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Abstract Background Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. Methods The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. Results We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. Conclusion These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis. Graphical Abstract

Abstract Objective To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. Methods A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children’s Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. Results Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636–0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759–0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741–0.884). Conclusion We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Background: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry. Methods: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry. Results: A total of 11160 COVID-19-associated emergency department (ED) visits and 1079 hospitalizations were analyzed. Seizures were the most common specific neurological symptom, while encephalitis and acute disseminated encephalomyelitis (ADEM) was the most prevalent severe involvement.In ED patients with neurological manifestations, severe neurological diagnosis was associated with visual hallucination, seizure with/without fever, behavior change, decreased GCS, myoclonic jerk, decreased activity/fatigue, and lethargy. In hospitalized patients with neurological manifestations, severe neurological diagnosis was associated with behavior change, visual hallucination, decreased GCS, seizure with/without fever, myoclonic jerk, fatigue, and hypoglycemia at admission. Encephalitis/ADEM was the only risk factor for poor neurological outcomes at discharge in hospitalized patients. Conclusion: Neurological complications are common in pediatric COVID-19. Visual hallucination, seizure, behavior change, myoclonic jerk, decreased GCS, and hypoglycemia at admission are the most important warning signs of severe neurological involvement such as encephalitis/ADEM.

A rising incidence of acute kidney injury (AKI) may lead to longer hospitalization stays and even greater mortality. Diabetes is an independent risk factor for AKI and using hypoglycemic agents has been a fundamental glycemic control in diabetics. Studies have shown that different types of hypoglycemic agents may have an effect on the occurrence of AKI, including metformin, SGLT2 inhibitors and entero-insulin analogues (GLP-1 receptor agonists, DPP4 inhibitors). This review focused upon the relationship between related drugs and AKI.

Abstract Background Both sleep-related breathing disorders (SRBDs) and HIV infection can interfere with normal sleep architecture, and also cause physical and psychological distress. We aimed to understand the differences in the obstructive patterns, sleep architecture, physical and psychological distress when compared between people living with HIV (PLWH) and matched the severity of SRBDs controls. Methods A comparative study using matched case-control design was conducted. Men with HIV infection (case group) were enrolled from 2016 to 2019. A control group with HIV seronegative men were matched for SRBDs severity, and were selected from sleep medicine center database for comparison. Results The mean age of the 108 men (including 54 cases and 54 matched controls) was 33.75 years. Central-apnea index (CI) was higher in the case group rather than matched controls (mean CI, 0.34 vs. 0.17, p = 0.049). PLWH had a lower mean percentage of stage 3 sleep (10.26% vs. 13.94%, p = 0.034) and a higher percentage of rapid eye movement sleep (20.59% vs. 17.85%, p = 0.011) compared to matched controls. Nocturnal enuresis and sleepiness causing traffic accidents were more frequent complaint in PLWH compared to controls. Conclusions Early detected SRBDs and subtypes in PLWH to begin treatment for the underlying cause could reduce the risk of sleepiness-related traffic accidents.

Abstract Tuning phase transition temperature is one of the central issues in phase transition materials. Herein, we report a case study of using enantiomer fraction engineering as a promising strategy to tune the Curie temperature (T C) and related properties of ferroelectrics. A series of metal-halide perovskite ferroelectrics (S−3AMP)x(R−3AMP)1−xPbBr4 was synthesized where 3AMP is the 3-(aminomethyl)piperidine divalent cation and enantiomer fraction x varies between 0 and 1 (0 and 1 = enantiomers; 0.5 = racemate). With the change of the enantiomer fraction, the T C, second-harmonic generation intensity, degree of circular polarization of photoluminescence, and photoluminescence intensity of the materials have been tuned. Particularly, when x = 0.70 − 1, a continuously linear tuning of the T C is achieved, showing a tunable temperature range of about 73 K. This strategy provides an effective means and insights for regulating the phase transition temperature and chiroptical properties of functional materials.

Soil microbial carbon metabolism is critical in wetland soil carbon cycling, and is also a research hotspot at present. However, most studies focus on the surface soil layer in the wetlands and the microorganisms associated with this layer. In this study, 0-75 cm soil profiles were collected from five widely separated reed wetlands in the Songnen Plain, which has a large number of middle-high latitude inland saline-sodic wetlands. The Biolog-ECO method was used to determine the carbon metabolic activity and functional diversity of soil microorganisms. The results showed that soil carbon metabolic activity decreased with increasing soil depth. The carbon metabolic activity of soil microorganisms in the 60-75 cm layer was approximately 57.41%-74.60% of that in the 0-15 cm layer. The soil microbial Shannon index and utilization rate of amines decreased with an increase in soil depth, while the Evenness index and utilization rate of polymers tended to increase with soil depth. Dissolved organic carbon (DOC) is the most important factor affecting microbial carbon source utilization preference, because microorganisms mainly obtain the carbon source from DOC. The result of the correlation analysis showed that the soil microbial carbon metabolic activity, Shannon index, and Evenness index significantly correlated with soil total carbon (TC), microbial biomass carbon (MBC), DOC, total nitrogen (TN), ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3−-N) contents, and electrical conductivity (EC). This study emphasized the important role of microbial carbon metabolic function in deep soil.

Sucrose constitutes a non-toxic, biodegradable, low-cost and readily available natural product. To expand its utility, we developed total synthesis for a ligand based on a sucrose scaffold for potential use as a metal chelation agent. The designed target (compound 2) has a metal-chelating functionality at both the C-6 and C-6’ positions, which can provide a first coordination sphere of eight valencies. The designed total synthesis was highly efficient. To demonstrate the utility of the ligand, we studied its complexation with Gd(III). Using potentiometric titration and high-resolution mass spectrometry, we confirmed the formation of a 1:1 complex with Gd(III), which has a respectable formation constant of ~1013.4. Further NMR relaxivity studies show that the Gd(III) complex has a relaxivity (r1) of 7.6958 mmol−1 s−1.

Herein, this work aims to demonstrate the topological effect on the mechanicalx characteristics of self-assembled block copolymers (BCPs). The lamellae-forming polystyrene-block-polydimethylsiloxane (PS-b-PDMS) can be self-assembled into various nanostructured monoliths with the use of PS-selective solvent for solvent annealing, giving diamond, gyroid, and cylinder structures with increasing the swelling degree of PS domain (the effective volume fraction of the PS segment after solvent annealing followed by evaporation). The stiffness of the self-assembled monoliths is scrutinized by nanoindentation test. For intrinsic PS-b-PDMS monolith with lamellar structure, the reduced elastic modulus as calculated from the measured stiffness is 0.91 GPa. By contrast, the PS-b-PDMS monolith with cylinder structure gives a significant reduction in reduced elastic modulus with the value of 0.52 GPa due to the introduced microporosity to the PS domain from solvent annealing using PS-selective solvent, resulting in the lower confrontation for continuous layer-by-layer deformation of hard PS and soft PDMS domains. In the case of gyroid-structured PS-b-PDMS monolith, it is unexpected to exhibit a significant increase in the reduced elastic modulus with a value of 1.6 GPa: note that the effect of microporosity is still significant. Accordingly, the enhancement of the reduced elastic modulus is attributed to the effect of deliberate structuring with network topology (i.e., three-dimensional co-continuous hard PS and soft PDMS domains) that is able to hold the occurrence of large-scale deformation. In contrast to the gyroid with a three-strut texture, the diamond-structured PS-b-PDMS monolith with a four-strut texture is superior to the gyroid with a reduced elastic modulus of 2.2 GPa, further confirming the suggested topology effect.

Background and objectiveFutile recanalization (FR) is defined as patients with acute ischemic stroke (AIS) due to large vessel occlusion who still exhibits functional dependence although undergoing successful mechanical thrombectomy (MT). We aimed to develop and validate a simple nomogram for predicting the probability of FR after MT treatment in AIS patients.MethodsClinical data of AIS patients in the Jrecan clinical trial in China from March 2018 to June 2019 were collected as the derivation set (n = 162). Meanwhile, clinical data of AIS patients who underwent MT in Baotou Central Hospital and Ningbo No.2 Hospital from 2019 to 2021 were collected as the validation set (n = 170). Multivariate logistic regression analysis was performed for all variables that had p

In this study, we report a novel per-6-substituted β-cyclodextrin (4) featuring seven phosphoramidate moieties as an innovative host for inclusion. This structurally well-defined host has remarkable water solubility and was isolated in pure form. Analytical techniques such as NMR and ITC were used to probe the molecular interactions with different drug molecules. Our investigations revealed that host 4 can form 2:1 inclusion complexes with various drugs. Further studies showed that the inclusions of drugs by β-CD host (4) are mostly enthalpy driven, highlighting the potential roles played by the phosphoramidate functionalities of the host. Comparatively, a per-O2, O3-acetylated analog (6) of compound 4 was also obtained, which also shows unusual water solubility but diminished inclusion capability.

The advancements of Internet of Things (IoT) technologies have enabled the implementation of smart and wearable sensors, which can be employed to provide older adults with affordable and accessible continuous biophysiological status monitoring. The quality of such monitoring data, however, is unsatisfactory due to excessive noise induced by various disturbances, such as motion artifacts. Existing methods take advantage of summary statistics, such as mean or median values, for denoising, without taking into account the biophysiological patterns embedded in data. In this research, a functional data analysis modeling method was proposed to enhance the data quality by learning individual subjects’ diurnal heart rate (HR) patterns from historical data, which were further improved by fusing newly collected data. This proposed data-fusion approach was developed based on a Bayesian inference framework. Its effectiveness was demonstrated in an HR analysis from a prospective study involving older adults residing in assisted living or home settings. The results indicate that it is imperative to conduct personalized healthcare by estimating individualized HR patterns. Furthermore, the proposed calibration method provides a more accurate (smaller mean errors) and more precise (smaller error standard deviations) HR estimation than raw HR and conventional methods, such as the mean.

Abstract Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway. Graphic Abstract

Abstract Herein, this work aims to develop a facile method for the fabrication of metallic mechanical metamaterial with a well-ordered diamond structure from a bottom-up approach using a self-assembled block copolymer for templated electrochemical deposition. By controlling the effective volume fraction of PDMS in PS-b-PDMS via solvent annealing followed by HF etching of PDMS, it is feasible to obtain nanoporous PS with diamond-structured nanochannels and used it as a template for templated electrochemical deposition. Subsequently, well-ordered nanonetwork gold (Au) can be fabricated. As evidenced by nanoindentation and micro-compression tests, the mechanical properties of the diamond-structured Au after removal of PS give the combination of lightweight and mechanically robust characteristics with an exceptionally high reduced elastic modulus of 11.9 ± 0.6 GPa and yield strength of 193 ± 11 MPa above the Hashin-Shtrikman upper bound of 72 MPa with a bending-dominated structure at equivalent density. The corresponding deformation mechanism can be elucidated by morphological observations experimentally and finite element analysis (FEA) numerically. This work demonstrates the bottom-up approach to fabricating metallic monolith with diamond structure in the nanoscale, giving a superior performance as mechanical metamaterials.

BackgroundThe past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT.MethodsA total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4–6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram.ResultsThe overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016–1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038–1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995–1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688–8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411–8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693–0.832) in the training set and 0.804 (0.719–0.889) in the validation set.ConclusionThe proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term ‘epigenetics’ was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term ‘epigenetics’. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.

Abstract Background Autophagy is a catabolic process that recycles damaged organelles and acts as a pro-survival mechanism, but little is known about autophagy dysfunction and epigenetic regulation in patients with obstructive sleep apnea (OSA). Methods Protein/gene expressions and DNA methylation levels of the autophagy-related genes (ATG) were examined in blood leukocytes from 64 patients with treatment-naïve OSA and 24 subjects with primary snoring (PS). Results LC3B protein expression of blood monocytes, and ATG5 protein expression of blood neutrophils were decreased in OSA patients versus PS subjects, while p62 protein expression of cytotoxic T cell was increased, particularly in those with nocturia. ATG5, ULK1, and BECN1 gene expressions of peripheral blood mononuclear cells were decreased in OSA patients versus PS subjects. LC3B gene promoter regions were hypermethylated in OSA patients, particularly in those with excessive daytime sleepiness, while ATG5 gene promoter regions were hypermethylated in those with morning headache or memory impairment. LC3B protein expression of blood monocytes and DNA methylation levels of the LC3B gene promoter region were negatively and positively correlated with apnea hyponea index, respectively. In vitro intermittent hypoxia with re-oxygenation exposure to human THP-1/HUVEC cell lines resulted in LC3B/ATG5/ULK1/BECN1 down-regulations and p62 up-regulation along with increased apoptosis and oxidative stress, while rapamycin and umbilical cord-mesenchymal stem cell treatment reversed these abnormalities through de-methylation of the ATG5 gene promoter. Conclusions Impaired autophagy activity in OSA patients was regulated by aberrant DNA methylation, correlated with clinical phenotypes, and contributed to increased cell apoptosis and oxidative stress. Autophagy enhancers may be novel therapeutics for OSA-related neurocognitive dysfunction.

WUSCHEL-related homeobox (WOX) genes are a class of plant-specific transcription factors, regulating the development of multiple tissues. However, the genomic characterizations and expression patterns of WOX genes have not been analyzed in lotus. In this study, 15 NnWOX genes were identified based on the well-annotated reference genome of lotus. According to the phylogenetic analysis, the NnWOX genes were clustered into three clades, i.e., ancient clade, intermediate clade, and WUS clade. Except for the conserved homeobox motif, we further found specific motifs of NnWOX genes in different clades and divergence gene structures, suggesting their distinct functions. In addition, two NnWOX genes in the ancient clade have conserved expression patterns and other NnWOX genes exhibit different expression patterns in lotus tissues, suggesting a low level of functional redundancy in lotus WOX genes. Furthermore, we constructed the gene co-expression networks for each NnWOX gene. Based on weighted gene co-expression network analysis (WGCNA), ten NnWOX genes and their co-expressed genes were assigned to the modules that were significantly related to the cotyledon and seed coat. We further performed RT-qPCR experiments, validating the expression levels of ten NnWOX genes in the co-expression networks. Our study reveals comprehensive genomic features of NnWOX genes in lotus, providing a solid basis for further function studies.

Stroke is the second leading cause of death worldwide and has two major subtypes: ischemic stroke and hemorrhagic stroke. Neuroinflammation is a pathological hallmark of ischemic stroke and intracerebral hemorrhage (ICH), contributing to the extent of brain injury but also in its repair. Neuroinflammation is intricately linked to the extracellular matrix (ECM), which is profoundly altered after brain injury and in aging. In the early stages after ischemic stroke and ICH, immune cells are involved in the deposition and remodeling of the ECM thereby affecting processes such as blood-brain barrier and cellular integrity. ECM components regulate leukocyte infiltration into the central nervous system, activate a variety of immune cells, and induce the elevation of matrix metalloproteinases (MMPs) after stroke. In turn, excessive MMPs may degrade ECM into components that are pro-inflammatory and injurious. Conversely, in the later stages after stroke, several ECM molecules may contribute to tissue recovery. For example, thrombospondin-1 and biglycan may promote activity of regulatory T cells, inhibit the synthesis of proinflammatory cytokines, and aid regenerative processes. We highlight these roles of the ECM in ischemic stroke and ICH and discuss their potential cellular and molecular mechanisms. Finally, we discuss therapeutics that could be considered to normalize the ECM in stroke. Our goal is to spur research on the ECM in order to improve the prognosis of ischemic stroke and ICH.

Three diets were formulated with dietary zinc (Zn) levels at 12.10 mg Zn/kg (L-Zn), 18.69 mg Zn/kg (M-Zn) and 120.82 mg Zn/kg (H-Zn) to explore effects of dietary Zn on growth, nutrient composition, muscle development, antioxidant and inflammatory responses in the muscle tissues of yellow catfish, one of the important economic fish in several Asian countries, including China. Zn content in M-Zn group could meet Zn requirement of yellow catfish. 270 juvenile yellow catfish (4.97 ± 0.01 g, mean ± S.E.M) were stocked in nine 300-L indoors tanks, 30 yellow catfish in each tank, and randomly provided with three diets for 10 weeks. Among three treatments, yellow catfish fed the middle Zn diets showed higher growth performance and condition factor but lower feed conversion rate than those fed the high Zn diets. Dietary Zn addition increased muscle Zn contents, but did not significantly influence feed intake, viscerosomatic and hepatosomatic index, survival, moisture, lipid, crude protein and ash contents in the muscle. Dietary Zn levels significantly influenced mRNA expression of several muscle development-related genes, such as mef2a, myod, myf5, myog, mef2d, pax7, mrf4, myhc and mstn. Middle dietary Zn levels increased antioxidant capability and reduced oxidative stress, as evaluated by enzymatic activities, gene and protein expression related to antioxidant response. Fish fed the middle Zn diets had the lower il8, tnf-α and tnf-β mRNA expression but higher il10 and tgf-β mRNA expression than those fed the high Zn diet, suggesting that optimal dietary Zn levels activated anti-inflammatory response and inhibited pro-inflammatory responses. Based on the observation, our study suggested that the suitable dietary Zn levels promoted the growth, muscle development, antioxidant and anti-inflammatory responses in fish.

Martensitic transformations are structural phase transition that usually bring about stimuli-responsive phenomena. Here authors present a 1D hybrid perovskite ferroelastic martensite that shows thermoelastic actuation behaviour with a significant photoelectric response around room temperature.

Abstract Background Leptin is important in physiological and pathological functions in various cancers, however, the significance and mechanisms of leptin in nasopharyngeal carcinoma remain ambiguous. Methods Leptin expression was analyzed by QPCR, immunohistochemistry, Western blotting, and TCGA database. The impact of gain- or loss-of-function of leptin were determined by MTT, colony formation, wound healing, and Transwell assays in NPC cells, and by a xenograft tumor model. Leptin-modulated glucose consumption and lactate production were assessed by ELISA. Furthermore, leptin-regulated signaling pathways were examined by QPCR and Western blotting assays. The immunoprecipitation assay was conducted to determine interaction between leptin and EGFR. In addition, miR-874-3p-regulated leptin expression was evaluated using bioinformatics, QPCR, luciferase assay, AGO2-RIP assay, and Western blotting. Results In this study, we found that leptin was highly expressed in the sera and tumor tissues of patients with NPC, and elevated leptin expression was associated with advanced clinical features and poor prognosis. Functional assays demonstrated that leptin remarkably promoted NPC cell growth, motility, and glycolysis in vitro and in vivo. Mechanistically, leptin associated with EGFR, resulting in enhanced cell growth through the regulation of cell-cycle related markers, glycolysis-related genes, and EGFR/AKT/c-Myc signaling. Moreover, leptin potentiated the invasive capacity of NPC cells by promoting EMT. We further explored that miR-874-3p influenced leptin-mediated NPC progression. Overexpression of miR-874-3p prevented cell growth, motility, glucose consumption, and lactate production in NPC cells, whereas miR-874-3p inhibition had the opposite effects. AGO-RIP assays confirmed that Argonaute 2 (AGO2), a protein associated with miR-874-3p, regulated leptin expression in NPC cells. The rescue assays indicated that inhibition of leptin suppressed the effects of miR-874-3p inhibitor. In clinical specimens, miR-874-3p was negatively correlated with leptin. Conclusions Leptin may serve as a novel prognostic factor and potential therapeutic target for patients with NPC. In addition, a newly discovered regulatory axis of leptin/EGFR/AKT/c-Myc can provide a novel therapeutic strategy for NPC.

Abstract The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo. Graphical Abstract

Ghorbani and colleagues describe versican-V1 as an inhibitor of remyelination using transgenic mice that illuminate new GFP + oligodendrocytes. Mechanisms of versican-V1 include the direct inhibition of oligodendrocytes, and elevating Th17 cells.

Introduction: Necroptosis is an alternative, caspase-independent programmed cell death that appears when apoptosis is inhibited. A gowing number of studies have reflected the link between necroptosis and tumors. However, only some systematical bibliometric analyses were focused on this field. In this study, we aimed to identify and visualize the cooperation between countries, institutions, authors, and journals through a bibliometric analysis to help understand the hotspot trends and emerging topics regarding necroptosis and cancer research.Methods: The articles and reviews on necroptosis and cancer were obtained from the Web of Science Core Collection on 16 September 2022. Countries, institutions, authors, references, and keywords in this field were visually analyzed by CtieSpace 5.8.R3, VOSviewer 1.6.18, and R package “bibliometrix.”Results: From 2006 to 2022, 2,216 qualified original articles and reviews on necroptosis in tumors were published in 685 academic journals by 13,009 authors in 789 institutions from 75 countries/regions. Publications focusing on necroptosis and cancer have increased violently in the past 16 years, while the citation number peaked around 2008–2011. Most publications were from China, while the United States maintained the dominant position as a “knowledge bridge” in necroptosis and cancer research; meanwhile, Ghent University and the Chinese Academy of Sciences were the most productive institutions. Moreover, only a tiny portion of the articles were multiple-country publications. Peter Vandenabeele had the most significant publications, while Alexei Degterev was most often co-cited. Peter Vandenabeele also gets the highest h-index and g-index in this research field. Cell Death and Disease was the journal with the most publications on necroptosis and cancer, which was confirmed to be the top core source by Bradford’s Law. At the same time, Cell was the leading co-cited journal, and the focus area of these papers was molecular, biology, and immunology. High-frequency keywords mainly contained those that are molecularly related (MLKL, NF-kB, TNF, RIPK3, RIPK1), pathological process related (necroptosis, apoptosis, cell-death, necrosis, autophagy), and mechanism related (activation, expression, mechanisms, and inhibition).Conclusion: This study comprehensively overviews necroptosis and cancer research using bibliometric and visual methods. Research related to necroptosis and cancer is flourishing. Cooperation and communication between countries and institutions must be further strengthened. The information in our paper would provide valuable references for scholars focusing on necroptosis and cancer.

Si3N4 ceramic as a tool material shows promising application prospects in high-speed machining fields; however, the required high mechanical properties and low-cost preparation of Si3N4 ceramic tool materials restrict its application. Herein, synergistic reinforced Si3N4 ceramic tool materials were fabricated by adding β-Si3N4 seeds, inexpensive Si3N4 whiskers and TiC particles into coarse commercial Si3N4 powder (D50 = 1.5 μm), then sintering by hot-pressing with low temperature and short holding time (1600 °C—30 min—40 MPa). The phase assemblage, microstructure evolution and toughening mechanisms were investigated. The results reveal that the sintered Si3N4 ceramics with synergistic reinforcement, compared to those with individual reinforcement, present an enhancement in relative density (from 94.92% to 97.15%), flexural strength (from 467.56 ± 36.48 to 809.10 ± 45.59 MPa), and fracture toughness (from 8.38 ± 0.19 to 10.67 ± 0.16 MPa·m1/2), as well as a fine Vickers hardness of 16.86 ± 0.19 GPa. Additionally, the various reinforcement modes of Si3N4 ceramics including intergranular fracture, crack deflection, crack bridging and whiskers extraction were observed in crack propagation, arising from the contributions of the added β-Si3N4 seeds, Si3N4 whiskers and TiC particles. This work is expected to serve as a reference for the production of ceramic cutting tools.

Circular RNAs (circRNAs) play important roles in carcinogenesis. Here, we investigated the mechanisms and clinical significance of circ-NOL10, a highly repressed circRNA in breast cancer. Subsequently, we also identified RNA-binding proteins (RBPs) that regulate circ-NOL10. Bioinformatics analysis was utilized to predict regulatory RBPs as well as circ-NOL10 downstream microRNAs (miRNAs) and mRNA targets. RNA immunoprecipitation, luciferase assay, fluorescence in situ hybridization, cell proliferation, wound healing, Matrigel invasion, cell apoptosis assays, and a xenograft model were used to investigate the function and mechanisms of circ-NOL10 in vitro and in vivo. The clinical value of circ-NOL10 was evaluated in a large cohort of breast cancer by quantitative real-time PCR. Circ-NOL10 is downregulated in breast cancer and associated with aggressive characteristics and shorter survival time. Upregulation of circ-NOL10 promotes apoptosis, decreases proliferation, and inhibits invasion and migration. Furthermore, circ-NOL10 binds multiple miRNAs to alleviate carcinogenesis by regulating PDCD4. CASC3 and metadherin (MTDH) can bind directly to circ-NOL10 with characterized motifs. Accordingly, ectopic expression or depletion of CASC3 or MTDH leads to circ-NOL10 expression changes, suggesting that these two RBPs modulate circ-NOL10 in cancer cells. circ-NOL10 is a novel biomarker for diagnosis and prognosis in breast cancer. These results highlight the importance of therapeutic targeting of the RBP-noncoding RNA (ncRNA) regulation network.

Abstract Background The albumin–bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. Aim This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. Method From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. Results There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p

Abstract The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

Background: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. Aims: The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. Methods: From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. Result: After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027–2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763–12.558, p = 0.002), but not in early recurrence. Conclusions: TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.

Abstract Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

Abstract Oral squamous cell carcinoma (OSCC) remains one of the most challenging clinical problems in the field due to its high rate of locoregional and distant metastases. However, studies that assess the association between aspirin use and survival in patients with OSCC are limited. Moreover, patients that recruited from those studies might have tumors that arose from different anatomic regions of the head and neck, including the oral cavity, oropharynx, etc. Since tumors within these distinct anatomic regions are unique in the context of epidemiology and tumor progression, we sought to evaluate the association of aspirin use with squamous cell carcinomas located within the oral cavity only. In this 10-year cohort study, we evaluated aspirin use and survival rates in relation to clinical characteristics as well as duration of aspirin use in patients with OSCC. Our findings suggest that OSCC patients with aspirin use for more than 180 days showed improved overall and disease-specific survival rates. Aspirin also improves survival in patients across various stages of OSCC. Cox regression models indicated that aspirin use was associated with a good prognosis. In conclusion, this evidence indicates that aspirin may be potentially used as an adjuvant therapy for OSCC.

BackgroundThe incidence rate of thyroid carcinoma (THCA) markedly increased in the recent few decades and has been likely over-diagnosed, especially papillary thyroid cancer (PTC) in women. However, the incidence of advanced-stage papillary thyroid cancer is also rising. According to earlier studies, tumors with identical pathology might have different clinical outcomes, which implies some variances in papillary thyroid cancer. Although the mortality of thyroid cancer has remained stable or declined, there is still an important problem in estimating whether it is benign or needs surgery for patients with papillary thyroid cancer.MethodsAfter obtaining data from The Cancer Genome Atlas (TCGA) Project-THCA database by R package TCGA bio links, 18 samples (11 at stage IV as high-risk group and 7 at stage I as low-risk group) were obtained using survival package and edgeR to ensure differential expression; ClusterProfiler package was used to carry on gene set enrichment analysis and searched the possible pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. STRING and Cytoscape were used to construct and modify the protein–protein interaction (PPI) network to get hub genes of differentially expressed genes. Next, the pROC package was used to get the receiver operating characteristic (ROC) curves of hub genes’ disease-free survival (DFS). Then, transcription factors (TFs) and miRNAs of key genes were predicted by ENCORI and AnimalTFDB. In the end, TF–target genes–miRNA regulatory network was also constructed by Cytoscape.ResultsOur research obtained the top 9 candidate genes from the whole network (IFNA1, MRC1, LGALS3, LOX, POSTN, TIMP1, CD276, SDC4, and TLR2). According to the ROC results, TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN were considered to play a more critical role in malignant papillary thyroid cancer or immature cancer of papillary thyroid cancer. Our analysis concludes that TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN are identified as thyroid cancer biomarkers, which lead to the different clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new biomarkers associated with the prognosis of thyroid cancer.ConclusionsTIMP1, LOX, CD276, IFNA1, TLR2, and POSTN have different expressions in PTCs, which lead to the various clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new potential biomarkers associated with the prognosis of thyroid cancer. In addition, TF–miRNA–target gene regulatory network may help further reach for PTC.

The multi-chiplet technique is expected to be a promising solution to achieve high-density system integration with low power consumption and high usage ratio. This technique can be integrated with a glass interposer to accomplish a competitive low fabrication cost compared with the silicon-based interposer architecture. In this study, process-oriented stress simulation is performed by the element activation and deactivation technique in finite element analysis architecture. The submodeling technique is also utilized to mostly conquer the scale mismatch and difficulty in mesh gridding design. It is also used to analyze the thermomechanical responses of glass interposers with chiplet arrangements and capped epoxy molding compounds (EMC) during curing. A three-factor, three-level full factorial design is applied using the analysis of variance method to explore the significance of various structural design parameters for stress generation. Analytic results reveal that the maximum first principal stresses of 130.75 and 17.18 MPa are introduced on the sidewall of Cu-filled via and the bottom of the glass interposer, respectively. Moreover, the EMC thickness and through glass via pitch are the dominant factors in the adopted vehicle. They significantly influence the stress magnitude during heating and cooling.

Histone methylation is an epigenetic change mediated by histone methyltransferase, and has been connected to the beginning and progression of several diseases. The most common ailments that affect the elderly are cardiovascular and cerebrovascular disorders. They are the leading causes of death, and their incidence is linked to vascular calcification (VC). The key mechanism of VC is the transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like phenotypes, which is a highly adjustable process involving a variety of complex pathophysiological processes, such as metabolic abnormalities, apoptosis, oxidative stress and signalling pathways. Many researchers have investigated the mechanism of VC and related targets for the prevention and treatment of cardiovascular and cerebrovascular diseases. Their findings revealed that histone lysine methylation modification may play a key role in the various stages of VC. As a result, a thorough examination of the role and mechanism of lysine methylation modification in physiological and pathological states is critical, not only for identifying specific molecular markers of VC and new therapeutic targets, but also for directing the development of new related drugs. Finally, we provide this review to discover the association between histone methylation modification and VC, as well as diverse approaches with which to investigate the pathophysiology of VC and prospective treatment possibilities.

ObjectiveWe retrospectively assessed the surgical results of PBC with preoperative multimodal image fusion and intraoperative Dyna Computed Tomography (CT) in 24 patients with primary trigeminal neuralgia (PTN) to explore a valuable aid for Percutaneous balloon compression (PBC).MethodsWe studied the data of 24 patients with PTN. All patients underwent PBC and were assessed with preoperative multimodal image fusion [computed tomography (CT) and magnetic resonance imaging (MRI)] and intraoperative Dyna CT in the Department of Neurosurgery of Zhuhai People’s Hospital between October 2020 and September 2021. Multimodal image fusion—three-dimensional (3D) reconstruction of CT and MRI data—was performed using 3D-Slicer software, and preoperative evaluation was performed according to the results of image fusion. Dyna CT was used to dynamically observe the position and shape of the metallic hollow introducer and Fogarty catheter and balloon during the operation to guide the operation in real time. We performed follow-up assessments each month and summarized the clinical characteristics, surgical effects, and complications in all patients.ResultsSurgery was successful for all patients; the patients reported immediate pain relief. Surgical complications included facial numbness in 24 patients (100%), mild masseter weakness in three (12.5%), herpes zoster in three (12.5%), and balloon rupture in one (4.2%). None of the patients had serious surgical complications. The mean follow-up time was 9.6 ± 2.7 months. During the follow-up period, 22 patients (91.7%) experienced no recurrence of pain, and two patients (8.3%) experienced recurrence of pain, of which one underwent secondary PBC surgery.ConclusionsPreoperative multimodal image reconstruction can help fully evaluate PBC surgery, clarify the etiology, and predict the volume of contrast medium required during the operation. It provided important assistance for PBC treatment of trigeminal neuralgia patients when preoperative multimodal image fusion is combined with intraoperative Dyna CT.

Vascular calcification is prevalent in aging, diabetes, chronic kidney disease, cardiovascular disease, and certain genetic disorders. However, the pathogenesis of vascular calcification is not well-understood. It has been progressively recognized that vascular calcification depends on the bidirectional interactions between vascular cells and their microenvironment. Exosomes are an essential bridge to mediate crosstalk between cells and organisms, and thus they have attracted increased research attention in recent years. Accumulating evidence has indicated that exosomes play an important role in cardiovascular disease, especially in vascular calcification. In this review, we introduce vascular biology and focus on the crosstalk between the different vessel layers and how their interplay controls the process of vascular calcification.

Objective The purpose of this paper is to investigate the effects of senescent nucleus pulposus cell (NPC)‐derived exosomes (SNPC‐Exo) and the roles of the P53/P21 pathway on the senescence of NPC. Methods The senescent phenotypes of NPC were induced by interleukin‐1β treatment. SNPC‐Exo was extracted from the culture medium of senescent NPC and purified by differential centrifugation. The structure of SNPC‐Exo was identified by transmission electron microscopy and western blot analysis was used to determine the exosomal marker proteins CD63 and Tsg101. Western blot analysis was performed to determine the relative expression levels of P16, P21, and P53 in NPC. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining was used to stain the senescent NPC and a phase contrast microscope was used to observe and count the SA‐β‐gal staining of NPC. The proliferation of SNPC‐Exo‐treated NPC was assessed using growth curve analysis and the colony formation assay. The cell cycle of SNPC‐Exo‐treated NPC was determined by flow cytometry. NPC were transfected with siRNA to knock down P53 and P21 expression. Results Interleukin‐1β‐treated NPC had a higher percentage of SA‐β‐gal positive cells (45%) than the control group (20%) and showed an increase in the relative expression of P16, P21, and P53 (P

A new species, Hemiptarsenus jilinus Tao, sp. nov., is described and illustrated. All the type specimens were reared from Chromatomyia horticola (Goureau) (Diptera: Agromyzidae), a leafminer attacking the plants Ixeris polycephala Cass. and Pterocypsela indica (L.) Shih, in Jilin Province, north-eastern China. A key to Chinese species of the genus is provided.

Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set out to explore the possible role of M2 macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3¢ UTR, as identified by dual luciferase reporter gene. Meanwhile, gain- and loss-of function experimentation on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3+ T cell proliferation and the proportion of interferon (IFN)-γ+ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.

Background/Purpose: Effective antiviral-therapy can reduce the risk of liver cirrhosis related hepatocellular carcinoma in patients with chronic hepatitis B and hepatitis C. Yet, the difference of hepatocellular carcinoma development in chronic hepatitis B and hepatitis C patients with cirrhosis after effective antiviral therapy treatment is unknown. In this study, We comprehensive explored the difference among them. Methods: 1363 patients with cirrhosis and hepatitis B virus treated with nucleos(t)ide analogues (NUCs) with completely suppressed virus, and patients with cirrhosis and hepatitis C virus treated with pegylated interferon (peg-IFN)/ribavirin (RBV) combination therapy who achieved sustained virologic response were enrolled. Results: Total 261 developed hepatocellular carcinoma within a median follow-up of 4.25 years. Univariate analysis, patients developed hepatocellular carcinoma tended to be of older age, and had lower platelet counts, were chronic hepatitis B carriers, and had higher serum alfa-fetoprotein (AFP) (≥20 ng/mL), FIB-4 index and APRI scores. Subsequent multivariate analysis revealed older age, lower platelet counts, high AFP levels and chronic hepatitis B carriers were independent risk factors of hepatocellular carcinoma. Conclusion: Our findings identify that chronic hepatitis B patients were with a higher risk of hepatocellular carcinoma compared to chronic hepatitis C patients after achieving virological response. Special attention should be paid to those patients.

Abstract Background Use of statins is associated with a reduced risk of hepatocellular carcinoma (HCC). However, the effect of statin use on HCC recurrence is unclear. This study aimed to evaluate the effect of statin use on recurrence after curative resection among patients with HCC. Methods We retrospectively assessed 820 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statins was defined as use of a statin for at least 3 months before HCC recurrence. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Results Of the 820 patients, 46 (5.6%) used statins (statin group) and 774 (94.4%) did not (non-statin group). During the mean follow-up of 76.5 months, 440 (53.7%) patients experienced recurrence and 146 (17.8%) patients died. The cumulative incidence of HCC recurrence was significantly lower in the statin group than the non-statin group (p = 0.001); OS was not significantly different between groups. In multivariate analysis, age (hazard ratio [HR]: 1.291; p = 0.010), liver cirrhosis (HR: 1.743; p

Objectives: This study aims to explore the role of M2a polarization and formyl peptide receptor (FPR) regulation in the reactivation of Mycobacterium tuberculosis (Mtb) infection. Methods: M1/M2a monocyte percentage and FPR1/2/3 protein expression of blood immune cells were measured in 38 patients with sputum culture (+) active pulmonary TB disease, 18 subjects with latent TB infection (LTBI), and 28 noninfected healthy subjects (NIHS) using flow cytometry method. Results: M1 percentage was decreased in active TB versus either NIHS or LTBI group, while M2a percentage and M2a/M1 percentage ratio were increased. FPR1 expression on M1/M2a, FPR2 expression on M1, and FPR3 expression of M1 were all decreased in active TB versus LTBI group, while FPR1 over FPR2 expression ratio on NK T cell was increased in active TB versus either NIHS or LTBI group. In 11 patients with active TB disease, M1 percentage became normal again after anti-TB treatment. In vitro Mtb-specific antigen stimulation of monocytic THP-1 cells resulted in M2a polarization in association with increased FPR2 expression on M2a. Conclusions: Increased M2a and decreased M1 phenotypes of blood monocyte may serve as a marker for active TB disease, while decreased FPR1 on blood monocyte may indicate LTBI status.

We investigated pneumococcal carriage between children ≦5 years old with otitis media (OM) and those without. Non-PCV13 serotypes were common in both groups; 19A remained the second most common serotype among children with OM despite high PCV13 coverage. This is important when considering a schedule with reduced vaccine doses or reduced valency, and the modification of pneumococcal immunization schedule should be followed up closely to monitor the result of protection against pneumococcal infections.

Introduction: The purpose of this study was to predict the 10-year risk of fracture among people living with HIV (PLWH) using FRAX™, and to determine the risk factors related to a high probability of fractures. Methodology: This study consisted of 288 subjects aged 40 years and above. The ten-year probability of major osteoporotic fractures (MOF) and hip fractures was assessed using the FRAX™ algorithm with bone mineral density (BMD) data. A logistic regression was used to determine risk factors related to a high probability of major osteoporotic fracture and hip fracture. Results: The median 10-year probability of fracture was 3.7% (IQR 2.2–6.2) for MOF and 0.8% (IQR 0.3–2.5) for hip fractures. In addition to old age, previous fracture history, and low T-scores, HCV co-infection was associated with a higher risk of hip fractures in PLWH (AOR: 4.3, 95% CI: 1.29–14.33). Old age and low T-scores were also associated with a high probability of MOF. Conclusions: HCV co-infection among PLWH is associated with a higher risk of hip fracture. Sustained efforts in terms of pharmacologic and non-pharmacologic interventions in PLWH are necessary to prevent osteoporotic fractures, especially in those with HCV co-infections.

IntroductionTo investigate the role of tumor galectin-1 and galectin-3 in patients with lung adenocarcinoma after definitive radiation therapy.MethodsA total of 41 patients with localized lung adenocarcinoma undergoing thoracic radiation therapy without concurrent chemotherapy were enrolled. Their paraffin-embedded lung tissues were sent for immunohistochemical staining for galectin-1 and galectin-3. The clinical treatment outcomes, including overall (OS), locoregional progression-free (LRPFS), and distant metastasis-free (DMFS) survivals, were evaluated. Univariable and multivariable Cox regression analyses were applied.ResultsOverexpression of tumor galectin-1 and galectin-3 were found in 26.8% and 19.5% of patients, respectively. Overexpression of tumor galectin-1 was the most significant prognosticator to predict worse LRPFS in both univariable (p = 0.007) and multivariable analyses (p = 0.022). Besides, patients with overexpression of tumor galectin-1 had a trend of worse OS (p = 0.066) than those with low expression in multivariable analysis, and worse DMFS (p = 0.035) in univariable analysis. The overexpression of tumor galectin-3 had no significant effect on survival outcomes.ConclusionsThe overexpression of tumor galectin-1, but not galectin-3, is associated with poor LRPFS of patients with lung adenocarcinoma after thoracic radiation therapy. Future research on the mechanism of galectin-1 affecting radiation response in lung adenocarcinoma may be worth exploring.