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1.
J Orthop Translat ; 45: 188-196, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38562945

RESUMO

Background: Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs). Methods: Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting. Results: The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate. Conclusion: The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes. The translational potential of this article: Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.

2.
Opt Express ; 32(7): 11560-11572, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571000

RESUMO

The Bessel beam has become significant in optical research due to its properties such as a long focal depth, self-healing, and non-diffraction. However, conventional methods for generating Bessel beams have drawbacks such as limited flexibility and tunability and the use of bulky optics. These factors lead to the complexity of the optical systems. This paper presents what we believe is a novel approach to generating Bessel beams by utilizing a fully phase-modulated all-dielectric metasurface. The proposed method enables the arbitrary and independent manipulation of cross-polarized and co-polarized components, allowing the creation of Bessel beams featuring multiple polarization conversions when subjected to left-handed circularly polarized (LCP) incidence. To demonstrate the versatility and effectiveness of the method, three metasurfaces with distinct characteristics are designed. The simulated generated Bessel beams exhibit qualities including long focal depth, non-diffraction behavior, self-healing capabilities, and polarization conversion, which align with the theoretical predictions. This work presents novel possibilities for effectively generating and multi-functional application of Bessel beams.

3.
Nat Commun ; 15(1): 3131, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605012

RESUMO

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.


Assuntos
Osteogênese , Tecidos Suporte , Osteogênese/fisiologia , Tecidos Suporte/química , Porosidade , Impressão Tridimensional , Zinco/farmacologia
4.
PLoS One ; 19(4): e0296787, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635585

RESUMO

In the context of green and sustainable development and rural revitalization, analysis of the relationship between economic development and the evolution of carbon metabolism is of great significance for China's future transformation of development models. This study analyzed the spatial characteristics and spatiotemporal evolution pattern of the decoupling status between carbon metabolism and economic development of Laiwu during two periods from 2001 to 2018 at the village and town unit scales by using the Tapio decoupling model. The results showed that the growth rate of carbon metabolism from 2001 to 2009 was significantly higher than that from 2009 to 2018. The spatial heterogeneity of the decoupling states between economic development and carbon metabolism from 2009 to 2018 was significantly stronger than that from 2001 to 2009 in two units. From 2001 to 2018, the development trend gradually trended towards spatial imbalance. The decoupling status between villages and towns had a high degree of consistency from 2001 to 2009 and inconsistency from 2009 to 2018. From 2001 to 2009, the decoupling status of about 78% of villages was consistent with that of towns. Moreover, from 2009 to 2018, the consistency reduced to 32.2%, and the decoupling status of about 48% of villages was weaker than that of towns. According to the reclassification results of different decoupling state change types, from 2001 to 2018, about 52.2% of the villages had a decoupling state evolution type of eco-deteriorated economic development, which is an unsatisfactory development trend in a short time. Moreover, about 12.1% of the villages had a decoupling state evolution type of eco-improved economic development, which is a satisfactory development trend.


Assuntos
Carbono , Desenvolvimento Econômico , Humanos , Cidades , Carbono/análise , População Rural , China , Dióxido de Carbono/análise
5.
Heliyon ; 10(8): e29422, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38638967

RESUMO

Spinal cord injury (SCI) is a severely disabling and catastrophic condition that poses significant global clinical challenges. The difficulty of SCI repair results from the distinctive pathophysiological mechanisms, which are characterised by limited regenerative capacity and inadequate neuroplasticity of the spinal cord. Additionally, the formation of cystic cavities and astrocytic scars after SCI further obstructs both the ascending and descending neural conduction pathways. Consequently, the urgent challenge in post-SCI recovery lies in repairing the damaged spinal cord to reconstruct a functional and intact neural conduction circuit. In recent years, significant advancements in biological tissue engineering technology and novel therapies have resulted in a transformative shift in the field of SCI repair. Currently, SCI treatment primarily involves drug therapy, stem cell therapy, the use of biological materials, growth factors, and other approaches. This paper comprehensively reviews the progress in SCI research over the years, with a particular focus on the concept of "Spinal Cord Fusion" as a promising technique for SCI reconstruction. By discussing this important research progress and the neurological mechanisms involved, our aim is to help solve the problem of SCI repair as soon as possible and to bring new breakthroughs in the treatment of paraplegia after SCI.

6.
Sci Rep ; 14(1): 9149, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644401

RESUMO

Taking thin gauge strip as an example, the deformation process of metal strip in bending roll straightening was studied. Based on the theory of discrete, curvature integral and elastic-plastic mechanics, the strip travel trajectory of the bending roll straightening process is analyzed, and the numerical analytical calculation method of the continuous straightening process of the strip bending roll is established. The results are verified by establishing MARC finite element simulation and designing straightening experiment. The effects of yield strength, plastic rate and bending amount on residual stress after straightening were studied. In the straightening process, with the increase of the amount of bending roll, the residual strain converges to the region Γ, and with the increase of the yield strength, the region Γ decreases. With the increase of the yield strength, the amount of bending roll and the plastic rate, the wave height increases. The results of the calculation of residual stress, finite element simulation and experiment are close and the trend is consistent. The results show that the logic of the calculation method is reasonable, and the prediction error is within the scope of engineering application, which is helpful to the realization of process intelligence in the process of bending roller straightening.

7.
Sheng Li Xue Bao ; 76(1): 59-76, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38444132

RESUMO

Intracerebral hemorrhage (ICH) is the most common subtype of stroke with high disability and high mortality rates. Due to the hypertension with arteriosclerosis, hemopathy and cerebrovascular amyloidosis, the influx of blood from ruptured vessels into the brain destroys the cerebral parenchyma and results in dysfunction of central nervous system because of hematoma compression and a series of toxic metabolites. The cerebral parenchyma consists of gray and white matter. The white matter consists of myelinated axons and oligodendrocytes, whereas the gray matter consists of neuronal cell bodies and dendrites. Currently, most of studies have explored the mechanisms of gray matter injury. But researches of white matter injury (WMI) are still in their infancy, which may be partially responsible for the failure of treatments with neuroprotectants targeting degenerating neuronal cells. In recent years, researchers have progressively identified pathophysiological mechanisms of WMI after ICH including mass effect, neuroinflammation and oxidative stress, but information on the molecular mechanisms of WMI and its effective treatment remains limited. In this paper, we will describe the structure and function of white matter, summarize pathology of WMI and focus on the research advances in the molecular mechanisms and therapeutic strategies of WMI after ICH.


Assuntos
Acidente Vascular Cerebral , Substância Branca , Humanos , Hemorragia Cerebral/terapia , Encéfalo , Córtex Cerebral
8.
Biotechnol J ; 19(3): e2300650, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38479990

RESUMO

S-Adenosyl-L-methionine (SAM) is a substrate for many enzyme-catalyzed reactions and provides methyl groups in numerous biological methylations, and thus has vast applications in the agriculture and medical field. Saccharomyces cerevisiae has been engineered as a platform with significant potential for producing SAM, but the current production has room for improvement. Thus, a method that consists of a series of metabolic engineering strategies was established in this study. These strategies included enhancing SAM synthesis, increasing ATP supply, down-regulating SAM metabolism, and down-regulating competing pathway. After combinatorial metabolic engineering, Bayesian optimization was conducted on the obtained strain C262P6S to optimize the fermentation medium. A final yield of 2972.8 mg·L-1 at 36 h with 29.7% of the L-Met conversion rate in the shake flask was achieved, which was 26.3 times higher than that of its parent strain and the highest reported production in the shake flask to date. This paper establishes a feasible foundation for the construction of SAM-producing strains using metabolic engineering strategies and demonstrates the effectiveness of Bayesian optimization in optimizing fermentation medium to enhance the generation of SAM.


Assuntos
Metionina , S-Adenosilmetionina , Metionina/metabolismo , S-Adenosilmetionina/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Engenharia Metabólica/métodos , Teorema de Bayes , Fermentação , Racemetionina/metabolismo
9.
Chem Soc Rev ; 53(7): 3302-3326, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38354058

RESUMO

Secondary batteries are a core technology for clean energy storage and conversion systems, to reduce environmental pollution and alleviate the energy crisis. Oxide cathodes play a vital role in revolutionizing battery technology due to their high capacity and voltage for oxide-based batteries. However, oxygen vacancies (OVs) are an essential type of defect that exist predominantly in both the bulk and surface regions of transition metal (TM) oxide batteries, and have a crucial impact on battery performance. This paper reviews previous studies from the past few decades that have investigated the intrinsic and anionic redox-mediated OVs in the field of secondary batteries. We focus on discussing the formation and evolution of these OVs from both thermodynamic and kinetic perspectives, as well as their impact on the thermodynamic and kinetic properties of oxide cathodes. Finally, we offer insights into the utilization of OVs to enhance the energy density and lifespan of batteries. We expect that this review will advance our understanding of the role of OVs and subsequently boost the development of high-performance electrode materials for next-generation energy storage devices.

10.
Hypertens Res ; 47(4): 1051-1062, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38326453

RESUMO

To provide a reliable, low-cost screening model for preeclampsia, this study developed an early screening model in a retrospective cohort (25,709 pregnancies) and validated in a validation cohort (1760 pregnancies). A data augmentation method (α-inverse weighted-GMM + RUS) was applied to a retrospective cohort before 10 machine learning models were simultaneously trained on augmented data, and the optimal model was chosen via sensitivity (at a false positive rate of 10%). The AdaBoost model, utilizing 16 predictors, was chosen as the final model, achieving a performance beyond acceptable with Area Under the Receiver Operating Characteristic Curve of 0.8008 and sensitivity of 0.5190. All predictors were derived from clinical characteristics, some of which were previously unreported (such as nausea and vomiting in pregnancy and menstrual cycle irregularity). Compared to previous studies, our model demonstrated superior performance, exhibiting at least a 50% improvement in sensitivity over checklist-based approaches, and a minimum of 28% increase over multivariable models that solely utilized maternal predictors. We validated an effective approach for preeclampsia early screening incorporating zero-cost predictors, which demonstrates superior performance in comparison to similar studies. We believe the application of the approach in combination with high performance approaches could substantially increase screening participation rate among pregnancies. Machine learning model for early preeclampsia screening, using 16 zero-cost predictors derived from clinical characteristics, was built on a 10-year Chinese cohort. The model outperforms similar research by at least 28%; validated on an independent cohort.


Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Primeiro Trimestre da Gravidez , Estudos Retrospectivos , Medição de Risco/métodos , Estudos Prospectivos , Biomarcadores
11.
Lab Chip ; 24(6): 1702-1714, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38321884

RESUMO

The suboptimal prognosis associated with drug therapy for renal cancer can be attributed to the presence of stem-cell-like renal cancer cells. However, the limited number of these cells prevents conventional drug screening assays from effectively assessing the response of renal cancer stem cells to anti-cancer agents. To address this issue, the present study employed microfluidic single-cell culture arrays to expand renal cancer stem cells by exploiting the anti-apoptosis and self-renewal properties of tumor stem cells. A microfluidic chip with 18 000 hydrophilic microwells was designed and fabricated to establish the single-cell culture array. Over a 7 day culture, the large-scale single-cell culture yielded a limited quantity of single-cell-derived tumorspheres. The sphere formation rates for Caki-1, 786-O, and ACHN cells were determined to be 8.74 ± 0.53%, 12.02 ± 1.43%, and 4.98 ± 1.68%, respectively. The expanded cells exhibited stemness characteristics, as indicated by immunofluorescence, flow cytometry, serial passaging, and in vitro differentiation assays. Additionally, the comparative transcriptomic analysis showed significant differences in the gene expression patterns of the expanded cells compared to the differentiated renal cancer cells. The drug testing indicated that renal cancer stem cells exhibited reduced sensitivity towards the tyrosine kinase inhibitors sorafenib and sunitinib, compared to differentiated renal cancer cells. This reduced sensitivity can be attributed to the elevated expression levels of tyrosine kinase in renal cancer stem cells. This present study provides evidence that the utilization of microfluidic single-cell culture arrays for selective cell expansion can facilitate drug testing of renal cancer stem cells.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Microfluídica , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Técnicas de Cultura de Células , Antineoplásicos/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
12.
EBioMedicine ; 101: 104993, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38324982

RESUMO

BACKGROUND: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. METHODS: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. FINDINGS: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo. INTERPRETATION: Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients. FUNDING: The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).


Assuntos
Acidente Vascular Cerebral Hemorrágico , Peritonite , Succinatos , Humanos , Camundongos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch , Acidente Vascular Cerebral Hemorrágico/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Macrófagos/metabolismo , Peritonite/tratamento farmacológico , Fagocitose , Prognóstico , Hidroliases/genética , Hidroliases/metabolismo , Hidroliases/farmacologia
13.
World J Clin Cases ; 12(4): 835-841, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38322693

RESUMO

BACKGROUND: Presently, there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). While vitamin K antagonists are the preferred choice for oral blood thinning, determining the best course of blood-thinning medication remains challenging. It is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating LVT. This study significantly contributes to the medical community. CASE SUMMARY: The blood-thinning treatment of a patient with AMI and LVT was analyzed. Triple blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g, daily clopidogrel hydrogen sulfate at 75 mg, and dabigatran etexilate at 110 mg twice daily. After 15 d, the patient's LVT did not decrease but instead increased. Clinical pharmacists comprehensively analyzed the cases from the perspective of the patient's disease status and drug interaction. The drug regimen was reformulated for the patient, replacing dabigatran etexilate with warfarin, and was administered for six months. The clinical pharmacist provided the patient with professional and standardized pharmaceutical services. The patient's condition was discharged after meeting the international normalized ratio value (2-3) criteria. The patient fully complied with the follow-up, and the time in the therapeutic range was 78.57%, with no serious adverse effects during pharmaceutical monitoring. CONCLUSION: Warfarin proves to be an effective drug for patients with AMI complicated by LVT, and its blood-thinning course lasts for six months.

14.
Sci Adv ; 10(8): eadj8632, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394212

RESUMO

Measurements of rovibrational spectra of clusters provide physical insight only if spectral lines can be assigned to pairs of quantum states, and further insight is obtained if one can deduce the quantitative energy-level pattern. Both steps can be so difficult that some measured spectra remain unassigned, one example is orthoH2-CO. To extend the scope of spectroscopic insights, we propose to use theoretical information in interpretation of spectra. We first performed high accuracy, full-dimensional calculations of the orthoH2-CO spectrum, at the highest practically achievable levels of electronic structure theory and quantum nuclear dynamics. Then, an iterative, theory-guided method developed here allowed us to fully interpret the spectrum of orthoH2-CO, extending the range of van der Waals clusters for which spectroscopy can provide physical insights.

15.
Opt Express ; 32(3): 4242-4253, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297629

RESUMO

We propose an optical encryption system that combines computational ghost imaging (CGI) with image authentication to enhance security. In this scheme, Hadamard patterns are projected onto the secret images, while their reflected light intensities are captured using a bucket detector (BD). To further strengthen the security of the collected secret data, we encrypt it as a series of binary matrices serving as ciphertext. During the authentication key generation, these encoded binary matrices serve as illumination patterns in the CGI system for a non-secret image, which is used as a reference image for authentication. The data captured by the BD is then binarized to generate the authentication key. Upon successful authentication, the receiver obtains the decryption keys. This method achieves both data compression for secret images and enhanced security during information transmission. We validate the feasibility of this method through computer simulations and optical experiments.

16.
Genome Res ; 34(1): 134-144, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38191205

RESUMO

Large-scale genetic mutant libraries are powerful approaches to interrogating genotype-phenotype correlations and identifying genes responsible for certain environmental stimuli, both of which are the central goal of life science study. We produced the first large-scale CRISPR-Cas9-induced library in a nonmodel multicellular organism, Bombyx mori We developed a piggyBac-delivered binary genome editing strategy, which can simultaneously meet the requirements of mixed microinjection, efficient multipurpose genetic operation, and preservation of growth-defect lines. We constructed a single-guide RNA (sgRNA) plasmid library containing 92,917 sgRNAs targeting promoters and exons of 14,645 protein-coding genes, established 1726 transgenic sgRNA lines following microinjection of 66,650 embryos, and generated 300 mutant lines with diverse phenotypic changes. Phenomic characterization of mutant lines identified a large set of genes responsible for visual phenotypic or economically valuable trait changes. Next, we performed pooled context-specific positive screens for tolerance to environmental pollutant cadmium exposure, and identified KWMTBOMO12902 as a strong candidate gene for breeding applications in sericulture industry. Collectively, our results provide a novel and versatile approach for functional B. mori genomics, as well as a powerful resource for identifying the potential of key candidate genes for improving various economic traits. This study also shows the effectiveness, practicality, and convenience of large-scale mutant libraries in other nonmodel organisms.


Assuntos
Bombyx , Animais , Bombyx/genética , RNA Guia de Sistemas CRISPR-Cas , Mutagênese , Edição de Genes/métodos , Animais Geneticamente Modificados/genética , Sistemas CRISPR-Cas
17.
PLoS One ; 19(1): e0295346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38181024

RESUMO

The cell division cycle associated (CDCA) genes regulate the cell cycle; however, their relationship with prognosis in glioma has been poorly reported in the literature. The Cancer Genome Atlas (TCGA) was utilized to probe the CDCA family in relation to the adverse clinical features of glioma. Glioma single-cell atlas reveals specific expression of CDCA3, 4, 5, 8 in malignant cells and CDCA7 in neural progenitor cells (NPC)-like malignant cells. Glioma data from TCGA, the China Glioma Genome Atlas Project (CGGA) and the gene expression omnibus (GEO) database all demonstrated that CDCA2, 3, 4, 5, 7 and 8 are prognostic markers for glioma. Further analysis identified CDCA2, 5 and 8 as independent prognostic factors for glioma. Lasso regression-based risk models for CDCA families demonstrated that high-risk patients were characterized by high tumor mutational burden (TMB), low levels of microsatellite instability (MSI), and low tumor immune dysfunction and rejection (TIDE) scores. These pointed to immunotherapy for glioma as a potentially viable treatment option Further CDCA clustering suggested that the high CDCA subtype exhibited a high macrophage phenotype and was associated with a higher antigen presentation capacity and high levels of immune escape. In addition, hsa-mir-15b-5p was predicted to be common regulator of CDCA3 and CDCA4, which was validated in U87 and U251 cells. Importantly, we found that CDCAs may indicate response to drug treatment, especially rapamycin, in glioma. In summary, our results suggest that CDCAs have potential applications in clinical diagnosis and as drug sensitivity markers in glioma.


Assuntos
Glioma , Humanos , Prognóstico , Glioma/tratamento farmacológico , Glioma/genética , Imunoterapia , Biologia Computacional , Biomarcadores , Proteínas de Ciclo Celular/genética , Proteínas Nucleares
18.
Biol Direct ; 19(1): 2, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163902

RESUMO

BACKGROUND: Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. METHODS: The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. RESULTS: DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. CONCLUSIONS: We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker.


Assuntos
Glioma , Animais , Humanos , Linhagem Celular Tumoral , Glioma/genética , Glioma/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Apoptose , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética
19.
Bioact Mater ; 34: 282-297, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38261845

RESUMO

Musculoskeletal injuries and bone defects represent a significant clinical challenge, necessitating innovative approaches for effective bone tissue regeneration. In this study, we investigated the potential of harnessing periosteal stem cells (PSCs) and glycosaminoglycan (GAG)-mimicking materials for in situ bone regeneration. Our findings demonstrated that the introduction of 2-N, 6-O sulfated chitosan (26SCS), a GAG-like polysaccharide, enriched PSCs and promoted robust osteogenesis at the defect area. Mechanistically, 26SCS amplifies the biological effect of endogenous platelet-derived growth factor-BB (PDGF-BB) through enhancing the interaction between PDGF-BB and its receptor PDGFRß abundantly expressed on PSCs, resulting in strengthened PSC proliferation and osteogenic differentiation. As a result, 26SCS effectively improved bone defect repair, even in an osteoporotic mouse model with lowered PDGF-BB level and diminished regenerative potential. Our findings suggested the significant potential of GAG-like biomaterials in regulating PSC behavior, which holds great promise for addressing osteoporotic bone defect repair in future applications.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38289852

RESUMO

6-DoF object pose estimation from a monocular image is a challenging problem, where a post-refinement procedure is generally needed for high-precision estimation. In this paper, we propose a framework, dubbed RNNPose, based on a recurrent neural network (RNN) for object pose refinement, which is robust to erroneous initial poses and occlusions. During the recurrent iterations, object pose refinement is formulated as a non-linear least squares problem based on the estimated correspondence field (between a rendered image and the observed image). The problem is then solved by a differentiable Levenberg-Marquardt (LM) algorithm enabling end-to-end training. The correspondence field estimation and pose refinement are conducted alternately in each iteration to improve the object poses. Furthermore, to improve the robustness against occlusion, we introduce a consistency-check mechanism based on the learned descriptors of the 3D model and observed 2D images, which downweights the unreliable correspondences during pose optimization. We evaluate RNNPose on several public datasets, including LINEMOD, Occlusion-LINEMOD, YCB-Video and TLESS. We demonstrate state-of-the-art performance and strong robustness against severe clutter and occlusion in the scenes. Extensive experiments validate the effectiveness of our proposed method. Besides, the extended system based on RNNPose successfully generalizes to multi-instance scenarios and achieves top-tier performance on the TLESS dataset.

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