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1.
Cell ; 179(4): 864-879.e19, 2019 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-31675497

RESUMEN

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.


Asunto(s)
Ansiedad/metabolismo , Conducta Animal/fisiología , Encefalopatías Metabólicas/metabolismo , Estrés Psicológico/metabolismo , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/patología , Animales , Ansiedad/genética , Ansiedad/inmunología , Ansiedad/fisiopatología , Encefalopatías Metabólicas/genética , Encefalopatías Metabólicas/fisiopatología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Modelos Animales de Enfermedad , Humanos , Ratones , Dinámicas Mitocondriales/genética , Oligodendroglía/metabolismo , Oligodendroglía/patología , Análisis de la Célula Individual , Estrés Psicológico/genética , Estrés Psicológico/fisiopatología , Transcriptoma/genética , Xantina/metabolismo
2.
Immunity ; 54(8): 1728-1744.e7, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34343498

RESUMEN

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.


Asunto(s)
Antioxidantes/farmacología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/inmunología , Selenio/farmacología , Selenoproteína W/metabolismo , Células TH1/citología , Diferenciación Celular/inmunología , Polaridad Celular , Colon/inmunología , Colon/patología , Glicina Hidroximetiltransferasa/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Ribonucleoproteínas/metabolismo , Células TH1/inmunología , Ubiquitina-Proteína Ligasas/metabolismo
3.
EMBO Rep ; 24(1): e55387, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36394357

RESUMEN

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.


Asunto(s)
Interferón Tipo I , Virosis , Ratones , Animales , Virosis/genética , Antivirales , Inmunidad Innata , Ubiquitinación , Factor 7 Regulador del Interferón/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis
4.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-34937700

RESUMEN

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a high-resolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the D1 subunit is flexible, some waters near the active site are partially occupied, and differences in the PsbV subunit block the Large (O1) water channel. These features strongly influence the structural picture of PSII, especially as it pertains to the mechanism of water oxidation.


Asunto(s)
Microscopía por Crioelectrón/métodos , Complejo de Proteína del Fotosistema II/ultraestructura , Synechocystis/química , Proteínas Bacterianas/metabolismo , Conformación Proteica
5.
J Infect Dis ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38284935

RESUMEN

Recent phylogenetic profiling of pneumococcal serotype 3 (Pn3) isolates revealed a dynamic interplay among major lineages with the emergence and global spread of a variant termed Clade II. The cause of Pn3 clade II dissemination along with epidemiological and clinical ramifications are currently unknown. Here, we sought to explore biological characteristics of dominant Pn3 clades in a mouse model of pneumococcal invasive disease and carriage. Carriage and virulence potential were strain dependent with marked differences among clades. We found that clinical isolates from Pn3 clade II are less virulent and less invasive in mice compared to clade I isolates. We also observed that clade II isolates are carried for longer and at higher bacterial densities in mice compared to clade I isolates. Taken together, our data suggest that the epidemiological success of Pn3 clade II could be related to alterations in the pathogen's ability to cause invasive disease and to establish a robust carriage episode.

6.
J Biomed Sci ; 31(1): 51, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741091

RESUMEN

BACKGROUND: The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. METHODS: In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRß, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. RESULTS: Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. CONCLUSION: Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.


Asunto(s)
Aneurisma Intracraneal , Miocitos del Músculo Liso , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Animales , Femenino , Humanos , Masculino , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/metabolismo , Mutación , Miocitos del Músculo Liso/metabolismo , Fenotipo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Pez Cebra/genética
7.
Nephrol Dial Transplant ; 39(2): 251-263, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-37458807

RESUMEN

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.


Asunto(s)
Fallo Renal Crónico , Diálisis Peritoneal , Peritonitis , Humanos , Femenino , Estudios Prospectivos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Hemoglobinas , Fallo Renal Crónico/epidemiología , Peritonitis/etiología , Estudios Retrospectivos
8.
Vet Res ; 55(1): 84, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965634

RESUMEN

Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses to benefit virus replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26), a TRIM family protein, has been shown to be involved in a broad range of biological processes involved in innate immunity, especially in regulating viral infection. Herein, we found that the expression of TRIM26 was significantly induced after PRV infection. Surprisingly, the overexpression of TRIM26 promoted PRV production, while the depletion of this protein inhibited virus replication, suggesting that TRIM26 could positively regulate PRV infection. Further analysis revealed that TRIM26 negatively regulates the innate immune response by targeting the RIG-I-triggered type I interferon signalling pathway. TRIM26 was physically associated with MAVS independent of viral infection and reduced MAVS expression. Mechanistically, we found that NDP52 interacted with both TRIM26 and MAVS and that TRIM26-induced MAVS degradation was almost entirely blocked in NDP52-knockdown cells, demonstrating that TRIM26 degrades MAVS through NDP52-mediated selective autophagy. Our results reveal a novel mechanism by which PRV escapes host antiviral innate immunity and provide insights into the crosstalk among virus infection, autophagy, and the innate immune response.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Autofagia , Inmunidad Innata , Animales , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Porcinos , Replicación Viral , Humanos , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética
9.
Int J Mol Sci ; 25(11)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38891875

RESUMEN

Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation (LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application. Three groups of rats were exposed to either intermittent, continuous, or sham tFUS. We analyzed the neuromodulatory effects on motor cortical excitability by examining changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We also investigated the effects of different stimulation patterns on excitatory and inhibitory neural biomarkers, examining c-Fos and glutamic acid decarboxylase (GAD-65) expression using immunohistochemistry staining. Additionally, we evaluated the safety of tFUS by analyzing glial fibrillary acidic protein (GFAP) expression. The current results indicated that intermittent tFUS produced a facilitation effect on motor excitability, while continuous tFUS significantly inhibited motor excitability. Furthermore, neither tFUS approach caused injury to the stimulation sites in rats. Immunohistochemistry staining revealed increased c-Fos and decreased GAD-65 expression following intermittent tFUS. Conversely, continuous tFUS downregulated c-Fos and upregulated GAD-65 expression. In conclusion, our findings demonstrate that both intermittent and continuous tFUS effectively modulate cortical excitability. The neuromodulatory effects may result from the activation or deactivation of cortical neurons following tFUS intervention. These effects are considered safe and well-tolerated, highlighting the potential for using different patterns of tFUS in future clinical neuromodulatory applications.


Asunto(s)
Potenciales Evocados Motores , Corteza Motora , Plasticidad Neuronal , Estimulación Magnética Transcraneal , Animales , Corteza Motora/fisiología , Ratas , Masculino , Potenciales Evocados Motores/fisiología , Estimulación Magnética Transcraneal/métodos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ondas Ultrasónicas , Ratas Sprague-Dawley , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamato Descarboxilasa/metabolismo
10.
Sheng Li Xue Bao ; 76(2): 341-345, 2024 Apr 25.
Artículo en Zh | MEDLINE | ID: mdl-38658382

RESUMEN

There are three main classes of actin nucleation factors: Arp2/3 complexes, Spire and Formin. Spire assembles microfilaments by nucleating stable longitudinal tetramers and binding actin to the growing end of the microfilament. As early as 1999, Wellington et al. identified Spire as an actin nucleating agent, however, over the years, most studies have focused on Arp2/3 and Formin proteins; there has been relatively less research on Spire as a member of the actin nucleating factors. Recent studies have shown that Spire is involved in the vesicular transport through the synthesis of actin and plays an important role in neural development. In this paper, we reviewed the structure, expression and function of Spire, and its association with disease in order to identify meaningful potential directions for studies on Spire.


Asunto(s)
Actinas , Proteínas de Microfilamentos , Proteínas Nucleares , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/fisiología , Humanos , Animales , Actinas/metabolismo , Actinas/fisiología , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/fisiología
11.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2783-2797, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812179

RESUMEN

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.


Asunto(s)
Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Animales , Ratas , Masculino , Humanos , Hígado/efectos de los fármacos , Hígado/química , Hígado/metabolismo , Espectrometría de Masas/métodos , Riñón/efectos de los fármacos , Riñón/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus/tratamiento farmacológico
12.
Angew Chem Int Ed Engl ; 63(12): e202319587, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38226832

RESUMEN

Radical cation salts of π-conjugated polycycles are rich in physical properties. Herein, two kinds of hetera-buckybowls, ethoxy-substituted trithiasumanene (3SEt) and triselenasumanene (3SeEt), are synthesized as electron donors. Galvanostatic oxidation of them affords radical cation salts (3SEt)5 (TTFMPB)3 , (3SeEt)5 (TTFMPB)3 , (3SEt)4 PMA, and (3SeEt)4 PMA, where PMA is Keggin-type phosphomolybdate and TTFMPB is tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate. In these salts, 3SEt/3SeEt are partially charged and show distinct conformation change with the site charge and counter anions. In TTFMPB salts, (TTFMPB)- forms hexagonal channels that accommodate the packing columns of 3SEt/3SeEt. In particular, (3SEt)5 (TTFMPB)3 adopts the R3c space group and is a polar crystal with the columns of 3SEt all in the up-bowl direction. The PMA salts of 3SEt/3SeEt are polar crystals (C2 space group) with 3SEt/3SeEt being planar and forming columnar stacks. (3SeEt)4 PMA shows a structural modulation below 200 K, namely, negative thermal expansion (NTE) of the unit cell volume and enlargement of the intermolecular distances between neighboring 3SeEt molecules. The four salts are semiconductors with an activation energy of 0.18-0.38 eV. The conductivity of (3SeEt)4 PMA shows a reversible transition upon cooling and heating, in accordance to the NTE structural modulation. This work paves the way toward conducting materials based on hetera-buckybowls.

13.
Angew Chem Int Ed Engl ; 63(21): e202400769, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38544401

RESUMEN

Generating circularly polarized luminescence (CPL) with simultaneous high photoluminescence quantum yield (PLQY) and dissymmetry factor (glum) is difficult due to usually unmatched electric transition dipole moment (µ) and magnetic transition dipole moment (m) of materials. Herein we tackle this issue by playing a "cascade cationic insertion" trick to achieve strong CPL (with PLQY of ~100 %) in lead-free metal halides with high glum values reaching -2.3×10-2 without using any chiral inducers. Achiral solvents of hydrochloric acid (HCl) and N, N-dimethylformamide (DMF) infiltrate the crystal lattice via asymmetric hydrogen bonding, distorting the perovskite structure to induce the "intrinsic" chirality. Surprisingly, additional insertion of Cs+ cation to substitute partial (CH3)2NH2 + transforms the chiral space group to achiral but the crystal maintains chiroptical activity. Further doping of Sb3+ stimulates strong photoluminescence as a result of self-trapped excitons (STEs) formation without disturbing the crystal framework. The chiral perovskites of indium-antimony chlorides embedded on LEDs chips demonstrate promising potential as CPL emitters. Our work presents rare cases of chiroptical activity of highly luminescent perovskites from only achiral building blocks via spontaneous resolution as a result of symmetry breaking.

14.
J Cell Physiol ; 238(1): 137-150, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36350183

RESUMEN

Our previous study demonstrated that ultrasound is able to promote differentiation on neural stem cells (NSCs), and dual-frequency ultrasound promotes this effect due to enhanced acoustic cavitation compared with single-frequency ultrasound. However, the underlying biological reasons have not been well disclosed. The purpose of this study was to investigate the underlying bioeffects, mechanisms and signaling pathways of dual-frequency ultrasound on NSC differentiation. The morphology, neurite outgrowth, and differentiation percentages were investigated under various dual-frequency simulation parameters with exposure periods varying from 5 to 15 min. Morphological observations identified that dual-frequency ultrasound stimulation promoted ultrasound dose-dependent neurite outgrowth. In particular, cells exposed for 10 min/2 days showed optimal neurite outgrowth and neuron differentiation percentages. In addition, live cell calcium images showed that dual-frequency ultrasound enhanced the internal calcium content of the cells, and calcium ions entering cells from the extracellular environment could be observed. Dual frequency ultrasound exposure enhanced extracellular calcium influx and upregulated extracellular signal-regulated kinases 1/2 (ERK1/2) expression. Observations from immunostaining and protein expression examinations also identified that dual-frequency ultrasound promoted brain-derived neurotrophic factor (BDNF) secretion from astrocytes derived from NSCs. In summary, evidence supports that dual-frequency ultrasound effectively enhances functional neuron differentiation via calcium channel regulation via the downstream ERK1/2 pathway and promotes BDNF secretion to serve as feedback to cascade neuron differentiation. The results may provide an alternative for cell-based therapy in brain injury.


Asunto(s)
Diferenciación Celular , Sistema de Señalización de MAP Quinasas , Células-Madre Neurales , Ondas Ultrasónicas , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Calcio/metabolismo , Células Cultivadas , Células-Madre Neurales/citología , Neuronas/citología , Transducción de Señal
15.
BMC Genomics ; 24(1): 378, 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37415124

RESUMEN

BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is a well-known traditional Chinese medicine with high content polysaccharides in stems. The SWEET (Sugars Will Eventually be Exported Transporters) family is a novel class of sugar transporters mediating sugar translocation among adjacent cells of plants. The expression patterns of SWEETs and whether they are associated with stress response in D. officinale remains uncovered. RESULTS: Here, 25 SWEET genes were screened out from D. officinale genome, most of which typically contained seven transmembrane domains (TMs) and harbored two conserved MtN3/saliva domains. Using multi-omics data and bioinformatic approaches, the evolutionary relationship, conserved motifs, chromosomal location, expression patterns, correlationship and interaction network were further analyzed. DoSWEETs were intensively located in nine chromosomes. Phylogenetic analysis revealed that DoSWEETs were divided into four clades, and conserved motif 3 specifically existed in DoSWEETs from clade II. Different tissue-specific expression patterns of DoSWEETs suggested the division of their roles in sugar transport. In particular, DoSWEET5b, 5c, and 7d displayed relatively high expression levels in stems. DoSWEET2b and 16 were significantly regulated under cold, drought, and MeJA treatment, which were further verified using RT-qPCR. Correlation analysis and interaction network prediction discovered the internal relationship of DoSWEET family. CONCLUSIONS: Taken together, the identification and analysis of the 25 DoSWEETs in this study provide basic information for further functional verification in D. officinale.


Asunto(s)
Dendrobium , Dendrobium/genética , Dendrobium/metabolismo , Filogenia , Genes de Plantas , Proteínas de Transporte de Membrana/genética , Transporte Biológico , Proteínas de Plantas/metabolismo
16.
Cancer Sci ; 114(11): 4355-4364, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37688294

RESUMEN

Accumulating evidence suggests an association between iron metabolism and lung cancer progression. In biological systems, iron is present in either reduced (Fe2+ ; ferrous) or oxidized (Fe3+ ; ferric) states. However, ferrous and ferric iron exhibit distinct chemical and biological properties, the role of ferrous and ferric iron in lung cancer cell growth has not been clearly distinguished. In this study, we manipulated the balance between cellular ferrous and ferric iron status by inducing gene mutations involving the FBXL5-IRP2 axis, a ubiquitin-dependent regulatory system for cellular iron homeostasis, and determined its effects on lung cancer cell growth. FBXL5 depletion (ferrous iron accumulation) was found to suppress lung cancer cell growth, whereas IRP2 depletion (ferric iron accumulation) did not suppress such growth, suggesting that ferrous iron but not ferric iron plays a suppressive role in cell growth. Mechanistically, the depletion of FBXL5 impaired the degradation of the cyclin-dependent kinase inhibitor, p27, resulting in a delay in the cell cycle at the G1/S phase. FBXL5 depletion in lung cancer cells also improved the survival of tumor-bearing mice. Overall, this study highlights the important function of ferrous iron in cell cycle progression and lung cancer cell growth.


Asunto(s)
Proteínas F-Box , Neoplasias Pulmonares , Animales , Ratones , Complejos de Ubiquitina-Proteína Ligasa/química , Complejos de Ubiquitina-Proteína Ligasa/genética , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Neoplasias Pulmonares/genética , Hierro/metabolismo , Ubiquitina/metabolismo , Compuestos Férricos , Proteínas F-Box/genética , Proteínas F-Box/metabolismo
17.
Small ; 19(49): e2303608, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37587787

RESUMEN

Topological insulators (TIs) are characterized by a full insulating gap in the bulk and gapless edge or surface states, which have attracted tremendous attention. 2D Bi (110), as a typical TI, is of particular interest due to its low symmetry structure and topologically protected and spin-momentum-locked Dirac surface states. However, the material's potential applications are hindered by difficulties in fabrication, due to its strong semi-metallic bonding and poor stability. In this study, a novel electrochemical intercalation method for the fabrication of ultrathin Bi (110) nanosheets with the highest yield ever reported is presented. These nanosheets are stabilized through cathodic exfoliation in a reductive environment and further modification with polymer ionic liquids. The versatility of these nanosheets is demonstrated by fabricating flexible acoustic sensors with ultrahigh sensitivity. These sensors can even detect sounds as quiet as 45 dB. Furthermore, these sensors are utilized for acoustic-to-electric energy conversion and information transfer. This work offers a promising approach for scalable fabrication and preservation of ultrathin 2D TI Bi (110) nanosheets and paves the way for their integration into smart devices.

18.
New Phytol ; 238(3): 1115-1128, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36751904

RESUMEN

Numerous plant endogenous mRNAs move via phloem and thus affect the growth and development of long-distant organs. mRNAs are transported with RNA-binding proteins forming a ribonucleoprotein complex. However, it remains elusive how such RNP complex assembles and facilitates mRNA trafficking. Protease digestion and RNA immunoprecipitation were used to investigate the RNP assembly function of the complete Chaperonin Containing T-complex Polypeptide-1. In situ hybridization, hairy root transformation, microprojectile bombardment, and grafting experiments demonstrate the role of CCT complex in the transport of a PbWoxT1-PbPTB3 RNP complex in Pyrus betulaefolia. PbCCT5 silenced caused defective movement of GFP-PbPTB3 and GFP-PbWoxT1 from hairy roots to new leaves via the phloem. PbCCT5 is shown to interact with PbPTB3. PbCCT complex enhanced PbPTB3 stabilization and permitted assembly of PbWoxT1 and PbPTB3 into an RNP complex. Furthermore, silencing of individual CCT subunits inhibited the intercellular movement of GFP-PbPTB3 and long-distance trafficking of PbWoxT1 and PbPTB3 in grafted plants. Taken together, the CCT complex assembles PbPTB3 and PbWoxT1 into an RNP complex in the phloem in order to facilitate the long-distance trafficking of PbWoxT1 in P. betulaefolia. This study therefore provides important insights into the mechanism of RNP complex formation and transport.


Asunto(s)
Pyrus , Chaperonina con TCP-1/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Planta/genética , ARN de Planta/metabolismo , Ribonucleoproteínas/metabolismo
19.
Chemistry ; 29(72): e202303085, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-37877318

RESUMEN

Chiral π-conjugated polycycles have garnered increasing attention due to versatile applications in optoelectronic materials and biological sciences. In this study, we report the synthesis of chiral π-conjugated polycycles incorporating a chiral epoxycyclooctadiene moiety. Our synthetic strategy capitalizes on the novel reactions of hetera-buckybowl triselenasumanene (TSS) and is achieved in two-step manner. Firstly, the TSS is regio-selectively transformed into its ortho-quinone form. Subsequently, the nucleophilic addition reactions of TSS ortho-quinone by phenylethynides are metal ion-dependent. When utilizing (phenylethynyl)magnesium bromide as the nucleophile, two phenylethynyls are furnished onto the edged benzene ring of TSS. When the nucleophile is (phenylethynyl)lithium, a cascade of nucleophilic addition, intermolecular electron-transfer, ring-opening, and tetradehydro-Diels-Alder (TDDA) reactions occur sequentially in one-pot, ultimately affording chiral π-conjugated polycycles featuring the epoxycyclooctadiene moiety as an integral part of their backbones. This work represents a step forward in the synthesis of chiral π-conjugated polycycles using TSS as synthon.

20.
Chemistry ; 29(19): e202203361, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-36449331

RESUMEN

Conjugated polymers with high charge mobilities have drawn increasing attention in organic field-effect transistors (OFETs) in recent years. However, OFETs of conjugated polymers with high mobility and good device stability remain a challenge. In this article, we report a hyperbranched polymer approach to improve the charge mobility and device stability. Three hyperbranched diketopyrrolopyrrole-based polymers were designed and synthesized via linear alkyl side-chain linkers. The results show that 2D topological hyperbranched polymers form stable thin film microstructures, and thus improve the device stability, since the conjugated moiety is interconnected by linear alkyl chain. Besides, the incorporation of linear alkyl chain instead of branching alkyl one reduce steric hindrance, and improve the microstructure ordering as well as the charge mobility. Bar-coated OFETs result demonstrates that the devices mobilities and operational stabilities (bias stability and bending resistance) are both improved. All these indicate that hyperbranched polymer is a potential candidate for future application.

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