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1.
Int J Biol Macromol ; : 133632, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971279

RESUMEN

In cyanobacteria, Elongation factor Tu (EF-Tu) plays a crucial role in the repair of photosystem II (PSII), which is highly susceptible to oxidative stress induced by light exposure and regulated by reactive oxygen species (ROS). However, the specific molecular mechanism governing the functional regulation of EF-Tu by ROS remains unclear. Previous research has shown that a mutated EF-Tu, where C82 is substituted with a Ser residue, can alleviate photoinhibition, highlighting the important role of C82 in EF-Tu photosensitivity. In this study, we elucidated how ROS deactivate EF-Tu by examining the crystal structures of EF-Tu in both wild-type and mutated form (C82S) individually at resolutions of 1.7 Šand 2.0 Šin Synechococcus elongatus PCC 7942 complexed with GDP. Specifically, the GDP-bound form of EF-Tu adopts an open conformation with C82 located internally, making it resistant to oxidation. Coordinated conformational changes in switches I and II create a tunnel that positions C82 for ROS interaction, revealing the vulnerability of the closed conformation of EF-Tu to oxidation. An analysis of these two structures reveals that the precise spatial arrangement of C82 plays a crucial role in modulating EF-Tu's response to ROS, serving as a regulatory element that governs photosynthetic biosynthesis.

2.
Sci Rep ; 14(1): 15693, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977834

RESUMEN

To mitigate the decrease in mechanical performance of Sn58Bi/Cu solder joints resulting from electromigration-induced damage. The CeO2 nanoparticles were incorporated into Sn58Bi solder by a melt-casting method, and their effects on the microstructure and properties of Sn58Bi/Cu solder joints under electromigration were investigated. The study results demonstrate that the addition of 0.125 ~ 0.5 wt% CeO2 nanoparticles refines the eutectic microstructure of Sn58Bi solder alloy. At an addition amount of 0.5 wt%, the composite solder alloy exhibits the maximum tensile strength of 68.9 MPa, which is 37% higher than that of the base solder. CeO2 nanoparticle-reinforced Sn58Bi solder can achieve excellent solderbility with Cu substrates and the joints can significantly inhibit the growth of the anodic Bi-rich layer, which is responsible for electromigration. With the extension of current stressing time, Bi-rich and Sn-rich layer are respectively formed on the anode and cathode in the joints. The intermetallic compound (IMC) layer grows asymmetrically, transitioning from a fan-shaped morphology to a flattened structure at the anode and to a thickened mountain-like morphology at the cathode. Adding the CeO2 nanoparticles helps to mitigate the decrease in mechanical performance caused by electromigration damage during current application to some extent. Over the current stressing period of 288 ~ 480 h, the fracture position shifts from the anodic IMC/Bi-rich interface to the cathodic Sn-rich/IMC interface. The fracture mechanism transitions from a brittle fracture characterized by plate-like cleavage to a ductile-brittle mixed fracture with fine dimples and cleavage.

3.
Clin Nutr ESPEN ; 62: 81-87, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901952

RESUMEN

BACKGROUND: To study the association of habitual coffee and tea consumption with the risk of cataract. METHODS: This prospective cohort study enrolled UK Biobank participants between 2006 and 2010, and prospectively followed them up for cataract diagnosis. We examined the associations of self-reported intake of tea and coffee and the calculated combined caffeine intake, with the risk of incident cataract. Cox proportional hazards models were analyzed after adjusting for age, sex, race, diabetes, Townsend Index, income, education, smoking and alcohol status. RESULTS: A total of 444,787 UK Biobank participants aged from 37 to 73 years old who had no cataract at baseline were included. Coffee intake of 2-3 cups/day (HR 0.973, 95% CI 0.949-0.998) or tea intake of 4-6 cups/day (HR 0.962, 95% CI 0.934-0.990) or combination caffeine intake of 160.0-235.0 mg/day (HR 0.950, 95% CI 0.925-0.976) were linked with the lowest risk of incident cataract. Cox models with restricted cubic splines showed J-shaped associations of coffee, tea, and combined caffeine intake with the risk of cataract (all p for nonlinear <0.001). CONCLUSIONS: Moderate habitual consumption of coffee and tea is associated with a lower risk of cataract. To maximize the protective effect against cataract, it is advisable to control total caffeine intake from coffee and tea within a range of 160.0-235.0 mg/day.


Asunto(s)
Catarata , Café , , Humanos , Catarata/epidemiología , Catarata/prevención & control , Estudios Prospectivos , Femenino , Masculino , Persona de Mediana Edad , Reino Unido/epidemiología , Anciano , Adulto , Factores de Riesgo , Modelos de Riesgos Proporcionales , Cafeína/administración & dosificación , Bancos de Muestras Biológicas , Incidencia , Biobanco del Reino Unido
4.
Ultrason Sonochem ; 108: 106953, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38879963

RESUMEN

Liquid-liquid separation, commonly referred to as oiling-out, frequently can occurs during crystallization, especially the anti-solvent crystallization process of phosphoryl compounds, and poses potential hurdle for high-quality product. Efficiently regulating oiling-out during crystallization remains a significant challenge. Among various techniques, ultrasound emerges as a green and effective approach to enhance the crystallization process. However, there is a dearth of in-depth research exploring the microscopic mechanisms of this process. Therefore, our research focused on the fructose-1,6-diphosphate (FDP), a typical phosphoryl compound, to gain a deeper understanding of how ultrasound influences the oiling-out process. The focused beam reflectance measurement (FBRM) technology was used to investigate the oiling-out phenomenon of FDPNa3 across various solvent ratios. In addition, the influence of ultrasound on the induction time was studied and the nucleation energy barrier was calculated. Finally, to further unravel the microscopic mechanisms, we utilized molecular simulation techniques to analyze the impact of ultrasound power on the dissolution-precipitation process. Our observations revealed a consistent oiling-out process that attainted a stable state regardless of the solvent employed. Notably, the results of the oiling-out induction time experiments indicated that ultrasound significantly reduced helped lower the nucleation energy barrier of FDP3- ions, thereby dismantling FDP3-clusters in solution. Thus, in turn, shortened the reduced induction time and promoted crystallization. Furthermore, ultrasound reduced the interactions between FDP3-ions and water molecules as well as FDP3- ions themselves. As simulated field intensity increased, these interaction forces gradually diminished, the thickness of the hydration layer surrounding the FDP3- clusters facilitating the disruption of clusters, ultimately enhancing the crystallization process.

5.
Theranostics ; 14(8): 3082-3103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855180

RESUMEN

Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.


Asunto(s)
Alginatos , Artritis Gotosa , Modelos Animales de Enfermedad , Inflamación , Oligosacáridos , Animales , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/metabolismo , Ratones , Oligosacáridos/farmacología , Alginatos/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Artralgia/tratamiento farmacológico , Artralgia/metabolismo , Ácido Úrico/metabolismo , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Articulación del Tobillo/patología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos
6.
Mol Cell Proteomics ; 23(6): 100783, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729610

RESUMEN

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.


Asunto(s)
Autoanticuerpos , Autoinmunidad , Epitelio Pigmentado de la Retina , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/metabolismo , Masculino , Femenino , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Persona de Mediana Edad , Miopía Degenerativa/inmunología , Miopía/inmunología , Adulto
7.
BMC Psychol ; 12(1): 265, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741161

RESUMEN

BACKGROUND: the AMORAL model emphasizes the close connection of individuals' belief system and malevolent creativity. Belief in a just world theory (BJW) states that people have a basic need to believe that the world they live in is just, and everyone gets what they deserve. Therefore, justice matters to all people. Justice sensitivity, as one of individual trait, has been found associated with negative goals. However, relevant studies have not tested whether justice sensitivity can affect malevolent creativity and its psychological mechanisms. Additionally, researchers have found that both anger and emotion regulation linked with justice sensitivity and malevolent creativity, but their contribution to the relationship between justice sensitivity and malevolent creativity remained unclear. The current study aims to explore the influence of justice sensitivity on malevolent creativity, the mediating effect of trait anger/state anger on the relationship between justice sensitivity and malevolent creativity, and the moderating effect of emotion regulation on this mediating effect. METHODS: A moderated mediating model was constructed to test the relationship between justice sensitivity and malevolent creativity. A sample of 395 Chinese college students were enrolled to complete the questionnaire survey. RESULTS: Justice sensitivity positively correlated with malevolent creativity, both trait anger and state anger partly mediated the connection between justice sensitivity and malevolent creativity. Moreover, emotion regulation moderated the indirect effect of the mediation model. The indirect effect of justice sensitivity on malevolent creativity through trait anger/state anger increased as the level of emotion regulation increased. The results indicated that justice sensitivity can affect malevolent creativity directly and indirectly through the anger. The level of emotion regulation differentiated the indirect paths of justice sensitivity on malevolent creativity. CONCLUSIONS: Justice sensitivity and malevolent creativity was mediated by trait anger/state anger. The higher sensitivity to justice, the higher level of trait anger/state anger, which in turn boosted the tendency of malevolent creativity. This indirect connection was moderated by emotion regulation, individuals with high emotion regulation are better able to buffer anger from justice sensitivity.


Asunto(s)
Ira , Creatividad , Regulación Emocional , Justicia Social , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Justicia Social/psicología , Adolescente , Estudiantes/psicología
8.
Mol Med ; 30(1): 52, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641575

RESUMEN

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.


Asunto(s)
Polietilenos , Polipropilenos , Enfermedades de la Piel , Factor de Crecimiento Transformador beta , Animales , Ratones , Bleomicina/efectos adversos , Colágeno/metabolismo , Fibrosis/tratamiento farmacológico , Hidrogeles/química , Hidrogeles/farmacología , Polietilenos/farmacología , Polipropilenos/farmacología , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/metabolismo , Proteínas Smad/efectos de los fármacos , Proteínas Smad/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología
9.
Int J Oncol ; 64(5)2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38456493

RESUMEN

Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis­related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis­related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.


Asunto(s)
Neoplasias de la Mama , Ferroptosis , Muerte Celular Regulada , Femenino , Humanos , Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Carcinogénesis , Microambiente Tumoral
10.
Phytomedicine ; 127: 155461, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38452697

RESUMEN

BACKGROUND: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored. PURPOSE: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances. METHODS: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results. RESULTS: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFß1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFß1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFß1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen. CONCLUSIONS: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFß1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.


Asunto(s)
Adenomiosis , Antineoplásicos , Diosgenina/análogos & derivados , Liliaceae , Humanos , Femenino , Animales , Ratones , Adenomiosis/tratamiento farmacológico , Línea Celular Tumoral , Antineoplásicos/farmacología , Transición Epitelial-Mesenquimal
11.
Signal Transduct Target Ther ; 9(1): 54, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38443334

RESUMEN

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.


Asunto(s)
COVID-19 , Hepatitis C Crónica , Humanos , Animales , Ratones , Ratas , Perros , Calpaína , Catepsina L , Antivirales/farmacología , Vacunas contra la COVID-19 , Modelos Animales de Enfermedad , Ratones Transgénicos , Antiinflamatorios
12.
Cell Death Discov ; 10(1): 129, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38467615

RESUMEN

The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.

13.
J Cancer ; 15(7): 1966-1982, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38434972

RESUMEN

Background: Hepatocellular carcinoma (HCC) is one of the common primary cancers of the liver worldwide and leading cause of mortality. Gasdermins (GSDMs) family genes play an important role in the regulation of the normal physiological processes and have been implicated in multiple diseases. However, little is known about the relationship between different GSDMs proteins and HCC. The aim of this study was to explore the potential relationship between the expression, prognosis, genetic variation and immune infiltration of GSDMs family genes and HCC. Methods: We used different bioinformatics common public databases such as GSCA, GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, LinkedOmics, GeneMANIA, STRING, cBioPortal, TIMER and TISIDB to analyze the differential expression of the different GSDMs, prognostic value, genetic alterations, immune cell infiltration and their functional networks in HCC patients. Results: All the members of the GSDMs family exhibited elevated mRNA expression levels in LIHC compared to the normal tissues, while only GSDMB, GSDMD and GSDME showed enhanced protein expression. The mRNA expression of most GSDMs members was found to be elevated in HCC patients at stages I-III (clinical stage) compared to the normal subjects. The expression of GSDMD was correlated with OS and DSS of patients, whereas GSDME was correlated with OS, DSS and RFS of patients. Gene amplification was observed to be main mode of variation in members of the GSDMs family. KEGG pathway analysis showed that genes associated with different members of the GSDMs family were enriched in the pathways of S. aureus infection, intestinal immunity, ribosome and protein assembly, oxidative phosphorylation, osteoclast differentiation and Fc gamma (γ) R-mediated phagocytosis. In addition, expression of both GSDMA and GSDME were found to be correlated most significantly with infiltration of immune cells, while GSDMA and GSDME somatic cell copy number alteration (CAN) were correlated significantly with the infiltration of immune cells. All GSDMs were noted to be associated with distinct subtypes of immune cells, except GSDMC. Conclusions: Our findings have provided useful insights to better understand the roles and functions of GSDMs in HCC that can provide novel direction for developing therapeutic modalities for HCC, including immunotherapy.

14.
J Colloid Interface Sci ; 665: 252-262, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38531272

RESUMEN

Covalent organic frameworks (COFs) present bright prospects in visible light photocatalysis with abundant active sites and exceptional stability. Tailoring an established COF with photoactive group is a prudent strategy to extend visible light absorption toward broad photocatalysis. Here, a ß-ketoenamine COF, TpBD-COF, constructed with 1,3,5-triformylphloroglucinol (Tp) and 4,4'-biphenyldiamine (BD), is tailored with azo to validate this strategy. The insertion of azo into BD affords 4,4'-azodianiline (Azo); TpAzo-COF is successfully constructed with Tp and Azo. Intriguingly, the insertion of azo enhances π-conjugation, thereby facilitating visible light absorption and intramolecular electron transfer. Moreover, TpAzo-COF, with an appropriate electronic structure and impressive specific surface area of 1855 m2 g-1, offers substantial active sites conducive to the reduction of oxygen (O2) to superoxide. Compared with TpBD-COF, TpAzo-COF exhibits superior performance for blue light-driven oxidation of amines with O2. Superoxide controls the selective formation of product imines. This work foreshadows the remarkable capacity of tailoring COFs with photoactive group toward broad visible light photocatalysis.

15.
Zhongguo Zhong Yao Za Zhi ; 49(2): 361-369, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403312

RESUMEN

The 4-coumarate: CoA ligase(4CL) is a key enzyme in the upstream pathway of phenylpropanoids such as flavonoids, soluble phenolic esters, lignans, and lignins in plants. In this study, 13 4CL family members of Arabidopsis thaliana were used as reference sequences to identify the 4CL gene family candidate members of Isatis indigotica from the reported I. indigotica genome. Further bioinformatics analysis and analysis of the expression pattern of 4CL genes and the accumulation pattern of flavonoids were carried out. Thirteen 4CL genes were obtained, named Ii4CL1-Ii4CL13, which were distributed on chromosomes 1, 2, 3, 4, and 6. The analysis of the gene structure and conserved structural domains revealed the intron number of I. indigotica 4CL genes was between 1 and 12 and the protein structural domains were highly conserved. Cis-acting element analysis showed that there were multiple response elements in the promoter sequence of I. indigotica 4CL gene family, and jasmonic acid had the largest number of reaction elements. The collinearity analysis showed that there was a close relationship between the 4CL gene family members of I. indigotica and A. thaliana. As revealed by qPCR results, the expression analysis of the 4CL gene family showed that 10 4CL genes had higher expression levels in the aboveground part of I. indigotica. The content assay of flavonoids in different parts of I. indigotica showed that flavonoids were mainly accumulated in the aboveground part of plants. This study provides a basis for further investigating the roles of the 4CL gene family involved in the biosynthesis of flavonoids in I. indigotica.


Asunto(s)
Isatis , Ligasas , Ligasas/genética , Isatis/genética , Regiones Promotoras Genéticas , Plantas/metabolismo , Flavonoides , Coenzima A Ligasas/genética , Coenzima A Ligasas/química , Coenzima A Ligasas/metabolismo
16.
Environ Pollut ; 345: 123476, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38311160

RESUMEN

A biochar-intensified phytoremediation experiment was designed to investigate the dynamic effects of different biochars on polycyclic aromatic hydrocarbon (PAH) removal in ryegrass rhizosphere contaminated soil. Maize and wheat straw biochar pyrolyzed at 300 °C and 500 °C were amended into PAH-contaminated soil, and then ryegrass (Lolium multiflorum L.) was planted for 90 days. Spearman's correlations among PAH removal, enzyme activity, abundance of PAH-ring hydroxylating dioxygenase (PAH-RHDα), and fungal and bacterial community structure were analyzed to elucidate the microbial degradation mechanisms during the combined remediation process. The results showed that 500 °C wheat straw biochar had higher surface area and more nutrients, and significantly accelerated the phytoremediation of PAHs (62.5 %), especially for high molecular weight PAH in contaminated soil. The activities of urease and dehydrogenase and the abundance of total and PAH-degrading bacteria, which improved with time by biochar and ryegrass, had a positive correlation with the removal rate of PAHs. Biochar enhanced the abundance of gram-negative (GN) PAH-RHDα genes. The GN PAH-degraders, Sphingomonas, bacteriap25, Haliangium, and Dongia may play vital roles in PAH degradation in biochar-amended rhizosphere soils. Principal coordinate analysis indicated that biochar led to significant differences in fungal community structures before 30 days, while the diversity of the bacterial community composition depended on planting ryegrass after 60 days. These findings imply that the structural reshaping of microbial communities results from incubation time and the selection of biochar and ryegrass in PAH-contaminated soils. Applying 500 °C wheat straw biochar could enhance the rhizoremediation of PAH-contaminated soil and benefit the soil microbial ecology.


Asunto(s)
Carbón Orgánico , Microbiota , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Suelo/química , Biodegradación Ambiental , Contaminantes del Suelo/análisis , Microbiología del Suelo , Bacterias/genética , Bacterias/metabolismo
17.
J Hazard Mater ; 466: 133684, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38310844

RESUMEN

In order to evaluate the feasibility of rice husk and rice husk biochar on assisting phytoremediation of polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) co-contaminated soils, a 150-day pot experiment planted with alfalfa was designed. Rice husk and its derived biochar were applied to remediate a PAHs, Zn, and Cr co-contaminated soil. The effects of rice husk and biochar on the removal and bioavailability of PAHs and HMs, PAH-ring hydroxylating dioxygenase gene abundance and bacterial community structure in rhizosphere soils were investigated. Results suggested that rice husk biochar had better performance on the removal of PAHs and immobilization of HMs than those of rice husk in co-contaminated rhizosphere soil. The abundance of PAH-degraders, which increased with the culture time, was positively correlated with PAHs removal. Rice husk biochar decreased the richness and diversity of bacterial community, enhanced the growth of Steroidobacter, Bacillus, and Sphingomonas in rhizosphere soils. However, Steroidobacter, Dongia and Acidibacter were stimulated in rice husk amended soils. According to the correlation analysis, Steroidobacter and Mycobacterium may play an important role in PAHs removal and HMs absorption. The combination of rice husk biochar and alfalfa would be a promising method to remediate PAHs and HMs co-contaminated soil.


Asunto(s)
Metales Pesados , Oryza , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Biodegradación Ambiental , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/análisis , Microbiología del Suelo , Carbón Orgánico/química , Bacterias/genética , Suelo/química , Medicago sativa
18.
Sci Rep ; 14(1): 2845, 2024 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310124

RESUMEN

Phenotype-guided gene prioritizers have proved a highly efficient approach to identifying causal genes for Mendelian diseases. In our previous study, we preliminarily evaluated the performance of ten prioritizers. However, all the selected software was run based on default settings and singleton mode. With a large-scale family dataset from Deciphering Developmental Disorders (DDD) project (N = 305) and an in-house trio cohort (N = 152), the four optimal performers in our prior study including Exomiser, PhenIX, AMELIE, and LIRCIAL were further assessed through parameter optimization and/or the utilization of trio mode. The in-depth assessment revealed high diagnostic yields of the four prioritizers with refined preferences, each alone or together: (1) 83.3-91.8% of the causal genes were presented among the first ten candidates in the final ranking lists of the four tools; (2) Over 97.7% of the causal genes were successfully captured within the top 50 by either of the four software. Exomiser did best in directly hitting the target (ranking the causal gene at the very top) while LIRICAL displayed a predominant overall detection capability. Besides, cases affected by low-penetrance and high-frequency pathogenic variants were found misjudged during the automated prioritization process. The discovery of the limitations shed light on the specific directions of future enhancement for causal-gene ranking tools.


Asunto(s)
Programas Informáticos , Humanos , Fenotipo
19.
Aging (Albany NY) ; 16(2): 1096-1110, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38180747

RESUMEN

Neuroinflammation plays a key role in early brain injury (EBI) of subarachnoid hemorrhage (SAH), and NLRP3 inflammasome plays an important role in the development of neuroinflammation after SAH, but the mechanism of NLRP3 inflammasome activation after SAH is still unclear. TRPV1 is a non-selective calcium channel that is involved in the pathology of neuroinflammation, but its role in SAH has not been revealed. Our study showed that TRPV1 was significantly upregulated after SAH and was predominantly expressed in microglia/macrophages. Antagonism of TRPV1 was effective in ameliorating neurological impairment, brain edema, neuronal damage, and reducing the inflammatory response (evidenced by reducing the number of CD16/32 positive microglia/macrophages, inhibiting the expression of CD16, CD32, CD86, IL-1b, TNF-a and blocking NLRP3 inflammasome activation). However, this effect can be abolished by NLRP3 inflammasome antagonist MCC950. In vitro experiment confirmed that TRPV1 activated NLRP3 inflammasome by increasing intracellular calcium levels. In conclusion, TRPV1 mediates EBI after SAH via calcium/NLRP3, and TRPV1 is a potential therapeutic target after SAH.


Asunto(s)
Lesiones Encefálicas , Hemorragia Subaracnoidea , Animales , Lesiones Encefálicas/tratamiento farmacológico , Calcio/uso terapéutico , Calcio de la Dieta/uso terapéutico , Inflamasomas/metabolismo , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/patología , Ratones , Ratas
20.
Retina ; 44(5): 810-819, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38194664

RESUMEN

PURPOSE: To investigate the efficacy of combined application of B-scan ultrasonography (US) and ultrawide field imaging (UWFI) in detecting retinal tears before cataract surgery. METHODS: Of 1,277 cataract patients, 2,552 eyes were enrolled and received both B-scan US and UWFI examinations preoperatively. Three types of combination were applied: type 1 (union, B-scan US or centered UWFI), type 2 (intersection, B-scan US and centered UWFI), and type 3 (B-scan US and eye-steering UWFI). Sensitivity and specificity of detecting retinal tears by different methods were assessed. RESULTS: Totally 4.55% (116/2,552) of eyes were presented with retinal tears. The sensitivity of B-scan US and UWFI was 87.93% and 84.48%, and specificity was 95.16% and 99.79%, respectively. By applying type 1 and type 2 combination, the sensitivity was 98.28% and 74.14%, and specificity was 95.03% and 99.92%, respectively. By type 3 combination, the sensitivity increased to 95.69% and specificity to 99.88%, both of which were comparable to indirect ophthalmoscopy regardless of the number, type, and location of tears ( P > 0.05). In eyes with any cataract type or axial length, type 3 combination also gained comparable performance to indirect ophthalmoscopy. CONCLUSION: Combined application of B-scan US and eye-steering UWFI presented satisfactory performance in detecting retinal tears before cataract surgery.


Asunto(s)
Extracción de Catarata , Perforaciones de la Retina , Ultrasonografía , Humanos , Masculino , Femenino , Anciano , Perforaciones de la Retina/diagnóstico por imagen , Perforaciones de la Retina/diagnóstico , Ultrasonografía/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Catarata , Sensibilidad y Especificidad , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Reproducibilidad de los Resultados
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