patients and healthy controls. Levels of serum tryptophan, CSF tryptophan and IA were significantly decreased in MOGAD patients who had received maintenance immunotherapy within 6 months before the attack. In MOGAD patients, serum and CSF tryptophan conversely correlated with disease duration and overall numbers of attacks, and serum IA negatively correlated with disease duration. Furthermore, serum tryptophan in MOGAD patients negatively correlated with the modified Rankin Scale (mRS) scores at 3 months. CONCLUSION: This study manifested decreased serum tryptophan levels and serum tryptophan may be the potential marker to predict the short-term outcome in MOGAD patients.


Asunto(s)
Triptófano , Humanos , Triptófano/sangre , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/sangre , Espectrometría de Masas en Tándem , Adulto Joven , Cromatografía Líquida de Alta Presión , Anciano
9.
Nat Nanotechnol ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684808

RESUMEN

Ferrotoroidicity-the fourth form of primary ferroic order-breaks both space and time-inversion symmetry. So far, direct observation of ferrotoroidicity in natural materials remains elusive, which impedes the exploration of ferrotoroidic phase transitions. Here we overcome the limitations of natural materials using an artificial nanomagnet system that can be characterized at the constituent level and at different effective temperatures. We design a nanomagnet array as to realize a direct-kagome spin ice. This artificial spin ice exhibits robust toroidal moments and a quasi-degenerate ground state with two distinct low-temperature toroidal phases: ferrotoroidicity and paratoroidicity. Using magnetic force microscopy and Monte Carlo simulation, we demonstrate a phase transition between ferrotoroidicity and paratoroidicity, along with a cross-over to a non-toroidal paramagnetic phase. Our quasi-degenerate artificial spin ice in a direct-kagome structure provides a model system for the investigation of magnetic states and phase transitions that are inaccessible in natural materials.

10.
Nano Lett ; 24(18): 5453-5459, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38682680

RESUMEN

Voltage-controlled oscillators, serving as fundamental components in semiconductor chips, find extensive applications in diverse modules such as phase-locked loops, clock generators, and frequency synthesizers within high-frequency integrated circuits. This study marks the first implementation of superconducting Josephson probe microscopy for near-field microwave detection on multiple voltage-controlled oscillators. Focusing on spectrum tracking, various phenomena, such as stray spectra and frequency drifts, were found under nonsteady operating states. Parasitic electromagnetic fields, originating from power supply lines and frequency divider circuits, were identified as sources of interference between units. The investigation further determined optimal working states by analyzing features of the microwave distributions. Our research not only provides insights into the optimization of circuit design and performance enhancement in oscillators but also emphasizes the significance of nondestructive near-field microwave microscopy as a pivotal tool in characterizing integrated millimeter-wave chips.

11.
Nano Lett ; 24(14): 4108-4116, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38536003

RESUMEN

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38453475

RESUMEN

BACKGROUND: Although trigeminal nerve involvement is a characteristic of multiple sclerosis (MS), its prevalence across studies varies greatly due to MRI resolution and cohort selection bias. The mechanism behind the site specificity of trigeminal nerve injury is still unclear. We aim to determine the prevalence of trigeminal nerve involvement in patients with MS in a consecutive 7T brain MRI cohort. METHODS: This observational cohort originates from an ongoing China National Registry of Neuro-Inflammatory Diseases. Inclusion criteria were the following: age 18 years or older, diagnosis of MS according to the 2017 McDonald criteria and no clinical relapse within the preceding 3 months. Each participant underwent 7T MAGNETOM Terra scanner (Siemens, Erlangen, Germany), using a 32-channel phased array coil at Beijing Tiantan Hospital. T1-weighted magnetisation-prepared rapid acquisition gradient echoes, fluid-attenuated inversion recovery (FLAIR) and fluid and white matter suppression images were used to identify lesions. FLAIR* and T2* weighted images were used to identify central vein sign (CVS) within the trigeminal lesions. RESULTS: 120 patients underwent 7T MRI scans between December 2021 and May 2023. 19/120 (15.8%) patients had a total of 45 trigeminal lesions, of which 11/19 (57.9%) were bilateral. The linear lesions extended along the trigeminal nerve, from the root entry zone (REZ) (57.8%, 26/45) to the pontine-medullary nucleus (42.2%, 19/45). 26.9% (7/26) of the lesions in REZ showed a typical central venous sign. CONCLUSION: In this 7T MRI cohort, the prevalence of trigeminal nerve involvement was 15.8%. Characteristic CVS was detected in 26.9% of lesions in REZ. This suggests an inflammatory demyelination mechanism of trigeminal nerve involvement in MS.

13.
Adv Mater ; 36(18): e2312823, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38308110

RESUMEN

Functional amyloid (FAs), particularly the bacterial proteins CsgA and FapC, have many useful properties as biomaterials: high stability, efficient, and controllable formation of a single type of amyloid, easy availability as extracellular material in bacterial biofilm and flexible engineering to introduce new properties. CsgA in particular has already demonstrated its worth in hydrogels for stable gastrointestinal colonization and regenerative tissue engineering, cell-specific drug release, water-purification filters, and different biosensors. It also holds promise as catalytic amyloid; existing weak and unspecific activity can undoubtedly be improved by targeted engineering and benefit from the repetitive display of active sites on a surface. Unfortunately, FapC remains largely unexplored and no application is described so far. Since FapC shares many common features with CsgA, this opens the window to its development as a functional scaffold. The multiple imperfect repeats in CsgA and FapC form a platform to introduce novel properties, e.g., in connecting linkers of variable lengths. While exploitation of this potential is still at an early stage, particularly for FapC, a thorough understanding of their molecular properties will pave the way for multifunctional fibrils which can contribute toward solving many different societal challenges, ranging from CO2 fixation to hydrolysis of plastic nanoparticles.


Asunto(s)
Amiloide , Materiales Biocompatibles , Animales , Humanos , Amiloide/química , Amiloide/metabolismo , Materiales Biocompatibles/química , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Hidrogeles/química
14.
Bioorg Med Chem Lett ; 101: 129648, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38331226

RESUMEN

In the treatment of non-small cell lung cancer (NSCLC), acquired drug resistance is a major factor that affects the efficacy of third-generation epidermal growth factor receptor (EGFR) inhibitors like Osimertinib. To overcome the L858R/T790M/C797S mutation, taking the Brigatinib as the positive control, two classes of 20 target compounds were designed and synthesized with 2-phenylaminopyrimidine as the core structure on the basis of summarizing the structure-activity relationship (SAR), following the basic principles of drug design. Representative compound I-10 potently inhibited EGFRL858R/T790M/C797S with an IC50 value of 33.26 nM and suppressed Ba/F3-EGFRL858R/T790M/C797S cells with an IC50 value of 106.4 nM, which is 5-fold more potent than Brigatinib. Besides, the compound exhibited an inhibition rate of less than 50 % against wild-type cell (NCI-H838), which reflected its toxicity or selectivity. Furthermore, this work serves as a foundation for future studies on EGFR inhibitors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Compuestos Organofosforados , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptores ErbB , Mutación , Inhibidores de Proteínas Quinasas/química , Resistencia a Antineoplásicos , Línea Celular Tumoral
15.
Nat Commun ; 15(1): 1119, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321010

RESUMEN

The metasurface platform with time-varying characteristics has emerged as a promising avenue for exploring exotic physics associated with Floquet materials and for designing photonic devices like linear frequency converters. However, the limited availability of materials with ultrafast responses hinders their applications in the terahertz range. Here we present a time-varying metasurface comprising an array of superconductor-metal hybrid meta-molecules. Each meta-molecule consists of two meta-atoms that are "bonded" together by double superconducting microbridges. Through experimental investigations, we demonstrate high-efficiency linear terahertz frequency conversion by rapidly breaking the bond using a coherent ultrashort terahertz pump pulse. The frequency and relative phase of the converted wave exhibit strong dependence on the pump-probe delay, indicating phase controllable wave conversion. The dynamics of the meta-molecules during the frequency conversion process are comprehensively understood using a time-varying coupled mode model. This research not only opens up new possibilities for developing innovative terahertz sources but also provides opportunities for exploring topological dynamics and Floquet physics within metasurfaces.

16.
Light Sci Appl ; 13(1): 25, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38253520

RESUMEN

Classical and quantum space-to-ground communications necessitate highly sensitive receivers capable of extracting information from modulated photons to extend the communication distance from near-earth orbits to deep space explorations. To achieve gigabit data rates while mitigating strong background noise photons and beam drift in a highly attenuated free-space channel, a comprehensive design of a multi-functional detector is indispensable. In this study, we present an innovative compact multi-pixel superconducting nanowire single-photon detector array that integrates near-unity detection efficiency (91.6%), high photon counting rate (1.61 Gcps), large dynamic range for resolving different photon numbers (1-24), and four-quadrant position sensing function all within one device. Furthermore, we have constructed a communication testbed to validate the advantages offered by such an architecture. Through 8-PPM (pulse position modulation) format communication experiments, we have achieved an impressive maximum data rate of 1.5 Gbps, demonstrating sensitivities surpassing previous benchmarks at respective speeds. By incorporating photon number information into error correction codes, the receiver can tolerate maximum background noise levels equivalent to 0.8 photons/slot at a data rate of 120 Mbps-showcasing a great potential for daylight operation scenarios. Additionally, preliminary beam tracking tests were conducted through open-loop scanning techniques, which revealed clear quantitative dependence indicating sensitivity variations based on beam location. Based on the device characterizations and communication results, we anticipate that this device architecture, along with its corresponding signal processing and coding techniques, will be applicable in future space-to-ground communication tasks.

17.
J Neuroimmunol ; 387: 578285, 2024 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-38219400

RESUMEN

BACKGROUND: Rituximab effectively targets B cells and reduces relapses in neuromyelitis optica spectrum disorder (NMOSD). But the ideal dosage and treatment intervals remain unanswered. We aimed to assess the efficacy and safety of low and ultralow-dose rituximab in NMOSD. METHODS: We conducted a retrospective analysis of NMOSD patients treated with rituximab at two Chinese tertiary hospitals. Patients received either a low-dose regimen (500 mg reinfusion every 6 months) or an ultralow-dose regimen: 100 to 300 mg rituximab based on CD19+B cells (100 mg for 1-1.5% of peripheral blood mononuclear cells, 200 mg for 1.5-5%, and 300 mg for over 5%). RESULTS: We analyzed data from 136 patients (41 in the low-dose group, 95 in the ultralow-dose group) with median follow-up durations of 43 and 34.2 months, respectively. Both groups exhibited similar sex distribution, age at disease onset, annual relapse rate, and baseline disease duration. Survival analysis showed that ultralow-dose rituximab was noninferior to low-dose rituximab in preventing relapses. Infusion reactions occurred in 20 of 173 (11.6%) low-dose treatments and 9 of 533 (1.7%) ultralow-dose treatments. B-cell re-emergence was observed in 137 of 236 (58.1%) monitors in the low-dose group and 367 of 1136 (32.3%) monitors in the ultralow-dose group. CONCLUSION: Ultralow dose rituximab was noninferior to low-dose rituximab in preventing NMOSD relapses. A randomized controlled trial is essential to validate these findings.


Asunto(s)
Neuromielitis Óptica , Humanos , Rituximab , Factores Inmunológicos , Estudios Retrospectivos , Leucocitos Mononucleares , Recurrencia , Acuaporina 4
18.
Pestic Biochem Physiol ; 196: 105610, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37945249

RESUMEN

The widespread use of pesticides hampers the immune system of non-target organisms, however, there is a lack of common biomarkers to detect such effects. Myeloid differentiation primary response factor 88 (MyD88) is a crucial junction protein in the Toll-like receptor signaling pathway, which plays an important role in the inflammatory response. In this study, we investigated MyD88 as a potential biomarker for pesticide-induced stress. Phylogenetic analysis revealed that MyD88 was a conserved protein in the evolution of vertebrates and invertebrates. MyD88s usually have death domain (DD) and Toll/interleukin-1 receptor (TIR) domain. Bombyx mori (B. mori) is an important economic insect that is sensitive to toxic substances. We found microbial pesticides enhanced the expression level of MyD88 in B. mori. Transcriptome analysis demonstrated that MyD88 expression level was increased in the fatbody after dinotefuran exposure, a third-generation neonicotinoid pesticide. Moreover, the expression of MyD88 was upregulated in fatbody and midgut by imidacloprid, a first-generation neonicotinoid pesticide. Additionally, insect growth regulator (IGR) pesticides, such as methoprene and fenoxycarb, could induce MyD88 expression in the fatbody of B. mori. These results indicated that MyD88 is a potential biomarker for pesticide-induced stress in B. mori. This study provides novel insights into screening common biomarkers for multiple pesticide stresses and important implications for the development of more sustainable pest management strategies.


Asunto(s)
Bombyx , Plaguicidas , Animales , Plaguicidas/farmacología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/farmacología , Filogenia , Biomarcadores , Neonicotinoides/toxicidad , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo
19.
Cell Mol Life Sci ; 80(11): 331, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37870631

RESUMEN

Juvenile hormone (JH) is an indispensable insect hormone that is critical in regulating insect development and physiology. N6-methyladenosine (m6A) is the most abundant modification of RNA that regulates RNA fate in eukaryotic organisms. However, the relationship between m6A and JH remains largely unknown. Here, we found that the application of a Juvenile hormone analog (JHA) extended the larval period of Bombyx mori and increased the weight and thickness of the cocoon. Interestingly, global transcriptional patterns revealed that m6A-related genes are specifically regulated by JHA in the posterior silk gland (PSG) that synthesizes the major component of cocoon silk. By transcriptome and m6A sequencing data conjointly, we discovered that JHA significantly regulated the m6A modification in the PSG of B. mori and many m6A-containing genes are related to nucleic acid binding, nucleus, and nucleobase-containing compound metabolism. Notably, 547 genes were significantly regulated by JHA at both the m6A modification and expression levels, especially 16 silk-associated genes, including sericin2, seroin1, Serine protease inhibitors 4 (BmSPI4), Serine protease inhibitors 5 (BmSPI5), and LIM domain-binding protein 2 (Ldb). Among them, 11 silk associated genes were significantly affected by METTL3 knockdown, validating that these genes are targets of m6A modification. Furthermore, we confirm that JHA directly regulates the expression of BmSPI4 and BmSPI5 through m6A modification of CDS regions. These results demonstrate the essential role of m6A methylation regulated by JH in PSG, and elucidate a novel mechanism by which JH affects silk gland development via m6A methylation. This study uncovers that m6A modification is a critical factor mediating the effect of JH in insects.


Asunto(s)
Bombyx , Seda , Animales , Seda/genética , Hormonas Juveniles/genética , Metilación , Bombyx/genética , Bombyx/metabolismo , Larva , Transcriptoma , ARN/metabolismo , Inhibidores de Serina Proteinasa , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo
20.
Sci Adv ; 9(42): eadi7565, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37851805

RESUMEN

Electrically controlled terahertz (THz) beamforming antennas are essential for various applications such as wireless communications, security checks, and radar to improve coverage and information capacity. The emerging programmable metasurface provides a flexible, cost-effective platform for THz beam steering. However, scaling such arrays to achieve high-gain beam steering faces several technical challenges. Here, we propose a pixelated liquid crystal THz metasurface with a crossbar structure, thereby increasing the array scale to more than 3000. The coding pattern on the programmable device is generated by the modulo-addition of the coding sequences on the top and bottom layers. We experimentally demonstrate the programmable liquid crystal metasurface capable of active beam deflection in the upper half-space. This scale-up of programmable devices opens exciting opportunities in pencil beamforming, high-speed information processing, and optical computing.

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