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In conventional superconductors, the phase transition into a zero-resistance and perfectly diamagnetic state is accompanied by a jump in the specific heat and the opening of a spectral gap1. In the high-transition-temperature (high-Tc) cuprates, although the transport, magnetic and thermodynamic signatures of Tc have been known since the 1980s2, the spectroscopic singularity associated with the transition remains unknown. Here we resolve this long-standing puzzle with a high-precision angle-resolved photoemission spectroscopy (ARPES) study on overdoped (Bi,Pb)2Sr2CaCu2O8+δ (Bi2212). We first probe the momentum-resolved electronic specific heat via spectroscopy and reproduce the specific heat peak at Tc, completing the missing link for a holistic description of superconductivity. Then, by studying the full momentum, energy and temperature evolution of the spectra, we reveal that this thermodynamic anomaly arises from the singular growth of in-gap spectral intensity across Tc. Furthermore, we observe that the temperature evolution of in-gap intensity is highly anisotropic in the momentum space, and the gap itself obeys both the d-wave functional form and particle-hole symmetry. These findings support the scenario that the superconducting transition is driven by phase fluctuations. They also serve as an anchor point for understanding the Fermi arc and pseudogap phenomena in underdoped cuprates.
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Wood formation involves consecutive developmental steps, including cell division of vascular cambium, xylem cell expansion, secondary cell wall (SCW) deposition, and programmed cell death. In this study, we identified PagMYB31 as a coordinator regulating these processes in Populus alba × Populus glandulosa and built a PagMYB31-mediated transcriptional regulatory network. PagMYB31 mutation caused fewer layers of cambial cells, larger fusiform initials, ray initials, vessels, fiber and ray cells, and enhanced xylem cell SCW thickening, showing that PagMYB31 positively regulates cambial cell proliferation and negatively regulates xylem cell expansion and SCW biosynthesis. PagMYB31 repressed xylem cell expansion and SCW thickening through directly inhibiting wall-modifying enzyme genes and the transcription factor genes that activate the whole SCW biosynthetic program, respectively. In cambium, PagMYB31 could promote cambial activity through TRACHEARY ELEMENT DIFFERENTIATION INHIBITORY FACTOR (TDIF)/PHLOEM INTERCALATED WITH XYLEM (PXY) signaling by directly regulating CLAVATA3/ESR-RELATED (CLE) genes, and it could also directly activate WUSCHEL HOMEOBOX RELATED4 (PagWOX4), forming a feedforward regulation. We also observed that PagMYB31 could either promote cell proliferation through the MYB31-MYB72-WOX4 module or inhibit cambial activity through the MYB31-MYB72-VASCULAR CAMBIUM-RELATED MADS2 (VCM2)/PIN-FORMED5 (PIN5) modules, suggesting its role in maintaining the homeostasis of vascular cambium. PagMYB31 could be a potential target to manipulate different developmental stages of wood formation.
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Cámbium , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Populus , Factores de Transcripción , Xilema , Populus/genética , Populus/crecimiento & desarrollo , Populus/metabolismo , Xilema/metabolismo , Xilema/genética , Xilema/crecimiento & desarrollo , Cámbium/genética , Cámbium/crecimiento & desarrollo , Cámbium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Pared Celular/metabolismo , Proliferación Celular , Madera/crecimiento & desarrollo , Madera/metabolismo , Madera/genéticaRESUMEN
Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Anciano , Humanos , Masculino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Envejecimiento/genética , Mutación , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , PronósticoRESUMEN
The perinuclear theca (PT) is a cytoskeletal element encapsulating the sperm nucleus; however, the physiological roles of the PT in sperm are largely uncertain. Here, we reveal that ACTRT1, ACTRT2, ACTL7A and ACTL9 proteins interact to form a multimeric complex and localize to the subacrosomal region of spermatids. Furthermore, we engineered Actrt1-knockout (KO) mice to define the functions of ACTRT1. Despite normal sperm count and motility, Actrt1-KO males were severely subfertile owing to a deficiency in fertilization. Loss of ACTRT1 caused a high incidence of malformed heads and detachment of acrosomes from sperm nuclei, caused by loosened acroplaxome structure during spermiogenesis. Furthermore, Actrt1-KO sperm showed reduced ACTL7A and PLCζ protein content as a potential cause of fertilization defects. Moreover, we reveal that ACTRT1 anchors developing acrosomes to the nucleus, likely by interacting with the inner acrosomal membrane protein SPACA1 and the nuclear envelope proteins PARP11 and SPATA46. Loss of ACTRT1 weakened the interaction between ACTL7A and SPACA1. Our study and recent findings of ACTL7A/ACTL9-deficient sperm together reveal that the sperm PT-specific ARP complex mediates the acrosome-nucleus connection.
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Acrosoma , Infertilidad Masculina , Acrosoma/metabolismo , Animales , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/metabolismo , Espermátides/metabolismo , Espermatogénesis/genética , Espermatozoides/metabolismoRESUMEN
Tektins are microtubule inner proteins (MIPs) and localize at the inside lumen of doublet microtubules (DMTs) of cilia/flagella. TEKTIP1, a newly identified protein by cryo-electron microscopy (cryo-EM), is proposed to be localized at the center of the tektin bundle and hypothesized to recruit tektins or stabilize the bundle. However, the physiological role of TEKTIP1 is unknown. In this study, we generated Tektip1-knockout (Tektip1-/-) mice and showed that they were male subfertile primarily due to reduced sperm motility. A high percentage of sperm from Tektip1-/- mice showed moderately disorganized axoneme structures and abnormal flagellar waveforms. TEKTIP1 predominately interacted with TEKT3 among tektins. Loss of TEKTIP1 partially disturbed the organization of tektin bundle by mainly affecting the native status of TEKT3 and its interaction with other tektins. Collectively, our study reveals the physiological role and potential molecular mechanism of TEKTIP1 in axonemal structure and sperm motility, highlights the importance of MIPs in stabilizing DMTs, and suggests a potential relevance of TEKTIP1 deficiency to human asthenospermia. Tektip1-/- mice will be an excellent animal model to study the DMT organization of sperm flagella using cryo-EM in future.
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Axonema , Proteínas de Microtúbulos , Semen , Humanos , Masculino , Animales , Ratones , Femenino , Microscopía por Crioelectrón , Motilidad Espermática , Espermatozoides , FlagelosRESUMEN
The effect of Lifshitz transition on thermodynamics and superconductivity in hole-doped cuprates has been heavily debated but remains an open question. In particular, an observed peak of electronic specific heat is proposed to originate from fluctuations of a putative quantum critical point p* (e.g., the termination of pseudogap at zero temperature), which is close to but distinguishable from the Lifshitz transition in overdoped La-based cuprates where the Fermi surface transforms from hole-like to electron-like. Here we report an in situ angle-resolved photoemission spectroscopy study of three-dimensional Fermi surfaces in La2-xSrxCuO4 thin films (x = 0.06 to 0.35). With accurate kz dispersion quantification, the said Lifshitz transition is determined to happen within a finite range around x = 0.21. Normal state electronic specific heat, calculated from spectroscopy-derived band parameters, reveals a doping-dependent profile with a maximum at x = 0.21 that agrees with previous thermodynamic microcalorimetry measurements. The account of the specific heat maximum by underlying band structures excludes the need for additionally dominant contribution from the quantum fluctuations at p*. A d-wave superconducting gap smoothly across the Lifshitz transition demonstrates the insensitivity of superconductivity to the dramatic density of states enhancement.
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The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Transcriptoma , Leucemia Mieloide Aguda/genética , Diferenciación Celular/genética , Células Madre HematopoyéticasRESUMEN
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Transcriptoma , Niño , Humanos , Mutación , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genéticaRESUMEN
Revealing the effect of surface structure changes on the electrocatalytic performance is beneficial to the development of highly efficient catalysts. However, precise regulation of the catalyst surface at the atomic level remains challenging. Here, we present a continuous strain regulation of palladium (Pd) on gold (Au) via a mechanically controllable surface strain (MCSS) setup. It is found that the structural changes induced by the strain setup can accelerate electron transfer at the solid-liquid interface, thus achieving a significantly improved performance toward hydrogen evolution reaction (HER). In situ X-ray diffraction (XRD) experiments further confirm that the enhanced activity is attributed to the increased interplanar spacing resulting from the applied strain. Theoretical calculations reveal that the tensile strain modulates the electronic structure of the Pd active sites and facilitates the desorption of the hydrogen intermediates. This work provides an effective approach for revealing the relationships between the electrocatalyst surface structure and catalytic activity.
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Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).
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Proteínas de Fusión Oncogénica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Proteína 2 de Unión a Repeticiones Teloméricas , Animales , Humanos , Ratones , Carcinogénesis , Transformación Celular Neoplásica , Mesilato de Imatinib , Inhibidores de Proteínas Quinasas/farmacología , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Transducción de Señal , Factor de Transcripción STAT5/genética , Proteína 2 de Unión a Repeticiones Teloméricas/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
The recent revolution in the superconductivity field stems from hydride superconductors. Multicomponent hydrides provide a crucial platform for tracking high-temperature superconductors. Besides high superconducting transition temperature (Tc), achieving both giant upper critical magnetic field [µ0Hc2(0)] and high critical current density [Jc(0)] is also key to the latent potential of the application for hydride superconductors. In this work, we have successfully synthesized quaternary La-Y-Ce hydrides with excellent properties under moderate pressure by using the concept of "entropy engineering." The obtained temperature dependence of the resistance provides evidence for the superconductivity of Fm3m-(La,Y,Ce)H10, with the maximum Tc â¼ 190 K (at 112 GPa). Notably, Fm3m-(La,Y,Ce)H10 boasts exceptional properties: µ0Hc2(0) reaching 292 T and Jc(0) surpassing 4.61 × 107 A/cm2. Compared with the binary LaH10/YH10, we find that the Fm3m structure in (La,Y,Ce)H10 can be stable at relatively low pressures (112 GPa). These results indicate that multicomponent hydrides can significantly enhance the superconducting properties and regulate stabilizing pressure through the application of "entropy engineering." This work stimulates the experimental exploration of multihydride superconductors and also provides a reference for the search of room-temperature superconductors in more diversified hydride materials in the future.
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OBJECTIVES: Increasing studies demonstrated the importance of C5a and anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation in the pathogenesis of ANCA-associated vasculitis (AAV). Sphingosine-1-phosphate (S1P) acts as a downstream effector molecule of C5a and enhances neutrophil activation induced by C5a and ANCA. The current study investigated the role of a S1P receptor modulator FTY720 in experimental autoimmune vasculitis (EAV) and explored the immunometabolism-related mechanisms of FTY720 in modulating ANCA-induced neutrophil activation. METHODS: The effects of FTY720 in EAV were evaluated by quantifying hematuria, proteinuria, crescent formation, tubulointerstitial injury and pulmonary hemorrhage. RNA sequencing of renal cortex and gene enrichment analysis were performed. The proteins of key identified pathways were analyzed in neutrophils isolated from peripheral blood of patients with active AAV and normal controls. We assessed the effects of FTY720 on ANCA-induced neutrophil respiratory burst and neutrophil extracellular traps formation (NETosis). RESULTS: FTY720 treatment significantly attenuated renal injury and pulmonary hemorrhage in EAV. RNA sequencing analyses of renal cortex demonstrated enhanced fatty acid oxidation (FAO) and peroxisome proliferators-activated receptors (PPAR) signalling in FTY720-treated rats. Compared with normal controls, patients with active AAV showed decreased FAO in neutrophils. FTY720-treated differentiated HL-60 cells showed increased expression of carnitine palmitoyltransferase 1A (CPT1a) and PPARα. Blocking or knockdown of CPT1a or PPARα in isolated human neutrophils and HL-60 cells reversed the inhibitory effects of FTY720 on ANCA-induced neutrophil respiratory burst and NETosis. CONCLUSION: FTY720 attenuated renal injury in EAV through upregulating FAO via the PPARα-CPT1a pathway in neutrophils, offering potential immunometabolic targets in AAV treatment.
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Oocyte activation failure, one of the main factors of total fertilization failure (TFF) after ICSI, could be induced by abnormal calcium oscillations. Phospholipase C zeta (PLCζ), a sperm factor, was associated with Ca2+ oscillations in oocytes of mammals. To date, only a limited number of mutations in PLCZ1 (the gene encodes PLCζ) have been linked to TFF demonstrated by the observed reduction in protein levels or activity. In this study, males with normozoospermic sperm suffering TFF after ICSI and their families were recruited. Firstly, mutations in the PLCZ1 sequence were identified by Whole exome sequencing and validated by Sanger sequencing. Then the transcript and protein levels and locations of PLCZ1/PLCζ in sperms of patients were studied followed by in vitro function analysis and in silico analysis to investigate the function-structure correlation of mutations identified in PLCZ1 through Western blotting, Immunofluorescence, RT-qPCR and Molecular Simulation. Ca2+ oscillations were detected after cRNA microinjection with M⠡ mouse oocyte to investigate the calcium oscillations of abnormal PLCζ. Five variants in compound heterozygosity were identified including five new mutations and three-reported mutations which were located across the main domains of PLCζ, except the EF hands domain. The transcript and protein levels were decreased among all the mutations identified in PLCZ1 at different degrees when transfected with HEK293T cells. Among these mutations, M138V and R391* of PLCζ could not trigger normal Ca2+ oscillations. In case 5, an abnormal location in the head of sperm and a higher expression of PLCζ in the sperm were found.
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Background: Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. Methods: The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged ≥ 20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Results: Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher CHA 2 DS 2 -VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). Conclusions: This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.
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Recent evidence has increasingly underscored the importance of the neuro-immune axis in mediating allergic airway diseases, such as allergic asthma and allergic rhinitis. The intimate spatial relationship between neurons and immune cells suggests that their interactions play a pivotal role in regulating allergic airway inflammation. Upon direct activation by allergens, neurons and immune cells engage in interactions, during which neurotransmitters and neuropeptides released by neurons modulate immune cell activity. Meanwhile, immune cells release inflammatory mediators such as histamine and cytokines, stimulating neurons and amplifying neuropeptide production, thereby exacerbating allergic inflammation. The dynamic interplay between the nervous and immune systems suggests that targeting the neuro-immune axis in the airway could represent a novel approach to treating allergic airway diseases. This review summarized recent evidence on the nervous system's regulatory mechanisms in immune responses and identified potential therapeutic targets along the peripheral nerve-immune axis for allergic asthma and allergic rhinitis. The findings will provide novel perspectives on the management of allergic airway diseases in the future.
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Asma , Neuropéptidos , Trastornos Respiratorios , Rinitis Alérgica , Humanos , Neuroinmunomodulación , Asma/tratamiento farmacológico , Sistema Respiratorio , Rinitis Alérgica/tratamiento farmacológico , InflamaciónRESUMEN
The experimentally discovered FeH5 exhibits a structure built of atomic hydrogen that only has bonding between hydrogen and iron atoms [C. M. Pepin, G. Geneste, A. Dewaele, M. Mezouar and P. Loubeyre, Science, 2017, 357, 382]. However, its superconductivity has remained unsolved since its discovery. In this work, we have synthesized I4/mmm-FeH5 at 139 GPa combined with laser-heating conditions. The electrical resistance measurements at ultrahigh pressures indicate that no evidence of superconducting transition of FeH5 is observed in the temperature range of 1.5 K to 270 K. These results indicate that I4/mmm-FeH5 does not exhibit superconductivity within the experimental temperature range, and the introduction of iron atoms is not beneficial to the formation of the superconducting phase.
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The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm.
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The incorporation of conductive materials to enhance electron transfer in bioelectrochemical systems (BES) is considered a promising approach. However, the specific effects and mechanisms of these materials on trichloroethylene (TCE) reductive dechlorination in BES remains are not fully understood. This study investigated the use of magnetite nanoparticles (MNP) and biochars (BC) as coatings on biocathodes for TCE reduction. Results demonstrated that the average dechlorination rates of MNP-Biocathode (122.89 µM Cl·d-1) and BC-Biocathode (102.88 µM Cl·d-1) were greatly higher than that of Biocathode (78.17 µM Cl·d-1). Based on MATLAB calculation, the dechlorination rate exhibited a more significantly increase in TCE-to-DCE step than the other dechlorination steps. Microbial community analyses revealed an increase in the relative abundance of electroactive and dechlorinating populations (e.g., Pseudomonas, Geobacter, and Desulfovibrio) in MNP-Biocathode and BC-Biocathode. Functional gene analysis via RT-qPCR showed the expression of dehalogenase (RDase) and direct electron transfer (DET) related genes was upregulated with the addition of MNP and BC. These findings suggest that conductive materials might accelerate reductive dechlorination by enhancing DET. The difference of physicochemical characteristics (e.g. particle size and specific surface area), electron transfer enhancement mechanism between MNP and BC as well as the reduction of Fe(III) by hydrogen may explain the superior dechlorination rate observed with MNP-Biocathode.
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Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.
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Hipoxia-Isquemia Encefálica , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Recién Nacido , Animales , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Antioxidantes/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Circumcision-a common pediatric procedure-can cause significant pain and anxiety. Virtual reality has been proposed as a nonpharmacological intervention to alleviate these negative experiences. OBJECTIVE: This systematic review and meta-analysis was conducted to evaluate the effects of virtual reality interventions on pain and anxiety in children undergoing circumcision. METHODS: This study comprehensively searched PubMed, Embase, and Cochrane Library for articles published from database inception to October 2, 2023. Randomized controlled trials that investigated the effects of virtual reality interventions on pain and anxiety during circumcision in children were included. The Cochrane risk-of-bias tool was used to appraise the included studies. The primary outcomes were pain and anxiety scores. RESULTS: Three randomized controlled trials and four data sets involving a total of 224 children were included in our meta-analysis. Virtual reality interventions significantly reduced children's pain and anxiety scores. CONCLUSIONS: Virtual reality interventions are promising nonpharmacological strategies for alleviating children's pain and anxiety during circumcision. Pediatric healthcare professionals use virtual reality interventions to create a child-friendly and healthy healthcare environment.