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1.
Clin Cardiol ; 47(7): e24317, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953595

RESUMO

INTRODUCTION: The DESyne novolimus-eluting coronary stent (NES) is a new-generation drug-eluting stent (DES) that is widely used, but clinical data are rarely reported for this stent. We compared the safety and effectiveness of the DESyne NES and the Orsiro bioresorbable polymer sirolimus-eluting stent (SES) in patients undergoing percutaneous coronary intervention (PCI). METHODS: This was a retrospective, single-center, observational study. Between July 2017 and December 2022, patients who presented with chronic or acute coronary syndrome undergoing PCI with DESyne NES or Orsiro SES were consecutively enrolled in the present study. The primary endpoint, major adverse cardiovascular event (MACE), was a composite of cardiovascular death, target-vessel myocardial infarction, or clinically driven target-lesion revascularization. RESULTS: A total of 776 patients (age 68.8 ± 12.2; 75.9% male) undergoing PCI were included. Overall, 231 patients with 313 lesions received NES and 545 patients with 846 lesions received SES. During a follow-up duration of 784 ± 522 days, the primary endpoint occurred in 10 patients (4.3%) in the NES group and in 36 patients (6.6%) in the SES group. After multivariate adjustment, the risk of MACE did not significantly differ between groups (NES vs. SES, hazard ratio 0.74, 95% CI, 0.35-1.55, p = 0.425). The event rate of individual components of the primary endpoint was comparable between the two groups. CONCLUSIONS: Favorable and similar clinical outcomes were observed in patients undergoing PCI with either NES or SES in a medium-term follow-up duration. Future studies with adequately powered clinical endpoints are required for further evaluation.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea , Desenho de Prótese , Sirolimo , Humanos , Masculino , Feminino , Sirolimo/administração & dosagem , Estudos Retrospectivos , Idoso , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/instrumentação , Resultado do Tratamento , Doença da Artéria Coronariana/terapia , Fatores de Tempo , Seguimentos , Síndrome Coronariana Aguda/terapia , Fatores de Risco , Pessoa de Meia-Idade , Angiografia Coronária , Macrolídeos
2.
Lancet Planet Health ; 8(7): e476-e488, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38969475

RESUMO

BACKGROUND: Climate actions targeting combustion sources can generate large ancillary health benefits via associated air-quality improvements. Therefore, understanding the health costs associated with ambient fine particulate matter (PM2·5) from combustion sources can guide policy design for both air pollution and climate mitigation efforts. METHODS: In this modelling study, we estimated the health costs attributable to ambient PM2·5 from six major combustion sources across 204 countries using updated concentration-response models and an age-adjusted valuation method. We defined major combustion sources as the sum of total coal, liquid fuel and natural gas, solid biofuel, agricultural waste burning, other fires, and 50% of the anthropogenic fugitive, combustion, and industrial dust source. FINDINGS: Global long-term exposure to ambient PM2·5 from combustion sources imposed US$1·1 (95% uncertainty interval 0·8-1·5) trillion in health costs in 2019, accounting for 56% of the total health costs from all PM2·5 sources. Comparing source contributions to PM2·5 concentrations and health costs, we observed a higher share of health costs from combustion sources compared to their contribution to population-weighted PM2·5 concentration across 134 countries, accounting for more than 87% of the global population. This disparity was primarily attributed to the non-linear relationship between PM2·5 concentration and its associated health costs. Globally, phasing out fossil fuels can generate 23% higher relative health benefits compared to their share of PM2·5 reductions. Specifically, the share of health costs for total coal was 36% higher than the source's contributions to corresponding PM2·5 concentrations and the share of health costs for liquid fuel and natural gas was 12% higher. Other than fossil fuels, South Asia was expected to show 16% greater relative health benefits than the percentage reduction in PM2·5 from the abatement of solid biofuel emissions. INTERPRETATION: In most countries, targeting combustion sources might offer greater health benefits than non-combustion sources. This finding provides additional rationale for climate actions aimed at phasing out combustion sources, especially those related to fossil fuels and solid biofuel. Mitigation efforts designed according to source-specific health costs can more effectively avoid health costs than strategies that depend solely on the source contributions to overall PM2·5 concentration. FUNDING: The Health Effects Institute, the National Natural Science Foundation of China, and NASA.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Saúde Global , Material Particulado , Material Particulado/análise , Poluição do Ar/economia , Poluição do Ar/prevenção & controle , Humanos , Poluentes Atmosféricos/análise , Modelos Teóricos , Exposição Ambiental/prevenção & controle , Carvão Mineral/economia
3.
Adv Sci (Weinh) ; : e2400196, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978353

RESUMO

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

4.
J Biophotonics ; : e202400105, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955359

RESUMO

Nail fold capillaroscopy is an important means of monitoring human health. Panoramic nail fold images improve the efficiency and accuracy of examinations. However, the acquisition of panoramic nail fold images is seldom studied and the problem manifests of few matching feature points when image stitching is used for such images. Therefore, this paper presents a method for panoramic nail fold image stitching based on vascular contour enhancement, which first solves the problem of few matching feature points by pre-processing the image with contrast-constrained adaptive histogram equalization (CLAHE), bilateral filtering (BF), and sharpening algorithms. The panoramic images of the nail fold blood vessels are then successfully stitched using the fast robust feature (SURF), fast library of approximate nearest neighbors (FLANN) and random sample agreement (RANSAC) algorithms. The experimental results show that the panoramic image stitched by this paper's algorithm has a field of view width of 7.43 mm, which improves the efficiency and accuracy of diagnosis.

5.
Environ Sci Technol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992920

RESUMO

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38944271

RESUMO

OBJECTIVE: This study aimed to compare the difference in perioperative outcomes and prognosis between neoadjuvant immunochemotherapy (nICT) and neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: The LA-ESCC patients receiving nICT or nCRT were identified from a prospectively maintained database at Zhongshan Hospital of Fudan University between Jan 2018 and March 2022. Propensity score matching (PSM) was performed to balance the two groups. RESULTS: A total of 124 patient pairs were enrolled in the final analysis. The complete pathological response rate (20.2% vs. 29.0%, p=0.140) was similar in the two groups while the lower major pathological response rate (44.4% vs. 61.3%, p=0.011) was observed in the nICT group. nICT was associated with a lower rate of adverse events (42.7% vs. 55.6%, p=0.047) without additional postoperative complications (38.7% vs. 35.5%, p=0.693). The nICT group had lower distant metastasis (6.5% vs. 16.1%, p=0.027) and overall recurrence (11.3% vs. 23.4%, p=0.019) in the postoperative 1 year. Also, nICT was associated with better progression-free survival (HR=0.50; 95% CI: 0.32-0.77; p=0.002). Cox proportional hazard analysis showed that nICT (univariable: HR=0.55; 95% CI: 0.37-0.82; p=0.003; multivariable: HR=0.44; 95% CI: 0.29-0.65; p<0.001) was one of the independent prognostic factors for progression-free survival. The two groups had similar overall survival (HR=0.62; 95%CI: 0.36-1.09; p=0.094) at the latest follow-up. CONCLUSION: This retrospective study showed that nICT was safe and effective for LA-ESCC patients. Further verification is needed in the randomized controlled trials.

7.
J Med Chem ; 67(13): 10743-10773, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38919032

RESUMO

Beta-1,3-glucuronosyltransferase (B3GAT3), overexpressed in hepatocellular carcinoma (HCC) and negatively correlated to prognosis, is a promising target for cancer therapy. Currently, no studies have reported small molecule inhibitors of B3GAT3. In this study, we designed and synthesized a series of small-molecule inhibitors of B3GAT3 through virtual screening and structure optimization. The lead compound TMLB-C16 exhibited potent B3GAT3 inhibitory activity (KD = 3.962 µM) by effectively suppressing proliferation and migration, and inducing cell cycle arrest and apoptosis in MHCC-97H (IC50= 6.53 ± 0.18 µM) and HCCLM3 (IC50= 6.22 ± 0.23 µM) cells. Furthermore, compound TMLB-C16 demonstrated favorable pharmacokinetic properties with a relatively high bioavailability of 68.37%. It significantly inhibited tumor growth in both MHCC-97H and HCCLM3 xenograft tumor models without causing obvious toxicity. These results indicate that compound TMLB-C16 is an effective small molecule inhibitor of B3GAT3, providing a basis for the future development of B3GAT3-targeted drugs.


Assuntos
Acetamidas , Antineoplásicos , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Acetamidas/química , Acetamidas/farmacologia , Acetamidas/síntese química , Acetamidas/uso terapêutico , Camundongos , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Camundongos Nus , Descoberta de Drogas , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto , Simulação de Acoplamento Molecular , Masculino , Movimento Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/síntese química
8.
Opt Express ; 32(12): 20852-20861, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859455

RESUMO

We report on a high-power and narrow-linewidth nanosecond pulsed intracavity crystalline Raman laser at 1.7 µm. Driven by an acousto-optically Q-switched 1314 nm two-crystal Nd:YLF laser, the highly efficient cascaded YVO4 Raman laser at 1715nm was obtained within the well-designed L-shaped resonator. Thanks to the absence of spatial hole burning in the stimulated Raman scattering process, significant spectral purification of second-Stokes radiation was observed by incorporating a fused silica etalon in the high-Q fundamental cavity. Under the repetition rate of 4 kHz, the highest average output power for single longitudinal mode operation was up to 2.2 W with the aid of precision vibration isolation and precision temperature controlling, corresponding to the pulse duration of ∼2.8 ns and the spectral linewidth of ∼330 MHz. Further increasing the launched pump power, the second-Stokes laser tended toward be always multimode, and the maximum average output power amounted to 4.8 W with the peak power of ∼0.8 MW and the spectral linewidth of ∼0.08 nm. The second-Stokes emission was near diffraction limited with M2 < 1.4 across the whole pump power range.

9.
Plant Commun ; : 101000, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38859586

RESUMO

Hybrid crops often exhibit increased yield and greater resilience, yet the genomic mechanism(s) underlying hybrid vigor or heterosis remain unclear, hindering our ability to predict the expression of phenotypic traits in hybrid breeding. Here, we generated haplotype-resolved T2T genome assemblies of two pear hybrid varieties 'Yuluxiangli' (YLX) and 'Hongxiangsu' (HXS) that share the same maternal parent, but differ in their paternal parents. We then used these assemblies to explore genome-scale landscape of allele-specific expression and create a pangenome graph for pear. Allele specific expression (ASE) was observed for close to 6000 genes in both hybrid cultivars. A subset of ASEGs related to fruit quality including sugar, organic acid and cuticular wax were identified, suggesting their important contributions to heterosis. Specifically, Ma1, a gene regulating fruit acidity, was absent in the paternal haplotypes of HXS and YLX. Further, a pangenome graph was built based on our assemblies and eight published pear genomes. Resequencing data for 139 cultivated pear genotypes (including 97 genotypes sequenced here) were subsequently aligned to the pangenome graph, revealing numerous SV hotspots and selective sweeps during pear diversification. As predicted, the Ma1 allele was found to be absent in varieties with low organic acid content, an association that was functionally validated by Ma1 over-expression in pear fruit and calli. Overall, the results unraveled contributions of allele-specific expression to heterosis involving fruit quality and provided a robust pangenome reference for high resolution allele discovery and association mapping.

10.
Brain ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916992

RESUMO

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischemic stroke and then focus on how different stem and progenitor cell sources can promote brain repair. Specifically, we examine how transplanted cell grafts contribute to improved functional recovery either through direct cell replacement or by stimulating endogenous repair pathways. Additionally, we discuss recently implemented preclinical refinement methods, such as preconditioning, microcarriers, genetic safety switches, and universal (immune evasive) cell transplants, as well as the therapeutic potential of these pharmacologic and genetic manipulations to further enhance the efficacy and safety of cell therapies. By gaining a deeper understanding of post-ischemic repair mechanisms, prospective clinical trials may be further refined to advance post-stroke cell therapy to the clinic.

11.
Oncogene ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914663

RESUMO

Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.

12.
J Sci Food Agric ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828647

RESUMO

BACKGROUND: In response to growing concerns regarding heavy metal contamination in food, particularly chromium (Cr)(VI) contamination, this study presented a simple, sensitive and practical method for Cr(VI) detection. RESULTS: A magnetic separation-based capture-exponential enrichment ligand system evolution (SELEX) method was used to identify and characterize DNA aptamers with a high affinity for Cr(VI). An aptamer, Cr-15, with a dissociation constant (Kd) of 4.42 ± 0.44 µmol L-1 was obtained after only eight rounds of selection. Further innovative methods combining molecular docking, dynamic simulation and thermodynamic analysis revealed that CrO4 2- could bind to the 19th and 20th guanine bases of Cr-15 via hydrogen bonds. Crucially, a label-free fluorometric aptasensor based on SYBR Green I was successfully constructed to detect CrO4 2-, achieving a linear detection range of 60-300 nmol L-1 with a lower limit of detection of 44.31 nmol L-1. Additionally, this aptasensor was able to quantitatively detect CrO4 2- in grapes and broccoli within 40 min, with spike recovery rates ranging from 89.22% to 108.05%. The designed fluorometric aptasensor exhibited high selectivity and could detect CrO4 2- in real samples without sample processing or target pre-enrichment. CONCLUSION: The aptasensor demonstrated its potential as a reliable tool for monitoring Cr(VI) contamination in fruit and vegetable products. © 2024 Society of Chemical Industry.

13.
Heliyon ; 10(10): e30985, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38826758

RESUMO

Objectives: FGFR4-variant and wild-type colorectal cancer (CRC) organoids were developed to investigate the effects of FGFR4-targeted drugs, including FGFR4-IN and erdafitinib, on CRC and their possible molecular mechanism. Methods: Clinical CRC tissues were collected, seven CRC organoids were developed, and whole exome sequencing (WES) was performed. CRC organoids were cultured and organoid drug sensitivity studies were conducted. Finally, an FGFR4-variant (no wild-type) CRC patient-derived orthotopic xenograft mouse model was developed. Western blot measured ERK/AKT/STAT3 pathway-related protein levels. Results: WES results revealed the presence of FGFR4-variants in 5 of the 7 CRC organoids. The structural organization and integrity of organoids were significantly altered under the influence of targeted drugs (FGFR4-IN-1 and erdafitinib). The effects of FGFR4 targeted drugs were not selective for FGFR4 genotypes. FGFR4-IN-1 and erdafitinib significantly reduced the growth, diameter, and Adenosine Triphosphate (ATP) activity of organoids. Furthermore, chemotherapeutic drugs, including 5-fluorouracil and cisplatin, inhibited FGFR4-variant and wild-type CRC organoid activity. Moreover, the tumor volume of mice was significantly reduced at week 6, and p-ERK1/2, p-AKT, and p-STAT3 levels were down-regulated following FGFR4-IN-1 and erdafitinib treatment. Conclusions: FGFR4-targeted and chemotherapeutic drugs inhibited the activity of FGFR4-variant and wild-type CRC organoids, and targeted drugs were more effective than chemotherapeutic drugs at the same concentration. Additionally, FGFR4 inhibitors hindered tumorigenesis in FGFR4-variant CRC organoids through ERK1/2, AKT, and STAT3 pathways. However, no wild-type control was tested in this experiment, which need further confirmation in the next study.

14.
Food Sci Nutr ; 12(6): 4173-4184, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873468

RESUMO

Diabetic nephropathy (DN) is a primary diabetic complication ascribed to the pathological changes in renal microvessels. This study investigated the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch ECH associating protein (Keap1)/antioxidant response element (ARE) signaling pathway impact of chitooligosaccharides (COS) with a certain degree of polymerization (DP) on DN mouse models and high glucose-damaged human kidney 2 (HK-2) cells. The findings indicated that COS effectively reduced the renal function indexes (uric acid [UA], urinary albumin excretion rate [UAER], urine albumin-to-creatinine ratio [UACR], blood urea nitrogen [BUN], and creatinine [Cre]) of DN mice. It increased (p < .05) the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) antioxidant enzyme activity in the serum and kidneys, and decreased (p < .05) the malondialdehyde (MDA) content. The mechanistic investigation showed that COS significantly increased (p < .05) Nrf2 and downstream target gene (GCLM, GCLC, HO-1, and NQO-1) expression, and substantially decreased (p < .05) Keap1 expression. The protein level was consistent with the messenger RNA (mRNA) level in in vitro and in vivo models. The docking data indicated that COS and Keap1 protein binding included six hydrogen bond formation processes (Gly364, Arg415, Arg483, His436, Ser431, and Arg380). The COS intervention mechanism may be related to the Nrf2/Keap1/ARE antioxidant pathway. Therefore, it provides a scientific basis for COS application in developing special medical food for DN patients.

15.
Cell ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38936359

RESUMO

Duplication is a foundation of molecular evolution and a driver of genomic and complex diseases. Here, we develop a genome editing tool named Amplification Editing (AE) that enables programmable DNA duplication with precision at chromosomal scale. AE can duplicate human genomes ranging from 20 bp to 100 Mb, a size comparable to human chromosomes. AE exhibits activity across various cell types, encompassing diploid, haploid, and primary cells. AE exhibited up to 73.0% efficiency for 1 Mb and 3.4% for 100 Mb duplications, respectively. Whole-genome sequencing and deep sequencing of the junctions of edited sequences confirm the precision of duplication. AE can create chromosomal microduplications within disease-relevant regions in embryonic stem cells, indicating its potential for generating cellular and animal models. AE is a precise and efficient tool for chromosomal engineering and DNA duplication, broadening the landscape of precision genome editing from an individual genetic locus to the chromosomal scale.

16.
Biomed Environ Sci ; 37(4): 354-366, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727158

RESUMO

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.


Assuntos
Inflamação , Mercúrio , PTEN Fosfo-Hidrolase , Humanos , Regulação para Baixo , Células HEK293 , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/sangue , Mercúrio/toxicidade , Exposição Ocupacional/efeitos adversos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Food Chem ; 454: 139734, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38810454

RESUMO

A fluorescent hybrid film composed of nitrogen-doped graphene quantum dots (N-GQDs) loaded on halloysite nanotubes (HNTs) (N-GQDs/HNTs nanocomposite) as a sensitive element and polyvinyl alcohol (PVA) as a film-forming matrix was designed for freshness detection. The PVA-N-GQDs/HNTs hybrid film exhibited significantly enhanced fluorescence attributed to the loading of N-GQDs onto the surface of HNTs through electrostatic interactions and hydrogen bonding, effectively reducing their aggregation. The fluorescence of the hybrid film could be quenched by ammonia via photoinduced electron transfer (PET), with good linearity in the range of 20 ppm to 500 ppm ammonia and a limit of detection (LOD) of 0.63 ppm. In addition, the hybrid film was applied to monitor the freshness of seawater fish and freshwater fish stored at refrigeration and room temperature to evaluate the practicality of this approach. The developed hybrid film showed promise for nondestructive and on-site monitoring of fish spoilage.


Assuntos
Amônia , Peixes , Grafite , Nanotubos , Álcool de Polivinil , Pontos Quânticos , Alimentos Marinhos , Pontos Quânticos/química , Grafite/química , Nanotubos/química , Animais , Álcool de Polivinil/química , Amônia/química , Amônia/análise , Alimentos Marinhos/análise , Fluorescência , Argila/química , Embalagem de Alimentos/instrumentação , Limite de Detecção , Espectrometria de Fluorescência , Contaminação de Alimentos/análise
18.
BMC Plant Biol ; 24(1): 481, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816698

RESUMO

BACKGROUND: LACS (long-chain acyl-CoA synthetase) genes are widespread in organisms and have multiple functions in plants, especially in lipid metabolism. However, the origin and evolutionary dynamics of the LACS gene family remain largely unknown. RESULTS: Here, we identified 1785 LACS genes in the genomes of 166 diverse plant species and identified the clades (I, II, III, IV, V, VI) of six clades for the LACS gene family of green plants through phylogenetic analysis. Based on the evolutionary history of plant lineages, we found differences in the origins of different clades, with Clade IV originating from chlorophytes and representing the origin of LACS genes in green plants. The structural characteristics of different clades indicate that clade IV is relatively independent, while the relationships between clades (I, II, III) and clades (V, VI) are closer. Dispersed duplication (DSD) and transposed duplication (TRD) are the main forces driving the evolution of plant LACS genes. Network clustering analysis further grouped all LACS genes into six main clusters, with genes within each cluster showing significant co-linearity. Ka/Ks results suggest that LACS family genes underwent purifying selection during evolution. We analyzed the phylogenetic relationships and characteristics of six clades of the LACS gene family to explain the origin, evolutionary history, and phylogenetic relationships of different clades and proposed a hypothetical evolutionary model for the LACS family of genes in plants. CONCLUSIONS: Our research provides genome-wide insights into the evolutionary history of the LACS gene family in green plants. These insights lay an important foundation for comprehensive functional characterization in future research.


Assuntos
Coenzima A Ligases , Evolução Molecular , Família Multigênica , Filogenia , Plantas , Coenzima A Ligases/genética , Plantas/genética , Plantas/classificação , Proteínas de Plantas/genética , Genes de Plantas , Genoma de Planta , Duplicação Gênica
19.
Biomimetics (Basel) ; 9(5)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38786498

RESUMO

Due to their advantages of good stability, adaptability, and flexibility, multi-legged robots are increasingly important in fields such as rescue, military, and healthcare. This study focuses on the millipede, a multi-segmented organism, and designs a novel multi-segment biomimetic robot based on an in-depth investigation of the millipede's biological characteristics and locomotion mechanisms. Key leg joints of millipede locomotion are targeted, and a mathematical model of the biomimetic robot's leg joint structure is established for kinematic analysis. Furthermore, a central pattern generator (CPG) control strategy is studied for multi-jointed biomimetic millipede robots. Inspired by the millipede's neural system, a simplified single-loop CPG network model is constructed, reducing the number of oscillators from 48 to 16. Experimental trials are conducted using a prototype to test walking in a wave-like gait, walking with a leg removed, and walking on complex terrain. The results demonstrate that under CPG waveform input conditions, the robot can walk stably, and the impact of a leg failure on overall locomotion is acceptable, with minimal speed loss observed when walking on complex terrain. The research on the structure and motion control algorithms of multi-jointed biomimetic robots lays a technical foundation, expanding their potential applications in exploring unknown environments, rescue missions, agriculture, and other fields.

20.
Nanomaterials (Basel) ; 14(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38786791

RESUMO

Electrochemical oxygen reduction reaction (ORR) via the 2e- pathway in an acidic media shows great techno-economic potential for the production of hydrogen peroxide. Currently, carbon-based single-atom catalysts (C-SACs) have attracted extensive attention due to their tunable electronic structures, low cost, and sufficient stability in acidic media. This review summarizes recent advances in metal centers and their coordination environment in C-SACs for 2e--ORR. Firstly, the reaction mechanism of 2e--ORR on the active sites of C-SACs is systematically presented. Secondly, the structural regulation strategies for the active sites of 2e--ORR are further summarized, including the metal active center, its species and configurations of nitrogen coordination or heteroatom coordination, and their near functional groups or substitute groups, which would provide available and proper ideas for developing superior acidic 2e--ORR electrocatalysts of C-SACs. Finally, we propose the current challenges and future opportunities regarding the acidic 2e--ORR pathway on C-SACs, which will eventually accelerate the development of the distributed H2O2 electrosynthesis process.

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