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1.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39000330

RESUMO

Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots' metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds.


Assuntos
Secas , Hordeum , Metabolômica , Hordeum/genética , Hordeum/metabolismo , Hordeum/crescimento & desenvolvimento , Hordeum/fisiologia , Metabolômica/métodos , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Metaboloma , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Amido/metabolismo , Resistência à Seca
2.
J Pharm Biomed Anal ; 248: 116338, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38971092

RESUMO

Tetrahydroxy stilbene glucoside (TSG) is a water-soluble natural product that has shown potential in treating atherosclerosis (AS). However, its underlying mechanisms remain unclear. Here, we demonstrate that an 8-week TSG treatment (100 mg/kg/d) significantly reduces atherosclerotic lesions and alleviates dyslipidemia symptoms in ApoE-/- mice. 1H nuclear magnetic resonance metabolomic analysis reveals differences in both lipid components and water-soluble metabolites in the livers of AS mice compared to control groups, and TSG treatment shifts the metabolic profiles of AS mice towards a normal state. At the transcriptional level, TSG significantly restores the expression of fatty acid metabolism-related genes (Srepb-1c, Fasn, Scd1, Gpat1, Dgat1, Pparα and Cpt1α), and regulates the expression levels of disturbed cholesterol metabolism-related genes (Srebp2, Hmgcr, Ldlr, Acat1, Acat2 and Cyp7a1) associated with lipid metabolism. Furthermore, at the cellular level, TSG remarkably polarizes aortic macrophages to their M2 phenotype. Our data demonstrate that TSG alleviates arthrosclerosis by dual-targeting to hepatic lipid metabolism and aortic M2 macrophage polarization in ApoE-/- mice, with significant implications for translational medicine and the treatment of AS using natural products.

3.
Opt Express ; 32(8): 13001-13013, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859282

RESUMO

The monitoring of hydrological elements in the polar region is the basis for the study of the dynamic environment under the ice. The traditional cross-season subglacial hydrological environment monitoring mainly relies on tether-type vertical profile measurement ice-based buoys, which have the advantages such as high reliability, high measurement accuracy, and real-time communication, while also has disadvantages of high-cost, large volume and weight, high power consumption, and complex layout. Therefore, it is urgent to develop a new type of ice-based profile buoy with low-cost, miniaturization, low power consumption, convenient deployment, and high reliability. In this paper, a novel optical fiber sensing scheme for ice-based buoy monitoring is proposed, which uses arrayed fiber grating to measure seawater temperature and depth profile and uses a dual-conduction mode resonance mechanism to measure seawater salinity. The temperature, depth, and salinity of seawater can be detected by an all-optical fiber technology in real-time. Preliminary experiments show that the temperature accuracy is ±0.1 °C in the range of -5∼35 °C, the salinity accuracy is ±0.03‰ in the range of 30‰âˆ¼40‰, and the vertical spatial resolution of depth can be adjusted in the range of 0∼1000 m, which can better meet the requirements of polar hydrological multi-layer profile observation. It can provide an innovative technology and equipment support for studying the spatiotemporal change process of the polar subglacial ocean.

4.
Physiol Plant ; 176(3): e14356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828569

RESUMO

Halophyte Halogeton glomeratus mostly grows in saline desert areas in arid and semi-arid regions and is able to adapt to adverse conditions such as salinity and drought. Earlier transcriptomic studies revealed activation of the HgS2 gene in the leaf of H. glomeratus seedlings when exposed to saline conditions. To identify the properties of HgS2 in H. glomeratus, we used yeast transformation and overexpression in Arabidopsis. Yeast cells genetically transformed with HgS2 exhibited K+ uptake and Na+ efflux compared with control (empty vector). Stable overexpression of HgS2 in Arabidopsis improved its resistance to salt stress and led to a notable rise in seed germination in salinity conditions compared to the wild type (WT). Transgenic Arabidopsis regulated ion homeostasis in plant cells by increasing Na+ absorption and decreasing K+ efflux in leaves, while reducing Na+ absorption and K+ efflux in roots. In addition, overexpression of HgS2 altered transcription levels of stress response genes and regulated different metabolic pathways in roots and leaves of Arabidopsis. These results offer new insights into the role of HgS2 in plants' salt tolerance.


Assuntos
Amaranthaceae , Arabidopsis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Amaranthaceae/genética , Amaranthaceae/fisiologia , Arabidopsis/genética , Arabidopsis/fisiologia , Germinação/genética , Germinação/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/fisiologia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Potássio/metabolismo , Tolerância ao Sal/genética , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/fisiologia , Plantas Tolerantes a Sal/metabolismo , Sódio/metabolismo , Cloreto de Sódio/farmacologia
5.
Regen Biomater ; 11: rbae059, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911700

RESUMO

Currently, the successful healing of critical-sized calvarial bone defects remains a considerable challenge. The immune response plays a key role in regulating bone regeneration after material grafting. Previous studies mainly focused on the relationship between macrophages and bone marrow mesenchymal stem cells (BMSCs), while dural cells were recently found to play a vital role in the calvarial bone healing. In this study, a series of 3D elastomers with different proportions of polycaprolactone (PCL) and poly(glycerol sebacate) (PGS) were fabricated, which were further supplemented with polydopamine (PDA) coating. The physicochemical properties of the PCL/PGS and PCL/PGS/PDA grafts were measured, and then they were implanted as filling materials for 8 mm calvarial bone defects. The results showed that a matched and effective PDA interface formed on a well-proportioned elastomer, which effectively modulated the polarization of M2 macrophages and promoted the recruitment of dural cells to achieve full-thickness bone repair through both intramembranous and endochondral ossification. Single-cell RNA sequencing analysis revealed the predominance of dural cells during bone healing and their close relationship with macrophages. The findings illustrated that the crosstalk between dural cells and macrophages determined the vertical full-thickness bone repair for the first time, which may be the new target for designing bone grafts for calvarial bone healing.

7.
Int J Surg ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905506

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP) has been established as a biomarker for hepatocellular carcinoma (HCC); however, whether its dynamic changes could predict the response to systemic therapy remains elusive. This study explored the AFP trajectory and the association with survival in patients received bevacizumab plus immunotherapy. METHODS: We retrospectively enrolled 536 HCC patients received bevacizumab plus immunotherapy between February 2021 and February 2023. Patients were divided into two groups according to AFP values before treatment (400 ng/ml). Dynamic changes of AFP were fitted using a latent class model to generate the AFP trajectories. Multivariable Cox models were utilized to compute hazard ratios (HRs) for survival. Inverse-probability-of-treatment weighted analyses were conducted to mitigate the influence of unmeasured confounding variables. The primary endpoint is progression free survival (PFS). The second endpoint is overall survival (OS). RESULTS: Three distinct trajectories were identified for AFP-low and AFP-high patients, respectively. In AFP-low group, compared with the high-rising class (25%; n=69), HRs of PFS were 0.39 and 0.2 for the low-stable class (59.1%; n=163) and sharp-falling class (15.9%; n=44), after adjusting by tumor diameter, tumor number, and extra-hepatic metastasis. In AFP-high group, compared with the high-stable class (18.5%; n=48), HRs of PFS were 0.3 and 0.04 for the middle-stable class (56.5%; n=147) and sharp-falling class (25%; n=65), after adjusting by tumor diameter, tumor number, and extra-hepatic metastasis. Furthermore, the AFP trajectories exhibited the utmost relative importance among all covariates regarding PFS and OS in the multivariable regression models. CONCLUSION: The AFP trajectories in HCC patients receiving bevacizumab and immunotherapy, constituted an independent biomarker indicative of clinical outcomes. Findings from this study hold potential clinical utility in dynamically forecasting the prognosis of systemic therapy in HCC patients and facilitating clinical decision-making. Rapid reduction of AFP post-treatment can lead to favorable patient prognoses.

8.
ChemSusChem ; : e202400738, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837662

RESUMO

Modifying the interface between the lithium metal anode (LMA) and the electrolyte is crucial for achieving high-performance lithium metal batteries (LMBs). Recent research indicates that altering Li-metal interfaces with polymer coatings is an effective approach to extend LMBs' cycling lifespan. However, the physical properties of these polymer-Li interfaces have not yet been fully investigated. Therefore, the structural stability, electronic conductivity, and ionic conductivity of polymer-Li interfaces were examined based on first-principles calculations in this study. Several representative polymer compounds utilized in LMBs were assessed, including polyacrylonitrile (PAN), polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE), and polyethylene oxide (PEO). Our research revealed that lithium fluoride is formed upon fluoropolymer degradation, explaining previously observed experimental results. Polymers containing nitrile groups exhibit strong adhesion to lithium metal, facilitating the formation of the stable interface layer. Regarding electronic conductivity, the fluoropolymers preserve a good insulating property, which diminished marginally in the presence of lithium, but that of PAN and PEO significantly reduces. Additionally, lithium diffusion on PTFE and PEO demonstrates low diffusion barriers and high coefficients, enabling easy transportation. Overall, our investigation reveals that the interfaces formed between various polymers and LMA have distinct characteristics, providing new fundamental insights for designing composites with tailored interface properties.

9.
Nat Commun ; 15(1): 3985, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734677

RESUMO

Pentamidine and melarsoprol are primary drugs used to treat the lethal human sleeping sickness caused by the parasite Trypanosoma brucei. Cross-resistance to these two drugs has recently been linked to aquaglyceroporin 2 of the trypanosome (TbAQP2). TbAQP2 is the first member of the aquaporin family described as capable of drug transport; however, the underlying mechanism remains unclear. Here, we present cryo-electron microscopy structures of TbAQP2 bound to pentamidine or melarsoprol. Our structural studies, together with the molecular dynamic simulations, reveal the mechanisms shaping substrate specificity and drug permeation. Multiple amino acids in TbAQP2, near the extracellular entrance and inside the pore, create an expanded conducting tunnel, sterically and energetically allowing the permeation of pentamidine and melarsoprol. Our study elucidates the mechanism of drug transport by TbAQP2, providing valuable insights to inform the design of drugs against trypanosomiasis.


Assuntos
Aquagliceroporinas , Microscopia Crioeletrônica , Melarsoprol , Simulação de Dinâmica Molecular , Pentamidina , Trypanosoma brucei brucei , Trypanosoma brucei brucei/metabolismo , Aquagliceroporinas/metabolismo , Aquagliceroporinas/química , Melarsoprol/metabolismo , Melarsoprol/química , Pentamidina/química , Pentamidina/metabolismo , Transporte Biológico , Tripanossomicidas/química , Tripanossomicidas/metabolismo , Tripanossomicidas/farmacologia , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Humanos
10.
PLoS One ; 19(5): e0301439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38781125

RESUMO

Single image raindrop removal aims at recovering high-resolution images from degraded ones. However, existing methods primarily employ pixel-level supervision between image pairs to learn spatial features, thus ignoring the more discriminative frequency information. This drawback results in the loss of high-frequency structures and the generation of diverse artifacts in the restored image. To ameliorate this deficiency, we propose a novel frequency-oriented Hierarchical Fusion Network (HFNet) for raindrop image restoration. Specifically, to compensate for spatial representation deficiencies, we design a dynamic adaptive frequency loss (DAFL), which allows the model to adaptively handle the high-frequency components that are difficult to recover. To handle spatially diverse raindrops, we propose a hierarchical fusion network to efficiently learn both contextual information and spatial features. Meanwhile, a calibrated attention mechanism is proposed to facilitate the transfer of valuable information. Comparative experiments with existing methods indicate the advantages of the proposed algorithm.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Chuva , Redes Neurais de Computação
11.
Front Pharmacol ; 15: 1389786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741587

RESUMO

Osteoarthritis (OA) is a common chronic disease characterized by progressive cartilage degeneration and secondary synovial inflammation. Bergamottin (Ber) is an important natural derivative of the furanocoumarin compound, extracted from natural foods, such as the pulp of grapefruits and pomelos. Ber exhibits several characteristicsthat are beneficial to human health, such as anti-inflammation, antioxidant, and anti-cancer effects. However, the role of Ber in the treatment of OA has not been elucidated to date. Therefore, in the present study, in vitro experiments were conducted, which demonstrated that Ber reduces the secretion of inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) under the stimulation of interleukin-1ß (IL-1ß). Ber also reversed the IL-1 ß-mediated aggrecan and type II collagen degradation within the extracellular matrix (ECM). In addition, in vivo experiments were conducted, in which Ber ameliorated the progression of OA in mice. It was revealed that Ber exerted its cellular effect by activating the Sirt1/NF-kB pathways. In conclusion, the present study demonstrated the therapeutic potential of Ber in the context of OA.

12.
Therap Adv Gastroenterol ; 17: 17562848241237631, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645513

RESUMO

Background: Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials. Objectives: The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making. Design: Systematic review and network meta-analysis. Data sources and methods: PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023. Results: After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib. Conclusion: Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies. Trial registration: PROSPERO, CRD42022288172.


Lay summary/Key points The efficiency of various systemic therapies in advanced HCC patients with specific characteristics remains to be explored. This study revealed that the efficacy of ICI combined therapies is influenced by factors such as tumor staging, etiology, patient demographics, and more. Additionally, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI combined therapies. Complementing to recent guidelines, this study indicated that several critical factors needed to be took into consideration for patients with advanced HCC.

13.
Sci Adv ; 10(16): eadl2063, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640232

RESUMO

All-perovskite tandem solar cells (TSCs) have exhibited higher efficiencies than single-junction perovskite solar cells (PSCs) but still suffer from the unsatisfactory performance of low-bandgap (LBG) tin-lead (Sn-Pb) subcells. The inherent properties of PEDOT:PSS are crucial to high-performance Sn-Pb perovskite films and devices; however, the underlying mechanism has not been fully explored and revealed. Here, we report a facile oxalic acid treatment of PEDOT:PSS (OA-PEDOT:PSS) to precisely regulate its work function and surface morphology. OA-PEDOT:PSS shows a larger work function and an ordered reorientation and fiber-shaped film morphology with efficient hole transport pathways, leading to the formation of more ideal hole-selective contact with Sn-Pb perovskite for suppressing interfacial nonradiative recombination losses. Moreover, OA-PEDOT:PSS induces (100) preferred orientation growth of perovskite for higher-quality Sn-Pb films. Last, the OA-PEDOT:PSS-tailored LBG PSC yields an impressive efficiency of up to 22.56% (certified 21.88%), enabling 27.81% efficient all-perovskite TSC with enhanced operational stability.

14.
J Hepatocell Carcinoma ; 11: 463-475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463545

RESUMO

Purpose: The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). Patients and Methods: Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed. Results: The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P<0.05) and 15.6 months (P<0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P<0.05) and 45.0 months (P<0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P<0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P<0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P<0.05) and 21.7 months (P<0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up. Conclusion: HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.

15.
Int J Biol Macromol ; 265(Pt 1): 130857, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38493812

RESUMO

Type 1 diabetes (T1D), a complex autoimmune disease, is intricately linked to the gut's epithelial barrier function. Emerging evidence emphasizes the role of irisin, an exercise-related hormone, in preserving intestinal integrity. This study investigates whether irisin could delay T1D onset by enhancing the colon intestinal barrier. Impaired colon intestinal barriers were observed in newly diagnosed T1D patients and non-obese diabetic (NOD) mice, worsening with age and accompanied by islet inflammation. Using an LPS-induced colonic inflammation model, a dose-dependent impact of LPS on colon cells irisin expression, secretion, and barrier function was revealed. Exogenous irisin demonstrated remarkable effects, mitigating islet insulitis, enhancing energy expenditure, and alleviating autoimmune symptoms by reducing colon intestinal permeability. Single-cell RNA sequencing (scRNA-seq) highlighted irisin's positive impact on colon epithelial cell clusters, effectively restoring the intestinal barrier. Irisin also selectively modulated bacterial composition, averting potential bacterial translocation. Mechanistically, irisin enhanced colon intestinal barrier tight junction proteins through the AMPK/PI3K/AKT pathway, with FAM120A playing a crucial role. Irisin upregulated MUC3 expression, a protector against damage and inflammation. Harnessing irisin's exercise-mimicking properties suggests therapeutic potential in clinical settings for preventing T1D progression, offering valuable insights into fortifying the colon's intestinal barrier and managing autoimmune conditions associated with T1DM.


Assuntos
Diabetes Mellitus Tipo 1 , Camundongos , Animais , Humanos , Camundongos Endogâmicos NOD , Fibronectinas , Lipopolissacarídeos , Fosfatidilinositol 3-Quinases , Inflamação , Camundongos Endogâmicos C57BL , Mucosa Intestinal
16.
Mol Ther ; 32(4): 1110-1124, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38341612

RESUMO

Whether and how tumor intrinsic signature determines macrophage-elicited metastasis remain elusive. Here, we show, in detailed studies of data regarding 7,477 patients of 20 types of human cancers, that only 13.8% ± 2.6%/27.9% ± 3.03% of patients with high macrophage infiltration index exhibit early recurrence/vascular invasion. In parallel, although macrophages enhance the motility of various hepatoma cells, their enhancement intensity is significantly heterogeneous. We identify that the expression of malignant Dicer, a ribonuclease that cleaves miRNA precursors into mature miRNAs, determines macrophage-elicited metastasis. Mechanistically, the downregulation of Dicer in cancer cells leads to defects in miRNome targeting NF-κB signaling, which in turn enhances the ability of cancer cells to respond to macrophage-related inflammatory signals and ultimately promotes metastasis. Importantly, transporting miR-26b-5p, the most potential miRNA targeting NF-κB signaling in hepatocellular carcinoma, can effectively reverse macrophage-elicited metastasis of hepatoma in vivo. Our results provide insights into the crosstalk between Dicer-elicited miRNome and cancer immune microenvironments and suggest that strategies to remodel malignant cell miRNome may overcome pro-tumorigenic activities of inflammatory cells.


Assuntos
Carcinoma Hepatocelular , MicroRNAs , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Carcinoma Hepatocelular/patologia , Transdução de Sinais/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral/genética
17.
Adv Mater ; 36(15): e2310347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38174663

RESUMO

Anode-free sodium metal battery (AFSMB) promises high energy density but suffers from the difficulty of maintaining high cycling stability. Nonuniform sodium (Na) deposition on the current collector is largely responsible for capacity decay in the cycling process of AFSMB. Here, a unique copper phosphide (Cu3P) nanowire is constructed on copper (Cu3P@Cu) as a sodium deposition substrate by an in situ growth method. Superior electrochemical performance of Cu3P@Cu anode is delivered in asymmetric cells with an average Coulombic efficiency of 99.8% for over 800 cycles at 1 mA cm-2 with 1 mA h cm-2. The symmetric cell of Cu3P@Cu displayed a cycling lifespan of over 2000 h at 2 mA cm-2 with 1 mA h cm-2. Cryo-transmission electron microscope characterization and first principles calculation revealed that the low Na+ absorption energy and low Na+ diffusion energy barrier on Na3P promoted uniform Na nucleation and deposition, thus enhancing the Na surface stability. Moreover, anode-free Na3V2(PO4)3//Cu3P@Cu full pouch cell delivered a considerable cycling capacity of ≈15 mA h in 170 cycles, demonstrating its practical feasibility.

18.
Photodiagnosis Photodyn Ther ; 45: 103986, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38272155

RESUMO

BACKGROUND: Prepubertal girls are one of the vulnerable populations of vulvar lichen sclerosus (VLS), which results in a decreased quality of life and increases risk of vulvar cancer. But the therapeutic effects of traditional topical remedies are unsatisfactory in some pediatric patients. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for refractory VLS patients, but no study has been conducted in child patients. METHODS: The patients included in this study underwent three sessions of ALA-PDT at 2-week intervals. All patients were evaluated for objective clinical appearances and subjective symptoms quantitatively. Statistical analysis comparing parameters at baseline and after three-time ALA-PDT was performed. RESULTS: A total of seven VLS girl patients were included in this study. Both primary objective appearances (lesion size and depigmentation) and subjective symptoms (itching and burning pain) were improved remarkably after the third treatment. Besides, adverse effects, mainly as pain and post-treatment edema, were mild and could be tolerated. CONCLUSIONS: ALA-PDT is an effective and safe therapeutic option for VLS girl patients. Compared with adult patients, the symptoms resolved more quickly in child patients.


Assuntos
Fotoquimioterapia , Líquen Escleroso Vulvar , Adulto , Feminino , Humanos , Criança , Fotoquimioterapia/métodos , Ácido Aminolevulínico/uso terapêutico , Qualidade de Vida , Líquen Escleroso Vulvar/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Dor
19.
J Hepatocell Carcinoma ; 10: 2133-2145, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058386

RESUMO

Purpose: To assess the clinical value of the pretherapeutic systemic inflammation score (SIS) in predicting the prognosis of hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). Methods: From February 2016 to April 2021, 415 advanced HCC patients who underwent HAIC at Sun Yat-sen University Cancer Center were randomly divided into training (n = 277) and validation cohorts (n = 138) and analyzed. The aspartate aminotransferase-alanine aminotransferase ratio (AAR), lymphocyte × albumin (L × A), and neutrophil × monocyte (N × M) were used to construct the SIS score based on a multivariate Cox analysis in the training cohort. A nomogram consisting of the SIS score was created and evaluated by calibration plot, areas under the receiver operating characteristic (AUC) curve, and decision curve analysis (DCA). Results: Univariate and multivariate Cox analyses revealed that the SIS score was an independent predictor of OS. A high SIS score was associated with large tumor size (P < 0.05), multiple lesions (P < 0.01), high AFP level (P < 0.01), extrahepatic metastasis (P < 0.05), and advanced BCLC stage (P < 0.01). Kaplan-Meier analysis showed that the patients with a high SIS had shorter OS than those with a low SIS in both the non-PD (p = 0.015) and PD group (p = 0.023). The calibration plots showed good concordance between the nomogram's prediction and the actual observations in both the training and validation cohorts. In the training cohort, the AUCs of the nomogram predicting the 2-year and 3-year survival rates were 0.749 and 0.739, respectively; in the validation cohort, they were 0.760 and 0.681, respectively. Based on the AUC and DCA, the nomogram showed better predictive ability than other predictors. Conclusion: The pretherapeutic SIS score is a potential prognostic predictor for HCC patients undergoing HAIC.

20.
J Hepatocell Carcinoma ; 10: 2117-2132, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053944

RESUMO

Purpose: The efficacy of entecavir (ETV) versus tenofovir (TDF) on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who underwent FOLFOX-hepatic arterial infusion chemotherapy (HAIC) remains unclear. In this study, we compared the outcomes between ETV and TDF in HBV-related advanced HCC patients who underwent FOLFOX-HAIC. Methods: A total of 683 patients diagnosed with HBV-related HCC who underwent FOLFOX-HAIC and received TDF or ETV between January 2016 and December 2021 were included. Overall survival (OS), progression-free survival (PFS), HBV reactivation, and liver function of patients were compared between the ETV and TDF groups by propensity score matching (PSM). Results: In the PSM cohort, for all patients and patients with ≥ 4 cycles of FOLFOX-HAIC, the median OS in the ETV group (15.2 months, 95% CI: 13.0-17.4 months; 16.6 months, 95% CI: 14.8-18.5 months; respectively) was shorter than that in the TDF group (23.0 months, 95% CI: 10.3-35.6 months; 27.3 months, 95% CI: 16.5-NA months; p=0.024, p=0.028; respectively). The median PFS in the ETV group (8.7 months, 95% CI: 7.9-9.5 months; 8.9 months, 95% CI: 8.0-9.8 months; respectively) was also shorter than that in the TDF group (11.8 months, 95% CI: 8.0-15.6 months; 12.7 months, 95% CI: 10.8-14.6 months; p=0.036, p=0.025; respectively). The rate of HBV reactivation in the ETV group was higher than that in the TDF group (12.3% vs 6.3%, p=0.040; 16.5% vs 6.2%, p=0.037, respectively). For liver function, the rate of ALBI grade that remained stable or improved in the ETV group was lower than that in the TDF group (44.6% vs 57.6%, p=0.006; 37.2% vs 53.8%, p=0.019, respectively). Conclusion: Compared with ETV, TDF was associated with a better prognosis, lower proportion of HBV reactivation, and better preservation of liver function in advanced HBV-HCC patients who underwent FOLFOX-HAIC, especially those who received ≥ 4 cycles.

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