Platelet count in heart failure patients undergoing left ventricular assist device.

AIMS: Left ventricular assist device (LVAD) implantation, a therapy for end-stage heart failure, is associated with platelet (PLT) activation. This study aims to evaluate the prognostic impact of PLT count in patients with LVAD implantation. METHODS AND RESULTS: Data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry were investigated, and patients were divided into three groups according to tertiles. The dynamic change of PLT counts and its associations with long-term outcomes were analysed. The primary outcome was long-term mortality. A total of 19 517 patients who received the first continuous-flow LVAD were identified from the INTERMACS registry. The PLT count underwent a dynamic change towards normalization after LVAD implantation. Compared with intermediate, both high (hazard ratio [HR], 1.09, 95% confidence interval [CI]: 1.01 to 1.17, P = 0.033) and low (HR, 1.18, 95% CI: 1.10 to 1.27, P < 0.001) pre-implant PLT counts were associated with an increased risk of 2 year mortality. Compared with intermediate, a high post-implant PLT count was associated with an increased risk of 4 year mortality (HR, 1.38, 95% CI: 1.26 to 1.52, P < 0.001). Besides, both pre- and post-implant PLT counts exhibit a U-shaped association with the risk of mortality. CONCLUSIONS: LVAD implantation could improve the PLT count towards normalization. Abnormal pre-/post-implant PLT counts were independently associated with increased risks of long-term mortality.

Mechanism and clinical role of TIMP-2 and IGFBP-7 in cardiac surgery-associated acute kidney injury: A review.

Acute kidney injury (AKI) is a common postoperative complication, but there is still a lack of accurate biomarkers. Cardiac surgery-associated AKI is the most common cause of major-surgery-related AKI, and patients requiring renal replacement therapy have high mortality rates. Early diagnosis, intervention, and management are crucial for improving patient prognosis. However, diagnosing AKI based solely on changes in serum creatinine level and urine output is insufficient, as these changes often lag behind actual kidney damage, making early detection challenging. Biomarkers such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) have been found to be significant predictors of moderate-to-severe AKI when combined with urine content analysis. This article reviews the mechanism of biomarkers TIMP-2 and IGFBP-7 in AKI and provides a comprehensive overview of the clinical effects of TIMP-2 and IGFBP-7 in cardiac surgery-associated AKI, including prediction, diagnosis, and progression.

Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis. Moreover, pharmacological inhibition of PKMYT1 shows efficacy in multiple PDAC cell models and effectively induces tumor regression without overt toxicity in PDAC cell line-derived xenograft and in more clinically relevant patient-derived xenograft models. Mechanistically, in addition to its canonical function of phosphorylating CDK1, PKMYT1 functions as an oncogene to promote PDAC tumorigenesis by regulating PLK1 expression and phosphorylation. Finally, TP53 function and PRKDC activation are shown to modulate the sensitivity to PKMYT1 inhibition. These results define PKMYT1 dependency in PDAC and identify potential therapeutic strategies for clinical translation.

Concomitant tricuspid valve surgery in patients undergoing left ventricular assist device: a systematic review and meta-analysis.

INTRODUCTION: This study aims to investigate the effect of concomitant tricuspid valve surgery (TVS) during left ventricular assist device (LVAD) implantation due to the controversy over the clinical outcomes of concomitant TVS in patients undergoing LVAD. METHODS: A systematic literature search was performed in PubMed and EMbase from the inception to 1 August 2023. Studies comparing outcomes in adult patients undergoing concomitant TVS during LVAD implantation (TVS group) and those who did not (no-TVS group) were included. The primary outcomes were right heart failure (RHF), right ventricular assist device (RVAD) implantation, and early mortality. All meta-analyses were performed using random-effects models, and a two-tailed P <0.05 was considered significant. RESULTS: Twenty-one studies were included, and 16 of them were involved in the meta-analysis, with 660 patients in the TVS group and 1291 in the no-TVS group. Patients in the TVS group suffered from increased risks of RHF [risk ratios (RR)=1.31, 95% CI: 1.01-1.70, P =0.04; I2 =38%, pH =0.13), RVAD implantation (RR=1.56, 95% CI: 1.16-2.11, P =0.003; I2 =0%, pH =0.74), and early mortality (RR=1.61, 95% CI: 1.07-2.42, P =0.02; I2 =0%, pH =0.75). Besides, the increased risk of RHF holds true in patients with moderate to severe tricuspid regurgitation (RR=1.36, 95% CI: 1.04-1.78, P =0.02). TVS was associated with a prolonged cardiopulmonary bypass time. No significant differences in acute kidney injury, reoperation requirement, hospital length of stay, or ICU stay were observed. CONCLUSIONS: Concomitant TVS failed to show benefits in patients undergoing LVAD, and it was associated with increased risks of RHF, RVAD implantation, and early mortality.

Tumor cell-intrinsic SETD2 inactivation sensitizes cancer cells to immune checkpoint blockade through the NR2F1-STAT1 pathway.

BACKGROUND: Cancer immunotherapies can induce durable tumor regression, but most patients do not respond. SETD2 mutation has been linked to the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy. The functional importance of the SETD2 inactivation and how to modulate immunotherapy response remains unclear. METHODS: To explore the function of SETD2 in immunotherapy, knockout and subsequent functional experiments were conducted. Bulk RNA-seq, ATAC-seq, Chip-seq and single-cell RNA-seq were performed to dissect the mechanism and explore the immune microenvironment of mouse tumor. Flow cytometry was used to assess cell surface antigen and intratumoral T cell levels. RESULTS: We comprehensively determine the effect of SETD2 inactivation in ICIs therapy and elucidate the mechanistic impact on tumor immunity. Murine syngeneic tumors harboring Setd2 inactivation are sensitive to ICIs. By bulk and single-cell RNA-seq, we further reveal that SETD2 inactivation reprograms intratumoral immune cells and inflames the tumor microenvironment, which is characterized by high infiltration of T cells and enhanced antigen presentation to activate CD8+ T cell-mediated killing. Mechanistically, via an integrated multiomics analysis using ATAC-seq, ChIP-seq and RNA-seq, we demonstrate that SETD2 inactivation reduces NR2F1 transcription by impairing H3K36me3 deposition and chromatin accessibility, which activates the STAT1 signaling pathway to promote chemokines and programmed cell death protein-1 (PD-1) expression and enhance antigen presentation. All these regulatory mechanisms synergistically promote the effects of anti-programmed cell death ligand 1 immunotherapy in Setd2-knockout syngeneic mouse models. The SETD2-NR2F1-STAT1 regulatory axis is conserved in human and murine cancers. Finally, cancer patients harboring SETD2 mutations who received ICIs show increased durable clinical benefits and survival. CONCLUSIONS: These findings provide novel insights into the biology of SETD2 inactivation regulation and reveal a new potential therapeutic biomarker for ICIs immunotherapy in various refractory cancers.

Microglia modulate general anesthesia through P2Y12 receptor.

General anesthesia (GA) is an unconscious state produced by anesthetic drugs, which act on neurons to cause overall suppression of neuronal activity in the brain. Recent studies have revealed that GA also substantially enhances the dynamics of microglia, the primary brain immune cells, with increased process motility and territory surveillance. However, whether microglia are actively involved in GA modulation remains unknown. Here, we report a previously unrecognized role for microglia engaging in multiple GA processes. We found that microglial ablation reduced the sensitivity of mice to anesthetics and substantially shortened duration of loss of righting reflex (LORR) or unconsciousness induced by multiple anesthetics, thereby promoting earlier emergence from GA. Microglial repopulation restored the regular anesthetic recovery, and chemogenetic activation of microglia prolonged the duration of LORR. In addition, anesthesia-accompanying analgesia and hypothermia were also attenuated after microglial depletion. Single-cell RNA sequencing analyses showed that anesthesia prominently affected the transcriptional levels of chemotaxis and migration-related genes in microglia. By pharmacologically targeting different microglial motility pathways, we found that blocking P2Y12 receptor (P2Y12R) reduced the duration of LORR of mice. Moreover, genetic ablation of P2Y12R in microglia also promoted quicker recovery in mice from anesthesia, verifying the importance of microglial P2Y12R in anesthetic regulation. Our work presents the first evidence that microglia actively participate in multiple processes of GA through P2Y12R-mediated signaling and expands the non-immune roles of microglia in the brain.

Superior mesenteric artery syndrome following lung cancer surgery: A case report.

INTRODUCTION AND IMPORTANCE: Superior mesenteric artery syndrome (SMAS) is a rare medical condition resulting from vascular compression of the third part of the duodenum in the angle between the aorta and the superior mesenteric artery, leading to partial or complete intestinal obstruction and causing a series of symptoms. We now introduce a case of SMAS after lung cancer surgery, which was unique in that it was most likely caused by weight loss after surgery. CASE PRESENTATION: A 58-year-old male patient gradually developed severe nausea, vomiting, and weight loss after lung cancer surgery. A diagnosis of SMAS was made after the computed tomography of the abdomen was performed. The patient's symptoms were relieved after immediate placement of a nasojejunal nutrition tube for gastrointestinal decompression and enteral nutrition support. CLINICAL DISCUSSION: SMAS is rare and the symptoms are not specific, the clinical diagnosis of it is mostly confirmed by imaging. The presence of SMAS should be considered as a possibility when recurrent nausea and vomiting occur after lung surgery that excludes the above-mentioned causes. CONCLUSION: The signs and symptoms of SMAS are usually non-specific, which leads to misdiagnosis in all probability. SMAS should be considered when unexplained significant weight loss accompanied by recurrent nausea and vomiting happens to postoperative patients.

Tree-Based Risk Factor Identification and Stroke Level Prediction in Stroke Cohort Study.

Objective. This study focuses on the identification of risk factors, classification of stroke level, and evaluation of the importance and interactions of various patient characteristics using cohort data from the Second Hospital of Lanzhou University. Methodology. Risk factors are identified by evaluation of the relationships between factors and response, as well as by ranking the importance of characteristics. Then, after discarding negligible factors, some well-known multicategorical classification algorithms are used to predict the level of stroke. In addition, using the Shapley additive explanation method (SHAP), factors with positive and negative effects are identified, and some important interactions for classifying the level of stroke are proposed. A waterfall plot for a specific patient is presented and used to determine the risk degree of that patient. Results and Conclusion. The results show that (1) the most important risk factors for stroke are hypertension, history of transient ischemia, and history of stroke; age and gender have a negligible impact. (2) The XGBoost model shows the best performance in predicting stroke risk; it also gives a ranking of risk factors based on their impact. (3) A combination of SHAP and XGBoost can be used to identify positive and negative factors and their interactions in stroke prediction, thereby providing helpful guidance for diagnosis.

Probiotics to prevent necrotizing enterocolitis in very low birth weight infants: A network meta-analysis.

Objective: This study aims to review the evidence for the optimal regimen of probiotics for the prevention of necrotizing enterocolitis (NEC) in very low birth weight infants. Design: Through searching PubMed, EMBASE, Cochrane Library, and Web of Science till September 30, 2022, only randomized controlled trials were included to evaluate the optimal regimen of probiotics for the prevention of NEC in very low birth weight infants. The methodological quality of the included studies was assessed by the Cochrane risk of bias assessment tool (RoB 2), and the collected data were analyzed accordingly using Stata software. Results: Twenty-seven RCTs were included, and the total sample size used in the study was 529. The results of the network meta-analysis showed that Bovine lactoferrin + Lactobacillus rhamnosus GG (RR 0.03; 95% CI 0.00-0.35), Lactobacillus rhamnosus + Lactobacillus plantarum + Lactobacillus casei + Bifidobacterium lactis (RR 0.06; 95% CI 0.00-0.70), Bifidobacterium lactis + inulin (RR 0.16; 95% CI 0.03-0.91) were superior to the control group (Bifidobacterium lactis + Bifidobacterium longum) in reducing the incidence of NEC. The reduction in the incidence of NEC were as follows: Bovine lactoferrin + Lactobacillus rhamnosus GG (SUCRA 95.7%) > Lactobacillus rhamnosus + Lactobacillus plantarum + Lactobacillus casei + Bifidobacterium lactis (SUCRA 89.4%) > Bifidobacterium lactis + inulin (SUCRA 77.8%). Conclusions: This network meta-analysis suggests that Lactobacillus rhamnosus GG combined with bovine lactoferrin maybe the most recommended regimen for the prevention of NEC in very low birth weight infants.

Integrated top-down and bottom-up proteomics mass spectrometry for the characterization of endogenous ribosomal protein heterogeneity.

Ribosomes are abundant, large RNA-protein complexes that are the sites of all protein synthesis in cells. Defects in ribosomal proteins (RPs), including proteoforms arising from genetic variations, alternative splicing of RNA transcripts, post-translational modifications and alterations of protein expression level, have been linked to a diverse range of diseases, including cancer and aging. Comprehensive characterization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets. In the present work, using E. coli 70S RPs as an example, we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry (MS) system, and then applied it to the HeLa 80S ribosome. The results were complemented by a bottom-up approach. In total, 50 out of 55 RPs were identified using the top-down approach. Among these, more than 30 RPs were found to have their N-terminal methionine removed. Additional modifications such as methylation, acetylation, and hydroxylation were also observed, and the modification sites were identified by bottom-up MS. In a HeLa 80S ribosomal sample, we identified 98 ribosomal proteoforms, among which multiple truncated 80S ribosomal proteoforms were observed, the type of information which is often overlooked by bottom-up experiments. Although their relevance to diseases is not yet known, the integration of top-down and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.

Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity.

Microglia continuously survey the brain parenchyma and actively shift status following stimulation. These processes demand a unique bioenergetic programme; however, little is known about the metabolic determinants in microglia. By mining large datasets and generating transgenic tools, here we show that hexokinase 2 (HK2), the most active isozyme associated with mitochondrial membrane, is selectively expressed in microglia in the brain. Genetic ablation of HK2 reduced microglial glycolytic flux and energy production, suppressed microglial repopulation, and attenuated microglial surveillance and damage-triggered migration in male mice. HK2 elevation is prominent in immune-challenged or disease-associated microglia. In ischaemic stroke models, however, HK2 deletion promoted neuroinflammation and potentiated cerebral damages. The enhanced inflammatory responses after HK2 ablation in microglia are associated with aberrant mitochondrial function and reactive oxygen species accumulation. Our study demonstrates that HK2 gates both glycolytic flux and mitochondrial activity to shape microglial functions, changes of which contribute to metabolic abnormalities and maladaptive inflammation in brain diseases.

Iron metabolism mediates microglia susceptibility in ferroptosis.

Ferroptosis is implicated in a range of brain disorders, but it is unknown whether neurons or glia in the brain are particularly effected. Here, we report that primary cortical astrocytes (PA), microglia (PM), and neurons (PN) varied in their sensitivities to ferroptosis. Specifically, PM were the most sensitive to ferroptosis, while PN were relatively insensitive. In contrast, PN and PM were equally susceptible to apoptosis, with PA being less affected, whereas all three cell types were similarly susceptible to autophagic cell death. In the tri-culture system containing PA, PM, and PN, the cells were more resistant to ferroptosis than that in the monoculture. These results demonstrated that brain cells exhibit different sensitivities under ferroptosis stress and the difference may be explained by the differentially regulated iron metabolism and the ability to handle iron. Continued elucidation of the cell death patterns of neurons and glia will provide a theoretical basis for related strategies to inhibit the death of brain cells.

Insights into Phosphorylation-Induced Protein Allostery and Conformational Dynamics of Glycogen Phosphorylase via Integrative Structural Mass Spectrometry and In Silico Modeling.

Allosteric regulation plays a fundamental role in innumerable biological processes. Understanding its dynamic mechanism and impact at the molecular level is of great importance in disease diagnosis and drug discovery. Glycogen phosphorylase (GP) is a phosphoprotein responding to allosteric regulation and has significant biological importance to glycogen metabolism. Although the atomic structures of GP have been previously solved, the conformational dynamics of GP related to allostery regulation remain largely elusive due to its macromolecular size (∼196 kDa). Here, we integrated native top-down mass spectrometry (nTD-MS), hydrogen-deuterium exchange MS (HDX-MS), protection factor (PF) analysis, molecular dynamics (MD) simulations, and allostery signaling analysis to examine the structural basis and dynamics for the allosteric regulation of GP by phosphorylation. nTD-MS reveals differences in structural stability as well as oligomeric state between the unphosphorylated (GPb) and phosphorylated (GPa) forms. HDX-MS, PF analysis, and MD simulations further pinpoint the structural differences between GPb and GPa involving the binding interfaces (the N-terminal and tower-tower helices), catalytic site, and PLP-binding region. More importantly, it also allowed us to complete the missing link of the long-range communication process from the N-terminal tail to the catalytic site caused by phosphorylation. This integrative MS and in silico-based platform is highly complementary to biophysical approaches and yields valuable insights into protein structures and dynamic regulation.

Feasibility of Video-Assisted Thoracoscopic Surgery via Subxiphoid Approach in Anterior Mediastinal Surgery: A Meta-Analysis.

Background: Accumulating researches show potential advantages of video-assisted thoracoscopic surgery (VATS) via the subxiphoid approach, and this meta-analysis aims to investigate the efficacy and safety of the subxiphoid approach for anterior mediastinal surgery. Methods: Relevant studies were retrieved by searching Embase and PubMed databases (from the inception to October 1, 2021). Primary outcomes included postoperative pain, intraoperative blood loss, operation time, chest tube duration, and hospital length of stay. All meta-analyses were performed by using random-effects models. Results: Overall, 14 studies with 1,279 patients were included, with 504 patients undergoing anterior mediastinal surgery via subxiphoid approach and 775 via other approaches. The pooled results indicated that the subxiphoid approach was associated with reduced postoperative pain indicated by visual analog scale [weight mean difference (WMD): 24 h: -2.27, 95% CI, -2.88 to -1.65, p < 0.001; 48-72 h: -1.87, 95% CI, -2.53 to -1.20, p < 0.001; 7 days: -0.98, 95% CI, -1.35 to -0.61, p < 0.001], shortened duration of chest tube drainage (WMD: -0.56 days, 95% CI, -0.82 to -0.29, p < 0.001), shortened hospital length of stay (WMD: -1.46 days, 95% CI, -2.28 to -0.64, p < 0.001), and reduced intraoperative blood loss (WMD: -26.44 mL, 95% CI, -40.21 to -12.66, p < 0.001) by comparison with other approaches in anterior mediastinal surgery. Besides, it has no impact on operation time and the incidence of complications of transition to thoracotomy, postoperative pleural effusion, phrenic nerve palsy, and lung infection. Conclusions: Our study suggests that the subxiphoid approach is a feasible alternative approach and even can be a better option for anterior mediastinal surgery. Further, large-scale multicenter randomized controlled trials are needed to validate this finding.

High-Reflective Templated Cholesteric Liquid Crystal Filters.

Cholesteric liquid crystals (CLCs) have been widely applied in optical filters due to Bragg reflection caused by their helical structure. However, the reflectivity of CLC filters is relatively low, commonly less than 50%, as the filters can only reflect light polarized circularly either left- or right-handedly. Therefore, a high-reflective CLC filter with a single-layer template was proposed which may reflect both right- and left-handed polarized light. The CLC filters of the red, green, blue color were fabricated by the templating technology, which show good wavelength consistency. Additionally, a multi-phase liquid crystal filter with high reflectance was demonstrated by the single-layer templating technology. The templated CLC or multi-phase liquid crystal filters show great potential applications in the optical community, reflective display, and lasing.

A Tension/Pressure Integrated Resistive Sensor Comprising of a PDMS-LC-MWCNT Composite.

A flexible strain sensor which integrates both pressure sensing and tension sensing functions is demonstrated with an active layer comprising of polydimethy-lsiloxane (PDMS) elastomer, liquid crystal (LC), and multi-walled carbon nanotubes (MWCNTs). The introduction of LC improves the agglomeration of MWCNTs in PDMS and decreases Young's modulus of flexible resistive sensors. The tension/pressure integrated resistive sensor not only shows a broad tensile sensing range of 140% strain but also shows a good sensitivity of the gauge factor, 40, with tensile force. Besides, the tension/pressure integrated resistive sensor also shows good linearity and sensitivity under pressure. The resistance of the pressure sensor increases as the applied pressure increases because of the decrease in the cross-sectional area of the path. The sensor also shows good hydrophobic properties which may help it to work under complex environment. The tension/pressure integrated sensor shows great promising applications in electronic skins and wearable devices.

E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non-small cell lung cancer.

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non-small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell-specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry-based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.

Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs).

Class I histone deacetylases (HDACs) are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections and neurological diseases. Although six HDAC inhibitors are now licensed for clinical treatments, they are all pan-inhibitors with little or no HDAC isoform selectivity, exhibiting undesirable side effects. A major issue with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Except for HDAC8, Class I HDACs (1, 2 and 3) are recruited to large multiprotein complexes to function. Therefore, there are rising needs to develop new, hopefully, therapeutically efficacious HDAC inhibitors with isoform or complex selectivity. Here, upon the introduction of the structures of Class I HDACs and their complexes, we provide an up-to-date overview of the structure-based discovery of Class I HDAC inhibitors, including pan-, isoform-selective and complex-specific inhibitors, aiming to provide an insight into the discovery of additional HDAC inhibitors with greater selectivity, specificity and therapeutic utility.

Research on Strain Measurements of Core Positions for the Chinese Space Station.

The Chinese space station is designed to carry out manned spaceflight, space science research, and so on. In serious applications, it is a common operation to inject gas into the hull, which can produce strain of the bulkhead. Accurate measurement of strain for the bulkhead is one of the key tasks in evaluating the health condition of the space station. This is the first work to perform strain detection for the Chinese space station bulkhead by using optical fiber Bragg grating. In the period of measurements, the resistance strain gauge is used as the strain standard. The measurement error of the fiber optical sensor in the circumferential direction is very small, being less than 4.52 µÎµ. However, the error in the axial direction is very large with the highest value of 28.93 µÎµ. Because the measurement error of bare fiber in the axial direction is very small, the transverse effect of the substrate of the fiber optical sensor likely plays a role. The comparison of the theoretical and experimental results of the transverse effect coefficients shows that they are fairly consistent, with values of 0.0271 and 0.0287, respectively. After the transverse effect is compensated, the strain deviation in the axial detection is smaller than 2.04 µÎµ. It is of great significance to carry out real-time health assessment for the bulkhead of the space station.

Voluntary exercise increases adult hippocampal neurogenesis by increasing GSK-3ß activity in mice.

Exercise has been proven to promote learning and memory, and is closely related to increased adult neurogenesis in the hippocampus. In our study, the ß subunit of Glycogen synthase kinase-3 (GSK3ß) can be significantly regulated by exercise, and the modulation of GSK3ß activity can enhance adult neurogenesis and memory. To explore the mechanism by which exercise can improve cognitive function and adult neurogenesis, and the role GSK3ß plays in this process, we established a mouse model of voluntary exercise to examine the expression and activity of GSK3ß, and its associated signaling pathways, in the hippocampus dentate gyrus. The results showed an obvious increase in adult neurogenesis and cognitive functions, and the up-regulation of GSK3ß, after exercise. The activity of the insulin pathway, which negatively regulates GSK3ß, was also increased. Moreover, our results showed that the dopamine D1 receptor (DARP D1) pathway and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) were also activated, which indicates a relationship between GSK3ß and neurogenesis. Overall, our findings demonstrated that voluntary exercise promotes cognition and neurogenesis in the adult mouse dentate gyrus by the regulation of GSK3ß expression and activity, which may be implemented through the DARP D1 receptor-signaling pathway.