Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 921
Filter
Add more filters

Publication year range
1.
Nature ; 629(8010): 86-91, 2024 May.
Article in English | MEDLINE | ID: mdl-38658763

ABSTRACT

Replacement of liquid electrolytes with polymer gel electrolytes is recognized as a general and effective way of solving safety problems and achieving high flexibility in wearable batteries1-6. However, the poor interface between polymer gel electrolyte and electrode, caused by insufficient wetting, produces much poorer electrochemical properties, especially during the deformation of the battery7-9. Here we report a strategy for designing channel structures in electrodes to incorporate polymer gel electrolytes and to form intimate and stable interfaces for high-performance wearable batteries. As a demonstration, multiple electrode fibres were rotated together to form aligned channels, while the surface of each electrode fibre was designed with networked channels. The monomer solution was effectively infiltrated first along the aligned channels and then into the networked channels. The monomers were then polymerized to produce a gel electrolyte and form intimate and stable interfaces with the electrodes. The resulting fibre lithium-ion battery (FLB) showed high electrochemical performances (for example, an energy density of about 128 Wh kg-1). This strategy also enabled the production of FLBs with a high rate of 3,600 m h-1 per winding unit. The continuous FLBs were woven into a 50 cm × 30 cm textile to provide an output capacity of 2,975 mAh. The FLB textiles worked safely under extreme conditions, such as temperatures of -40 °C and 80 °C and a vacuum of -0.08 MPa. The FLBs show promise for applications in firefighting and space exploration.

2.
Nature ; 612(7941): 787-794, 2022 12.
Article in English | MEDLINE | ID: mdl-36450980

ABSTRACT

Medulloblastoma (MB) is the most common malignant childhood brain tumour1,2, yet the origin of the most aggressive subgroup-3 form remains elusive, impeding development of effective targeted treatments. Previous analyses of mouse cerebella3-5 have not fully defined the compositional heterogeneity of MBs. Here we undertook single-cell profiling of freshly isolated human fetal cerebella to establish a reference map delineating hierarchical cellular states in MBs. We identified a unique transitional cerebellar progenitor connecting neural stem cells to neuronal lineages in developing fetal cerebella. Intersectional analysis revealed that the transitional progenitors were enriched in aggressive MB subgroups, including group 3 and metastatic tumours. Single-cell multi-omics revealed underlying regulatory networks in the transitional progenitor populations, including transcriptional determinants HNRNPH1 and SOX11, which are correlated with clinical prognosis in group 3 MBs. Genomic and Hi-C profiling identified de novo long-range chromatin loops juxtaposing HNRNPH1/SOX11-targeted super-enhancers to cis-regulatory elements of MYC, an oncogenic driver for group 3 MBs. Targeting the transitional progenitor regulators inhibited MYC expression and MYC-driven group 3 MB growth. Our integrated single-cell atlases of human fetal cerebella and MBs show potential cell populations predisposed to transformation and regulatory circuitries underlying tumour cell states and oncogenesis, highlighting hitherto unrecognized transitional progenitor intermediates predictive of disease prognosis and potential therapeutic vulnerabilities.


Subject(s)
Brain Neoplasms , Cell Transformation, Neoplastic , Fetus , Medulloblastoma , Humans , Brain Neoplasms/pathology , Cell Transformation, Neoplastic/pathology , Cerebellar Neoplasms/pathology , Cerebellum/cytology , Cerebellum/pathology , Fetus/cytology , Fetus/pathology , Medulloblastoma/pathology , Neural Stem Cells/cytology , Neural Stem Cells/pathology , Prognosis
3.
Nature ; 597(7874): 57-63, 2021 09.
Article in English | MEDLINE | ID: mdl-34471277

ABSTRACT

Fibre lithium-ion batteries are attractive as flexible power solutions because they can be woven into textiles, offering a convenient way to power future wearable electronics1-4. However, they are difficult to produce in lengths of more than a few centimetres, and longer fibres were thought to have higher internal resistances3,5 that compromised electrochemical performance6,7. Here we show that the internal resistance of such fibres has a hyperbolic cotangent function relationship with fibre length, where it first decreases before levelling off as length increases. Systematic studies confirm that this unexpected result is true for different fibre batteries. We are able to produce metres of high-performing fibre lithium-ion batteries through an optimized scalable industrial process. Our mass-produced fibre batteries have an energy density of 85.69 watt hour per kilogram (typical values8 are less than 1 watt hour per kilogram), based on the total weight of a lithium cobalt oxide/graphite full battery, including packaging. Its capacity retention reaches 90.5% after 500 charge-discharge cycles and 93% at 1C rate (compared with 0.1C rate capacity), which is comparable to commercial batteries such as pouch cells. Over 80 per cent capacity can be maintained after bending the fibre for 100,000 cycles. We show that fibre lithium-ion batteries woven into safe and washable textiles by industrial rapier loom can wirelessly charge a cell phone or power a health management jacket integrated with fibre sensors and a textile display.


Subject(s)
Cobalt/chemistry , Electric Power Supplies , Electronics , Lithium/chemistry , Oxides/chemistry , Textiles , Wearable Electronic Devices , Graphite/chemistry , Humans , Ions , Male , Wireless Technology
4.
Proc Natl Acad Sci U S A ; 121(8): e2319696121, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38346181

ABSTRACT

The phylogeny and divergence timing of the Neoavian radiation remain controversial despite recent progress. We analyzed the genomes of 124 species across all Neoavian orders, using data from 25,460 loci spanning four DNA classes, including 5,756 coding sequences, 12,449 conserved nonexonic elements, 4,871 introns, and 2,384 intergenic segments. We conducted a comprehensive sensitivity analysis to account for the heterogeneity across different DNA classes, leading to an optimal tree of Neoaves with high resolution. This phylogeny features a novel Neoavian dichotomy comprising two monophyletic clades: a previously recognized Telluraves (land birds) and a newly circumscribed Aquaterraves (waterbirds and relatives). Molecular dating analyses with 20 fossil calibrations indicate that the diversification of modern birds began in the Late Cretaceous and underwent a constant and steady radiation across the KPg boundary, concurrent with the rise of angiosperms as well as other major Cenozoic animal groups including placental and multituberculate mammals. The KPg catastrophe had a limited impact on avian evolution compared to the Paleocene-Eocene Thermal Maximum, which triggered a rapid diversification of seabirds. Our findings suggest that the evolution of modern birds followed a slow process of gradualism rather than a rapid process of punctuated equilibrium, with limited interruption by the KPg catastrophe. This study places bird evolution into a new context within vertebrates, with ramifications for the evolution of the Earth's biota.


Subject(s)
Fossils , Magnoliopsida , Pregnancy , Female , Animals , Magnoliopsida/genetics , Placenta , Phylogeny , Birds/genetics , Mammals/genetics , DNA, Mitochondrial/genetics , Biological Evolution
5.
Development ; 150(14)2023 07 15.
Article in English | MEDLINE | ID: mdl-37350382

ABSTRACT

Retinoic acid (RA) is the proposed mammalian 'meiosis inducing substance'. However, evidence for this role comes from studies in the fetal ovary, where germ cell differentiation and meiotic initiation are temporally inseparable. In the postnatal testis, these events are separated by more than 1 week. Exploiting this difference, we discovered that, although RA is required for spermatogonial differentiation, it is dispensable for the subsequent initiation, progression and completion of meiosis. Indeed, in the absence of RA, the meiotic transcriptome program in both differentiating spermatogonia and spermatocytes entering meiosis was largely unaffected. Instead, transcripts encoding factors required during spermiogenesis were aberrant during preleptonema, and the subsequent spermatid morphogenesis program was disrupted such that no sperm were produced. Taken together, these data reveal a RA-independent model for male meiotic initiation.


Subject(s)
Testis , Tretinoin , Animals , Female , Male , Tretinoin/pharmacology , Spermatogenesis/genetics , Spermatogonia , Spermatozoa , Meiosis/genetics , Mammals
6.
FASEB J ; 38(13): e23758, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38923594

ABSTRACT

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.


Subject(s)
Bone and Bones , Circadian Rhythm , Humans , Circadian Rhythm/physiology , Animals , Bone and Bones/metabolism , Bone and Bones/physiology , Bone Diseases/physiopathology , Bone Diseases/metabolism , Circadian Clocks/physiology
7.
Proc Natl Acad Sci U S A ; 119(36): e2205562119, 2022 09 06.
Article in English | MEDLINE | ID: mdl-36037332

ABSTRACT

Hydrogen peroxide (H2O2) molecules play important roles in many green chemical reactions. However, the high activation energy limits their application efficiency, and there is still huge controversy about the activation path of H2O2 molecules over the presence of *OOH intermediates. Here, we confirmed the formation of the key species *OOH in the heterogeneous system, via in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), isotope labeling, and theoretical calculation. In addition, we found that compared with *H2O2, *OOH was more conducive to the charge transfer behavior with the catalyst and the activation of an O-O bond. Furthermore, we proposed to improve the local coordination structure and electronic density of the YFeO3 catalyst by regulating the surface relaxation with Ti modification so as to reduce the activation barrier of H2O2 and to improve the production efficiency of •OH. As a result, the kinetics rates of the Fenton-like (photo-Fenton) reaction had been significantly increased several times. The •OH free radical activity mechanism and molecular transformation pathways of 4-chloro phenol (4-CP) were also revealed. This may provide a clearer vision for the further study of H2O2 activation and suggest a means of designing catalysts for efficient H2O2 activation.


Subject(s)
Hydrogen Peroxide , Photochemical Processes , Catalysis , Hydrogen Peroxide/chemistry , Iron/chemistry , Light , Phenol
8.
BMC Genomics ; 25(1): 625, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902611

ABSTRACT

BACKGROUND: Autophagy is a conserved catabolic process in eukaryotes that contributes to cell survival in response to multiple stresses and is important for organism fitness. Extensive research has shown that autophagy plays a pivotal role in both viral infection and replication processes. Despite the increasing research dedicated to autophagy, investigations into shrimp autophagy are relatively scarce. RESULTS: Based on three different methods, a total of 20 members of the ATGs were identified from F. chinensis, all of which contained an autophagy domain. These genes were divided into 18 subfamilies based on their different C-terminal domains, and were found to be located on 16 chromosomes. Quantitative real-time PCR (qRT-PCR) results showed that ATG genes were extensively distributed in all the tested tissues, with the highest expression levels were detected in muscle and eyestalk. To clarify the comprehensive roles of ATG genes upon biotic and abiotic stresses, we examined their expression patterns. The expression levels of multiple ATGs showed an initial increase followed by a decrease, with the highest expression levels observed at 6 h and/or 24 h after WSSV injection. The expression levels of three genes (ATG1, ATG3, and ATG4B) gradually increased until 60 h after injection. Under low-salt conditions, 12 ATG genes were significantly induced, and their transcription abundance peaked at 96 h after treatment. CONCLUSIONS: These results suggested that ATG genes may have significant roles in responding to various environmental stressors. Overall, this study provides a thorough characterization and expression analysis of ATG genes in F. chinensis, laying a strong foundation for further functional studies and promising potential in innate immunity.


Subject(s)
Penaeidae , Stress, Physiological , Animals , Stress, Physiological/genetics , Penaeidae/genetics , Penaeidae/virology , Autophagy/genetics , Gene Expression Profiling , Phylogeny , Autophagy-Related Proteins/genetics , Transcriptome
9.
Apoptosis ; 29(5-6): 743-756, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38478170

ABSTRACT

Chemotherapy is an effective therapeutic modality; nevertheless, a significant proportion of patients diagnosed with lung adenocarcinoma (LUAD) demonstrate resistance to chemotherapy. Therefore, it is crucial to understand the potential regulatory mechanisms to develop novel treatment strategies. This study aims to understand how increased FAM83B expression impacts mitochondrial activity, cell apoptosis, and chemotherapy effectiveness in LUAD. Multiple assays, such as CCK8, wound healing, EdU, and transwell assays, were employed to confirm the augmented chemotherapy resistance, heightened cell proliferation, migration, and invasion caused by FAM83B overexpression in LUAD cells. Furthermore, MIMP, MTG, and ATP assays were utilized to quantify changes in mitochondrial metabolism. In vitro functional assays were performed to evaluate the influence of FAM83B overexpression on the malignant progression and resistance mechanisms to chemotherapy in LUAD. In the context of this study, it was determined that LUAD patients with increased FAM83B expression had shorter survival times, and tissue samples with FAM83B overexpression were more prone to metastasis compared to primary samples. As a result, FAM83B is identified as an adverse prognostic marker. The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis.


Subject(s)
Adenocarcinoma of Lung , Apoptosis , Cell Proliferation , Lung Neoplasms , Mitochondria , Female , Humans , Male , Middle Aged , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/genetics , Mitochondria/pathology , Prognosis
10.
Anal Chem ; 96(25): 10274-10282, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38860851

ABSTRACT

Multiple intracellular microRNA (miRNA) detection is essential for disease diagnosis and management. Nonetheless, the real-time detection of multiple intracellular miRNAs has remained challenging. Herein, we have developed an ultrasound (US)-powered nanomotor-based dynamic fluorescent probe for the real-time OFF-ON fluorescent determination of multiple intracellular miRNAs. The new probe relies on the utilization of multicolored quantum dot (QD)-labeled single-stranded DNA (ssDNA)/graphene oxide (GO)-coated US-powered gold nanowire (AuNW) nanomotors. The fluorescence of QDs is quenched due to π-π interactions with the GO. Upon binding to target miRNAs, the QDs-ssDNA is now distant from the AuNWs, resulting in effective OFF-ON QD fluorescence switching. Compared with conventional passive probes, the dynamic fluorescent probe enhances probe-target interactions by using the US-propelled nanomotor, resulting in exceptionally efficient and prompt hybridization. Simultaneous quantitative analysis of miR-10b and miR-21 in vitro can be achieved within 15 min with high sensitivity and specificity. Additionally, multicolor QDs provide strong signal intensity and multiplexed detection, enabling one-step real-time discrimination between cancer cells (A549) and normal cells (L02). The obtained results are in good agreement with those from qRT-PCR. This dynamic fluorescent probe based on a nanomotor and QDs enables rapid "on the move" specific detection of multiple intracellular miRNAs in intact cells, facilitating real-time monitoring of diverse intracellular miRNA expression, and it could pave the way for novel applications of nanomotors in biodetection.


Subject(s)
Fluorescent Dyes , Graphite , MicroRNAs , Quantum Dots , MicroRNAs/analysis , Humans , Fluorescent Dyes/chemistry , Quantum Dots/chemistry , Graphite/chemistry , Gold/chemistry , DNA, Single-Stranded/chemistry , Nanowires/chemistry , Ultrasonic Waves , A549 Cells
11.
Anal Chem ; 96(17): 6609-6617, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38639728

ABSTRACT

Complex structures and devices, both natural and artificial, can often undergo assembly and disassembly. Assembly and disassembly allow multiple stimuli to initiate, for example, the assembly and disassembly of primary cilia under the control of E3 ubiquitin ligases and deubiquitinases. Although biology relies on such schemes, they are rarely available in materials science. Here, we demonstrate a DNA-functionalized colloidal Au response to endogenous biomarkers to trigger simultaneous assembly and disassembly techniques. Colloidal Au is initially inert because the starting DNA strands are paired and prehybridized. TK1 mRNA competes to bind one of the paired strands and release its complement. The released complement binds to the next colloidal Au to initiate assembly, and APE1 can shear the colloidal Au assembly binding site to initiate disassembly. Our strategy provides temporal and spatial logic control during colloidal Au assembly and disassembly, and this simultaneous assembly and disassembly process can be used for sequential detection and cellular imaging of two biomarkers, effectively reducing signal false-positive results and shortening detection time. This work highlights biomarker-controlled colloidal Au simultaneous assembly and disassembly in ways that are simple and versatile, with the potential to enrich the application scope of DNA nanotechnology and provide an idea for the application of precision medicine testing.


Subject(s)
DNA , Thymidine Kinase , Humans , DNA/chemistry , DNA/metabolism , Biomarkers/metabolism , Biomarkers/analysis , RNA, Messenger/metabolism , Colloids/chemistry , Gold/chemistry , Gold Colloid/chemistry , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism
12.
Cell Commun Signal ; 22(1): 313, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844957

ABSTRACT

BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer and is the leading cause of cancer-related deaths globally. Although various treatment strategies have been introduced, the 5-year survival rate of patients with NSCLC is only 20-30%. Thus, it remains necessary to study the pathogenesis of NSCLC and develop new therapeutic drugs. Notably, PYK2 has been implicated in the progression of many tumors, including NSCLC, but its detailed mechanism remains unclear. In this study, we aimed to elucidate the mechanisms through which PYK2 promotes NSCLC progression. METHODS: The mRNA and protein levels of various molecules were measured using qRT-PCR, western blot (WB), and immunohistochemistry (IHC), respectively. We established stable PYK2 knockdown and overexpression cell lines, and CCK-8, EdU, and clonogenic assays; wound healing, transwell migration, and Matrigel invasion assays; and flow cytometry were employed to assess the phenotypes of tumor cells. Protein interactions were evaluated with co-immunoprecipitation (co-IP), immunofluorescence (IF)-based colocalization, and nucleocytoplasmic separation assays. RNA sequencing was performed to explore the transcriptional regulation mediated by PYK2. Secreted VGF levels were examined using ELISA. Dual-luciferase reporter system was used to detect transcriptional regulation site. PF4618433 (PYK2 inhibitor) and Stattic (STAT3 inhibitor) were used for rescue experiments. A public database was mined to analyze the effect of these molecules on NSCLC prognosis. To investigate the role of PYK2 in vivo, mouse xenograft models of lung carcinoma were established and examined. RESULTS: The protein level of PYK2 was higher in human NSCLC tumors than in the adjacent normal tissue, and higher PYK2 expression was associated with poorer prognosis. PYK2 knockdown inhibited the proliferation and motility of tumor cells and caused G1-S arrest and cyclinD1 downregulation in A549 and H460 cells. Meanwhile, PYK2 overexpression had the opposite effect in H1299 cells. The siRNA-induced inhibition of integrins alpha V and beta 1 led to the downregulation of p-PYK2(Tyr402). Activated PYK2 could bind to STAT3 and enhance its phosphorylation at Tyr705, regulating the nuclear accumulation of p-STAT3(Tyr705). This further promoted the expression of VGF, as confirmed by RNA sequencing in a PYK2-overexpressing H1299 cell line and validated by rescue experiments. Two sites in promoter region of VGF gene were confirmed as binding sites of STAT3 by Dual-luciferase assay. Data from the TGCA database showed that VGF was related to the poor prognosis of NSCLC. IHC revealed higher p-PYK2(Tyr402) and VGF expression in lung tumors than in adjacent normal tissues. Moreover, both proteins showed higher levels in advanced TNM stages than earlier ones. A positive linear correlation existed between the IHC score of p-PYK2(Tyr402) and VGF. Knockdown of VGF inhibited tumor progression and reversed the tumor promoting effect of PYK2 overexpression in NSCLC cells. Finally, the mouse model exhibited enhanced tumor growth when PYK2 was overexpressed, while the inhibitors PF4618433 and Stattic could attenuate this effect. CONCLUSIONS: The Integrin αVß1-PYK2-STAT3-VGF axis promotes NSCLC development, and the PYK2 inhibitor PF4618433 and STAT3 inhibitor Stattic can reverse the pro-tumorigenic effect of high PYK2 expression in mouse models. Our findings provide insights into NSCLC progression and could guide potential therapeutic strategies against NSCLC with high PYK2 expression levels.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Disease Progression , Focal Adhesion Kinase 2 , Lung Neoplasms , STAT3 Transcription Factor , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Focal Adhesion Kinase 2/metabolism , Focal Adhesion Kinase 2/genetics , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Animals , Cell Proliferation/genetics , Mice , Cell Movement/genetics , Mice, Nude , Cell Line, Tumor , Signal Transduction/genetics , Gene Expression Regulation, Neoplastic , Mice, Inbred BALB C
13.
Cell Commun Signal ; 22(1): 339, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898473

ABSTRACT

BACKGROUND: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. METHODS: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. RESULTS: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. CONCLUSION: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.


Subject(s)
Drug Resistance, Neoplasm , GTPase-Activating Proteins , Prostatic Neoplasms , Receptors, Androgen , Male , Humans , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Cell Line, Tumor , Animals , Proto-Oncogene Mas , Gene Expression Regulation, Neoplastic/drug effects , Phenylthiohydantoin/pharmacology , Mice, Nude , Nitriles/pharmacology , Mice , Benzamides/pharmacology , Cell Proliferation/drug effects , Cell Proliferation/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Signal Transduction/drug effects , Signal Transduction/genetics
14.
Org Biomol Chem ; 22(22): 4574-4579, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38775030

ABSTRACT

Metabolic glycoengineering provides a powerful tool to label proteins with chemical tags for cell imaging and protein enrichment. The structures of per-O-acetylation on unnatural sugars facilitate membrane permeability and increase cellular uptake and are widely used for metabolic glycan labeling. However, unexpected S-glyco modification was discovered via a non-enzymatic reaction with protein cysteines, which was initially conducted with the hydrolysis of anomeric acetate by esterase. Herein, we synthesized a series of GalNAz derivatives that were protected with various lengths of short-chain fatty acid, including acetate, propionate, butyrate, valerate and pivalate, to detect differences in labeling efficiencies and occurrence of S-glyco modification. Our results demonstrate that all the GalNAz derivatives could effectively label proteins in HeLa cells, except the pivalate group. Of note, But4GalNAz exhibited excellent labeling abilities compared with Ac4GalNAz from the results for western blot, flow cytometry and confocal laser scanning microscopy. Moreover, the results for the S-glyco-modification assay by western blot and chemoproteomic analysis indicated that But4GalNAz generated negligible unexpected labeling signals compared to Ac4GalNAz. Our study uncovers the distinct labeling efficiency of different protected groups on unnatural sugars, which provides an alternative strategy to explore novel glycan probes.


Subject(s)
Fatty Acids , Humans , HeLa Cells , Fatty Acids/chemistry , Fatty Acids/metabolism , Staining and Labeling , Proteins/chemistry , Proteins/metabolism , Molecular Structure
15.
Nanotechnology ; 35(13)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38035400

ABSTRACT

In recent years, notable headway has been made in augmenting supercapacitor functioning through employment of pioneering components, exceptional nanostructures and additional investigation of electrolytes. Nonetheless, achieving superior performance with straightforward techniques remains a significant hurdle. In order to surmount this, an experimental three-dimensional nanospherical pore structure (TPB-20@Ni(OH)2) was designed and prepared. TPB-1 was obtained through carbonisation and activation. TPB-20@Ni(OH)2nanoparticles were synthesized using TPB-1 as the carbon source and nickel chloride hexahydrate as the nickel source. Furthermore, the TPB-20@Ni(OH)2//AC supercapacitor displayed an impressive energy density of 22.1 Wh kg-1. The TPB-20@Ni(OH)2composites exhibited a specific capacity of 978 F-1, which is noteworthy. The exceptional output exhibited by the TPB-20@Ni(OH)2composite derives from its innovative structure, presenting an extensive specific surface area of 237.4 m2g-1and porosity of roughly 4.0 nm. Following 20 000 cycles (at a current density of 1 A g-1), asymmetric supercapacitors assembled from TPB-20@Ni(OH)2//AC retained 80.0% of its initial specific electrostatic capacity, indicating superior electrochemical stability and high electrochemical reversibility.

16.
Environ Sci Technol ; 58(12): 5589-5597, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38485130

ABSTRACT

Heavy metal pollution treatment in industrial wastewater is crucial for protecting biological and environmental safety. However, the highly efficient and selective removal of heavy metal ions from multiple cations in wastewater is a significant challenge. This work proposed a pulse electrochemical method with a low-/high-voltage periodic appearance to selectively recover heavy metal ions from complex wastewater. It exhibited a higher recovery efficiency for heavy metal ions (100% for Pb2+ and Cd2+, >98% for Mn2+) than other alkali and alkaline earth metal ions (Na+, Ca2+, and Mg2+ were kept below 3.6, 1.3, and 2.6%, respectively) in the multicomponent solution. The energy consumption was only 34-77% of that of the direct current electrodeposition method. The results of characterization and experiment unveil the mechanism that the low-/high-voltage periodic appearance can significantly suppress the water-splitting reaction and break the mass-transfer limitation between heavy metal ions and electrodes. In addition, the plant study demonstrates the feasibility of treated wastewater for agricultural use, further proving the high sustainability of the method. Therefore, it provides new insights into the selective recovery of heavy metals from industrial wastewater.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Wastewater , Metals, Heavy/chemistry , Electricity , Water , Ions , Adsorption , Water Pollutants, Chemical/chemistry
17.
Environ Res ; 257: 119254, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815715

ABSTRACT

In recent years, increasing demand for inland river water quality precision management has heightened the necessity for real-time, rapid, and continuous monitoring of water conditions. By analyzing the optical properties of water bodies remotely, unmanned aerial vehicle (UAV) hyperspectral imaging technology can assess water quality without direct contact, presenting a novel method for monitoring river conditions. However, there are currently some challenges to this technology that limit the promotion application of this technology, such as underdeveloped sensor calibration, atmospheric correction algorithms, and limitations in modeling non-water color parameters. This article evaluates the advantages and disadvantages of traditional sensor calibration methods and considers factors like sensor aging and adverse weather conditions that impact calibration accuracy. It suggests that future improvements should target hardware enhancements, refining models, and mitigating external interferences to ensure precise spectral data acquisition. Furthermore, the article summarizes the limitations of various traditional atmospheric correction methods, such as complex computational requirements and the need for multiple atmospheric parameters. It discusses the evolving trends in this technology and proposes streamlining atmospheric correction processes by simplifying input parameters and establishing adaptable correction algorithms. Simplifying these processes could significantly enhance the accuracy and feasibility of atmospheric correction. To address issues with the transferability of water quality inversion models regarding non-water color parameters and varying hydrological conditions, the article recommends exploring the physical relationships between spectral irradiance, solar zenith angle, and interactions with water constituents. By understanding these relationships, more accurate and transferable inversion models can be developed, improving the overall effectiveness of water quality assessment. By leveraging the sensitivity and versatility of hyperspectral sensors and integrating interdisciplinary approaches, a comprehensive database for water quality assessment can be established. This database enables rapid, real-time monitoring of non-water color parameters which offers valuable insights for the precision management of inland river water quality.

18.
Environ Res ; 247: 118357, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38325782

ABSTRACT

The widespread occurrence of organic antibiotic pollution in the environment and the associated harmful effects necessitate effective treatment method. Heterogeneous electro-Fenton (hetero-EF) has been regarded as one of the most promising techniques towards organic pollutant removal. However, the preparation of efficient cathode still remains challenging. Herein, a novel metal-organic framework (MOF)-derived Fe/Ni@C marigold-like nanosheets were fabricated successfully for the degradation of oxytetracycline (OTC) by serving as the hetero-EF cathode. The FeNi3@C (Fe/Ni molar ratio of 1:3) based hetero-EF system exhibited 8.2 times faster OTC removal rate than that of anodic oxidation and possessed many advantages such as excellent OTC degradation efficiency (95.4% within 90 min), broad environmental adaptability (satisfactory treatment performance for multiple antibiotics under various actual water matrixes), good stability and reusability, and significant toxicity reduction. The superior hetero-EF catalytic performance was mainly attributed to: 1) porous carbon and Ni existence were both conducive to the in-situ generation of H2O2 from dissolved O2; 2) the synergistic effects of bimetals together with electron transfer from the cathode promoted the regeneration of ≡ FeII/NiII, thereby accelerating the production of reactive oxygen species; 3) the unique nanosheet structure derived from the precursor two-dimensional Fe-Ni MOFs enhanced the accessibility of active sites. This work presented a promising hetero-EF cathode for the electrocatalytic treatment of antibiotic-containing wastewaters.


Subject(s)
Metal-Organic Frameworks , Oxytetracycline , Water Pollutants, Chemical , Anti-Bacterial Agents , Hydrogen Peroxide/chemistry , Oxidation-Reduction , Electrodes , Water Pollutants, Chemical/analysis
19.
Nucleic Acids Res ; 50(D1): D265-D272, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34871445

ABSTRACT

Piwi-interacting RNAs are a type of small noncoding RNA that have various functions. piRBase is a manually curated resource focused on assisting piRNA functional analysis. piRBase release v3.0 is committed to providing more comprehensive piRNA related information. The latest release covers >181 million unique piRNA sequences, including 440 datasets from 44 species. More disease-related piRNAs and piRNA targets have been collected and displayed. The regulatory relationships between piRNAs and targets have been visualized. In addition to the reuse and expansion of the content in the previous version, the latest version has additional new content, including gold standard piRNA sets, piRNA clusters, piRNA variants, splicing-junction piRNAs, and piRNA expression data. In addition, the entire web interface has been redesigned to provide a better experience for users. piRBase release v3.0 is free to access, browse, search, and download at http://bigdata.ibp.ac.cn/piRBase.


Subject(s)
Databases, Nucleic Acid , Genome , RNA, Small Interfering/genetics , User-Computer Interface , Animals , Datasets as Topic , Humans , Internet , Molecular Sequence Annotation , Multigene Family , RNA Splicing , RNA, Small Interfering/classification , RNA, Small Interfering/metabolism
20.
Nurs Res ; 73(2): 149-157, 2024.
Article in English | MEDLINE | ID: mdl-37916850

ABSTRACT

BACKGROUND: There is heterogeneity in depressive symptoms. However, latent classes of depressive symptoms and the transition and influences of these in young and middle-aged stroke patients are unclear. OBJECTIVES: The aim of this study was to identify the latent classes of depressive symptoms and their transition patterns over time and the influencing factors in young and middle-aged stroke patients from stabilization to 6 months after discharge. METHODS: This is a longitudinal study following the Strengthening the Reporting of Observational Studies in Epidemiology checklist. A total of 272 young and middle-aged stroke participants were recruited from a hospital neurology ward in Henan Province, China. Participants completed a questionnaire on sociodemographic and health information. Latent transition analysis was used to evaluate the transition pattern of latent classes from stabilization to 6 months after discharge and its influencing factors. RESULTS: One hundred seventy-nine participants were included in the analysis. Three latent classes of depressive symptoms were identified as "mild symptoms," "grief-sleep-fatigue symptoms," and "severe symptoms." Most participants remained in the original latent class from stabilization to 6 months after discharge (probability of 83.8%, 83.8%, and 88.8%). From 3 to 6 months after discharge, the participants with fewer complications were more likely to transition into the mild symptom class. DISCUSSION: The findings indicate that from stabilization to 6 months after discharge, depressive symptoms in young and middle-aged stroke patients in China transitioned gradually from the severe symptom class to the mild symptom. Patients with fewer numbers of poststroke complications were more likely to transition to the mild symptoms class. Future research should focus on depressive symptoms in early-stage stroke patients and provide sufficient psychological support to patients with a high number of complications.


Subject(s)
Depression , Stroke , Humans , Middle Aged , Depression/epidemiology , Depression/etiology , Depression/psychology , Grief , Longitudinal Studies , Patients , Stroke/complications
SELECTION OF CITATIONS
SEARCH DETAIL