Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

The prevalence of comorbidity of eating disorders(ED)and bipolar disorder(BD)is high,and patients with comorbid conditions often have a high risk of suicide and poor prognosis.Exploring the pathogenesis of BD comorbid with ED is of great significance for improving clinical efficacy and adverse prognosis in patients.The mechanisms underlying BD comorbid ED remain unclear,involving multifaceted neurobiological factors such as serotonin system dysfunction,dopamine reward pathway disruption,abnormal immune system activation,fluctuations in sex hormone levels,and functional and structural abnormalities in brain regions associated with emotional control and reward system pathways.Therefore,this article provides ideas for the research direction of BD comorbid with ED by analyzing the roles of genetic metabolism,neurobiochemistry,immune,and imaging changes in the comorbidity mechanism.

The prevalence of comorbidity of eating disorders(ED)and bipolar disorder(BD)is high,and patients with comorbid conditions often have a high risk of suicide and poor prognosis.Exploring the pathogenesis of BD comorbid with ED is of great significance for improving clinical efficacy and adverse prognosis in patients.The mechanisms underlying BD comorbid ED remain unclear,involving multifaceted neurobiological factors such as serotonin system dysfunction,dopamine reward pathway disruption,abnormal immune system activation,fluctuations in sex hormone levels,and functional and structural abnormalities in brain regions associated with emotional control and reward system pathways.Therefore,this article provides ideas for the research direction of BD comorbid with ED by analyzing the roles of genetic metabolism,neurobiochemistry,immune,and imaging changes in the comorbidity mechanism.

The leukocyte immunoglobulin-like receptor LILRB4(ILT3 or CD85k),a member of the immunosuppressive re-ceptor family,is expressed predominantly on the cell membranes of immune cells of myeloid origin,and exerts an immunosuppressive effect in immune regulation by activating either the autoinhibitory motif(ITIM)or by inhibiting Fc receptor activation motif(ITAM).In tumors,activation of LILRB4 receptor generates an immunosuppressive tumor microenvironment that assists in tumor invasion and metastasis,and in inflammatory diseases,LILRB4 is expressed on a variety of cells,such as monocytes,macrophages,mast cells,etc.,and attenuates inflammatory responses.Currently,LILRB4 has become a therapeutic target for tumors and various inflammatory diseases,and anti-LILRB4 monoclonal antibodies against acute myeloid leukemia(AML)have entered clinical trials.This review dis-cusses LILRB4 in terms of its structural distribution,signaling,therapeutic targets,and new drug development.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

Objective To evaluate the value of perfusion imaging mismatch and low perfusion ratio(HIR)based on CT perfusion imaging in predicting acute intracranial large vessel occlusion(LVO)associated with intracranial atherosclerotic stenosis(ICAS).Methods A total of 82 pa-tients with acute intracranial LVO who underwent emergency thrombectomy in our hospital from February 2019 to December 2020 were enrolled in this study.According to the etiology,they were divided into ICAS-related LVO group(ICAS-LVO,65 cases)and cardiogenic embolism group(17 cases).ROC curve was plotted to analyze the predictive value of CT perfusion imaging parame-ters.Results Compared with the cardiogenic embolism group,the ICAS-LVO group had signifi-cantly larger male ratio,higher BMI and TG level,more severe progression of disease,longer time from onset to surgery,larger proportion of ischemic penumbra and higher mismatch ratio,and ob-viously less ratio of atrial fibrillation,lower BNP and HDL levels,smaller infarct volume,and lower HIR(P＜0.05,P＜0.01).ROC curve analysis showed that HIR and mismatch ratio had good predictive value for the etiology of ICAS-LVO.The optimal cut-off value of HIR was 0.26,with an AUC value of 0.74,a specificity of 0.88,and a sensitivity of 0.54.The optimal cutoff for the mismatch ratio was 3.84,with an AUC value of 0.84,a specificity of 0.75,and a sensitivity of 0.90.Generalized linear model revealed that HIR and cerebral blood volume index had no signifi-cant difference in prognostic performance(P=0.175).Conclusion HIR and mismatch ratio are helpful to identify the pathogenesis earlier and formulate surgical strategies more accurately,thereby reducing iatrogenic injury to a greater extent,increasing the effective reperfusion rate,re-ducing the disability and mortality,and improving the prognosis of clinical outcomes.

Objective : To explore whether the NLRP3 inflammasome is activated after Newcastle disease virus (NDV) exposure to esophageal cancer ECA109 cells , whether its activation is related to K + efflux , and the effect of ATP/P2X7 axis on the activation of NLRP3 inflammasome. Methods: The expression of NLRP3 and IL⁃1β was detected by Western blot; the content of IL⁃1β in the supernatant was detected by ELISA ; the formation of ASC spots was detected by fluorescence immunoassay; the change of intracellular K + concentration was detected by fluorescent probe technology; Interventions with ATPase , ATP and P2X7 receptor inhibitors were used to investigate their role in NLRP3 inflammasome activation. Results: Compared with the control group , the expression of NLRP3 , IL⁃1β and ASC protein in cells was up⁃regulated after NDV F3 infection ; the intracellular potassium concen tration decreased with the prolongation of infection time (P < 0. 05) . After the intervention of P2X7 receptor inhibitor, the efflux of intracellular K + was blocked. With the increase of inhibitor concentration , the efflux of K + was maximally inhibited at 10 μmol/L (P < 0. 05) . The results of ATPase and ATP intervention showed that ATPase inhibited K + efflux , while ATP promoted K + efflux. Western blot results showed that compared with the control group , P2X7 receptor was inhibited , and the expressions of NLRP3 and IL⁃1β were down⁃regulated ; after ATPase intervened cells , the expressions of NLRP3 and IL⁃1β decreased ; After ATP intervention in cells , the protein expressions of NLRP3 and IL⁃1β were up⁃regulated (P < 0. 05) . Conclusion NDV F3 infection of ECA109 cells can activate the NLRP3 inflammasome , the mechanism may be related to the ATP/P2X7 axis.

Background There is a lack of research evidence on the association between sugar-sweetened beverage (SSB) consumption and gestational diabetes mellitus (GDM) in China. Objective To explore the association between frequency of SSB consumption before pregnancy and risk of GDM in pregnant women in Shaanxi Province, and to provide a scientific basis for targeted interventions to control maternal blood glucose. Methods The recruitment to the China Birth Cohort study started in October 2020. Pregnant women at 6-16 weeks who had their first prenatal examination at five hospitals in Shaanxi Province were recruited. A maternal health questionnaire was used to collect basic information about pregnant women. A semi-quantitative food frequency questionnaire was used to collect the consumption of carbonated beverages, fruit and vegetable juice beverages, coffee beverages, and milk tea beverages in one year before pregnancy, which were summed to obtain the SSB consumption. Pregnant women were divided into three groups according to SSB consumption, namely <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹. GDM was confirmed by oral glucose tolerance test (OGTT) between 24-28 weeks of gestation. A binary logistic regression model was applied to explore the association between SSB consumption and risk of GDM. Multiple linear regression was applied to investigate the associations between SSB consumption (per 1-serving·d⁻¹ increase) and OGTT fasting plasma glucose, 1-hour glucose, and 2-hour glucose. Results A total of 3811 pregnant women were finally enrolled in this study, of which 752 developed GDM, with an incidence rate of 19.7%. The incidence rates of GDM in pregnant women with SSB consumption frequency of <1 serving·week⁻¹, 1-4 servings·week⁻¹, and ≥5 servings·week⁻¹ were 18.0%, 21.1%, and 26.8%, respectively. After adjusting for maternal age, pre-pregnancy body mass index (BMI), education, number of children born, family history of diabetes, smoking, alcohol consumption, physical activity level, and total energy intake, the risk of GDM increased by 26% (OR=1.26, 95%CI: 1.05, 1.50) in the 1-4 servings·week⁻¹ group and by 76% (OR=1.76, 95%CI: 1.31, 2.38) in the ≥5 servings·week⁻¹ group compared to the <1 serving·week⁻¹ SSB consumption group, respectively. Further stratified analysis revealed no interaction effect (P_interaction>0.05) between SSB consumption and maternal age, pre-pregnancy BMI, or first labor or not. For each additional SSB consumption per day, the risk of GDM increased by 94% (OR=1.94, 95%CI: 1.37, 2.75); and the maternal OGTT 1-hour glucose and 2-hour glucose increased by 0.33 mmol·L⁻¹ and 0.18 mmol·L⁻¹, respectively (P<0.05), and no significant increase in fasting plasma glucose was found (P>0.05). Conclusion Higher SSB consumption before pregnancy increases the risk of GDM in pregnant women.

Objective:To investigate the effects of compound matrine injection on the proliferation of bladder cancer cell line BIU-87 and bladder orthotopic transplantated tumor in nude mice.Methods:BIU-87 cells in logarithmic growth phase were divided into experimental group (adding 300.00, 150.00, 75.00, 37.50, 18.75 μl/ml compound matrine injection 200μl) and negative control group (adding equal volume of culturing medium). The proliferation inhibition rate and the half inhibitory concentration ( IC50) of BIU-87 cells were detected and calculated by methyl thiazole tetrazolium (MTT) method. Twenty BALB/c-nu female nude mice were injected with 100 μl of BIU-87 cell suspension with a cell density of 2×10 7/ml in the bladder to establish an animal model of bladder orthotopic transplanted tumor. After 24 hours of perfusion of BIU-87 cell suspension, intravesical perfusion administration (100 μl per nude mouse) was started, and the mice were divided into compound matrine injection group (intravesical perfusion of matrine solution) and pirarubicin group (intravesical perfusion of 1 mg/ml pirarubicin), model control group (intravesical perfusion of the same volume of sterile water), blank control group (without intravesical perfusion of BIU-87 cell suspension or administration). The observation time was 90 d. The survival status and bladder wet weight of the animals were observed and recorded, and the tumor formation rate, tumor inhibition rate and life prolongation rate were calculated. Results:Different concentrations of compound matrine injection acted on BIU-87 cells for 48 hours, and the absorbance ( A) values ??of 300.00, 150.00, 75.00, 37.50, 18.75 μl/ml compound matrine injection group and negative control group were 0.027±0.006, 0.065±0.010, 1.695±0.105, 2.387±0.017, 2.427±0.134 and 2.721±0.080 ( F = 742.67, P < 0.05), the A values ??of each concentration of compound matrine injection group were compared with the negative control group, and the differences were statistically significant (all P < 0.05). The IC50 of compound matrine injection on BIU-87 cells was 70.05 μl/ml. On the 90th day of observation, the bladder wet weights of nude mice in blank control group, model control group, pirarubicin group and compound matrine injection group were (0.018±0.004) mg, (0.422±0.130) mg, (0.219±0.136) mg and (0.237±0.113) mg ( F = 14.01, P < 0.001), and the survival time of nude mice was (90±0) d, (54±12) d, (72±4) d and (69±8) d ( F = 18.53, P < 0.001). The inhibition rates of bladder cancer in the pirarubicin group and compound matrine injection group were 48.10% and 43.84%, and the life prolongation rates of the nude mice were 34.95% and 29.53%. Conclusions:Compound matrine injection can inhibit the proliferation of BIU-87 cells in a concentration-dependent manner. Compound matrine injection can increase the tumor inhibition rate and prolong the survival time of nude mice models of bladder orthotopic transplanted tumor.

Objective::To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta (PA).Methods::This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. According to the intraoperative findings after delivery, the study population was divided into PA and non-PA groups. We compared the pregnancy outcomes between the two groups, used multivariate logistic regression to analyze the risk factors for placental accreta.Results::For this study we included 11,074 pregnant women with a history of cesarean section; and of these, 869 cases were in the PA group and 10,205 cases were in the non-PA group. Compared with the non-PA group, the probability of postpartum hemorrhage (236/10,205, 2.31% vs. 283/869, 32.57%), severe postpartum hemorrhage (89/10,205, 0.87% vs. 186/869, 21.75%), diffuse intravascular coagulation (3/10,205, 0.03% vs. 4/869, 0.46%), puerperal infection (33/10,205, 0.32% vs. 12/869, 1.38%), intraoperative bladder injury (1/10,205, 0.01% vs. 16/869, 1.84%), hysterectomy (130/10,205, 1.27% vs. 59/869, 6.79%), and blood transfusion (328/10,205,3.21 % vs. 231/869,26.58%) was significantly increased in the PA group ( P < 0.05). At the same time, the neonatal birth weight (3250.00 (2950.00-3520.00) g vs. 2920.00 (2530.00-3250.00) g), the probability of neonatal comorbidities (245/10,205, 2.40% vs. 61/869, 7.02%), and the rate of neonatal intensive care unit admission (817/10,205, 8.01% vs. 210/869, 24.17%) also increased significantly ( P < 0.05). Weight (odds ratio ( OR)= 1.03, 95% confidence interval ( CI): 1.01-1.05)), parity ( OR= 1.18, 95% CI: 1.03-1.34), number of miscarriages ( OR= 1.31, 95% CI: 1.17-1.47), number of previous cesarean sections ( OR= 2.57, 95% CI: 2.02-3.26), history of premature rupture of membrane ( OR= 1.61, 95% CI: 1.32-1.96), previous cesarean-section transverse incisions ( OR= 1.38, 95% CI: 1.12-1.69), history of placenta previa ( OR= 2.44,95% CI: 1.50-3.96), and the combination of prenatal hemorrhage ( OR= 9.95,95% CI: 8.42-11.75) and placenta previa ( OR= 91.74, 95% CI: 74.11-113.56) were all independent risk factors for PA. Conclusion::There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section, and this required close clinical attention. Weight before pregnancy, parity, number of miscarriages, number of previous cesarean sections, history of premature rupture of membranes, past transverse incisions in cesarean sections, a history of placenta previa, prenatal hemorrhage, and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section. These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.