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Numerous studies reported inconsistent results concerning gender influences on the functional organization of the brain for language in children and adults. However, data for the gender differences in the functional language networks at birth are sparse. Therefore, we investigated gender differences in resting-state functional connectivity in the language-related brain regions in newborns using functional near-infrared spectroscopy. The results revealed that female newborns demonstrated significantly stronger functional connectivities between the superior temporal gyri and middle temporal gyri, the superior temporal gyri and the Broca's area in the right hemisphere, as well as between the right superior temporal gyri and left Broca's area. Nevertheless, statistical analysis failed to reveal functional lateralization of the language-related brain areas in resting state in both groups. Together, these results suggest that the onset of language system might start earlier in females, because stronger functional connectivities in the right brain in female neonates were probably shaped by the processing of prosodic information, which mainly constitutes newborns' first experiences of speech in the womb. More exposure to segmental information after birth may lead to strengthened functional connectivities in the language system in both groups, resulting in a stronger leftward lateralization in males and a more balanced or leftward dominance in females.
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Lenguaje , Caracteres Sexuales , Espectroscopía Infrarroja Corta , Humanos , Femenino , Espectroscopía Infrarroja Corta/métodos , Masculino , Recién Nacido , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Descanso/fisiología , Lateralidad Funcional/fisiología , Vías Nerviosas/fisiología , Mapeo Encefálico/métodosRESUMEN
Carcinoembryonic antigen (CEA) of human plasma is a biomarker of many cancer diseases, and its N-glycosylation accounts for 60% of molecular mass. It is highly desirable to characterize its glycoforms for providing additional dimension of features to increase its performance in prognosis and diagnosis of cancers. However, to systematically characterize its site-specific glycosylation is challenging because of its low abundance. Here, we developed a highly sensitive strategy for in-depth glycosylation profiling of plasma CEA through chemical proteomics combined with multienzymatic digestion. A trifunctional probe was utilized to generate covalent bond of plasma CEA and its antibody upon UV irradiation. As low as 1 ng/ml CEA in plasma could be captured and digested with trypsin and chymotrypsin for intact glycopeptide characterization. Twenty six of 28 potential N-glycosylation sites were well identified, which were the most comprehensive N-glycosylation site characterization of CEA on intact glycopeptide level as far as we known. Importantly, this strategy was applied to the glycosylation analysis of plasma CEA in cancer patients. Differential site-specific glycoforms of plasma CEA were observed in patients with colorectal cancers (CRCs) and lung cancer. The distributions of site-specific glycoforms were different as the progression of CRC, and most site-specific glycoforms were overexpressed in stage II of CRC. Overall, we established a highly sensitive chemical proteomic method to profile site-specific glycosylation of plasma CEA, which should generally applicable to other well-established cancer glycoprotein biomarkers for improving their cancer diagnosis and monitoring performance.
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Antígeno Carcinoembrionario , Neoplasias Pulmonares , Humanos , Glicosilación , Antígeno Carcinoembrionario/metabolismo , Proteómica/métodos , Biomarcadores de Tumor , Glicopéptidos/análisisRESUMEN
The current treatment of skin fibrosis is limited in its effectiveness due to a lack of understanding of the underlying mechanisms. Previous research has shown a connection between microRNAs (miRNAs) and the development of skin fibrosis. Therefore, investigating miRNA for the treatment of skin fibrotic diseases is highly important and merits further exploration. In this study, we have discovered that let-7f-5p could suppress the proliferation, migration, and expression of collagen type I alpha 1 (COL1A1) in human dermal fibroblasts (HDFs). It was further determined that let-7f-5p could target thrombospondin-1 (THBS1), thereby inhibiting the TGF-ß2/Smad3 signaling pathway and exerting its biological effects. Additionally, let-7f-5p is regulated by Hsa_circ_0000437, which acts as a sponge molecule for let-7f-5p and consequently regulates the biological function of HDFs. Furthermore, our findings indicate that in vivo overexpression of let-7f-5p leads to a reduction in dermal thickness and COL1A1 expression, effectively inhibiting the progression of bleomycin (BLM)-induced skin fibrosis in mice. Hence, our research enhances the comprehension of the Hsa_circ_0000437/let-7f-5p/THBS1/TGF-ß2/Smad3 regulatory network, highlighting the potential of let-7f-5p as a therapeutic approach for the treatment of skin fibrosis.
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Electrocatalytic CO2 reduction (CO2RR) to alcohols offers a promising strategy for converting waste CO2 into valuable fuels/chemicals but usually requires large overpotentials. Herein, we report a catalyst comprising unique oxygen-bridged Cu binuclear sites (CuOCu-N4) with a Cu···Cu distance of 3.0-3.1 Å and concomitant conventional Cu-N4 mononuclear sites on hierarchical nitrogen-doped carbon nanocages (hNCNCs). The catalyst exhibits a state-of-the-art low overpotential of 0.19 V (versus reversible hydrogen electrode) for ethanol and an outstanding ethanol Faradaic efficiency of 56.3% at an ultralow potential of -0.30 V, with high-stable Cu active-site structures during the CO2RR as confirmed by operando X-ray adsorption fine structure characterization. Theoretical simulations reveal that CuOCu-N4 binuclear sites greatly enhance the C-C coupling at low potentials, while Cu-N4 mononuclear sites and the hNCNC support increase the local CO concentration and ethanol production on CuOCu-N4. This study provides a convenient approach to advanced Cu binuclear site catalysts for CO2RR to ethanol with a deep understanding of the mechanism.
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Precious-metal single-atom catalysts (SACs), featured by high metal utilization and unique coordination structure for catalysis, demonstrate distinctive performances in the fields of heterogeneous and electrochemical catalysis. Herein, gold SACs are constructed on hierarchical nitrogen-doped carbon nanocages (hNCNC) via a simple impregnation-drying process and first exploited for electrocatalytic carbon dioxide reduction reaction (CO2RR) to produce syngas. The as-constructed Au SAC exhibits the high mass activity of 3319 A g-1 Au at -1.0 V (vs reversible hydrogen electrode, RHE), much superior to the Au nanoparticles supported on hNCNC. The ratio of H2/CO can be conveniently regulated in the range of 0.4-2.2 by changing the applied potential. Theoretical study indicates such a potential-dependent H2/CO ratio is attributed to the different responses of HER and CO2RR on Au single-atom sites coordinating with one N atom at the edges of micropores across the nanocage shells. The catalytic mechanism of the Au active sites is associated with the smooth switch between twofold and fourfold coordination during CO2RR, which much decreases the free energy changes of the rate-determining steps and promotes the reaction activity.
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IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.
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Alphacoronavirus , Infecciones por Coronavirus , Endopeptidasas , Glicoproteínas , Enfermedades de los Porcinos , Porcinos , Internalización del Virus , Animales , Alphacoronavirus/fisiología , Infecciones por Coronavirus/enzimología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Endopeptidasas/metabolismo , Glicoproteínas/química , Glicoproteínas/metabolismo , Porcinos/virología , Enfermedades de los Porcinos/enzimología , Enfermedades de los Porcinos/metabolismo , Enfermedades de los Porcinos/virología , Internalización del Virus/efectos de los fármacos , Tunicamicina/farmacología , GlicosilaciónRESUMEN
Laser triggered and photothermally induced vapor bubbles have emerged as promising approaches to facilitate optomechanical energy conversion for numerous applications in microfluidics and nanofluidics. Here, we report an observation of spontaneously triggered periodic nucleation of plasmonic vapor bubbles near a rigid sidewall with readily tuned nucleation frequency from 0.8 kHz to over 200 kHz. The detailed collapsing process of the vapor bubbles was experimentally and numerically investigated. We find that the lateral migration of residual bubbles toward the sidewall refreshes the laser spot area, terminates the subsequent steady bubble growth, and leads to the repeatable bubble nucleation. A mathematic model regarding the Kelvin impulses was derived. It shows that the competition between the rigid boundary induced Bjerknes force and laser irradiation caused thermal Marangoni force on collapsing bubbles governs the process. The model also leads to a criterion of γζ<0.34 for repeatable bubble nucleation, where γ is the normalized distance and ζ thermal Marangoni coefficient. This study demonstrates nucleation of violent vapor bubbles at extreme high frequencies, providing an approach to remotely realize strong localized flows in microfluidics and nanofluidics.
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The poor prognosis of immunotherapy in patients with colorectal cancer (CRC) necessitates a comprehensive understanding of the immunosuppressive mechanisms within tumor microenvironment (TME). Undoubtedly, the anti-tumor immune cells play an indispensable role in immune tolerance. Therefore, it is imperative to investigate novel immune-related factors that have the capacity to enhance anti-tumor immunity. Here, we employed bioinformatic analysis using R and Cytoscape to identify the hub gene chemokine (C-X-C motif) ligand 8 (CXCL8), which is overexpressed in CRC, in the malignant progression of CRC. However, its specific role of CXCL8 in CRC immunity remains to be elucidated. For this purpose, we evaluated how tumor-derived CXCL8 promotes M2 macrophage infiltration by in vivo and in vitro, which can be triggered by IL-1ß within TME. Mechanistically, CXCL8-induced polarization of M2 macrophages depends on the activation of the STAT3 signaling. Finally, immunohistochemistry and multiplexed immunohistochemistry analysis identified that CXCL8 not only enhances PD-L1+ M2 macrophage infiltration but also attenuates the recruitment of PD-1+ CD8+ T cells in murine CRC models. Together, these findings emphasize the critical role for CXCL8 in promoting M2 macrophage polarization and inhibiting CD8+ T cell infiltration, thereby links CXCL8 to the emergency of immunosuppressive microenvironment facilitating tumor evasion. Overall, these findings may provide novel strategy for CRC immunotherapy.
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Linfocitos T CD8-positivos , Neoplasias Colorrectales , Interleucina-8 , Animales , Humanos , Ratones , Biología Computacional , Inmunosupresores , Macrófagos , Microambiente Tumoral , Interleucina-8/genéticaRESUMEN
The complex diffusion behaviors of rod-shaped nanoparticles near the solid-liquid interface are closely related to various biological processes and technological applications. Despite recent advancements in understanding the diffusion dynamics of nanoparticles near some specific solid-liquid interfaces, systematical studies to tune the interfacial interaction or fabricating nonuniform wall to see their effects on the nanorod (NR) diffusion are still lacking. This work utilized molecular dynamics simulations to investigate the rotational and translational diffusion dynamics of a single NR near the solid-liquid interface. We constructed a patterned wall featuring adjustable nonuniformity, which was accomplished by modifying the interaction between NR and the wall, noting that the resulting nonuniformity limits both the translational and rotational diffusion of NR, evident from decreases in diffusion coefficients and exponents. By trajectory analysis, we categorized the diffusion modes of NRs near the patterned wall with varied nonuniformities into three types: Fickian diffusion, desorption-mediated flight, and in-plane diffusion. Furthermore, energy analysis based on the adsorption-desorption mechanism has demonstrated that the three diffusion states are driven by interactions between the NR and the wall, which are primarily influenced by rotational diffusion. These results could significantly deepen the understanding of anisotropic nanoparticle interfacial diffusion and would provide new insights into the transport mechanisms of nanoparticles within confined environments.
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BACKGROUND: Previous studies have shown that TREM2 plays a protective role in acute lung injury (ALI). This prospective study aimed to investigate the role of sTREM2 as a forecasting factor for ALI in infants after pediatric cardiac surgery undergoing cardiopulmonary bypass (CPB). METHODS: Seventy-five consecutive patients younger than 1 year who underwent cardiac surgery were enrolled in this study. Sixty-one fulfilled the inclusion criteria and had been divided into ALI and non-ALI groups. Children's demographic characteristics and clinical data were collected. Perioperative sTREM2 levels were analyzed at five timepoints. RESULTS: In this study, children in the ALI group were younger, lighter, with higher RACHS-1 scores and underwent significantly longer CPB time. Post-CPB ALI had an impact on clinical outcomes, which contributed to a longer duration of mechanical ventilation, ICU and hospital stay than non-ALI group. Significant differences were manifested off-CPB, 1 h/6 h after CPB, and day 1 after surgery between the two groups. Binary logistic models revealed that off-CPB sTREM2 was significantly associated with the incidence of post-CPB ALI after adjustment. ROC analysis showed that the AUC of off-CPB sTREM2 level was 0.791, and the optimal cutoff value was 788.6 pg/ml. CONCLUSIONS: The off-CPB sTREM2 level was an independent prognostic factor for post-CPB ALI in infants. IMPACT: Plasma sTREM2 works together with downstream TREM2 to regulate inflammation response by binding the receptor to other cells. Previous studies have shown that TREM2 plays a protective role in ischemia-reperfusion and has anti-inflammatory effects on acute lung injury (ALI). This study analyzed the risk factors of post-cardiopulmonary bypass (CPB) ALI. We found that weight and off-CPB sTREM2 level were independent prognostic factors for post-CPB ALI. Plasma sTREM2 may serve as an early biomarker in the prognostic evaluation of acute lung injury after cardiac surgery in infants.
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Lesión Pulmonar Aguda , Procedimientos Quirúrgicos Cardíacos , Lactante , Humanos , Niño , Pronóstico , Estudios Prospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lesión Pulmonar Aguda/diagnóstico , Lesión Pulmonar Aguda/etiología , Puente Cardiopulmonar/efectos adversosRESUMEN
In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model. The computational results indicated that DDQ, serving as a photo-catalyst, would be excited under visible light of 450 nm, aligning well with experimental observations as reflected in the UV-vis spectrum. Gibbs free energy surface analyses of the three reactions suggested that the path involving 3DDQ* activating the reactant (-COOH, H2O, or CH3OH) is favorable. Additionally, the role of O2 was investigated, revealing that it could facilitate the recycling of DDQ by lowering the energy barrier for the conversion of the DDQHË radical (not DDQH2) into DDQ. The use of ρhole and ρele can reveal the photo-catalytic reaction and charge transfer processes, while localized orbital locator isosurfaces and electron spin density isosurface graphs were employed to analyze structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes, shedding light on the mechanisms governing C-O bond formation from arenes catalyzed by DDQ.
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The chemical kinetic studies of hydrogen atom (H-atom) abstraction reactions by hydroperoxyl (HȮ2) radicals from five branched pentanol isomers, including 3-methyl-1-butanol, 2-methyl-1-butanol, 1,1-dimethyl-1-propanol, 1,2-dimethyl-1-propanol, and 2,2-dimethyl-1-propanol were investigated systematically through high-level ab initio calculations. Geometry optimization, frequency analysis, and zero-point energy (ZPE) corrections were performed for six reactants, twenty-three transition states (TSs), and twenty-four products at the M06-2X/6-311++G(d,p) level of theory. The intrinsic reaction coordinate calculation was performed at the same level of theory to confirm the transition state connection. The one-dimensional hindered rotor treatment for low-frequency torsional modes was also treated at the M06-2X/6-311++G(d,p) level of theory. The QCISD(T)/CBS level of theory was used to calculate the single-point energies for the species whose T1 diagnostic value was lower than 0.035. At the same time, the CASPT2/CBS level of theory was used to calculate the single-point energies for the channel in which the T1 diagnostic value of transition states was greater than 0.035. Rate constants for the H-atom abstraction reactions from the five branched pentanol isomers by HȮ2 radicals were calculated by using conventional transition state theory with asymmetric Eckart tunneling corrections in the temperature range of 500-2000 K. Rate constants and branching ratios for the title reactions and the rate rules for ten different H-atom abstraction types were investigated. Temperature-dependent thermochemistry properties for all reactants and products were calculated by the composite methods of G3/G4/CBS-QB3/CBS-APNO, which were in good agreement with the data available in the literature. Rate constants for the H-atom abstraction reactions by HȮ2 radical from branched pentanol isomers were investigated in this work as part I, and those for linear pentanol isomers will be analyzed in part II. All the calculated kinetics and thermochemistry data can be utilized in the model development for branched pentanol isomers oxidation.
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KEY MESSAGE: Innovatively, we consider stomatal detection as rotated object detection and provide an end-to-end, batch, rotated, real-time stomatal density and aperture size intelligent detection and identification system, RotatedeStomataNet. Stomata acts as a pathway for air and water vapor in the course of respiration, transpiration, and other gas metabolism, so the stomata phenotype is important for plant growth and development. Intelligent detection of high-throughput stoma is a key issue. Nevertheless, currently available methods usually suffer from detection errors or cumbersome operations when facing densely and unevenly arranged stomata. The proposed RotatedStomataNet innovatively regards stomata detection as rotated object detection, enabling an end-to-end, real-time, and intelligent phenotype analysis of stomata and apertures. The system is constructed based on the Arabidopsis and maize stomatal data sets acquired destructively, and the maize stomatal data set acquired in a non-destructive way, enabling the one-stop automatic collection of phenotypic, such as the location, density, length, and width of stomata and apertures without step-by-step operations. The accuracy of this system to acquire stomata and apertures has been well demonstrated in monocotyledon and dicotyledon, such as Arabidopsis, soybean, wheat, and maize. The experimental results that the prediction results of the method are consistent with those of manual labeling. The test sets, the system code, and their usage are also given ( https://github.com/AITAhenu/RotatedStomataNet ).
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Arabidopsis , Fenotipo , Estomas de Plantas , Zea mays , Estomas de Plantas/fisiología , Zea mays/genética , Zea mays/fisiología , Zea mays/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/fisiologíaRESUMEN
Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.
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Lesión Pulmonar Aguda , Plantas Medicinales , Neumonía Viral , Neumonía , Ratones , Animales , Macrófagos Alveolares/metabolismo , Pulmón/metabolismo , Neumonía Viral/tratamiento farmacológico , Lesión Pulmonar Aguda/patología , Mitocondrias/patología , Ácido gamma-Aminobutírico/metabolismo , Neumonía/metabolismoRESUMEN
OBJECTIVE: We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: The retrospective study included a total of 77 pediatric cases (7 neonates and 70 children) who underwent ECPR after in-hospital and out-of-hospital cardiac arrest between July 2007 and December 2022. Primary endpoints were complications, while secondary endpoints included all-cause in-hospital mortality. RESULTS: Among the 45 cases experiencing complications, 4 neonates and 41 children had multiple simultaneous complications, primarily neurological issues in 25 cases. Additionally, organ failure occurred in 11 cases, and immunodeficiency was present in two cases. Furthermore, 9 cases experienced bleeding events, and 13 cases showed thrombosis. Patients with complications had lower weight, shorter ECMO durations, and longer CPR durations. Non-survivors had longer CPR durations and shorter durations of ECMO, ICU stay, and mechanical ventilation compared to survivors. Complications were more prevalent in non-survivors, particularly organ failure and bleeding events. CONCLUSION: Weight, CPR duration, and ECMO duration were associated with complications, suggesting areas for treatment optimization. The higher occurrence of complications in non-survivors underscores the importance of early detection and management to improve survival rates. Our findings suggest clinicians consider these factors in prognostic assessments to enhance the effectiveness of ECPR programs.
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Reanimación Cardiopulmonar , Oxigenación por Membrana Extracorpórea , Mortalidad Hospitalaria , Humanos , Estudios Retrospectivos , Masculino , Femenino , Oxigenación por Membrana Extracorpórea/métodos , Lactante , China/epidemiología , Preescolar , Reanimación Cardiopulmonar/métodos , Recién Nacido , Niño , Paro Cardíaco/terapia , Paro Cardíaco/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidad , AdolescenteRESUMEN
Achieving a pear-shaped balloon holds pivotal significance in the context of successful percutaneous microcompression procedures for trigeminal neuralgia. However, inflated balloons may assume various configurations, whether it is inserted into Meckel's cave or not. The absence of an objective evaluation metric has become apparent. To investigate the relationship between the morphology of Meckel's Cave and the balloon used in percutaneous microcompression for trigeminal neuralgia and establish objective criteria for assessing balloon shape in percutaneous microcompression procedures. This retrospective study included 58 consecutive patients with primary trigeminal neuralgia. Data included demographic, clinical outcomes, and morphological features of Meckel's cave and the balloon obtained from MRI and Dyna-CT imaging. MRI of Meckel's cave and Dyna-CT of intraoperative balloon were modeled, and the morphological characteristics and correlation were analyzed. The reconstructed balloon presented a fuller morphology expanding outward and upward on the basis of Meckel's cave. The projected area of balloon was strongly positively correlated with the projected area of Meckel's cave. The Pearson correlation coefficients were 0.812 (P<0.001) for axial view, 0.898 (P<0.001) for sagittal view and 0.813 (P<0.001) for coronal view. Similarity analysis showed that the sagittal projection image of Meckel's cave and that of the balloon had good similarity. This study reveals that the balloon in percutaneous microcompression essentially represents an expanded morphology of Meckel's cave, extending outward and upward. There is a strong positive correlation between the volume and projected area of the balloon and that of Meckel's cave. Notably, the sagittal projection image of Meckel's cave serves as a reliable predictor of the intraoperative balloon shape. This method has a certain generalizability and can help providing objective criteria for judging balloon shape during percutaneous microcompression procedures.
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Imagen por Resonancia Magnética , Neuralgia del Trigémino , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Neuralgia del Trigémino/cirugía , Neuralgia del Trigémino/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Tomografía Computarizada por Rayos X/métodos , Procedimientos Neuroquirúrgicos/métodos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN 177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN 177STYR (H3N4) of IgG4, EEQYN 227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.
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BACKGROUND: Hypoxic-ischemic injury of neurons is a pathological process observed in several neurological conditions, including ischemic stroke and neonatal hypoxic-ischemic brain injury (HIBI). An optimal treatment strategy for these conditions remains elusive. The present study delved deeper into the molecular alterations occurring during the injury process in order to identify potential therapeutic targets. METHODS: Oxygen-glucose deprivation/reperfusion (OGD/R) serves as an established in vitro model for the simulation of HIBI. This study utilized RNA sequencing to analyze rat primary hippocampal neurons that were subjected to either 0.5 or 2 h of OGD, followed by 0, 9, or 18 h of reperfusion. Differential expression analysis was conducted to identify genes dysregulated during OGD/R. Time-series analysis was used to identify genes exhibiting similar expression patterns over time. Additionally, functional enrichment analysis was conducted to explore their biological functions, and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for validation of hub-gene expression. RESULTS: The study included a total of 24 samples. Analysis revealed distinct transcriptomic alterations after OGD/R processes, with significant dysregulation of genes such as Txnip, Btg2, Egr1 and Egr2. In the OGD process, 76 genes, in two identified clusters, showed a consistent increase in expression; functional analysis showed involvement of inflammatory responses and signaling pathways like tumor necrosis factor (TNF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and interleukin 17 (IL-17). PPI network analysis suggested that Ccl2, Jun, Cxcl1, Ptprc, and Atf3 were potential hub genes. In the reperfusion process, 274 genes, in three clusters, showed initial upregulation followed by downregulation; functional analysis suggested association with apoptotic processes and neuronal death regulation. PPI network analysis identified Esr1, Igf-1, Edn1, Hmox1, Serpine1, and Spp1 as key hub genes. qRT-PCR validated these trends. CONCLUSIONS: The present study provides a comprehensive transcriptomic profile of an in vitro OGD/R process. Key hub genes and pathways were identified, offering potential targets for neuroprotection after hypoxic ischemia.
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Hipoxia-Isquemia Encefálica , Neuronas , Transcriptoma , Animales , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/genética , Ratas , Neuronas/metabolismo , Hipocampo/metabolismo , Ratas Sprague-Dawley , Glucosa/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Mapas de Interacción de ProteínasRESUMEN
PURPOSE: The aim of this study was to comparatively assess the efficacy and safety of double balloon catheter (DBC) and dinoprostone as labor-inducing agents just for multipara at term. METHODS: A retrospective cohort study was conducted among multipara at term with a Bishop score < 6 who needed planned labor induction from January 1, 2020, to December 30, 2020 in Maternal and Child Health Hospital of Hubei province, Tongji Medical College, Huazhong University of Science and Technology. They were divided into DBC group and dinoprostone group, respectively. Baseline maternal data, maternal and neonatal outcomes were recorded for statistical analysis. Total vaginal delivery rate, rate of vaginal delivery within 24 h, rate of uterine hyperstimulation combined with abnormal fetal heart rate(FHR) were regarded as the primary outcome variables. The difference between groups was considered statistically significant when p value < 0.05. RESULTS: A total of 202 multiparas was included for analysis (95 women in DBC group vs 107 women in dinoprostone group). There were no significant differences in total vaginal delivery rate and rate of vaginal delivery within 24 h between groups. Uterine hyperstimulation combined with abnormal FHR occurred exclusively in dinoprostone group. CONCLUSION: DBC and dinoprostone seem to be equally effective, while, DBC seems to be safer than dinoprostone.
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Dinoprostona , Oxitócicos , Embarazo , Recién Nacido , Niño , Femenino , Humanos , Dinoprostona/efectos adversos , Oxitócicos/efectos adversos , Estudios Retrospectivos , Administración Intravaginal , Trabajo de Parto Inducido , Catéteres Urinarios , Maduración Cervical/fisiologíaRESUMEN
Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a continuous threat to global wheat production. In 2021, the epidemic of wheat stripe rust in China affected approximately 4.5 million hectares, resulting in severe yield losses. When confronted with the epidemic, tracing the sources of the pathogen can offer valuable insights for disease prevention and control. This study was conducted to analyze the genetic structure, aerodynamics, geographical features, and cultivation practices of the pathogen population in various wheat-producing regions, and to further reveal the spread patterns of the stripe rust pathogens in China. The findings indicated an overall trend of the pathogen dissemination from the west to the east. The pathogen was primarily spread from the northwestern region to the Huang-Huai-Hai region through the Guanzhong Plain and the NanXiang Plain. Meanwhile, the pathogen was also spread eastward from the southwestern region to the lower reaches of the Yangtze River, utilizing the Jianghan Plain as a bridge and the Yangtze River Valley in southwestern Anhui as the main pathway. Furthermore, the pathogen spread northward into Shandong under the driving force of the southeast winds. The findings of this study may provide valuable insights for the integrated management of wheat stripe rust in China.