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1.
Artigo em Inglês | MEDLINE | ID: mdl-39356833

RESUMO

Nowadays, covalent-organic frameworks (COFs) integrated with the electrochemiluminescence (ECL) behavior are highly desired owing to the significant advantages including multifunctionality, high sensitivity, and low background noise. Here, two ionic COFs (iCOFs) consisting of the anthryl-extended viologen as the backbone were designed and synthesized via the Zincke reaction. It is found for the first time that the as-prepared iCOFs accompanied by potassium persulfate as the coreactant can provide a clear ECL response in a water-bearing medium. The maximum ECL emissions of the iCOFs were in agreement with the photoluminescence spectra. Besides, cyclic voltammetry and electron paramagnetic resonance measurements reveal that the pyridinium unit was electrochemically reduced to afford the free radical. Then, it reacted with SO4·- to generate the excited-state [iCOF]*. Finally, [iCOF]* quickly returned to its ground state coupled with a clear ECL emission, yielding a maximum ECL quantum efficiency of 23.4% compared with tris(2,2'-bipyridyl) ruthenium(II) as the benchmark. In brief, the current study opens a way to develop a kind of ECL emitter that holds great potential in sensing, imaging, and light-emitting devices.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39352682

RESUMO

Apple replant disease (ARD) is a significant factor restricting the healthy development of the apple industry. Biological control is an important and sustainable method for mitigating ARD. In this study, a strain of Paenibacillus polymyxa GRY-11 was isolated and screened from the rhizosphere soil of healthy apple trees in old apple orchards in Shandong Province, China, and the effects of strain GRY-11 on soil microbial community and ARD were studied. The result showed that P. polymyxa GRY-11 could effectively inhibit the growth of the main pathogenic fungi that caused ARD, and the inhibition rates of the strain against Fusarium moniliforme, Fusarium proliferatum, Fusarium solani, and Fusarium oxysporum were 80.00%, 71.60%, 75.00%, and 70.00%, respectively. In addition, the fermentation supernatant played an active role in suppressing the growth of pathogenic fungi. The results of the pot experiment showed that the bacterial fertilizer of the GRY-11 promoted the growth of Malus hupehensis seedlings, improved the activity of protective enzymes in plant roots, enhanced the soil enzyme content, and optimized the soil microbial environment. In general, the GRY-11 can be used as an effective microbial preparation to alleviate ARD. Our study offers novel perspectives for the prevention of ARD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39226423

RESUMO

Two new two-dimensional (2D) coordination polymers (CPs), namely, poly[diaqua[µ4-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato-κ4O:O':O'':O''']cadmium(II)], [Cd(C14H6N2O8)(H2O)2]n (1), and poly[[tetraaqua[µ4-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato-κ4O:O':O'':O'''][µ2-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato-κ2O:O']dizinc(II)] dihydrate], {[Zn(C14H6N2O8(H2O)2]·H2O}n (2), have been synthesized by the microwave-irradiated reaction of Cd(CH3COO)2·2H2O and Zn(CH3COO)2·2H2O, respectively, with N,N'-bis(glycinyl)pyromellitic diimide {BGPD, namely, 2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetic acid, H2L}. In the crystal structure of 1, the CdII ion is six-coordinated by four carboxylate O atoms from four symmetry-related L2- dianions and two coordinated water molecules, furnishing an octahedral coordination geometry. The bridging L2- dianion links four symmetry-related CdII cations into a 2D layer-like structure with a 3,4-connected bex topology. In the crystal structure of 2, the ZnII ion is five-coordinated by three carboxylate O atoms from three different L2- dianions and two coordination water molecules, furnishing a trigonal bipyramidal coordination geometry. Two crystallographically independent ligands serve as µ4- and µ2-bridges, respectively, to connect the ZnII ions, thereby forming a 2D layer with a 3,3-connected hcb topology. Crystal structure analysis reveals the presence of n→π* interactions between two carbonyl groups of the pyromellitic diimide moieties in 1 and 2. CP 1 exhibits an enhanced fluorescence emission compared with free H2L. The framework of 2 decomposes from 720 K, indicating its high thermal stability. A comparative analysis of a series of structures based on the BGPD ligand indicates that the metal-ion size has a great influence on the connection modes of the metal ions due to different steric effects, which, in turn, affects the structures of the SBUs (secondary building units) and frameworks.

4.
Heliyon ; 10(17): e36835, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39263080

RESUMO

Background: Obesity is linked to a variety of psychosocial and behavioral outcomes but the causalities remain unclear yet. Determining the causalities and distinguishing between the separate effects of childhood and adult obesity is critical to develop more targeted strategies to prevent adverse outcomes. Methods: With single nucleotide polymorphisms (SNPs) used as genetic variables, we employed univariable Mendelian randomization (UVMR) to explore the causalities between childhood and adult body mass index (BMI) and socioeconomic status, psychological status, and substance use. Genetic data for childhood and adult BMI came respectively from 47,541 children aged 10 years and 339,224 adult participants. The outcome data were obtained from corresponding consortia. The direct impact of childhood BMI and adult BMI was then examined using a multivariable MR (MVMR). Results: UVMR found that higher childhood BMI was linked causally to lower household income (ß = -0.06, 95 % CI = -0.08 âˆ¼ -0.03, P = 4.86 × 10-5), decreased subjective well-being (ß = -0.07, 95 % CI = -0.12 âˆ¼ -0.03, P = 1.74 × 10-3), and an increased tendency of smoking regularly (OR = 1.12, 95 % CI = 1.04-1.20, P = 1.52 × 10-3). Similar results were observed in adult BMI. MVMR further revealed that after adjusting with adult BMI, childhood BMI remained an isolated impact on household income. The impacts of adult BMI on the outcomes were diminished when adjusting with childhood BMI. Conclusion: The findings indicate the impacts of childhood obesity on subjective well-being and smoking initiation are a result of higher BMI sustaining into adulthood, whereas the effect on household income is attributed to a lasting impact of obesity in early life. The results would help facilitate more targeted strategies for obesity management to prevent adverse outcomes.

6.
World J Surg Oncol ; 22(1): 254, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39300515

RESUMO

Hypopharyngeal carcinoma is one of the malignant tumors of the head and neck with a particularly poor prognosis. Recurrence and metastasis are important reasons for poor prognosis of hypopharyngeal cancer patients, and malignant proliferation, migration, and invasion of tumor cells are important factors for recurrence and metastasis of hypopharyngeal cancer. Therefore, elucidating hypopharyngeal cancer cells' proliferation, migration, and invasion mechanism is essential for improving diagnosis, treatment, and prognosis. Plasmacytoma Variant Translocation 1 (PVT1) is considered a potential diagnostic marker and therapeutic target for tumors. However, it remains unclear whether PVT1 is related to the occurrence and development of hypopharyngeal cancer and its specific mechanism. In this study, the promoting effect of PVT1 on the proliferation, migration, and invasion of hypopharyngeal carcinoma FaDu cells was verified by cell biology experiments and animal studies, and it was found that PVT1 inhibited the expression of TGF-ß, suggesting that PVT1 may regulate the occurrence and development of hypopharyngeal carcinoma FaDu cells through TGF-ß.


Assuntos
Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofaríngeas , Invasividade Neoplásica , RNA Longo não Codificante , Animais , Humanos , Camundongos , Apoptose , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino
7.
J Environ Manage ; 370: 122567, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303598

RESUMO

Integrated fixed-film activated sludge (IFAS) system, an improvement of the activated sludge process, combines the advantages of both attached sludge (AS) and suspended sludge (SS). This study aimed to fully decipher the roles of AS and SS in simultaneous N and P removal in an IFAS system through metagenomic analysis. It was found that AS contributed about 84.04%, 97%, and 95.12% to exogenous NO3--N reduction, endogenous NO3--N reduction, and endogenous NO2--N reduction, respectively. Compared with AS, SS exhibited a greater contribution to anaerobic P release (69.06%) and aerobic P uptake (73.48%). Nitrate and nitrite reductase enzymes showed higher activities in AS, while the activities of exopolyphosphatase and alkaline phosphatase D were more active in SS. P content further indicated that in AS, only a small amount of P was stored in EPS, with most presented intracellularly. In SS, the amount of P stored in EPS was found to be higher. Metagenomic analysis revealed genes related to the synthesis and degradation of endogenous carbon were higher in AS, whereas the TCA cycle exhibited higher activity in SS. P removal-related genes (such as ppk2, ppx, and adk) was significantly higher in SS than in AS. The alteration of genes associated with nitrogen metabolism suggested that the microbes in AS had a higher capacity for nitrification and denitrification. In summary, the discrepancy in the roles of AS and SS in N and P removal in IFAS can be attributed to variations in enzyme activity, P storage in EPS, microbial community composition, and functional gene abundance.

8.
Brain Behav ; 14(9): e70036, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39295106

RESUMO

BACKGROUND: The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research. METHODS: Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R). RESULTS: Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), and junctional adhesion molecule-1 (JAM-1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRß and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN. CONCLUSIONS: SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately.


Assuntos
Fármacos Neuroprotetores , Panax notoginseng , Ratos Wistar , Traumatismo por Reperfusão , Saponinas , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Panax notoginseng/química , Saponinas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Masculino , Ratos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Polifenóis/farmacologia , Polifenóis/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Alcenos/farmacologia , Alcenos/administração & dosagem , Modelos Animais de Doenças , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Quimioterapia Combinada
9.
Viruses ; 16(9)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39339943

RESUMO

Influenza viruses remain a major threat to human health. Four classes of drugs have been approved for the prevention and treatment of influenza infections. Oseltamivir, a neuraminidase inhibitor, is a first-line anti-influenza drug, and baloxavir is part of the newest generation of anti-influenza drugs that targets the viral polymerase. The emergence of drug resistance has reduced the efficacy of established antiviral drugs. Combination therapy is one of the options for controlling drug resistance and enhancing therapeutical efficacies. Here, we evaluate the antiviral effects of baloxavir combined with neuraminidase inhibitors (NAIs) against wild-type influenza viruses, as well as influenza viruses with drug-resistance mutations. The combination of baloxavir with NAIs led to significant synergistic effects; however, the combination of baloxavir with laninamivir failed to result in a synergistic effect on influenza B viruses. Considering the rapid emergence of drug resistance to baloxavir, we believe that these results will be beneficial for combined drug use against influenza.


Assuntos
Antivirais , Dibenzotiepinas , Farmacorresistência Viral , Sinergismo Farmacológico , Inibidores Enzimáticos , Morfolinas , Neuraminidase , Piridonas , Triazinas , Dibenzotiepinas/farmacologia , Antivirais/farmacologia , Triazinas/farmacologia , Morfolinas/farmacologia , Piridonas/farmacologia , Neuraminidase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Humanos , Vírus da Influenza B/efeitos dos fármacos , Animais , Piridinas/farmacologia , Tiazóis/farmacologia , Guanidinas/farmacologia , Orthomyxoviridae/efeitos dos fármacos , Cães , Células Madin Darby de Rim Canino , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Ácidos Siálicos , Vírus da Influenza A/efeitos dos fármacos , Tiepinas/farmacologia , Triazóis/farmacologia , Benzimidazóis/farmacologia , Piranos
10.
Food Chem X ; 23: 101748, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39280219

RESUMO

This study investigated the impact of three different charged hydrocolloids, anionic polysaccharide (soluble soybean polysaccharide, SSPS), neutral polysaccharide (pullulan polysaccharide, PUL), and cationic polysaccharide (chitosan, CS), and their complexation on the stabilization efficiency of fermented tomato juice (FTJ). The effect of hydrocolloids on FTJ under different treatment conditions were comprehensively evaluated by determining the particle size distribution, zeta potential, rheological properties, Fourier transform infrared spectroscopy, surface tension, and LUMiSizer. The combined conditions suggest that PUL exhibits better storage stability than SSPS and CS when used individually. Compared with the use of the stabilizers, the combination of hydrocolloids had a greater impact on the storage stability of the FTJ, and the storage stability of the FTJ increased when 0.15% SSPS + 0.03% PUL + 0.15% CS was added. This study lays the groundwork for the development of stable fruit juice beverages.

11.
Food Chem ; 463(Pt 2): 141168, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39276553

RESUMO

Blending two or more materials to create better high-moisture meat analogues has been actively studied in the food science and technology field. Walnut protein is a high-quality plant-based protein resource, yet its full potential remains underexploited. Thus, this study focused on exploring the quality characteristics and fibrous structure formation mechanism of walnut protein (WP) and wheat gluten (WG) meat analogues during high-moisture extrusion cooking process. Results showed that the optimized WP and WG-blended high-moisture meat analogues exhibited a more pronounced anisotropic and oriented fibrous structure. The blending of WP and WG can protect the molecular chains from the thermal transition, and promote the aggregation of protein molecules mainly by enhancing the interaction between hydrophobic interactions and hydrogen bonds, increasing the apparent viscosity and forming protein subunits with larger molecular weights (>100 kDa) to stabilize the newly formed conformation. Additionally, the content of α-helix was the highest among the secondary structures. This study provides a theoretical basis for the application of WG and WP to produce HMMAs with rich fibrous structures.

12.
FEBS J ; 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39279038

RESUMO

Disrupted cholesterol homeostasis plays a critical role in the development of multiple diseases, such as cardiovascular disease and cancer. However, the role of cholesterol in inflammatory bowel disease (IBD) remains unclear. In the present study, we investigated whether and how high levels of cholesterol in the diet affect experimental colitis in mice. A normal diet supplemented with 1.25% cholesterol (high cholesterol diet) caused more severe colitis and aggravated the disruption of intestinal tight junction structure, accompanied by higher colonic tissue total cholesterol (TC) levels in a dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Cholesterol aggravated DSS-induced intestinal epithelial barrier impairment and nuclear sterol regulatory element-binding protein 2 (nSREBP2) inhibition both in vivo and in vitro. In addition, nSREBP2 overexpression ameliorated cholesterol-induced intestinal epithelial barrier disruption in Caco2 cells. Interestingly, inhibition of SREBP2 disrupted intestinal epithelial barrier in the absence of cholesterol. Furthermore, SREBP2 regulated the protein expression of tight junction proteins (occludin/Zo-1) via modulating caveolin-1-mediated endocytosis and lysosomal degradation. Analysis of UK Biobank data indicated that, in fully adjusted models, higher serum TC concentrations were an independent protective factor for IBD incidence. The sterol regulatory element-binding factor 2 (SREBF2) gene rs2228313 (G/C) genetic variant was associated with the incidence of IBD and the CC genotype of SREBF2 rs2228313 was associated with higher serum TC levels and decreased the risk of IBD. In summary, a high cholesterol diet aggravates DSS-induced colitis in mice by down-regulating nSREBP2 expression, thereby promoting the endocytic degradation of tight junction proteins. In humans, SREBF2 gene single nucleotide polymorphism rs2228313 and serum TC levels are associated with IBD incidence.

13.
J Colloid Interface Sci ; 678(Pt C): 159-167, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39293360

RESUMO

The severe hydrogen evolution reaction and parasitic side reaction on Zn anode are the key issues which hinder the development of aqueous Zn-based energy storage devices. Herein, a polyacrylamide/carboxylated cellulose nanofibers/betaine citrate supramolecular zwitterionic hydrogels with molecular slip effects are proposed for enhancing Zn2+ diffusion and protecting Zn anodes. Non-covalent interactions within supramolecular hydrogels forms the skeleton for molecular slip and the strong coordination of carboxyl and amino groups with Zn2+ further facilitates the rapid Zn2+ transfer. Additionally, anchoring carboxyl and amino groups at the anode promotes the uniform deposition of Zn2+and protects Zn anode. On the basis of molecular slip mechanism and anchoring effect in the supramolecular zwitterionic hydrogels, Zn||Zn symmetric batteries undergo 800 h of stable electroplating stripping at a depth of discharge of 80 %. Zn||Cu asymmetric batteries exhibit an impressive average coulombic efficiency of 99.4 % over a remarkable span of 900 cycles at a current density of 15 mA cm-2. Furthermore, Zn||NH4V4O10 batteries successfully undergo over 1,000 cycles at a current density of 0.5 A g-1. Intrinsic ion diffusion mechanism of supramolecular hydrogel electrolytes provides an original strategy for the application of high-performance Zn-based energy storage devices.

14.
J Exp Clin Cancer Res ; 43(1): 255, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243109

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is one of the most lethal malignancies and highly heterogeneous. We thus aimed to identify and characterize iCCA cell subpopulations with severe malignant features. METHODS: Transcriptomic datasets from three independent iCCA cohorts (iCCA cohorts 1-3, n = 382) and formalin-fixed and paraffin-embedded tissues from iCCA cohort 4 (n = 31) were used. An unbiased global screening strategy was established, including the transcriptome analysis with the activated malignancy/stemness (MS) signature in iCCA cohorts 1-3 and the mass spectrometry analysis of the sorted stemness reporter-positive iCCA cells. A group of cellular assays and subcutaneous tumor xenograft assay were performed to investigate functional roles of the candidate. Immunohistochemistry was performed in iCCA cohort 4 to examine the expression and localization of the candidate. Molecular and biochemical assays were used to evaluate the membrane localization and functional protein domains of the candidate. Cell sorting was performed and the corresponding cellular molecular assays were utilized to examine cancer stem cell features of the sorted cells. RESULTS: The unbiased global screening identified RRM2 as the top candidate, with a significantly higher level in iCCA patients with the MS signature activation and in iCCA cells positive for the stemness reporter. Consistently, silencing RRM2 significantly suppressed iCCA malignancy phenotypes both in vitro and in vivo. Moreover, immunohistochemistry in tumor tissues of iCCA patients revealed an unreported cell membrane localization of RRM2, in contrast to its usual cytoplasmic localization. RRM2 cell membrane localization was then confirmed in iCCA cells via immunofluorescence with or without cell membrane permeabilization, cell fractionation assay and cell surface biotinylation assay. Meanwhile, an unclassical signal peptide and a transmembrane domain of RRM2 were revealed experimentally. They were essential for RRM2 trafficking to cell membrane via the conventional endoplasmic reticulum (ER)-Golgi secretory pathway. Furthermore, the membrane RRM2-positive iCCA cells were successfully sorted. These cells possessed significant cancer stem cell malignant features including cell differentiation ability, self-renewal ability, tumor initiation ability, and stemness/malignancy gene signatures. Patients with membrane RRM2-positive iCCA cells had poor prognosis. CONCLUSIONS: RRM2 had an alternative cell membrane localization. The membrane RRM2-positive iCCA cells represented a malignant subpopulation with cancer stem cell features.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Células-Tronco Neoplásicas , Ribonucleosídeo Difosfato Redutase , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Colangiocarcinoma/genética , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Animais , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/genética , Ribonucleosídeo Difosfato Redutase/metabolismo , Ribonucleosídeo Difosfato Redutase/genética , Linhagem Celular Tumoral , Feminino , Masculino , Biomarcadores Tumorais/metabolismo
15.
Phytomedicine ; 135: 156002, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39326134

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignancy and a growing global health problem. Reserpine (Res), a plant-derived hypertension drug, has been reported to possess anti-tumor efficacy. However, the role and function of Res in N6-methyladenosine (m6A) regulation and Lenvatinib (Len) resistance in HCC have not been clarified. PURPOSE: To verify whether Res can be used as a natural small-molecule regulator of m6A to reverse Len resistance in HCC. METHODS: Dot blotting, Western blotting and m6A quantification were used to compare and analyze the differential expression of m6A and its methyltransferase METTL3. Western blotting, Real-Time PCR (RT-PCR), cellular thermal shift assay (CETSA) and molecular docking were used to explore the mechanism of interaction between Res and m6A. The effects of Res on the biological characteristics of Lenvatinib-resistant HCC cells were investigated through CCK-8, clone formation, and Transwell assays. Cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models were used to assess the ability of Res to reverse Len resistance in vivo. MeRIP m6A sequencing, PATHWAY analysis and Western blotting were used to analyze the downstream signaling pathways and genes involved in Res-mediated reversal of Len resistance. RESULTS: Len resistance in HCC is related to the increased m6A level and the high expression of METTL3. Res affects the activity of METTL3 protein by binding to it, thereby downregulating the level of m6A. In vitro study showed that Res can sensitize HCC cells to the anti-tumor effects of Len treatment, including blocking proliferation, inhibiting migration, and inducing apoptosis. Len-resistant CDX and PDX models revealed that Res can reverse the resistant phenotype, with the tumor inhibition rates of 77.46 % and 62.1 %, respectively, when combined with Len treatment. Analysis of xenograft tissues showed that the combination of Res and Len down-regulates the m6A level, reduces proliferation biomarkers, and induces apoptosis, which is consistent with the in vitro data. Mechanistically, our preliminary results indicate that Res can up-regulate the SMAD3 level by down-regulating m6A in Len-resistant cells. CONCLUSIONS: Reserpine, a small-molecule regulator of m6A, reverses Lenvatinib-resistant phenotypes, including proliferation, migration and anti-apoptosis, in vitro and in vivo by targeting SMAD3 and down-regulating the m6A level in HCC.

16.
J Environ Manage ; 370: 122631, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39321678

RESUMO

The implementation of green financial reform and innovation pilot zones is a pivotal initiative aimed at directing financial resources more effectively towards green transformation and national sustainable development strategy. To this end, this study adopts a dual machine learning model to examine the effect of this pilot policy on energy intensity and the underlying mechanisms, drawing upon data from 254 cities in China spanning from 2006 to 2019. The conclusions obtained confirm that the establishment of these pilot zones has exerted a substantial impact on mitigating energy intensity. This inhibitory effect is particularly evident in cities with lower administrative levels, cities in western regions, smaller and medium-sized cities, and cities dominated by the secondary industry. It should be emphasized that the reduction in energy intensity is achieved through fostering green technology innovation and enhancing green financial development. The results not only provide empirical evidence for the effectiveness of green finance pilot policies in reducing energy intensity, thereby enriching the inclusive impact of financial innovation, but also offer practical insights for strengthening the green financial system and replicating and expanding the pilot zones.

17.
Insects ; 15(9)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39336603

RESUMO

The disposal of slaughterhouse blood poses significant environmental challenges due to its biological instability and high nutrient content. We used a gradient of 10% blood increments (0-100%) to feed BSFL, and the correlation between the proportion of bovine blood and the BSFL weight gain, mortality rate, fatty acid content, and amino acid content was researched. Results indicate a positive correlation between the bovine blood content and BSFL mortality, with survival rates above 95% for blood proportions below 60%. Larval weight exhibited a negative correlation as the bovine blood content increased. Nutritional analysis revealed that the crude protein content in BSFL increased proportionally with bovine blood (14.75-25.45 g/100 g), while the crude fat content decreased correspondingly (10.70-4.66 g/100 g). The sugar content remained relatively constant across groups. Fatty acid analysis showed increased levels of C16:0, C14:0, and C16:1 and decreased levels of C18:1, C18:2, and C18:3 with higher bovine blood contents. The amino acid content generally increased with higher blood proportions. This study highlights the bioconversion potential of BSFL for bovine blood and underscores the impact of protein, lipid, and sugar concentrations in feed on BSFL growth. These findings provide valuable insights for utilizing slaughterhouse waste in BSFL rearing, contributing to the development of more sustainable waste management and animal feed production methods.

18.
Front Microbiol ; 15: 1448710, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39328917

RESUMO

Background: Invasive pulmonary aspergillosis (IPA) typically occurs in immunocompromised individuals. Severe fever with thrombocytopenia syndrome (SFTS) patients are typically characterized by fever, thrombocytopenia, and leukopenia. These patients typically present with dysregulation of cellular and humoral immunity, which may predispose them to IPA. Our study aimed to identify risk factors for SFTS-associated invasive pulmonary aspergillosis (SAPA) and evaluate its associated prognostic impact. Methods: We conducted a cohort study between January 2017 and December 2022 in a tertiary hospital in Wuhan City, China. All SFTS patients hospitalized in our department who formally consented were divided into a SAPA group and a non-SAPA group according to whether they were coinfected with aspergillosis or not. The independent risk factors for the SAPA group were determined by multivariate logistic regression. Receiver operating characteristic (ROC) analysis was used to assess the statistical value of parameters to predict SAPA patients. The survival analysis was carried out using the Kaplan-Meier (KM) method. Results: Of the 269 hospitalized SFTS patients enrolled in the study, 118 (43.87%) cases were diagnosed with SAPA with an average age of 65.71 ± 9.7 years. Multivariate logistic regression analysis revealed that age, neurological complications, serum severe fever with thrombocytopenia syndrome virus (SFTSV) RNA loads, the white blood cell (WBC) count, platelet (PLT) count, albumin (ALB) and globulin (GLB) concentrations, and cardiac troponin I (cTNI) were complementary risk factors for the development of IPA in SFTS patients. The risk score is calculated as 5 times age, plus 6 times neurological complications, plus 10 times RNA (log), plus 5 times WBC, minus 5 times PLT, minus 5 times ALB, plus 5 times GLB, and plus 6 times cTNI. ROC curve analysis showed that the area under the receiver operating characteristic (AUROC) curve represented a risk score of 0.837 (95% CI: 0.789-0.885, p < 0.001) for predicting IPA in SFTS patients. The average length of hospitalization in the SAPA group was more prolonged than non-SAPA. SAPA and non-SAPA groups had significantly different mortality rates: 25.42% (SAPA) and 3.97% (non-SAPA) (p < 0.05). Conclusion: SFTS patients with IPA have high morbidity and mortality. Early monitoring of neurological complications, SFTSV RNA loads, WBC, PLT, ALB, GLB, and cTNI in SFTS patients may be useful in predicting the occurrence of IPA.

19.
J Hazard Mater ; 480: 135913, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39332256

RESUMO

The coal-hosted germanium (Ge) deposit in Lincang, China, contains an abnormally high concentration of beryllium (Be), which is of significant organic affinity. However, the specific species of Be at the atomic scale remain unclear. In this study, thirteen model compounds representing O/S/N-containing functional groups in coal were calculated to probe the local environment of Be. The results indicate that hydroxyl and carboxyl groups are the primary acceptors of Be. Various Be-O complexes with a saturated four coordination of Be can achieve best stabilization. In contrast, the heteroatoms S and N are less likely to act as the acceptors for Be. In addition, the calculation results provide theoretical insights into the vertical distribution of Be. Unlike the upper coal seam, a fraction of Be in the middle and lower seams occurs in a mineral phase, which can be attributed to the limited capacity of organic matter to bond with all available Be. Furthermore, competition from other organically-associated metals, such as Ge and W, for bonding sites affects the local distribution of Be. This study reveals the molecular mechanism for Be enrichment in the organic matter of the Lincang Ge deposit, and suggests potential strategies for the removal of organically bonded Be in coal through the destruction of O-bridged complexes.

20.
Sensors (Basel) ; 24(18)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39338779

RESUMO

Underwater target detection is of great significance in underwater ecological assessment and resource development. To better protect the environment and optimize the development of underwater resources, we propose a new underwater target detection model with several innovations based on the YOLOv8 framework. Firstly, the SAConv convolutional operation is introduced to redesign C2f, the core module of YOLOv8, to enhance the network's feature extraction capability for targets of different scales. Secondly, we propose the RFESEConv convolution module instead of the conventional convolution operation in neural networks to cope with the degradation of image channel information in underwater images caused by light refraction and reflection. Finally, we propose an ESPPF module to further enhance the model's multi-scale feature extraction efficiency. Simultaneously, the overall parameters of the model are reduced. Compared to the baseline model, the proposed one demonstrates superior advantages when deployed on underwater devices with limited computational resources. The experimental results show that we have achieved significant detection accuracy on the underwater dataset, with an mAP@50 of 78% and an mAP@50:95 of 43.4%. Both indicators are 2.1% higher compared to the baseline models. Additionally, the proposed model demonstrates superior performance on other datasets, showcasing its strong generalization capability and robustness. This research provides new ideas and methods for underwater target detection and holds important application value.


Assuntos
Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos
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