The effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery.

BACKGROUND: Craniocerebral interventional surgery is a common and essential treatment for cerebrovascular diseases. Despite continuous progress in interventional diagnosis and treatment technology, there is no effective method to alleviate contrast-induced kidney injuries. In this retrospective cohort study, we investigated the effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery. METHODS: We identified 228 cases of patients underwent craniocerebral interventional surgery from January 2018 to March 2022. Patients who used DEX during general anesthesia were in the DEX group (DEX group) or that did not use dexmedetomidine as the control group (CON group). The markers of kidney injury were recorded before and within 48 h after surgery. RESULTS: Compared with CON group, the urea nitrogen (BUN) of the DEX group decreased significantly on the first day and the second day after surgery (p < 0.05). The serum cystatin-C and the blood urea nitrogen/creatinine ratio (BUN/Cr) was significantly lower than that in CON group on the second day (p < 0.05). The urine output in the DEX group increased significantly, and the mean arterial pressure (MAP) was higher than the CON group (p < 0.01). There was no difference in postoperative complications, ICU stay time and hospitalization time between the two groups. CONCLUSION: The combined use of dexmedetomidine in general anesthesia for craniocerebral interventional surgery can reduce BUN levels within 48 h after surgery, significantly increase intraoperative urine volume, maintain intraoperative circulation stability.

T-type voltage-gated channels, Na+/Ca2+-exchanger, and calpain-2 promote photoreceptor cell death in inherited retinal degeneration.

Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, a connection between excessive Ca2+ influx and photoreceptor loss has yet to be proven.Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca2+-signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca2+-chelator BAPTA-AM or inhibitors of different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and - 2 were monitored, cell death was assessed via the TUNEL assay.While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca2+-channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors.These results suggest that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca2+-levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract.

The correlation between brain structure characteristics and emotion regulation ability in children at high risk of autism spectrum disorder.

As indicated by longitudinal observation, autism has difficulty controlling emotions to a certain extent in early childhood, and most children's emotional and behavioral problems are further aggravated with the growth of age. This study aimed at exploring the correlation between white matter and white matter fiber bundle connectivity characteristics and their emotional regulation ability in children with autism using machine learning methods, which can lay an empirical basis for early clinical intervention of autism. Fifty-five high risk of autism spectrum disorder (HR-ASD) children and 52 typical development (TD) children were selected to complete the skull 3D-T1 structure and diffusion tensor imaging (DTI). The emotional regulation ability of the two groups was compared using the still-face paradigm (SFP). The classification and regression models of white matter characteristics and white matter fiber bundle connections of emotion regulation ability in the HR-ASD group were built based on the machine learning method. The volume of the right amygdala (R2 = 0.245) and the volume of the right hippocampus (R2 = 0.197) affected constructive emotion regulation strategies. FA (R2 = 0.32) and MD (R2 = 0.34) had the predictive effect on self-stimulating behaviour. White matter fiber bundle connection predicted constructive regulation strategies (positive edging R2 = 0.333, negative edging R2 = 0.334) and mother-seeking behaviors (positive edging R2 = 0.667, negative edging R2 = 0.363). The emotional regulation ability of HR-ASD children is significantly correlated with the connections of multiple white matter fiber bundles, which is a potential neuro-biomarker of emotional regulation ability.

An End-to-End Inclination State Monitoring Method for Collaborative Robotic Drilling Based on Resnet Neural Network.

The collaborative robot can complete various drilling tasks in complex processing environments thanks to the high flexibility, small size and high load ratio. However, the inherent weaknesses of low rigidity and variable rigidity in robots bring detrimental effects to surface quality and drilling efficiency. Effective online monitoring of the drilling quality is critical to achieve high performance robotic drilling. To this end, an end-to-end drilling-state monitoring framework is developed in this paper, where the drilling quality can be monitored through online-measured vibration signals. To evaluate the drilling effect, a Canny operator-based edge detection method is used to quantify the inclination state of robotic drilling, which provides the data labeling information. Then, a robotic drilling inclination state monitoring model is constructed based on the Resnet network to classify the drilling inclination states. With the aid of the training dataset labeled by different inclination states and the end-to-end training process, the relationship between the inclination states and vibration signals can be established. Finally, the proposed method is verified by collaborative robotic drilling experiments with different workpiece materials. The results show that the proposed method can effectively recognize the drilling inclination state with high accuracy for different workpiece materials, which demonstrates the effectiveness and applicability of this method.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1ß, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism.

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(µ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.

Advanced strategies in high-throughput droplet screening for enzyme engineering.

Enzymes, as biocatalysts, play a cumulatively important role in environmental purification and industrial production of chemicals and pharmaceuticals. However, natural enzymes are limited by their physiological properties in practice, which need to be modified driven by requirements. Screening and isolating certain enzyme variants or ideal industrial strains with high yielding of target product enzymes is one of the main directions of enzyme engineering research. Droplet-based high-throughput screening (DHTS) technology employs massive monodisperse emulsion droplets as microreactors to achieve single strain encapsulation, as well as continuous monitoring for the inside mutant library. It can effectively sort out strains or enzymes with desired characteristics, offering a throughput of 108 events per hour. Much of the early literature focused on screening various engineered strains or designing signalling sorting strategies based on DHTS technology. However, the field of enzyme engineering lacks a comprehensive overview of advanced methods for microfluidic droplets and their cutting-edge developments in generation and manipulation. This review emphasizes the advanced strategies and frontiers of microfluidic droplet generation and manipulation facilitating enzyme engineering development. We also introduce design for various screening signals that cooperate with DHTS and devote to enzyme engineering.

Hyaluronic Acid Unveiled: Exploring the Nanomechanics and Water Retention Properties at the Single-Molecule Level.

Hyaluronic acid (HA), a vital glycosaminoglycan in living organisms, possesses remarkable mechanical and viscoelastic properties that have garnered significant attention in therapeutic, biomedical, and cosmetic applications. However, a comprehensive picture of the physicochemical and biocharacterization of HA at the single-molecule level remains elusive. In this work, atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and molecular dynamics (MD) simulation were used to investigate the nanomechanics and water retention properties of HA at the single-molecule level. The present study aims to unravel the intricate details of the influence of molecular structure on HA behavior and shed light on its unique attributes. According to the force measurements, the energy used to stretch a HA chain in water is 8.45 kJ/mol, significantly surpassing that of Curdlan (3.45 kJ/mol) and chitin (2.23 kJ/mol), both of which possess molecular structures partially similar to that of HA. Intriguingly, the strength of the intrachain interaction of HA (5.54 kJ/mol) was considerably weaker compared to Curdlan (11.06 kJ/mol) and chitin (or cellulose, 10.76 kJ/mol). This result indicates that HA exhibits a preference for interacting with water rather than with itself, thereby showing enhanced water affinity. Moreover, the force measurements demonstrated that changing the glycosidic bond from ß-(1-3) (Curdlan) or ß-(1-4) (chitin or cellulose) to ß-(1-3) + ß-(1-4) (HA) resulted in polysaccharides displaying improved water affinity and more extended conformation. These conclusions were further verified by molecular dynamics (MD) simulations. Overall, our work sheds new light on the nanomechanics and water retention properties of HA at the single-molecule level, offering valuable insights for future research in this field.

Analysis of three-dimensional visualization imaging of severe portal vein stenosis after liver transplantation and clinical efficacy of portal vein stent implantation / 器官移植

Objective To analyze three-dimensional imaging characteristics and advantages for severe portal vein stenosis after liver transplantation, and to evaluate clinical efficacy of portal vein stent implantation. Methods Clinical data of 10 patients who received portal vein stent implantation for severe portal vein stenosis after liver transplantation were retrospectively analyzed. Imaging characteristics of severe portal vein stenosis, and advantages of three-dimensional reconstruction imaging and interventional treatment efficacy for severe portal vein stenosis were analyzed. Results Among 10 patients, 3 cases were diagnosed with centripetal stenosis, tortuosity angulation-induced stenosis in 2 cases, compression-induced stenosis in 2 cases, long-segment stenosis and/or vascular occlusion in 3 cases. Three-dimensional reconstruction images possessed advantages in accurate identification of stenosis, identification of stenosis types and measurement of stenosis length. All patients were successfully implanted with portal vein stents. After stent implantation, the diameter of the minimum diameter of portal vein was increased [(6.2±0.9) mm vs. (2.6±1.7) mm, P<0.05], the flow velocity at anastomotic site was decreased [(57±19) cm/s vs. (128±27) cm/s, P<0.05], and the flow velocity at the portal vein adjacent to the liver was increased [(41±6) cm/s vs. (18±6) cm/s, P<0.05]. One patient suffered from intrahepatic hematoma caused by interventional puncture, which was mitigated after conservative observation and treatment. The remaining patients did not experience relevant complications. Conclusions Three-dimensional visualization technique may visually display the location, characteristics and severity of stenosis, which is beneficial for clinicians to make treatment decisions and assist interventional procedures. Timely implantation of portal vein stent may effectively reverse pathological process and improve portal vein blood flow.

Identification of A Novel Gene Signature Combining Ferroptosis- and Immunity-Related Genes for Prognostic Prediction, Immunotherapy and Potential Therapeutic Targets in Gastric Cancer.

Gastric cancer (GC) is one of the most prevalent cancers worldwide. Ferroptosis and the immune status of tumor tissue play vital roles in the initiation and progression of GC. However, the role and functional mechanisms of ferroptosis- and immunity-related genes (FIRGs) in GC pathogenesis and their correlations with GC prognosis have not been elucidated. We aim to establish a prognostic prediction model based on the FIRGs signature for GC patients. Differentially expressed genes were screened from the Cancer Genome Atlas (TCGA) GC cohorts. The least absolute shrinkage and selection operator (LASSO) regression was performed to establish a FIRGs-based risk model. This gene signature with 7 FIRGs was identified as an independent prognostic factor. A nomogram incorporating clinical parameters and the FIRG signature was constructed to individualize outcome predictions. Finally, we provided in vivo and in vitro evidence to verify the reliability of FIRG signature for GC prognosis, and validate the expression and function of FIRGs contributing to the development and progression of GC. Herein, our work represents great therapeutic and prognostic potentials for GC.

Mechanism Insights of Antibacterial Surfaces Coated with Dead Probiotics.

To understand the antimicrobial effect of surfaces fabricated with dead probiotics, we prepared surfaces decorated with dead probiotics Lactobacillus rhamnosus GG (LGG) with varied inactivation methods and explored their inhibitory interactions with Pseudomonas aeruginosa (PAO1). By combining several techniques, i.e., digital holographic microscopy (DHM), atomic force microscopy (AFM), RNA sequencing, and metabolomic analysis, we studied the three-dimensional (3D) swimming behaviors, surface adhesion, biofilm formation, and adaptive responses of PAO1 near such surfaces. The results show that planktonic PAO1 decreases their flick and reverse motions by downregulating the chemotaxis pathway and accelerates with less accumulation near dead LGG surfaces by upregulating the flagellar assembly pathway and decreasing cyclic adenosine monophosphate. Distinct from live siblings, the surfaces decorated with dead LGG show a significant reduction in adhesion strength with PAO1 and inhibit biofilm formation with more downregulated genes in the Pseudomonas quinolone signal and biofilm formation pathway. We demonstrate that the antibacterial ability of such surfaces stems from the gradually released lysate from the dead LGG that is unfavorable to PAO1 in close proximity. The releasing rate and order depend on the cell membrane integrity, which closely relates to the inactivation methods.

Surprising Nanomechanical and Conformational Transition of Neutral Polyacrylamide in Monovalent Saline Solutions.

Polyacrylamide (PAM) is one of the most important water-soluble polymers that has been extensively applied in water treatment, drug delivery, and flexible electronic devices. The basic properties, e.g., microstructure, nanomechanics, and solubility, are deeply involved in the performance of PAM materials. Current research has paid more attention to the development and expansion of the macroscopic properties of PAM materials, and the study of the mechanism involved with the roles of water and ions on the properties of PAM is insufficient, especially for the behaviors of neutral amide side groups. In this study, single molecule force spectroscopy was combined with molecular dynamic (MD) simulations, atomic force microscope imaging, and dynamic light scattering to investigate the effects of monovalent ions on the nanomechanics and molecular conformations of neutral PAM (NPAM). These results show that the single-molecule elasticity and conformation of NPAM exhibit huge variation in different monovalent salt solutions. NPAM adopts an extended conformation in aqueous solutions of strong hydrated ion (acetate), while transforms into a collapse globule in the existence of weakly hydrated ion (SCN-). It is believed that the competition between intramolecular and intermolecular weak interactions plays a key role to adjust the molecular conformation and elasticity of NPAM. The competition can be largely influenced by the type of monovalent ions through hydration or a chaotropic effect. Methods utilized in this study provide a means to better understand the Hofmeister effect of ions on other macromolecules containing amide groups at the single-molecule level.

ß-cell neogenesis: A rising star to rescue diabetes mellitus.

BACKGROUND: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional ß-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). AIM OF REVIEW: Elucidating the underlying mechanisms of ß-cell failure, and exploring approaches for ß-cell neogenesis to reverse ß-cell dysfunction may provide novel strategies for DM therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional ß-cell by ß-cell neogenesis to restore the number and function of pancreatic ß-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of ß-cell failure in DM, highlight the effective approaches for ß-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of ß-cell neogenesis. Insights into the challenges of translating ß-cell neogenesis into clinical application for DM treatment are also offered.

Revealing the Control Mechanisms of pH on the Solution Properties of Chitin via Single-Molecule Studies.

Chitin is one of the most common polysaccharides and is abundant in the cell walls of fungi and the shells of insects and aquatic organisms as a skeleton. The mechanism of how chitin responds to pH is essential to the precise control of brewing and the design of smart chitin materials. However, this molecular mechanism remains a mystery. Results from single-molecule studies, including single-molecule force spectroscopy (SMFS), AFM imaging, and molecular dynamic (MD) simulations, have shown that the mechanical and conformational behaviors of chitin molecules show surprising pH responsiveness. This can be compared with how, in natural aqueous solutions, chitin tends to form a more relaxed spreading conformation and show considerable elasticity under low stretching forces in acidic conditions. However, its molecular chain collapses into a rigid globule in alkaline solutions. The results show that the chain state of chitin can be regulated by the proportions of inter- and intramolecular H-bonds, which are determined via the number of water bridges on the chain under different pH values. This basic study may be helpful for understanding the cellular activities of fungi under pH stress and the design of chitin-based drug carriers.

Decrypting the circular RNAs does a favor for us: Understanding, diagnosing and treating diabetes mellitus and its complications.

Circular RNAs (circRNAs), a novel type of single-stranded noncoding RNAs with a covalently closed loop structure, are generated in a circular conformation via non-canonical splicing or back-splicing events. Functionally, circRNAs have been elucidated to soak up microRNAs (miRNAs) and RNA binding proteins (RBPs), serve as protein scaffolds, maintain mRNA stability, and regulate gene transcription and translation. Notably, circRNAs are strongly implicated in the regulation of ß-cell functions, insulin resistance, adipocyte functions, inflammation as well as oxidative stress via acting as miRNA sponges and RBP sponges. Basic and clinical studies have demonstrated that aberrant alterations of circRNAs expressions are strongly associated with the initiation and progression of diabetes mellitus (DM) and its complications. Here in this review, we present a summary of the biogenesis, transportation, degradation and functions of circRNAs, and highlight the recent findings on circRNAs and their action mechanisms in DM and its complications. Overall, this review should contribute greatly to our understanding of circRNAs in DM pathogenesis, offering insights into the further perspectives of circRNAs for DM diagnosis and therapy.

Representativeness of Patients Enrolled in the Lung Cancer Master Protocol (Lung-MAP).

PURPOSE: Lung Cancer Master Protocol (Lung-MAP), a public-private partnership, established infrastructure for conducting a biomarker-driven master protocol in molecularly targeted therapies. We compared characteristics of patients enrolled in Lung-MAP with those of patients in advanced non-small-cell lung cancer (NSCLC) trials to examine if master protocols improve trial access. METHODS: We examined patients enrolled in Lung-MAP (2014-2020) according to sociodemographic characteristics. Proportions for characteristics were compared with those for a set of advanced NSCLC trials (2001-2020) and the US advanced NSCLC population using SEER registry data (2014-2018). Characteristics of patients enrolled in Lung-MAP treatment substudies were examined in subgroup analysis. Two-sided tests of proportions at an alpha of .01 were used for all comparisons. RESULTS: A total of 3,556 patients enrolled in Lung-MAP were compared with 2,215 patients enrolled in other NSCLC studies. Patients enrolled in Lung-MAP were more likely to be 65 years and older (57.2% v 46.3%; P < .0001), from rural areas (17.3% v 14.4%; P = .004), and from socioeconomically deprived neighborhoods (42.2% v 36.7%, P < .0001), but less likely to be female (38.6% v 47.2%; P < .0001), Asian (2.8% v 5.1%; P < .0001), or Hispanic (2.4% v 3.8%; P = .003). Among patients younger than 65 years, Lung-MAP enrolled more patients using Medicaid/no insurance (27.6% v 17.8%; P < .0001). Compared with the US advanced NSCLC population, Lung-MAP under represented patients 65 years and older (57.2% v 69.8%; P < .0001), females (38.6% v 46.0%; P < .0001), and racial or ethnic minorities (14.8% v 21.5%; P < .0001). CONCLUSION: Master protocols may improve access to trials using novel therapeutics for older patients and socioeconomically vulnerable patients compared with conventional trials, but specific patient exclusion criteria influenced demographic composition. Further research examining participation barriers for under represented racial or ethnic minorities in precision medicine clinical trials is warranted.

Knowledge, attitude, and practice of monitoring early gastric cancer after endoscopic submucosal dissection.

BACKGROUND: Early gastric cancer (EGC) is typically treated with endoscopic submucosal dissection (ESD). However, recurrence may occur after ESD, requiring surveillance. AIM: To examine the knowledge, attitude, and practice (KAP) of EGC survivors following ESD regarding gastric cancer recurrence. METHODS: This cross-sectional study was conducted between June 1, 2022 and October 1, 2022 in Zhejiang, China. A total of 400 EGC survivors who underwent ESD at the Affiliated Jinhua Hospital, Zhejiang University School of Medicine participated in this study. A self-administered questionnaire was developed to assess KAP monitoring gastric cancer after ESD. RESULTS: The average scores for KAP were 3.34, 23.76, and 5.75 out of 5, 30, and 11, respectively. Pearson correlation analysis revealed positive and significant correlations between knowledge and attitude, knowledge and practice, and attitude and practice (r = 0.405, 0.511, and 0.458, respectively; all P < 0.001). Multivariate logistic regression analysis showed that knowledge, attitude, 13-24 mo since the last ESD (vs ≤ 12 mo since the last ESD), and ≥ 25 mo since the last ESD (vs ≤ 12 mo since the last ESD) were independent predictors of proactive practice (odds ratio = 1.916, 1.253, 3.296, and 5.768, respectively, all P < 0.0001). CONCLUSION: EGC survivors showed inadequate knowledge, positive attitude, and poor practices in monitoring recurrences after ESD. Adequate knowledge, positive attitude, and a longer time since the last ESD were associated with practice.

Prophylactic effects of Periplaneta americana L. extract on anxiety-like and depression-like behaviors in rats exposed to chronic stress.

The effect of P. americana L. on anxiety and depression-behavior after chronic stress (CS) is still unknown. Here, CS were induced by a combined stimulation of chronic restraint stress, excess failure and improper diet in SD rats. At 15 days after CS, except for normal group and model group, all the groups were continuously administrated P. americana L. (i.g., 400, 200, 100 mg/kg) treatment for 14 days. Anxiety and depression-behavior was determined by sucrose preference test, forced swimming and open field. The contents of cortisol (CORT), adrenocorticotropic hormone (ACTH), adrenocorticotropic hormone-releasing hormone (CRH), interleukin (IL)-4, IL-6, IL-17 and interferon (IFN) -γ were detected by ELISA. 16S rRNA analysis was performed to examine the composition of gut microbiota. Our results indicated that P. americana L. improved the anxiety and depression-behavior. P. americana L. reduced the release of IL-6, IL-17 and IFN-γ and increased the release of IL-4. Comparably, remarkably decreased CRH, ACTH and CORT were observed by the treatment of P. americana L. 16S rRNA analysis suggested that Bifidobacterium and sulfate-reducing bacteria may be responsible for improving CS in P. americana L. -treated rats. Collectively, P. americana L. could relieve CS are associated with regulation of intestinal flora.

Silibinin exerts neuroprotective effects against cerebral hypoxia/reoxygenation injury by activating the GAS6/Axl pathway.

Ischemic stroke is regarded one of the most common causes of brain vulnerability. Silibinin (SIL), extracted from the seeds of Silybinisus laborinum L., has been found to exhibit obvious therapeutic effects on neurodegenerative diseases. GAS6 has been proven to have significant neuroprotective effects; however, the role of SIL and GAS6 in ischemic stroke remains unclear. This study aimed to investigate the protective effects of SIL against cerebral ischemia-reperfusion injury in neuroblastoma N2a cells, as well as the mechanisms involved. Firstly, the toxicity of SIL was evaluated, and safe concentrations were chosen for subsequent experiments. Then, SIL exerts significant neuroprotection against hypoxia/reoxygenation (HR) injury in N2a cells, as manifested by increased cell viability, decreased apoptotic rate, LDH, and ROS generation. Additionally, SIL was found to inhibit HR-induced apoptosis, mitochondria dysfunction, and oxidative stress. However, silencing of GAS6 inhibited the neuroprotective effects of SIL. To sum up, these results suggest that SIL may be a promising therapeutic agent for the treatment of ischemic stroke.

Nanoparticles carrying paclitaxel and anti-miR-221 for breast cancer therapy triggered by ultrasound.

Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.