RESUMEN

Purpose: Systemic Immune-Inflammation Index (SII), calculated by (neutrophils count × platelet count)/lymphocytes count, is a novel index of the local immune response and systemic inflammation response. The SII has been shown to play an important role in the prognosis of many diseases, including cardiovascular diseases, cancer and COPD. However, its role in the prognosis of bronchiectasis remains unclear and requires further investigation. This study aimed to investigate the association between SII and readmissions in patients with acute exacerbations of bronchiectasis. Patients and Methods: We conducted a retrospective cohort study of all bronchiectasis patients admitted to the respiratory ward in Beijing Chaoyang Hospital from January 2020 to January 2022. Patients were classified into four groups according to the quartiles of log2(SII) at admission. The primary endpoint was readmission at 1-year follow up. Univariate and multivariate cox regression models were applied to investigate the relationship between SII and readmissions at 1-year follow up in patients with bronchiectasis. Results: A total of 521 patients were included in our study. The median (IQR) SII at admission were 506.10 (564.84). Patients with higher SII tended to be older, male, past and current smokers, have lower BMI, and more dyspnea symptoms. They also had higher inflammatory markers and received a greater spectrum of antibiotics and more intravenous glucocorticoids. Higher SII at admission were independently associated with readmission in patients with acute exacerbations for bronchiectasis following confounder adjustment (OR =1.007; 95% CI, 1.003-1.011; p <0.001). Conclusion: Patients with elevated SII levels were typically older males, often smokers, with lower BMI and increased dyspnea. They received more antibiotics and intravenous glucocorticoids. Higher SII at admission are associated with readmission in patients with acute exacerbations of bronchiectasis. SII has potential clinical value as a predictive biomarker for clinical outcomes in bronchiectasis, offering a valuable tool for management strategies.

RESUMEN

Flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV), represent a substantial public health challenge as there are currently no approved treatments available. Here, we investigated the antiviral effects of bis-benzylisoquinoline alkaloids (BBAs) on flavivirus infections. We evaluated five specific BBAs-berbamine, tetrandrine, iso-tetrandrine, fangchinoline, and cepharanthine-and found that they effectively inhibited infections by ZIKV, DENV, or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle. Furthermore, we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes, causing lysosomal pH alkalization. Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels, leading to lysosomal dysfunction and reducing the expression of NCAM1, a key receptor for the entry of ZIKV into cells, thereby decreasing cells susceptibility to ZIKV infection. Additionally, BBAs inhibited the fusion of autophagosomes and lysosomes, significantly reducing viral RNA replication. Collectively, our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy, respectively, underscoring the potential of BBAs as therapeutic agents against flavivirus infections.

RESUMEN

Targeting altered expression and/or activity of GABA transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABAA inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon (IFN I)-independent manner. Stimulation of the STING-GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GATs expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.Significance Statement GABA concentration in extracellular space is maintained by GABA release and clearance of GABA back to brain cells for degradation. GABA clearance from the synaptic cleft predominantly depends on level and activity of GABA transporters (GATs) in the brain. Insufficient GABA clearance resulted to an aberrant tonic GABAA inhibition in brain. In this study, we have identified an unusually high GABA content in brain of STING-deficient mice, resulting in cognitive impairment. Our results show that STING regulates GATs expression through STING-TBK1-IRF3 pathway and thus regulates GABAergic tone. This is the first study that indicates that the STING-TBK1-IRF3 signaling pathway maintains GABA homeostasis in brain, which may offer a novel therapeutic target for modulating GABAergic tone in cases of cognitive dysfunction.

RESUMEN

This paper introduces a compact end-effector ankle rehabilitation robot (CEARR) system for addressing ankle range of motion (ROM) rehabilitation. The CEARR features a bilaterally symmetrical rehabilitation structure, with each side possessing three degrees of freedom (DOF) driven by three independently designed actuators. The working intervals of each actuator are separated by a series connection, ensuring they operate without interference to accommodate the dorsiflexion/plantarflexion (DO/PL), inversion/eversion (IN/EV), and adduction/abduction (AD/AB) DOF requirements for comprehensive ankle rehabilitation. In addition, we integrated an actuator and foldable brackets to accommodate patients in varied postures. We decoded the motor intention based on the surface electromyography (sEMG) and torque signals generated by the subjects' ankle joints in voluntary rehabilitation. Besides, we designed a real-time voluntary-triggered control (VTC) strategy to enhance the rehabilitation effect, in which the root mean square (RMS) of sEMG was utilized to trigger and adjust the CEARR rehabilitation velocity support. We verified the consistency of voluntary movement with CEARR rehabilitation support output for four healthy subjects on a nonlinear sEMG signal with an R 2 metric of approximately 0.67. We tested the consistency of triggering velocity trends with a linear torque signal for one healthy individual with an R 2 metric of approximately 0.99.

RESUMEN

Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ß-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.

RESUMEN

Diabetic Nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Studies have indicated that Transforming Growth Factor beta1 (TGFß1) is the most potent factor contributing to renal fibrosis, and understanding the exact pathogenic mechanism of renal fibrosis is crucial for alleviating the condition. Previous research has identified Yin Yang 1 (YY1) as an effective inhibitor of TGF-ß1. Our study, through dual-luciferase reporter gene assays and Western blot experiments, screened and obtained the small molecule compound PdⅡ. Subsequently, validation in a high-glucose-induced renal mesangial cell injury model showed that PdⅡ treatment significantly increased the expression of YY1 protein and mRNA, while correspondingly reducing the expression of TGFß1 protein and mRNA. Dual-luciferase reporter gene assay results revealed that, compared to the control group, the luciferase transcription activity of YY1 molecules increased in the PdⅡ treatment group, and the luciferase transcription activity of TGFß1 decreased. By further designing mutations in the binding sites between TGFß1 and YY1 on the promoter, transfecting fluorescent enzyme reporter gene plasmids with TGFß1 mutant promoter into mesangial cells damaged by high glucose, and then treating the cells with PdⅡ, it was observed that the luciferase transcription activity of TGFß1 did not decrease. Therefore, these results suggest that PdⅡ may inhibit TGFß1 transcriptional activity by activating YY1, thereby slowing down the progression of diabetic nephropathy.

RESUMEN

AIM: This study analysed and summarized the correlation between various indicators of ICU nurses' personal lives, hospital work situation, social opinion, psychological assessment, and their intention to resign. DESIGN: A descriptive quantitative study. METHODS: This study was a multicentre questionnaire on factors influencing intensive care unit (ICU) nurses' intention to resign. This study was completed through the Critical Care E Institute (CCEI) and China Calm Therapy Research Group Academic Organization (CNCSG) by contacting ICU nurses in three hospitals in 34 provinces in China. The questionnaire was in the form of a cell phone WeChat scan code. The survey included 22 indicators, including basic information about nurses (marital and child status, personal income, etc.), hospital work (weekly working hours, night shift, hospital environment, etc.), and psychological symptoms. RESULTS: A total of 1904 nurses were included in this study. Among them, 1060 (55.67%) had the intention to resign. In this study, among the 22 indicators involved, 16 factors, including hospital work hours, job title, satisfaction with current income, having children, and evaluation of the hospital, significantly impact nurses' intentions to resign (all p < 0.05). Logistic regression analysis showed that six indicators influenced nurses' choice of resignation intention (all p < 0.05), including hospital work time, professional title, income satisfaction, hospital work pride, satisfaction of nurses with the compassion and care given to them by their hospitals, and career vision score. The ROC curve showed that all six indicators were <0.70, but the model receiver operating characteristic (ROC) curve constructed for the indicators was 0.756. In China, increasing the income of ICU nurses, fostering pride in hospital work, reducing working hours, ensuring smooth promotion processes, and enhancing career prospects can all decrease their likelihood of choosing to resign. Absorbing practical nursing management and work experience from other countries will help decrease the intention to resign within this group. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Asunto(s)

RESUMEN

BACKGROUND: This study explores the significance of computed tomography (CT) radiomic features, along with inflammation and nutrition biomarkers, in the prognosis of postoperative patients with T3N0M0 esophageal squamous cell carcinoma (ESCC). The study aims to construct a related nomogram. METHODS: A total of 114 patients were enrolled and randomly assigned to training and validation cohorts in a 7:3 ratio. Radiomic features were extracted from their preoperative chest-enhanced CT arterial images of the primary tumor, and inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI), were calculated based on laboratory data from the 3 days before surgery. Intra-class correlations coefficient (ICC) and least absolute shrinkage and selection operator (Lasso) were applied to screen valuable radiomics features predicting overall survival (OS), and the Rad-score was calculated. In the training cohort, univariate and multivariate Cox regression analyses identified independent prognostic factors, which were adopted to establish the nomogram. RESULTS: Eight radiomic features were selected for Rad-score calculation. Multivariate Cox regression revealed Rad-score, PNI, NLR, and PLR as independent prognostic factors for ESCC patients (p < 0.05). A nomogram was constructed based on these variables. The concordance index (C-index) for the nomogram was 0.797 (95% CI: 0.726-0.868) in the training cohort and 0.796 (95% CI: 0.702-0.890) in the validation cohort. Calibration curves indicated good calibration ability, and the receiver operating characteristic (ROC) analysis demonstrated superior discriminative ability for the nomogram in comparison to the Rad-score alone. Decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSION: We developed and validated a nomogram for predicting the OS of postoperative T3N0M0 ESCC patients, integrating nutritional, inflammatory markers, and radiomic signature. The combined nomogram can serve as a robust tool for risk stratification and clinical management.

RESUMEN

The membrane process is an effective way to realize resource reutilization. Most membrane devices are made of cold-roll steel (CRS), which is easy to corrode when operating in acid conditions. Herein, the biodegradable surfactant dodecyl dimethyl betaine (BS-12) was used as the inhibitor to protect the CRS in the trichloroacetic acid (TCA) solution. The long-term stability membrane tests showed that adding BS-12 will not harm the membrane performance. The weight loss experiments proved that adding BS-12 with trace amount (10 mg·L-1) endowed the CRS with good inhibition efficiency (95.3 %). The electrochemical tests indicated that the mixed inhibitor- BS-12 works by inhibiting the anode and cathode simultaneously, and the polarization resistance increased to 21 times. The SEM, AFM, and CLSM tests proved that adding BS-12 enabled the CRS surface to remain stable. The FTIR and XPS tests proved that BS-12 adsorbed on the CRS surface via physical and chemical adsorption. The theoretical calculations proved the horizontal adsorption of BS-12 on the CRS surface and the existence of the electron transfer within the BS-12 and CRS. The BS-12 showed great potential in the CRS inhibition of the membrane separation and purification processing.

RESUMEN

BACKGROUND: Understanding the effects of different additions of adzuki bean flour (ABF) on structural and functional characteristics of extruded buckwheat noodles is important in developing high-quality starchy foods with desirable glycemic indexes. This study explored how varying amounts of ABF in extruded buckwheat noodles influenced their structural and functional characteristics. RESULTS: The findings indicated that adding ABF substantially boosted the levels of protein and flavonoids, while decreasing the content of fat and starch. Adding ABF to the noodles extended the optimum cooking time and led to a reduction in both the stickiness of the cooked noodles and the pore size of the starch gel structure, compared with pure buckwheat noodles. Fourier transform infrared spectroscopy indicated that R1047/1022 increased with the content of ABF increased, while R1022/995 decreased. X-ray diffraction showed that the relative crystallinity of buckwheat noodles was enhanced with increasing ABF amount. Adding ABF notably significantly decreased the estimated glycemic index. The buckwheat noodles extruded with 20% ABF addition demonstrated notably stronger α-glucosidase inhibitory effects than those extruded with no ABF addition. CONCLUSION: The present study demonstrates that the additions of ABF improved the structure and hypoglycemic activity of extruded buckwheat noodles while decreasing starch digestibility, and the optimal value was reached at an ABF addition of 20%. The study might fill gaps in starch noodle research and provide a new strategy for the development of functional food in the food industry. © 2024 Society of Chemical Industry.

RESUMEN

Ovarian development was traditionally recognized as a "default" sexual outcome and therefore received much less scientific attention than testis development. In turtles with temperature-dependent sex determination (TSD), how the female pathway is initiated to induce ovary development remains unknown. In this study, we have found that phosphorylation of the signal transducer and activator of transcription 3 (pSTAT3) and Foxl2 exhibit temperature-dependent sexually dimorphic patterns and tempo-spatial coexpression in early embryos of the red-eared slider turtle (Trachemys scripta elegans). Inhibition of pSTAT3 at a female-producing temperature of 31 °C induces 64.7% female-to-male sex reversal, whereas activation of pSTAT3 at a male-producing temperature of 26 °C triggers 75.6% male-to-female sex reversal. In addition, pSTAT3 directly binds to the locus of the female sex-determining gene Foxl2 and promotes Foxl2 transcription. Overexpression or knockdown of Foxl2 can rescue the sex reversal induced by inhibition or activation of pSTAT3. This study has established a direct genetic link between warm temperature-induced STAT3 phosphorylation and female pathway initiation in a TSD system, highlighting the critical role of pSTAT3 in the cross talk between female and male pathways.

Asunto(s)

RESUMEN

Transmembrane channel-like (TMC) proteins are a highly conserved ion channel family consisting of eight members (TMC1-TMC8) in mammals. TMC1/2 are components of the mechanotransduction channel in hair cells, and mutations of TMC1/2 cause deafness in humans and mice. However, the physiological roles of other TMC proteins remain largely unknown. Here, we show that Tmc7 is specifically expressed in the testis and that it is required for acrosome biogenesis during spermatogenesis. Tmc7-/- mice exhibited abnormal sperm head, disorganized mitochondrial sheaths, and reduced number of elongating spermatids, similar to human oligo-astheno-teratozoospermia. We further demonstrate that TMC7 is colocalized with GM130 at the cis-Golgi region in round spermatids. TMC7 deficiency leads to aberrant Golgi morphology and impaired fusion of Golgi-derived vesicles to the developing acrosome. Moreover, upon loss of TMC7 intracellular ion homeostasis is impaired and ROS levels are increased, which in turn causes Golgi and endoplasmic reticulum stress. Taken together, these results suggest that TMC7 is required to maintain pH and ion homeostasis, which is needed for acrosome biogenesis. Our findings unveil a novel role for TMC7 in acrosome biogenesis during spermiogenesis.

Asunto(s)

RESUMEN

The development of novel adsorption materials is of significance for the efficient and low-energy purification of acetylene (C2H2). Emerging metal-organic framework (MOF) adsorbents demonstrate great application prospects in the field of gas adsorption and separation. Herein, we synthesized a Eu-MOF asymmetrically modified with cyclopentadienyl cobalt exhibiting two different types of cages, denoted as UPC-119. Adsorption isotherms and dynamic breakthrough curves confirm its potential in C2H2/CO2 separation, which is further evidenced by theoretical simulations. The high adsorption capacity and low adsorption enthalpy render UPC-119 as a promising adsorbent for C2H2/CO2 separation with ease of regeneration.

RESUMEN

BACKGROUND: Plerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni. METHODS: In this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults. RESULTS: A total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni. CONCLUSIONS: The dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni.

Asunto(s)

RESUMEN

Highly integrated information sharing among people, vehicles, roads, and cloud systems, along with the rapid development of autonomous driving technologies, has spurred the evolution of automobiles from simple "transportation tools" to interconnected "intelligent systems". The intelligent cockpit is a comprehensive application space for various new technologies in intelligent vehicles, encompassing the domains of driving control, riding comfort, and infotainment. It provides drivers and passengers with safety, comfort, and pleasant driving experiences, serving as the gateway for traditional automobile manufacturing to upgrade towards an intelligent automotive industry ecosystem. This is the optimal convergence point for the intelligence, connectivity, electrification, and sharing of automobiles. Currently, the form, functions, and interaction methods of the intelligent cockpit are gradually changing, transitioning from the traditional "human adapts to the vehicle" viewpoint to the "vehicle adapts to human", and evolving towards a future of natural interactive services where "humans and vehicles mutually adapt". This article reviews the definitions, intelligence levels, functional domains, and technical frameworks of intelligent automotive cockpits. Additionally, combining the core mechanisms of human-machine interactions in intelligent cockpits, this article proposes an intelligent-cockpit human-machine interaction process and summarizes the current state of key technologies in intelligent-cockpit human-machine interactions. Lastly, this article analyzes the current challenges faced in the field of intelligent cockpits and forecasts future trends in intelligent cockpit technologies.

RESUMEN

The centralized coordination of Connected and Automated Vehicles (CAVs) at unsignalized intersections aims to enhance traffic efficiency, driving safety, and passenger comfort. Autonomous Intersection Management (AIM) systems introduce a novel approach for centralized coordination. However, existing rule-based and optimization methods often face the challenges of poor generalization and low computational efficiency when dealing with complex traffic environments and highly dynamic traffic conditions. Additionally, current Reinforcement Learning (RL)-based methods encounter difficulties around policy inference and safety. To address these issues, this study proposes Constraint-Guided Behavior Transformer for Safe Reinforcement Learning (CoBT-SRL), which uses transformers as the policy network to achieve efficient decision-making for vehicle driving behaviors. This method leverages the ability of transformers to capture long-range dependencies and improve data sample efficiency by using historical states, actions, and reward and cost returns to predict future actions. Furthermore, to enhance policy exploration performance, a sequence-level entropy regularizer is introduced to encourage policy exploration while ensuring the safety of policy updates. Simulation results indicate that CoBT-SRL exhibits stable training progress and converges effectively. CoBT-SRL outperforms other RL methods and vehicle intersection coordination schemes (VICS) based on optimal control in terms of traffic efficiency, driving safety, and passenger comfort.

RESUMEN

Paris polyphylla Smith var. Chinensis (Franch.) Hara is a medicinal plant that belongs to the Liliaceae family. Its main components are parissaponins, which have excellent medicinal effects such as anti-inflammatory, anti-tumor, etc. Improving the quality of parissaponins through artificial directional regulation has emerged as a practice to meet medical demand and is a new research hotspot. In this paper, P. polyphylla plants were treated with UVA, UVB, and UVC, and the contents of PolyPhyllin VI (PPVI) and PolyPhyllin VII (PPVII), saponin synthase (squalene synthase, SS; cycloartenol synthase, CAS; cytochrome P450, CYP450; and glycosyl transferases, GT) activity, MDA, and the photosynthetic pigment indexes were measured and analyzed. The results showed that PPVII content increased by 32.43% with UVC treatment after 4 h (3.43 mg/g), but the PPVI and PPVII contents in the other groups decreased compared with CK (control group) and they did not return to the original level after 4 h. SS, CAS, CYP450, and GT synthases were activated in varying degrees via UV treatment and increased, respectively, by 22.93%, 10.83%, 20.15%, and 25.98%. Among them, GT, as the last of the synthetases, had a shorter response time to UVB (30 min) and UVC (15 min); the difference was sensible compared with CK. Moreover, UV had a stressing effect and promoted the rapid accumulation of MDA content (increased 17.66%, 34.53%, and 9.65%) and carotenoid (increased 7.58, 5.60, and 7.76 times) within 4 h compared to CK. UVB and UVC radiation visibly improved chlorophyll a content (42.56% and 35.45%), but UVA did not, and the change in chlorophyll b content showed no overt statistical difference. In addition, PPVI and PPVII were negatively correlated with SS, CAS, carotenoids, and MDA (p < 0.05) and positively correlated with CYP450, GT, and chlorophyll a (p < 0.05). This study provides a theoretical basis for using UV light to regulate secondary metabolism in P. polyphylla, which is of great value for production management.

RESUMEN

Endoplasmic reticulum (ER) stress induces the repression of protein synthesis throughout the cell. Attempts to understand how localized stress leads to widespread repression have been limited by difficulties in resolving translation rates at the subcellular level. Here, using live-cell imaging of reporter mRNA translation, we unexpectedly found that during ER stress, active translation at mitochondria was significantly protected. The mitochondrial protein ATPase family AAA domain-containing protein 3A (ATAD3A) interacted with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and mediated this effect on localized translation by competing for binding with PERK's target, eukaryotic initiation factor 2 (eIF2). PERK-ATAD3A interactions increased during ER stress, forming mitochondria-ER contact sites. Furthermore, ATAD3A binding attenuated local PERK signaling and rescued the expression of some mitochondrial proteins. Thus, PERK-ATAD3A interactions can control translational repression at a subcellular level, mitigating the impact of ER stress on the cell.

Asunto(s)