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1.
ChemSusChem ; : e202401121, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39171666

RESUMO

Electrocatalytic oxygen reduction reaction via 2e- pathway is a safe and friendly route for hydrogen peroxide (H2O2) synthesis. In order to achieve efficient synthesis of H2O2, it is essential to accurately control the active sites. Here, fragmented polymetric carbon nitride with rich defects (DCN) is designed for H2O2 electrosynthesis. The multi-type defects, including the sodium atom doping in six-fold cavities, the boron atom doping at N-B-N sites and the cyano groups, are successfully created. Owing to the synergistic effect of these defects, the fragmented DCN achieves a high H2O2 yield of 2.28 mol gcat.-1 h-1 and a high Faradic efficiency of nearly 90% in alkaline media at 0.4 V vs. RHE in H-type cell. In neutral media, the H2O2 concentration produced by DCN can reach 1815 mM within 6 h at a potential of 0.2 V vs. RHE, and the H2O2 production rate of DCN is 0.23 mol gcat.-1 h-1. In addition, DCN shows excellent long-term durability in alkaline and neutral media. This study provides a new approach for the design and development of the boron, nitrogen doped carbon-based electrocatalysts for H2O2 electrochemical synthesis.

2.
ACS Nano ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058358

RESUMO

Photocatalytic H2O2 production has attracted much attention as an alternative way to the industrial anthraquinone oxidation process but is limited by the weak interaction between the catalysts and reactants as well as inefficient proton transfer. Herein, we report on a hydrogen-bond-broken strategy in carbon nitride for the enhancement of H2O2 photosynthesis without any sacrificial agent. The H2O2 photosynthesis is promoted by the hydrogen bond formation between the exposed N atoms on hydrogen-bond-broken carbon nitride and H2O molecules, which enhances proton-coupled electron transfer and therefore the photocatalytic activity. The exposed N atoms serve as proton buffering sites for the proton transfer from H2O molecules to carbon nitride. The H2O2 photosynthesis is also enhanced through the enhanced adsorption and reduction of O2 gas toward H2O2 on hydrogen-bond-broken carbon nitride because of the formation of nitrogen vacancies (NVs) and cyano groups after the intralayer hydrogen bond breaking on carbon nitride. A high light-to-chemical conversion efficiency (LCCE) value of 3.85% is achieved. O2 and H2O molecules are found to undergo a one-step two-electron reduction pathway by photogenerated hot electrons and a four-electron oxidation process to produce O2 gas, respectively. Density functional theory (DFT) calculations validate the O2 adsorption and reaction pathways. This study elucidates the significance of the hydrogen bond formation between the catalyst and reactants, which greatly increases the proton tunneling dynamics.

3.
Small ; : e2403050, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984752

RESUMO

Applications of aqueous zinc ion batteries (ZIBs) for grid-scale energy storage are hindered by the lacking of stable cathodes with large capacity and fast redox kinetics. Herein, the intercalation of tetramethylammonium (TMA+) cations is reported into MoS2 interlayers to expand its spacing from 0.63 to 1.06 nm. The pre-intercalation of TMA+ induces phase transition of MoS2 from 2H to 1T phase, contributing to an enhanced conductivity and better wettability. Besides, The calculation from density functional theory indicates that those TMA+ can effectively shield the interactions between Zn2+ and MoS2 layers. Consequently, two orders magnitude high Zn2+ ions diffusion coefficient and 11 times enhancement in specific capacity (212.4 vs 18.9 mAh g‒1 at 0.1 A g‒1) are achieved. The electrochemical investigations reveal both Zn2+ and H+ can be reversibly co-inserted into the MoS2-TMA electrode. Moreover, the steady habitat of TMA+ between MoS2 interlayers affords the MoS2-TMA with remarkable cycling stability (90.1% capacity retention after 2000 cycles at 5.0 A g‒1). These performances are superior to most of the recent zinc ion batteries assembled with MoS2 or VS2-based cathodes. This work offers a new avenue to tuning the structure of MoS2 for aqueous ZIBs.

4.
Inorg Chem ; 63(27): 12433-12444, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38907721

RESUMO

High-entropy oxides are a new type of material with significant application potential. However, the lack of a universal HEO preparation method severely limits the property study and application of HEOs. Herein, we report a universal approach of spray pyrolysis for the preparation of various HEOs and study the electrocatalytic performance of HEOs toward the oxygen evolution reaction. FeCoNiMoWOx HEO exhibits an overpotential of 281 mV at 10 mA cm-2 and a Tafel slope of 34.5 mV dec-1, which are far superior to those of the corresponding medium-entropy oxide and low-entropy oxide. It is found that the high entropy of the HEO greatly strengthens the interaction between Fe and Mo/W and produces abundant oxygen vacancies (OVs) around Mo and W. This work not only provides a universal preparation method for HEOs but also deepens our understanding of OER catalytic activity of HEOs.

5.
Adv Sci (Weinh) ; 11(7): e2305991, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087938

RESUMO

Ti3 C2 Tx Quantum dots (QDs)/L-Ti3 C2 Tx fiber electrode (Q3 M7 ) with high capacitance and excellent flexibility is prepared by a wet spinning method. The assembled units Ti3 C2 Tx nanosheets (NSs) with large size (denoted as L-Ti3 C2 Tx ) is obtained by natural sedimentation screen raw Ti3 AlC2 , etching, and mechanical delamination. The pillar agent Ti3 C2 Tx QDs is fabricated by an ultrasound method. Q3 M7 fiber electrode gave a specific capacitance of 1560 F cm-3 , with a capacity retention rate of 79% at 20 A cm-3 , and excellent mechanical strength of 130 Mpa. A wide temperature all-solid-state the delaminated montmorillonite (F-MMT)/Polyvinyl alcohol (PVA) dimethyl sulfoxide (DMSO) flexible hydrogel (DHGE) (F-MMT/PVA DHGE) Q3 M7 fiber supercapacitor is assembled by using Q3 M7 fiber as electrodes and F-MMT/PVA DHGE as electrolyte and separator. It showed a volume specific capacitance of 413 F cm-3 at 0.5 A cm-3 , a capacity retention of 97% after 10 000 cycles, an energy density of 36.7 mWh cm-3 at a power density of 311 mW cm-3 , and impressive capacitance and flexibility over a wide temperature range of -40 to 60 °C. This work provides an effective strategy for designing and assembling wide temperature all-solid-state fiber supercapacitors with optimal balance of capacitive performance and flexibility.

6.
Nano Lett ; 23(18): 8734-8742, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37669506

RESUMO

In order to improve the fluorescence quantum yield (QY) of NIR-II-emitting nanoparticles, D-A-D fluorophores are typically linked to intramolecular rotatable units to reduce aggregation-induced quenching. However, incorporating such units often leads to a twisted molecular backbone, which affects the coupling within the D-A-D unit and, as a result, lowers the absorption. Here, we overcome this limitation by cross-linking the NIR-II fluorophores to form a 2D polymer network, which simultaneously achieves a high QY by well-controlled fluorophore separation and strong absorption by restricting intramolecular distortion. Using the strategy, we developed polymer dots with the highest NIR-II single-particle brightness among reported D-A-D-based nanoparticles and applied them for imaging of hindlimb vasculatures and tumors as well as fluorescence-guided tumor resection. The high brightness of the polymer dots offered exceptional image quality and excellent surgical results, showing a promising performance for these applications.


Assuntos
Nanopartículas , Neoplasias , Pontos Quânticos , Animais , Humanos , Polímeros , Imagem Óptica/métodos , Corantes Fluorescentes
7.
Nat Commun ; 14(1): 4212, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452037

RESUMO

Kinase inhibitors against Cyclin Dependent Kinase 4 and 6 (CDK4/6i) are promising cancer therapeutic drugs. However, their effects are limited by primary or acquired resistance in virtually all tumor types. Here, we demonstrate that Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) controls CDK4/6i response in lung cancer by forming a feedback loop with CDK6. LRPPRC binds to CDK6-mRNA, increasing the stability and expression of CDK6. CDK6 and its downstream E2F Transcription Factor 1 (E2F1), bind to the LRPPRC promoter and elevate LRPPRC transcription. The activation of the LRPPRC-CDK6 loop facilitates cell cycle G1/S transition, oxidative phosphorylation, and cancer stem cell generation. Gossypol acetate (GAA), a gynecological medicine that has been repurposed as a degrader of LRPPRC, enhances the CDK4/6i sensitivity in vitro and in vivo. Our study reveals a mechanism responsible for CDK4/6i resistance and provides an enlightening approach to investigating the combinations of CDK4/6 and LRPPRC inhibitors in cancer therapy.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Linhagem Celular Tumoral , Quinase 4 Dependente de Ciclina/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Quinase 6 Dependente de Ciclina/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas de Neoplasias/genética
8.
J Transl Med ; 21(1): 504, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496051

RESUMO

BACKGROUND: Ovarian cancer (OC) is the most lethal malignant gynecological tumor type for which limited therapeutic targets and drugs are available. Enhanced mitochondrial oxidative phosphorylation (OXPHOS), which enables cell growth, migration, and cancer stem cell maintenance, is a critical driver of disease progression and a potential intervention target of OC. However, the current OXPHOS intervention strategy mainly suppresses the activity of the electron transport chain directly and cannot effectively distinguish normal tissues from cancer tissues, resulting in serious side effects and limited efficacy. METHODS: We screened natural product libraries to investigate potential anti-OC drugs that target OXPHOS. Additionally, LC-MS, qRT-PCR, western-blot, clonogenic assay, Immunohistochemistry, wound scratch assay, and xenograft model was applied to evaluate the anti-tumor mechanism of small molecules obtained by screening in OC. RESULTS: Gossypol acetic acid (GAA), a widely used gynecological medicine, was screened out from the drug library with the function of suppressing OXPHOS and OC progression by targeting the leucine-rich pentatricopeptide repeat containing (LRPPRC) protein. Mechanically, LRPPRC promotes the synthesis of OXPHOS subunits by binding to RNAs encoded by mitochondrial DNA. GAA binds to LRPPRC directly and induces LRPPRC rapid degradation in a ubiquitin-independent manner. LRPPRC was overexpressed in OC, which is highly correlated with the poor outcomes of OC and could promote the malignant phenotype of OC cells in vitro and in vivo. GAA management inhibits cell growth, clonal formation, and cancer stem cell maintenance in vitro, and suppresses subcutaneous graft tumor growth in vivo. CONCLUSIONS: Our study identified a therapeutic target and provided a corresponding inhibitor for OXPHOS-based OC therapy. GAA inhibits OC progression by suppressing OXPHOS complex synthesis via targeting LRPPRC protein, supporting its potential utility as a natural therapeutic agent for ovarian cancer.


Assuntos
Neoplasias Ovarianas , Fosforilação Oxidativa , Feminino , Animais , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Mitocôndrias/metabolismo , Modelos Animais de Doenças , Proliferação de Células , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Proteínas de Neoplasias/metabolismo
9.
J Am Chem Soc ; 145(23): 12861-12869, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37276358

RESUMO

Targeted protein degradation (TPD) is an emerging technique for protein regulation. Currently, all TPD developed in eukaryotic cells relies on either ubiquitin-proteasome or lysosomal systems, thus are powerless against target proteins in membrane organelles lacking proteasomes and lysosomes, such as mitochondria. Here, we developed a mitochondrial protease targeting chimera (MtPTAC) to address this issue. MtPTAC is a bifunctional small molecule that can bind to mitochondrial caseinolytic protease P (ClpP) at one end and target protein at the other. Mechanistically, MtPTAC activates the hydrolase activity of ClpP while simultaneously bringing target proteins into proximity with ClpP. Taking mitochondrial RNA polymerase (POLRMT) as a model protein, we have demonstrated the powerful proteolytic ability and antitumor application prospects of MtPTAC, both in vivo and in vitro. This is the first modularly designed TPD that can specifically hydrolyze target proteins inside mitochondria.


Assuntos
Mitocôndrias , Proteínas , Proteólise , Mitocôndrias/metabolismo , Proteínas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Endopeptidases/metabolismo
10.
Inorg Chem ; 62(24): 9749-9757, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37300494

RESUMO

Metallic-phase MoS2 exhibits Pt-comparable electrocatalytic hydrogen evolution reaction (HER) performance in acidic conditions. However, the controllable synthesis of metallic-phase MoS2 is quite challenging because the key factor determining the phase types of MoS2 during synthesis is still unclear. Herein, the effect of organic sulfur sources on the formed MoS2 phase is studied by use of thioacetamide (TAA), l-cysteine, and thiourea as sulfur sources. The TAA and l-cysteine produce metallic MoS2, while thiourea gives rise to semiconducting MoS2. Owing to the metallic phase and smaller size, the MoS2 prepared with TAA and l-cysteine has a higher electrocatalytic HER activity than the MoS2 obtained from thiourea. The HER overpotential of MoS2 synthesized with TAA is only 210 mV for reaching the current density of 10 mA/cm2, and the corresponding Tafel slope is 44 mV/decade. Further studies find that the decomposition temperature of sulfur precursors is the key factor for the formation of metallic MoS2. Sulfur precursors with a lower decomposition temperature release sulfur ions quickly, which in turn stabilize the metallic phase and inhibit the growth of MoS2 into large sizes. Our findings unveil the key factor for controlling the phase type of MoS2 synthesized from organic sulfur precursors and will be very helpful for the synthesis of MoS2 with high electrocatalytic activity.

11.
Adv Sci (Weinh) ; 10(22): e2301682, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37195010

RESUMO

Photo-assisted Li-O2 batteries are introduced as a promising strategy for reducing severe overpotential by directly employing photocathodes. Herein, a series of size-controlled single-element boron photocatalysts are prepared by the meticulous liquid phase thinning methods by combining probe and water bath sonication, and their bifunctional photocathodes in the photo-assisted Li-O2 batteries are systematically investigated. The boron-based Li-O2 batteries have shown incremental round-trip efficiencies as the sized reduction of boron under illumination. It is noteworthy that the completely amorphous boron nanosheets (B4 ) photocathode not only delivers an optimizing round-trip efficiency of 190% on the basis of the ultra-high discharge voltage (3.55 V) and ultra-low charge voltage (1.87 V) but also gives a high rate performance and ultralong durability with a round-trip efficiency of 133% after 100 cycles (200 h) compared with the other-sized boron photocathodes. This remarkable photoelectric performance of the B4 sample can be attracted to the synergistic effect on the suitable semiconductor property, high conductivity, and strengthened catalytic ability of boron nanosheets coated with ultrathin amorphous boron-oxides overlayer. This research can open a new avenue to facilitate the rapid development of high-efficiency photo-assisted Li-O2 batteries.

12.
Adv Healthc Mater ; 12(23): e2300490, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37053081

RESUMO

Nanoenzymes have been widely explored for chemodynamic therapy (CDT) in cancer treatment. However, poor catalytic efficiency of nanoenzymes, especially in the tumor microenvironment with insufficient H2 O2 and mild acidity, limits the effect of CDT. Herein, a new ultrathin RuCu nanosheet (NS) based nanoenzyme which has a large specific surface area and abundant channels and defects is developed. The RuCu NSs show superb catalytic efficiency for the oxidation of peroxidase substrate H2 O2 at a wide range of pH and their catalytic efficiency (kcat /Km = 177.2 m-1  s-1 ) is about 14.9 times higher than that of the single-atom catalyst FeN3 P. Besides being an efficient nanozyme as peroxidase, the RuCu NSs possess other two enzyme activities, not only disproportionating superoxide anion to produce H2 O2 but also consuming glutathione to keep a high concentration of H2 O2 in the tumor microenvironment for Fenton reaction. With these advantages, the RuCu NSs exhibit good performance to kill cancer cells and inhibit tumor growth in mice, demonstrating a promising potential as new CDT reagent.


Assuntos
Neoplasias , Peroxidase , Animais , Camundongos , Peroxidases , Catálise , Glutationa , Superóxidos , Microambiente Tumoral , Peróxido de Hidrogênio , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
13.
J Colloid Interface Sci ; 643: 92-101, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37054547

RESUMO

All-solid-state Ti3C2Tx neutral symmetric fiber supercapacitors (PVA EGHG Ti3C2Tx FSCs) with high energy density and wide temperature range are constructed by using polyvinyl alcohol (PVA)-ethylene glycol hydrogel (EGHG)-sodium perchlorate (NaClO4) as electrolyte and separator, and Ti3C2Tx fiber as electrodes. Ti3C2Tx fiber is prepared using 130 mg mL-1 Ti3C2Tx nanosheet ink as an assembly unit in a coagulation bath of isopropyl alcohol (IPA) and distilled water with 5 wt% CaCl2 by a wet spinning method. The prepared Ti3C2Tx fiber exhibits a specific capacity of 385 F cm-3 and a capacitance retention of 94 % after 10,000 cycles in 1 M NaClO4 electrolyte. The assembled PVA EGHG Ti3C2Tx FSCs deliver a specific capacitance of 41 F cm-3, a volumetric energy density of 5 mWh cm-3, and a capacitance retention of 92 % after 500 times continuous bending. Furthermore, it shows good flexibility and excellent capacitance over a wide temperature range of -40 to 40 °C and maintains its electrochemical performance under varying degrees of bending. This study provides a viable strategy for designing and assembling all-solid-state neutral symmetric fiber supercapacitors with high energy density and wide temperature range.

14.
J Proteomics ; 277: 104864, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36870674

RESUMO

The present study sought to investigate the correlation between CAAP1 and platinum resistance in ovarian cancer and to preliminarily explore the potential biological function of CAAP1. Proteomic analysis was used to analyze differentially expressed proteins in platinum-sensitive and -resistant tissue samples of ovarian cancer. The Kaplan-Meier plotter was used for prognostic analysis. Immunohistochemistry assay and chi-square test were employed to explore the relationship between CAAP1 and platinum resistance in tissue samples. Lentivirus transfection, immunoprecipitation-mass spectrometry, and bioinformatics analysis were used to determine the potential biological function of CAAP1. Based on results, the expression level of CAAP1 was significantly higher in platinum-sensitive tissues compared to that in resistant tissues. Chi-square test demonstrated that there is a negative correlation between high expression of CAAP1 and platinum resistance. Overexpression of CAAP1 increased cis­platinum sensitivity of the A2780/DDP cell line likely via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. In summary, there is a negative correlation between high expression of CAAP1 and platinum resistance. CAAP1 might be a potential biomarker for platinum resistance in ovarian cancer. SIGNIFICANCE: Platinum resistance is a key factor affecting the survival of ovarian cancer patients. Understanding the mechanisms of platinum resistance is highly important for ovarian cancer management. Here, we performed the DIA- and DDA-based proteomics to analyze differentially expressed proteins in tissue and cell samples of ovarian cancer. We found that the protein identified as CAAP1, which was first reported to be involved in the regulation of apoptosis, may be negatively correlates with platinum resistance in ovarian cancer. In addition, we also found that CAAP1 enhanced the sensitivity of platinum-resistant cells to cis­platinum via the mRNA splicing pathway by interacting with the splicing factor AKAP17A. Our data would be useful to reveal novel molecular mechanisms of platinum resistance in ovarian cancer.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Linhagem Celular Tumoral , Cisplatino , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Platina , Proteômica/métodos , RNA Mensageiro
15.
ACS Appl Mater Interfaces ; 15(13): 16732-16743, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36972415

RESUMO

The sluggish four-electron processes of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) limit the development of rechargeable Zn-air batteries (RZABs). Highly efficient ORR/OER bifunctional electrocatalysts are therefore highly desired for the commercialization of RZABs in large scale. Herein, the Fe-N4-C (ORR active sites) and NiFe-LDH clusters (OER active sites) are successfully integrated within a NiFe-LDH/Fe,N-CB electrocatalyst. The NiFe-LDH/Fe,N-CB electrocatalyst is first prepared by the introduction of Fe-N4 into carbon black (CB), followed by the growth of NiFe-LDH clusters. The cluster nature of NiFe-LDH effectively avoids the blocking of Fe-N4-C ORR active centers and affords excellent OER activity. The NiFe-LDH/Fe,N-CB electrocatalyst thus exhibits an excellent bifunctional ORR and OER performance, with a potential gap of only 0.71 V. The NiFe-LDH/Fe,N-CB-based RZAB exhibits an open-circuit voltage of 1.565 V and a specific capacity of 731 mAh gZn-1, which is much better than the RZAB composed of Pt/C and IrO2. Particularly, the NiFe-LDH/Fe,N-CB-based RZAB displays excellent long-term charging/discharging cyclic stability and rechargeability. Even at a large charging/discharging current density (20 mA cm-2), the charging/discharging voltage gap is only ∼1.33 V and exhibits an increase smaller than 5% after 140 cycles. This work provides a new low-cost bifunctional ORR/OER electrocatalyst with high activity and superior long-term stability and will be helpful to the commercialization of RZAB in large scale.

16.
Drug Resist Updat ; 67: 100930, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36736043

RESUMO

5-Fluorouracil (5-Fu) is a first-line drug for colorectal cancer (CRC) therapy. However, the development of 5-Fu resistance limits its chemotherapeutic effectiveness and often leads to poor prognoses of CRC. Transglutaminase 2 (TGM2), a member of the transglutaminase family, is considered to be associated with chemoresistance through apoptotic prevention in various cancers including CRC. TGM2 was found to be overexpressed in two 5-Fu-resistant CRC cell lines and down-regulated by increased thiol oxidative stress induced by inhibition of glutathione reductase (GR). The present study aimed to explore the role of TGM2 in 5-Fu-resistant CRC and the mechanism of action by which the elevated thiol oxidative stress down-regulates TGM2 protein level. The results revealed that 5-Fu-resistance induced by overexpression of TGM2 in CRC cells was reversed through up-regulation of thiol oxidative stress. Knockdown of TGM2 increased the chemosensitivity of CRC cells to 5-Fu. Thiol oxidative stress potentially enhanced the therapeutic effect of 5-Fu in the resistant CRC cells by promotion of 5-Fu-induced apoptosis through down-regulation of TGM2. The elevated thiol oxidative stress increased the S-glutathionylation of TGM2 and led to proteasomal degradation of TGM2. Furthermore, Cys193 was identified as the S-glutathionylation site in TGM2, and its mutation resulted in thiol oxidative stress-mediated CRC cell apoptotic resistance. TGM2-induced EMT was also suppressed by the elevated thiol oxidative stress. A xenograft tumor model confirmed the effect of thiol oxidative stress in the reversal of 5-Fu resistance in CRC cells in vivo. TGM2 protein expression level was found to be significantly higher in human CRC specimens than in non-cancerous colorectal tissues. Taken together, the present data suggest an important role of TGM2 in 5-Fu resistance in CRC cells. Up-regulation of thiol oxidative stress could be a potential therapeutic approach for treating 5-Fu-resistant CRC and TGM2 may serve as a potential therapeutic target of thiol oxidative stress.


Assuntos
Neoplasias Colorretais , MicroRNAs , Animais , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Estresse Oxidativo
17.
Nat Commun ; 14(1): 778, 2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36774361

RESUMO

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences. The S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression and metastasis in vitro and in vivo. Our comparative analyses reveal distinct genomic features in AEG subtypes. We find a specific decrease of fibroblasts in the S-III subtype. Further phosphoproteomic comparisons reveal different kinase-phosphosubstrate regulatory networks among AEG subtypes. Our proteogenomics dataset provides valuable resources for understanding molecular mechanisms and developing precision treatment strategies of AEG.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Proteínas F-Box , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteômica , Adenocarcinoma/patologia , Junção Esofagogástrica/metabolismo , Metástase Linfática/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia
18.
Nanoscale ; 15(10): 4830-4838, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36800192

RESUMO

Mn-based mixed phosphate Na4Mn3(PO4)2(P2O7) (NMPP) is a promising cathode for high-potential, low-cost and eco-friendly sodium-ion batteries. However, this material still faces some bottleneck issues in terms of low conductivity, disturbance of impure crystalline phase, micron-sized agglomerated particles and the Mn3+ Jahn-Teller effect. Herein, a Mg-substituted NMPP (NM2.7Mg0.3PP)@C composite was constructed via modified solution combustion and subsequent calcination treatment. The obtained NM2.7Mg0.3PP presents a highly pure phase and single-crystalline characteristics. It is noteworthy that the sample shows a smaller particle size of 100-300 nm due to the Mg2+ incorporation, and the prepared NM2.7Mg0.3PP@C cathode exhibits considerable discharge capacity (119 mA h g-1), an improved rate capability and excellent long cycling stability of 1000 cycles. A series of measurements indicated that the Mg-substitution enhanced the electronic conductivity and ion diffusion rate, and effectively relieved the lattice distortion influenced by the multiphase transition from the Mn Jahn-Teller effect of the NM2.7Mg0.3PP@C cathode. In addition, NM2.7Mg0.3PP adopts an optimal 3Mg0.1-Mn1-Mn2-Mn3 crystal structure based on density functional theory (DFT) calculations and refined X-ray diffractometry results. These findings provide new insight into the design of highly stabilized and high-conductivity polyanionic cathodes for sodium-ion batteries.

19.
Mol Carcinog ; 62(5): 716-726, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36807309

RESUMO

The therapeutic effects of existing drug regimens against pancreatic neuroendocrine neoplasms (pNENs) remain limited, and identifying ideal therapeutic targets is warranted. PDZ binding kinase (PBK) may play an oncogenic role in most solid tumors. However, its function in pNEN remains unclear. In this study, pNEN samples and International Cancer Genome Consortium data were used to determine the clinical significance of PBK. Cell counting and CCK8 assays were used to assess cell proliferation. Flow cytometry was used to assess drug-induced apoptosis and cell cycle arrest. An in vivo PBK-targeting experiment was performed in mice bearing pNENs. Western blotting, quantitative PCR, and immunohistochemistry were performed to assess the molecular mechanisms. PBK was significantly upregulated in pNEN tissues compared with paracancerous tissues. Additionally, PBK was a poor prognostic factor for pNEN patients. PBK was found to promote the proliferation of pNEN cells by activating the AKT/mTOR pathway. Furthermore, PBK inhibition combined with everolimus treatment had enhanced antitumour effects on pNEN via inhibiting AKT/mTOR pathway and inducing G0/G1 phase cell cycle arrest. This study highlights that PBK plays an oncogenic role in and is a promising therapeutic target for pNEN.


Assuntos
Quinases de Proteína Quinase Ativadas por Mitógeno , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Animais , Camundongos , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
20.
ACS Nano ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622112

RESUMO

Directly integrating the bifunctional photoelectrode into Li-O2 batteries has been considered an effective way to reduce the overpotential and promote electric energy saving. However, more regular investigations on various bifunctional photocatalysts have still been desired for high-performance photoassisted Li-O2 batteries. Herein, a systematic exploration of various-sized siloxene photocatalysts affected by Li-O2 batteries has been introduced. Compared with the utilization of larger-sized siloxene nanosheets (SNSs), the photoassisted Li-O2 battery with a siloxene quantum dot (SQD) photoelectrode delivers a superior round-trip efficiency of 230% based on the highest discharge potential up to 3.72 V and lowest charge potential of 1.60 V and enables the maintenance of a long-term cycling life with only 13% efficiency attenuation after 200 cycles at 0.075 mA/cm2. Furthermore, this system exhibits a record-high rate-cycling performance (162% round-trip efficiency, even at 3 mA/cm2) and a high discharge capacity of 2212 mAh/g at 1 mA/cm2. These ground-breaking performances could be attributed to the synergistic effect of the photocatalytic and electrocatalytic activities of SQD photocatalysts with the ideal conduction band/valence band values, the abundant defective sites, and the stronger O2 and lower LiO2 adsorption strengths of SQD photocatalysts. These systematic research studies highlight the significance of SQD bifunctional photocatalysts and could be extended to other photocatalysts for further high-efficiency photoelectric conversion and storage.

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