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1.
J Cell Sci ; 137(18)2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39239853

RESUMEN

Cytokinesis is the final stage of the cell cycle that results in the physical separation of daughter cells. To accomplish cytokinesis, many organisms build an actin- and myosin-based cytokinetic ring (CR) that is anchored to the plasma membrane (PM). Defects in CR-PM anchoring can arise when the PM lipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is depleted. In Schizosaccharomyces pombe, reduced PM PI(4,5)P2 results in a CR that cannot maintain a medial position and slides toward one cell end, resulting in two differently sized daughter cells. S. pombe PM PI(4,5)P2 is synthesized by the phosphatidylinositol 4-phosphate 5-kinase (PI5-kinase) Its3, but what regulates this enzyme to maintain appropriate PM PI(4,5)P2 levels in S. pombe is not known. To identify Its3 regulators, we used proximity-based biotinylation, and the uncharacterized protein Duc1 was specifically detected. We discovered that Duc1 decorates the PM except at the cell division site and that its unique localization pattern is dictated by binding to the endoplasmic reticulum (ER)-PM contact site proteins Scs2 and Scs22. Our evidence suggests that Duc1 also binds PI(4,5)P2 and helps enrich Its3 at the lateral PM, thereby promoting PM PI(4,5)P2 synthesis and robust CR-PM anchoring.


Asunto(s)
Membrana Celular , Citocinesis , Retículo Endoplásmico , Fosfatidilinositol 4,5-Difosfato , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Retículo Endoplásmico/metabolismo , Membrana Celular/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética
2.
World J Gastroenterol ; 30(32): 3766-3782, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39221071

RESUMEN

BACKGROUND: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM: To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS: Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS: A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION: In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.


Asunto(s)
Cirrosis Hepática , Trasplante de Células Madre Mesenquimatosas , Animales , Humanos , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hígado/patología , Hígado/efectos de los fármacos , Cirrosis Hepática/patología , Cirrosis Hepática/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
3.
IEEE J Transl Eng Health Med ; 12: 550-557, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39155923

RESUMEN

The objective of this study was to develop a sound recognition-based cardiopulmonary resuscitation (CPR) training system that is accessible, cost-effective, easy-to-maintain and provides accurate CPR feedback. Beep-CPR, a novel device with accordion squeakers that emit high-pitched sounds during compression, was developed. The sounds emitted by Beep-CPR were recorded using a smartphone, segmented into 2-second audio fragments, and then transformed into spectrograms. A total of 6,065 spectrograms were generated from approximately 40 minutes of audio data, which were then randomly split into training, validation, and test datasets. Each spectrogram was matched with the depth, rate, and release velocity of the compression measured at the same time interval by the ZOLL X Series monitor/defibrillator. Deep learning models utilizing spectrograms as input were trained using transfer learning based on EfficientNet to predict the depth (Depth model), rate (Rate model), and release velocity (Recoil model) of compressions. Results: The mean absolute error (MAE) for the Depth model was 0.30 cm (95% confidence interval [CI]: 0.27-0.33). The MAE of the Rate model was 3.6/min (95% CI: 3.2-3.9). For the Recoil model, the MAE was 2.3 cm/s (95% CI: 2.1-2.5). External validation of the models demonstrated acceptable performance across multiple conditions, including the utilization of a newly-manufactured device, a fatigued device, and evaluation in an environment with altered spatial dimensions. We have developed a novel sound recognition-based CPR training system, that accurately measures compression quality during training. Significance: Beep-CPR is a cost-effective and easy-to-maintain solution that can improve the efficacy of CPR training by facilitating decentralized at-home training with performance feedback.


Asunto(s)
Reanimación Cardiopulmonar , Reanimación Cardiopulmonar/educación , Reanimación Cardiopulmonar/instrumentación , Humanos , Sonido , Espectrografía del Sonido , Procesamiento de Señales Asistido por Computador/instrumentación , Aprendizaje Profundo , Teléfono Inteligente , Diseño de Equipo
4.
Chemistry ; : e202402488, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120485

RESUMEN

We report an H-bond donor controlled diastereoselective switchable intramolecular aza-Henry reaction of ketimines derived from α-ketoesters and 2-(2-nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza-quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide-bearing quaternary ammonium salt C2 selectively give cis-adducts in up to 20:1 dr and 99% ee, the corresponding urea-bearing analogue C8 preferentially give trans-adducts in up to 20:1 dr and 99% ee.

5.
Mol Biol Cell ; 35(8): ar112, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38985524

RESUMEN

Centrosomes and spindle pole bodies (SPBs) are important for mitotic spindle formation and serve as cellular signaling platforms. Although centrosomes and SPBs differ in morphology, many mechanistic insights into centrosome function have been gleaned from SPB studies. In the fission yeast Schizosaccharomyces pombe, the α-helical protein Ppc89, identified based on its interaction with the septation initiation network scaffold Sid4, comprises the SPB core. High-resolution imaging has suggested that SPB proteins assemble on the Ppc89 core during SPB duplication, but such interactions are undefined. Here, we define a connection between Ppc89 and the essential pericentrin Pcp1. Specifically, we found that a predicted third helix within Ppc89 binds the Pcp1 pericentrin-AKAP450 centrosomal targeting (PACT) domain complexed with calmodulin. Ppc89 helix 3 contains similarity to present in the N-terminus of Cep57 (PINC) motifs found in the centrosomal proteins fly SAS-6 and human Cep57 and also to the S. cerevisiae SPB protein Spc42. These motifs bind pericentrin-calmodulin complexes and AlphaFold2 models suggest a homologous complex assembles in all four organisms. Mutational analysis of the S. pombe complex supports the importance of Ppc89-Pcp1 binding interface in vivo. Our studies provide insight into the core architecture of the S. pombe SPB and suggest an evolutionarily conserved mechanism of scaffolding pericentrin-calmodulin complexes for mitotic spindle formation.


Asunto(s)
Centrosoma , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Huso Acromático , Cuerpos Polares del Huso , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Cuerpos Polares del Huso/metabolismo , Centrosoma/metabolismo , Huso Acromático/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Antígenos/metabolismo , Calmodulina/metabolismo , Unión Proteica
6.
Angew Chem Int Ed Engl ; : e202412533, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083348

RESUMEN

Alloy-type materials are attractive for anodes in sodium-ion batteries (SIBs) owing to their high theoretical capacities and overall performance. However, the accumulation of stress/strain during repeated cycling results in electrode pulverization, leading to rapid capacity decay and eventual disintegration, thus hindering their practical applications. Herein, we report a 3D coral-like Sb-Cu alloy nanoarray with gradient distribution of both elements. The array features a Sb-rich bottom and a Cu-rich top with increasing Sb and decreasing Cu concentrations from top to bottom. The former is the active component that provides the high capacity, whereas the latter serves as an inert additive that acts against volume variation. The gradual transition in composition within the electrode introduces a ladder-type volume expansion effect, facilitating a smooth distribution and effective release of stress, thereby ensuring the wanted mechanical stability and structural integrity. The as-developed nanoarray affords a high reversible capacity (460 mAh g-1 at 0.5 C), stable cycling (89% retention over 120 cycles at 1.0 C), and superior rate capability (354 mAh g-1 at 10 C). The concentration dual-gradient strategy paves a new pathway of designing alloy-type materials for SIBs.

7.
Sci Adv ; 10(19): eadj5185, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728403

RESUMEN

CK1 kinases participate in many signaling pathways, and their regulation is of meaningful biological consequence. CK1s autophosphorylate their C-terminal noncatalytic tails, and eliminating these tails increases substrate phosphorylation in vitro, suggesting that the autophosphorylated C-termini act as inhibitory pseudosubstrates. To test this prediction, we comprehensively identified the autophosphorylation sites on Schizosaccharomyces pombe Hhp1 and human CK1ε. Phosphoablating mutations increased Hhp1 and CK1ε activity toward substrates. Peptides corresponding to the C-termini interacted with the kinase domains only when phosphorylated, and substrates competitively inhibited binding of the autophosphorylated tails to the substrate binding grooves. Tail autophosphorylation influenced the catalytic efficiency with which CK1s targeted different substrates, and truncating the tail of CK1δ broadened its linear peptide substrate motif, indicating that tails contribute to substrate specificity as well. Considering autophosphorylation of both T220 in the catalytic domain and C-terminal sites, we propose a displacement specificity model to describe how autophosphorylation modulates substrate specificity for the CK1 family.


Asunto(s)
Proteínas de Schizosaccharomyces pombe , Humanos , Secuencia de Aminoácidos , Caseína Cinasa 1 épsilon/metabolismo , Caseína Cinasa 1 épsilon/genética , Dominio Catalítico , Mutación , Péptidos/metabolismo , Péptidos/química , Fosforilación , Unión Proteica , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/genética , Especificidad por Sustrato
8.
Angew Chem Int Ed Engl ; 63(30): e202406441, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38742483

RESUMEN

Transition-metal carbides with metallic properties have been extensively used as electrocatalysts due to their excellent conductivity and unique electronic structures. Herein, NbC nanoparticles decorated carbon nanofibers (NbC@CNFs) are proposed as an efficient and robust catalyst for electrochemical synthesis of ammonia from nitrate/nitrite reduction, which achieves a high Faradaic efficiency (FE) of 94.4 % and a large ammonia yield of 30.9 mg h-1 mg-1 cat.. In situ electrochemical tests reveal the nitrite reduction at the catalyst surface follows the *NO pathway and theoretical calculations reveal the formation of NbC@CNFs heterostructure significantly broadens density of states nearby the Fermi energy. Finite element simulations unveil that the current and electric field converge on the NbC nanoparticles along the fiber, suggesting the dispersed carbides are highly active for nitrite reduction.

9.
Chem Commun (Camb) ; 60(42): 5554-5557, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38712366

RESUMEN

Zirconia as a polycrystalline catalyst can be effectively tuned by doping low-valence elements and meanwhile form abundant oxygen vacancies. Herein, the crystalline structures of zirconia are modulated by scandium doping and proposed as a robust catalyst for nitrate reduction to ammonia. The tetragonal zirconia achieves a maximum ammonia yield of 16.03 mg h-1 mgcat.-1, superior to the other crystal forms. DEMS tests unveil the reaction pathway and theoretical calculations reveal the low free energy of -0.22 eV for nitrate adsorption at the tetragonal zirconia.

10.
J Pharm Anal ; 14(3): 335-347, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38618242

RESUMEN

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-ß/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-ß/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

11.
Heliyon ; 10(8): e29504, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655349

RESUMEN

Despite growing evidence suggesting an important contribution of Tumor Protein P53 Inducible Protein 11 (TP53I11) in cancer progression, the role of TP53I11 remains unclear. Our first pan-cancer analysis of TP53I11 showed some tumor tissues displayed reduced TP53I11 expression compared to normal tissues, while others exhibited high TP53I11 expression. Meanwhile, TP53I11 expression carries a particular pan-cancer risk, as high TP53I11 expression levels are detrimental to survival for BRCA, KIRP, MESO, and UVM, but to beneficial survival for KIRC. We demonstrated that TP53I11 expression negatively correlates with DNA methylation in most cancers, and the S14 residue of TP53I11 is phosphorylated in several cancer types. Additionally, TP53I11 was found to be associated with endothelial cells in pan-cancer, and functional enrichment analysis provided strong evidence for its role in tumor angiogenesis. In vitro angiogenesis assays confirmed that TP53I11 can promote angiogenic function of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistic investigations reveal that TP53I11 is transcriptionally up-regulated by HIF2A under hypoxia.

12.
Nano Lett ; 24(13): 3961-3970, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38526195

RESUMEN

Developing a high-performance membrane electrode assembly (MEA) poses a formidable challenge for fuel cells, which lies in achieving both high metal loading and efficient catalytic activity concurrently for MEA catalysts. Here, we introduce a porous Co@NC carrier to synthesize sub-4 nm PtCo intermetallic nanocrystals, achieving an impressive Pt loading of 27 wt %. The PtCo-CoNC catalyst demonstrates exceptional catalytic activity and remarkable stability for the oxygen reduction reaction. Advanced characterization techniques and theoretical calculations emphasize the synergistic effect between PtCo alloys and single Co atoms, which enhances the desorption of the OH* intermediate. Furthermore, the PtCo-CoNC-based cathode delivers a high power density of 1.22 W cm-2 in the MEA test owing to the enhanced mass transport, which is verified by the simulation results of the O2 distributions and current density inside the catalyst layer. This study lays the groundwork for the design of efficient catalysts with practical applications in fuel cells.

13.
Small ; 20(31): e2311750, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38459645

RESUMEN

The commercialization of lithium-sulfur (Li-S) battery is seriously hindered by the shuttle behavior of lithium (Li) polysulfide, slow conversion kinetics, and Li dendrite growth. Herein, a novel hierarchical p-type iron nitride and n-type vanadium nitride (p-Fe2N/n-VN) heterostructure with optimal electronic structure, confined in vesicle-like N-doped nanofibers (p-Fe2N/n-VN⊂PNCF), is meticulously constructed to work as "one stone two birds" dual-functional hosts for both the sulfur cathode and Li anode. As demonstrated, the d-band center of high-spin Fe atom captures more electrons from V atom to realize more π* and moderate σ* bond electron filling and orbital occupation; thus, allowing moderate adsorption intensity for polysulfides and more effective d-p orbital hybridization to improve reaction kinetics. Meanwhile, this unique structure can dynamically balance the deposition and transport of Li on the anode; thereby, more effectively inhibiting Li dendrite growth and promoting the formation of a uniform solid electrolyte interface. The as-assembled Li-S full batteries exhibit the conspicuous capacities and ultralong cycling lifespan over 2000 cycles at 5.0 C. Even at a higher S loading (20 mg cm-2) and lean electrolyte (2.5 µL mg-1), the full cells can still achieve an ultrahigh areal capacity of 16.1 mAh cm-2 after 500 cycles at 0.1 C.

14.
World Neurosurg ; 186: e173-e180, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38537785

RESUMEN

OBJETIVE: This study aims to introduce the unilateral biplanar screw-rod fixation (UBSF) technique (a hybrid fixation technique: 2 sets of atlantoaxial screws were placed on the same side), which serves as a salvage method for traditional posterior atlantoaxial fixation. To summarize the indications of this technique and to assess its safety, feasibility, and clinical effectiveness in the treatment of odontoid fractures. METHODS: Patients with odontoid fractures were enrolled according to special criteria. Surgical duration and intraoperative blood loss were documented. Patients were followed up for a minimum of 12 months. X-ray and computerized tomography scans were conducted and reviewed at 1 day, and patients were asked to return for computerized tomography reviews at 3, 6, 9, and 12 months after surgery until fracture union. Recorded and compared the Neck Visual Analog Scale and Neck Disability Index presurgery and at 1 week and 12 months postsurgery. RESULTS: Between January 2016 and December 2022, our study enrolled 7 patients who were diagnosed with odontoid fractures accompanied by atlantoaxial bone or vascular abnormalities. All 7 patients underwent successful UBSF surgery, and no neurovascular injuries were recorded during surgery. Fracture union was observed in all patients, and the Neck Visual Analog Scale and Neck Disability Index scores improved significantly at 1 week and 12 months postoperative (P < 0.01). CONCLUSIONS: The UBSF technique has been demonstrated to be safe, feasible, and effective in treating odontoid fractures. In cases where the atlantoaxial bone or vascular structure exhibits abnormalities, it can function as a supplementary or alternative approach to the conventional posterior C1-2 fixation.


Asunto(s)
Articulación Atlantoaxoidea , Tornillos Óseos , Fijación Interna de Fracturas , Apófisis Odontoides , Fracturas de la Columna Vertebral , Humanos , Apófisis Odontoides/cirugía , Apófisis Odontoides/lesiones , Apófisis Odontoides/diagnóstico por imagen , Masculino , Femenino , Adulto , Persona de Mediana Edad , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Articulación Atlantoaxoidea/cirugía , Articulación Atlantoaxoidea/diagnóstico por imagen , Resultado del Tratamiento , Anciano , Adulto Joven
15.
Front Pharmacol ; 15: 1344983, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455959

RESUMEN

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

16.
Artif Cells Nanomed Biotechnol ; 52(1): 156-174, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38423139

RESUMEN

Osteoarthritis (OA) is a degenerative disease closely associated with Anoikis. The objective of this work was to discover novel transcriptome-based anoikis-related biomarkers and pathways for OA progression.The microarray datasets GSE114007 and GSE89408 were downloaded using the Gene Expression Omnibus (GEO) database. A collection of genes linked to anoikis has been collected from the GeneCards database. The intersection genes of the differential anoikis-related genes (DEARGs) were identified using a Venn diagram. Infiltration analyses were used to identify and study the differentially expressed genes (DEGs). Anoikis clustering was used to identify the DEGs. By using gene clustering, two OA subgroups were formed using the DEGs. GSE152805 was used to analyse OA cartilage on a single cell level. 10 DEARGs were identified by lasso analysis, and two Anoikis subtypes were constructed. MEgreen module was found in disease WGCNA analysis, and MEturquoise module was most significant in gene clusters WGCNA. The XGB, SVM, RF, and GLM models identified five hub genes (CDH2, SHCBP1, SCG2, C10orf10, P FKFB3), and the diagnostic model built using these five genes performed well in the training and validation cohorts. analysing single-cell RNA sequencing data from GSE152805, including 25,852 cells of 6 OA cartilage.


Asunto(s)
Anoicis , Osteoartritis , Humanos , Anoicis/genética , Aprendizaje Automático , Cadherinas , Osteoartritis/diagnóstico , Osteoartritis/genética , Análisis de Secuencia de ARN , Proteínas Adaptadoras de la Señalización Shc
17.
J Cell Physiol ; 239(5): e31213, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38308641

RESUMEN

Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen-glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin-related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2-D08 (a small-molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy-related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2-D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3-Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.


Asunto(s)
Autofagia , Daño del ADN , Lamina Tipo B , Neuronas , Traumatismos de la Médula Espinal , Sumoilación , Enzimas Ubiquitina-Conjugadoras , Animales , Ratones , Núcleo Celular/metabolismo , Lamina Tipo B/metabolismo , Lamina Tipo B/genética , Neuronas/metabolismo , Neuronas/patología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/patología , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Ratones Endogámicos C57BL , Línea Celular Tumoral
18.
Adv Sci (Weinh) ; 11(7): e2308238, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38064182

RESUMEN

Alkenylboronates are highly versatile building blocks and valuable reagents in the synthesis of complex molecules. Compared with that of monosubstituted alkenylboronates, the synthesis of multisubstituted alkenylboronates is challenging. The copper-catalyzed carboboration of alkynes is an operationally simple and straightforward method for synthesizing bis/trisubstituted alkenylboronates. In this work, a series of copper-metallized N-Heterocyclic Carbene (NHC) ligand porous polymer catalysts are designed and synthesized in accordance with the mechanism of carboboration. By using CuCl@POL-NHC-Ph as the optimal nanocatalyst, this study realizes the ß-regio- and stereoselective (syn-addition) 1,2-carboboration of alkynes (regioselectivity up to >99:1) with satisfactory yields and a wide range of substrates. This work not only overcomes the selectivity of carboboration but also provides a new strategy for the design of nanocatalysts and their application in organic synthesis.

19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031400

RESUMEN

It is believed that traditional Chinese medicine (TCM) Daoyin (conduction exercise) therapy has potential in treating diabetic foot, which is a concrete embodiment of HUANG Yuanyu's theory of one qi circulation applied in practice. Based on Daoyin therapy of Baduanjin and the Origin and Indicators of Disease (《诸病源候论》), a Daoyin prescription for diabetic foot was compiled and created. Based on the zang-fu concept of "One Qi Circulation", combined with the theory of chief, deputy, assistant and envoy, this article explained the theoretical basis and functional mechanism of the Daoyin prescription for diabetic foot. This Daoyin therapy is mainly based on the prone position movements, which includes seven movements, namely, pull-up, knee bending, toe tilting, phoenix nodding, internal rotation of taiji, two hands climbing feet and closing. With "phoenix nodding" and "tilting toes" as the chief, with the help of toes opening-closing and pointing-pressing momentum in prone position, regulating the central qi; with "bending the knee" and "internal rotation of taiji" as the deputy, knee and ankle flexion and extension can unblock the meridians of liver and lungs; with "pull-up" and "two hands climbing feet" as the assistant, on the one hand, assisting to unblock zang-fu organs, on the other hand, applying the yang of the foot taiyang bladder channel and du mai to warm the cold and dampness; with "closing" as the envoy to regulate all organs, so that the blood return to the natural flow of circulation. Diabetic foot Daoyin therapy could regulate internal organs and qi circulation of body, and provides a new idea for the treatment of diabetic foot.

20.
Chinese Journal of School Health ; (12): 609-614, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031784

RESUMEN

Abstract@#Currently, the school health system in China is transitioning from basic safeguarding to comprehensive health management and has been elevated to a national strategic level. However, the diversification of students health issues and the imbalance in resource allocation remain major challenges. To address issues such as adolescent myopia, obesity, spinal curvature, mental health, and infectious diseases, there is an urgently need to build a highlevel school health system that encompasses multiple aspects such as resource allocation optimization, professional skill enhancement, and health education improvement. Simultaneously, it is need to deepen the research and implementation of common disease prevention strategies for students. It will play a vital role in promoting the construction of Healthy China, the modernization of education, and the establishment of a highquality disease control system.

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