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1.
J Biol Chem ; : 107598, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39059495

RESUMO

In recent years, a surge in studies investigating N6-methyladenosine (m6A) modification in human diseases has occurred. However, the specific roles and mechanisms of m6A in kidney disease remain incompletely understood. This study revealed that m6A plays a positive role in regulating renal fibrosis (RF) by inducing epithelial-to-mesenchymal phenotypic transition (EMT) in renal tubular cells. Through comprehensive analyses, including m6A sequencing, RNA sequencing, and functional studies, we confirmed the pivotal involvement of zinc finger E-box binding homeobox 2 (ZEB2) in m6A-mediated RF and EMT. Notably, the m6A-modified coding sequence (CDS) of ZEB2 mRNA significantly enhances its translational elongation and mRNA stability by interacting with the YTHDF1/eEF-2 complex and IGF2BP3, respectively. Moreover, targeted demethylation of ZEB2 mRNA using the dm6ACRISPR system substantially decreases ZEB2 expression and disrupts the EMT process in renal tubular epithelial cells. In vivo and clinical data further support the positive influence of m6A/ZEB2 on RF progression. Our findings highlight the m6A-mediated regulation of RF through ZEB2, revealing a novel therapeutic target for RF treatment and enhancing our understanding of the impact of mRNA methylation on kidney disease.

2.
Cancer Immunol Immunother ; 73(8): 138, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833177

RESUMO

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies-MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)-has yet to be explored in the context of cancer treatment.In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs.Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.


Assuntos
Inibidores de Checkpoint Imunológico , Interleucinas , Receptor de Morte Celular Programada 1 , Microambiente Tumoral , Interleucinas/metabolismo , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Humanos , Microambiente Tumoral/imunologia , Terapia Combinada , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Feminino , Neoplasias/imunologia , Neoplasias/terapia , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral
3.
Opt Lett ; 49(10): 2833-2836, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748173

RESUMO

Yellow lasers with high efficiency and tunability play an essential role in many applications. Here, we demonstrate the sum-frequency generation (SFG) of yellow light on a periodically poled thin-film lithium niobate (PP-TFLN) waveguide. Taking advantage of large χ(2) nonlinearity, a high normalized conversion efficiency of 10,097% (W·cm2) is obtained with pump wavelengths of 1317.7 and 1064 nm. An absolute conversion efficiency of 24.17% is recorded with on-chip pump powers of 10.4 dBm (O-band) and 13.5 dBm (1064 nm).

4.
Diabetes Obes Metab ; 26(6): 2305-2317, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38465784

RESUMO

AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.


Assuntos
Bandagens , Pé Diabético , Hidrogéis , Cicatrização , Pé Diabético/terapia , Humanos , Hidrogéis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Feminino , Masculino , Curativos Hidrocoloides , Pessoa de Meia-Idade
5.
Environ Sci Technol ; 58(26): 11791-11801, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38871647

RESUMO

The effect of aqueous solution chemistry on the ionic hydration structure and its corresponding nanofiltration (NF) selectivity is a research gap concerning ion-selective transport. In this study, the hydration distribution of two typical monovalent anions (Cl- and NO3-) under different aqueous solution chemical conditions and the corresponding transmembrane selectivity during NF were investigated by using in situ liquid time-of-flight secondary ion mass spectrometry in combination with molecular dynamics simulations. We demonstrate the inextricable link between the ion hydration structure and the pore steric effect and further find that ionic transmembrane transport can be regulated by breaking the balance between the hydrogen bond network (i.e., water-water) and ion hydration (i.e., ion-water) interactions of hydrated ion. For strongly hydrated (H2O)nCl- with more intense ion-water interactions, a higher salt concentration and coexisting ion competition led to a larger hydrated size and, thus, a higher ion rejection by the NF membrane, whereas weakly hydrated (H2O)nNO3- takes the reverse under the same conditions. Stronger OH--anion hydration competition resulted in a smaller hydrated size of (H2O)nCl- and (H2O)nNO3-, showing a lower observed average hydration number at pH 10.5. This study deepens the long-overlooked understanding of NF separation mechanisms, concerning the hydration structure.


Assuntos
Filtração , Água/química , Íons , Simulação de Dinâmica Molecular , Soluções , Ânions/química
6.
Phys Chem Chem Phys ; 26(5): 4447-4454, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38240154

RESUMO

A one-dimensional optical biosensing metastructure (OBM) with graphene layers is presented in this paper. It is realized by coherent perfect absorption (CPA) and operates in the transverse electric mode. It shows a strong linear fitting relationship between the refractive index (RI) of the analysis layer and the frequency corresponding to the absorption peak, and the R-square is up to 1. Additionally, based on the principle of CPA, the OBM can realize the function of multiple cancer cell detection by adjusting the detection range by controlling the phase difference of coherent electromagnetic waves. Its detection ranges are 1.34-1.355 and 1.658-1.662. Thanks to its high-quality factor, great figure of merit, and low detection limit, whose best values are, respectively, 6.9 × 104, 1.2 × 104 RIU-1, and 3.6 × 10-6 RIU, the detection of weak changes in the RI of a cancer cell is possible. Additionally, its sensitivity can reach 26.57 THz RIU-1. This OBM based on CPA has major implications for advancing the study and investigation into the application of CPA. It also provides a simple and efficient approach to distinguish cancer cells and may be widely used in the biomedical field.


Assuntos
Grafite , Neoplasias , Humanos , Eletricidade , Neoplasias/diagnóstico
7.
Gen Comp Endocrinol ; 354: 114543, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692521

RESUMO

Relaxin3 (rln3) has been associated with various emotional and cognitive processes, including stress, anxiety, learning, memory, motivational behavior, and circadian rhythm. Notably, previous report revealed that Rln3a played an indispensable role in testicular development and male fertility in Nile tilapia (Oreochromis niloticus). However, the underlying molecular mechanisms remain largely unknown. We found that Rln3a is expressed exclusively in the diencephalon* (Di*) of the brain. Deficiency of Rln3a resulted in a significant increase in serum dopamine level and an upregulation of gene expression of gnrh1 and kisspeptin2. To further elucidate the role of Rln3a in fish fertility, we collected two different regions of Di* and hypothalamus (Hyp) tissues for subsequent RNA-seq analysis of both wild-type (rln3a+/+) and rln3a-/- male tilapia. Upon the transcriptomic data, 1136 and 755 differentially expressed genes (DEGs) were identified in the Di* and Hyp tissues, respectively. In Di*, the up-regulated genes were enriched in circadian rhythm, chemical carcinogenesis, while the down-regulated genes were enriched in type II diabetes mellitus, dopaminergic synapse, and other pathways. In Hyp, the up-regulated genes were enriched in circadian rhythm, pyrimidine metabolism, while the down-regulated genes were enriched in type I diabetes mellitus, autoimmune thyroid disease, and other pathways. Subsequently, the results of both qRT-PCR and FISH assays highlighted a pronounced up-regulation of core circadian rhythm genes, cry1b and per3, whereas genes such as clocka, clockb, and arntl exhibited down-regulation. Furthermore, the genes associated with dopamine biosynthesis were significantly increased in the Hyp. In summary, the mutation of rln3a in male tilapia resulted in notable changes in circadian rhythm and disease-linked signaling pathways in the Di* and Hyp. These changes might account for the fertility defects observed in rln3a-/- male mutants in tilapia.


Assuntos
Encéfalo , Ciclídeos , Fertilidade , Animais , Masculino , Ciclídeos/genética , Ciclídeos/metabolismo , Encéfalo/metabolismo , Fertilidade/genética , Relaxina/genética , Relaxina/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo
8.
Ecotoxicol Environ Saf ; 283: 116787, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39067079

RESUMO

T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.

9.
Ecotoxicol Environ Saf ; 284: 116877, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142118

RESUMO

Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25 mg/kg and 5 mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.

10.
Chem Biodivers ; 21(6): e202400567, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602253

RESUMO

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4 µM.


Assuntos
Ascomicetos , Citocalasinas , Ensaios de Seleção de Medicamentos Antitumorais , Thymelaeaceae , Citocalasinas/química , Citocalasinas/farmacologia , Citocalasinas/isolamento & purificação , Humanos , Thymelaeaceae/química , Thymelaeaceae/microbiologia , Ascomicetos/química , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Conformação Molecular , Sobrevivência Celular/efeitos dos fármacos
11.
J Sci Food Agric ; 104(10): 5869-5881, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38407005

RESUMO

BACKGROUND: Flax lignan has attracted much attention because of its potential bioactivities. However, the bioavailability of secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, depends on the bioconversion by the colon bacteria. Lactic acid bacteria (LAB) with ß-glucosidase activity has found wide application in preparing bioactive aglycone. RESULTS: LAB strains with good ß-glucosidase activity were isolated from fermented tofu. Their bioconversion of flax lignan extract was investigated by resting cell catalysis and microbial fermentation, and the metabolism of SDG by Lactiplantibacillus plantarum C5 following fermentation was characterized by widely targeted metabolomics. Five L. plantarum strains producing ß-glucosidase with broad substrate specificity were isolated and identified, and they all can transform SDG into secoisolariciresinol (SECO). L. plantarum C5 resting cell reached a maximum SDG conversion of 49.19 ± 3.75%, and SECO generation of 21.49 ± 1.32% (0.215 ± 0.013 mm) at an SDG substrate concentration of 1 mM and 0.477 ± 0.003 mm SECO was produced at 4 mm within 24 h. Although sixteen flax lignan metabolites were identified following the fermentation of SDG extract by L. plantarum C5, among them, four were produced following the fermentation: SECO, demethyl-SECO, demethyl-dehydroxy-SECO and isolariciresinol. Moreover, seven lignans increased significantly. CONCLUSION: Fermentation significantly increased the profile and level of flax lignan metabolites, and the resting cell catalysis benefits from higher bioconversion efficiency and more straightforward product separation. Resting cell catalysis and microbial fermentation of flax lignan extract by the isolated ß-glucosidase production L. plantarum could be potentially applied in preparing flax lignan ingredients and fermented flaxseed. © 2024 Society of Chemical Industry.


Assuntos
Biotransformação , Fermentação , Linho , Lignanas , beta-Glucosidase , Lignanas/metabolismo , Lignanas/química , Linho/química , Linho/metabolismo , beta-Glucosidase/metabolismo , beta-Glucosidase/química , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/enzimologia , Proteínas de Bactérias/metabolismo , Butileno Glicóis/metabolismo , Catálise , Glucosídeos
12.
J Med Syst ; 48(1): 56, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801505

RESUMO

The rapid growth of internet users in China presents opportunities for advancing the "Healthy China 2030" initiative through online health education. Platforms like "Shanghai Health Cloud" and "National Health Information Platform" improve health literacy and management, enhancing overall public health. However, challenges such as the digital divide and the spread of unverified health information hinder progress. Addressing these issues requires enhancing digital infrastructure, employing advanced technologies for information validation, and setting high standards for online health services. Integrated efforts from various sectors are essential to maximize the benefits of online health education in China.


Assuntos
Educação em Saúde , Letramento em Saúde , Internet , China , Humanos , Educação em Saúde/organização & administração , Educação a Distância/organização & administração , Educação a Distância/métodos , Exclusão Digital
13.
Cell Mol Biol (Noisy-le-grand) ; 69(13): 210-216, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38158664

RESUMO

This study investigated the impact of combining traditional Chinese medicine, Buyang Huanwu Tang, with intravenous thrombolysis using alteplase (rt-PA) in treating ischemic stroke patients with qi deficiency and blood stasis. A single-center clinical randomized trial involved 117 ischemic stroke patients treated with rt-PA in the neurology department from January 2019 to December 2021. Patients were randomly divided into two groups: the control group (58 patients) received rt-PA alone, while the combined group (59 patients) received rt-PA along with Buyang Huanwu Tang. Neurological deficit scores (NIHSS) were assessed before and after treatment, along with hemorheological indicators, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and Keap1-Nrf2/ARE pathway oxidative stress indicators (Keap1, Nrf2, ARE, and NQO1 proteins). Before treatment, there were no significant differences between the groups. After treatment, the combination group exhibited lower NIHSS scores at 4, 8, and 12 weeks, indicating significant improvement compared to the control group. Additionally, the combination group demonstrated reduced plasma viscosity, low and high shear viscosity, and improved red blood cell aggregation compared to the control group after 8 weeks of treatment. Furthermore, the combination group showed elevated MMP-9 levels and reduced VEGF levels, suggesting favorable outcomes. Regarding the Keap1-Nrf2/ARE pathway, Nrf2 and NQO1 protein expression levels were higher in the combination group after 8 weeks of treatment. Clinical efficacy assessment revealed that the combined treatment group had a significantly better overall treatment response. In conclusion, combining Buyang Huanwu Tang with rt-PA intravenous thrombolysis effectively mitigated oxidative stress damage in the Keap1-Nrf2/ARE pathway among ischemic stroke patients with qi deficiency and blood stasis. This approach promoted neurological function recovery and improved overall treatment outcomes.


Assuntos
Medicamentos de Ervas Chinesas , AVC Isquêmico , Ativador de Plasminogênio Tecidual , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ativador de Plasminogênio Tecidual/administração & dosagem , AVC Isquêmico/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Estresse Oxidativo , Resultado do Tratamento , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Int J Mol Sci ; 24(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38139421

RESUMO

WNK (With No Lysine) kinases are members of serine/threonine protein kinase family, which lack conserved a catalytic lysine (K) residue in protein kinase subdomain II and this residue is replaced by either asparagine, serine, or glycine residues. They are involved in various physiological regulations of flowering time, circadian rhythms, and abiotic stresses in plants. In this study, we identified the WNK gene family in two species of Acorus, and analyzed their phylogenetic relationship, physiochemical properties, subcellular localization, collinearity, and cis-elements. The results showed twenty-two WNKs in two Acorus (seven in Ac. gramineus and fifteen in Ac. calamus) have been identified and clustered into five main clades phylogenetically. Gene structure analysis showed all WNKs possessed essential STKc_WNK or PKc_like superfamily domains, and the gene structures and conserved motifs of the same clade were similar. All the WNKs harbored a large number of light response elements, plant hormone signaling elements, and stress resistance elements. Through a collinearity analysis, two and fourteen segmental duplicated gene pairs were identified in the Ac. gramineus and Ac. calamus, respectively. Moreover, we observed tissue-specificity of WNKs in Acorus using transcriptomic data, and their expressions in response to salt stress and cold stress were analyzed by qRT-PCR. The results showed WNKs are involved in the regulation of abiotic stresses. There were significant differences in the expression levels of most of the WNKs in the leaves and roots of Acorus under salt stress and cold stress, among which two members in Ac. gramineus (AgWNK3 and AgWNK4) and two members in Ac. calamus (AcWNK8 and AcWNK12) were most sensitive to stress. In summary, this paper will significantly contribute to the understanding of WNKs in monocots and thus provide a set up for functional genomics studies of WNK protein kinases.


Assuntos
Acorus , Acorus/metabolismo , Filogenia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Serina/metabolismo , Regulação da Expressão Gênica de Plantas
15.
Nanomaterials (Basel) ; 14(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38921930

RESUMO

The recombination of charge carriers at the interface between carrier transport layers such as nickel oxide (NiOx) and the perovskite absorber has long been a challenge in perovskite solar cells (PSCs). To address this issue, we introduced a polymer additive poly(vinyl butyral) into NiOx and subjected it to high-temperature annealing to form a void-containing structure. The formation of voids is confirmed to increase light transmittance and surface area of NiOx, which is beneficial for light absorption and carrier separation within PSCs. Experimental results demonstrate that the incorporation of the polymer additive helped to enhance the hole conductivity and carrier extraction of NiOx with a higher Ni3+/Ni2+ ratio. This also optimized the energy levels of NiOx to match with the perovskite to raise the open-circuit voltage to 1.01 V. By incorporating an additional NiOx layer beneath the polymer-modified NiOx, the device efficiency was further increased as verified from the dark current measurement of devices.

16.
Curr Cancer Drug Targets ; 24(7): 749-759, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38310464

RESUMO

INTRODUCTION: The purpose of this research was to settle the role of brucine in pancreatic ductal adenocarcinoma (PDAC) and the mechanisms involved. METHODS: The findings of this study suggest that brucine exerts inhibitory effects on cell growth, clonogenicity, and invasive potential of Panc02 and Mia Paca-2 cells. These effects may be linked to an increase in apoptotic-prone cell population. RESULTS: Gene sequencing data suggests that these effects are mediated through the induction of apoptosis. Experimental evidence further supports the notion that brucine reduces mitochondrial membrane potential and upregulates Bax expression while downregulating Bcl-2 expression. These effects are believed to be a result of brucine-mediated suppression of PI3K/Akt activity, which serves as a regulatory factor of mTOR, Bax, and Bcl-2. Suppression of PI3K activity enhances the tumor-suppressing effects of brucine. CONCLUSION: Overall, these findings suggest that brucine has therapeutic potential as a remedy option for PDAC.


Assuntos
Apoptose , Carcinoma Ductal Pancreático , Mitocôndrias , Neoplasias Pancreáticas , Estricnina , Humanos , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estricnina/farmacologia , Estricnina/análogos & derivados
17.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38454952

RESUMO

Signaling by the Ral small GTPase is poorly understood in vivo . Caenorhabditis elegans animals with constitutively activated RAL-1 or deficient for the inhibitory RalGAP, HGAP-1 /2, display pale intestines. Staining with Oil Red O detected decreased intestinal lipids in the hgap-1 deletion mutant relative to the wild type. Constitutively activated RAL-1 decreased lipid detected by stimulated Raman scattering (SRS) microscopy, a label-free method of detecting lipid by laser excitation and detection. A signaling-deficient missense mutant for RAL-1 also displayed reduced lipid staining via SRS. We conclude that RAL-1 signaling regulates lipid homeostasis, biosynthesis or storage in live animals.

18.
Ann Surg Treat Res ; 106(2): 68-77, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38318090

RESUMO

Purpose: This study aimed to investigate whether nighttime elective surgery influenced the short-term outcomes and prognosis of hepatocellular carcinoma (HCC) patients. Methods: The 1,339 HCC patients who underwent hepatectomy were divided into the daytime surgery group (8 a.m.-6 p.m., n = 1,105) and the nighttime surgery group (after 6 p.m., n = 234) based on the start time of surgery. The 1:2 propensity score matching (PSM) analysis was used to control confounding factors. The short-term outcomes of HCC patients in the 2 groups were compared before and after PSM. Factors associated with major complications (Clavien-Dindo grade, ≥III) and textbook oncologic outcomes (TOO) were separately identified by multivariable logistic regression based on variables screened via least absolute shrinkage and selection operator (LASSO). The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: TOO was achieved after surgery in 897 HCC patients. HCC patients in the nighttime surgery group had a higher body mass index (P = 0.010). After 1:2 PSM, the baseline characteristics of patients between the 2 groups were similar. Short-term outcomes in HCC patients were comparable both before and after PSM (all Ps > 0.05), as were TOO in the 2 groups before (P = 0.673) and after PSM (P = 0.333). In our LASSO-logistic regression, nighttime surgery was not an independent factor associated with major complications or TOO. Both groups also had similar OS (P = 0.950) and RFS (P = 0.740) after PSM. Conclusion: Our study revealed the safety of nighttime elective hepatectomy for HCC patients.

19.
Front Bioeng Biotechnol ; 12: 1324049, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562666

RESUMO

Introduction: Dental pulp stem cells from humans possess self-renewal and versatile differentiation abilities. These cells, known as DPSC, are promising for tissue engineering due to their outstanding biological characteristics and ease of access without significant donor site trauma. Existing methods for isolating DPSC mainly include enzyme digestion and explant techniques. Compared with the enzymatic digestion technique, the outgrowth method is less prone to cell damage and loss during the operation, which is essential for DPSC with fewer tissue sources. Methods: In order to maximize the amount of stem cells harvested while reducing the cost of DPSC culture, the feasibility of the optimized explant technique was evaluated in this experiment. Cell morphology, minimum cell emergence time, the total amount of cells harvested, cell survival, and proliferative and differentiation capacity of DPSC obtained with different numbers of explant attachments (A1-A5) were evaluated. Results: There was a reduction in the survival rate of the cells in groups A2-A5, and the amount of harvested DPSC decreased in A3-A5 groups, but the DPSC harvested in groups A1-A4 had similar proliferative and differentiation abilities. However, starting from group A5, the survival rate, proliferation and differentiation ability of DPSC decreased significantly, and the adipogenic trend of the cells became more apparent, indicating that the cells had begun to enter the senescence state. Discussion: The results of our study demonstrated that the DPSC obtained by the optimized explant method up to 4 times had reliable biological properties and is available for tissue engineering.

20.
Autoimmunity ; 57(1): 2290909, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084896

RESUMO

Increase of regulatory T cells (Tregs) in the tumour microenvironment predicts worse survival of patients with various types of cancer. Recently, B cells play a significant role in the maintenance of Treg cells. However, the relevance of regulatory B cells (Bregs) to tumour immunity in humans remains elusive. Flow cytometry analysis was used to detect the Bregs and Tregs. Double staining results illustrated that the proportion of Bregs and Tregs were prominently higher in cervical cancer than normal tissues. Increase of Bregs and Tregs in cervical cancer microenvironment was associated with poor survival. Furthermore, Bregs cocultured with cervical cancer cell lines increased and induced Tregs. To sum up, the increased expression of Bregs contributes to the differentiation of CD4+ T cells into Tregs in the cervical cancer.


Assuntos
Linfócitos B Reguladores , Neoplasias do Colo do Útero , Feminino , Humanos , Linfócitos T Reguladores , Linfócitos B Reguladores/metabolismo , Interleucina-10/metabolismo , Antígenos CD19/metabolismo , Microambiente Tumoral
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