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BACKGROUND AIMS: Studies have shown that blocking the PD-1/PD-L1 pathway may lead to a potential cure for HBV infections. ASC22 (Envafolimab) is a humanized, single-domain PD-L1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed chronic hepatitis B (CHB) patients on nucleos(t)ide analogs (NAs). APPROACH AND RESULTS: This randomized, single-blind, phase IIb trial enrolled CHB patients in two cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22 and PBO, respectively. The mean HBsAg changes from baseline at week 24 and 24 week follow-up periods were -0.309 (p<0.001) and -0.272 (p<0.023) log10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 (p=0.007) and -0.205 (p=0.12) log10 IU/mL in the 2.5 mg/kg ASC22 group, and-0.003 and -0.063 log10 IU/mL in the PBO group, respectively (ITT population). Three out of ten patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most AEs were mild (97.9%). There were no study drug-related serious AEs in the 1.0 mg/kg ASC22 group. CONCLUSIONS: Subcutaneous administration of 1.0 mg/kg ASC22 Q2W for 24 weeks was shown to be safe and well tolerated in virally suppressed CHB patients on NAs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.
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High-entropy alloys (HEAs) involving more than four elements, as emerging alloys, have brought about a paradigm shift in material design. The unprecedented compositional diversities and structural complexities of HEAs endow multidimensional exploration space and great potential for practical benefits, as well as a formidable challenge for synthesis. To further optimize performance and promote advanced applications, it is essential to synthesize HEAs with desired characteristics to satisfy the requirements in the application scenarios. The properties of HEAs are highly related to their chemical compositions, microstructure, and morphology. In this review, a comprehensive overview of the controllable synthesis of HEAs is provided, ranging from composition design to morphology control, structure construction, and surface/interface engineering. The fundamental parameters and advanced characterization related to HEAs are introduced. We also propose several critical directions for future development. This review can provide insight and an in-depth understanding of HEAs, accelerating the synthesis of the desired HEAs.
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Hepatocellular carcinoma (HCC) poses a significant challenge with dismal survival rates, necessitating a deeper understanding of its molecular mechanisms and the development of improved therapies. Metabolic reprogramming, particularly heightened glycolysis, plays a crucial role in HCC progression. Glycolysis-associated genes (GAGs) emerge as key players in HCC pathogenesis, influencing the tumor microenvironment and immune responses. This study aims to investigate the intricate interplay between GAGs and the immune landscape within HCC, offering valuable insights into potential prognostic markers and therapeutic targets to enhance treatment strategies and patient outcomes. Through the exploration of GAGs, we have identified two distinct molecular glycolytic subtypes in HCC patients, each exhibiting significant differences in both the immune microenvironment and prognosis. A risk model comprising five key GAGs was formulated and subsequently evaluated for their predictive accuracy. Our findings underscore the diverse tumor microenvironment and immune responses associated with the varying glycolytic subtypes observed in HCC. The identified key GAGs hold promise as prognostic indicators for evaluating HCC risk levels, predicting patient outcomes, and guiding clinical treatment decisions, particularly in the context of anticipating responses to immunotherapy drugs.
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Carcinoma Hepatocelular , Glicólise , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Glicólise/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Feminino , Masculino , Pessoa de Meia-Idade , Relevância ClínicaRESUMO
High-entropy oxides (HEOs) with an ultrathin geometric structure are especially expected to exhibit extraordinary performance in different fields. The phase structure is deemed as a key factor in determining the properties of HEOs, rendering their phase control synthesis tempting. However, the disparity in intrinsic phase structures and physicochemical properties of multiple components makes it challenging to form single-phase HEOs with the target phase. Herein, we proposed a self-lattice framework-guided strategy to realize the synthesis of ultrathin HEOs with desired phase structures, including rock-salt, spinel, perovskite, and fluorite phases. The participation of the Ga assistor was conducive to the formation of the high-entropy mixing state by decreasing the formation energy. The as-prepared ultrathin spinel HEOs were demonstrated to be an excellent catalyst with high activity and stability for the oxygen evolution reaction in water electrolysis. Our work injects new vitality into the synthesis of HEOs for advanced applications and undoubtedly expedites their phase engineering.
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Gallium-based (Ga-based) liquid metals have attracted considerable interest due to their low melting points, enabling them to feature both liquid properties and metallic properties at room temperature. In light of this, Ga-based liquid metals also possess excellent deformability, high electrical and thermal conductivity, superior metal affinity, and unique self-limited surface oxide, making them popular functional materials in energy storage. This provides a possibility to construct high-performance rechargeable batteries that are deformable, free of dendrite growth, and so on. This review primarily starts with the property of Ga-based liquid metal, and then focuses on the potential applications in rechargeable batteries by exploiting these advantages, aiming to construct the correlation between properties and structures. The glorious applications contain interface protection, self-healing electrode construction, thermal management, and flexible batteries. Finally, the opportunities and obstacles for the applications of liquid metal in batteries are presented.
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We investigated secondary cavitation bubble dynamics during laser-induced bubble formation in a small container with a partially confined free surface and elastic thin walls. We employed high-speed photography to record the dynamics of sub-mm-sized laser-induced bubbles and small secondary bubble clouds. Simultaneous light scattering and acoustic measurements were used to detect the oscillation times of laser-induced bubbles. We observed that the appearance of secondary bubbles coincides with a prolonged collapse phase and with re-oscillations of the laser-induced bubble. We observed an asymmetric distribution of secondary bubbles with a preference for the upstream side of the focus, an absence of secondary bubbles in the immediate vicinity of the laser focus, and a migration of laser-induced bubble toward secondary bubbles at large pulse energies. We found that secondary bubbles are created through heating of impurities to form initial nanobubble nuclei, which are further expanded by rarefaction waves. The rarefaction waves originate from the vibration of the elastic thin walls, which are excited either directly by laser-induced bubble or by bubble-excited liquid-mass oscillations. The oscillation period of thin walls and liquid-mass were Twall = 116 µs and Tlm ≈ 160 µs, respectively. While the amplitude of the wall vibrations increases monotonically with the size of laser-induced bubbles, the amplitude of liquid-mass oscillation undulates with increasing bubble size. This can be attributed to a phase shift between the laser-induced bubble oscillation and the liquid-mass oscillator. Mutual interactions between the laser-induced bubble and secondary bubbles reveal a fast-changing pressure gradient in the liquid. Our study provides a better understanding of laser-induced bubble dynamics in a partially confined environment, which is of practical importance for microfluidics and intraluminal laser surgery.
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A series of genipin derivatives were designed and synthesized as potential inhibitors targeted KRAS G12D mutation. The majority of these compounds demonstrated potential antiproliferative effects against KRAS G12D mutant tumor cells (CT26 and A427). Notably, seven compounds exhibited the anticancer effects with IC50 values ranging from 7.06 to 9.21 µM in CT26 (KRASG12D) and A427 (KRASG12D) cells and effectively suppressed the colony formation of CT26 cells. One representative compound SK12 was selected for further investigation into biological activity and action mechanisms. SK12 markedly induced apoptosis in CT26 cells in a concentration-dependent manner. Moreover, SK12 elevated the levels of reactive oxygen species (ROS) in tumor cells and exhibited a modulatory effect on the KRAS signaling pathway, thereby inhibiting the activation of downstream phosphorylated proteins. The binding affinity of SK12 to KRAS G12D protein was further confirmed by the surface plasmon resonance (SPR) assay with a binding KD of 157 µM. SK12 also exhibited notable anticancer efficacy in a nude mice tumor model. The relative tumor proliferation rate (T/C) of the experimental group (50 mg/kg) was 31.04 % (P < 0.05), while maintaining a commendable safety profile.
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Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Iridoides , Camundongos Nus , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Iridoides/farmacologia , Iridoides/química , Animais , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Camundongos , Estrutura Molecular , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Linhagem Celular Tumoral , Mutação , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismoRESUMO
With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.
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Antineoplásicos , Apoptose , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Potencial da Membrana Mitocondrial , Mitocôndrias , Espécies Reativas de Oxigênio , Tiazóis , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Relação Estrutura-Atividade , Tiazóis/farmacologia , Tiazóis/química , Tiazóis/síntese química , Estrutura Molecular , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Compostos Organofosforados/farmacologia , Compostos Organofosforados/química , Compostos Organofosforados/síntese químicaRESUMO
BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficiency and safety of percutaneous nephrolithotomy (PCNL) between flank position and prone position for the treatment of renal stones. METHODS: PubMed, Embase, OVID, and Cochrane Library were comprehensively searched from their inception to Jul 2024. Randomized and nonrandomized trials evaluating renal calculi patients who underwent PCNL via flank position or prone position were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes and complications of both groups were compared in this meta-analysis. RESULTS: This review involved five articles (554 patients). Specifically, four articles were randomized controlled trials, and the remaining publication was prospective cohort study. No significant difference was found in stone-free rate between the flank group and prone group after the PCNL procedure. Similarly, the percutaneous access time, operative time, and hospital stay of flank position had no significant difference compared with the prone group. There was no significant difference in the comparison of complication rates between the flank group and the prone group. Although further analysis indicated that patients in the prone position suffered more hemoglobin drop than the flank group, no significant difference was found in the hemorrhage and blood transfusion rates. CONCLUSIONS: Both surgical positions were appropriate for most PCNL procedures and had shown similar efficacy and safety. In practice, the optimal choice should be made according to the patients' conditions and urologists' acquaintance.
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Cálculos Renais , Nefrolitotomia Percutânea , Posicionamento do Paciente , Humanos , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Decúbito Ventral , Posicionamento do Paciente/métodos , Cálculos Renais/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologiaRESUMO
BACKGROUND: Psoriasis is a persistent inflammatory dermatological disorder. Tanshinone IIA (tan-IIA) is a biologically active compound in the self-made Xiao-Yin decoction (SMXYD) and exhibits diverse biological properties, such as anti-proliferative and anti-inflammatory effects. The objective of this investigation was to assess the potential of tan-IIA as a therapeutic agent against psoriasis. METHODS: Network pharmacology was employed to ascertain the active constituents and potential pathways associated with SMXYD and psoriasis. We conducted CCK-8, qRT-PCR, and western blotting to assess the proliferation of HaCaT keratinocytes and the expression of IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. Additionally, we used H&E staining, western blotting, and ELISA to evaluate the therapeutic effects and signaling pathways of tan-IIA in psoriasis-like mice induced by imiquimod (IMQ). RESULTS: Network pharmacology analysis identified eight hub compounds. The Th17/IL-17 signaling was found to be a potential therapeutic pathway of SMXYD against psoriasis, with JUN (AP-1) as the core molecule. Next, PTGS2 was selected as the target of tan-IIA against psoriasis using network pharmacology analysis. Molecular docking showed a high affinity between PTGS2 and tan-IIA. Tan-IIA treatment attenuated M-5-induced hyperproliferation and inflammation in HaCaT keratinocytes. Additionally, Tan-IIA downregulated the PTGS2/NF-κB/AP-1 pathway in HaCaT keratinocytes. In the IMQ-induced psoriasis-like mouse, tan-IIA significantly reduced the severity of skin lesions and downregulated the PTGS2/NF-κB/AP-1 pathway. Moreover, the combination of methotrexate (MTX) and tan-IIA further inhibited the IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. CONCLUSION: The administration of tan-IIA has shown a positive effect on psoriasis by inhibiting the IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. The findings suggest that it has promising qualities that make it a potential candidate for the development of future anti-psoriatic agents.
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Abietanos , NF-kappa B , Psoríase , Animais , Camundongos , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Imiquimode/efeitos adversos , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Queratinócitos/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Psoríase/tratamento farmacológico , Psoríase/patologia , Fator de Transcrição AP-1/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis. METHODS: This web-based cross-sectional study was conducted at Guangdong Provincial People's Hospital between December 2022, and May 2023. RESULTS: A total of 545 valid questionnaires were collected, with an average age of 57.72 ± 13.47 years. The mean knowledge, attitudes and practices scores were 8.17 ± 2.9 (possible range: 0-24), 37.63 ± 3.80 (possible range: 10-50), 33.07 ± 6.10 (possible range: 10-50) respectively. Multivariate logistic regression analysis showed that patients from non-urban area had lower knowledge compared to those from urban area (odds ratio (OR) = 0.411, 95% CI: 0.262-0.644, P < 0.001). Furthermore, higher levels of education were associated with better knowledge, as indicated by OR for college and above (OR = 4.858, 95% CI: 2.483-9.504), high school/vocational school (OR = 3.457, 95% CI: 1.930-6.192), junior high school (OR = 3.300, 95% CI: 1.945-5.598), with primary school and below as reference group (all P < 0.001). Besides, better knowledge (OR = 1.220, 95% CI: 1.132-1.316, P < 0.001) and higher educational levels were independently associated with positive attitudes. Specifically, individuals with a college degree and above (OR = 2.986, 95% CI: 1.411-6.321, P = 0.004) and those with high school/vocational school education (OR = 2.418, 95% CI: 1.314-4.451, P = 0.005) have more positive attitude, with primary school and below as reference group. Next, better attitude (OR = 1.174, 95% CI: 1.107-1.246, P < 0.001) and higher education were independently associated with proactive practices. Those with college and above (OR = 2.870, 95% CI: 1.359-6.059, P = 0.006), and those with high school/vocational school education (OR = 1.886, 95% CI: 1.032-3.447, P = 0.039) had more proactive practices, with primary school and below as reference group. CONCLUSIONS: End-stage renal disease patients undergoing maintenance hemodialysis demonstrated insufficient knowledge, positive attitudes, and moderate practices regarding cardiovascular complications. Targeted interventions should prioritize improving knowledge and attitudes, particularly among patients with lower educational levels and income, to enhance the management of cardiovascular complications in end-stage renal disease.
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Doenças Cardiovasculares , Conhecimentos, Atitudes e Prática em Saúde , Falência Renal Crônica , Diálise Renal , Humanos , Masculino , Feminino , Diálise Renal/psicologia , Estudos Transversais , Falência Renal Crônica/terapia , Falência Renal Crônica/psicologia , Pessoa de Meia-Idade , Adulto , Idoso , Inquéritos e Questionários , China/epidemiologiaRESUMO
Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.
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Ferroptose , Neoplasias Ovarianas , Animais , Feminino , Humanos , Masculino , Camundongos , Sistema y+ de Transporte de Aminoácidos/genética , Camundongos Nus , Neoplasias Ovarianas/genética , Proteína Supressora de Tumor p53RESUMO
The liver is the central metabolic organ and produces 85-90% of the proteins found in plasma. Accordingly, the plasma proteome is an attractive source of liver disease biomarkers that reflects the different cell types present in this organ, as well as the processes such as responses to acute and chronic injury or the formation of an extracellular matrix. In the first part, we summarize the biomarkers routinely used in clinical evaluations and their biological relevance in the different stages of non-malignant liver disease. Later, we describe the current proteomic approaches, including mass spectrometry and affinity-based techniques, that allow a more comprehensive assessment of the liver function but also require complex data processing. The many approaches of analysis and interpretation and their potential caveats are delineated. While these advances hold the promise to transform our understanding of liver diseases and support the development and validation of new liver-related drugs, an interdisciplinary collaboration is needed.
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Hepatopatias , Proteoma , Humanos , Proteoma/metabolismo , Proteômica/métodos , Biomarcadores/metabolismoRESUMO
Multifactorial diseases demand therapeutics that can modulate multiple targets for enhanced safety and efficacy, yet the clinical approval of multitarget drugs remains rare. The integration of machine learning (ML) and deep learning (DL) in drug discovery has revolutionized virtual screening. This study investigates the synergy between ML/DL methodologies, molecular representations, and data augmentation strategies. Notably, we found that SVM can match or even surpass the performance of state-of-the-art DL methods. However, conventional data augmentation often involves a trade-off between the true positive rate and false positive rate. To address this, we introduce Negative-Augmented PU-bagging (NAPU-bagging) SVM, a novel semi-supervised learning framework. By leveraging ensemble SVM classifiers trained on resampled bags containing positive, negative, and unlabeled data, our approach is capable of managing false positive rates while maintaining high recall rates. We applied this method to the identification of multitarget-directed ligands (MTDLs), where high recall rates are critical for compiling a list of interaction candidate compounds. Case studies demonstrate that NAPU-bagging SVM can identify structurally novel MTDL hits for ALK-EGFR with favorable docking scores and binding modes, as well as pan-agonists for dopamine receptors. The NAPU-bagging SVM methodology should serve as a promising avenue to virtual screening, especially for the discovery of MTDLs.
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Descoberta de Drogas , Descoberta de Drogas/métodos , Humanos , Simulação de Acoplamento Molecular , Ligantes , Máquina de Vetores de Suporte , Aprendizado Profundo , Aprendizado de Máquina Supervisionado , Aprendizado de MáquinaRESUMO
This article systematically reviews the extraction and purification methods, structural characteristics, structure-activity relationship, and health benefits of C. speciosa polysaccharides, and their potential application in food, medicine, functional products, and feed, in order to provide a useful reference for future research. Chaenomeles speciosa (Sweet) Nakai. has attracted the attention of health consumers and medical researchers as a traditional Chinese medicine with edible, medicinal, and nutritional benefits. According to this study, C. speciosa polysaccharides have significant health benefits, such as anti-diaetic, anti-inflammatory and analgesic, anti-tumor, and immunomodulatory effects. Researchers determined the molecular weight, structural characteristics, and monosaccharide composition and ratio of C. speciosa polysaccharides by water extraction and alcohol precipitation. This study will lay a solid foundation for further optimization of the extraction process of C. speciosa polysaccharides and the development of their products. As an active ingredient with high value, C. speciosa polysaccharides are worthy of further study and full development. C. speciosa polysaccharides should be further explored in the future, to innovate their extraction methods, enrich their types and biological activities, and lay a solid foundation for further research and development of products containing polysaccharides that are beneficial to the human body.
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Polissacarídeos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Rosaceae/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Medicina Tradicional Chinesa , Monossacarídeos/química , Monossacarídeos/análise , Relação Estrutura-Atividade , AnimaisRESUMO
The Cartesian coordinate system is not sufficient to study wave propagation on the coastline or in the sea where the terrain is extremely complicated, so it is necessary to study it in an unconventional coordinate system, fractals. In this paper, from the governing equations of fluid, the fractional nonlinear Schrödinger equation is derived to describe the evolution of Rossby waves in fractal by using multi-scale analysis and perturbation method. Based on the equation, the rogue-wave solution is obtained by the integral preserving transformation to explain some serious threats at sea.
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OBJECTIVE: Urinary tract infection (UTI) is a common postoperative complication, so exploring its risk factors is helpful to provide a basis for clinical prevention. This study aims to analyse the risk factors for UTI after lumbar interbody fusion (LIF). METHODS: A single-centre retrospective study was conducted on the clinical data of 358 patients treated with LIF from April 2020 to April 2023. In accordance with the results of postoperative urine culture, the patients were divided into UTI group (n = 19, those with UTI after LIF) and control group (n = 332, those without UTI after LIF). Binary logistic regression analysis was carried out through collecting the medical records of the two groups to probe into the risk factors for UTI after LIF. RESULTS: After seven patients were excluded, the remaining 351 patients were included in the analysis. In this study, 19 patients (5.41%) developed postoperative UTI, whereas 332 patients (94.59%) had no UTI. Regression analysis results showed drinking (odds ratio (OR) = 16.193, 95% confidence interval (CI): 1.017-257.860) and high preoperative C-reactive protein (CRP) level (OR = 3.237, 95% CI: 1.213-8.636) as risk factors for UTI after LIF. A high professional title of main surgeon (OR = 0.095, 95% CI: 0.010-0.932) and preoperative red blood cell (RBC) count (OR = 0.001, 95% CI: 0.000-0.198) were protective factors for UTI after LIF (p < 0.05). CONCLUSIONS: This study advocated strengthening the prevention and treatment of UTI in patients who had drinking history, high preoperative CRP level and low preoperative RBC count, and received LIF based on the study results. Attention should be paid to the training of physicians with low professional title.
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Vértebras Lombares , Complicações Pós-Operatórias , Fusão Vertebral , Infecções Urinárias , Humanos , Fusão Vertebral/efeitos adversos , Infecções Urinárias/etiologia , Infecções Urinárias/epidemiologia , Masculino , Fatores de Risco , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Vértebras Lombares/cirurgia , Idoso , Medição de RiscoRESUMO
Because of their unique layer structure, 2D materials have demonstrated to be promising electrode materials for rechargeable batteries. However, individual 2D materials cannot meet all the performance requirements of energy density, power density, and cycle life. Constructing 2D materials-based heterostructures offers an opportunity to synergistically handle the deficiencies of individual 2D materials and modulate the physical and electrochemical properties. The enlarged interlayer distance and increased binding energy with ions of heterostructures can facilitate charge transfer, boost electrochemical reactivities, resulting in an enhanced performance in rechargeable batteries. Here we summarize the latest development of heterostructures consisted of 2D materials and their applications in rechargeable batteries. Firstly, different preparation strategies and optimized structure engineering strategies of 2D materials-based heterostructures are systematically introduced. Secondly, the unique functions of 2D materials-based heterostructures in rechargeable batteries are discussed respectively. Finally, challenges and perspectives are presented to inspire the future study of 2D materials-based heterostructures.
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This work studied the membrane curvature generated by anchored proteins lacking amphipathic helices and intrinsic morphologies, including the Epsin N-terminal homology domain, intrinsically disordered C-terminal domain, and truncated C-terminal fragments, by using coarse-grained molecular dynamics simulations. We found that anchored proteins can stabilize the thermal undulation of membranes at a wavelength five times the protein's binding size. This proportional connection is governed by the membrane bending rigidity and protein density. Extended intrinsically disordered proteins with relatively high hydrophobicity favor colliding with the membrane, leading to a much larger binding size, and show superiority in generating membrane curvature at low density over folded proteins.
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Proteínas Intrinsicamente Desordenadas , Simulação de Dinâmica Molecular , Estrutura Secundária de Proteína , Proteínas Intrinsicamente Desordenadas/metabolismo , Membrana Celular/químicaRESUMO
Tuberculosis (TB) remains one of the infectious diseases with high incidence and high mortality. About a quarter of the population has been latently infected with Mycobacterium tuberculosis. At present, the available TB treatment strategies have the disadvantages of too long treatment duration and serious adverse reactions. The sustained inflammatory response leads to permanent tissue damage. Unfortunately, the current selection of treatment regimens does not consider the immunomodulatory effects of various drugs. In this study, we preliminarily evaluated the effects of commonly used anti-tuberculosis drugs on innate immunity at the cellular level. The results showed that clofazimine (CFZ) has a significant innate immunosuppressive effect. CFZ significantly inhibited cytokines and type I interferons (IFNα and IFNß) expression under both lipopolysaccharide stimulation and CFZ-resistant strain infection. In further mechanistic studies, CFZ strongly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65 and had no significant effect on the phosphorylation of p38. In conclusion, our study found that CFZ suppresses innate immunity against Mycobacterium tuberculosis by NF-κB, which should be considered in future regimen development. IMPORTANCE: The complete elimination of Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, from TB patients is a complicated process that takes a long time. The excessive immune inflammatory response of the host for a long time causes irreversible organic damage to the lungs and liver. Current antibiotic-based treatment options involve multiple complex drug combinations, often targeting different physiological processes of Mtb. Given the high incidence of post-tuberculosis lung disease, we should also consider the immunomodulatory properties of other drugs when selecting drug combinations.