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1.
BMC Psychiatry ; 24(1): 338, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711061

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined. METHODS: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits. RESULTS: Our MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW ß (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume. CONCLUSIONS: Overall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance.


Asunto(s)
Encéfalo , Análisis de la Aleatorización Mendeliana , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cognición/fisiología , Estudio de Asociación del Genoma Completo , Imagen por Resonancia Magnética , Masculino , Disfunción Cognitiva/genética , Disfunción Cognitiva/fisiopatología
2.
Cereb Cortex ; 34(13): 172-186, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696606

RESUMEN

Individuals with autism spectrum disorder (ASD) experience pervasive difficulties in processing social information from faces. However, the behavioral and neural mechanisms underlying social trait judgments of faces in ASD remain largely unclear. Here, we comprehensively addressed this question by employing functional neuroimaging and parametrically generated faces that vary in facial trustworthiness and dominance. Behaviorally, participants with ASD exhibited reduced specificity but increased inter-rater variability in social trait judgments. Neurally, participants with ASD showed hypo-activation across broad face-processing areas. Multivariate analysis based on trial-by-trial face responses could discriminate participant groups in the majority of the face-processing areas. Encoding social traits in ASD engaged vastly different face-processing areas compared to controls, and encoding different social traits engaged different brain areas. Interestingly, the idiosyncratic brain areas encoding social traits in ASD were still flexible and context-dependent, similar to neurotypicals. Additionally, participants with ASD also showed an altered encoding of facial saliency features in the eyes and mouth. Together, our results provide a comprehensive understanding of the neural mechanisms underlying social trait judgments in ASD.


Asunto(s)
Trastorno del Espectro Autista , Encéfalo , Reconocimiento Facial , Imagen por Resonancia Magnética , Percepción Social , Humanos , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/psicología , Masculino , Femenino , Adulto , Adulto Joven , Reconocimiento Facial/fisiología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Juicio/fisiología , Mapeo Encefálico , Adolescente
3.
Langmuir ; 40(13): 7078-7086, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38514080

RESUMEN

The correlation between structure and properties in the photodegradation reaction of bismuth oxychloride (BiOCl) was explored in this work. Three BiOCl samples with different sizes, morphological structures, and defects were prepared through a hydrothermal method with experimental manipulation. Their structural properties were comprehensively characterized using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, electron spin resonance, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy, and photoluminescence. Taking the photodegradation of tetracycline hydrochloride (TC-HCl) as the probe reaction, we found that high activity could be achieved by decreasing their crystal size and thickness, introducing proper defects in the structure, and assembling the nanosheets to get microball structure. Combined with radical-scavenge experiments and electron spin resonance (ESR) spin-trap spectra, we conclude that ̇O2- was the dominant reactive oxygen species for the degradation reaction. The degradation detailed pathway of TC-HCl was further analyzed using liquid chromatography-mass spectrometry. This work explores the structure-property correlation of BiOCl and provides strategies for the rational design of active photocatalysts for water remediation.

4.
Sci Immunol ; 9(94): eadn1452, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38530158

RESUMEN

Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys191/Cys192 (human/mouse), catalyzed by palmitoyl acyltransferases ZDHHC5 and ZDHHC9 and facilitated by reactive oxygen species (ROS), directly mediated membrane translocation of GSDMD-NT but not full-length GSDMD (GSDMD-FL). Palmitoylation of GSDMD-FL could be induced before inflammasome activation by stimuli such as lipopolysaccharide (LPS), consequently serving as an essential molecular event in macrophage priming. Inhibition of GSDMD palmitoylation suppressed macrophage pyroptosis and IL-1ß release, mitigated organ damage, and enhanced the survival of septic mice. Thus, GSDMD-NT palmitoylation is a key regulatory mechanism controlling GSDMD membrane localization and activation, which may offer an additional target for modulating immune activity in infectious and inflammatory diseases.


Asunto(s)
Piroptosis , Animales , Humanos , Ratones , Gasderminas , Lipoilación , Proteómica
5.
Sci Rep ; 14(1): 5400, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443486

RESUMEN

Neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) make different judgments of social traits from others' faces; they also exhibit different social emotional responses in social interactions. A common hypothesis is that the differences in face perception in ASD compared with NT is related to distinct social behaviors. To test this hypothesis, we combined a face trait judgment task with a novel interpersonal transgression task that induces measures social emotions and behaviors. ASD and neurotypical participants viewed a large set of naturalistic facial stimuli while judging them on a comprehensive set of social traits (e.g., warm, charismatic, critical). They also completed an interpersonal transgression task where their responsibility in causing an unpleasant outcome to a social partner was manipulated. The purpose of the latter task was to measure participants' emotional (e.g., guilt) and behavioral (e.g., compensation) responses to interpersonal transgression. We found that, compared with neurotypical participants, ASD participants' self-reported guilt and compensation tendency was less sensitive to our responsibility manipulation. Importantly, ASD participants and neurotypical participants showed distinct associations between self-reported guilt and judgments of criticalness from others' faces. These findings reveal a novel link between perception of social traits and social emotional responses in ASD.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Juicio , Emociones , Culpa
6.
J Clin Med ; 13(3)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38337567

RESUMEN

The surgery first approach (SFA) and clear aligners technique can address traditional treatment defects, such as prolonged waiting times for surgery and a less desirable facial appearance due to wire aligners. However, the curative effect of the combination remains uncertain. The randomized controlled study aimed to evaluate the skeletal stability of the SFA compared to the conventional orthodontic first approach (OFA), both of which were applied with clear aligners. A total of 74 participants were randomly allocated to two groups: the SFA group (experimental) and the OFA group (control). The skeletal deviation was calculated using reconstruction models from computed tomography scans taken immediately and 6 months after surgery. The largest median deviations were detected in the y-axis of the mandible for both two groups, separately 1.36 mm in the experimental group and 1.19 mm in the control group. Apart from the maxillary yaw dimension (p = 0.005), there were no significant differences between the two groups in terms of linear and angular deviation. The experimental group had an overall treatment time of 18.05 ± 2.53 months, while the control group took 22.83 ± 3.60 months (p < 0.05). Therefore, the combined surgery-first and clear aligners treatment can achieve comparable skeletal stability to the conventional approach, while also saving significant time.

7.
Polymers (Basel) ; 16(4)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38399903

RESUMEN

The performance of ethylene/1-octene copolymer primarily depends on the microstructure of the polymer chain. This study employed a new method to control the inter-distribution of hexyl chain branches directly on the backbone of the ethylene/1-octene copolymer. Three ethylene/1-octene copolymers with different inter-distributions of hexyl chain branches were synthesized using [Me2Si(C5Me4) (NtBu)] TiCl2 (Ti-CGC) by different feeding sequences in the semi-continuous polymerization reaction system. The three copolymers were named according to the feeding sequence of the materials: ethylene/1-octene/Ti-CGC (EOC), 1-octene/Ti-CGC/ethylene (OCE), and ethylene/Ti-CGC/1-octene (ECO), respectively. The structure and properties of the copolymers were characterized using HT-GPC, 13C-NMR, DSC, WAXD, DMA, MI, and Uniaxial Tension Test. The results showed that the feeding sequence greatly affected the comonomer distribution of the molecular chains, molecular weight, molecular weight distribution, and chemical composition of the copolymers, consequently influencing their thermal performance and mechanical properties. Thus, it is probable that one could obtain an ethylene/1-octene copolymer with designed properties by controlling the feeding sequence during the ethylene/1-octene semi-continuous copolymerization process.

8.
Nat Commun ; 15(1): 68, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167846

RESUMEN

Receiving a favor from another person may induce a negative feeling of indebtedness for the beneficiary. In this study, we explore these hidden costs by developing and validating a conceptual model of indebtedness across three studies that combine a large-scale online questionnaire, an interpersonal game, computational modeling, and neuroimaging. Our model captures how individuals perceive the altruistic and strategic intentions of the benefactor. These inferences produce distinct feelings of guilt and obligation that together comprise indebtedness and motivate reciprocity. Perceived altruistic intentions convey care and communal concern and are associated with activity in insula, ventromedial prefrontal cortex and dorsolateral prefrontal cortex, while inferred strategic intentions convey expectations of future reciprocity and are associated with activation in temporal parietal junction and dorsomedial prefrontal cortex. We further develop a neural utility model of indebtedness using multivariate patterns of brain activity that captures the tradeoff between these feelings and reliably predicts reciprocity behavior.


Asunto(s)
Emociones , Culpa , Humanos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Altruismo , Intención , Imagen por Resonancia Magnética/métodos
9.
Nat Commun ; 15(1): 386, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195694

RESUMEN

Both lytic and apoptotic cell death remove senescent and damaged cells in living organisms. However, they elicit contrasting pro- and anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of death remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil lytic pyroptotic death. The tightly regulated GSDME cleavage and activation in aging neutrophils are mediated by proteinase-3 and caspase-3, leading to pyroptosis. GSDME deficiency does not alter neutrophil overall survival rate; instead, it specifically precludes pyroptosis and skews neutrophil death towards apoptosis, thereby attenuating inflammatory responses due to augmented efferocytosis of apoptotic neutrophils by macrophages. In a clinically relevant acid-aspiration-induced lung injury model, neutrophil-specific deletion of GSDME reduces pulmonary inflammation, facilitates inflammation resolution, and alleviates lung injury. Thus, by controlling the mode of neutrophil death, GSDME dictates host inflammatory outcomes, providing a potential therapeutic target for infectious and inflammatory diseases.


Asunto(s)
Gasderminas , Lesión Pulmonar , Humanos , Neutrófilos , Apoptosis , Piroptosis
10.
Ann N Y Acad Sci ; 1531(1): 29-48, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37965931

RESUMEN

Faces are among the most important visual stimuli that humans perceive in everyday life. While extensive literature has examined emotional processing and social evaluations of faces, most studies have examined either topic using unimodal approaches. In this review, we promote the use of multimodal cognitive neuroscience approaches to study these processes, using two lines of research as examples: ambiguity in facial expressions of emotion and social trait judgment of faces. In the first set of studies, we identified an event-related potential that signals emotion ambiguity using electroencephalography and we found convergent neural responses to emotion ambiguity using functional neuroimaging and single-neuron recordings. In the second set of studies, we discuss how different neuroimaging and personality-dimensional approaches together provide new insights into social trait judgments of faces. In both sets of studies, we provide an in-depth comparison between neurotypicals and people with autism spectrum disorder. We offer a computational account for the behavioral and neural markers of the different facial processing between the two groups. Finally, we suggest new practices for studying the emotional processing and social evaluations of faces. All data discussed in the case studies of this review are publicly available.


Asunto(s)
Trastorno del Espectro Autista , Reconocimiento Facial , Humanos , Juicio , Emociones/fisiología , Electroencefalografía , Expresión Facial
11.
Adv Mater ; 36(13): e2309862, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38133487

RESUMEN

The extracellular potassium ion concentration in the brain exerts a significant influence on cellular excitability and intercellular communication. Perturbations in the extracellular potassium ion level are closely correlated with various chronic neuropsychiatric disorders including depression. However, a critical gap persists in performing real-time and long-term monitoring of extracellular potassium ions, which is necessary for comprehensive profiling of chronic neuropsychiatric diseases. Here, a fiber potassium ion sensor (FKS) that consists of a soft conductive fiber with a rough surface and a hydrophobic-treated transduction layer interfaced with a potassium ion-selective membrane is found to solve this problem. The FKS demonstrates stable interfaces between its distinct functional layers in an aqueous environment, conferring an exceptional stability of 6 months in vivo, in stark contrast to previous reports with working durations from hours to days. Upon implantation into the mouse brain, the FKS enables effective monitoring of extracellular potassium ion dynamics under diverse physiological states including anesthesia, forced swimming, and tail suspension. Using this FKS, tracking of extracellular potassium ion fluctuations that align with behaviors associated with the progression of depression over months is achieved, demonstrating its usability in studying chronic neuropsychiatric disorders from a new biochemical perspective.


Asunto(s)
Encéfalo , Potasio , Animales , Ratones , Iones
12.
Shanghai Kou Qiang Yi Xue ; 32(4): 342-350, 2023 Aug.
Artículo en Chino | MEDLINE | ID: mdl-38044725

RESUMEN

PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.


Asunto(s)
Magnesio , Osteogénesis , Magnesio/farmacología , Magnesio/química , Aleaciones/farmacología , Aleaciones/química , Fosfatos de Calcio/farmacología , Diferenciación Celular , Polietilenglicoles/farmacología
13.
J Clin Med ; 12(24)2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38137607

RESUMEN

Hemifacial Microsomia (HFM) is the second most common congenital craniofacial malformation syndrome, and the complexity of HFM makes its treatment challenging. The present study aimed to introduce a new approach of utilization of virtual surgical planning (VSP) and 3D-printed surgical adjuncts for maxillofacial reconstruction. Five HFM patients were included in this study. All participants were provided with a full VSP, including the design of osteotomy lines, the design and fabrication of 3D-printed cutting guides, fixation plates, and titanium mesh for implantation. With the assistance of 3D-printed cutting guides and fixation plates, the orbital deformities were corrected, and a 3D-printed titanium mesh combined with iliac cancellous bone graft was applied to reconstruct the zygomatic arch. The surgical accuracy, effectiveness, and bone absorption rate were evaluated. All patients completed the entirely digital treatment process without experiencing severe complications. The surgical adjuncts were effective in aligning the movement of the bone segments with the surgical plan, resulting in mean 3D deviations (1.0681 ± 0.15 mm) and maximum 3D deviations (3.1127 ± 0.44 mm). The image fusion results showed that the patients' postoperative position of the maxilla, zygoma, and orbital rim was consistent with the virtual surgical plan, with only a slight increase in the area of bone grafting. The postoperative measurements showed significant improvement in the asymmetry indices of Er (AI of Er: from 17.91 ± 3.732 to 5.427 ± 1.389 mm, p = 0.0001) and FZ (AI of FZ: from 7.581 ± 1.435 to 4.070 ± 1.028 mm, p = 0.0009) points. In addition, the observed bone resorption rate at the 6-month follow-up across the five patients was 45.24% ± 3.13%. In conclusion, the application of VSP and 3D-printed surgical adjuncts demonstrates significant value in enhancing the precision and effectiveness of surgical treatments for HFM. A 3D-printed titanium mesh combined with iliac cancellous bone graft can be considered an ideal alternative for the reconstruction of the zygomatic arch.

14.
Mol Immunol ; 164: 28-38, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37944204

RESUMEN

The immune system contributes to the pathophysiology of endometriosis. The role of ThGM cells, which produce granulocyte macrophage-colony-stimulating factor (GM-CSF), in the pathogenesis of endometriosis remains unknown. To analyze the features of ThGM cells in endometriosis, a mouse endometriosis model was established. ThGM cells in the spleen, peritoneal fluid (PF), and endometriotic lesions (EL) were measured by flow cytometry, based on the expression of surface markers and intracellular proteins. Live ThGM cells were sorted according to chemokine receptor expression profiles and their effects on other CD4+ T cell subsets were determined by co-culture assays. An adoptive transfer assay was performed to characterize the effect of ThGM cells on endometriosis. We found that ThGM cells were present in endometriotic PF and EL. Live EL ThGM cells were enriched in CD4+CXCR3-CCR8-CCR4+CCR10+ T cells. EL ThGM cells differentially express interleukin-35 receptor (IL-35R), consisting of an IL-35R+ subset and an IL-35R- subset. The IL-35R+ subset expressed less GM-CSF, interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α) and proliferated slower than the IL-35R- subset. Meanwhile, the IL-35R+ subset was weaker than the IL-35R- subset in promoting the functions of Th1 and Th17 cells. ThGM cell transfer did not influence EL development but significantly alleviated pro-inflammatory cytokines in PF and ELs. Interleukin-35 (IL-35), the ligand of IL-35R, suppressed ThGM cell function and proliferation in an IL-35R-dependent manner. In summary, ThGM cells in the PF and ELs might exacerbate endometriotic inflammation. IL-35 might suppress the function of ThGM cells via IL-35R.


Asunto(s)
Endometriosis , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Receptores de Interleucina , Animales , Femenino , Humanos , Ratones , Endometriosis/metabolismo , Endometriosis/patología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Granulocitos/metabolismo , Macrófagos/metabolismo , Receptores de Interleucina/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo
15.
BMC Oral Health ; 23(1): 876, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978486

RESUMEN

BACKGROUND: Accurate cephalometric analysis plays a vital role in the diagnosis and subsequent surgical planning in orthognathic and orthodontics treatment. However, manual digitization of anatomical landmarks in computed tomography (CT) is subject to limitations such as low accuracy, poor repeatability and excessive time consumption. Furthermore, the detection of landmarks has more difficulties on individuals with dentomaxillofacial deformities than normal individuals. Therefore, this study aims to develop a deep learning model to automatically detect landmarks in CT images of patients with dentomaxillofacial deformities. METHODS: Craniomaxillofacial (CMF) CT data of 80 patients with dentomaxillofacial deformities were collected for model development. 77 anatomical landmarks digitized by experienced CMF surgeons in each CT image were set as the ground truth. 3D UX-Net, the cutting-edge medical image segmentation network, was adopted as the backbone of model architecture. Moreover, a new region division pattern for CMF structures was designed as a training strategy to optimize the utilization of computational resources and image resolution. To evaluate the performance of this model, several experiments were conducted to make comparison between the model and manual digitization approach. RESULTS: The training set and the validation set included 58 and 22 samples respectively. The developed model can accurately detect 77 landmarks on bone, soft tissue and teeth with a mean error of 1.81 ± 0.89 mm. Removal of region division before training significantly increased the error of prediction (2.34 ± 1.01 mm). In terms of manual digitization, the inter-observer and intra-observer variations were 1.27 ± 0.70 mm and 1.01 ± 0.74 mm respectively. In all divided regions except Teeth Region (TR), our model demonstrated equivalent performance to experienced CMF surgeons in landmarks detection (p > 0.05). CONCLUSIONS: The developed model demonstrated excellent performance in detecting craniomaxillofacial landmarks when considering manual digitization work of expertise as benchmark. It is also verified that the region division pattern designed in this study remarkably improved the detection accuracy.


Asunto(s)
Aprendizaje Profundo , Humanos , Tomografía Computarizada por Rayos X/métodos , Radiografía , Cefalometría/métodos , Huesos , Procesamiento de Imagen Asistido por Computador/métodos
16.
Appl Environ Microbiol ; 89(10): e0052223, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37800939

RESUMEN

Rhodococcus opacus PD630 is a high oil-producing strain with the ability to convert lignin-derived aromatics to high values, but limited research has been done to elucidate its conversion pathway, especially the upper pathways. In this study, we focused on the upper pathways and demethylation mechanism of lignin-derived aromatics metabolism by R. opacus PD630. The results of the aromatic carbon resource utilization screening showed that R. opacus PD630 had a strong degradation capacity to the lignin-derived methoxy-containing aromatics, such as guaiacol, 3,4-veratric acid, anisic acid, isovanillic acid, and vanillic acid. The gene of gcoAR, which encodes cytochrome P450, showed significant up-regulation when R. opacus PD630 grew on diverse aromatics. Deletion mutants of gcoAR and its partner protein gcoBR resulted in the strain losing the ability to grow on guaiacol, but no significant difference to the other aromatics. Only co-complementation alone of gcoAR and gcoBR restored the strain's ability to utilize guaiacol, demonstrating that both genes were equally important in the utilization of guaiacol. In vitro assays further revealed that GcoAR could convert guaiacol and anisole to catechol and phenol, respectively, with the production of formaldehyde as a by-product. The study provided robust evidence to reveal the molecular mechanism of R. opacus PD630 on guaiacol metabolism and offered a promising study model for dissecting the demethylation process of lignin-derived aromatics in microbes.IMPORTANCEAryl-O-demethylation is believed to be the key rate-limiting step in the catabolism of heterogeneous lignin-derived aromatics in both native and engineered microbes. However, the mechanisms of O-demethylation in lignin-derived aromatic catabolism remain unclear. Notably, guaiacol, the primary component unit of lignin, lacks in situ demonstration and illustration of the molecular mechanism of guaiacol O-demethylation in lignin-degrading bacteria. This is the first study to illustrate the mechanism of guaiacol metabolism by R. opacus PD630 in situ as well as characterize the purified key O-demethylase in vitro. This study provided further insight into the lignin metabolic pathway of R. opacus PD630 and could guide the design of an efficient biocatalytic system for lignin valorization.


Asunto(s)
Lignina , Rhodococcus , Lignina/metabolismo , Guayacol/metabolismo , Fenoles/metabolismo , Rhodococcus/genética , Rhodococcus/metabolismo
17.
Transl Psychiatry ; 13(1): 334, 2023 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-37898626

RESUMEN

Processing facial expressions of emotion draws on a distributed brain network. In particular, judging ambiguous facial emotions involves coordination between multiple brain areas. Here, we applied multimodal functional connectivity analysis to achieve network-level understanding of the neural mechanisms underlying perceptual ambiguity in facial expressions. We found directional effective connectivity between the amygdala, dorsomedial prefrontal cortex (dmPFC), and ventromedial PFC, supporting both bottom-up affective processes for ambiguity representation/perception and top-down cognitive processes for ambiguity resolution/decision. Direct recordings from the human neurosurgical patients showed that the responses of amygdala and dmPFC neurons were modulated by the level of emotion ambiguity, and amygdala neurons responded earlier than dmPFC neurons, reflecting the bottom-up process for ambiguity processing. We further found parietal-frontal coherence and delta-alpha cross-frequency coupling involved in encoding emotion ambiguity. We replicated the EEG coherence result using independent experiments and further showed modulation of the coherence. EEG source connectivity revealed that the dmPFC top-down regulated the activities in other brain regions. Lastly, we showed altered behavioral responses in neuropsychiatric patients who may have dysfunctions in amygdala-PFC functional connectivity. Together, using multimodal experimental and analytical approaches, we have delineated a neural network that underlies processing of emotion ambiguity.


Asunto(s)
Emociones , Imagen por Resonancia Magnética , Humanos , Vías Nerviosas , Emociones/fisiología , Amígdala del Cerebelo , Corteza Prefrontal , Mapeo Encefálico , Expresión Facial
18.
Biomaterials ; 302: 122324, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37738740

RESUMEN

An embolic reagent with easy injection, well-controlled target embolization, and sustained release of chemotherapy drugs is urgently needed for successful trans-arterial chemo-embolization (TACE) treatment. However, the development of a highly effective embolic reagent is still challenged. Here, inspired and guided by the structural supporting properties and defense mechanisms of wood cell walls, an ideal lignin-based embolic nanogel (DOX-pN-KL) was explored. Based on the mechanical support of branched lignin and the π-π stacking force between the lignin aromatic ring with anti-tumor drug doxorubicin (DOX), DOX-pN-KL showed the highest mechanical strength among the reported thermosensitive embolization nanogel and performed high drug-loading and favorable sustained-release. Moreover, further TACE treatment and tumor microenvironment evaluation of VX2 tumor-bearing rabbits showed that this nanogel can completely block all levels of vessels in long term and continuously release DOX, thus having effective inhibition on tumor growth and metastasis. DOX-pN-KL is expected to be a promising alternative reagent for interventional therapy.


Asunto(s)
Lignina , Neoplasias Hepáticas , Animales , Conejos , Nanogeles , Madera , Neoplasias Hepáticas/terapia , Doxorrubicina , Stents , Microambiente Tumoral
19.
iScience ; 26(10): 107870, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37766973

RESUMEN

Even though the discovery of lytic polysaccharide monooxygenases (LPMOs) has fundamentally shifted our understanding of biomass degradation, most of the current studies focused on their roles in carbohydrate oxidation. However, no study demonstrated if LPMO could directly participate to the process of lignin degradation in lignin-degrading microbes. This study showed that LPMO could synergize with lignin-degrading enzymes for efficient lignin degradation in white-rot fungi. The transcriptomics analysis of fungi Irpex lacteus and Dichomitus squalens during their lignocellulosic biomass degradation processes surprisingly highlighted that LPMOs co-regulated with lignin-degrading enzymes, indicating their more versatile roles in the redox network. Biochemical analysis further confirmed that the purified LPMO from I. lacteus CD2 could use diverse electron donors to produce H2O2, drive Fenton reaction, and synergize with manganese peroxidase for lignin oxidation. The results thus indicated that LPMO might uniquely leverage the redox network toward dynamic and efficient degradation of different cell wall components.

20.
Proc Natl Acad Sci U S A ; 120(40): e2302484120, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37769254

RESUMEN

Two behavioral motivations coexist in transgressors following an interpersonal transgression-approaching and compensating the victim and avoiding the victim. Little is known about how these motivations arise, compete, and drive transgressors' decisions. The present study adopted a social interaction task to manipulate participants' (i.e., the transgressor) responsibility for another's (i.e., the victim) monetary loss and measure the participants' tradeoff between compensating the victim and avoiding face-to-face interactions with the victim. Following each transgression, participants used a computer mouse to choose between two options differing in the amount of compensation to the victim and the probability of face-to-face contact with the victim. Results showed that as participants' responsibility increased, 1) the decision weights on contact avoidance relative to compensation increased, and 2) the onset of the contact-avoidance attribute was expedited and that of the compensation attribute was delayed. These results demonstrate how competing social motivations following transgression evolve and determine social decision-making and shed light on how social-affective state modulates the dynamics of decision-making in general.


Asunto(s)
Emociones , Motivación , Humanos , Conducta Social , Interacción Social , Relaciones Interpersonales
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