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1.
Nature ; 631(8021): 531-536, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39020034

RESUMEN

The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.

2.
J Am Chem Soc ; 146(3): 2257-2266, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38195401

RESUMEN

Metallic Al has been deemed an ideal electrode material for aqueous batteries by virtue of its abundance and high theoretical capacity (8056 mAh cm-3). However, the development of aqueous Al metal batteries has been hindered by several side reactions, including water decomposition, Al corrosion, and passivation, which arise from the solvation reaction of Al and H2O in conventional aqueous electrolytes. In this work, we report that water activity in electrolyte can be suppressed by optimizing the Al3+ solvation structure through intercalation of polar pyridine-3-carboxylic acid in an aluminum trifluoromethanesulfonate aqueous environment. Furthermore, the pyridine-3-carboxylic acid molecules are inclined to alter the surface energy of Al, thus suppressing the random deposition of Al. As a result, the Al corrosion in the hybrid electrolyte is restrained, and the long-term electrochemical stability of the electrolyte is tremendously improved. These merits bring remarkable reversibility to aqueous Al batteries using Al-preintercalated MnO2 cathodes, delivering a retaining energy density of >250 Wh kg-1 at 0.2 A g-1 after 600 cycles.

3.
Biochem Biophys Res Commun ; 735: 150651, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39260333

RESUMEN

Multiple sclerosis (MS) is an inflammatory demyelination neurodegenerative disease of the central nervous system (CNS). Ferroptosis has been implicated in a range of brain disorders, and iron-loaded microglia are frequently found in affected brain regions. However, the molecular mechanisms linking ferroptosis with MS have not been well-defined. The present study seeks to bridge this gap and investigate the impact of matrine (MAT), a herbal medicine with immunomodulatory capacities, on the regulation of oxidative stress and ferroptosis in the CNS of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. CNS of EAE mice contained elevated levels of ferroptosis-related molecules, e.g., MDA, LPCAT3 and PTGS2, but decreased expression of antioxidant molecules, including GSH and SOD, GPX4 and SLC7A11. This pathogenic process was reversed by MAT treatment, together with significant reduction of disease severity and CNS inflammatory demyelination. Furthermore, the expression of PTGS2 and LOX was largely increased in microglia of EAE mice, accompanied with increased production of IL-6 and TNF-α, indicating a proinflammatory phenotype of microglia that undergo oxidative stress/ferroptosis, and their expression was significantly reduced after MAT treatment. Together, our results indicate that ferroptosis/inflammation plays an important role in the pathogenesis of CNS autoimmunity, and inhibiting ferroptosis-induced microglial activation/inflammation could be a novel mechanism underlying the therapeutic effects of MAT on CNS inflammatory demyelination in EAE.

4.
Small ; 20(26): e2310387, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38312084

RESUMEN

Rational design of heterostructure catalysts through phase engineering strategy plays a critical role in heightening the electrocatalytic performance of catalysts. Herein, a novel amorphous/crystalline (a/c) heterostructure (a-CoS/Ni3S2) is manufactured by a facile hydrothermal sulfurization method. Strikingly, the interface coupling between amorphous phase (a-CoS) and crystalline phase (Ni3S2) in a-CoS/Ni3S2 is much stronger than that between crystalline phase (c-CoS) and crystalline phase (Ni3S2) in crystalline/crystalline (c/c) heterostructure (c-CoS/Ni3S2) as control sample, which makes the meta-stable amorphous structure more stable. Meanwhile, a-CoS/Ni3S2 has more S vacancies (Sv) than c-CoS/Ni3S2 because of the presence of an amorphous phase. Eventually, for the oxygen evolution reaction (OER), the a-CoS/Ni3S2 exhibits a significantly lower overpotential of 192 mV at 10 mA cm-2 compared to the c-CoS/Ni3S2 (242 mV). An exceptionally low cell voltage of 1.51 V is required to achieve a current density of 50 mA cm-2 for overall water splitting in the assembled cell (a-CoS/Ni3S2 || Pt/C). Theoretical calculations reveal that more charges transfer from a-CoS to Ni3S2 in a-CoS/Ni3S2 than in c-CoS/Ni3S2, which promotes the enhancement of OER activity. This work will bring into play a fabrication strategy of a/c catalysts and the understanding of the catalytic mechanism of a/c heterostructures.

5.
Small ; 20(31): e2310340, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38456789

RESUMEN

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.


Asunto(s)
Condrosarcoma , Doxorrubicina , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos , Hidrogeles , Nanocompuestos , Condrosarcoma/tratamiento farmacológico , Condrosarcoma/patología , Condrosarcoma/metabolismo , Nanocompuestos/química , Animales , Resistencia a Antineoplásicos/efectos de los fármacos , Hidrogeles/química , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Humanos , Línea Celular Tumoral , Temperatura , Polietilenglicoles/química , Ratones
6.
J Virol ; 97(3): e0198422, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36877059

RESUMEN

The paramyxoviruses represent a large family of human and animal pathogens that cause significant health and economic burdens worldwide. However, there are no available drugs against the virus. ß-carboline alkaloids are a family of naturally occurring and synthetic products with outstanding antiviral activities. Here, we examined the antiviral effect of a series of ß-carboline derivatives against several paramyxoviruses, including Newcastle disease virus (NDV), peste des petits ruminants virus (PPRV), and canine distemper virus (CDV). Among these derivatives, 9-butyl-harmol was identified as an effective antiviral agent against these paramyxoviruses. Further, a genome-wide transcriptome analysis in combination with target validation strategies reveals a unique antiviral mechanism of 9-butyl-harmol through the targeting of GSK-3ß and HSP90ß. On one hand, NDV infection blocks the Wnt/ß-catenin pathway to suppress the host immune response. 9-butyl-harmol targeting GSK-3ß dramatically activates the Wnt/ß-catenin pathway, which results in the boosting of a robust immune response. On the other hand, NDV proliferation depends on the activity of HSP90. The L protein, but not the NP protein or the P protein, is proven to be a client protein of HSP90ß, rather than HSP90α. 9-butyl-harmol targeting HSP90ß decreases the stability of the NDV L protein. Our findings identify 9-butyl-harmol as a potential antiviral agent, provide mechanistic insights into the antiviral mechanism of 9-butyl-harmol, and illustrate the role of ß-catenin and HSP90 during NDV infection. IMPORTANCE Paramyxoviruses cause devastating impacts on health and the economy worldwide. However, there are no suitable drugs with which to counteract the viruses. We determined that 9-butyl-harmol could serve as a potential antiviral agent against paramyxoviruses. Until now, the antiviral mechanism of ß-carboline derivatives against RNA viruses has rarely been studied. Here, we found that 9-butyl-harmol exerts dual mechanisms of antiviral action, with its antiviral activities being mediated by two targets: GSK-3ß and HSP90ß. Correspondingly, the interaction between NDV infection and the Wnt/ß-catenin pathway or HSP90 is demonstrated in this study. Taken together, our findings shed light on the development of antiviral agents against paramyxoviruses, based on the ß-carboline scaffold. These results present mechanistic insights into the polypharmacology of 9-butyl-harmol. Understanding this mechanism also deepens the host-virus interaction and reveals new drug targets for anti-paramyxoviruses.


Asunto(s)
Antivirales , Enfermedad de Newcastle , Animales , Humanos , Antivirales/farmacología , beta Catenina/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Harmina , Virus de la Enfermedad de Newcastle/fisiología , Proteínas HSP90 de Choque Térmico/metabolismo
7.
Transgenic Res ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39249190

RESUMEN

Dehydroascorbate reductase (DHAR), an indispensable enzyme in the production of ascorbic acid (AsA) in plants, is vital for plant tolerance to various stresses. However, there is limited research on the stress tolerance functions of DHAR genes in sweet potato (Ipomoea batatas [L.] Lam). In this study, the full-length IbDHAR1 gene was cloned from the leaves of sweet potato cultivar Xu 18. The IbDHAR1 protein is speculated to be located in both the cytoplasm and the nucleus. As revealed by qRT-PCR, the relative expression level of IbDHAR1 in the proximal storage roots was much greater than in the other tissues, and could be upregulated by high-temperature, salinity, drought, and abscisic acid (ABA) stress. The results of pot experiments indicated that under high salinity and drought stress conditions, transgenic Arabidopsis and sweet potato plants exhibited decreases in H2O2 and MDA levels. Conversely, the levels of antioxidant enzymes APX, SOD, POD, and ACT, and the content of DHAR increased. Additionally, the ratio of AsA/DHA was greater in transgenic lines than in the wild type. The results showed that overexpression of IbDHAR1 intensified the ascorbic acid-glutathione cycle (AsA-GSH) and promoted the activity of the related antioxidant enzyme systems to improve plant stress tolerance and productivity.

8.
Cell Biol Int ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886911

RESUMEN

Lung cancer is one of the most prevalent human cancers with a high lethality rate worldwide. In this study, we demonstrated that GSE1 (genetic suppressor element 1) expression is aberrantly upregulated in lung adenocarcinoma and that GSE1 depletion inhibits the proliferation and migration of both A549 and H1299 cells. Immunoprecipitation assays demonstrated that GSE1 interacts with histone deacetylase 1 (HDAC1) and other BRAF-HDAC complex (BHC) components in cells. The transcriptome of GSE1-knockdown A549 cells indicated that 207 genes were upregulated and 159 were downregulated based on a p-value < .05 and fold change ≥ 1.5. Bioinformatics analysis suggested that 140 differentially expressed genes harbor binding sites for HDAC1, including the tumor suppressor gene KLF6 (Kruppel-like factor 6). Indeed, quantitative reverse-transcription polymerase chain reaction and western blot analysis revealed that GSE1 could inhibit the transcription of KLF6 in lung cancer cells. In conclusion, GSE1 cooperates with HDAC1 to promote the proliferation and metastasis of non-small cell lung cancer cells through the downregulation of KLF6 expression.

9.
Nanotechnology ; 35(36)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38861952

RESUMEN

The development of bifunctional catalysts with subtle structures, high efficiencies, and good durabilities for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is crucial for overall water splitting. In this work, a multicomponent S-doped NiFe2O4/Ni-Fe micro nano flower electrocatalyst was synthesized rapidly on foam copper using a simple one-step constant current electrodeposition method. The introduction of S leads to the transformation of the microsphere structure of the Ni-Fe alloy into a cauliflower-like morphology and induces changes in the surface electronic structure, significantly enhancing the catalytic performance for the HER and OER. The S-NiFe2O4/Ni-Fe alloy/CF showed low overpotentials of 220 and 66 mV at 10 mA cm-2in 1.0 M KOH for the OER and HER, respectively. High durability OER and HER performances were demonstrated through 60 h of chronopotentiometry and 6000 CV cycles test. Excellent overall water splitting electrocatalytic activity was observed in the S-NiFe2O4/Ni-Fe alloy/CF‖S-NiFe2O4/Ni-Fe alloy/CF two-electrode system. In particular, active-phase NiOOH, a highly active substance for OER, can be controllably formed in the reaction process owing to the nanoflower structure of multi-layer sulfur which slows down the dissolution of NiFe2O4/Ni-Fe alloy. These results suggest that this composite structure is a promising bifunctional electrocatalyst.

10.
Bioorg Med Chem ; 97: 117539, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-38070351

RESUMEN

A series of 1-(2-oxocyclohexyl)butane-1, 3-dione derivatives were designed and synthesized as TLR4 inhibitors by modifying the core structure of the lead compound ((6, 8-dioxo-1, 2, 3, 4, 6, 7, 8, 8a-octahydronaphthalen-2-yl) carbamate)). In vitro, compound 3p significantly inhibited the proliferation of rat synovial cells, inhibited the proliferation of LPS-induced RAW264.7 cells, and inhibited TLR4 activity, with IC50 values of 1.21 ± 0.09 µM, 0.73 ± 0.05 µM and 0.43 ± 0.03 µM, respectively, which was superior to the positive control methotrexate. In vivo anti-rheumatoid arthritis evaluation, compound 3p can significantly inhibit the inflammatory factors TNF-α, IL-1ß and IL-6, so as to achieve the therapeutic purpose. In the preliminary mechanism study, compound 3p has obvious regulatory effects on the abnormal increase of TLR4, JAK2 and STAT3 protein and gene expression related to inflammatory signaling pathway in RAW264.7 cells. In summary, this study aims to develop more effective candidates for rheumatoid arthritis.


Asunto(s)
Artritis Reumatoide , Sinoviocitos , Ratas , Animales , Receptor Toll-Like 4/genética , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Sinoviocitos/metabolismo , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo
11.
Arch Insect Biochem Physiol ; 116(4): e22128, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39166358

RESUMEN

High temperature stress has long-term negative effects on the growth and development of silkworm (Bombyx mori). Different silkworm varieties show the different tolerance to high temperature. The induction of autophagy is linked to increased thermotolerance in diverse ectothermic organisms. However, the function of autophagy in the thermotolerant and thermosensitive silkworm strains under high-temperature conditions remains unclear. The thermotolerant Liangguang NO.2 and thermosensitive Jingsong × Haoyue strains were used to explore the role of autophagy in thermotolerance. Here, we first found that the larval body weight gain was increased in the thermosensitive Jingsong × Haoyue strain, but there was no difference in the thermotolerant Liangguang NO.2 strain under high temperature conditions. High temperature stress had a negative influence on the cocoon performance in both the Liangguang NO.2 and Jingsong × Haoyue strains. Additionally, the autophagy-related gene Atg5 mRNA expression in the Liangguang NO.2 strain was upregulated by high temperature, while the expression of Atg12 mRNA was reduced in the Jingsong × Haoyue strain. Titers of 20-Hydroxyecdysone and the ultraspiracle 1 mRNA expression in the Liangguang NO.2 strain were upregulated by high temperature, which might be associated with the induction of autophagy. These results demonstrate the potentially regulatory mechanism of autophagy in silkworms' tolerance to high temperature, providing a theoretical basis for exploring the physiological mechanism of thermotolerance in insects.


Asunto(s)
Autofagia , Bombyx , Calor , Larva , Termotolerancia , Animales , Bombyx/crecimiento & desarrollo , Bombyx/fisiología , Bombyx/genética , Larva/crecimiento & desarrollo , Tracto Gastrointestinal/crecimiento & desarrollo , Ecdisterona , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética
12.
Artículo en Inglés | MEDLINE | ID: mdl-39174430

RESUMEN

BACKGROUND AND AIM: The relationship between walking pace and heart failure (HF) has been recognized, yet the directionality and underlying mediating risk factors remain unclear. METHODS AND RESULTS: This study utilized bidirectional two-sample Mendelian randomization (MR) with genome-wide association studies (GWAS) summary statistics to assess the causal relationships between walking pace and HF. Additionally, we employed a two-step Multivariable Mendelian Randomization (MVMR) to explore potential mediating factors. We further validated our findings by conducting two-sample MR with another available GWAS summary data on heart failure. Results indicated that genetically predicted increases in walking pace were associated with a reduced risk of HF (odds ratio (OR), 0.589, 95% confidence interval (CI): 0.417-0.832). Among the considered mediators, the waist-to-hip ratio (WHR) accounts for the largest proportion of the effect (45.7%, 95% CI: 13.2%, 78.2%). This is followed by type 2 diabetes at 24.4% (95% CI: 6.7%, 42.0%) and triglycerides at 18.6% (95% CI: 4.5%, 32.7%). Furthermore, our findings reveal that genetically predicted HF risk (OR, 0.975, 95% CI: 0.960-0.991) is associated with a slower walking pace. Validated findings were consistent with the main results. CONCLUSIONS: In conclusion, MR analysis demonstrates that a slow walking pace is a reliable indicator of an elevated risk of HF, and the causal relationship is bidirectional. Interventions focusing on waist-to-hip ratio, type 2 diabetes, and triglycerides may provide valuable strategies for HF prevention in individuals with a slow walking pace.

13.
Nutr Metab Cardiovasc Dis ; 34(11): 2562-2569, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39174425

RESUMEN

BACKGROUND AND AIM: Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. METHODS AND RESULTS: We included 15,575 postmenopausal women aged 35-75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59-4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16-1.72) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48-2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. CONCLUSION: In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category.


Asunto(s)
Enfermedades Cardiovasculares , Síndrome Metabólico , Obesidad , Fenotipo , Posmenopausia , Humanos , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Anciano , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , China/epidemiología , Adulto , Medición de Riesgo , Obesidad/epidemiología , Obesidad/diagnóstico , Factores de Tiempo , Factores de Riesgo de Enfermedad Cardiaca , Obesidad Metabólica Benigna/epidemiología , Obesidad Metabólica Benigna/diagnóstico , Obesidad Metabólica Benigna/sangre , Obesidad Metabólica Benigna/fisiopatología , Estudios Prospectivos , Pronóstico , Factores de Riesgo , Biomarcadores/sangre , Incidencia
14.
J Plant Res ; 137(4): 669-683, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38758249

RESUMEN

Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T3 Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance.


Asunto(s)
Arabidopsis , Sequías , Regulación de la Expresión Génica de las Plantas , Glutamato-Cisteína Ligasa , Ipomoea batatas , Plantas Modificadas Genéticamente , Arabidopsis/genética , Arabidopsis/fisiología , Ipomoea batatas/genética , Ipomoea batatas/fisiología , Ipomoea batatas/enzimología , Glutamato-Cisteína Ligasa/genética , Glutamato-Cisteína Ligasa/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Estrés Salino/genética , Ácido Abscísico/metabolismo , Malondialdehído/metabolismo , Glutatión/metabolismo , Antioxidantes/metabolismo , Germinación/efectos de los fármacos
15.
Nucleic Acids Res ; 50(21): 12235-12250, 2022 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-36477888

RESUMEN

Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation. Combination analysis of ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers, leading to upregulated expression of neural differentiation-associated genes and therefore early neural differentiation. This study suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation.


Asunto(s)
Cromatina , Células Madre Embrionarias , Factor 4 Similar a Kruppel , Diferenciación Celular/genética , Cromatina/metabolismo , Células Madre Embrionarias/metabolismo , Regulación de la Expresión Génica , Factores de Transcripción/metabolismo , Factor 4 Similar a Kruppel/metabolismo
16.
BMC Musculoskelet Disord ; 25(1): 360, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714980

RESUMEN

OBJECTIVE: Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). METHODS: A total of 383 patients (aged 24-76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors. RESULTS: Among the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05). CONCLUSION: In patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.


Asunto(s)
Densidad Ósea , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Imagen por Resonancia Magnética , Osteoporosis , Músculos Paraespinales , Humanos , Persona de Mediana Edad , Femenino , Masculino , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patología , Músculos Paraespinales/fisiopatología , Adulto , Densidad Ósea/fisiología , Vértebras Lumbares/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/fisiopatología , Estudios Retrospectivos , Anciano , Osteoporosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto Joven , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/etiología
17.
Proc Natl Acad Sci U S A ; 118(20)2021 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-33975955

RESUMEN

Bismuth and rare earth elements have been identified as effective substituent elements in the iron garnet structure, allowing an enhancement in magneto-optical response by several orders of magnitude in the visible and near-infrared region. Various mechanisms have been proposed to account for such enhancement, but testing of these ideas is hampered by a lack of suitable experimental data, where information is required not only regarding the lattice sites where substituent atoms are located but also how these atoms affect various order parameters. Here, we show for a Bi-substituted lutetium iron garnet how a suite of advanced electron microscopy techniques, combined with theoretical calculations, can be used to determine the interactions between a range of quantum-order parameters, including lattice, charge, spin, orbital, and crystal field splitting energy. In particular, we determine how the Bi distribution results in lattice distortions that are coupled with changes in electronic structure at certain lattice sites. These results reveal that these lattice distortions result in a decrease in the crystal-field splitting energies at Fe sites and in a lifted orbital degeneracy at octahedral sites, while the antiferromagnetic spin order remains preserved, thereby contributing to enhanced magneto-optical response in bismuth-substituted iron garnet. The combination of subangstrom imaging techniques and atomic-scale spectroscopy opens up possibilities for revealing insights into hidden coupling effects between multiple quantum-order parameters, thereby further guiding research and development for a wide range of complex functional materials.

18.
J Integr Plant Biol ; 66(2): 176-195, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38294064

RESUMEN

Sweet potato (Ipomoea batatas [L.] Lam.) is a crucial staple and bioenergy crop. Its abiotic stress tolerance holds significant importance in fully utilizing marginal lands. Transcriptional processes regulate abiotic stress responses, yet the molecular regulatory mechanisms in sweet potato remain unclear. In this study, a NAC (NAM, ATAF1/2, and CUC2) transcription factor, IbNAC087, was identified, which is commonly upregulated in salt- and drought-tolerant germplasms. Overexpression of IbNAC087 increased salt and drought tolerance by increasing jasmonic acid (JA) accumulation and activating reactive oxygen species (ROS) scavenging, whereas silencing this gene resulted in opposite phenotypes. JA-rich IbNAC087-OE (overexpression) plants exhibited more stomatal closure than wild-type (WT) and IbNAC087-Ri plants under NaCl, polyethylene glycol, and methyl jasmonate treatments. IbNAC087 functions as a nuclear transcriptional activator and directly activates the expression of the key JA biosynthesis-related genes lipoxygenase (IbLOX) and allene oxide synthase (IbAOS). Moreover, IbNAC087 physically interacted with a RING-type E3 ubiquitin ligase NAC087-INTERACTING E3 LIGASE (IbNIEL), negatively regulating salt and drought tolerance in sweet potato. IbNIEL ubiquitinated IbNAC087 to promote 26S proteasome degradation, which weakened its activation on IbLOX and IbAOS. The findings provide insights into the mechanism underlying the IbNIEL-IbNAC087 module regulation of JA-dependent salt and drought response in sweet potato and provide candidate genes for improving abiotic stress tolerance in crops.


Asunto(s)
Ciclopentanos , Ipomoea batatas , Oxilipinas , Cloruro de Sodio , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Resistencia a la Sequía , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estrés Fisiológico/genética , Sequías , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
19.
Angew Chem Int Ed Engl ; : e202410127, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39030819

RESUMEN

Polyrotaxanes (PRs) have attracted significant research attention due to their unique topological structures and high degrees of conformational freedom. Herein, we take advantage of an oligo[2]rotaxane to  construct a novel class of dynamically cross-linked rotaxane network (DCRN) mediated by metal-coordination. The oligo[2]rotaxane skeleton offers several distinct advantages: In addition to retaining the merits of traditional polymer backbones, the ordered intramolecular motion of the [2]rotaxane motifs introduced dangling chains into the network, thereby enhancing the stretchability of the DCRN. Additionally, the dissociation of host‒guest recognition and subsequent sliding motion, along with the breakage of metal-coordination interactions, represented an integrated energy dissipation pathway to enhance mechanical properties. Moreover, the resulting DCRN demonstrated responsiveness to multiple stimuli and displayed exceptional self-healing capabilities in a gel state. Upon exposure to PPh3, which induced network deconstruction by breaking the coordinated cross-linking points, the oligo[2]rotaxane could be recovered, showcasing good recyclability. These findings demonstrate the untapped potential of the oligo[2]rotaxane as a polymer skeleton to develop DCRN and open the door to extend their advanced applications in intelligent mechanically interlocked materials.

20.
Angew Chem Int Ed Engl ; 63(28): e202404481, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38699952

RESUMEN

The pursuit of fabricating high-performance graphene films has aroused considerable attention due to their potential for practical applications. However, developing both stretchable and tough graphene films remains a formidable challenge. To address this issue, we herein introduce mechanical bond to comprehensively improve the mechanical properties of graphene films, utilizing [2]rotaxane as the bridging unit. Under external force, the [2]rotaxane cross-link undergoes intramolecular motion, releasing hidden chain and increasing the interlayer slip distance between graphene nanosheets. Compared with graphene films without [2]rotaxane cross-linking, the presence of mechanical bond not only boosted the strength of graphene films (247.3 vs 74.8 MPa) but also markedly promoted the tensile strain (23.6 vs 10.2 %) and toughness (23.9 vs 4.0 MJ/m3). Notably, the achieved tensile strain sets a record high and the toughness surpasses most reported results, rendering the graphene films suitable for applications as flexible electrodes. Even when the films were stretched within a 20 % strain and repeatedly bent vertically, the light-emitting diodes maintained an on-state with little changes in brightness. Additionally, the film electrodes effectively actuated mechanical joints, enabling uninterrupted grasping movements. Therefore, the study holds promise for expanding the application of graphene films and simultaneously inspiring the development of other high-performance two-dimensional films.

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