Fisetin disrupts mitochondrial homeostasis via superoxide dismutase 2 acetylation in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is one of the most lethal malignant tumors with an urgent need for precision medicine strategies. The present study seeks to assess the antitumor effects of fisetin, and characterize its impact on PDAC. Multi-omic approaches include proteomic, transcriptomic, and metabolomic analyses. Further validation includes the assessment of mitochondria-derived reactive oxygen species (mtROS), mitochondrial membrane potential, as well as ATP generation. Molecular docking, immunoprecipitation, and proximity ligation assay were used to detect the interactions among fiseitn, superoxide dismutase 2 (SOD2), and sirtuin 2 (SIRT2). We showed that fisetin disrupted mitochondrial homeostasis and induced SOD2 acetylation in PDAC. Further, we produced site mutants to determine that fisetin-induced mtROS were dependent on SOD2 acetylation. Fisetin inhibited SIRT2 expression, thus blocking SOD2 deacetylation. SIRT2 overexpression could impede fisetin-induced SOD2 acetylation. Additionally, untargeted metabolomic analysis revealed an acceleration of folate metabolism with fisetin. Collectively, our findings suggest that fisetin disrupts mitochondrial homeostasis, eliciting an important cancer-suppressive role; thus, fisetin may serve as a promising therapeutic for PDAC.

Nanostructured MoS2 with Interlayer Controllably Regulated by Ionic Liquids/Cellulose for High-Capacity and Durable Sodium Storage Properties.

Low intrinsic conductivity and structural instability of MoS2 as an anode of sodium-ion batteries limit the liberation of its theoretical capacity. Herein, density functional theory simulations for the first time optimize MoS2 interlayer distance between 0.80 and 1.01 nm for sodium storage. 1-Butyl-3-methyl-imidazolium acetate ([BMIm]Ac) induces cellulose oligomers to intercalate MoS2 interlayers for achieving controllable distance by changing the mass ratio of cellulose to [BMIm]Ac. Based on these findings, porous carbon loading the interlayer-expanded MoS2 allowing Na+ to insert with fast kinetics is synthesized. A carbon layer derived from [BMIm]Ac and cellulose coating the composite prevents the MoS2 from contacting electrolytes, leading to less sulfur loss for a more reversible specific capacity. Meanwhile, MoS2 and carbon have a strong interfacial connection through MoN binding, contributing to enhanced structural stability. As expected, while cycling 250 times at 0.1 A g-1 , the MoS2 -porous carbon composite displays an optimal reversible capacity at 517.79 mAh g-1 as a sodium-ion batteries anode. The cyclic test of 1.0 A g-1 also shows considerable stability (310.74 mAh g-1 after 1000 cycles with 86.26% retentive capacity). This study will open up new possibilities of modifying MoS2 that serves as an applicable material as sodium-ion battery anode.

Syntactic Errors in Older Adults with Depression.

Background and Objectives: This study investigated the differences in syntactic errors in older individuals with and without major depressive disorder and cognitive function disparities between groups. We also explored the correlation between syntax scores and depression severity. Materials and Methods: Forty-four participants, assessed for dementia with the Mini-Cog, completed the 15-item Geriatric Depression Scale (TGDS-15) and specific language tests. Following a single-anonymized procedure, clinical psychologists rated the tests and syntax scores. Results: The results showed that the depressive disorders group had lower syntax scores than the non-depressed group, primarily on specific subtests. Additionally, cognitive test scores were generally lower among the depressed group. A significant relationship between depression severity and syntax scores was observed (r = -0.426, 95% CI = -0.639, -0.143). Conclusions: In conclusion, major depressive disorder is associated with reduced syntactic abilities, particularly in specific tests. However, the relatively modest sample size limited the sensitivity of this association. This study also considered the potential influence of cultural factors. Unique linguistic characteristics in the study's context were also addressed and considered as potential contributors to the observed findings.

Genome-wide association study of agronomic traits related to nitrogen use efficiency in wheat.

KEY MESSAGE: GWAS identified 347 QTLs associated with eight traits related to nitrogen use efficiency in a 389-count wheat panel. Four novel candidate transcription factor genes were verified using qRT-PCR. Nitrogen is an essential nutrient for plants that determines crop yield. Improving nitrogen use efficiency (NUE) should considerably increase wheat yield and reduce the use of nitrogen fertilisers. However, knowledge on the genetic basis of NUE during wheat maturity is limited. In this study, a diversity panel incorporating 389 wheat accessions was phenotyped for eight NUE-related agronomic traits across five different environments. A total of 347 quantitative trait loci (QTLs) for low nitrogen tolerance indices (ratio of agronomic characters under low and high nitrogen conditions) were identified through a genome-wide association study utilising 397,384 single nucleotide polymorphisms (SNPs) within the MLM (Q + K) model, including 11 stable QTLs. Furthermore, 69 candidate genes were predicted for low nitrogen tolerance indices of best linear unbiased predictions values of the eight studied agronomic traits, and four novel candidate transcription factors (TraesCS5A02G237500 for qFsnR5A.2, TraesCS5B02G384500 and TraesCS5B02G384600 for qSLR5B.1, and TraesCS3B02G068800 for qTKWR3B.1) showed differing expression patterns in contrasting low-nitrogen-tolerant wheat genotypes. Moreover, the number of favourable marker alleles calculated using NUE that were significantly related to SNP in accessions decreased over the decades, indicating a decline in the NUE of the 389 wheat varieties. These findings denote promising NUE markers that could be useful in breeding high-NUE wheat varieties, and the candidate genes could further detail the NUE-related regulation network in wheat.

SiMYB19 from Foxtail Millet (Setaria italica) Confers Transgenic Rice Tolerance to High Salt Stress in the Field.

Salt stress is a major threat to crop quality and yield. Most experiments on salt stress-related genes have been conducted at the laboratory or greenhouse scale. Consequently, there is a lack of research demonstrating the merit of exploring these genes in field crops. Here, we found that the R2R3-MYB transcription factor SiMYB19 from foxtail millet is expressed mainly in the roots and is induced by various abiotic stressors such as salt, drought, low nitrogen, and abscisic acid. SiMYB19 is tentatively localized to the nucleus and activates transcription. It enhances salt tolerance in transgenic rice at the germination and seedling stages. SiMYB19 overexpression increased shoot height, grain yield, and salt tolerance in field- and salt pond-grown transgenic rice. SiMYB19 overexpression promotes abscisic acid (ABA) accumulation in transgenic rice and upregulates the ABA synthesis gene OsNCED3 and the ABA signal transduction pathway-related genes OsPK1 and OsABF2. Thus, SiMYB19 improves salt tolerance in transgenic rice by regulating ABA synthesis and signal transduction. Using rice heterologous expression analysis, the present study introduced a novel candidate gene for improving salt tolerance and increasing yield in crops grown in saline-alkali soil.

Impact of epidural labor analgesia using sufentanil combined with low-concentration ropivacaine on maternal and neonatal outcomes: a retrospective cohort study.

BACKGROUND: Whether epidural administered sufentanil combined with low-concentration ropivacaine affected labor progress as well as maternal and neonatal outcomes still remained unknown. The aim of this study was to assess the impact of epidural sufentanil plus ropivacaine on maternal and neonatal outcomes. METHODS: This is a retrospective cohort study. Data of singleton full-term pregnancy women who received epidural labor analgesia for vaginal delivery from May 2018 to June 2020 were collected. Parturients were divided into two groups (the R group and the SR group) according to different medication regimens for epidural labor analgesia. The implementation of epidural analgesia during labor was performed with 0.167 % ropivacaine in the R group and 0.1 % ropivacaine in combination with 0.5 µg/ml sufentanil in the SR group. The primary outcome of our study included the duration of labor progress and the incidence of maternal fever, postpartum hemorrhage, fetal distress and neonatal Apgar scores less than 7 at 1 and 5 min. The secondary outcome included the incidence of episiotomy, instrumental delivery, caesarean section and grade III meconium-stained amniotic fluid. RESULTS: There were a total 3778 deliveries during the study period, 1994 and 1784 parturients were included in the R group and in the SR group, respectively. The length of the first stage of labor was remarkably shorter in the R group in comparison to the SR group (548.0 ± 273.0 vs. 570.9 ± 273.0, P = 0.013). No significant difference was found in the incidence of maternal fever, postpartum hemorrhage, fetal distress and in the neonatal Apgar scores less than 7 at 1 and 5 min between two groups. Other Maternal outcomes were comparable in the R group and the SR group. CONCLUSIONS: 0.5 µg/ml sufentanil plus 0.1 % ropivacaine for epidural labor analgesia prolonged the duration of the first stage of labor, but did not have additional impact on maternal and neonatal outcomes compared with the sole 0.167 % ropivacaine. TRIAL REGISTRATION: Clinical Research Information Service with registration number ChiCTR2100045162 . Registered 7 April 2021.

Advantages of Small Bone-Window Craniotomy Under Microscope Combined Postoperative Intracranial Pressure Monitoring in the Treatment of Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: The aim of this study is to analyze the clinical effect of small bone-window craniotomy with microscope combined postoperative ICP monitoring, and further explore an appropriate treatment for HICH patients. METHODS: One hundred fifty patients with HICH were selected according to inclusion and exclusion criteria and divided into 3 groups at random, 50 each group. Patients in 3 groups were treated with conventional craniotomy, small bone-window craniotomy and small bone-window craniotomy combined ICP monitoring respectively. The surgical efficiency, treatment effect and outcomes were recorded and analyzed. RESULTS: The intraoperative blood loss and operation time of small window groups were significantly less than that of conventional group, and the hematoma clearance rate in small window groups were significantly higher than in conventional group (P < 0.05). Compared with conventional group, the hospital stays and mannitol dose used were less in small window groups and least in small window combined ICP monitoring group (P < 0.05). The complication rate in small window combined ICP monitoring group was 10%, which was significantly lower than in conventional group (26%, P < 0.05), while no significant difference was found between small window group (18%) compared with the other 2 groups respectively (P > 0.05). The difference of morality rate between 3 groups wasn't significant (P > 0.05). Three treatment significantly increased the Barthel index score, and the improvement of small window combined ICP monitoring group was significantly higher than in other 2 groups respectively (P < 0.05), while the difference between this two groups wasn't significant (P > 0.05). CONCLUSION: Small bone-window craniotomy is more efficient and convenient than conventional craniotomy in the treatment of HICH. In the meantime, small bone-window craniotomy simultaneous with ICP monitoring significantly improved clinical effect and treatment outcomes of HICH patients.

Transcriptome Differences in Response Mechanisms to Low-Nitrogen Stress in Two Wheat Varieties.

Nitrogen plays a crucial role in wheat growth and development. Here, we analyzed the tolerance of wheat strains XM26 and LM23 to low-nitrogen stress using a chlorate sensitivity experiment. Subsequently, we performed transcriptome analyses of both varieties exposed to low-nitrogen (LN) and normal (CK) treatments. Compared with those under CK treatment, 3534 differentially expressed genes (DEGs) were detected in XM26 in roots and shoots under LN treatment (p < 0.05, and |log2FC| > 1). A total of 3584 DEGs were detected in LM23. A total of 3306 DEGs, including 863 DEGs in roots and 2443 DEGs in shoots, were specifically expressed in XM26 or showed huge differences between XM26 and LM23 (log2FC ratio > 3). These were selected for gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The calcium-mediated plant-pathogen interaction, MAPK signaling, and phosphatidylinositol signaling pathways were enriched in XM26 but not in LM23. We also verified the expression of important genes involved in these pathways in the two varieties using qRT-PCR. A total of 156 transcription factors were identified among the DEGs, and their expression patterns were different between the two varieties. Our findings suggest that calcium-related pathways play different roles in the two varieties, eliciting different tolerances to low-nitrogen stress.

High Carbonization Temperature to Trigger Enzyme Mimicking Activities of Silk-Derived Nanosheets.

Herein, it is demonstrated that N-rich carbonized silk fibroin materials (CSFs) can serve as efficient peroxidase, and oxidase mimics. Their enzyme-like activities are highly dependent on carbonization conditions. CSFs obtained at low temperatures do not exhibit significant catalytic reactivity, while their enzyme-like catalysis performance is greatly activated after high-temperature treatment. Such a phenomenon is mainly ascribed to the increase of graphitization degree and graphitic nitrogen and the emergence of disordered graphitic structures during the formation of turbostratic carbon. In addition, inspired by the excellent photothermal conversion efficiency, and temperature-dependent catalytic behavior of CSFs, near-infrared light can be used to remotely control their enzyme-like activities. More importantly, as-prepared robust silk-derived nanosheets can be applied to photothermal-catalytic cancer therapy and sensing. It is believed that such a smart artificial enzyme system will throw up exciting new opportunities for the chemical industry and biotechnology.

Serum biomarkers for predicting microvascular complications of diabetes mellitus.

INTRODUCTION: Diabetic microvascular complications such as retinopathy, nephropathy, and neuropathy are primary causes of blindness, terminal renal failure, and neuropathic disorders in type 2 diabetes mellitus patients. Identifying reliable biomarkers promptly is pivotal for early detection and intervention in these severe complications. AREAS COVERED: This review offers a thorough examination of the latest research concerning serum biomarkers for the prediction and assessment of diabetic microvascular complications. It encompasses biomarkers associated with glycation, oxidative stress, inflammation, endothelial dysfunction, basement membrane thickening, angiogenesis, and thrombosis. The review also highlights the potential of emerging biomarkers, such as microRNAs and long non-coding RNAs. EXPERT OPINION: Serum biomarkers are emerging as valuable tools for the early assessment and therapeutic guidance of diabetic microvascular complications. The biomarkers identified not only reflect the underlying pathophysiology but also align with the extent of the disease. However, further validation across diverse populations and improvement of the practicality of these biomarkers in routine clinical practice are necessary. Pursuing these objectives is essential to advance early diagnosis, risk assessment, and individualized treatment regimens for those affected by diabetes.

Synthesis of core-shell silicon-carbon nanocomposites via in-situ molten salt-based reduction of rice husks: A promising approach for the manufacture of lithium-ion battery anodes.

Silicon (Si) has gained substantial interest as a potential component of lithium-ion battery (LIB) anodes due to its high theoretical specific capacity. However, conventional methods for producing Si for anodes involve expensive metal reductants and stringent reducing environments. This paper describes the development of a calcium hydride (CaH2)-aluminum chloride (AlCl3) reduction system that was used for the in-situ low-temperature synthesis of a core-shell structured silicon-carbon (Si-C) material from rice husks (RHs), and the material was denoted RHs-Si@C. Moreover, as an LIB anode, RHs-Si@C exhibited exceptional cycling performance, exemplified by 90.63 % capacity retention at 5 A g-1 over 2000 cycles. Furthermore, the CaH2-AlCl3 reduction system was employed to produce Si nanoparticles (Si NPs) from RHs (R-SiO2, where SiO2 is silica) and from commercial silica (C-SiO2). The R-SiO2-derived Si NPs exhibited a higher residual silicon oxides (SiOx) content than the C-SiO2-derived Si NPs. This was advantageous, as there was sufficient SiOx in the R-SiO2-derived Si NPs to mitigate the volumetric expansion typically associated with Si NPs, resulting in enhanced cycling performance. Impressively, Si NPs were fabricated on a kilogram scale from C-SiO2 in a yield of 82 %, underscoring the scalability of the low-temperature reduction technique.

Discovery of an 8-oxoguanine regulator PCBP1 inhibitor by virtual screening and its synergistic effects with ROS-modulating agents in pancreatic cancer.

Introduction: Drugs that target reactive oxygen species (ROS) metabolism have progressed the treatment of pancreatic cancer treatment, yet their efficacy remains poor because of the adaptation of cancer cells to high concentration of ROS. Cells cope with ROS by recognizing 8-oxoguanine residues and processing severely oxidized RNA, which make it feasible to improve the efficacy of ROS-modulating drugs in pancreatic cancer by targeting 8-oxoguanine regulators. Methods: Poly(rC)-binding protein 1 (PCBP1) was identified as a potential oncogene in pancreatic cancer through datasets of The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO). High-throughput virtual screening was used to screen out potential inhibitors for PCBP1. Computational molecular dynamics simulations was used to verify the stable interaction between the two compounds and PCBP1 and their structure-activity relationships. In vitro experiments were performed for functional validation of silychristin. Results: In this study, we identified PCBP1 as a potential oncogene in pancreatic cancer. By applying high-throughput virtual screening, we identified Compound 102 and Compound 934 (silychristin) as potential PCBP1 inhibitors. Computational molecular dynamics simulations and virtual alanine mutagenesis verified the structure-activity correlation between PCBP1 and the two identified compounds. These two compounds interfere with the PCBP1-RNA interaction and impair the ability of PCBP1 to process RNA, leading to intracellular R loop accumulation. Compound 934 synergized with ROS agent hydrogen peroxide to strongly improve induced cell death in pancreatic cancer cells. Discussion: Our results provide valuable insights into the development of drugs that target PCBP1 and identified promising synergistic agents for ROS-modulating drugs in pancreatic cancer.

Characteristics of Serum Lipid Metabolism among Women Complicated with Hypertensive Disorders in Pregnancy: A Retrospective Cohort Study in Mainland China.

Background: Altered maternal serum lipid metabolism is associated with hypertensive disorders in pregnancy (HDP). However, its range in pregnancy and characteristic among different subgroups of HDPs are unclear. Methods: Pregnant women with HDP who underwent antenatal care and delivered in Obstetrics and Gynecology Hospital of Fudan University during January 2018 to August 2022 were enrolled. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), apolipoprotein (Apo)-A, B, and E, free fatty acids (FFA), and small and dense low-density lipoprotein cholesterol (sdLDL) were measured during 4-16 weeks and 28-42 weeks of pregnancy. Results: A total of 2648 pregnant women were diagnosed with HDP, 1,880 of whom were enrolled for final analysis, including 983 (52.3%) preeclampsia (PE), 676 (36.0%) gestational hypertension (GH), and 221 (11.7%) chronic hypertension (CH). For all HDPs, serum TC, TG, LDLC, HDLC, Apo-A, Apo-B, Apo-E, and sdLDL increased significantly during pregnancy, while FFA decreased significantly. Notably, the levels of TC, LDLC, Apo-B, and sdLDL in PE group were equal to or lower than those in CH group at 4-16 weeks of pregnancy, but increased greatly during pregnancy (P < 0.05). Conclusions: Maternal serum lipid levels changed through pregnancy among women with HDPs. Women complicated with PE seem to have undergone a more significant serum lipid change compared to those with GH or CH.

Compound synchronization of four memristor chaotic oscillator systems and secure communication.

In this paper, a novel kind of compound synchronization among four chaotic systems is investigated, where the drive systems have been conceptually divided into two categories: scaling drive systems and base drive systems. Firstly, a sufficient condition is obtained to ensure compound synchronization among four memristor chaotic oscillator systems based on the adaptive technique. Secondly, a secure communication scheme via adaptive compound synchronization of four memristor chaotic oscillator systems is presented. The corresponding theoretical proofs and numerical simulations are given to demonstrate the validity and feasibility of the proposed control technique. The unpredictability of scaling drive systems can additionally enhance the security of communication. The transmitted signals can be split into several parts loaded in the drive systems to improve the reliability of communication.

[Impact and potential mechanism of human α-defensin 1 on low-density lipoprotein oxidation ability of ECV304 cells].

OBJECTIVE: To explore the role and potential mechanism of human α-defensin 1 (HNP-1) on low-density lipoprotein (LDL) oxidation ability of human endothelial cells (EVC304). METHODS: Post incubation with LDL for 3 h, the malondialdehyde (MDA) and protein carbonyl (PCO) were detected in untreated ECV304 (control) and in HNP-1 transfected ECV304 in the presence and absence of siRNA against HNP-1. Flow cytometry and fluorescence microscopy were used to detect the generation of oxygen free radical in the ECV304 which have been pretreated by LDL, LPS and HNP-1, respectively. RESULT: Compared with control group, MDA level was significantly increased in HNP-1 transfected [(4.21 ± 0.03) vs. (3.15 ± 0.02) nmol/mg · pro] or in HNP-1 stimulated ECV304 cells [(14.49 ± 1.10) vs. (9.47 ± 1.18) nmol/mg · pro], which could be significantly downregulated by siRNA [(3.76 ± 0.48) vs. (4.54 ± 0.28) nmol/mg·pro, all P < 0.05]. PCO was also significantly increased in HNP-1 transfected ECV304 cells. The levels of free radical were significantly increased in HNP-1 transfected or HNP-1 stimulated ECV304 cells. CONCLUSION: HNP-1 can enhance the LDL oxidation ability of human endothelial cells via promoting the generation of free radicals.

Observer-Based Dynamic Event-Triggered Semiglobal Bipartite Consensus of Linear Multi-Agent Systems With Input Saturation.

Observer-based dynamic event-triggered semiglobal bipartite consensus (SGBC) is investigated for linear multi-agent systems (MASs) with input saturation under a competitive network. Based on the estimated relative information and low-gain feedback technology, distributed dynamic event-triggered control (DETC) protocols are proposed for solving the observer-based SGBC problems for MASs under a fixed topology and a jointly connected topology, respectively. It is turned out that the SGBC of MASs can be achieved under the proposed protocols. By using gauge transformation and the Lyapunov theory, the bipartite consensus conditions are obtained. Moreover, Zeno behaviors will be excluded. Finally, two simulation examples are presented to verify the theoretical results efficiently.

Prenatal Magnetic Resonance Imaging helps Discover Cerebellar Dysplasia or Malformations in Foetuses.

OBJECTIVE: This study aimed to characterize and assess the diagnostic value of prenatal magnetic resonance (MR) imaging in detecting fetal cerebellar hypoplasia/dysplasia and developmental malformations. METHODS: Reports of suspected intracranial abnormalities were retrospectively collected on ultrasound screening (US), and MR images of fetuses were reviewed at our institution over a 5-year period on picture archiving and communication system (PACS) servers. Two experienced radiologists recorded major abnormalities and coexisting abnormalities at the reading of the census. The results of the MRI were compared against the US in each case. RESULTS: For prenatal MR imaging, we enlisted a total of 121 patients (mean gestational week, 24.5 ± 4.7 weeks). This included 28 cases with normal findings of MR imaging, 62 cases with findings of cerebellar hypoplasia or dysplasia, and the remaining 31 cases with other abnormities findings. Cerebral malformations cases included agenesis of the corpus callosum, cerebral hemorrhage, hydrocephalus, holoprosencephaly, ventriculomegaly, and brainstem/gyri malformation. Cerebellar abnormalities included vermis absence, cerebellar tonsil hernia, Dandy-Walker malformation, Blake's pouch cysts, arachnoid cysts, and intracranial hemorrhage. Other systemic malformation cases included tethered cord syndromes (9 cases), cleft lip and palate (1 case), club foot (1 case), and cardiac malformation (1 case). In 12 cases (24.5%), compared to the US, MR imaging proved the value of confirming the diagnosis and/or even yielded more findings on abnormalities. CONCLUSION: Prenatal MR imaging can better visualize systemic malformations coexisting with cerebellar abnormalities. MR imaging, a complementary means to the US, can aid in prenatal counseling and treatment selection for term delivery.

A pan-cancer analysis reveals the diagnostic and prognostic role of CDCA2 in low-grade glioma.

BACKGROUND: Cell division cycle associated 2 (CDCA2), a member of the cell division cycle associated proteins (CDCA) family, is crucial in the regulation of cell mitosis and DNA repair. CDCA2 was extensively examined in our work to determine its role in a wide range of cancers. METHODS: CDCA2 differential expression was studied in pan-cancer and in diverse molecular and immunological subgroups in this research. Additionally, the diagnostic and prognostic significance of CDCA2 in pan-cancer was also evaluated using receiver operating characteristic (ROC) and Kaplan-Meier (KM) curves. Prognostic value of CDCA2 in distinct clinical subgroups of lower grade glioma (LGG) was also investigated and a nomogram was constructed. Lastly, potential mechanisms of action of CDCA2 were interrogated including biological functions, ceRNA networks, m6A modification and immune infiltration. RESULTS: CDCA2 is shown to be differentially expressed in a wide variety of cancers. Tumors are diagnosed and forecasted with a high degree of accuracy by CDCA2, and the quantity of expression CDCA2 is linked to the prognosis of many cancers. Additionally, the expression level of CDCA2 in various subgroups of LGG is also closely related to prognosis. The results of enrichment analyses reveal that CDCA2 is predominantly enriched in the cell cycle, mitosis, and DNA replication. Subsequently, hsa-miR-105-5p is predicted to target CDCA2. In addition, 4 lncRNAs were identified that may inhibit the hsa-miR-105-5p/CDCA2 axis in LGG. Meanwhile, CDCA2 expression is shown to be associated to m6A-related genes and levels of immune cell infiltration in LGG. CONCLUSION: CDCA2 can serve as a novel biomarker for the diagnosis and prognosis in pan-cancer, especially in LGG. For the development of novel targeted therapies in LGG, it may be a potential molecular target. However, to be sure, we'll need to do additional biological experiments to back up our results from bioinformatic predictions.

Comparison of the left and right ventricular size and systolic function of low-risk fetuses in the third trimester: Which is more dominant?

Objective: To quantify fetal cardiovascular parameters utilizing fetal-specific 2D speckle tracking technique and to explore the differences in size and systolic function of the left and right ventricles in low-risk pregnancy. Methods: A prospective cohort study was performed in 453 low-risk single fetuses (28+0-39+6 weeks) to evaluate ventricular size [i.e., end-diastolic length (EDL), end-systolic length (ESL), end-diastolic diameter (ED), end-systolic diameter (ES), end-diastolic area, end-systolic area, end-diastolic volume (EDV), and end-systolic volume (ESV)] and systolic function [i.e., ejection fraction (EF), stroke volume (SV), cardiac output (CO), cardiac output per kilogram (CO/KG), and stroke volume per kilogram (SV/KG)]. Results: This study showed that (1) the reproducibility of the interobserver and intraobserver measurements was good to excellent (ICC 0.626-0.936); (2) with advancing gestation, fetal ventricular size and systolic function increased, whereas right ventricular (RV) EF decreased and left ventricular (LV) EF was not significantly changed; (3) LV length was longer than RV length in diastole (2.24 vs. 1.96 cm, P < 0.001) and systole (1.72 vs. 1.52 cm, P < 0.001); (4) LV ED-S1 and ES-S1 were shorter than the RV ED-S1 and ES-S1 (12.87 vs. 13.43 mm, P < 0.001; 5.09 vs. 5.61 mm, P < 0.001); (5) there were no differences between the LV and RV in EDA or EDV; (6) the mean EDV ratio of right-to-left ventricle was 1.076 (95% CI, 1.038-1.114), and the mean ESV ratio was 1.628 (95% CI, 1.555-1.701); (7) the EF, CO and SV of the LV were greater than the RV (EF: 62.69% vs. 46.09%, P < 0.001; CO: 167.85 vs. 128.69 ml, P < 0.001; SV: 1.18 vs. 0.88 ml, P < 0.001); (8) SV and CO increased with ED-S1 and EDL, but EF was not significantly changed. Conclusion: Low-risk fetal cardiovascular physiology is characterized by a larger RV volume (especially after 32 weeks) and greater LV outputs (EF, CO, SV, SV/KG and CO/KG).

Post-translational modification of CDK1-STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties.

BACKGROUND: Pancreatic cancer stem cells (CSCs) promote pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and chemoresistance. Cyclin-dependent kinase 1 (CDK1) plays an important role in tumor initiation in other tumors, but the function of CDK1 in PDAC remains unclear. Fisetin is a bioactive flavonoid with anti-tumor properties in multiple tumors, while its function in CSCs remains elusive. RESULTS: In this study, we demonstrated that CDK1 was correlated with prognosis and was highly expressed in pancreatic cancer tissue and gemcitabine-resistant cells. Silencing CDK1 impaired tumor stemness and reduced a subset of CSCs. We found that fisetin blocked the kinase pocket domain of CDK1 and inhibited pancreatic CSC characteristics. Using acetylation proteomics analysis and phosphorylation array assay, we confirmed that fisetin reduced CDK1 expression and increased CDK1 acetylation at lysine 33 (K33), which resulted in the suppression of CDK1 phosphorylation. Silencing CDK1 or STAT3 suppressed tumor stemness properties, while overexpressing CDK1 or STAT3 showed the opposite effect. Mutation or acetylation of CDK1 at K33 weakened STAT3 phosphorylation at Y705, impairing the expression of stem-related genes and pancreatic cancer stemness. In addition, lack of histone deacetylase 3 (HDAC3), which deacetylates CDK1, contributed to weakening STAT3 phosphorylation by regulating the post-translational modification of CDK1, thereby decreasing the stemness of PDAC. Moreover, our results revealed that fisetin enhanced the effect of gemcitabine through eliminating a subpopulation of pancreatic CSCs by inhibiting the CDK1-STAT3 axis in vitro and in vivo. CONCLUSION: Our findings highlight the role of post-translational modifications of CDK1-STAT3 signaling in maintaining cancer stemness of PDAC, and indicated that targeting the CDK1-STAT3 axis with inhibitors such as fisetin is a potential therapeutic strategy to diminish drug resistance and eliminate PDAC.