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1.
Natl Sci Rev ; 11(5): nwae076, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38577669

RESUMEN

China's aging demographic poses a challenge for treating prevalent bone diseases impacting life quality. As bone regeneration capacity diminishes with age due to cellular dysfunction and inflammation, advanced biomaterials-based approaches offer hope for aged bone regeneration. This review synthesizes materiobiology principles, focusing on biomaterials that target specific biological functions to restore tissue integrity. It covers strategies for stem cell manipulation, regulation of the inflammatory microenvironment, blood vessel regeneration, intervention in bone anabolism and catabolism, and nerve regulation. The review also explores molecular and cellular mechanisms underlying aged bone regeneration and proposes a database-driven design process for future biomaterial development. These insights may also guide therapies for other age-related conditions, contributing to the pursuit of 'healthy aging'.

2.
Microorganisms ; 12(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38674644

RESUMEN

Heavy metals migrate easily and are difficult to degrade in the soil environment, which causes serious harm to the ecological environment and human health. Thus, soil heavy metal pollution has become one of the main environmental issues of global concern. Plant-growth-promoting rhizobacteria (PGPR) is a kind of microorganism that grows around the rhizosphere and can promote plant growth and increase crop yield. PGPR can change the bioavailability of heavy metals in the rhizosphere microenvironment, increase heavy metal uptake by phytoremediation plants, and enhance the phytoremediation efficiency of heavy-metal-contaminated soils. In recent years, the number of studies on the phytoremediation efficiency of heavy-metal-contaminated soil enhanced by PGPR has increased rapidly. This paper systematically reviews the mechanisms of PGPR that promote plant growth (including nitrogen fixation, phosphorus solubilization, potassium solubilization, iron solubilization, and plant hormone secretion) and the mechanisms of PGPR that enhance plant-heavy metal interactions (including chelation, the induction of systemic resistance, and the improvement of bioavailability). Future research on PGPR should address the challenges in heavy metal removal by PGPR-assisted phytoremediation.

3.
Nat Commun ; 15(1): 3393, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649349

RESUMEN

Sluggish kinetics of the CO2 reduction/evolution reactions lead to the accumulation of Li2CO3 residuals and thus possible catalyst deactivation, which hinders the long-term cycling stability of Li-CO2 batteries. Apart from catalyst design, constructing a fluorinated solid-electrolyte interphase is a conventional strategy to minimize parasitic reactions and prolong cycle life. However, the catalytic effects of solid-electrolyte interphase components have been overlooked and remain unclear. Herein, we systematically regulate the compositions of solid-electrolyte interphase via tuning electrolyte solvation structures, anion coordination, and binding free energy between Li ion and anion. The cells exhibit distinct improvement in cycling performance with increasing content of C-N species in solid-electrolyte interphase layers. The enhancement originates from a catalytic effect towards accelerating the Li2CO3 formation/decomposition kinetics. Theoretical analysis reveals that C-N species provide strong adsorption sites and promote charge transfer from interface to *CO22- during discharge, and from Li2CO3 to C-N species during charge, thereby building a bidirectional fast-reacting bridge for CO2 reduction/evolution reactions. This finding enables us to design a C-N rich solid-electrolyte interphase via dual-salt electrolytes, improving cycle life of Li-CO2 batteries to twice that using traditional electrolytes. Our work provides an insight into interfacial design by tuning of catalytic properties towards CO2 reduction/evolution reactions.

4.
Blood ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38551807

RESUMEN

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response and resistance to InO. Pre- and post-InO patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation, protein destabilization) and epitope alteration. Two CD22 mutant cases were post-InO hypermutators resulting from error-prone DNA damage repair (non-homologous/alternative end joining, mismatch repair deficiency), suggesting hypermutation drove escape from CD22-directed therapy. CD22-mutant relapses occurred after InO and subsequent hematopoietic stem cell transplantation (HSCT), suggesting InO eliminated predominant clones, leaving subclones with acquired CD22 mutations that conferred resistance to InO and subsequently expanded. Acquired loss-of-function mutations in TP53, ATM and CDKN2A were observed, consistent with compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. Genome wide CRISPR/Cas9 screening in cell lines identified DNTT (TdT) loss as a marker of InO resistance. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. Our findings highlight the importance of defining the basis of CD22 escape, and eradication of residual disease prior to HSCT. The identified mechanisms of escape from CD22-targeted therapy extend beyond antigen loss, and provide opportunities to improve therapeutic approaches and overcome resistance.

5.
J Vis Exp ; (204)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38436379

RESUMEN

Hematopoietic stem cell transplantation (HSCT) requires a sufficient number of therapeutic hematopoietic stem/progenitor cells (HSPCs). To identify an adequate source of HSPCs, we developed an in vivo osteo-organoid by implanting scaffolds loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) into an internal muscle pouch near the femur in mice. After 12 weeks of implantation, we retrieved the in vivo osteo-organoids and conducted flow cytometry analysis on HPSCs, revealing a significant presence of HSPC subsets within the in vivo osteo-organoids. We then established a sublethal model of hematopoietic/immune system injury in mice through radiation and performed hematopoietic stem cell transplantation (HSCT) by injecting the extracted osteo-organoid-derived cells into the peripheral blood of radiated mice. The effect of hematopoietic recovery was evaluated through hematological, peripheral blood chimerism, and solid organ chimerism analyses. The results confirmed that in vivo osteo-organoid-derived cells can rapidly and efficiently reconstruct damaged peripheral and solid immune organs in irradiated mice. This approach holds potential as an alternative source of HSPCs for HSCT, offering benefits to a larger number of patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Recolección de Tejidos y Órganos , Humanos , Animales , Ratones , Organoides , Quimerismo , Células Madre Hematopoyéticas
6.
Cancer Cell ; 42(4): 605-622.e11, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38458188

RESUMEN

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma.


Asunto(s)
Haploinsuficiencia , Linfoma de Células B , Animales , Humanos , Ratones , Cromatina , ADN Helicasas/genética , Hiperplasia , Linfoma de Células B/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética
7.
Artículo en Inglés | MEDLINE | ID: mdl-38417787

RESUMEN

BACKGROUND: Preterm infants with low birth weight are at heightened risk of developmental sequelae, including neurological and cognitive dysfunction that can persist into adolescence or adulthood. In addition, preterm birth and low birth weight can provoke changes in endocrine and metabolic processes that likely impact brain health throughout development. However, few studies have examined associations among birth weight, pubertal endocrine processes, and long-term neurological and cognitive development. METHODS: We investigated the associations between birth weight and brain morphometry, cognitive function, and onset of adrenarche assessed 9 to 11 years later in 3571 preterm and full-term children using the ABCD (Adolescent Brain Cognitive Development) Study dataset. RESULTS: The preterm children showed lower birth weight and early adrenarche, as expected. Birth weight was positively associated with cognitive function (all Cohen's d > 0.154, p < .005), global brain volumes (all Cohen's d > 0.170, p < .008), and regional volumes in frontal, temporal, and parietal cortices in preterm and full-term children (all Cohen's d > 0.170, p < .0007); cortical volume in the lateral orbitofrontal cortex partially mediated the effect of low birth weight on cognitive function in preterm children. In addition, adrenal score and cortical volume in the lateral orbitofrontal cortex mediated the associations between birth weight and cognitive function only in preterm children. CONCLUSIONS: These findings highlight the impact of low birth weight on long-term brain structural and cognitive function development and show important associations with early onset of adrenarche during the puberty. This understanding may help with prevention and treatment.

8.
Reprod Sci ; 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38379072

RESUMEN

Dietary supplements are gaining recognition as potential influencers of female reproductive health, but their connection to endometriosis risk remains underexplored. This study addressed this gap, examining the impact of daily dietary supplement intake on the initiation and progression of endometriosis. To explore this, a cross-sectional study was conducted involving 3950 participants representative of the US population from the 1999-2006 National Health and Nutrition Examination Survey (NHANES). Infertility was determined by a question on year-long attempts to become pregnant. Unweighted and weighted multivariate logistic regression analyses assessed the association between dietary supplements and endometriosis risk. Subgroup analysis was conducted based on the participants' body mass index (BMI). The results revealed intriguing patterns. Specifically, higher dietary fiber content (Q4 vs Q1: OR = 0.56, 95% CI = (0.37,0.84), P = 0.0062) and density (Q4 vs Q1: OR = 0.55, 95% CI = (0.38,0.81), P = 0.0035) were linked to reduced risk of endometriosis. Protein content (Q4 vs Q1: OR = 0.47, 95% CI = (0.31,0.74), P = 0.0011) and density (Q4 vs Q1: OR = 0.63, 95% CI = (0.45,0.88), P = 0.0096) similarly exhibited a negative association with endometriosis risk. Interestingly, when stratified by BMI, these effects were pronounced in normal-weight women, whereas they were not evident in the overweight and obese subgroup. Protein content and density showed no significant associations across subpopulations. In conclusion, this study established a negative relationship between dietary fiber and endometriosis, particularly notable in normal-weight women. Future research is essential to validate these findings and establish a causal link between dietary fiber and endometriosis.

9.
Mol Biotechnol ; 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38393632

RESUMEN

MicroRNAs (miRNAs) play a crucial role in gene regulation and the development of keloid. This research aimed to identify and verify miRNAs associated with keloids by microarray analysis and in vitro experiments, shedding light on seeking for potential therapeutic molecular targets. In this study, the weighted gene co-expression network analysis was performed based on the GSE113620. The key miRNA module most relevant to the keloid was further screened to identify hub miRNAs, and then hub miRNAs was verified by the microarray analysis and qRT-PCR experiments. Additionally, targeted genes of hub miRNAs were predicted and verified. Gene ontology (GO) analysis and KEGG enrichment analysis were also conducted. Five miRNA modules were divided, and the blue module exhibited the highest correlation with keloids. Then, hsa-miR-127-3p, hsa-miR-214-3p, hsa-miR-155-5p, hsa-miR-409-5p, and hsa-miR-542-5p were identified as the hub miRNAs. Subsequently, the microarray analysis and qRT-PCR results demonstrated that the expression of five miRNAs were upregulated in keloid tissues. The GO analysis revealed that the target genes of these miRNAs were mainly enriched in biological processes including gene transcription, protein phosphorylation and the MAPK (mitogen-activated protein kinase) cascade, and the KEGG pathway enrichment analysis showed that the PI3K-AKT signaling pathway were significantly enriched. In conclusion, these five miRNAs (hsa-miR-127-3p, hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-409-5p, and hsa-miR-542-5p) play vital roles in the pathogenesis of keloid and might be potential therapeutic targets. These miRNAs might regulate genes enriched in gene transcription, protein phosphorylation, the MAPK cascade, and the PI3K-Akt signaling pathway.

10.
Sci Total Environ ; 918: 170697, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38331272

RESUMEN

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.


Asunto(s)
Fuentes de Energía Bioeléctrica , Aguas Residuales , Amoníaco/metabolismo , Electricidad , Reactores Biológicos , Electrodos
11.
J Hazard Mater ; 468: 133797, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38377906

RESUMEN

Heavy metals raise a global concern and can be easily retained by ubiquitous iron (oxyhydr)oxides in natural and engineered systems. The complex interaction between iron (oxyhydr)oxides and heavy metals results in various mineral-metal binding configurations, such as outer-sphere complexes and edge-sharing inner-sphere complexes, which determine the accumulation and release of heavy metals in the environment. However, traditional experimental approaches are time-consuming and inadequate to elucidate the complex binding relationships and configurations between iron (oxyhydr)oxides and heavy metals. Herein, a workflow that integrates the binding configuration data of 11 heavy metals on 7 iron (oxyhydr)oxides and then trains machine learning models to predict unknown binding configurations was proposed. The well-trained multi-grained cascade forest models exhibited high accuracy (> 90%) and predictive performance (R2 ∼ 0.75). The underlying effects of mineral properties, metal ion species, and environmental conditions on mineral-metal binding configurations were fully interpreted with data mining. Moreover, the metal release rate was further successfully predicted based on mineral-metal binding configurations. This work provides a method to accurately and quickly predict the binding configuration of heavy metals on iron (oxyhydr)oxides, which would provide guidance for estimating the potential release behavior of heavy metals and remediating heavy metal pollution in natural and engineered environments.

12.
Cereb Cortex ; 34(2)2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38300178

RESUMEN

Obesity has been linked to abnormal frontal function, including the white matter fibers of anterior portion of the corpus callosum, which is crucial for information exchange within frontal cortex. However, alterations in white matter anatomical connectivity between corpus callosum and cortical regions in patients with obesity have not yet been investigated. Thus, we enrolled 72 obese and 60 age-/gender-matched normal weight participants who underwent clinical measurements and diffusion tensor imaging. Probabilistic tractography with connectivity-based classification was performed to segment the corpus callosum and quantify white matter anatomical connectivity between subregions of corpus callosum and cortical regions, and associations between corpus callosum-cortex white matter anatomical connectivity and clinical behaviors were also assessed. Relative to normal weight individuals, individuals with obesity exhibited significantly greater white matter anatomical connectivity of corpus callosum-orbitofrontal cortex, which was positively correlated with body mass index and self-reported disinhibition of eating behavior, and lower white matter anatomical connectivity of corpus callosum-prefrontal cortex, which was significantly negatively correlated with craving for high-calorie food cues. The findings show that alterations in white matter anatomical connectivity between corpus callosum and frontal regions involved in reward and executive control are associated with abnormal eating behaviors.


Asunto(s)
Cuerpo Calloso , Sustancia Blanca , Humanos , Cuerpo Calloso/diagnóstico por imagen , Encéfalo , Imagen de Difusión Tensora/métodos , Sustancia Blanca/diagnóstico por imagen , Obesidad/diagnóstico por imagen
13.
Artículo en Inglés | MEDLINE | ID: mdl-38409281

RESUMEN

Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, PFDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, PFDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.

14.
Water Res ; 252: 121191, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38309065

RESUMEN

The solid-liquid separation is an indispensable and primary link in the process of sludge treatment and disposal. The past research was focused primarily on the technique explorations of sludge dewatering and always disregarded the internal pore structure and water migration behavior in sludge. In this work, the real three-dimensional pore structure of sludge was obtained by Nano-CT. Based on this, a pore-scale heterogeneous sludge micromodel was firstly presented, and the water flooding experiment was carried out to visualize the water migration behavior. The results showed that the sludge structure transformed from sheet-like floc to microsphere particles, and then agglomerated into large globular granules during anaerobic ammonia oxidation. And the equivalent pore size increases from 342 µm to 617 µm, improving the sludge dewaterability characterized by capillary suction time (CST). The most significant implication of this work was revealing the critical role of invalid connected pore in sludge dewatering. Such pore was not contributed to fluid flow but the circulating vortex in it even induced energy dissipation, thus deteriorated the sludge dewaterability. This work may be helpful to understand the critical role of pore characteristic in water migration and shed light on the new dewatering techniques from the perspective of regulating sludge structure.


Asunto(s)
Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Agua/química
15.
Angew Chem Int Ed Engl ; 63(9): e202317941, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38197798

RESUMEN

Wadsley-Roth niobium oxide phases have attracted extensive research interest recently as promising battery anodes. We have synthesized the niobium-molybdenum oxide shear phase (Nb, Mo)13 O33 with superior electrochemical Li-ion storage performance, including an ultralong cycling lifespan of at least 15000 cycles. During electrochemical cycling, a reversible single-phase solid-solution reaction with lithiated intermediate solid solutions is demonstrated using in situ X-ray diffraction, with the valence and short-range structural changes of the electrode probed by in situ Nb and Mo K-edge X-ray absorption spectroscopy. This work reveals that the superior stability of niobium molybdenum oxides is underpinned by changes in octahedral distortion during electrochemical reactions, and we report an in-depth understanding of how this stabilizes the oxide structure during cycling with implications for future long-life battery material design.

16.
Plast Reconstr Surg ; 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38194623

RESUMEN

BACKGROUND: Each breast augmentation technique has advantages and indications, and the quest for the perfect implant pocket plane is ongoing. An ideal dual plane should meet three requirements: adequate implant coverage, optimal control of breast shape, and maximal muscle preservation. This paper reports a modified procedure for breast augmentation named subfascial mini muscle-release dual plane technique. METHODS: From an inframammary or periareolar approach, the implant pocket is dissected in a subfascial plane up to the pectoralis major. The muscle is split 3 cm above the lateral margin and then pocket dissection proceeds in the submuscular plane. A small portion of the costal origin is divided inferomedially creating a dual plane. RESULTS: A total of 178 patients with hypoplasia or breast atrophy were included, among whom 34 had breast ptosis and 20 had tubular breast deformity. The median follow-up period was 20 months. With an average implant volume of 268.8 ml and a smooth implant type of 85.4%, there was 1 case of hematoma, 2 cases of wound healing issues, 2 cases of rippling sign, 2 cases of grade III/IV capsular contracture, 5 cases of implant malposition and 12 cases of mild muscle contraction-associated deformity. Revision surgeries were performed on 2 patients. CONCLUSION: The subfascial mini muscle-release dual plane technique is an easy method for breast augmentation and is especially indicated for ptotic breasts and tubular breast deformities. This technique combines the advantages of traditional dual plane and muscle-splitting techniques, yielding a satisfactory aesthetic outcome.

17.
Inorg Chem ; 63(3): 1642-1651, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38198689

RESUMEN

Advanced energetic materials (EMs) play a crucial role in the advancement of microenergetic systems as actuation parts, igniters, propulsion units, and power. The sustainable electrosynthesis of EMs has gained momentum and achieved substantial improvements in the past decade. This study presents the facile synthesis of a new type of high-performance CuN3@CuCl hybrids via a co-electrodeposition methodology utilizing porous Cu as the sacrificial template. The composition, morphology, and energetic characteristics of the CuN3@CuCl hybrids can be easily tuned by adjusting the deposition times. The resulting hybrids demonstrate remarkable energy output (1120 J·g-1) and good laser-induced initiating ability. As compared with porous CuN3, the uniform doping of inert CuCl enhances the electrostatic safety of the hybridized material without compromising its overall energetic characteristics. Notably, the special oxidizing behavior of CuCl gradually lowers the susceptibility of the hybrid material to laser and electrostatic stimulation. This has significant implications for the passivation or self-destruction of highly sensitive EMs. Overall, this study pioneers a new path for the development of MEMS-compatible EMs, facilitating further microenergetic applications.

18.
Blood Cancer J ; 14(1): 1, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38177095

RESUMEN

Classical myeloproliferative neoplasms (MPNs) are characterized by the proliferation of myeloid cells and the risk of transformation into myelofibrosis or acute myeloid leukemia (AML) and TP53 mutations in MPN patients are linked to AML. However, JAK2V617F has been reported to impact the TP53 response to DNA damage, suggesting potential overlapping role of TP53 inactivation in MPN. We established a mouse model showing that JAK2V617F/Vav-Cre/Trp53-/- mice displayed a similar phenotype to JAK2V617F/Vav-Cre mice, but their proliferation was outcompeted in competitive grafts. RNA-Seq revealed that half of the genes affected by JAK2V617F were affected by p53-inactivation, including the interferon pathway. To validate this finding, mice were repopulated with a mixture of wild-type and JAK2V617F (or JAK2V617F/Vav-Cre/Trp53-/-) cells and treated with pegylated interferonα. JAK2V617F-reconstituted mice entered complete hematological remission, while JAK2V617F/Vav-Cre /Trp53-/--reconstituted mice did not, confirming that p53 loss induced interferon-α resistance. KEGG and Gene Ontology analyses of common deregulated genes showed that these genes were mainly implicated in cytokine response, proliferation, and leukemia evolution, illustrating that in this mouse model, the development of MPN is not affected by TP53 inactivation. Taken together, our results show that many genetic modifications induced by JAK2V617F are influenced by TP53, the MPN phenotype may not be. Trp53 loss alone is insufficient to induce rapid leukemic transformation in steady-state hematopoiesis in JAK2V617F MPN, and Trp53 loss may contribute to interferon resistance in MPN.


Asunto(s)
Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Humanos , Ratones , Animales , Proteína p53 Supresora de Tumor/genética , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Mutación , Interferón-alfa/farmacología , Genómica
19.
JAMA Netw Open ; 7(1): e2353252, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38270949

RESUMEN

Importance: Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an opportunity for preventive interventions, there is still a lack of pharmacologic prevention strategies for PPD. Objective: To assess the efficacy and safety of dexmedetomidine for prevention of PPD among women with prenatal depression undergoing cesarean delivery. Design, Setting, and Participants: This randomized clinical trial enrolled 338 women who screened positive for prenatal depression at 2 hospitals in Hunan, China from March 28, 2022, to April 16, 2023. Women with an Edinburgh Postnatal Depression Scale score of more than 9 who were 18 years of age or older and were scheduled for elective cesarean delivery were eligible. Interventions: Eligible participants were randomly assigned in a 1:1 ratio to either the dexmedetomidine group or the control group via centrally computer-generated group randomization. Dexmedetomidine, 0.5 µg/kg and 0.9% saline were intravenously infused for 10 minutes after delivery in the dexmedetomidine and control groups, respectively. After infusion, sufentanil or dexmedetomidine plus sufentanil was administered via patient-controlled intravenous analgesia for 48 hours in the control group and dexmedetomidine group, respectively. Main Outcomes and Measures: The primary outcome was positive PPD screening results at 7 and 42 days post partum, defined as a postpartum Edinburgh Postnatal Depression Scale score of more than 9. Analysis was on an intention-to-treat basis. Results: All 338 participants were female, with a mean (SD) age of 31.5 (4.1) years. Positive PPD screening incidence at 7 and 42 days post partum in the dexmedetomidine group vs the control group was significantly decreased (day 7, 21 of 167 [12.6%] vs 53 of 165 [32.1%]; risk ratio, 0.39 [95% CI, 0.25-0.62]; P < .001; day 42, 19 of 167 [11.4%] vs 50 of 165 [30.3%]; risk ratio, 0.38 [95% CI, 0.23-0.61]; P < .001). The dexmedetomidine group showed no significant difference in adverse events vs the control group (46 of 169 [27.2%] vs 33 of 169 [19.5%]; P = .10), but the incidence of hypotension increased (31 of 169 [18.3%] vs 16 of 169 [9.5%]; risk ratio, 2.15 [95% CI, 1.13-4.10]; P = .02). Conclusions and Relevance: Dexmedetomidine administration in the early postpartum period significantly reduced the incidence of a positive PPD screening and maintained a favorable safety profile. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200057213.


Asunto(s)
Depresión Posparto , Dexmedetomidina , Adulto , Femenino , Humanos , Embarazo , Administración Intravenosa , Depresión Posparto/tratamiento farmacológico , Dexmedetomidina/uso terapéutico , Sufentanilo
20.
Lab Chip ; 24(4): 719-727, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38275006

RESUMEN

Traditional lead-based primary explosives present challenges in application to micro-energetics-on-a-chip. It is highly desired but still remains challenging to design a primary explosive for the development of powerful yet safe energetic films. Copper-based azides (Cu(N3)2 or CuN3, CA) are expected to be ideal alternatives owing to their properties such as excellent device compatibility, excellent detonation performance, and low environmental pollution. However, the significantly high electrostatic sensitivity of CA limits its use in micro-electro-mechanical systems (MEMS). This study presents an in situ electrochemical approach to preparing and modifying a CA film with excellent electrostatic safety using a Cu chip. Herein, a CA film is prepared by employing Cu nanorod arrays as precursors. Next, polypyrrole (PPy) is directly coated on the surface of the CA materials to produce a CA@PPy composite energetic film using the electrochemical process. The results show that CuN3 is first generated and gradually oxidized to Cu(N3)2, essentially forming enclosed nest-like structures during electrochemical azidation. The microstructure and composition of the product can be regulated by varying the current density and reaction time, which leads to controllable heat output of the CA from 521 to 1948 J g-1. Notably, the composite energetic film exhibits excellent electrostatic sensitivity (2.69 mJ) owing to the excellent conductivity of PPy. Thus, this study offers novel ideas for the further advances of composite energetic materials and applications in MEMS explosive systems.

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