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Abstract Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states. Analysing the structural integrity along different release paths via molecular dynamic simulations, we found substantial disintegration rates upon shock release, increasing with the on-Hugnoiot shock temperature. We also find that recrystallization can occur after the expansion and hence during the release, depending on subsequent cooling mechanisms. Our study suggests higher ND recovery rates from off-Hugoniot states, e.g., via double-shocks, due to faster cooling. Laser-driven shock compression experiments of polyethylene terephthalate (PET) samples with in situ X-ray probing at the simulated conditions found diamond signal that persists up to 11 ns after breakout. In the diffraction pattern, we observed peak shifts, which we attribute to thermal expansion of the NDs and thus a total release of pressure, which indicates the stability of the released NDs.

The fabrication of carbon nanostructured material for biomedical application has gained a lot of interest in recent years. Herein, the preparation of carbon dots (CDs) using Allium sativum L. leaf extract were demonstrated using hydrothermal process. The CDs were characterized using various techniques including UV-Vis, DLS, FT-IR, XPS and TEM methods. The green synthesized CDs were mostly spherical with diameter of 2.1 ±0.6 nm with high colloidal stability. Good antioxidant activity versus DPPH was observed using the prepared CDs. Furthermore, the cytotoxicity effect of carbon CDs was investigated using MTT strategy. Moreover, the prepared CDs were applied as scavengers of reactive oxygen species in osteoarthritis (OA). For clinical applications, the green source CDs demonstrated positive effects in terms of antioxidant, anti-osteoarthritis, and cytotoxicity properties. The obtained results have the potential to offer fresh perspectives on the treatment of different inflammatory diseases caused by reactive oxygen species. Additionally, the CDs were used to determine Fe(III) by fluorescence (FL) procedure. The decrease of FL intensity allowed to measure Fe(III) in a wide linear range (10 nM-0.5 mM) with a low detection limit of 4.0 nM. These findings show that the prepared CDs have great potential for various applications.

Abstract Long non‐coding RNA RP11‐64B16.4 (myocardial infarction protection‐related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re‐expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta‐8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL‐mediated anti‐apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia‐enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

There is a gradual transition from water to dryland rearing of geese. In this study, we performed 16S rRNA sequencing (16S rRNA-seq) and transcriptome sequencing (RNA-seq) to reveal the effects of cage rearing (CR) and floor rearing (FR) systems on the microbial composition and transcriptome of the goose ileum. Through 16S rRNA-seq, Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 2 (hgcI_clade and Faecalibacterium) and 14 (Bacteroides, Proteiniphilum, Proteiniclasticum, etc.) differential microbiota in CR and FR, respectively. The rearing system influenced 4 pathways including biosynthesis of amino acids in ileal microbiota. Moreover, we identified 1,198 differentially expressed genes (DEGs) in the ileum mucosa, with 957 genes up-regulated in CR and 241 genes up-regulated in FR. In CR, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the significant enrichment (p

ABSTRACT: Age at first egg (AFE) has consistently garnered interest as a crucial reproductive indicator within poultry production. Previous studies have elucidated the involvement of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-thyroid (HPT) axes in regulating poultry sexual maturity. Concurrently, there was evidence suggesting a potential co-regulatory relationship between these 2 axes. However, as of now, no comprehensive exploration of the key pathways and genes responsible for the crosstalk between the HPO and HPT axes in the regulation of AFE has been reported. In this study, we conducted a comparative analysis of morphological differences and performed transcriptomic analysis on the hypothalamus, pituitary, thyroid, and ovarian stroma between normal laying group (NG) and abnormal laying group (AG). Morphological results showed that the thyroid index difference (D-) value (thyroid index D-value=right thyroid index-left thyroid index) was significantly (P < 0.05) lower in the NG than in the AG, while the ovarian index was significantly (P < 0.01) higher in the NG than in the AG. Furthermore, between NG and AG, we identified 99, 415, 167, and 1182 differentially expressed genes (DEGs) in the hypothalamus, pituitary, thyroid, and ovarian stroma, respectively. Gene ontology (GO) analysis highlighted that DEGs from 4 tissues were predominantly enriched in the “biological processes” category. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that 16, 14, 3, and 26 KEGG pathways were significantly enriched (P < 0.05) in the hypothalamus, pituitary, thyroid, and ovarian stroma. The MAPK signaling pathway emerged as the sole enriched pathway across all 4 tissues. Employing an integrated analysis of the protein-protein interaction (PPI) network and correlation analysis, we found GREB1 emerged as a pivotal component within the HPO axis to regulate estrogen-related signaling in the HPT axis, meanwhile, the HPT axis influenced ovarian development by regulating thyroid hormone-related signaling mainly through OPN5. Then, 10 potential candidate genes were identified, namely IGF1, JUN, ERBB4, KDR, PGF, FGFR1, GREB1, OPN5, DIO3, and THRB. These findings establish a foundation for elucidating the physiological and genetic mechanisms by which the HPO and HPT axes co-regulate goose AFE.

Abstract Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications. Graphical Abstract

Abstract Background Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China’s national database of rare diseases during the same period. Results A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories. Conclusion Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies.

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS (p

The use of broadband laser technology is a novel approach for inhibiting processes related to laser plasma interactions (LPIs). In this study, several preliminary experiments into broadband-laser-driven LPIs are carried out using a newly established hundreds-of-joules broadband second-harmonic-generation laser facility. Through direct comparison with LPI results for a traditional narrowband laser, the actual LPI-suppression effect of the broadband laser is shown. The broadband laser had a clear suppressive effect on both back-stimulated Raman scattering and back-stimulated Brillouin scattering at laser intensities below 1 × 1015 W cm−2. An abnormal hot-electron phenomenon is also investigated, using targets of different thicknesses.

Abstract Background Danon disease is characterized by the failure of lysosomal biogenesis, maturation, and function due to a deficiency of lysosomal membrane structural protein (LAMP2). Methods The current report describes a female patient with a sudden syncope and hypertrophic cardiomyopathy phenotype. We identified the pathogenic mutations in patients by whole‐exon sequencing, followed by a series of molecular biology and genetic approaches to identify and functional analysis of the mutations. Results Suggestive findings by cardiac magnetic resonance (CMR), electrocardiogram (ECG), and laboratory examination suggested Danon disease which was confirmed by genetic testing. The patient carried a novel de novo mutation, LAMP2 c.2T>C located at the initiation codon. The quantitative polymerase chain reaction (qPCR) and Western blot (WB) analysis of peripheral blood leukocytes from the patients revealed evidence of LAMP2 haploinsufficiency. Labeling of the new initiation codon predicted by the software with green fluorescent protein followed by fluorescence microscopy and Western blotting showed that the first ATG downstream from the original initiation codon became the new translational initiation codon. The three‐dimensional structure of the mutated protein predicted by alphafold2 revealed that it consisted of only six amino acids and failed to form a functional polypeptide or protein. Overexpression of the mutated LAMP2 c.2T>C showed a loss of function of the protein, as assessed by the dual‐fluorescence autophagy indicator system. The mutation was confirmed to be null, AR experiments and sequencing results confirmed that 28% of the mutant X chromosome remained active. Conclusion We propose possible mechanisms of mutations associated with haploinsufficiency of LAMP2: (1) The inactivation X chromosome carrying the mutation was not significantly skewed. However, it decreased in the mRNA level and the expression ratio of the mutant transcripts; (2) The identified mutation is null, and the active mutant transcript fails to translate into the normal LAMP2 proteins. The presence of haploinsufficiency in LAMP2 and the X chromosome inactivation pattern were crucial factors contributing to the early onset of Danon disease in this female patient.

Abstract Pyroptosis, systemic inflammation, and mitochondrial apoptosis are the three primary contributors to sepsis's multiple organ failure, the ultimate cause of high clinical mortality. Currently, the drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid‐responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that is highly capable of carrying both the hydrophilic drug NAD+ and the hydrophobic drug BAPTA‐AM, with its outer layer being sealed by the inflammatory targeting peptide PEG‐LSA, is developed. Once targeted to the region of inflammation, HMPDA begins depolymerization, releasing the drugs NAD+ and BAPTA‐AM. Depletion of polydopamine on excessive reactive oxygen species production, promotion of ATP production and anti‐inflammation by NAD+ replenishment, and chelation of BAPTA (generated by BA‐AM hydrolysis) on overloaded Ca2+ can comprehensively block the three stages of sepsis, i.e., precisely inhibit the activation of pyroptosis pathway (NF‐κB‐NLRP3‐ASC‐Casp‐1), inflammation pathway (IL‐1β, IL‐6, and TNF‐α), and mitochondrial apoptosis pathway (Bcl‐2/Bax‐Cyt‐C‐Casp‐9‐Casp‐3), thereby restoring intracellular homeostasis, saving the cells in a state of “critical survival,” further reducing LPS‐induced systemic inflammation, finally restoring the organ functions. In conclusion, the synthesis of this agent provides a simple and effective synergistic drug delivery nanosystem, which demonstrates significant therapeutic potential in a model of LPS‐induced sepsis.

BackgroundAs rare diseases (RDs) receive increasing attention, obtaining accurate RD incidence estimates has become an essential concern in public health. Since RDs are difficult to diagnose, include diverse types, and have scarce cases, traditional epidemiological methods are costly in RD registries. With the development of the internet, users have become accustomed to searching for disease-related information through search engines before seeking medical treatment. Therefore, online search data provide a new source for estimating RD incidences. ObjectiveThe aim of this study was to estimate the incidences of multiple RDs in distinct regions of China with online search data. MethodsOur research scale included 15 RDs in China from 2016 to 2019. The online search data were obtained from Sogou, one of the top 3 commercial search engines in China. By matching to multilevel keywords related to 15 RDs during the 4 years, we retrieved keyword-matched RD-related queries. The queries used before and after the keyword-matched queries formed the basis of the RD-related search sessions. A two-step method was developed to estimate RD incidences with users’ intents conveyed by the sessions. In the first step, a combination of long short-term memory and multilayer perceptron algorithms was used to predict whether the intents of search sessions were RD-concerned, news-concerned, or others. The second step utilized a linear regression (LR) model to estimate the incidences of multiple RDs in distinct regions based on the RD- and news-concerned session numbers. For evaluation, the estimated incidences were compared with RD incidences collected from China’s national multicenter clinical database of RDs. The root mean square error (RMSE) and relative error rate (RER) were used as the evaluation metrics. ResultsThe RD-related online data included 2,749,257 queries and 1,769,986 sessions from 1,380,186 users from 2016 to 2019. The best LR model with sessions as the input estimated the RD incidences with an RMSE of 0.017 (95% CI 0.016-0.017) and an RER of 0.365 (95% CI 0.341-0.388). The best LR model with queries as input had an RMSE of 0.023 (95% CI 0.017-0.029) and an RER of 0.511 (95% CI 0.377-0.645). Compared with queries, using session intents achieved an error decrease of 28.57% in terms of the RER (P=.01). Analysis of different RDs and regions showed that session input was more suitable for estimating the incidences of most diseases (14 of 15 RDs). Moreover, examples focusing on two RDs showed that news-concerned session intents reflected news of an outbreak and helped correct the overestimation of incidences. Experiments on RD types further indicated that type had no significant influence on the RD estimation task. ConclusionsThis work sheds light on a novel method for rapid estimation of RD incidences in the internet era, and demonstrates that search session intents were especially helpful for the estimation. The proposed two-step estimation method could be a valuable supplement to the traditional registry for understanding RDs, planning policies, and allocating medical resources. The utilization of search sessions in disease detection and estimation could be transferred to infoveillance of large-scale epidemics or chronic diseases.

ABSTRACT: The meat and egg of goose is one of the main components of human food supply. The improvement of goose egg production is particularly important for the increasing human population. However, limited information is available about the effective molecular markers and mechanisms of egg production in goose. In this study, we jointly utilized the data of genome resequencing in different egg production Sichuan white goose and transcriptome at different follicle development stages to identified the molecular markers and mechanisms of egg production. The coefficient of variation of individual egg production in Sichuan white goose population is 0.42 to 0.49. Fifty individuals with the highest (laying 365 days egg number, LEN365 = 79–145) and 50 individuals with the lowest (LEN365 = 8–48) egg production were divided into high and low egg production groups. Based on whole-genome sequencing data of the selected samples, 36 SNPs (annotation novel.12.470, CELF2, ATP1A1, KCNJ6, RAB4A, UST, REV3L, DHX15, CAVN2, SLC5A9, Cldn5, MRPS23, and Tspan2) associated with the LEN365 were identified, involving multiple pathways such as metabolism and endocrinology. Notably, 5 SNPs located in the exon9 of ATP1A1 were identified by GWAS analysis. The association analysis with LEN365 showed the phenotypic variance explained of this haplotype consisting of 5 SNPs is 20.51%. Through transcriptome data analysis, we found the expression of ATP1A1 in the granular layers was increased in the stage of small yellow follicle to large yellow follicle (LYF) and LYF to F5, while decreased in F2 to F1. For the first time, we report the haplotype region formed by 5 SNPS on exon9 of ATP1A1 is associated with egg production in goose and involved in follicle selection and maturation processes.

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte–macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte–macrophage differentiation. The role of Morrbid in monocyte–macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte–macrophage phenotypes, which is involved in atherogenesis.

A new approach to target development for laboratory astrophysics experiments at high-power laser facilities is presented. With the dawn of high-power lasers, laboratory astrophysics has emerged as a field, bringing insight into physical processes in astrophysical objects, such as the formation of stars. An important factor for success in these experiments is targetry. To date, targets have mainly relied on expensive and challenging microfabrication methods. The design presented incorporates replaceable machined parts that assemble into a structure that defines the experimental geometry. This can make targets cheaper and faster to manufacture, while maintaining robustness and reproducibility. The platform is intended for experiments on plasma flows, but it is flexible and may be adapted to the constraints of other experimental setups. Examples of targets used in experimental campaigns are shown, including a design for insertion in a high magnetic field coil. Experimental results are included, demonstrating the performance of the targets.

ABSTRACT: The importance of thyroid-related genes has been repeatedly mentioned in the transcriptome studies of poultry with different laying performance, yet there are few systematic studies to unravel the regulatory mechanisms of the thyroid-ovary axis in the poultry egg production process. In this study, we compared the transcriptome profiles in the thyroid and ovarian stroma between high egg production (GP) and low egg production (DP) ducks, and then revealed the pathways and candidate genes involved in the process. We identified 1,114 and 733 differentially expressed genes (DEGs) in the thyroid and ovarian stroma, separately. The Gene Ontology (GO) analysis showed that a total of 504 and 189 GO terms were identified in the thyroid and ovarian stroma (P < 0.05). Three common GO terms were identified from the top 5 GO terms with the highest significant level in two tissues, including extracellular space, calcium ion binding, and integral component of plasma membrane. The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that 15 and 14 KEGG pathways were significantly (P < 0.05) enriched in the thyroid and ovarian stroma, respectively. And, there were 8 common pathways, including neuroactive ligand-receptor interaction, calcium signaling pathway, ECM-receptor interaction, PPAR signaling pathway, melanogenesis, wnt signaling pathway, vascular smooth muscle contraction, and cytokine-cytokine receptor interaction. Notably, the neuroactive ligand-receptor interaction pathway was the most significantly enriched by the DEGs both in the thyroid and ovarian stroma. The interaction among DEGs enriched in the neuroactive ligand-receptor interaction and ECM-receptor interaction suggested that the thyroid may regulate ovarian development by these genes. Through integrated analysis of the protein-protein interaction (PPI) network and KEGG pathway maps, 9 key DEGs (PTH, THBS2, THBS4, CD36, ADIPOQ, ACSL6, PRKAA2, CRH, and PCK1) were identified, which could play crucial roles in the thyroid to regulate ovarian function and then affect egg-laying performance between GP and DP. This study serves as a basis to explore the molecular mechanism of the thyroid affecting ovarian function and egg production in female ducks and may help to identify molecular markers that can be used for duck genetic selection.

(1) Background: The role of estrogen receptor gene 1 (ESR1) in female reproduction and lipid metabolism has been extensively investigated. However, its contribution to lipid metabolism during the development of poultry follicles remains unclear. (2) Methods: This study aimed to explore the function of ESR1 via overexpressing (ESR1ov) and interfering (ESR1si) with its expression in pre-hierarchical granulosa cells (phGCs) and hierarchical granulosa cells (poGCs). (3) Results: We successfully cloned and obtained an 1866 bp segment of the full-length CDS region of the Sichuan white goose ESR1 gene. In phGCs of the ESR1ov and ESR1si groups, there were no significant changes compared to the control group. However, in poGCs, the ESR1ov group exhibited decreased lipid deposition, triglycerides, and cholesterol compared to the control group, while the ESR1si group showed increased lipid deposition, triglycerides, and cholesterol. The expression of APOB and PPARα was significantly reduced in the ESR1ov group compared to the ESR1ov-NC group. Moreover, significant changes in the expression of ACCα, DGAT1, SCD, CPT1, and ATGL were observed between the ESR1si and ESR1si-NC group. (4) Conclusions: These findings shed light on the function and molecular mechanism of ESR1 in lipid metabolism in goose poGCs, providing a better understanding of the physiological process of goose follicular development.

Abstract The sound velocities of water in the Hugoniot states are investigated by laser shock compression of precompressed water in a diamond anvil cell. The obtained sound velocities in the off-Hugoniot region of liquid water at precompressed conditions are used to test the predictions of quantum molecular dynamics (QMD) simulations and the SESAME equation-of-state (EOS) library. It is found that the prediction of QMD simulations agrees with the experimental data while the prediction of SESAME EOS library underestimates the sound velocities probably due to its improper accounting for the ionization processes.

Abstract This work deals with the problem of insufficient energy caused by the frequent use of relay nodes in wireless sensor networks. Here, energy cooperation relay selection algorithm is proposed in energy heterogeneous networks. It is assumed that the location of relay nodes obeys a homogeneous Poisson point process (PPP), and the relay nodes adopt an adaptive energy collection technology, which can harvest energy from the surrounding environment and decide whether to use or store it according to the current energy status of the battery. The relay nodes are divided into three kinds: the communication relay, the candidate relay and the ordinary relay. The candidate relay nodes are determined by K‐medoids clustering algorithms and the ordinary relay nodes transmit energy to them. Finally, the number of data packets sent by relay nodes and the expression of the energy status of the battery are derived correspond to the relay cooperation selection algorithm. The simulation results show that the energy cooperation relay selection scheme effectively extends lifetime of the network when the total network energy is relatively small.

Long non-coding RNA (lncRNA) is widely reported to be involved in cardiac (patho)physiology. Acute myocardial infarction, in which cardiomyocyte apoptosis plays an important role, is a life-threatening disease. Here, we report the lncRNA Chaer that is anti-apoptotic in cardiomyocytes during Acute myocardial infarction. Importantly, lncRNA Chaer is significantly downregulated in both oxygen-glucose deprivation (oxygen-glucose deprivation)-treated cardiomyocytes in vitro and AMI heart. In vitro, overexpression of lncRNA Chaer with adeno virus reduces cardiomyocyte apoptosis induced by OGD-treated while silencing of lncRNA Chaer increases cardiomyocyte apoptosis instead. In vivo, forced expression of lncRNA Chaer with AAV9 attenuates cardiac apoptosis, reduces infarction area and improves mice heart function in AMI. Interestingly, overexpression of lncRNA Chaer promotes the phosphorylation of AMPK, and AMPK inhibitor Compound C reverses the overexpression of lncRNA Chaer effect of reducing cardiomyocyte apoptosis under OGD-treatment. In summary, we identify the novel ability of lncRNA Chaer in regulating cardiomyocyte apoptosis by promoting phosphorylation of AMPK in AMI.

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown.Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function.Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-β1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-β1 dependent.Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis.

Abstract Background Midazolam has some potential in pain control of patients undergoing knee arthroscopy. However, the results remain controversial. We conduct a systematic review and meta-analysis to explore the effect of midazolam on pain control after knee arthroscopy. Methods PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases are systematically searched. Randomized controlled trials (RCTs) assessing the effect of midazolam on pain management after knee arthroscopy are included. Two investigators have independently searched articles, extracted the data, and assessed the quality of the included studies. This meta-analysis is performed using the random-effect model. Results Six RCTs are included in this meta-analysis. Compared with control intervention after knee arthroscopy, midazolam intervention can significantly reduce the pain scores (standard mean difference (Std. MD) = − 3.70; 95% confidence interval (CI) = − 6.81 to − 0.60; P = 0.02), the number of patients requiring analgesics (risk ratio (RR) = 0.66; 95% CI = 0.49 to 0.88; P = 0.005), and analgesic consumption (Std. MD = −1.62; 95% CI = − 3.04 to − 0.19; P = 0.03), as well as increase the time to first analgesic requirement (Std. MD = 1.58; 95% CI = 0.17 to 2.99; P = 0.03). In addition, midazolam intervention results in no increase in adverse events following knee arthroscopy (RR = 0.74; 95% CI = 0.18 to 2.98; P = 0.67). Conclusions Midazolam intervention is revealed to substantially reduce the pain scores, the number of patients requiring analgesics, and analgesic consumption, as well as improve the time to first analgesic requirement after knee arthroscopy.

Non-small-cell lung cancer (NSCLC) accounts for over 85% of clinical lung cancer cases, which is the leading cause of cancer-related death. To develop new therapeutic strategy for NSCLC, a library of L-phenylalanine-based poly(ester amide) (Phe-PEA) polymers was synthesized and assembled with docetaxel (Dtxl) to form Dtxl-loaded Phe-PEA nanoparticles (NPs). The hydrophobic Phe-PEA polymers were able to form NPs by nanoprecipitation method and the characterization results showed that the screened Dtxl-8P4 NPs have small particle size (∼100 nm) and high Dtxl loading (∼20 wt%). In vitro experiments showed that Dtxl-8P4 NPs were rapidly trafficked into cancer cells, then effectively escaped from lysosomal degradation and achieved significant tumor cell inhibition. In vivo results demonstrated that Dtxl-8P4 NPs with prolonged blood circulation could efficiently deliver Dtxl to A549 tumor sites, leading to reduced cell proliferation, block metastasis, and increase apoptosis, then persistent inhibition of tumor growth. Therefore, Phe-PEA NPs are able to load high amount of hydrophobic drugs and could be a promising therapeutic approach for NSCLC and other cancer treatments.

AimThe role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence.MethodsAll observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.ResultsA total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence). Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence). Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer.ConclusionsResults from the meta-analysis don't support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.

Optimization on trajectory planning is significant offering the driver or automatic train operation system a guidance to drive the train efficiently. An optimal trajectory is subject to operational, geographic, physical and dynamic constraints. In previous studies, researchers have put much effort into offline optimization. However, operational errors in real situation are rarely taken into consideration. Thus, this paper proposes a dynamic trajectory planning to address the deviation. Specifically, first, we design an online optimization framework to display model predictive control-based train trajectory planning theory. Various constraints are set for optimization problem. Second, taking energy consumption and punctuality into consideration, we propose a moving window method to search the optimal variables, which are applied to evaluate the fitness function. Plus, to improve global search ability and convergence rate, we present a multi-swarm particle swarm optimization by dividing the population into several parts. On the basis of operational time error at reallocation positions, we design a novel weight allocation mechanism for the revaluation of fitness function. At last, taking real data from Beijing-Shanghai high-speed railway as an example, the robustness and effectiveness of the proposed algorithm is proved by comparing multiple parameters with some numerical results of simulations. The results show that the proposed method can adjust operating strategy dynamically so that the train runs in an energy-efficient way. Additionally, in delay scene, the proposed method can also guide the train to catch up with the scheduled time and save energy consumption. [ABSTRACT FROM AUTHOR]