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Within the family of two-dimensional dielectrics, rhombohedral boron nitride (rBN) is considerably promising owing to having not only the superior properties of hexagonal boron nitride1-4-including low permittivity and dissipation, strong electrical insulation, good chemical stability, high thermal conductivity and atomic flatness without dangling bonds-but also useful optical nonlinearity and interfacial ferroelectricity originating from the broken in-plane and out-of-plane centrosymmetry5-23. However, the preparation of large-sized single-crystal rBN layers remains a challenge24-26, owing to the requisite unprecedented growth controls to coordinate the lattice orientation of each layer and the sliding vector of every interface. Here we report a facile methodology using bevel-edge epitaxy to prepare centimetre-sized single-crystal rBN layers with exact interlayer ABC stacking on a vicinal nickel surface. We realized successful accurate fabrication over a single-crystal nickel substrate with bunched step edges of the terrace facet (100) at the bevel facet (110), which simultaneously guided the consistent boron-nitrogen bond orientation in each BN layer and the rhombohedral stacking of BN layers via nucleation near each bevel facet. The pure rhombohedral phase of the as-grown BN layers was verified, and consequently showed robust, homogeneous and switchable ferroelectricity with a high Curie temperature. Our work provides an effective route for accurate stacking-controlled growth of single-crystal two-dimensional layers and presents a foundation for applicable multifunctional devices based on stacked two-dimensional materials.
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Phytohormone signalling pathways have an important role in defence against pathogens mediated by cell-surface pattern recognition receptors and intracellular nucleotide-binding leucine-rich repeat class immune receptors1,2 (NLR). Pathogens have evolved counter-defence strategies to manipulate phytohormone signalling pathways to dampen immunity and promote virulence3. However, little is known about the surveillance of pathogen interference of phytohormone signalling by the plant innate immune system. The pepper (Capsicum chinense) NLR Tsw, which recognizes the effector nonstructural protein NSs encoded by tomato spotted wilt orthotospovirus (TSWV), contains an unusually large leucine-rich repeat (LRR) domain. Structural modelling predicts similarity between the LRR domain of Tsw and those of the jasmonic acid receptor COI1, the auxin receptor TIR1 and the strigolactone receptor partner MAX2. This suggested that NSs could directly target hormone receptor signalling to promote infection, and that Tsw has evolved a LRR resembling those of phytohormone receptors LRR to induce immunity. Here we show that NSs associates with COI1, TIR1 and MAX2 through a common repressor-TCP21-which interacts directly with these phytohormone receptors. NSs enhances the interaction of COI1, TIR1 or MAX2 with TCP21 and blocks the degradation of corresponding transcriptional repressors to disable phytohormone-mediated host immunity to the virus. Tsw also interacts directly with TCP21 and this interaction is enhanced by viral NSs. Downregulation of TCP21 compromised Tsw-mediated defence against TSWV. Together, our findings reveal that a pathogen effector targets TCP21 to inhibit phytohormone receptor function, promoting virulence, and a plant NLR protein has evolved to recognize this interference as a counter-virulence strategy, thereby activating immunity.
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Capsicum , Enfermedades de las Plantas , Reguladores del Crecimiento de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Receptores de Reconocimiento de Patrones , Leucina , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/virología , Reguladores del Crecimiento de las Plantas/metabolismo , Inmunidad de la Planta/inmunología , Proteínas de Plantas/química , Proteínas de Plantas/inmunología , Proteínas de Plantas/metabolismo , Receptores de Reconocimiento de Patrones/química , Receptores de Reconocimiento de Patrones/inmunología , Receptores de Reconocimiento de Patrones/metabolismo , Reconocimiento de Inmunidad Innata , Capsicum/inmunología , Capsicum/metabolismo , Capsicum/virología , VirulenciaRESUMEN
Plant intracellular nucleotide-binding and leucine-rich repeat immune receptors (NLRs) play a key role in activating a strong pathogen defense response. Plant NLR proteins are tightly regulated and accumulate at very low levels in the absence of pathogen effectors. However, little is known about how this low level of NLR proteins is able to induce robust immune responses upon recognition of pathogen effectors. Here, we report that, in the absence of effector, the inactive form of the tomato NLR Sw-5b is targeted for ubiquitination by the E3 ligase SBP1. Interaction of SBP1 with Sw-5b via only its N-terminal domain leads to slow turnover. In contrast, in its auto-active state, Sw-5b is rapidly turned over as SBP1 is upregulated and interacts with both its N-terminal and NB-LRR domains. During infection with the tomato spotted wilt virus, the viral effector NSm interacts with Sw-5b and disrupts the interaction of Sw-5b with SBP1, thereby stabilizing the active Sw-5b and allowing it to induce a robust immune response.
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Proteínas NLR , Inmunidad de la Planta , Proteínas de Plantas , Solanum lycopersicum , Ubiquitinación , Solanum lycopersicum/inmunología , Solanum lycopersicum/virología , Solanum lycopersicum/metabolismo , Solanum lycopersicum/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/inmunología , Proteínas de Plantas/genética , Proteínas NLR/metabolismo , Proteínas NLR/inmunología , Proteínas NLR/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/inmunología , Tospovirus/inmunología , Proteínas Virales/metabolismo , Proteínas Virales/inmunología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/inmunología , Interacciones Huésped-Patógeno/inmunologíaRESUMEN
Plant intracellular nucleotide-binding domain, leucine-rich repeat-containing receptors (NLRs) activate a robust immune response upon detection of pathogen effectors. How NLRs induce downstream immune defense genes remains poorly understood. The Mediator complex plays a central role in transducing signals from gene-specific transcription factors to the transcription machinery for gene transcription/activation. In this study, we demonstrate that MED10b and MED7 of the Mediator complex mediate jasmonate-dependent transcription repression, and coiled-coil NLRs (CNLs) in Solanaceae modulate MED10b/MED7 to activate immunity. Using the tomato CNL Sw-5b, which confers resistance to tospovirus, as a model, we found that the CC domain of Sw-5b directly interacts with MED10b. Knockout/down of MED10b and other subunits including MED7 of the middle module of Mediator activates plant defense against tospovirus. MED10b was found to directly interact with MED7, and MED7 directly interacts with JAZ proteins, which function as transcriptional repressors of jasmonic acid (JA) signaling. MED10b-MED7-JAZ together can strongly repress the expression of JA-responsive genes. The activated Sw-5b CC interferes with the interaction between MED10b and MED7, leading to the activation of JA-dependent defense signaling against tospovirus. Furthermore, we found that CC domains of various other CNLs including helper NLR NRCs from Solanaceae modulate MED10b/MED7 to activate defense against different pathogens. Together, our findings reveal that MED10b/MED7 serve as a previously unknown repressor of jasmonate-dependent transcription repression and are modulated by diverse CNLs in Solanaceae to activate the JA-specific defense pathways.
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Proteínas de Arabidopsis , Inmunidad de la Planta , Inmunidad de la Planta/genética , Ciclopentanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Complejo Mediador/genética , Complejo Mediador/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMEN
Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen-glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin-related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2-D08 (a small-molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy-related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2-D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3-Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.
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Autofagia , Daño del ADN , Lamina Tipo B , Neuronas , Traumatismos de la Médula Espinal , Sumoilación , Enzimas Ubiquitina-Conjugadoras , Animales , Ratones , Núcleo Celular/metabolismo , Lamina Tipo B/metabolismo , Lamina Tipo B/genética , Neuronas/metabolismo , Neuronas/patología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/patología , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Ratones Endogámicos C57BL , Línea Celular TumoralRESUMEN
Chiral nanographenes (NGs) have garnered significant interest as optoelectronic materials in recent years. While helically chiral NGs have been extensively studied, axially chiral NGs have only witnessed limited examples, with no prior reports of axially chiral nonbenzenoid NGs. Herein we report an axially chiral nonbenzenoid nanographene featuring six pentagons and four heptagons. This compound, denoted as 2, was efficiently synthesized via an efficient Pd-catalyzed aryl silane homocoupling reaction. The presence of two bulky 3,5-di-tert-butylphenyl groups around the axis connecting the two nonbenzenoid PAH (AHR) segments endows 2 with atropisomeric chirality and high racemization energy barrier, effectively preventing racemization of both R- and S-enantiomers at room temperature. Optically pure R-2 and S-2 were obtained by chiral HPLC separation, and they exhibit circular dichroism (CD) activity at wavelengths up to 660 nm, one of the longest wavelengths with CD responses reported for the chiral NGs. Interestingly, racemic 2 forms a homoconfiguration π-dimer in the crystal lattice, belonging to the I222 chiral space group. Consequently, this unique structure renders crystals of 2 with a second harmonic generation (SHG) response, distinguishing it from all the reported axially chiral benzenoid NGs. Moreover, R-2 and S-2 also exhibit SHG-CD properties.
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We present comprehensive computational and experimental studies on the mechanism of an asymmetric photoredox/Pd dual-catalytic reductive C(sp3)-C(sp3) homocoupling of allylic electrophiles. In stark contrast to the canonical assumption that photoredox promotes bond formation via facile reductive elimination from high-valent metal-organic species, our computational analysis revealed an intriguing low-valent allylpalladium pathway that features tandem operation of Pd(0/II/I)-Pd(0/II/I/II) cycles. Specifically, we propose that (i) the photoredox/Pd system enables the in situ generation of allyl radicals from low-valent Pd(I)-allyl species, and (ii) effective interception of the fleeting allyl radical by the chiral Pd(I)-allyl species results in the formation of an enantioenriched product. Notably, the cooperation of the two pathways highlights the bifunctional role of Pd(I)-allyl species in the generation and interception of transient allyl radicals. Moreover, the mechanism implies divergent substrate-activation modes in this homocoupling reaction, suggesting a theoretical possibility for cross-coupling. Combined, the current study offers a novel mechanistic hypothesis for photoredox/Pd dual catalysis and highlights the use of low-valent allylpalladium as a means to efficiently intercept radicals for selective asymmetric bond constructions.
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Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder characterized by hyperinflammation. Recently, ruxolitinib (RUX), targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy. In this study (www.chictr.org.cn, ChiCTR2000031702), we designed ruxolitinib as a first-line agent for pediatric HLH and stratified the treatment based on its early response. Fifty-two newly diagnosed patients were enrolled. The overall response rate (ORR) of ruxolitinib monotherapy (day 28) was 69.2% (36/52), with 42.3% (22/52) achieving sustained complete remission (CR). All responders achieved their first response to ruxolitinib within 3 days. The response to ruxolitinib was significantly associated with the underlying etiology at enrollment (P = .009). Epstein-Barr virus (EBV)-HLH patients were most sensitive to ruxolitinib, with an ORR of 87.5% (58.3% in CR). After ruxolitinib therapy, 57.7% (30/52) of the patients entered intensive therapy with additional chemotherapy. Among them, 53.3% (16/30) patients achieved CR, and 46.7% (14/30) patients dominated by chronic active EBV infection-associated HLH (CAEBV-HLH) developed refractory HLH by week 8. The median interval to additional treatment since the first ruxolitinib administration was 6 days (range, 3-25 days). Altogether, 73.1% (38/52) of the enrolled patients achieved CR after treatment overall. The 12-month overall survival (OS) for all patients was 86.4% (95% confidence interval [CI], 77.1% to 95.7%). Ruxolitinib had low toxicity and was well tolerated compared with intensive chemotherapy. Our study provides clinical evidence for ruxolitinib as a frontline agent for pediatric HLH. The efficacy was particularly exemplified with stratified regimens based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000031702.
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Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Nitrilos , Pirazoles/efectos adversos , PirimidinasRESUMEN
Approaching the long-time dynamics of non-Markovian open quantum systems presents a challenging task if the bath is strongly coupled. Recent proposals address this problem through a representation of the so-called process tensor in terms of a tensor network. We show that for Gaussian environments highly efficient contraction to a matrix product operator (MPO) form can be achieved with infinite MPO evolution methods, leading to significant computational speed-up over existing proposals. The result structurally resembles open system evolution with carefully designed auxiliary degrees of freedom, as in hierarchical or pseudomode methods. Here, however, these degrees of freedom are generated automatically by the MPO evolution algorithm. Moreover, the semigroup form of the resulting propagator enables us to explore steady-state physics, such as phase transitions.
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Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.
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Histiocitosis de Células de Langerhans , Receptor de Factor Estimulante de Colonias de Macrófagos , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/patología , Histiocitosis de Células de Langerhans/sangre , Masculino , Femenino , Niño , Pronóstico , Preescolar , Lactante , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Adolescente , Estudios Prospectivos , Estudios de SeguimientoRESUMEN
In arthropods, the involvement of Dscam (Down syndrome cell adhesion molecule) in innate immunity has been extensively demonstrated. Its cytoplasmic tail contains multiple conserved functional sites, which indicates its involvement in different intracellular signaling pathways. In this study, we focused on the role of the cytoplasmic tail of Dscam in the Chinese mitten crab (Eriocheir sinensis) immune defense. In the group with cytoplasmic tail knockdown (the site was located on constant exons 37 and 38), 3885 differentially expressed genes (DEGs) were identified. The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. The expression of selected genes were validated using quantitative real-time reverse transcription PCR. We identified key Cell cycle, Janus kinase (JAK)-signal transducer, activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathway genes, the results indicated that the cytoplasmic tail of Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes.
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Proteínas de Artrópodos , Braquiuros , Hemocitos , Inmunidad Innata , Animales , Braquiuros/genética , Braquiuros/inmunología , Hemocitos/inmunología , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/química , Inmunidad Innata/genética , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/inmunología , Regulación de la Expresión Génica/inmunología , Proliferación CelularRESUMEN
BACKGROUND: Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years. METHODS: The ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated. RESULTS: ACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females. CONCLUSIONS: The results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients.
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Peptidil-Dipeptidasa A , Receptor de Angiotensina Tipo 1 , Humanos , Masculino , Femenino , Anciano , Receptor de Angiotensina Tipo 1/genética , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/sangre , Polimorfismo de Nucleótido Simple , Lípidos/sangre , Lípidos/genética , Pueblo Asiatico/genética , Triglicéridos/sangre , Anciano de 80 o más Años , HDL-Colesterol/sangre , HDL-Colesterol/genética , Diabetes Mellitus/genética , Diabetes Mellitus/sangre , Mutación INDEL , LDL-Colesterol/sangre , LDL-Colesterol/genética , Estudios de Asociación Genética , China/epidemiología , Predisposición Genética a la Enfermedad , Pueblos del Este de AsiaRESUMEN
PURPOSE: To evaluate the incidence, associated factors, and outcome of persistent subretinal fluid (SRF) after vitrectomy for macular hole-associated retinal detachment (MHRD). METHODS: A total of 158 eyes from 156 patients with MHRD who achieved macular hole closure after primary vitrectomy were included in the analysis; persistent SRF was defined as the presence of SRF for more than 1 month after first surgery. Preoperative and postoperative parameters were analyzed for their relationship with SRF development. RESULTS: Persistent SRF was observed in 19 eyes (12.0% of 158) postoperatively. Seven eyes (36.8% of 19) with persistent SRF eventually displayed complete absorption during follow-up. Univariate analysis revealed that eyes with persistent SRF were statistically associated with internal limiting membrane inverted flap, duration of symptoms, tamponade (perfluoropropane/silicone oil: 14/5 vs. 35/104, P < 0.001), and MHRD subtype (Type 1/Type 2/Type 3: 15/4/0 vs. 60/40/39, P = 0.003). In multivariate analysis, only internal limiting membrane inverted flap (odds ratio, 15.778, 95% confidence interval, 3.170-78.523; P = 0.001) was positively associated with persistent SRF. There were no significant differences in best-corrected visual acuity improvement ( P = 0.425) between the SRF involved foveal and without involved foveal groups and no significant differences between the SRF complete absorption and incomplete absorption groups. CONCLUSION: Absorption of persistent SRF may be more difficult in MHRD eyes than in ordinary rhegmatogenous retinal detachment eyes. The internal limiting membrane inverted flap in MHRD was associated with a greater likelihood of persistent SRF. The location and incomplete absorption of persistent SRF did not seem to be associated with the final visual outcome.
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Endotaponamiento , Desprendimiento de Retina , Perforaciones de la Retina , Líquido Subretiniano , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía , Humanos , Vitrectomía/métodos , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Masculino , Femenino , Perforaciones de la Retina/cirugía , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/etiología , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Endotaponamiento/métodos , Tomografía de Coherencia Óptica/métodos , Complicaciones Posoperatorias , Estudios de Seguimiento , Fluorocarburos/administración & dosificación , IncidenciaRESUMEN
Excessive activation of T cells and microglia represents a hallmark of the pathogenesis of human multiple sclerosis (MS). However, the regulatory molecules overactivating these immune cells remain to be identified. Previously, we reported that extracellular IFP35 family proteins, including IFP35 and NMI, activated macrophages as proinflammatory molecules in the periphery. Here, we investigated their functions in the process of neuroinflammation both in the central nervous system (CNS) and the periphery. Our analysis of clinical transcriptomic data showed that expression of IFP35 family proteins was up-regulated in patients with MS. Additional in vitro studies demonstrated that IFP35 and NMI were released by multiple cells. IFP35 and NMI subsequently triggered nuclear factor kappa B-dependent activation of microglia via the TLR4 pathway. Importantly, we showed that both IFP35 and NMI activated dendritic cells and promoted naïve T cell differentiation into Th1 and Th17 cells. Nmi-/- , Ifp35-/- , or administration of neutralizing antibodies against IFP35 alleviated the immune cells' infiltration and demyelination in the CNS, thus reducing the severity of experimental autoimmune encephalomyelitis. Together, our findings reveal a hitherto unknown mechanism by which IFP35 family proteins facilitate overactivation of both T cells and microglia and propose avenues to study the pathogenesis of MS.
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Péptidos y Proteínas de Señalización Intracelular/sangre , Péptidos y Proteínas de Señalización Intracelular/genética , Esclerosis Múltiple/patología , Enfermedades Neuroinflamatorias/patología , Animales , Anticuerpos Neutralizantes/farmacología , Estudios de Casos y Controles , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/etiología , Encefalomielitis Autoinmune Experimental/patología , Humanos , Péptidos y Proteínas de Señalización Intracelular/inmunología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Lisofosfatidilcolinas/toxicidad , Ratones Endogámicos C57BL , Ratones Mutantes , Microglía/metabolismo , Microglía/patología , Esclerosis Múltiple/genética , Enfermedades Neuroinflamatorias/genética , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
BACKGROUND: The rapidly evolving field of artificial intelligence (AI) holds great potential for plastic surgeons. ChatGPT, a recently released AI large language model (LLM), promises applications across many disciplines, including healthcare. OBJECTIVES: The aim of this article was to provide a primer for plastic surgeons on AI, LLM, and ChatGPT, including an analysis of current demonstrated and proposed clinical applications. METHODS: A systematic review was performed identifying medical and surgical literature on ChatGPT's proposed clinical applications. Variables assessed included applications investigated, command tasks provided, user input information, AI-emulated human skills, output validation, and reported limitations. RESULTS: The analysis included 175 articles reporting on 13 plastic surgery applications and 116 additional clinical applications, categorized by field and purpose. Thirty-four applications within plastic surgery are thus proposed, with relevance to different target audiences, including attending plastic surgeons (n = 17, 50%), trainees/educators (n = 8, 24.0%), researchers/scholars (n = 7, 21%), and patients (n = 2, 6%). The 15 identified limitations of ChatGPT were categorized by training data, algorithm, and ethical considerations. CONCLUSIONS: Widespread use of ChatGPT in plastic surgery will depend on rigorous research of proposed applications to validate performance and address limitations. This systemic review aims to guide research, development, and regulation to safely adopt AI in plastic surgery.
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Procedimientos de Cirugía Plástica , Cirujanos , Humanos , Inteligencia Artificial , Algoritmos , LenguajeRESUMEN
BACKGROUND: Despite increasing demand for breast capsular surgery to treat various benign and malignant implant-related pathologies, high-quality evidence elucidating complication profiles of capsulectomy and capsulotomy is lacking. OBJECTIVES: The aim of this study was to provide the largest-scale analysis of associated outcomes and complications using the Tracking Operations and Outcomes for Plastic Surgeons (TOPS) database, and to investigate clinical scenarios that may subject patients to increased risks for complications, most notably extent of capsular surgery (complete vs partial) and index indication of implantation (aesthetic vs reconstructive). METHODS: An analysis of the TOPS database from 2008 to 2019 was performed. CPT codes were used to identify complete capsulectomy and partial capsulectomy/capsulotomy cases. Breast implant exchange procedures constituted procedural controls. RESULTS: In total, 7486 patients (10,703 breasts) undergoing capsulectomy or capsulotomy were assessed. Relative to controls, capsulectomy (4.40% vs 5.79%), but not capsulotomy (4.40% vs 4.50%), demonstrated higher overall complication rates. Both capsulectomies (0.83% vs 0.23%) and capsulotomies (0.56% vs 0.23%) also had greater rates of seroma relative to controls. Subgroup analyses demonstrated that reconstructive patients, relative to aesthetic patients, experienced greater overall complications (6.76% vs 4.34%), and increased risks for seroma (1.06% vs 0.47%), dehiscence (0.46% vs 0.14%), surgical site infections (1.03% vs 0.23%), and implant loss (0.52% vs 0.23%). A detailed synthesis of 30-day outcomes, including all patient- and breast-specific complications, for both capsulectomy and capsulotomy, stratified according to all potential confounders, is presented herein. CONCLUSIONS: Surgeries on the breast capsule are safe overall, although complete capsulectomies and reconstructive patients are associated with significantly increased operative risks. The present findings will enhance patient selection, counseling, and informed consent.
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Implantación de Mama , Implantes de Mama , Bases de Datos Factuales , Complicaciones Posoperatorias , Humanos , Femenino , Implantes de Mama/efectos adversos , Implantación de Mama/efectos adversos , Implantación de Mama/métodos , Implantación de Mama/instrumentación , Persona de Mediana Edad , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano , Seroma/etiología , Seroma/epidemiología , Estados Unidos/epidemiología , Resultado del Tratamiento , Estética , Adulto JovenRESUMEN
BACKGROUND: Social media platforms have come to represent integral components of the professional marketing and advertising strategy for plastic surgeons. Effective and consistent content development, however, remains technically demanding and time consuming, prompting most to employ, at non-negligible costs, social media marketing specialists for content planning and development. OBJECTIVES: In the present study, we aimed to investigate the ability of presently available artificial intelligence (AI) models to assist plastic surgeons in their social media content development and sharing plans. METHODS: An AI large language model was prompted on the study's objectives through a series of standardized user interactions. Social media platforms of interest, on which the AI model was prompted, included Instagram, TikTok, and X (formerly Twitter). RESULTS: A 1-year, entirely AI-generated social media plan, comprising a total of 1091 posts for the 3 aforementioned social media platforms, is presented. Themes of the AI-generated content proposed for each platform were classified in 6 categories, including patient-related, practice-related, educational, "uplifting," interactive, and promotional posts. Overall, 91 publicly recognized holidays and observant and awareness days were incorporated into the content calendars. The AI model demonstrated an ability to differentiate between the distinct formats of each of the 3 social media platforms investigated, generating unique ideas for each, and providing detailed content development and posting instructions, scripts, and post captions, leveraging features specific to each platform. CONCLUSIONS: By providing detailed and actionable social media content creation and posting plans to plastic surgeons, presently available AI models can be readily leveraged to assist in and significantly alleviate the burden associated with social media account management, content generation, and potentially patient conversion.
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Inteligencia Artificial , Medios de Comunicación Sociales , Cirujanos , Cirugía Plástica , Humanos , Comercialización de los Servicios de Salud/métodosRESUMEN
BACKGROUND: Large language models (LLMs) have revolutionized the way plastic surgeons and their patients can access and leverage artificial intelligence (AI). OBJECTIVES: The present study aims to compare the performance of 2 current publicly available and patient-accessible LLMs in the potential application of AI as postoperative medical support chatbots in an aesthetic surgeon's practice. METHODS: Twenty-two simulated postoperative patient presentations following aesthetic breast plastic surgery were devised and expert-validated. Complications varied in their latency within the postoperative period, as well as urgency of required medical attention. In response to each patient-reported presentation, Open AI's ChatGPT and Google's Bard, in their unmodified and freely available versions, were objectively assessed for their comparative accuracy in generating an appropriate differential diagnosis, most-likely diagnosis, suggested medical disposition, treatments or interventions to begin from home, and/or red flag signs/symptoms indicating deterioration. RESULTS: ChatGPT cumulatively and significantly outperformed Bard across all objective assessment metrics examined (66% vs 55%, respectively; P < .05). Accuracy in generating an appropriate differential diagnosis was 61% for ChatGPT vs 57% for Bard (P = .45). ChatGPT asked an average of 9.2 questions on history vs Bard's 6.8 questions (P < .001), with accuracies of 91% vs 68% reporting the most-likely diagnosis, respectively (P < .01). Appropriate medical dispositions were suggested with accuracies of 50% by ChatGPT vs 41% by Bard (P = .40); appropriate home interventions/treatments with accuracies of 59% vs 55% (P = .94), and red flag signs/symptoms with accuracies of 79% vs 54% (P < .01), respectively. Detailed and comparative performance breakdowns according to complication latency and urgency are presented. CONCLUSIONS: ChatGPT represents the superior LLM for the potential application of AI technology in postoperative medical support chatbots. Imperfect performance and limitations discussed may guide the necessary refinement to facilitate adoption.
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Inteligencia Artificial , Complicaciones Posoperatorias , Humanos , Femenino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Mamoplastia/métodos , Mamoplastia/efectos adversos , Adulto , Diagnóstico DiferencialRESUMEN
With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon centered chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This review summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.