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1.
J Cancer ; 15(10): 3024-3033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706890

RESUMO

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

2.
Cell Death Dis ; 15(5): 332, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740744

RESUMO

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.


Assuntos
Fatores de Transcrição Forkhead , Neoplasias Ovarianas , Receptores Proteína Tirosina Quinases , Via de Sinalização Wnt , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/genética , Linhagem Celular Tumoral , Animais , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , beta Catenina/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos , Camundongos Nus , Proliferação de Células
3.
Bioact Mater ; 37: 459-476, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38698920

RESUMO

Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.

4.
Heliyon ; 10(9): e29981, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699029

RESUMO

Amidst the global COVID-19 pandemic, the urgent need for timely and precise patient prognosis assessment underscores the significance of leveraging machine learning techniques. In this study, we present a novel predictive model centered on routine clinical laboratory test data to swiftly forecast patient survival outcomes upon admission. Our model integrates feature selection algorithms and binary classification algorithms, optimizing algorithmic selection through meticulous parameter control. Notably, we developed an algorithm coupling Lasso and SVM methodologies, achieving a remarkable area under the ROC curve of 0.9277 with the use of merely 8 clinical laboratory parameters collected upon admission. Our primary contribution lies in the utilization of straightforward laboratory parameters for prognostication, circumventing data processing intricacies, and furnishing clinicians with an expeditious and precise prognostic assessment tool.

5.
J Hazard Mater ; 471: 134410, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38677121

RESUMO

Heavy metal (HM) pollution in agricultural soils has arisen sharply in recent years. However, the impact of main factors on available HMs concentrations in agricultural soils of the three main industries (smelting, chemical and mining industry) is unclear. Herein, soil properties (pH, cation exchange capacity (CEC) and texture (sand, slit, clay)), total and available concentrations were concluded based on the results of 165 research papers from 2000 to 2023 in Web of Science database. In the three industries, the correlation and redundancy analysis were used to study the correlation between main factors and available concentrations, and quantitatively analyzed the contribution of each factor to available concentrations with gradient boosting decision tree model. The results showed that different factors had varying degrees of impact on available metals in the three main industries, and the importance of same factors varied in each industry, as for soil pH, it was most important for available Pb and Zn in the chemical industry, but the total concentrations were most important in the smelting and mining industry. There was no significant correlation between total and available concentrations. Soil properties involved in this paper (especially soil pH) were negatively correlated with available concentrations. This study provides effective guidance for the formulation of soil pollution control and risk assessment standards based on industry classification in the three major industrial impact areas.

6.
J Neuroinflammation ; 21(1): 101, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632579

RESUMO

BACKGROUND: Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear. METHODS: The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured. RESULTS: The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis. CONCLUSIONS: Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.


Assuntos
Hipertensão , Microbiota , Humanos , Ratos , Animais , Ratos Endogâmicos SHR , Doenças Neuroinflamatórias , Hipertensão/metabolismo , Pressão Sanguínea , Bulbo/metabolismo , Acetatos/farmacologia
7.
Front Microbiol ; 15: 1335664, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633697

RESUMO

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis. Methods: A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves. Results: Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively). Discussion: The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.

8.
J Phys Chem Lett ; 15(16): 4494-4500, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38634706

RESUMO

In the last few decades, massive effort has been expended in heterogeneous catalysis to develop new materials presenting high conversion, selectivity, and stability even under high-temperature and high-pressure conditions. In this context, CO2 hydrogenation is an interesting reaction where the catalyst local structure is strongly related to the development of an active and stable material under hydrothermal conditions at T/P > 300 °C/30 bar. In order to clarify the relationship between catalyst local ordering and its activity/stability, we herein report a combined laboratory and synchrotron investigation of aliovalent element (Ce/Zn/Ga)-containing ZrO2 matrixes. The results reveal the influence of similar average structures with different short-range orderings on the catalyst properties. Moreover, a further step toward the comprehension of the oxygen vacancy formation mechanism in Ce- and Ga-ZrO2 catalysts is reported. Finally, the reported results illustrate a robust method to guide local structure determination and ultimately help to avoid overuse of the "solid solution" definition.

9.
Cell Rep Med ; : 101510, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38614093

RESUMO

Key gene mutations are essential for colorectal cancer (CRC) development; however, how the mutated tumor cells impact the surrounding normal cells to promote tumor progression has not been well defined. Here, we report that PIK3CA mutant tumor cells transmit oncogenic signals and result in malignant transformation of intestinal epithelial cells (IECs) via paracrine exosomal arachidonic acid (AA)-induced H3K4 trimethylation. Mechanistically, PIK3CA mutations sustain SGK3-FBW7-mediated stability of the cPLA2 protein, leading to the synthetic increase in AA, which is transported through exosome and accumulated in IECs. Transferred AA directly binds Menin and strengthens the interactions of Menin and MLL1/2 methyltransferase. Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

10.
Nat Commun ; 15(1): 2850, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565855

RESUMO

Accurately placing very small amounts of electrolyte on tiny micro-supercapacitors (MSCs) arrays in close proximity is a major challenge. This difficulty hinders the development of densely-compact monolithically integrated MSCs (MIMSCs). To overcome this grand challenge, we demonstrate a controllable electrolyte directed assembly strategy for precise isolation of densely-packed MSCs at micron scale, achieving scalable production of MIMSCs with ultrahigh areal number density and output voltage. We fabricate a patterned adhesive surface across MIMSCs, that induce electrolyte directed assembly on 10,000 highly adhesive MSC regions, achieving a 100 µm-scale spatial separation between each electrolyte droplet within seconds. The resultant MIMSCs achieve an areal number density of 210 cells cm-2 and a high areal voltage of 555 V cm-2. Further, cycling the MIMSCs at 190 V over 9000 times manifests no performance degradation. A seamlessly integrated system of ultracompact wirelessly-chargeable MIMSCs is also demonstrated to show its practicality and versatile applicability.

11.
Nature ; 628(8007): 313-319, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570689

RESUMO

Transition metal tellurides (TMTs) have been ideal materials for exploring exotic properties in condensed-matter physics, chemistry and materials science1-3. Although TMT nanosheets have been produced by top-down exfoliation, their scale is below the gram level and requires a long processing time, restricting their effective application from laboratory to market4-8. We report the fast and scalable synthesis of a wide variety of MTe2 (M = Nb, Mo, W, Ta, Ti) nanosheets by the solid lithiation of bulk MTe2 within 10 min and their subsequent hydrolysis within seconds. Using NbTe2 as a representative, we produced more than a hundred grams (108 g) of NbTe2 nanosheets with 3.2 nm mean thickness, 6.2 µm mean lateral size and a high yield (>80%). Several interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance, were observed that are generally restricted to highly crystalline MTe2 nanosheets. The TMT nanosheets also perform well as electrocatalysts for lithium-oxygen batteries and electrodes for microsupercapacitors (MSCs). Moreover, this synthesis method is efficient for preparing alloyed telluride, selenide and sulfide nanosheets. Our work opens new opportunities for the universal and scalable synthesis of TMT nanosheets for exploring new quantum phenomena, potential applications and commercialization.

12.
Cell Signal ; 119: 111180, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38642782

RESUMO

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.


Assuntos
Proliferação de Células , Proteínas de Ligação a DNA , Proteína 1 de Resposta de Crescimento Precoce , Regulação Neoplásica da Expressão Gênica , Inflamação , Neoplasias Ovarianas , Transativadores , Ativação Transcricional , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/genética , Linhagem Celular Tumoral , Transativadores/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Animais , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Camundongos Nus , Transdução de Sinais , Camundongos
13.
Int Immunopharmacol ; 132: 111988, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38583239

RESUMO

PURPOSE: Clinical application of immunotherapy represented by Programmed Death-1 (PD-1) monoclonal antibody has changed the treatment paradigm for colorectal cancer (CRC), and tumor-infiltrating T lymphocytes are critical for anti-PD-1 therapy in CRC. However, there are few studies on the relationship between the expression CXCR3 on T lymphocytes and the clinical aspects of CRC. In this study, we analyzed the expression levels of CXCR3 and PD-1 in CD8+ and CD4+ T lymphocytes in healthy donors (HDs) and patients with CRC. METHODS: We detected the expressions of CXCR3 and PD-1 on T lymphocytes in peripheral blood of healthy donors as well as peripheral blood, tumor tissue and para-cancerous tissues of patients with CRC using flow cytometry. We also analyzed the relationship between the expressions of CXCR3 and PD-1 on T lymphocytes and the pathological characteristics of CRC using t test. RESULTS: Expression of CXCR3 on tumor-infiltrating T lymphocytes was lower, whereas the expression of PD-1 was higher than that on para-cancerous tissues and PB in patients with CRC. In patients with lymph node metastasis of CRC, the expressions levels of CXCR3+ PD-1+ on tumor-infiltrating CD8+ and CD4+ T lymphocytes were higher than those in patients without lymph node metastasis. The levels of CXCR3+ PD-1+ expressions differed depending on the primary tumor site. CONCLUSION: Expressions of CXCR3 and PD-1 on tumor-infiltrating T lymphocytes are related to the development of CRC and metastasis, providing clues for exploring the pathogenesis of CRC and developing new strategies for tumor immunotherapy.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Neoplasias Colorretais , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Receptores CXCR3 , Humanos , Receptores CXCR3/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Receptor de Morte Celular Programada 1/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T CD8-Positivos/imunologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Metástase Linfática , Adulto , Relevância Clínica
14.
Chem Sci ; 15(11): 3949-3956, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38487223

RESUMO

An in-depth understanding of cancer-cell mitosis presents unprecedented advantages for solving metastasis and proliferation of tumors, which has aroused great interest in visualizing the behavior via a luminescence tool. We developed a fluorescent molecule CBTZ-yne based on substituent engineering to acquire befitting lipophilicity and electrophilicity for anchoring lipid droplets and the nucleus, in which the low polarity environment and nucleic acids triggered a "weak-strong" fluorescence and "short-long" fluorescence-lifetime response. Meaningfully, CBTZ-yne visualized chromatin condensation, alignment, pull-push, and separation as well as lipid droplet dynamics, for the first time, precisely unveiling the asynchronous cellular mitosis processes affected by photo-generation reactive oxygen species according to the subtle change of fluorescence-lifetime. Our work suggested a new guideline for tracking the issue of the proliferation of malignant tumors in photodynamic therapy.

15.
J Affect Disord ; 355: 239-246, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38552917

RESUMO

BACKGROUND: Systemic immune-inflammatory index (SII) has been recognized as a novel inflammatory indicator in numerous diseases. It remains unknown how SII affects all-cause mortality among patients with osteoarthritis (OA). In this prospective cohort study, we intended to examine the relationship of SII with all-cause mortality among OA populations and assess the interaction between depression and SII. METHODS: Data was collected from National Health and Nutrition Examination Survey (NHANES) in 2005-2018. The National Death Index (NDI) provided vital status records. Multivariable Cox regression analyses with cubic spines were applied to estimate the association between SII and all-cause and CVD mortality. Stratified analysis and interaction tests assessed the interaction of SII and depression on all-cause mortality. RESULTS: In total 3174 OA adults were included. The lowest quartile Q1 (HR:1.44, 95%CI:1.02-2.04) and highest quartile Q4 (HR:1.44, 95%CI:1.02-2.04) of SII presented a higher risk of death compared with those in second quartile Q2 (Ref.) and third quartile Q3 (HR:1.23, 95%CI:0.89-1.68. Restricted cubic splines analysis revealed a U-shaped association of SII with all-cause mortality, the inflection points were 412.93 × 109/L. The interaction test observed a more significant relationship of SII with all-cause mortality in depression patients than in non-depression patients, indicating that depression can modify this association. LIMITATIONS: First, the observational study design failed to make causal inferences. Second, the baseline SII cannot reflect the long-term level of inflammation. Finally, there may be potential bias. CONCLUSION: SII was U-shaped associated with all-cause mortality in OA patients, and this association was significantly heightened by depression.


Assuntos
Depressão , Osteoartrite , Adulto , Humanos , Inquéritos Nutricionais , Estudos Prospectivos , Inflamação
16.
PLoS Biol ; 22(3): e3002565, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38527087

RESUMO

K+ channels regulate morphogens to scale adult fins, but little is known about what regulates the channels and how they control morphogen expression. Using the zebrafish pectoral fin bud as a model for early vertebrate fin/limb development, we found that K+ channels also scale this anatomical structure, and we determined how one K+-leak channel, Kcnk5b, integrates into its developmental program. From FLIM measurements of a Förster Resonance Energy Transfer (FRET)-based K+ sensor, we observed coordinated decreases in intracellular K+ levels during bud growth, and overexpression of K+-leak channels in vivo coordinately increased bud proportions. Retinoic acid, which can enhance fin/limb bud growth, decreased K+ in bud tissues and up-regulated regulator of calcineurin (rcan2). rcan2 overexpression increased bud growth and decreased K+, while CRISPR-Cas9 targeting of rcan2 decreased growth and increased K+. We observed similar results in the adult caudal fins. Moreover, CRISPR targeting of Kcnk5b revealed that Rcan2-mediated growth was dependent on the Kcnk5b. We also found that Kcnk5b enhanced depolarization in fin bud cells via Na+ channels and that this enhanced depolarization was required for Kcnk5b-enhanced growth. Lastly, Kcnk5b-induced shha transcription and bud growth required IP3R-mediated Ca2+ release and CaMKK activity. Thus, we provide a mechanism for how retinoic acid via rcan2 can regulate K+-channel activity to scale a vertebrate appendage via intercellular Ca2+ signaling.


Assuntos
Cálcio , Peixe-Zebra , Animais , Peixe-Zebra/genética , Cálcio/metabolismo , Tretinoína , Nadadeiras de Animais/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Regulação da Expressão Gênica no Desenvolvimento
17.
Biosens Bioelectron ; 253: 116194, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38467100

RESUMO

The multiplexed detection of metabolites in parallel within a single biosensor plate is sufficiently valuable but also challenging. Herein, we combine the inherent light addressability of silicon with the high selectivity of enzymes, for the construction of multiplexed photoelectrochemical enzymatic biosensors. To conduct a stable electrochemistry and reagentless biosensing on silicon, a new strategy involving the immobilization of both redox mediators and enzymes using an amide bond-based hydrogel membrane was proposed. The membrane characterization results demonstrated a covalent coupling of ferrocene mediator to hydrogel, in which the mediator acted as not only a signal generator but also a renewable sacrifice agent. By adding corresponding enzymes on different spots of hydrogel membrane modified silicon and recording local photocurrents with a moveable light pointer, this biosensor setup was used successfully to detect multiple metabolites, such as lactate, glucose, and sarcosine, with good analytical performances. The limits of detection of glucose, sarcosine and lactate were found to be 179 µM, 16 µM, and 780 µM with the linear ranges of 0.5-2.5 mM, 0.3-1.5 mM, and 1.0-3.0 mM, respectively. We believe this proof-of-concept study provides a simple and rapid one-step immobilization approach for the fabrication of reagentless enzymatic assays with silicon-based light-addressable electrochemistry.


Assuntos
Técnicas Biossensoriais , Silício , Eletroquímica/métodos , Sarcosina , Técnicas Biossensoriais/métodos , Hidrogéis , Lactatos , Glucose
18.
Nature ; 628(8009): 758-764, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538800

RESUMO

Van der Waals encapsulation of two-dimensional materials in hexagonal boron nitride (hBN) stacks is a promising way to create ultrahigh-performance electronic devices1-4. However, contemporary approaches for achieving van der Waals encapsulation, which involve artificial layer stacking using mechanical transfer techniques, are difficult to control, prone to contamination and unscalable. Here we report the transfer-free direct growth of high-quality graphene nanoribbons (GNRs) in hBN stacks. The as-grown embedded GNRs exhibit highly desirable features being ultralong (up to 0.25 mm), ultranarrow (<5 nm) and homochiral with zigzag edges. Our atomistic simulations show that the mechanism underlying the embedded growth involves ultralow GNR friction when sliding between AA'-stacked hBN layers. Using the grown structures, we demonstrate the transfer-free fabrication of embedded GNR field-effect devices that exhibit excellent performance at room temperature with mobilities of up to 4,600 cm2 V-1 s-1 and on-off ratios of up to 106. This paves the way for the bottom-up fabrication of high-performance electronic devices based on embedded layered materials.

19.
Opt Express ; 32(4): 5793-5808, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439297

RESUMO

Color phase-shifting fringe projection profilometry is one of the single-shot three-dimensional shape measurement techniques. The color crosstalk of the projector-camera system yields undesired phase errors when using phase-shifting method. In this paper, a color crosstalk compensation method based on phase correction matrix is proposed. In this method, the phase correction matrix is established to compensate the deviations between the actual phase-shift values in the acquired fringes and the standard ones in the ideal fringes. Only two fringe patterns are utilized to obtain the phase correction matrix. The quadratic equations for calculating the actual phase-shift values of the fringes in the three color channels are derived. The actual phase-shift values and the corresponding standard ones are employed to form the equilibrium equations for computing the phase correction coefficients in the matrix. Experimental results demonstrate the feasibility of the proposed method and it can effectively reduce the induced overall phase error caused by the color crosstalk.

20.
Genes (Basel) ; 15(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38540329

RESUMO

Kadsura coccinea is a medicinal plant from the Schisandraceae family that is native to China and has great pharmacological potential due to its lignans. However, there are significant knowledge gaps regarding the genetic and molecular mechanisms of lignans. We used transcriptome sequencing technology to analyze root, stem, and leaf samples, focusing on the identification and phylogenetic analysis of Cytochrome P450 (CYP) genes. High-quality data containing 158,385 transcripts and 68,978 unigenes were obtained. In addition, 36,293 unigenes in at least one database, and 23,335 across five databases (Nr, KEGG, KOG, TrEMBL, and SwissProt) were successfully annotated. The KEGG pathway classification and annotation of these unigenes identified 10,825 categorized into major metabolic pathways, notably phenylpropanoid biosynthesis, which is essential for lignan synthesis. A key focus was the identification and phylogenetic analysis of 233 Cytochrome P450 (CYP) genes, revealing their distribution across 38 families in eight clans, with roots showing specific CYP gene expression patterns indicative of their role in lignan biosynthesis. Sequence alignment identified 22 homologous single genes of these CYPs, with 6 homologous genes of CYP719As and 1 of CYP81Qs highly expressed in roots. Our study significantly advances the understanding of the biosynthesis of dibenzocyclooctadiene lignans, offering valuable insights for future pharmacological research and development.


Assuntos
Kadsura , Lignanas , Humanos , Transcriptoma/genética , Filogenia , Perfilação da Expressão Gênica , Sistema Enzimático do Citocromo P-450/genética , Lignanas/farmacologia
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