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Plasma membrane heterogeneity is a key biophysical regulatory principle of membrane protein dynamics, which further influences downstream signal transduction. Although extensive biophysical and cell biology studies have proven membrane heterogeneity is essential to cell fate, the direct link between membrane heterogeneity regulation to cellular function remains unclear. Heterogeneous structures on plasma membranes, such as lipid rafts, are transiently assembled, thus hard to study via regular techniques. Indeed, it is nearly impossible to perturb membrane heterogeneity without changing plasma membrane compositions. In this study, we developed a high-spatial resolved DNA-origami-based nanoheater system with specific lipid heterogeneity targeting to manipulate the local lipid environmental temperature under near-infrared (NIR) laser illumination. Our results showed that the targeted heating of the local lipid environment influences the membrane thermodynamic properties, which further triggers an integrin-associated cell migration change. Therefore, the nanoheater system was further applied as an optimized therapeutic agent for wound healing. Our strategy provides a powerful tool to dynamically manipulate membrane heterogeneity and has the potential to explore cellular function through changes in plasma membrane biophysical properties.
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Calor , Microdominios de Membrana , Membrana Celular/metabolismo , Microdominios de Membrana/metabolismo , Transducción de Señal , Movimiento Celular , Lípidos/análisisRESUMEN
Centromeres have an essential and conserved role in eukaryotes, and represent a paradoxical feature of rapid evolution. A recent study by Naish et al. applied long-read sequencing to survey a genome assembly of all five Arabidopsis (Arabidopsisthaliana) centromeres. Analyses of these centromeres showed characteristic genetic and epigenetic features, providing new insights into centromere evolution.
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Arabidopsis , Arabidopsis/genética , Centrómero/genética , Histonas/genéticaRESUMEN
BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.
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BACKGROUND: Malignant progression is the major cause of poor prognosis in breast cancer (BC) patients. Plasma exosomal miRNAs have been reported to be involved in tumor progression, but their roles in BC remain unclear. METHODS: We performed plasma exosomal miRNA sequencing on 45 individuals, including healthy controls and nonmetastatic and metastatic BC patients. We examined the correlation between miRNA expression in tumor tissues and plasma exosomes in BC patients by qRTâPCR. The effects of exosomal miR-361-3p on BC cells were determined by CellTiter-Glo, migration and wound healing assays. The target genes of miR-361-3p and downstream pathways were explored by dual-luciferase reporter assay, RNA knockdown, rescue experiments, and western blotting. We utilized murine xenograft model to further assess the impact of plasma exosomal miR-361-3p on the malignant progression of BC. RESULTS: We found that the expression level of plasma exosomal miR-361-3p gradually increased with malignant progression in BC patients, and the expression of miR-361-3p in plasma exosomes and BC tissues was positively correlated. Consistently, exosomal miR-361-3p enhanced the migration and proliferation of two BC cell lines, MDA-MB-231 and SK-BR-3. Furthermore, our data showed that miR-361-3p inhibited two novel target genes, ETV7 and BATF2, to activate the PAI-1/ERK pathway, leading to increased BC cell viability. Finally, the consistency of the in vivo experimental results supported that elevated plasma exosomal miR-361-3p promote the malignant progression of BC. CONCLUSIONS: We found for the first time that plasma exosomal miR-361-3p was associated with malignant progression in BC patients. Mechanistically, exosomal miR-361-3p can enhance the migration and proliferation of BC cells by targeting the ETV7 and BATF2/PAI-1/ERK pathways. Our data suggest that plasma exosomal miR-361-3p has the potential to serve as a biomarker for predicting malignant progression in BC patients.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Neoplasias de la Mama , Exosomas , MicroARNs , Proteínas Proto-Oncogénicas c-ets , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/genética , Exosomas/metabolismo , Sistema de Señalización de MAP Quinasas , MicroARNs/genética , Inhibidor 1 de Activador Plasminogénico/metabolismo , Proteínas Proto-Oncogénicas c-ets/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
In rice (Oryza sativa L.), vascular bundle phloem tissue in the panicle neck is vital for the transport of photosynthetic products from leaf to panicle and is positively associated with grain yield. However, genetic regulation of the single large vascular bundle phloem area (LVPA) in rice panicle neck tissue remains poorly understood. In this study, we carried out genome-wide association analysis of LVPA in the panicle neck using 386 rice accessions and isolated and characterized the gene LVPA4, which is allelic to NARROW LEAF1 (NAL1). Phenotypic analyses were carried out on the near-isogenic line (NIL) NIL-LVPA4LT in the high-yielding indica (xian) cultivar Teqing and on overexpression lines transformed with a vector carrying the Lemont alleles of LVPA4. Both NIL-LVPA4LT and LVPA4 overexpression lines exhibited significantly increased LVPA, enlarged flag leaf size, and improved panicle type. NIL-LVPA4LT had a 7.6%-9.6% yield increase, mainly due to the significantly higher filled grain number per panicle, larger vascular system for transporting photoassimilates to spikelets, and more sufficient source supply that could service the increased sink capacity. Moreover, NIL-LVPA4LT had improved grain quality compared with Teqing, which was mainly attributed to substantial improvement in grain filling, especially for inferior spikelets in NIL-LVPA4LT. The single-nucleotide variation in the third exon of LVPA4 was associated with LVPA, spikelet number, and leaf size throughout sequencing analysis in 386 panels. The results demonstrate that LVPA4 has synergistic effects on source capacity, sink size, and flow transport and plays crucial roles in rice productivity and grain quality, thus revealing the value of LVPA4 in rice breeding programs for improved varieties.
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Oryza , Oryza/genética , Estudio de Asociación del Genoma Completo , Floema/genética , Fitomejoramiento , Haz Vascular de Plantas/genética , Grano Comestible/genéticaRESUMEN
N 6-methyladenosine (m6A) modification on messenger RNAs (mRNAs) is deposited by evolutionarily conserved methyltransferases (writers). How individual m6A writers sculpt the overall landscape of the m6A methylome and the resulting biological impact in multicellular organisms remains unknown. Here, we systematically surveyed the quantitative m6A methylomes at single-nucleotide resolution and their corresponding transcriptomes in Arabidopsis (Arabidopsis thaliana) bearing respective impaired m6A writers. The m6A sites associated with the five Arabidopsis writers were located mostly within 3' untranslated regions with peaks at around 100 bp downstream of stop codons. m6A predominantly promoted the usage of distal poly(A) sites but had little effect on RNA splicing. Notably, impaired m6A writers resulted in hypomethylation and downregulation of transcripts encoding ribosomal proteins, indicating a possible correlation between m6A and protein translation. Besides the common effects on mRNA metabolism and biological functions uniquely exerted by different Arabidopsis m6A writers compared with their counterparts in human cell lines, our analyses also revealed the functional specificity of individual Arabidopsis m6A writers in plant development and response to stresses. Our findings thus reveal insights into the biological roles of various Arabidopsis m6A writers and their cognate counterparts in other multicellular m6A methyltransferase complexes.
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Arabidopsis , Humanos , Metilación , Arabidopsis/genética , Arabidopsis/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Adenosina/genética , Adenosina/metabolismo , ARN/metabolismoRESUMEN
The escalating surge in datacenter traffic creates a pressing demand for augmenting the capacity of cost-effective intensity modulation and direct detection (IM/DD) systems. In this Letter, we report the demonstration of the single-lane 128-GBaud probabilistically shaped (PS)-PAM-20 IM/DD transmission using only a single digital-to-analog converter (DAC) for a net 400â G/λ system. Based on the advanced digital signal processing (DSP), we achieve net bitrates of up to 437â Gb/s for optical back-to-back and 432â Gb/s after the 0.5-km SSMF transmission in the C-band with 128-Gbaud PS-PAM-20 signals. This work is the latest demonstration on ultra-high-order PS-PAM signals achieving net bitrates exceeding 400â Gb/s despite symbol rate limitations. Notably, to the best of our knowledge, the realized net information rate ([net bitrate]/[symbol rate]) of 3.37 marks a new achievement within the domain of 400â G/λ IM/DD systems, with promising implications for enhancing bandwidth efficiency in the upcoming 1.6-Tb Ethernet scenario.
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BACKGROUND: Acute myocardial injury, cytokine storms, hypoxemia and pathogen-mediated damage were the major causes responsible for mortality induced by coronavirus disease 2019 (COVID-19)-related myocarditis. These need ECMO treatment. We investigated differentially expressed genes (DEGs) in patients with COVID-19-related myocarditis and ECMO prognosis. METHODS: GSE150392 and GSE93101 were analyzed to identify DEGs. A Venn diagram was used to obtain the same transcripts between myocarditis-related and ECMO-related DEGs. Enrichment pathway analysis was performed and hub genes were identified. Pivotal miRNAs, transcription factors, and chemicals with the screened gene interactions were identified. The GSE167028 dataset and single-cell sequencing data were used to validate the screened genes. RESULTS: Using a Venn diagram, 229 overlapping DEGs were identified between myocarditis-related and ECMO-related DEGs, which were mainly involved in T cell activation, contractile actin filament bundle, actomyosin, cyclic nucleotide phosphodiesterase activity, and cytokine-cytokine receptor interaction. 15 hub genes and 15 neighboring DEGs were screened, which were mainly involved in the positive regulation of T cell activation, integrin complex, integrin binding, the PI3K-Akt signaling pathway, and the TNF signaling pathway. Data in GSE167028 and single-cell sequencing data were used to validate the screened genes, and this demonstrated that the screened genes CCL2, APOE, ITGB8, LAMC2, COL6A3 and TNC were mainly expressed in fibroblast cells; IL6, ITGA1, PTK2, ITGB5, IL15, LAMA4, CAV1, SNCA, BDNF, ACTA2, CD70, MYL9, DPP4, ENO2 and VEGFC were expressed in cardiomyocytes; IL6, PTK2, ITGB5, IL15, APOE, JUN, SNCA, CD83, DPP4 and ENO2 were expressed in macrophages; and IL6, ITGA1, PTK2, ITGB5, IL15, VCAM1, LAMA4, CAV1, ACTA2, MYL9, CD83, DPP4, ENO2, VEGFC and IL32 were expressed in vascular endothelial cells. CONCLUSION: The screened hub genes, IL6, ITGA1, PTK2, ITGB3, ITGB5, CCL2, IL15, VCAM1, GZMB, APOE, ITGB8, LAMA4, LAMC2, COL6A3 and TNFRSF9, were validated using GEO dataset and single-cell sequencing data, which may be therapeutic targets patients with myocarditis to prevent MI progression and adverse cardiovascular events.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Miocarditis , Humanos , COVID-19/genética , COVID-19/terapia , COVID-19/complicaciones , Miocarditis/genética , Miocarditis/terapia , Miocarditis/virología , Pronóstico , Perfilación de la Expresión Génica , Bases de Datos Genéticas , SARS-CoV-2 , Redes Reguladoras de Genes , TranscriptomaRESUMEN
Understanding the molecular and cellular mechanisms of human primordial germ cells (hPGCs) is essential in studying infertility and germ cell tumorigenesis. Many RNA-binding proteins (RBPs) and non-coding RNAs are specifically expressed and functional during hPGC developments. However, the roles and regulatory mechanisms of these RBPs and non-coding RNAs, such as microRNAs (miRNAs), in hPGCs remain elusive. In this study, we reported a new regulatory function of DAZL, a germ cell-specific RBP, in miRNA biogenesis and cell proliferation. First, DAZL co-localized with miRNA let-7a in human PGCs and up-regulated the levels of >100 mature miRNAs, including eight out of nine let-7 family, miR21, miR22, miR125, miR10 and miR199. Purified DAZL directly bound to the loops of precursor miRNAs with sequence specificity of GUU. The binding of DAZL to the precursor miRNA increased the maturation of miRNA by enhancing the cleavage activity of DICER. Furthermore, cell proliferation assay and cell cycle analysis confirmed that DAZL inhibited the proliferation of in vitro PGCs by promoting the maturation of these miRNAs. Evidently, the mature miRNAs up-regulated by DAZL silenced cell proliferation regulators including TRIM71. Moreover, DAZL inhibited germline tumor cell proliferation and teratoma formation. These results demonstrate that DAZL regulates hPGC proliferation by enhancing miRNA processing.
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MicroARNs , Humanos , Proliferación Celular/genética , Células Germinativas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.
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Moléculas de Adhesión Celular/fisiología , Heterocromatina/metabolismo , Inmunoglobulinas/fisiología , Profase Meiótica I , Animales , Moléculas de Adhesión Celular/genética , Cromosomas , Femenino , Genes Reporteros , Humanos , Inmunoglobulinas/genética , Masculino , Ratones , Células de Sertoli/metabolismo , Espermatocitos/metabolismoRESUMEN
The inheritance of predisposition to nonsyndromic familial nonmedullary thyroid cancer (FNMTC) remains unclear. Here, we report six individuals with papillary thyroid cancer (PTC) in two unrelated nonsyndromic FNMTC families. Whole-exome sequencing revealed two germ-line loss-of-function variants occurring within a 28-bp fragment of WDR77, which encodes a core member of a transmethylase complex formed with the protein arginine methyltransferase PRMT5 that is responsible for histone H4 arginine 3 dimethylation (H4R3me2) in frogs and mammals. To date, the association of WDR77 with susceptibility to cancer in humans is unknown. A very rare heterozygous missense mutation (R198H) in WDR77 exon 6 was identified in one family of three affected siblings. A heterozygous splice-site mutation (c.619+1G > C) at the 5' end of intron 6 is present in three affected members from another family. The R198H variant impairs the interaction of WDR77 with PRMT5, and the splice-site mutation causes exon 6 skipping and results in a marked decrease in mutant messenger RNA, accompanied by obviously reduced H4R3me2 levels in mutation carriers. Knockdown of WDR77 results in increased growth of thyroid cancer cells. Whole-transcriptome analysis of WDR77 mutant patient-derived thyroid tissue showed changes in pathways enriched in the processes of cell cycle promotion and apoptosis inhibition. In summary, we report WDR77 mutations predisposing patients to nonsyndromic familial PTC and link germ-line WDR77 variants to human malignant disease.
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Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Cáncer Papilar Tiroideo/genética , Glándula Tiroides/patología , Neoplasias de la Tiroides/genética , Factores de Transcripción/genética , Adulto , Secuencia de Aminoácidos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Modelos Moleculares , Mutación , Mutación Missense , Conformación Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Secuenciación del ExomaRESUMEN
As an important direction in computer vision, human pose estimation has received extensive attention in recent years. A High-Resolution Network (HRNet) can achieve effective estimation results as a classical human pose estimation method. However, the complex structure of the model is not conducive to deployment under limited computer resources. Therefore, an improved Efficient and Lightweight HRNet (EL-HRNet) model is proposed. In detail, point-wise and grouped convolutions were used to construct a lightweight residual module, replacing the original 3 × 3 module to reduce the parameters. To compensate for the information loss caused by the network's lightweight nature, the Convolutional Block Attention Module (CBAM) is introduced after the new lightweight residual module to construct the Lightweight Attention Basicblock (LA-Basicblock) module to achieve high-precision human pose estimation. To verify the effectiveness of the proposed EL-HRNet, experiments were carried out using the COCO2017 and MPII datasets. The experimental results show that the EL-HRNet model requires only 5 million parameters and 2.0 GFlops calculations and achieves an AP score of 67.1% on the COCO2017 validation set. In addition, PCKh@0.5mean is 87.7% on the MPII validation set, and EL-HRNet shows a good balance between model complexity and human pose estimation accuracy.
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PURPOSE: The step-cut osteotomy has been recognized as a valuable approach for addressing cubitus varus deformity, albeit one that necessitates technical proficiency. This study aims to evaluate the efficacy of the modified step-cut osteotomy technique in conjunction with patient-specific instruments by clinical and radiological assessment. METHODS: We conducted a retrospective review of patients who underwent modified step-cut osteotomy with the use of patient-specific instruments in conjunction with Kirschner wires fixation for the correction of cubitus varus deformity between April 2016 and April 2022. Follow-up was performed for a minimum of two years, during which pre-operative and post-operative clinical and radiological parameters were compared. RESULTS: Fifteen patients were enrolled in this study. The mean pre-operative humeral-elbow-wrist (HEW) of the affected side was -21.7° (ranging from -14° to -34°), while the normal side was 9.4° (ranging from 5° to 15°). The post-operation HEW of affected side was 9° (ranging from 4° to 16°). There was no significant difference between the normal side and affected side after operation (p = 0.74). Pre-operative range of motion in the affected side was 130°, while the post-operative range of motion was 132°. Fourteen patients (93.3%) were pleased with the overall appearance of their elbow. None lazy-S deformity was observed in these cases. There were no major complications. CONCLUSION: The modified step-cut osteotomy technique, utilizing patient-specific instrument in conjunction with Kirschner wires fixation was found to be a safe, reliable, and technically easy procedure for correcting cubitus varus deformity.
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CONTEXT: Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear. OBJECTIVE: This study elucidates the possible mechanisms of QGSTW in treating AAMI. MATERIALS AND METHODS: Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks. RESULTS: Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from -16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from -19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG. DISCUSSION AND CONCLUSIONS: This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.
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Medicamentos Herbarios Chinos , Trastornos de la Memoria , Ratones , Animales , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Western Blotting , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
In contrast to seed plants, the gametophytes of seed-free plants develop pluripotent meristems, which promote and sustain their independent growth and development. To date, the cellular basis of meristem development in gametophytes of seed-free ferns remains largely unknown. In this study, we used Woodsia obtusa, the blunt-lobe cliff fern, to quantitatively determine cell growth dynamics in two different types of apical meristems - the apical initial centered meristem and the multicellular apical meristem in gametophytes. Through confocal time-lapse live imaging and computational image analysis and quantification, we determined unique patterns of cell division and growth that sustain or terminate apical initials, dictate the transition from apical initials to multicellular apical meristems, and drive proliferation of apical meristems in ferns. Quantitative results showed that small cells correlated to active cell division in fern gametophytes. The marginal cells of multicellular apical meristems in fern gametophytes undergo division in both anticlinal and periclinal orientations, not only increasing cell numbers but also playing a dominant role in increasing cell layers during gametophyte development. All these findings provide insights into the function and regulation of meristems in gametophytes of seed-free vascular plants, suggesting both conserved and diversified mechanisms underlying meristem cell proliferation across land plants.
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Helechos , Meristema , División Celular , Células Germinativas de las Plantas/metabolismoRESUMEN
Jute (Corchorus sp.) is the most important bast fiber crop worldwide; however, the mechanisms underlying domestication and improvement remain largely unknown. We performed multi-omics analysis by integrating de novo sequencing, resequencing, and transcriptomic and epigenetic sequencing to clarify the domestication and improvement of dark jute Corchorus olitorius. We demonstrated that dark jute underwent early domestication and a relatively moderate genetic bottleneck during improvement breeding. A genome-wide association study of 11 important agronomic traits identified abundant candidate loci. We characterized the selective sweeps in the two breeding stages of jute, prominently, soil salinity differences played an important role in environmental adaptation during domestication, and the strongly selected genes for improvement had an increased frequency of favorable haplotypes. Furthermore, we speculated that an encoding auxin/indole-3-acetic acid protein COS07g_00652 could enhance the flexibility and strength of the stem to improve fiber yield. Our study not only provides valuable genetic resources for future fiber breeding in jute, but also is of great significance for reviewing the genetic basis of early crop breeding.
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Corchorus , Corchorus/genética , Corchorus/metabolismo , Domesticación , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Análisis de Secuencia de ADNRESUMEN
Delayed fracture union and nonunion are common complications of fracture encountered, while Low-intensity pulsed ultrasound (LIPUS) can stimulate bone regeneration. Still, the underlying mechanism of LIPUS on bone regeneration has been poorly understood, which resulted in varied outcomes in the clinic. Therefore, figuring out the mechanism of LIPUS on bone regeneration can lay the foundation for better use of LIPUS in clinical bone regenerative therapies. In this study, we created transgenic mice to reveal the relationship between the periosteal cells' fate and the number of ciliated cells under the LIPUS stimulation. In vitro, we isolated the periosteal cell and aim to figure out the relationship between LIPUS and HDAC6-mediated ciliogenesis and find out a potential target for LIPUS-based bone regeneration strategies. The results showed that LIPUS promoted femoral bone defect regeneration and enhanced osteogenic differentiation of Prrx1+ cells. However, these pro-effects were significantly weakened when the Prrx1+ cell's primary cilia were knocked down. Besides, LIPUS stimulated the formation of Prrx1+ cells' primary cilia in the bone defect microenvironment. In vitro, the results supported that LIPUS enhanced the osteogenic differentiation of Prrx1+ cells through HDAC6-mediated ciliogenesis. In conclusion, λ LIPUS could promote the osteogenic differentiation of Prrx1+ cells to stimulate bone regeneration and inhibit the expression of HDAC6 to increase the prevalence of primary cilia in Prrx1+ cells. LIPUS could enhance the osteogenic differentiation of Prrx1+ cells mainly through HDAC6-mediated ciliogenesis.
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Fracturas Óseas , Osteogénesis , Animales , Ratones , Regeneración Ósea , Diferenciación Celular , Ratones Transgénicos , Osteogénesis/fisiología , Ondas UltrasónicasRESUMEN
Plants are capable of regenerating new organs after mechanical injury. The regeneration process involves genome-wide reprogramming of transcription, which usually requires dynamic changes in the chromatin landscape. We show that the histone 3 variant HISTONE THREE RELATED 15 (H3.15) plays an important role in cell fate reprogramming during plant regeneration in Arabidopsis H3.15 expression is rapidly induced upon wounding. Ectopic overexpression of H3.15 promotes cell proliferation to form a larger callus at the wound site, whereas htr15 mutation compromises callus formation. H3.15 is distinguished from other Arabidopsis histones by the absence of the lysine residue 27 that is trimethylated by the POLYCOMB REPRESSIVE COMPLEX 2 (PRC2) in constitutively expressed H3 variants. Overexpression of H3.15 promotes the removal of the transcriptional repressive mark H3K27me3 from chromatin, which results in transcriptional de-repression of downstream genes, such as WUSCHEL RELATED HOMEOBOX 11 (WOX11). Our results reveal a new mechanism for a release from PRC2-mediated gene repression through H3.15 deposition into chromatin, which is involved in reprogramming cell fate to produce pluripotent callus cells.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Histonas/metabolismo , Secuencia de Aminoácidos , Proteínas de Arabidopsis/clasificación , Proteínas de Arabidopsis/genética , Cromatina/metabolismo , Regulación de la Expresión Génica de las Plantas , Histonas/clasificación , Histonas/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Metilación , Mutagénesis Sitio-Dirigida , Filogenia , Plantas Modificadas Genéticamente/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Alineación de Secuencia , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Multi-mode fiber (MMF) has emerged as a promising platform for spatial information transmission attributed to its high capacity. However, the scattering characteristic and time-varying nature of MMF pose challenges for long-term stable transmission. In this study, we propose a spatial pilot-aided learning framework for MMF image transmission, which effectively addresses these challenges and maintains accurate performance in practical applications. By inserting a few reference image frames into the transmitting image sequence and leveraging a fast-adapt network training scheme, our framework adaptively accommodates to the physical channel variations and enables online model update for continuous transmission. Experimented on 100 m length unstable MMFs, we demonstrate transmission accuracy exceeding 92% over hours, with pilot frame overhead around 2%. Our fast-adapt learning scheme requires training of less than 2% of network parameters and reduces the computation time by 70% compared to conventional tuning approaches. Additionally, we propose two pilot-insertion strategies and elaborately compare their applicability to a wide range of scenarios including continuous transmission, burst transmission and transmission after fiber re-plugging. The proposed spatial pilot-aided fast-adapt framework opens up the possibility for MMF spatial transmission in practical complicated applications.
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Inverse design has been widely studied as an efficient method to reduce footprint and improve performance for integrated silicon photonic (SiP) devices. In this study, we have used inverse design to develop a series of ultra-compact dual-band wavelength demultiplexing power splitters (WDPSs) that can simultaneously perform both wavelength demultiplexing and 1:1 optical power splitting. These WDPSs could facilitate the potential coexistence of dual-band passive optical networks (PONs). The design is performed on a standard silicon-on-insulator (SOI) platform using, what we believe to be, a novel two-step direct binary search (TS-DBS) method and the impact of different hyperparameters related to the physical structure and the optimization algorithm is analyzed in detail. Our inverse-designed WDPS with a minimum feature size of 130â nm achieves a 12.77-times reduction in footprint and a slight increase in performance compared with the forward-designed WDPS. We utilize the optimal combination of hyperparameters to design another WDPS with a minimum feature size reduced to 65â nm, which achieves ultra-low insertion losses of 0.36â dB and 0.37â dB and crosstalk values of -19.91â dB and -17.02â dB at wavelength channels of 1310â nm and 1550â nm, respectively. To the best of our knowledge, the hyperparameters of optimization-based inverse design are systematically discussed for the first time. Our work demonstrates that appropriate setting of hyperparameters greatly improves device performance, throwing light on the manipulation of hyperparameters for future inverse design.