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1.
Food Chem ; 462: 141063, 2025 Jan 01.
Article in English | MEDLINE | ID: mdl-39226640

ABSTRACT

In this research, the TT-COF(Fe)@NH2-CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH2-CNTs with active site (Fe), where TT-COF@NH2-CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH2-CNTs) as raw materials. The complex TT-COF(Fe)@NH2-CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH2-CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 µM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH2-CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH2-CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs.


Subject(s)
Electrochemical Techniques , Luteolin , Nanotubes, Carbon , Nanotubes, Carbon/chemistry , Luteolin/chemistry , Luteolin/analysis , Electrochemical Techniques/instrumentation , Limit of Detection , Metal-Organic Frameworks/chemistry , Food Contamination/analysis , Catalytic Domain
2.
Vet Res ; 55(1): 126, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350238

ABSTRACT

Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs.


Subject(s)
Fatty Acid Transport Proteins , Helminth Proteins , Larva , Lipid Metabolism , Trichinella spiralis , Animals , Trichinella spiralis/genetics , Trichinella spiralis/physiology , Trichinella spiralis/metabolism , Trichinella spiralis/growth & development , Fatty Acid Transport Proteins/metabolism , Fatty Acid Transport Proteins/genetics , Larva/growth & development , Larva/metabolism , Helminth Proteins/metabolism , Helminth Proteins/genetics , Molting/physiology , Mice , Female , Trichinellosis/parasitology , Trichinellosis/veterinary
3.
J Am Chem Soc ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39353155

ABSTRACT

Interfacial contact electrification can catalyze redox reactions through a process called contact-electro-catalysis (CEC). The two main reaction paths for producing reactive oxygen species via CEC are the water oxidation reaction (WOR) and the oxygen reduction reaction (ORR). Herein, we designed a polymer/metal Janus composite catalyst that regulated the reaction rates of the WOR and ORR based on the catalyst composition. The ORR was preferentially enhanced when the polymer was negatively charged during contact electrification, while the WOR was preferentially enhanced when the polymer was positively charged. This phenomenon was observed for various conductive materials. The increase in the enhancement of the reaction rates depended on the conductivity and work function of the metal. We expect that this efficient CEC method can form a universal strategy for improving the performance of existing catalysts, as contact electrification is common in nature.

4.
Biomaterials ; 314: 122871, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39368275

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 µA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.

5.
Plant Physiol Biochem ; 216: 109181, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39369647

ABSTRACT

MYB12 is a key regulator that has been shown to promote the accumulation of various phenylpropanoid compounds in plants. However, the regulation of MYB12 gene is largely unknown. In this study, we found that overexpression of the NtMYB59 gene significantly inhibited the accumulation of chlorogenic acid (CGA), flavonols, and anthocyanins in tobacco, while knock-down and knock-out of NtMYB59 significantly increased the contents of these polyphenol compounds. Transcriptome analysis between WT and NtMYB59-OE plants revealed several differentially expressed genes (DEGs) encoding crucial enzymes in the phenylpropanoid pathway and the transcription factor NtMYB12. ChIP-seq assay further indicated that NtMYB12 might be a direct target of NtMYB59. Subsequent yeast one-hybrid, electrophoretic mobility shift assay, and Dual-Luciferase assays confirmed that NtMYB59 directly binds to the promoter of NtMYB12 to inhibit its expression. Moreover, loss-function of NtMYB59 significantly promoted the accumulation of flavonols and anthocyanins in ntmyb59, but their contents in ntmyb59/ntmyb12 double mutants were significantly lower than that of WT and ntmyb59 plants, indicating that the regulation of NtMYB59 on flavonoids biosynthesis depends on the activity of NtMYB12. Our study revealed that NtMYB59 regulates the expression of NtMYB12, and provided new potential strategies for modulating phenylpropanoids biosynthesis in tobacco.

6.
Chem Sci ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39386906

ABSTRACT

In this study, Förster resonance energy transfer (FRET) is harnessed to construct a novel stimulus-responsive long-persistent luminescence (LPL) system. Two organic molecules, DPSD and DPOD, were initially found to have no afterglow under ambient conditions, but exhibited prolonged afterglow upon friction with paper, showing a significantly promoted transition of triplet excited states. Substituting paper with α-cellulose (the main composition of paper) reveals a novel host-guest long afterglow system and allows for a deeper investigation of the above paper-promoted LPL phenomenon. The activation of the LPL effect was achieved by matrixing these components through a grinding process, capitalizing on the efficient FRET from the host to the guest owing to the appropriate energy level match, and the robust intersystem crossing (ISC) capability of the guest. This model presents a new matrix strategy to achieve efficient LPL by a facile, low cost and easy-to-handle process. Furthermore, we successfully implemented anti-counterfeiting, encryption and decryption, decoration, and water/heat stimulus-responsive applications of the obtained materials. These advancements bring LPL materials one step closer to practical commercialization.

7.
Langmuir ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39383311

ABSTRACT

An ingenious microstructure of electromagnetic microwave absorption materials is crucial to achieve strong absorption and a broad bandwidth. Herein, one-dimensional (1D) carbon fibers with implantation of zero-dimensional (0D) ZIF-8-derived carbon frameworks and construction of a three-dimensional (3D) microcosmic multichannel porous structure are fabricated by electro-blown spinning, solvent-thermal reaction, and high-temperature pyrolysis techniques. The 1D carbon fiber skeleton with a multichannel structure provides a direct axial conductive pathway for charge transport, which plays an important role in dielectric loss. The 0D surface carbon frameworks offer plenty of heterogeneous interfaces to trigger intensive interfacial polarization loss and act as dihedral angles for microwave scattering. The 3D microcosmic multichannel pores can not only generate multiple reflections as much as possible to dissipate electromagnetic microwave energy but also supply huge interior cavities to improve impedance matching. Thanks to the synergistic effect of a strong electrically conductive pathway for enhancing the conductive loss, a plenteous heterogeneous interface for triggering intensive interfacial polarization loss, microcosmic multichannel pores for generating multiple reflections and improving impedance matching, and N and O atom doping for inducing dipole polarization, the optimal sample with an ingenious microstructure delivers an excellent absorption performance of a minimum reflection loss of -35.5 dB at a thickness of 5.0 mm and an effective absorption bandwidth of 6.72 GHz (10.96-17.68 GHz) at a thickness of 2.0 mm. Such a well-designed multichannel porous carbon fiber may pave the way for the exploitation of high-performance microwave absorbing materials.

8.
Angew Chem Int Ed Engl ; : e202417593, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39384546

ABSTRACT

Afterglow materials have garnered significant interest due to distinct photophysical characteristics. However, it is still difficult to achieve long afterglow phosphorescence from organic molecules due to aggregation-caused quenching (ACQ) and energy dissipation. In addition, most materials reported so far have long afterglow emission only at room or even low temperatures, and mainly use UV light as an excitation source. In this work, we report a strategy to achieve high temperature long afterglow emission through the assembly of isolated 0D metal-organic cages (MOCs). In which, both ACQ and phosphorescence quenching effects are effectively mitigated by altering the stacking mode of organic chromophores through orthogonally anchoring into the edges of cubic MOCs. Furthermore, improvement in molecular rigidity, promotion of spin-orbit coupling and broadening of the absorption range are achieved through the MOC- engineering strategy. As a result, we successfully synthesized MOCs that can produce afterglow emission even after excitation by WLEDs at high temperatures (380 K). Moreover, the MOCs are capable of generating afterglow emissions when excited by mobile phone flashlight at room temperature. Given these features, the potential applications of MOCs in the visual identification of explosives, information encryption and multicolor display are explored.

9.
CNS Neurosci Ther ; 30(10): e70077, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39385316

ABSTRACT

AIMS: Bipolar depression poses an overwhelming suicide risk. We aimed to examine the efficacy and safety of transcranial direct current stimulation (tDCS) combined with quetiapine in bipolar patients as a suicidal intervention. METHODS: In a single-center, double-blind, treatment-naive bipolar depression patients with suicidal ideation were randomly assigned to quetiapine in combination with either active (n = 16) or sham (n = 15) tDCS over the left dorsolateral prefrontal cortex for three consecutive weeks. The 30-min, 2-mA tDCS was conducted twice a day on the weekday of the first week and then once a day on the weekdays of the two following weeks. Primary efficacy outcome measure was the change in the Beck Scale for Suicidal Ideation (BSSI). Secondary outcomes included changes on the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Outcome was evaluated on Day 3 and weekend. Safety outcome was based on the reported adverse reactions. RESULTS: Active tDCS was superior to sham tDCS on the BSSI at Day 3 and tended to sustain every weekend during the treatment process, compared to baseline. However, no difference between active and sham in HDRS-17 and MADRS was found. Response and remission rate also supported the antisuicide effect of tDCS, with higher response and remission rate in BSSI, but no antidepressant effect, compared to sham, over time. Regarding safety, active tDCS was well tolerated and all the adverse reactions reported were mild and limited to transient scalp discomfort. CONCLUSION: The tDCS was effective as an antisuicide treatment for acute bipolar depression patients with suicidal ideation, with minimal side effects reported.


Subject(s)
Bipolar Disorder , Suicidal Ideation , Transcranial Direct Current Stimulation , Humans , Bipolar Disorder/therapy , Bipolar Disorder/psychology , Male , Female , Transcranial Direct Current Stimulation/methods , Adult , Double-Blind Method , Middle Aged , Treatment Outcome , Psychiatric Status Rating Scales , Quetiapine Fumarate/therapeutic use , Young Adult , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/adverse effects , Combined Modality Therapy/methods
10.
Drug Resist Updat ; 77: 101158, 2024 Oct 06.
Article in English | MEDLINE | ID: mdl-39395327

ABSTRACT

AIMS: Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC). METHODS: We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies. RESULTS: The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume. CONCLUSION: Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.

11.
Chem Asian J ; : e202400930, 2024 Oct 14.
Article in English | MEDLINE | ID: mdl-39400508

ABSTRACT

Heteroatom-doped porous carbons (HPCs) have been considered promising electrode materials for supercapacitors due to their improvement of energy density by providing extra pseudocapacity. Covalent organic frameworks (COFs) are obtaining great importance in energy storage because of their designable structure and versatile functionality. Herein, we designed and fabricated oxygen and sulfur dual-doped covalent organic framework (COF) derived HPCs with very high heteroatoms content (up to 25.76 atom%) via a facile coupling reaction. The optimized HPCs exhibit a porous structure with high specific surface area (up to 2835 m2 g-1) along with a high specific capacitance (430 F g-1 at 0.5 A g-1), excellent capacitance retention (96.9%), and high coulombic efficiency (98.5%) after 10000 cycles at 5 A g-1. As electrodes for aqueous symmetric supercapacitors, the HPCs exhibits a high energy density of 60 Wh kg-1 at a 250 W kg-1 power density, excellent cycling stability of capacity retention (82.2%) and a high coulombic efficiency (92.3%) after 10000 cycles at 10 A g-1, indicating attractive application potential in chemical energy storage. This work establishes a promising strategy for preparation of high heteroatom content HPCs using COFs and demonstrates great potential for energy storage/conversion devices.

12.
Org Biomol Chem ; 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39387614

ABSTRACT

In the presence of Na2CO3, the combination of PdCl2(dppf), dppp and CuI catalyzes the decarbonylative coupling of arylcarboxylic acid 2-pyridyl esters with terminal alkynes to afford 1,2-disubstituted acetylenes. (Hetero)aryl, alkyl, and silylacetylenes and various electron-donating and -withdrawing group-substituted arylcarboxylic acid 2-pyridyl esters can be used in this transformation, with a range of functional groups showing compatibility.

13.
Int J Biol Macromol ; 280(Pt 4): 135958, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39322156

ABSTRACT

C-type lectin (CTL) plays a vital role in parasite adhesion, invading host's cells and immune escape. The objective of this research was to explore whether recombinant T. spiralis CTL (rTsCTL) binding with syndecan-1 damages intestine epithelial integrity and mediates T. spiralis intrusion in mice. The results showed that rTsCTL interacted with syndecan-1 and activated STAT3 pathway in gut epithelium, decreased tight junctions (TJs) expressions and damaged gut epithelium integrity, promoted T. spiralis intrusion, and increased expression level of inflammatory cytokine and mucin. The syndecan-1 inhibitor (ß-xyloside) and STAT3 phosphorylation inhibitor (Stattic) significantly suppressed syndecan-1 expression and STAT3 pathway activation, reduced the expression levels of TJs, pro-inflammatory cytokines (TNF-α and IL-1ß), Muc2 and Muc5ac, and declined intestinal permeability in T. spiralis-infected mice. These results revealed that the inhibitors suppressed T. spiralis invasion and development in gut mucosa, decreased intestinal adult burdens and relieved gut inflammation. These findings further testified that the in vivo binding of TsCTL with syndecan-1 destroyed enteral mucosal epithelial integrity and promoted T. spiralis intrusion of gut mucosa via activating STAT3 pathway and decreasing TJs expression. TsCTL could be deemed as a promising vaccine target to interrupt T. spiralis infection.

14.
J Phys Chem Lett ; 15(38): 9575-9584, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39269336

ABSTRACT

Ligand engineering of aromatic heterocyclic cations in two-dimensional (2D) Dion-Jacobson (DJ) perovskites has been widely explored in recent years. In this study, how the positional isomers of aromatic heterocyclic cations tune the lattice of 2D perovskites, thereby influencing the transport and recombination dynamics of charge carriers, has been investigated through nonadiabatic molecular dynamics simulations. We demonstrate that the meta-substituted 3-(aminomethyl)pyridinium (3AMPY) cations greatly reduce the strength of electron-vibration coupling since the strong hydrogen-bonding network introduced by the changes in the arrangement of spacer cations significantly suppresses the structural thermal fluctuations. Compared to the para-substituted 4-(aminomethyl)pyridinium (4AMPY) cation, using the asymmetric 3AMPY as a spacer cation can achieve improved in-plane transport performance, enhanced thermal stability, and suppressed charge carrier recombination through weakening electron-vibration interactions. Our results explain the observed lifetime difference between the two types of DJ-phase perovskites in experiments and provide new guidance for optimizing the performance of perovskite devices.

15.
Front Microbiol ; 15: 1422941, 2024.
Article in English | MEDLINE | ID: mdl-39318431

ABSTRACT

The McMurdo Dry Valleys (MDVs) of Antarctica are a mosaic of extreme habitats which are dominated by microbial life. The MDVs include glacial melt holes, streams, lakes, and soils, which are interconnected through the transfer of energy and flux of inorganic and organic material via wind and hydrology. For the first time, we provide new data on the viral community structure and function in the MDVs through metagenomics of the planktonic and benthic mat communities of Lakes Bonney and Fryxell. Viral taxonomic diversity was compared across lakes and ecological function was investigated by characterizing auxiliary metabolic genes (AMGs) and predicting viral hosts. Our data suggest that viral communities differed between the lakes and among sites: these differences were connected to microbial host communities. AMGs were associated with the potential augmentation of multiple biogeochemical processes in host, most notably with phosphorus acquisition, organic nitrogen acquisition, sulfur oxidation, and photosynthesis. Viral genome abundances containing AMGs differed between the lakes and microbial mats, indicating site specialization. Using procrustes analysis, we also identified significant coupling between viral and bacterial communities (p = 0.001). Finally, host predictions indicate viral host preference among the assembled viromes. Collectively, our data show that: (i) viruses are uniquely distributed through the McMurdo Dry Valley lakes, (ii) their AMGs can contribute to overcoming host nutrient limitation and, (iii) viral and bacterial MDV communities are tightly coupled.

16.
J Exp Med ; 221(10)2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39321257

ABSTRACT

Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.


Subject(s)
CD4-Positive T-Lymphocytes , Cell Differentiation , Immunologic Memory , Memory T Cells , Humans , CD4-Positive T-Lymphocytes/immunology , Cell Differentiation/immunology , Animals , Immunologic Memory/immunology , Memory T Cells/immunology , Mice , Interferon Type I/metabolism , Interferon Type I/immunology , Lymphocyte Activation/immunology
17.
Neoplasia ; 57: 101055, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39260131

ABSTRACT

BACKGROUND: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. METHODS: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. RESULTS: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. CONCLUSION: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.


Subject(s)
Disease Progression , Glioblastoma , Heat Shock Transcription Factors , Sumoylation , Glioblastoma/metabolism , Glioblastoma/pathology , Glioblastoma/genetics , Humans , Heat Shock Transcription Factors/metabolism , Heat Shock Transcription Factors/genetics , Animals , Mice , Cell Line, Tumor , Cell Proliferation , Apoptosis , Disease Models, Animal , Unfolded Protein Response , Xenograft Model Antitumor Assays , Cell Movement , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics
18.
Neoplasia ; 57: 101049, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39265220

ABSTRACT

Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa. ELAVL1 interacts with PD-L1 mRNA and promotes PD-L1 RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression.


Subject(s)
B7-H1 Antigen , CD4-Positive T-Lymphocytes , ELAV-Like Protein 1 , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms , RNA Stability , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/immunology , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/immunology , ELAV-Like Protein 1/metabolism , ELAV-Like Protein 1/genetics , Cell Line, Tumor , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , RNA, Messenger/genetics
19.
Aging Cell ; : e14342, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39312903

ABSTRACT

The locus coeruleus (LC)-prefrontal cortex (PFC) circuitry is crucial for cognition, planning, posture and mobility. This study examines the role of norepinephrine (NE) in elucidating the neurobiological basis of age-related cognitive and motor declines. Aged mice exhibited reduced spatial learning, impaired memory, decreased physical endurance, and notable changes in locomotor behavior. The neurochemical foundations of these deficits were investigated through fast-scan cyclic voltammetry to measure NE release in the PFC and LC, both in vivo and in brain slices. Additionally, oxygen levels were monitored as a proxy for PFC neuronal function, and NE levels were analyzed in the extracellular space via microdialysis and total content in the PFC. Aged mice exhibited a frequency-dependent increase in NE release in the PFC upon LC stimulation, suggesting alterations in neural responsiveness due to aging. We also recorded slower NE reuptake rates and increased NE content and neuronal activity, indicated by higher oxygen levels and facilitated neuron activation due to membrane depolarization recorded via whole-cell patch-clamp. To understand the basis for LC-driven NE surges in the PFC with aging, we examined the expression levels of two proteins critical for presynaptic NE release and NE reuptake: the α2a-adrenergic receptor and the NE transporter. Both showed a significant decrease in the PFC with aging. These findings support the concept that aging significantly alters the structural and functional dynamics within the LC-PFC neural circuit, impacting NE modulation and neuronal activity, which may underlie the observed declines in cognitive and motor functions in aging populations.

20.
Genes (Basel) ; 15(9)2024 Sep 08.
Article in English | MEDLINE | ID: mdl-39336770

ABSTRACT

Fertilization significantly affects the growth and development of wheat. However, the precise mechanisms underlying gene regulation during flowering in response to fertilization deficiency remain elusive. In this study, fertilization (F) and non-fertilization (CK) ) treatments were set up to reveal examine the effect of fertilization on the photosynthetic capacity of winter wheat during the flowering period through physiological, biochemical, and transcriptome analyses. Upon analyzing analysing their yield, leaf photosynthetic system exchange parameters during flowering, antioxidant enzyme activity, and endogenous hormone parameters, we found that the F treatment resulted in higher net photosynthetic rates during flowering periods than the CK treatment. The superoxide dismutase (SOD) (83.92%), peroxidase (POD) (150.75%), and catalase (CAT) (22.74%) activities of leaves in treated with F during the flowering period were notably elevated compared to those of CK-treated leaves. Abscisic acid (ABA) (1.86%) and gibberellin acid (GA3) (33.69%) levels were reduced, whereas Auxin auxin (IAA) (98.27%) content was increasedwas increased under F treatment compared to those the results under the CK treatment. The chlorophyll a (32.53%), chlorophyll b (56%), total chlorophyll (37.96%), and carotenoid contents (29.80%) under F treatment were also increased compared to CK., exceeded exceeding those obtained under the CK treatment. Furthermore, transcriptional differences between the F and CK conditions were analyzed, and key genes were screened and validated by using q-PCR. Transcriptome analysis identified 2281 differentially expressed genes (DEGs), with enriched pathways related to photosynthesis and light harvesting. DEGs were subjected to cluster simulation, which revealed that 53 DEGS, both up- and down-regulated, responded to the F treatment. qRT-PCR-based validation confirmed the differential expression of genes associated with carbohydrate transport and metabolism, lipid transport, and signal transduction. This study revealed distinctive transcriptional patterns and crucial gene regulation networks in wheat during flowering under fertilization, providing transcriptomic guidance for the precise regulation of wheat breeding.


Subject(s)
Flowers , Gene Expression Regulation, Plant , Photosynthesis , Plant Leaves , Triticum , Triticum/genetics , Triticum/growth & development , Triticum/metabolism , Photosynthesis/genetics , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/metabolism , Flowers/genetics , Flowers/growth & development , Gene Expression Profiling/methods , Abscisic Acid/metabolism , Transcriptome , Plant Growth Regulators/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Chlorophyll/metabolism , Gibberellins/metabolism , Fertilizers , Indoleacetic Acids/metabolism
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