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Moiré excitons are emergent optical excitations in two-dimensional semiconductors with moiré superlattice potentials. Although these excitations have been observed on several platforms, a system with dynamically tunable moiré potential to tailor their properties is yet to be realized. Here we present a continuously tunable moiré potential in monolayer WSe2, enabled by its proximity to twisted bilayer graphene (TBG) near the magic angle. By tuning local charge density via gating, TBG provides a spatially varying and dynamically tunable dielectric superlattice for modulation of monolayer WSe2 exciton wave functions. We observed emergent moiré exciton Rydberg branches with increased energy splitting following doping of TBG due to exciton wave function hybridization between bright and dark Rydberg states. In addition, emergent Rydberg states can probe strongly correlated states in TBG at the magic angle. Our study provides a new platform for engineering moiré excitons and optical accessibility to electronic states with small correlation gaps in TBG.
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We show that interlayer charge transfer in 2D materials can be driven by an in-plane electric field, giving rise to electrical multipole generation in linear and second order in-plane field. The linear and nonlinear effects have quantum geometric origins in the Berry curvature and quantum metric, respectively, defined in extended parameter spaces characteristic of layered materials. We elucidate their symmetry characters and demonstrate sizable dipole and quadrupole polarizations, respectively, in twisted bilayers and trilayers of transition metal dichalcogenides. Furthermore, we show that this effect is strongly enhanced during the topological phase transition tuned by interlayer translation. The effects point to a new electric control on the layer quantum degree of freedom.
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The degradation of oncoproteins mediated by proteolysis-targeting chimera (PROTAC) has emerged as a potent strategy in cancer therapy. However, the clinical application of PROTACs is hampered by challenges such as poor water solubility and off-target adverse effects. Herein, we present an ultrasound (US)-activatable PROTAC prodrug termed NPCe6+PRO for actuating efficient sono-immunotherapy in a spatiotemporally controllable manner. Specifically, US irradiation, which exhibits deep-tissue penetration capability, results in Ce6-mediated generation of ROS, facilitating sonodynamic therapy (SDT) and inducing immunogenic cell death (ICD). Simultaneously, the generated ROS cleaves the thioketal (TK) linker through a ROS-responsive mechanism, realizing the on-demand activation of the PROTAC prodrug in deep tissues. This prodrug activation results in the degradation of the target protein BRD4, while simultaneously reversing the upregulation of PD-L1 expression associated with the SDT process. In the orthotopic mouse model of pancreatic tumors, NPCe6+PRO effectively suppressed tumor growth in conjunction with US stimulation.
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Inmunoterapia , Neoplasias Pancreáticas , Profármacos , Animales , Profármacos/farmacología , Profármacos/uso terapéutico , Profármacos/química , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Ratones , Humanos , Línea Celular Tumoral , Proteolisis/efectos de los fármacos , Terapia por Ultrasonido/métodos , Antígeno B7-H1 , Factores de Transcripción , Proteínas de Ciclo Celular , Especies Reactivas de Oxígeno/metabolismo , Proteínas que Contienen BromodominioRESUMEN
The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.
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Oxalato de Calcio , Endocitosis , Cálculos Renales , Polisacáridos , Humanos , Oxalato de Calcio/metabolismo , Adhesión Celular/efectos de los fármacos , Línea Celular , Cristalización , Endocitosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Cálculos Renales/prevención & control , Cálculos Renales/tratamiento farmacológico , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/metabolismo , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Supervivencia Celular/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Calcio/metabolismo , Espacio Intracelular/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.
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Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.
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Inmunoterapia , Manganeso , Terapia Fototérmica , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/terapia , Inmunoterapia/métodos , Manganeso/química , Humanos , Animales , Terapia Fototérmica/métodos , Línea Celular Tumoral , Femenino , Imagen por Resonancia Magnética/métodos , Ratones , Microambiente Tumoral , Nanopartículas/química , Fototerapia/métodosRESUMEN
Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.
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Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).
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Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.
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BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma is the tumor type with the highest incidence of perineural invasion. This study tries to identify the differentially expressed genes regulated between pancreatic ductal adenocarcinoma tissues with perineural invasion and without perineural invasion. MATERIALS AND METHODS: The GSE102238 profile was downloaded. Gene function and pathway analysis were subsequently conducted. A protein-protein interaction network was constructed to search for hub genes. Both univariate Cox analysis and multivariate Cox analysis were calculated to identify prognostic factors. Quantitative real-time polymerase chain reaction (RT-PCR) and overall survival analysis of hub genes were used to verify. RESULTS: Our study identified 242 differentially expressed genes including 68 upregulated differentially expressed genes and 174 downregulated differentially expressed genes, which were involved in important functions and pathways. Nine relevant core genes using protein-protein interaction analysis as well as nestin (NES)/vascular endothlial growth factor (VEGF) signaling pathway which is highly related to the pathological process of perineural invasion in pancreatic ductal adenocarcinoma were also discovered. The differentiation was identified as an independent prognostic factor (P < .05) after multivariate Cox analysis. Three upregulated genes (JUP, CALM1, and NES) and 6 downregulated genes (EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3) were validated by quantitative RT-PCR and they all had markedly worse overall survival (P < .05). CONCLUSION: This analysis showed that 9 core genes including JUP, CALM1, NES, EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3, as well as NES/VEGF signaling pathway, have a relationship with the development process of perineural invasion in pancreatic ductal adenocarcinoma. Cox analysis and overall survival analysis suggested differentiation as an independent prognostic factor and key roles for these 9 hub genes in perineural invasion prognosis in pancreatic ductal adenocarcinoma.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Interleucina-18/genética , Factor A de Crecimiento Endotelial Vascular/genética , Biomarcadores de Tumor/genética , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Pronóstico , Proto-Oncogenes , Expresión GénicaRESUMEN
Background: Although the gut microbiota is one of the risk factors for liver cancer, it remains unclear whether the level of metabolites mediates this association. Methods: Utilizing summary data from genome-wide association studies (GWAS), we conducted a two-sample Mendelian Randomization (MR) analysis to explore the causal links between GM, metabolites, and HCC. A two-step MR analysis quantitatively assessed the effect of metabolite-mediated GM on HCC. Results: In our study, we demonstrated that Clostridium leptum was identified as a protective factor against HCC, with no evidence of reverse causality (Inverse-variance weighted [IVW], OR: 0.62 [95% CI, 0.42-0.91]; p = 0.016). Our study also found that the potential connection between the GM and HCC may be mediated by the level of metabolites. An increase of one standard deviation in C. leptum abundance led to a 38% decrease in HCC risk (OR: 0.62 [95% CI, 0.42-0.91]), with a 9% reduction in phosphoethanolamine (PE) levels (OR: 0.91 [95% CI: 0.84-0.99]). PE's mediation proportion was established as -6.725% (95% CI, 12.96% to -26.41%). Conclusion: Our results demonstrate that increasing specific GM abundance can lower HCC risk, mediated by PE levels. We offer new prevention and treatment targets for HCC by adjusting GM.
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An efficient interface and composition modification strategy is proposed to significantly increase the rate capacity and initial Coulombic efficiency (ICE) of SnO anodes via energy band structure modulation for Na-ion batteries (SIBs). The as-fabricated SnO@Bi@C material with Bi nanocrystals homogeneously dispersed on and around the SnO surface is prepared by an electrospinning method. The excellently dispersed Bi nanocrystals realize an effective interface contact with SnO and Na2O, which effectively lowers the electron conduction barriers and promotes sodium-ion release and transport upon the desodiation process, increasing the rate capacity and ICE of the SnO anode. The prepared SnO@Bi@C exhibits a much higher rate capacity up to 10 A g-1, except an improved ICE of 80.67%, compared to 57.38% of SnO@C. Importantly, the intercalation of Na+ between layer-structured Bi galleries provides a good basis for excellent cycle stability due to the highways constructed inside the prepared composites. This finding provides an effective tactic to establish ion transport high-speed channels, which essentially increase the rate performance and the ICE of the SnO-based anodes.
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AIM: This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). METHODS: From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. RESULTS: The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. CONCLUSIONS: The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.
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Carcinoma Hepatocelular , Infusiones Intraarteriales , Neoplasias Hepáticas , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Longitudinales , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Arteria Hepática , Biomarcadores de Tumor/sangre , Resultado del Tratamiento , PronósticoRESUMEN
Rationale and objectives: The primary aim of this study was to conduct a retrospective comparative analysis of the survival outcomes in patients with recurrent cervical cancer (CC). Specifically, we aimed to compare the efficacy of chemotherapy alone versus the combined approach of chemotherapy and 125I brachytherapy subsequent to the failure of initial chemotherapy treatment. Materials and methods: Patients diagnosed with recurrent CC subsequent to the failure of initial chemotherapy from January 2007 to December 2016 were enrolled from 2 hospitals. These patients were then divided into two groups: Group A, which underwent second-line chemotherapy alone, and Group B, which received both second-line chemotherapy and 125I brachytherapy. The assessment of overall survival (OS) and progression-free survival (PFS) was carried out through propensity score matching (PSM) (1:1), Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression for survival analysis. Results: A matched cohort comprising 88 patients each in Group A and Group B was included in the study. In Group A, the 1-, 2-, and 3-year cumulative PFS rates were 40.9 %, 15.9 %, and 5.7 % respectively, while in Group B, these rates were significantly higher at 79.5 %, 48.9 %, and 25.0 % (P = 0.003). Similarly, the 1-, 2-, and 3-year cumulative OS rates among Group A were 67.0 %, 27.3 %, and 5.7 % compared to 89.8 %, 63.6 %, and 30.7 % among Group B, suggesting a difference with statistical significance (P < 0.001) between the two groups. Moreover, the incidence of complications was similar between groups (P = 0.698). Conclusions: Our findings suggest that the combined approach of chemotherapy and 125I brachytherapy yields superior therapeutic effects but similar complication rates compared to chemotherapy alone in patients experiencing local recurrence of CC following failed initial chemotherapy.
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The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.
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Enfermedades Cardiovasculares , Humanos , Histona Demetilasas , Histonas , Cognición , Daño del ADNRESUMEN
This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.
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Oxalato de Calcio , Cálculos Renales , Humanos , Estrés Oxidativo , Inflamación/tratamiento farmacológico , Células Epiteliales , Cálculos Renales/tratamiento farmacológico , Cálculos Renales/prevención & controlRESUMEN
Purpose: Adhesion between calcium oxalate crystals and renal tubular epithelial cells is a vital cause of renal stone formation; however, the drugs that inhibit crystal adhesion and the mechanism of inhibition have yet to be explored. Methods: The cell injury model was constructed using nano-COM crystals, and changes in oxidative stress levels, endoplasmic reticulum (ER) stress levels, downstream p38 MAPK protein expression, apoptosis, adhesion protein osteopontin expression, and cell-crystal adhesion were examined in the presence of Laminarin polysaccharide (DLP) and sulfated DLP (SDLP) under protected and unprotected conditions. Results: Both DLP and SDLP inhibited nano-COM damage to human kidney proximal tubular epithelial cell (HK-2), increased cell viability, decreased ROS levels, reduced the opening of mitochondrial membrane permeability transition pore, markedly reduced ER Ca2+ ion concentration and adhesion molecule OPN expression, down-regulated the expression of ER stress signature proteins including CHOP, Caspase 12, and p38 MAPK, and decreased the apoptosis rate of cells. SDLP has a better protective effect on cells than DLP. Conclusions: SDLP protects HK-2 cells from nano-COM crystal-induced apoptosis by reducing oxidative and ER stress levels and their downstream factors, thereby reducing crystal-cell adhesion interactions and the risks of kidney stone formation.
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Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Disulfuros , Glicoproteínas Hemaglutininas del Virus de la Influenza , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Anticuerpos Antivirales/inmunología , Ratones , Disulfuros/química , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Anticuerpos Neutralizantes/inmunología , Femenino , Protección Cruzada/inmunología , Reacciones Cruzadas , Humanos , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/virología , Epítopos/inmunología , Epítopos/genética , Epítopos/química , Multimerización de Proteína , Virus de la Influenza B/inmunología , Virus de la Influenza B/genética , Virus de la Influenza B/químicaRESUMEN
RATIONALE: Coagulation factor V deficiency is rare, and perioperative management of patients with this condition is particularly important, especially during major abdominal surgery. We present a case of a patient with pancreatic duct stones combined with coagulation factor V deficiency. We share our perioperative management experience. PATIENT CONCERNS: A 31-year-old man presented with recurrent upper abdominal pain for 2 years. DIAGNOSES: The diagnosis of pancreatic duct stones in the patient has been established through abdominal computed tomography and magnetic resonance imaging examinations. The diagnosis of factor V deficiency was initially identified through coagulation function tests, revealing significant prolongation of both aPTT and PT. Subsequent testing of coagulation factors and inhibitors demonstrated that the patient has a deficiency in coagulation factor V. Finally, genetic testing revealed that the factor V deficiency in this case is hereditary. INTERVENTIONS: The patient underwent a partial resection of the pancreatic head, and FFP was infused 1 hour before surgery. 600 mL of FFP was instilled 1 hour before the start of surgery along with 10 U of cryoprecipitate. and 600 ml of FFP were added during surgery. Postoperative treatment included intermittent FFP supplemental infusion in the first 5 days after surgery while monitoring the coagulation function. OUTCOMES: The patient underwent a successful surgery without any abnormal bleeding or oozing during the procedure. The postoperative recovery was smooth, with no abnormal bleeding. LESSONS: Patients with a deficiency of coagulation factor V are not contraindicated for surgery. Appropriate Fresh Frozen Plasma (FFP) replacement therapy can ensure the safe conduct of the surgical procedure. For patients with abnormal blood coagulation function, we recommend testing for coagulation factors and inhibitors, as well as performing genetic testing for abnormal coagulation factors, which can provide guidance on marriage and childbirth.