Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate.

Activated CD8+ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 toward the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc-translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.

Mitotic bookmarking by SWI/SNF subunits.

For cells to initiate and sustain a differentiated state, it is necessary that a 'memory' of this state is transmitted through mitosis to the daughter cells1-3. Mammalian switch/sucrose non-fermentable (SWI/SNF) complexes (also known as Brg1/Brg-associated factors, or BAF) control cell identity by modulating chromatin architecture to regulate gene expression4-7, but whether they participate in cell fate memory is unclear. Here we provide evidence that subunits of SWI/SNF act as mitotic bookmarks to safeguard cell identity during cell division. The SWI/SNF core subunits SMARCE1 and SMARCB1 are displaced from enhancers but are bound to promoters during mitosis, and we show that this binding is required for appropriate reactivation of bound genes after mitotic exit. Ablation of SMARCE1 during a single mitosis in mouse embryonic stem cells is sufficient to disrupt gene expression, impair the occupancy of several established bookmarks at a subset of their targets and cause aberrant neural differentiation. Thus, SWI/SNF subunit SMARCE1 has a mitotic bookmarking role and is essential for heritable epigenetic fidelity during transcriptional reprogramming.

cBAF complex components and MYC cooperate early in CD8+ T cell fate.

The identification of mechanisms to promote memory T (Tmem) cells has important implications for vaccination and anti-cancer immunotherapy1-4. Using a CRISPR-based screen for negative regulators of Tmem cell generation in vivo5, here we identify multiple components of the mammalian canonical BRG1/BRM-associated factor (cBAF)6,7. Several components of the cBAF complex are essential for the differentiation of activated CD8+ T cells into T effector (Teff) cells, and their loss promotes Tmem cell formation in vivo. During the first division of activated CD8+ T cells, cBAF and MYC8 frequently co-assort asymmetrically to the two daughter cells. Daughter cells with high MYC and high cBAF display a cell fate trajectory towards Teff cells, whereas those with low MYC and low cBAF preferentially differentiate towards Tmem cells. The cBAF complex and MYC physically interact to establish the chromatin landscape in activated CD8+ T cells. Treatment of naive CD8+ T cells with a putative cBAF inhibitor during the first 48 h of activation, before the generation of chimeric antigen receptor T (CAR-T) cells, markedly improves efficacy in a mouse solid tumour model. Our results establish cBAF as a negative determinant of Tmem cell fate and suggest that manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

Associations between essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid cancer.

Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The concentrations of 10 essential microelements in urine [cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I)] were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1 cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.

The anterior talofibular ligament-posterior talofibular ligament angle decreased after ankle lateral stabilization surgery.

PURPOSE: The angle between the anterior talofibular ligament (ATFL) and the posterior talofibular ligament (PTFL) is increased in patients with chronic ATFL injury. This study aimed to compare the AFTL-PTFL angle before versus after ankle lateral stabilization surgery, and to evaluate whether the ATFL-PTFL angle correlates with the ligament injury severity. METHODS: This retrospective study included 48 patients with mechanical ankle instability treated between 2016 and 2018. After arthroscopic evaluation, all patients underwent ankle lateral stabilization surgery comprising ligament repair (n = 28) or reconstruction (n = 20). The ATFL-PTFL angle was measured in the axial plane on pre- and postoperative MRI. Comparisons were made of the pre- versus postoperative ATFL-PTFL angles, and the ATFL-PTFL angle of the repair versus reconstruction groups. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the ATFL-PTFL angle in selecting the surgical technique. RESULTS: The postoperative ATFL-PTFL angle was significantly decreased compared with preoperatively. The ATFL-PTFL angle was significantly smaller in the repair group than the reconstruction group preoperatively and postoperatively. The area under the ROC curve was 0.741 (P < 0.01). The optimal cutoff point for the selection of ligament reconstruction was an ATFL-PTFL angle of 89.4° (sensitivity 0.85, specificity 0.61). CONCLUSION: The ATFL-PTFL angle decreases after ankle lateral stabilization surgery. The ATFL-PTFL angle is related to the severity of the ATFL injury. Ankle lateral ligament reconstruction should be considered when the ATFL-PTFL angle is > 89.4°. LEVEL OF EVIDENCE: Level III.

The role of CSDE1 in translational reprogramming and human diseases.

CSDE1 (cold shock domain containing E1) plays a key role in translational reprogramming, which determines the fate of a number of RNAs during biological processes. Interestingly, the role of CSDE1 is bidirectional. It not only promotes and represses the translation of RNAs but also increases and decreases the abundance of RNAs. However, the mechanisms underlying this phenomenon are still unknown. In this review, we propose a "protein-RNA connector" model to explain this bidirectional role and depict its three versions: sequential connection, mutual connection and facilitating connection. As described in this molecular model, CSDE1 binds to RNAs and cooperates with other protein regulators. CSDE1 connects with different RNAs and their regulators for different purposes. The triple complex of CSDE1, a regulator and an RNA reprograms translation in different directions for each transcript. Meanwhile, a number of recent studies have found important roles for CSDE1 in human diseases. This model will help us to understand the role of CSDE1 in translational reprogramming and human diseases. Video Abstract.

Alkylation of Allyl/Alkenyl Sulfones by Deoxygenation of Alkoxyl Radicals.

A challenging deoxygenation of alkoxyl radicals from readily accessible alcohol derivatives was developed, affording facile synthesis of functionalized alkenes with good functional group tolerance under mild reaction conditions. Because alkoxyl radicals can easily undergo ß-fragmentations or hydrogen abstractions, this new strategy for deoxygenation of alkoxyl radicals is highly valuable. Moreover, mechanistic studies revealed that the electron-neutral phosphine acts as the deoxygenation reagent.

NF-κB directly regulates ß-arrestin-1 expression and forms a negative feedback circuit in TNF-α-induced cell death.

ß-Arrestins (ß-arrestin-1 and -2) are multifunctional proteins that play important roles in the regulation of inflammation and cell survival that need to be tightly controlled; however, the mechanism that underlies their gene expression is largely unclear. Here, we demonstrate that ß-arrestin-1 is a transcriptional target of NF-κB. mRNA and protein levels of ß-arrestin-1 were up-regulated by NF-κB inducers. Inhibition of NF-κB prevented the up-regulation of ß-arrestin-1 mRNA, whereas activation of NF-κB led to increased ß-arrestin-1 expression. ß-Arrestin-1 promoter activity was consistently enhanced upon NF-κB activation as a result of the presence of a highly conserved κB site. ß-Arrestin-1, in turn, suppressed the transcriptional activity of NF-κB by interfering with the interaction between p65 and p50. ß-Arrestin-1-deficient mice displayed reduced TNF-α-induced cell death and increased expression of antiapoptotic genes. Reintroduction of ß-arrestin-1, but not its mutant, which is unable to interfere with the p65-p50 interaction, into ß-arrestin-deficient mouse embryonic fibroblasts partially restored sensitivity to TNF-α-induced cell death. These findings reveal NF-κB and ß-arrestin-1 to be key components of a negative feedback circuit that is necessary to regulate cell death.-Li, J., Guo, A., Wang, Q., Li, Y., Zhao, J., Lu, J., Pei, G. NF-κB directly regulates ß-arrestin-1 expression and forms a negative feedback circuit in TNF-α-induced cell death.

Identification of Hub Genes and Pathways in a Rat Model of Renal Ischemia-Reperfusion Injury Using Bioinformatics Analysis of the Gene Expression Omnibus (GEO) Dataset and Integration of Gene Expression Profiles.

BACKGROUND This study aimed to identify hub genes and pathways in a rat model of renal ischemia-reperfusion injury (IRI) using bioinformatics analysis of the Gene Expression Omnibus (GEO) microarray dataset and integration of gene expression profiles. MATERIAL AND METHODS GEO software and the GEO2R calculation method were used to analyze two mRNA profiles, including GSE 39548 and GSE 108195. The co-expression of differentially expressed genes (DEGs) were identified and searched in the DAVID and STRING databases for pathway and protein-protein interaction (PPI) analysis. Cytoscape was used to draw the PPI network. DEGs were also analyzed using the Molecular Complex Detection (MCODE) algorithm. Cytoscape and cytoHubba were used to analyze the hub genes and visualize the molecular interaction networks. Rats (n=20) included the IRI model group (n=10) and a control group (n=10). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure and compare the expression of the identified genes in rat renal tissue in the IRI model and the control group. RESULTS Ten hub genes were identified, STAT3, CD44, ITGAM, CCL2, TIMP1, MYC, THBS1, IGF1, SOCS3, and CD14. Apart from IGF1, qRT-PCR showed that expression of these genes was significantly increased in renal tissue in the rat model of IRI. The HIF-1alpha signaling pathway was involved in IRI in the rat model, which was supported by MCODE analysis. CONCLUSIONS In a rat model of renal IRI, bioinformatics analysis of the GEO dataset and integration of gene expression profiles identified involvement of HIF-1alpha signaling and the STAT3 hub gene.

A Novel Direction-of-Arrival Estimation via Phase Retrieval with Unknown Sensor Gain-and-Phase Errors.

In signal array processing, high-resolution direction-of-arrival (DOA) estimation algorithms work well on the assumption that the system models are perfect. However, in practicality, there are imperfect system models in which sensor gain-and-phase errors are considered. In this paper, we propose a novel framework that can effectively solve direction-of-arrival estimation tasks in the presence of sensor gain-and-phase errors. In contrast to existing approaches based on phase retrieval, our method eliminates gain errors by using the compensated covariance matrix. Meanwhile, we propose a data preprocessing method by taking only one column of the compensated covariance matrix without losing any magnitude information. Additionally, the phase retrieval problem is formed by the proposed data preprocessing method. Furthermore, the phase retrieval problem is solved by the recently proposed sparse feasible point pursuit algorithm, and DOA estimates are obtained. To prevent the model from ambiguities, we employ the known DOA to place reference sources. Numerical results show that the proposed scheme achieves better performance compared to state-of-the-art approaches.

Baicalein inhibits acinar-to-ductal metaplasia of pancreatic acinal cell AR42J via improving the inflammatory microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.

Archetype-Based Modeling of Persona for Comprehensive Personality Computing from Personal Big Data.

A model describing the wide variety of human behaviours called personality, is becoming increasingly popular among researchers due to the widespread availability of personal big data generated from the use of prevalent digital devices, e.g., smartphones and wearables. Such an approach can be used to model an individual and even digitally clone a person, e.g., a Cyber-I (cyber individual). This work is aimed at establishing a unique and comprehensive description for an individual to mesh with various personalized services and applications. An extensive research literature on or related to psychological modelling exists, i.e., into automatic personality computing. However, the integrity and accuracy of the results from current automatic personality computing is insufficient for the elaborate modeling in Cyber-I due to an insufficient number of data sources. To reach a comprehensive psychological description of a person, it is critical to bring in heterogeneous data sources that could provide plenty of personal data, i.e., the physiological data, and the Internet data. In addition, instead of calculating personality traits from personal data directly, an approach to a personality model derived from the theories of Carl Gustav Jung is used to measure a human subject's persona. Therefore, this research is focused on designing an archetype-based modeling of persona covering an individual's facets in different situations to approach a comprehensive personality model. Using personal big data to measure a specific persona in a certain scenario, our research is designed to ensure the accuracy and integrity of the generated personality model.

Deficiency of ß-arrestin1 ameliorates collagen-induced arthritis with impaired TH17 cell differentiation.

Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (T(H)17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator ß-arrestin1 was significantly up-regulated in peripheral and synovial CD4(+) T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of ß-arrestin1 ameliorated disease with decreased T(H)17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that ß-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for T(H)17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for ß-arrestin1 in the pathogenesis of collagen-induced arthritis and T(H)17 cell differentiation and suggest ß-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA.

The small GTPase MoYpt7 is required for membrane fusion in autophagy and pathogenicity of Magnaporthe oryzae.

Rab GTPases are required for vesicle-vacuolar fusion during vacuolar biogenesis in fungi. To date, little is known about the biological functions of the Rab small GTPase components in Magnaporthe oryzae. In this study, we investigated MoYpt7 of M. oryzae, a homologue of the small Ras-like GTPase Ypt7 in Saccharomyces cerevisiae. Cellular localization assays showed that MoYpt7 was predominantly localized to vacuolar membranes. Using a targeted gene disruption strategy, a ΔMoYPT7 mutant was generated that exhibited defects in mycelial growth and production of conidia. The conidia of the ΔMoYPT7 mutant were malformed and defective in the formation of appressoria. Consequently, the ΔMoYPT7 mutant failed to cause disease in rice and barley. Furthermore, the ΔMoYPT7 mutant showed impairment in autophagy, breached cell wall integrity, and higher sensitivity to both calcium and heavy metal stress. Transformants constitutively expressing an active MoYPT7 allele (MoYPT7-CA, Gln67Leu) exhibited distinct phenotypes from the ΔMoYPT7 mutant. Expression of MoYPT7-CA in MoYpt7 reduced pathogenicity and produced more appressoria-forming single-septum conidia. These results indicate that MoYPT7 is required for fungal morphogenesis, vacuole fusion, autophagy, stress resistance and pathogenicity in M. oryzae.

The experimental study of mir-99a-5p negative regulation of TLR8 receptor mediated-mediated innate immune response in rabbit knee cartilage injury.

BACKGROUND: Traumatic cartilage injury is an important cause of osteoarthritis (OA) and limb disability, and toll-like receptors (TLRs) mediated innate immune response has been confirmed to play a crucial role in cartilage injury. In the previous study, we found that the activation of TLR8 molecules in injured articular cartilage was more obvious than other TLRs by establishing an animal model of knee impact injury in rabbits, and the changes of TLR8 molecules could significantly affect the process of articular cartilage injury and repair. OBJECTIVE: To verify how mir-99a-5p regulates TLR8 receptor mediated innate immune response to treat traumatic cartilage injury. METHODS: The impact of a heavy object on the medial condyle of the rabbit's knee joint caused damage to the medial condylar cartilage. Through pathological and imaging analysis, it was demonstrated whether the establishment of an animal model of traumatic cartilage injury was successful. Establishing a cell model by virus transfection of chondrocytes to demonstrate the role of TLR8 in the innate immune response to impact cartilage injury. Through transcriptome sequencing, potential targets of TLR8, mir-99a-5p, were predicted, and basic experiments were conducted to demonstrate how they interact with innate immune responses to impact cartilage damage. RESULTS: TLR8 is a receptor protein of the immune system, which is widely expressed in immune cells. In our study, we found that TLR8 expression is localized in lysosomes and endosomes. Mir-99a-5p can negatively regulate TLR8 to activate PI3K-AKT molecular pathway and aggravate cartilage damage. Inhibiting TLR8 expression can effectively reduce the incidence of articular cartilage damage. CONCLUSION: Based on the results from this study, mir-99a-5p may be an effective molecular marker for predicting traumatic cartilage injury and targeting TLR8 is a novel and promising approach for the prevention or early treatment of cartilage damage.

Model construction and application for predicting pre-eclampsia by Sonoclot coagulation analyzer.

Maternal age has significantly increased among Chinese women, thereby posing risk of pregnancy-related complications. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, and coagulation analysis in conjunction with clinical signs and symptoms are generally used for its diagnosis with limited efficacy. Sonoclot coagulation analyzer is effective in assessing coagulation function used during cerebral surgery and cardiovascular surgery. However, its use has not been explored in preeclampsia. Here, we investigated the potential use of Sonoclot in diagnosing preeclampsia in obstetrics cases. Subjects meeting the screening criteria were divided either into a test group or a control group, according to whether they were preeclamptic or not. We recorded the Sonoclot-derived coagulation and the routine coagulation parameters including platelet function (PF), activated clotting time (ACT) and clot rate (CR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and platelet count. Regression analysis was done on the relevant parameters to assess the feasibility of Sonoclot analyzer in preeclampsia diagnosis. In parallel, changes in preeclampsia lncRNAs was also evaluated. Significant differences were recorded in PT and ACT between the two groups. In the monovariant logistic regression, PT and ACT appeared to be reliable predictor variables. In the multinomial logistic regression, a total of five regression steps were performed with decreasing AIC values. The K-fold cross validation resulted in an accuracy rate (ACC) of 77.5%, a false positive rate of 16.4%, and a false negative rate of 33.2%. lncRNAs ANRIL and HOXD-AS1 were found deregulated. Our findings indicate that Sonoclot may be useful for diagnosis of preeclampsia in obstetrics.

Personality prediction from task-oriented and open-domain human-machine dialogues.

If a dialogue system can predict the personality of a user from dialogue, it will enable the system to adapt to the user's personality, leading to better task success and user satisfaction. In a recent study, personality prediction was performed using the Myers-Briggs Type Indicator (MBTI) personality traits with a task-oriented human-machine dialogue using an end-to-end (neural-based) system. However, it is still not clear whether such prediction is generally possible for other types of systems and user personality traits. To clarify this, we recruited 378 participants, asked them to fill out four personality questionnaires covering 25 personality traits, and had them perform three rounds of human-machine dialogue with a pipeline task-oriented dialogue system or an end-to-end task-oriented dialogue system. We also had another 186 participants do the same with an open-domain dialogue system. We then constructed BERT-based models to predict the personality traits of the participants from the dialogues. The results showed that prediction accuracy was generally better with open-domain dialogue than with task-oriented dialogue, although Extraversion (one of the Big Five personality traits) could be predicted equally well for both open-domain dialogue and pipeline task-oriented dialogue. We also examined the effect of utilizing different types of dialogue on personality prediction by conducting a cross-comparison of the models trained from the task-oriented and open-domain dialogues. As a result, we clarified that the open-domain dialogue cannot be used to predict personality traits from task-oriented dialogue, and vice versa. We further analyzed the effects of system utterances, task performance, and the round of dialogue with regard to the prediction accuracy.

Mechanisms of surface groups regulating developmental toxicity of graphene-based nanomaterials via glycerophospholipid metabolic pathway.

Surface modification of graphene-based nanomaterials (GBNs) may occur in aquatic environment and during intentional preparation. However, the influence of the surface groups on the developmental toxicity of GBNs has not been determined. In this study, we evaluated the developmental toxicity of three GBNs including GO (graphene oxide), RGO (reduced GO) and RGO-N (aminated RGO) by employing zebrafish embryos at environmentally relevant concentrations (1-100 µg/L), and the underlying metabolic mechanisms were explored. The results showed that both GO and RGO-N disturbed the development of zebrafish embryos, and the adverse effect of GO was greater than that of RGO-N. Furthermore, the oxygen-containing groups of GBNs play a more important role in inducing developmental toxicity compared to size, defects and nitrogen-containing groups. Specifically, the epoxide and hydroxyl groups of GBNs increased their intrinsic oxidative potential, promoted the generation of ROS, and caused lipid peroxidation. Moreover, a significant decrease in guanosine and abnormal metabolism of multiple glycerophospholipids were observed in all three GBN-treated groups. Nevertheless, GO exposure triggered more metabolic activities related to lipid peroxidation than RGO or RGO-N exposure, and the disturbance intensity of the same metabolite was greater than that of the other two agents. These findings reveal underlying metabolic mechanisms of GBN-induced developmental toxicity.

Exploring patient delay in people with chronic kidney disease: A cross-sectional study.

To examine the factors that contribute to patient delays among individuals with chronic kidney disease (CKD) and offer insights to help develop specific risk management strategies. Conducted as a cross-sectional study between September 2021 and April 2022, this study used a convenient sampling technique to select 245 individuals diagnosed with CKD from a Grade 3 Class A hospital located in Shanxi Province. These individuals were chosen as the subjects of the study. The research participants underwent an investigation using several assessment tools, including socio-demographic information questionnaire, medical behavior, the social support rating scale, the simplified coping style questionnaire, and the General Self-efficacy Scale. The study revealed that 35.4% of individuals with CKD experienced patient delay (the interval between the initial onset and the time of seeking medical attention being longer than or equal to 3 months). Through a multifactorial logistic regression analysis, it was determined that various factors independently influenced patient delay in patients with CKD. These factors included the level of knowledge about CKD, educational level, frequency of attending physical examinations, severity of initial symptoms, social support, self-efficacy, positive coping, and negative coping. Numerous factors contribute to the Patient Delay. To effectively enhance awareness and coping abilities regarding CKD in high-risk groups, it is essential to implement focused and continuous interventions throughout the medical seeking process.