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1.
Soft Matter ; 20(40): 8089-8097, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39356209

RESUMO

Due to the sustainability and widespread use of proteins, protein-based materials are extensively utilized in the preparation of Pickering emulsions. However, the relationship between the secondary structure of proteins and their emulsifying ability has not been further investigated. This study used the addition of three different amino acids to influence the interaction between zein chains, which may induce changes in the secondary structure of the prepared zein complex particles. This study demonstrates that the emulsifying properties of proteins, such as dispersibility, zeta potential, three-phase contact angles, interfacial affinity, adsorption rates, and the volume of the stabilized oil phase, are closely related to the ß-sheet content of the complex particles, providing a theoretical reference for protein-based stabilizers. Additionally, amino acids, as the blocks of proteins, have high compatibility with proteins, and using amino acids as modifiers aligns with the safety requirements for food processing. In this study, the prepared zein-lysine complex particles have good emulsifying ability, capable of stabilizing a 50 (v/v)% emulsion at a lower concentration (10 mg mL-1), and the prepared emulsion exhibits high-temperature stability and ionic resistance. This characteristic makes the emulsion potentially valuable for application in systems with high salt concentrations and those that may undergo heat treatment.


Assuntos
Emulsões , Lisina , Zeína , Zeína/química , Emulsões/química , Lisina/química , Estrutura Secundária de Proteína , Emulsificantes/química
2.
J Environ Manage ; 370: 123026, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39447368

RESUMO

The filling substrate is one of key factors influencing effectiveness of sulfate reducing packed-bed bioreactor (SRPB) treating acid mine drainage (AMD). The effects of four substrates (i.e. quartz sand, steel residue, biochar, and peanut shell) on remediation performance and sulfur transformation of SRPB treating AMD was studied. The results showed that steel residue and biochar improved sulfate reduction efficiency (61% and 49%) compared to quartz sand (32%), whereas peanut shell inhibited sulfate reduction efficiency (19%), attributed to its decomposition process leading to a severe accumulation of acetic acid. More amounts of sulfides generated in steel residue bioreactor were converted into acid volatile sulfide and elemental sulfur, resulting in a significant decrease in dissolved sulfide in the effluent. Metals (Fe, Al, Zn, Cd and Cr) except for Mn were effectively immobilized in the bioreactors, particularly for Al and Cd. Sulfate reducing bacteria and sulfide oxidizing bacteria lived symbiotically in all bioreactors which exhibited similar heterogeneity in microbial distribution and function, i.e. bacterial sulfate reduction mainly occurring in bottom-middle layers and photoautotrophic sulfide oxidation in upper layer close to outlet. The microbial response mechanism to various substrate environments was revealed through co-occurrence networks analysis. This study suggests that attention should be paid to the inhibitory effect of acetic acid accumulation on sulfate reduction when using sole lignocellulosic waste (peanut shell), and steel residue and biochar could be utilized as filling substances to promote sulfate reduction.

3.
Sci Rep ; 14(1): 24636, 2024 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-39428498

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and metabolic abnormality disease that mainly affects women of reproductive age. LINC00173, a novel long noncoding RNA (lncRNA), has emerged as an important factor in the development of PCOS. However, the role of LINC00173 in PCOS development and its specific upstream and downstream mechanisms remain to be further clarified. Here, we found that LINC00173 was significantly upregulated in granulosa cells (GCs) of PCOS patients, and played a crucial role in promoting apoptosis of GCs. Mechanistically, we observed the activation of endoplasmic reticulum (ER) stress in the GCs of PCOS patients, and the ER stress sensor ATF4 could directly induce LINC00173 expression by binding to its promoter. LINC00173 further upregulated the expression of Harakiri (HRK) and subsequently inhibited downstream PI3K/AKT pathway. In conclusions, our study uncovered that ER stress-induced upregulation of LINC00173 leads to increased HRK expression and inhibition of the PI3K/AKT pathway, thereby promoting the progression of PCOS. These findings provide a new therapeutic strategy for the treatment of PCOS.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Células da Granulosa , Fosfatidilinositol 3-Quinases , Síndrome do Ovário Policístico , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante , Feminino , Humanos , Apoptose/genética , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais
4.
ACS Macro Lett ; : 1403-1410, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377265

RESUMO

Clusteroluminescent polymers have the most potential to be used in light conversion agricultural films due to tunable emission wavelength and large-scale production, but they are still limited by shortcomings such as poor stability and sensitivity to melting processes. In this work, we propose a core-shell confined stable clusteroluminescent polymeric nanoparticle strategy with adjustable shell thickness. By the employment of a combination of solvent and heat treatment methods, the structures, rigid-flexible properties, and aggregation states of the core polymer chains have been modified. The presence of cross-linked shells has significantly enhanced the stability of the clusteroluminescent nanoparticles, ensuring that they retain their structure form even after undergoing high temperature and shear. Finally, the stable agricultural light conversion films with tunable clusteroluminescence are obtained via melt blending of the core-shell confined nanoparticles and polyethylene (PE). Due to the shell confinement effect, when melt-blended, the shell can protect the clusteroluminescent polymer within the core from the effects of high temperature and shear. It is anticipated that the completion of this work will provide a significant foundation for the large-scale application of cluster-luminescent polymers in agriculture.

5.
Discov Oncol ; 15(1): 549, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39394548

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer. METHODS: We utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways. RESULTS: Our analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways. CONCLUSION: Our findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis.

6.
Mikrochim Acta ; 191(11): 678, 2024 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420129

RESUMO

Methidathion (MTDT), a common organophosphorus pesticide with high insecticidal activity, is widely used for pest control. However, the misuse of MTDT leads to widespread residues and endangers human health. Therefore, it is crucial to develop a simple and highly sensitive method for the detection of MTDT residues. Herein, ZIF-90/MnO2/g-C3N4/Fe3O4 composite particles were synthesized: The  MnO2 nanosheets could absorb the energy of the excited g-C3N4 to quench the ECL of g-C3N4 while ZIF-90 acted as a mimetic enzyme to catalyze the formation of thiocholine from MTDT. The thiocholine caused the reduction of MnO2 to Mn2+, restoring the ECL signal of g-C3N4. Combined with molecular imprinting technique, an electrochemiluminescence sensor was constructed for the determination of MTDT. The determination range was 1.00 × 10-9 ~ 7.00 × 10-7 g/L, and the detection limit was 6.58 × 10-10 g/L. Structurally similar organophosphorus pesticides showed no cross-reactivity. The method has high sensitivity and specificity, and has been successfully applied to the determination of MTDT residue in fruits with recoveries in the range 93.75% ~ 102.37%.


Assuntos
Técnicas Eletroquímicas , Limite de Detecção , Medições Luminescentes , Compostos de Manganês , Compostos Organotiofosforados , Óxidos , Compostos de Manganês/química , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , Óxidos/química , Compostos Organotiofosforados/análise , Compostos Organotiofosforados/química , Impressão Molecular , Grafite/química , Zeolitas/química , Inseticidas/análise , Compostos de Nitrogênio/química , Nanopartículas de Magnetita/química , Nitrilas/química
7.
J Environ Manage ; 370: 122848, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39405844

RESUMO

Iron (Fe) modified biochar has been widely used for cadmium (Cd) contaminated soil remediation. However, the accompanying anions introduced during the modification process potentially affect the behavior of Cd in soil. In this study, we investigated the distinct Cd immobilization mechanisms by Fe2(SO4)3 modified biochar (FSBC) and Fe(NO3)3 modified biochar (FNBC) in a two-year pot experiment. Results showed that both FSBC and FNBC significantly reduced Cd concentrations in rice grains by 23%-42% and 30%-37% compared to pristine biochar (BC). Specifically, NFBC promoted the formation of amorphous Fe oxides by enhancing the NO3--reducing Fe(II) oxidation process, which significantly increased Fe/Mn oxide-bound Cd and decreased soil CaCl2-extractable Cd. For FSBC, the introduction of SO42- significantly promoted the formation of Fe plaques by enhancing the Fe(III) reduction process, which blocked the Cd transfer from the soil to the rice roots. More importantly, after two years of biochar application, an organo-mineral complex layer is formed on the biochar surface, which immobilized a large amount of Cd. The Cd immobilization on the surface of aged biochar could be due to the fixation by the secondary Fe oxides within the organo-mineral layer and the complexation by the surface functional groups. The result of laser ablation inductively coupled plasma mass spectrometry showed that the Cd content on aged FNBC and FSBC was 5.9 and 2.6 times higher than on aged BC. This might be attributed to the Fe-modified biochar's higher electron exchange capability (EEC), which promoted the development of organo-mineral complexes. Notably, the EEC of biochar was maintained during its aging process, which may keep the biochar surface active and facilitate continual Cd immobilization. This study revealed the complex mechanisms of soil Cd immobilization with Fe-modified biochar, providing new insights into sustainable biochar environmental remediation.

8.
Langmuir ; 40(39): 20763-20772, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39287408

RESUMO

Slippery liquid-infused porous surfaces (SLIPS) have promising applications in chip laboratories, nanofriction power generation, and microfluidics due to their excellent properties such as good hydrophobicity and low adhesion. However, the self-driven stability of conventionally lubricated surfaces is not high, and the velocity of liquid droplets is difficult to regulate. This greatly limits the potential applications of SLIPS. A strategy is offered to prepare microporous structures of SLIPS directly on a stainless-steel substrate using femtosecond laser processing technology as the main means to realize exhibiting smoothness to liquids. At the same time, the principle of bionics is utilized, the porous structure of SLIPS is combined with the groove structure of rice leaves, or porous structures are combined with the wedge structure of shorebird beak to prepare the three-dimensional structure of SLIPS. Droplets exhibit significant individual anisotropy on three-dimensional (3D) SLIPS of leaf-like groove stripe structure in rice, enabling the precise control of droplet motion direction. When droplets are transported in wedge-shaped SLIPS with an asymmetric structure, the wedge edge can limit the direction of droplet motion while squeezing the droplet to generate Laplace pressure gradient, which achieves continuous self-driven transport of droplets. In addition, based on the above two processing strategies, an information transfer device is designed: the splicing of the self-driven transport surface with anisotropic topological channels enables the differential drive for liquid transport, which provides the conditions for the information transfer of the droplets. This strategy not only is simple and efficient but also provides new ideas for the effective development of multifunctional SLIPS as well as lab-on-a-chip and microfluidic domains.

9.
Wei Sheng Yan Jiu ; 53(5): 746-754, 2024 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-39308106

RESUMO

OBJECTIVE: To determine the percentile reference values and reference curves of total body fat percentage in children and adolescents by sex and age, and to evaluate the reliability of different anthropometric indicators in screening for obesity in children and adolescents in order to explore the validity and practicality of a large-scale screening tool for childhood obesity and its desirable thresholds. METHODS: A total of 5983 children and adolescents aged 6-18 years from six primary and secondary schools were selected by stratified randomised cluster sampling in Hangzhou City in 2023, and their weight, height, waist and hip circumferences were measured, and the children's total body fat content was measured using the bioelectrical resistance-antibody composition analyser. A generalised additive model(GAMLSS) was used to construct a percentile reference curve for children's body fat percentage, and the performance of each anthropometric measure in correctly classifying children and adolescents as obese was assessed using receiver operating characteristic(ROC) curves. RESULTS: Over the period 6-18 years, body fat percentage in girls tended to increase with age from year to year, whereas in boys it tended to increase and then decrease. Fat mass index was the main factor contributing to the difference in BMI at the same age and sex(the optimal cutoff values were 26.82 and 24.52, with AUC values of 0.988 and 0.992, respectively), and the contribution of fat mass index was greater in those with a higher BMI. BMI, which had the largest area under the curve for both boys and girls, was the best indicator for assessing obesity in children and adolescents; the waist-to-height ratio(WHtR), with small variability and equally large area under curve values(0.980 for boys and 0.970 for girls), could simultaneously meet the requirements of accuracy and practicality for obesity assessment in mass screening of children and adolescents. CONCLUSION: This study establish the percentile reference value and reference curve of body fat percentage of children and adolescents aged 6-18 years in Hangzhou based on bioelectrical impedance method, and found that WHtR is a simple, effective and practical screening tool for childhood obesity with low variability, which can provide a reference basis for evaluating growth and development and identifying obesity in children aged 6-18 years in this region.


Assuntos
Índice de Massa Corporal , Humanos , Adolescente , Criança , Masculino , Feminino , China , Valores de Referência , Obesidade Infantil/diagnóstico , Programas de Rastreamento/métodos , Antropometria/métodos , Peso Corporal , Tecido Adiposo
10.
Exp Eye Res ; 247: 110041, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39147192

RESUMO

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.


Assuntos
Compostos de Benzalcônio , Modelos Animais de Doenças , Síndromes do Olho Seco , Vesículas Extracelulares , Macrófagos , Camundongos Endogâmicos C57BL , Lágrimas , Animais , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/induzido quimicamente , Vesículas Extracelulares/metabolismo , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Lágrimas/metabolismo , Conservantes Farmacêuticos , Soluções Oftálmicas , Córnea/metabolismo , Córnea/efeitos dos fármacos , Córnea/patologia , Citocinas/metabolismo , Feminino
11.
Nutr Metab Cardiovasc Dis ; 34(11): 2498-2510, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39117486

RESUMO

BACKGROUND AND AIM: Identifying a more suitable marker among various measures of adiposity, demonstrating strong associations and predictive ability for clinical use, remains a topic of debate. Weight-adjusted waist index (WWI) has been proposed as a novel index of adiposity, yet its exploration is limited, especially in Chinese populations. This study seeks to examine the associations between body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHTR), weight-adjusted waist index (WWI), waist circumference divided by body mass to the power of 0.333 (WC/M0.333), visceral adiposity index (VAI), lipid accumulation product (LAP), and the incidence of diabetes, cardiovascular disease, and non-accidental mortality in Chinese populations. Furthermore, our goal is to compare the respective predictive values of these measures for these health outcomes. METHODS AND RESULTS: This prospective cohort study included 21,750 subjects with a 9-year follow-up period. Cox proportional hazard models were used to investigate the relationship between eight anthropometric indexes and the incidence of diabetes, cardiovascular disease, and non-accidental mortality. The predictive value of these eight indexes was compared using the area under the curve metric. Significant positive associations were found between WWI and the risk of diabetes. Using the first quartile (Q1) of WWI as the reference group, hazard ratios with 95% confidence intervals for the risk of diabetes were 1.58 (0.98-2.55) for Q2, 2.18 (1.34-3.35) for Q3, and 2.27 (1.41-3.67) for Q4. Significant associations were observed with the highest quartile of WWI for the risk of cardiovascular disease [Q2: HR 1.45 (95% CI 1.06-1.98); Q3: 1.33 (0.97-1.83); Q4: 1.55 (1.13-2.14)] and risk of non-accidental mortality [Q2: 0.94 (0.80-1.11); Q3: 1.24 (1.04-1.48); Q4: 1.44 (1.16-1.79)]. Receiver operating characteristic analysis revealed that WWI exhibited superior discrimination and accuracy in predicting cardiovascular disease and non-accidental mortality compared to other adiposity indexes (BMI, WC, WHR, WHTR, WC/M0.333, VAI, and LAP). CONCLUSION: WWI exhibited the most robust and consistent association with the incidence of cardiovascular disease and non-accidental mortality. Given its simplicity and widespread use, WWI emerges as a novel and practical predictor of diabetes, cardiovascular disease, and non-accidental mortality among the eight adiposity indexes investigated in this study.


Assuntos
Adiposidade , Doenças Cardiovasculares , Diabetes Mellitus , Valor Preditivo dos Testes , Circunferência da Cintura , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Medição de Risco , Incidência , Estudos Prospectivos , China/epidemiologia , Adulto , Diabetes Mellitus/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Fatores de Tempo , Prognóstico , Índice de Massa Corporal , Razão Cintura-Estatura , Fatores de Risco , Idoso , Obesidade/mortalidade , Obesidade/diagnóstico , Obesidade/epidemiologia , Produto da Acumulação Lipídica , Relação Cintura-Quadril , Fatores de Risco de Doenças Cardíacas
12.
Faraday Discuss ; 253(0): 365-384, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39176453

RESUMO

Ionic liquids (ILs) are an extremely exciting class of electrolytes for energy storage applications. Upon dissolving alkali metal salts, such as Li or Na based salts, with the same anion as the IL, an intrinsically asymmetric electrolyte can be created for use in batteries, known as a salt-in-ionic liquid (SiIL). These SiILs have been well studied in the bulk, where negative transference numbers of the alkali metal cation have been observed from the formation of small, negatively charged clusters. The properties of these SiILs at electrified interfaces, however, have received little to no attention. Here, we develop a theory for the electrical double layer (EDL) of SiILs where we consistently account for the thermoreversible association of ions into Cayley tree aggregates. The theory predicts that the IL cations first populate the EDL at negative voltages, as they are not strongly bound to the anions. However, at large negative voltages, which are strong enough to break the alkali metal cation-anion associations, these IL cations are exchanged for the alkali metal cation because of their higher charge density. At positive voltages, we find that the SiIL actually becomes more aggregated while screening the electrode charge from the formation of large, negatively charged aggregates. Therefore, in contrast to conventional intuition of associations in the EDL, SiILs appear to become more associated in certain electric fields. We present these theoretical predictions to be verified by molecular dynamics simulations and experimental measurements.

14.
Carbohydr Polym ; 343: 122498, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39174107

RESUMO

In recent years, active substances have been extensively applied in the fields of food, cosmetics, and pharmaceuticals. However, their preservation and transportation have posed challenges due to issues such as oxidation and photodegradation. This study proposes a method for synthesizing Zein-Hyaluronic Acid (Zein-HA) conjugate particles via the Schiff base reaction, utilizing these conjugate particles to encapsulate and protect active substances within a stable emulsion system. Compared to zein, the modified conjugate particles exhibit significantly improved dispersibility, amphiphilicity, interfacial affinity, and emulsifying properties. Consequently, these particles are capable of stabilizing high internal phase Pickering emulsions with an oil phase volume fraction of up to 80 (v/v)%, thereby enabling the carriage of a higher load of active components. Furthermore, the prepared emulsions demonstrate excellent storage stability, resistance to ionic strength (250-2000 mM NaCl), and outstanding antioxidative characteristics. Moreover, after 8 h of UV light exposure, the retention rates of the active substances (curcumin, astaxanthin, and resveratrol) exceed 60 %. Therefore, these emulsions hold substantial potential to be applied as a carrier system in the food, cosmetics, and pharmaceutical industries.

15.
PLoS Pathog ; 20(8): e1012291, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39102426

RESUMO

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.


Assuntos
COVID-19 , Senescência Celular , Células Gigantes , Insuficiência Cardíaca , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/virologia , Animais , Células Gigantes/virologia , Células Gigantes/metabolismo , Células Gigantes/patologia , COVID-19/metabolismo , COVID-19/complicações , COVID-19/virologia , COVID-19/patologia , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Camundongos , Vesículas Extracelulares/metabolismo
16.
ACS Macro Lett ; 13(9): 1112-1118, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39133642

RESUMO

A robust and fully biobased covalent adaptable network (CAN) that allows recyclability, biocompatibility, and controlled biodegradability is reported. The CAN was fabricated through a simple photo-cross-linking method, wherein low-molecular-weight poly(lactic acid) (∼3 kDa) was modified with end 1,2-dithiolane rings through a one-step Steglich esterification reaction with thioctic acid (TA). These incorporated 1,2-dithiolane rings undergo photoinduced ring-opening polymerization, thus enabling the cross-linking of poly(lactic acid) with abundant dynamic disulfide bonds. The resultant CAN demonstrates excellent transparency, effective UV-blocking capabilities below 320 nm, robust tensile strength (∼39 MPa), and superior dimensional stability at 80 °C, alongside attractive biocompatibility. Moreover, owing to the dynamic exchange and redox-responsiveness of disulfide bonds, the material can be recycled by hot-pressing and a reduction-oxidation process while also being capable of controllably biodegrading at the end of its lifecycle. Furthermore, it exhibits reconfigurable shape memory properties with fast recovery. This study elucidates a straightforward approach to fabricating multifunctional and sustainable polymer materials with potential applications in diverse fields such as packaging, coating, and biomedicine.

17.
Discov Med ; 36(186): 1477-1485, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39054718

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as RAS, BRAF, and microsatellite instability (MSI). Novel genomic changes, including ERBB2 amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies. METHODS: A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated. RESULTS: The cohort's genomic profiling revealed TP53 mutations in 78%, APC in 60%, and KRAS in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. ERBB2/HER2 amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent KRAS mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except TP53) that could be targeted therapeutically. The KRAS (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a BRAF V600E mutation. Notably, survival analysis showed no significant differences in OS between KRAS mutant loci and NRAS mutations (p = 0.436). However, BRAF V600E mutations were associated with a poorer prognosis than BRAF wild-type and non-V600E mutations (16.3 months vs. 29.5 and 31.1 months, respectively; p < 0.001). CONCLUSIONS: This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.


Assuntos
Neoplasias Colorretais , Mutação , Metástase Neoplásica , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , China/epidemiologia , Instabilidade de Microssatélites , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Idoso de 80 Anos ou mais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , População do Leste Asiático
18.
BMC Urol ; 24(1): 149, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026274

RESUMO

OBJECTIVES: To compare the clinical efficacy and safety of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones. METHODS: We enrolled 135 patients underwent reusable flexible ureteroscopy (FURS) and 78 patients underwent single-use digital FURS. Demographic, clinical variables, anatomical parameters of the lower calyx and perioperative indicators were compared in the two groups. RESULTS: Thirty-six patients in the infundibuloureter angle (IPA) < 45° subgroup had a mini-percutaneous nephrolithotomy (mini-PCNL), including 25 patients in the reusable FURS group and 11 patients in the single-use FURS group. The demographic and clinical variables in the two FURS groups were comparable. There was no statistical difference in the success rate of stone searching (P > 0.05). In terms of the success rate of lithotripsy, there was also no statistical difference in the IPA ≥ 45° subgroup (P > 0.05), whereas single-use FURS was superior in the IPA < 45° subgroup (χ2 = 6.513, P = 0.011). The length of the working fiber in the reusable FURS and single-use FURS groups was 3.20 ± 0.68 mm and 1.75 ± 0.47 mm, respectively (t = 18.297, P < 0.05). The use of a stone basket in the reusable FURS (31/135, 23.0%) was significantly higher than that in the single-use FURS (8/78, 10.3%) (χ2 = 5.336, P = 0.021). Compared with the reusable FURS group, the single-use FURS group had shorter operation times (P < 0.05) and higher stone-free rate (SFR) (χ2 = 4.230, P = 0.040). There was no statistical difference in the intraoperative transfer of mini-PCNL and postoperative complications between the two groups (P > 0.05). CONCLUSIONS: Single-use and reusable FURS are alternative methods for removal of lower pole stones (i.e., 2 cm or less). Single-use FURS has a high success rate of lithotripsy, shorter operation time, and high stone-free rate.


Assuntos
Reutilização de Equipamento , Cálculos Renais , Ureteroscópios , Ureteroscopia , Humanos , Ureteroscopia/métodos , Ureteroscopia/instrumentação , Masculino , Feminino , Estudos Retrospectivos , Cálculos Renais/cirurgia , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Resultado do Tratamento , Desenho de Equipamento , Equipamentos Descartáveis , Idoso
19.
Arab J Gastroenterol ; 25(3): 275-283, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043541

RESUMO

BACKGROUND AND STUDY AIMS: The clinicopathological risk factors in the prognosis of stage IV gastric cancer have been comprehensively studied. However, the influencing factors of stage IV gastric cancer prognosis at genomic and transcriptional levels have not been well defined. PATIENTS AND METHODS: The mutational and transcriptional data, along with demographic, clinicopathological and prognostic information of 44 stage IV gastric cancer patients were downloaded from the TCGA database. Univariate and multivariate analyses were performed to identify the significant risk factors and a Nomogram model was established to predict the patient prognosis. RESULTS: TTN, TP53, FLG, LRP1B, SYNE1 and ARID1A were among the top mutated genes without hot-spot mutations. The mutational status of AHNAK2, ASCC3, DNAH3, DOP1A, MYLK, SIPA1L1, SORBS2, SYNE1 and ANF462 significantly stratified the patient prognosis. The transcription of several genes, such as AQP10, HOXC8/9/10, COL10A1/COL11A1, WNT7B, KRT17 and KLK6 was significantly up-regulated or down-regulated. Enrichment analysis on mutations and transcription revealed cell skeleton and membrane function, extracellular matrix function, HPV infection, and several cancer-related pathways as the main aberrancies. Univariate analyses revealed a series of significant factors stratifying patient prognosis, mainly including cancer location, several mutated genes and many up- or down-regulated genes. However, subsequent multivariate analysis revealed SYNE1 mutation, DNAH3 mutation, COMMD3 transcription level, and cancer location as the independent risk factors. A Nomogram model has been established with these significant risk factors to predict the patient prognosis. Further validation is needed to ensure the effectiveness of the model in real clinical practice. CONCLUSIONS: Cancer location, along with the mutational status of SYNE1 and DNAH3 and the transcriptional level of COMMD3 were independent risk factors of stage IV gastric cancer. A Nomogram model was established with these factors for prognosis prediction.


Assuntos
Mutação , Estadiamento de Neoplasias , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Fatores de Risco , Proteínas Nucleares/genética , Proteínas Filagrinas , Proteínas do Tecido Nervoso/genética , Proteínas dos Microfilamentos/genética , Idoso , Proteínas de Ligação a DNA/genética , Biomarcadores Tumorais/genética , Regulação para Baixo , Proteínas do Citoesqueleto , Receptores de LDL
20.
Aging Male ; 27(1): 2363267, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38867423

RESUMO

OBJECTIVE: To investigate the practical value of the transrectal two-dimensional shear-wave elastography (SWE) in benign prostatic hyperplasia (BPH). METHODS: Consecutive male participants with and without BPH constituted the BPH and control group respectively were enrolled prospectively between March and December 2022. Transrectal conventional ultrasound and SWE examinations for the prostate were performed on these participants. Data of quantitative stiffness of the transitional zone (TZ) and peripheral zone (PZ) of prostate, volume of prostate (VP) and volume of TZ (VTZ) and prostate specific androgen (PSA), etc., were collected. Linear regression analyses were used to investigate the associations between quantitative stiffness data and other clinical parameters. RESULTS: There were 200 participants evaluated, including 100 healthy participants and 100 BPH patients. For every one-year increment in age, it was correlated with 0.50 kPa increasement of TZ stiffness. VP and VTZ were correlated with TZ stiffness. Higher TZ stiffness was associated with higher free prostate specific antigen (PSA) and total PSA. CONCLUSIONS: The prostate is stiffer and larger in BPH group compared to control group. Quantitative stiffness of the TZ was related with age, VP, VTZ and PSA.


Assuntos
Técnicas de Imagem por Elasticidade , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Casos e Controles , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue
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