Search

Ulcerative colitis (UC) is a chronic systematic inflammation disorder with increasing incidence, unknown pathogenesis, limited drug treatment, and abundant medical expenses. Dietary intake, as a daily indispensable environment factor, is closely related to UC pathogenesis and prevention. The underlying interactions between dietary intake and UC progression are implicated with the modulation of gut microbiome as well as microbial metabolites, suggesting the complex and systematic characteristics of UC. However, the triangular relationships with dietary intake, gut microbiota homeostasis, and UC have not been well summarized so far. Here we review the recent studies of dietary intake on the regulation of gut microbiome homeostasis as well as modulation of UC progression. These findings suggest that varieties in dietary patterns result in the production of diverse microbial fermentation metabolites, which contribute to gut microbiome homeostasis through multiple manipulations including immune modulation, inflammation restriction as well as epithelial barrier maintenance, thus finally determine the fate of UC progression and give implications for functional food development for prevention and treatment of UC patients.

Non-orthogonal multiple access (NOMA)-enabled coordinated multipoint (CoMP) transmission has great potential in balancing spectrum utilization and interference mitigation in dense cellular networks. However, NOMA reforms the spectrum sharing policy of CoMP transmission due to introducing additional interference among coordinated base stations (BSs), which deteriorates the CoMP transmission rate. In this paper, we investigate the joint optimization of BS clustering and power control for NOMA-enabled CoMP transmission in dense cellular networks to maximize system sum-rate. We first characterize the impact of interference among coordinated BSs on CoMP transmission rate and find that the BS clustering is dependent on NOMA user grouping and restricted by the NOMA decoding condition. We then derive a tight lower bound on the system sum-rate and exploit it to design a joint BS clustering and power control scheme. Specifically, a power control algorithm is designed by a penalty convex-concave procedure to satisfy the NOMA decoding condition and users’ rate requirements. A BS clustering algorithm based on successive convex approximation is designed to iteratively update the BS clustering and NOMA user grouping to increase system sum-rate. Finally, two algorithms are alternately performed until all users successfully access and the system sum-rate converges. Simulation results show that the proposed scheme can efficiently alleviate interference among coordinated BSs to improve system sum-rate and spectrum efficiency of NOMA-enabled CoMP transmission even under high user density.

Osteosarcoma is the most common primary malignancy of the skeleton in children and adults. The outcomes of people with osteosarcomas are unsatisfied. β-Phenethyl isothiocyanate (PEITC) exhibits chemoprevention and chemotherapeutic activities against many human cancers. The molecular mechanism underlying its action on osteosarcoma is still unknown. This study was aimed at investigating the effect of PEITC on human osteosarcoma both in vitro and in vivo. The results showed that PEITC reduced cell viability, inhibited proliferation, and caused G2/M cell cycle arrest in four human osteosarcoma cell lines (MNNG/HOS, U-2 OS, MG-63, and 143B). Then, we found that PEITC altered iron metabolism related to the processes of iron import, storage, and export, which resulted in increased labile iron. Expectedly, PEITC caused oxidative stress as a consequence of GSH depletion-inducing ROS generation and lipid peroxidation. Multiple cell death modalities, including ferroptosis, apoptosis, and autophagy, were triggered in human osteosarcoma cells. Three MAPKs (ERK, p38, and JNK) were all activated after PEITC treatment; however, they presented different responses among the four human osteosarcoma cell lines. ROS generation was proved to be the major cause of PEITC-induced decreased proliferative potential, altered iron metabolism, cell death, and activated MAPKs in human osteosarcoma cells. In addition, PEITC also significantly delayed tumor growth in a xenograft osteosarcoma mouse model with a 30 mg/kg administration dose. In conclusion, this study reveals that PEITC simultaneously triggers ferroptosis, apoptosis, and autophagy in human osteosarcoma cells by inducing oxidative stress.

In mobile edge computing (MEC), the computation offloading of massive users could cause the task uploading congestion to deteriorate the users’ offloading delay. The non-orthogonal multiple access (NOMA) enabled MEC is envisioned to address this issue by allowing multiple users to simultaneously upload their tasks on one subchannel. However, the differentiated uploading delay of users may make task uploading completion inconsistent with NOMA decoding order, which complicates the co-channel interference and restricts NOMA to reducing the uploading delay. In this paper, we characterize the interaction between the differentiated uploading delay and co-channel interference for a pair of NOMA users. Furthermore, we propose a computation offloading scheme to reduce the users’ average offloading delay by jointly optimizing offloading decision and resource allocation. Specifically, the proposed scheme first obtains the optimal power allocation based on the characterized interaction and the closed-form solution of computation resource allocation by convex programming. Then, the NOMA user pairing and offloading decision are iteratively determined by semidefinite relaxation and convex-concave procedure. Simulation results show that the proposed scheme effectively mitigates co-channel interference under differentiated uploading delay of users and outperforms in reducing the users’ average offloading delay and increasing the number of users to offload tasks.

Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC50 value of 33.49 μM at 24 h. PEITC (1, 15, 30 μM) dose-dependently inhibited the cell proliferation, caused G2/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher dose of PEITC (90 mg/kg every day) compromised its anti-osteosarcoma effect. Histological examination showed that multiple cell death processes were initiated, iron metabolism was altered and MAPK signaling pathway was activated in the tumor tissues. In conclusion, we demonstrate that PEITC induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. PEITC has promising anti-osteosarcoma activity. This study sheds light on the redox signaling-based chemotherapeutics for cancers.

BackgroundThe pandemic of COVID-19 is causing a crisis in public health, food systems, and employment. Vaccination is considered as one of the most effective ways for containing the pandemic, but widespread vaccine hesitation on social media may curtail uptake progress. Fully comprehending public sentiment towards the COVID-19 vaccine is critical to building confidence on the vaccines and achieving herd immunity, especially in Japan with inadequate vaccine confidence.ObjectiveThis study aims to explore the opinion and sentiment towards the COVID-19 vaccine in Japanese tweets, before and at the beginning of large-scale vaccinations.MethodsWe collected 144,101 Japanese tweets containing COVID-19 vaccine-related keywords between August 1, 2020, and June 30, 2021. We visualized the trend of number of tweets and identified the critical events that triggered a surge and provided high-frequency unigram and bigram tokens. Also, we performed sentiment analysis and calculated the correlation of number of tweets and positive/negative sentiments with infection, death, and vaccinated cases. we also used the latent Dirichlet allocation (LDA) model to identify topics of tweets. In addition, we conducted analysis on three vaccine brands (Pfizer/Moderna/AstraZeneca).ResultsDaily number of tweets continued growing and the growth accelerated since the large-scale vaccinations in Japan. The sentiment of around 85% tweets were neutral, and the negative sentiment overwhelmed the positive sentiment in the other tweets. Number of tweets strongly correlated (r≥0.5) with infection/death/vaccinated cases, and the number of negative tweets correlated strongly with the number of infection/death cases but weakened after the first vaccination in Japan. LDA identified three public-concerned topics: vaccine appointment and distribution strategy; Different vaccines development progress and approval status of countries; Side effects and effectiveness against mutated viruses. Among vaccines of the three manufactures, Pfizer won the most attention and Moderna the least.ConclusionsOur findings indicated that negative sentiment towards vaccines dominated than positive sentiment in Japan. Changes in number of tweets and sentiments might be driven by critical events related to the COVID-19 vaccine, and negative sentiment continued increasing when numerous adverse accidents occurred at the beginning of large-scale vaccinations. Under the negative sentiment, the concerns of three vaccine brands remains effectiveness and safety with slight differences. The policymakers should provide more evidence about the effectiveness and safety of vaccines and optimize the process of vaccinations.

Introduction: aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease caused by intracranial aneurysm (IA) rupture. Lysyl oxidase (LOX) family genes (LOX-like [LOXL] 1–4) have roles in collagen cross-linking in the extracellular matrix and may be associated with IA rupture. We aimed to explore the association between LOX polymorphisms and the risk of aSAH. Methods This case-control study included two cohorts: 133 and 115 single ruptured and unruptured IA patients, and 65 and 71 multiple ruptured and unruptured IAs patients, respectively. Genotyping of 27 single nucleotide polymorphisms (SNPs) in LOX was performed. Logistic regression analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) of the SNPs of LOX and risk of aSAH. Results LOX rs180044 and LOXL4 rs3793692 were positively associated with the risk of single IA rupture in the recessive model (OR = 5.66, 2.06; 95% CI = 1.22–26.24, 1.11–3.82, respectively) and LOX rs10519694 demonstrated a protective effect on single IA rupture (dominant model: OR = 0.42, 95% CI = 0.21–0.83; recessive model: OR = 0.16, 95% CI = 0.04–0.65; additive model: OR = 0.46, 95% CI = 0.28–0.78). LOXL1 rs2165241, LOXL2 rs1063582, and LOXL3 rs17010021 demonstrated risk effects on multiple IAs rupture. LOXL3 rs17010022 showed a protective effect on multiple IAs rupture (dominant model: OR = 0.41, 95% CI = 0.21–0.82; additive model: OR = 0.51, 95% CI = 0.30–0.85). Discussion LOX and LOXL4 may be susceptible to single IA rupture, whereas LOXL1-3 may have a role in susceptibility to multiple IAs rupture in the Chinese population, suggesting LOX family genes may associated with aSAH.

Background The aim of this study is to explore the spatial heterogeneity of the retention of PFS in children aged 7–9 years in Shanxi Province, North China and investigate the risk factors associated with PFS retention. Methods In this study, 937 children aged 7–9 years from Shanxi Province, China were randomly selected, all of whom had at least one first permanent tooth sealed with PFS in 2016. The children were surveyed after 12 months (in 2017) and 24 months (in 2018). The Geo-detector model was used to explore the spatial heterogeneity of the retention rate of PFS and analyze the influence and interactions of the ecological factors on PFS. Results 3299 teeth from 937 children were analyzed. The PFS full retention rates after 12 months (in 2017) and 24 months (in 2018) were 81.6% and 75.1%, respectively. The incidence of caries of the first molar was 2.1% after 12 months and 5.4% after 24 months. The spatial heterogeneity of the PFS retention rate after 24 months was significant, which was shown as the retention rate of PFS increased from north to south after 24 months. Remarkably, the natural environmental factors exerted greater influence than the socioeconomic and medical resources factors after 12 months, where the interaction of fluorine in water (FW) had the strongest explanatory power of 52% (P P Conclusion The natural environmental factors and medical resources factors are important ecological factors determining the spatial pattern. The government should strengthen medical and technician construction in North China, comprehensively control fluoride in water, optimize the allocation of medical resources, and promote the balanced development of regional medicine.

Background This retrospective study aimed to explore the curative effect of amphotericin B (AMB) and fluorocytosine (5-FC) combined with voriconazole (VOR) in the induction period for the treatment of non-HIV- and non-transplant-associated cryptococcal meningitis (CM). Methods Clinical data from patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. The patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). Results The length of hospital stay in group I was significantly shorter than those in group II (p = 0.000) and group III (p = 0.000). Among the patients who achieved CSF sterility within 10 weeks, the number of days to reach CSF sterility in group I was shorter than that in group II (p = 0.046). The incidence of hypokalemia in group I was significantly lower than those in group II (p = 0.003) and group III (p = 0.004). The incidence of gastrointestinal discomfort in group I was significantly lower than that in group II (p = 0.004). Conclusion AMB plus 5-FC combined with VOR for the induction treatment of non-HIV- and non-transplant-associated cryptococcal meningitis is a better choice than AMB plus 5-FC combined with FLU and AMB plus 5-FC. This new triple antifungal treatment method rapidly cleared the cryptococci from the CSF, substantially shortened the hospital stay, and decreased the incidences of hypokalemia and gastrointestinal discomfort.

This paper aims at shedding light on the impact of unsaturated traffic on the performance of uplink non-orthogonal multiple access (NOMA) transmissions. Nevertheless, the unsaturated traffic gives rise to the discontinuous interference and the inherent interaction of queues, which in turn highly complicates the performance evaluation. By utilizing tools from queuing theory, we first explicitly characterize the stable throughput region, which represents the region of traffic arrival rates on the condition that the queuing delay converges in distribution to a bounded random variable. In light of this, the critical condition under which NOMA can extend the stable throughput region of orthogonal multiple access (OMA) is derived. Then, we propose an algorithmic solution to evaluate the average delay incurred from both queuing and transmission. It is interestingly found that the superiority of NOMA over OMA in terms of average delay heavily hinges on the temporal traffic dynamics of each user. In particular, NOMA enjoys a clear advantage when the traffic arrival rate of the user with stronger channel condition considerably exceeds the traffic arrival rate of the user with weaker channel condition. The derived results can provide helpful guidance to fully leverage the comparative advantages of NOMA under various traffic conditions.

Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells in order to meet the enhanced metabolism and vicious proliferation; meanwhile, they also have to develop an increased antioxidant defense system to cope with the higher oxidant state. Growing numbers of studies have implicated that altering the glutathione antioxidant system is associated with multiple forms of programmed cell death in cancer cells. In this review, we firstly focus on glutathione homeostasis from the perspectives of glutathione synthesis, distribution, transportation, and metabolism. Then, we discuss the function of glutathione in the antioxidant process. Afterwards, we also summarize the recent advance in the understanding of the mechanism by which glutathione plays a key role in multiple forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, and autophagy. Finally, we highlight the glutathione-targeting therapeutic approaches toward cancers. A comprehensive review on the glutathione homeostasis and the role of glutathione depletion in programmed cell death provide insight into the redox-based research concerning cancer therapeutics.

PurposeIntracranial aneurysms (IA) comprise a multifactorial disease with unclear physiological mechanisms. The lysyl oxidase (LOX) family genes (LOX, LOX–like 1–4) plays important roles in extracellular matrix (ECM) reconstruction and has been investigated in terms of susceptibility to IA in a few populations. We aimed to determine whether polymorphisms in LOX family genes are associated with susceptibility to IA in a Chinese population.MethodsThis case-control study included 384 patients with IA and 384 healthy individuals without IA (controls). We genotyped 27 single nucleotide polymorphisms (SNPs) of LOX family genes using the Sequenom MassARRAY® platform. These SNPs were adjusted for known risk factors and then, odds ratios (OR) and 95% confidence intervals (CI) were evaluated using binary logistic regression analysis.ResultsThe result showed that LOX rs10519694 was associated with the risk of IA in recessive (OR, 3.88; 95% CI, 1.12–13.47) and additive (OR, 1.56; 95%CI, 1.05–2.34) models. Stratified analyses illustrated that LOX rs10519694 was associated with the risk of single IA in the recessive (OR, 3.95; 95%CI, 1.04–15.11) and additive (OR, 1.64; 95%CI, 1.04–2.56) models. The LOXL2 rs1010156 polymorphism was associated with multiple IA in the dominant model (OR, 1.92; 95%CI, 1.02–3.62). No associations were observed between SNPs of LOXL1, LOXL3, and LOXL4 and risk of IA.ConclusionLOX and LOXL2 polymorphisms were associated with risk of single IA and multiple IA in a Chinese population, suggesting potential roles of these genes in IA. The effects of these genes on IA require further investigation.

Intracranial aneurysm (IA) is a cerebrovascular disorder in which abnormal dilation of a blood vessel results from weakening of the blood vessel wall. The aneurysm may rupture, leading to subarachnoid hemorrhage with severe outcomes. This study was conducted to identify the genetic factors involved in the etiology of IA. Whole-exome sequencing was performed in three IA-aggregate families to identify candidate variants. Further association studies of candidate variants were performed among sporadic cases and controls. Bioinformatic analysis was used to predict the functions of candidate genes and variants. Twenty variants were identified after whole-exome sequencing, among which eight were selected for replicative association studies. ANK3 c.4403G>A (p.R1468H) was significantly associated with IA (odds ratio 4.77; 95% confidence interval 1.94–11.67; p-value = 0.00019). Amino acid R1468 in ANK3 was predicted to be located in the spectrin-binding domain of ankyrin-G and may regulate the migration of vascular endothelial cells and affect cell–cell junctions. Therefore, the variation p.R1468H may cause weakening of the artery walls, thereby accelerating the formation of IA. Thus, ANK3 is a candidate gene highly related to IA.

Pancreatic lipase (PL) is a key enzyme related to the prevention and treatment of obesity. The aim of the study was to evaluate the inhibitory effects of mulberry leaf polysaccharides (MLP) on PL and possible interaction mechanism, inhibition on lipid accumulation in vitro and in vivo. The results revealed that MLP had obvious inhibitory effects on PL (P 0.05). The interaction of MLP-PL complexes was in a spontaneous way driven by enthalpy, and hydrogen bonds were the main factors in the binding. MLP could significantly inhibit the development of lipid accumulation in HepG2 cells (P 0.05). Furthermore, consumption of high-fat diet containing MLP showed protective effects on liver and adipose tissue damages in mice, and inhibited the lipid absorption in digestive tract. MLP also significantly reduced the increased expression level of pancreatic digestive enzymes (P 0.05). The study indicated that the anti-obesity effect of MLP might be caused by inhibition of lipid absorption via reducing PL activity.

The bone healing defects resulting from bone disease remain a significant clinical challenge. The bone tissue engineering scaffolds combined with osteoinductive compounds represent an effective approach to overcome this challenge. In this study, a novel chitosan-based scaffold was prepared by incorporating modified natural diatomite (DE) as filler and adsorption element. Specifically, modified-diatomite (MDE) was synthesized by grafting polyethyleneimine (PEI) on the surface of diatomite

Ethnopharmacological relevance Cremastra appendiculata (D.Don) Makino is a herbal medicine with a medicinal history of more than a thousand years in China. It is traditionally used to treat carbuncle, swelling, abscess, fistula, scrofula and scleroma (related to modern lymph node enlargement and various tumors.). Aim of the review: This paper comprehensively reviewed the botany, traditional application, phytochemistry, pharmacological activities, and quality control of C. appendiculata, discussesed the application of ethnic medicine, modern scientific research and the relationship between them, and put forward some suggestions to promote the further development and utilization of C. appendiculata. We hope to provide a valuable reference for all researchers who are interested in obtaining relevant information about C. appendiculata. Materials and methods The relevant information on C. appendiculata was collected through published materials and electronic databases, including ancient and modern books, Chinese Pharmacopoeia, Ph.D. and M. Sc. dissertations, PubMed, ScienceDirect, Wiley, ACS, CNKI, Springer, Taylor & Francis, Web of Science, Google Scholar, and Baidu Scholar. Results At present, 190 compounds have been isolated from C. appendiculata, including phenanthrene, dihydrophenanthrene, bibenzyl, flavonoids, terpenoids, glycosides, aromatics, and other compounds. These compounds have been reported to have a variety of pharmacological activities, such as anti-tumor, anti-bacterial, anti-angiogenesis, anti-oxidation, etc. Modern pharmacological studies have proved that C. appendiculata has significant anti-tumor activity and has a good therapeutic effect on liver cancer, gastric cancer, colon cancer, breast cancer, thyroid cancer and other malignant tumors. Conclusions C. appendiculata is not only an excellent traditional Chinese medicine for the treatment of tumors, but also a source of bioactive molecules with good application prospects. At present, the close relationship between the chemical components and pharmacological activities of C. appendiculata has not been established, and there is a lack of systematic and in-depth research on its anti-tumor components and its mechanism. In addition, it is necessary to establish systematic and effective index components and determination standards of C. appendiculata to better explore its therapeutic potential. Therefore, it is necessary to carry out further research on C. appendiculata.

Diabetes mellitus (DM) is a chronic metabolic disorder with various complications that poses a huge worldwide healthcare burden. Wounds in diabetes, especially diabetic foot ulcers (DFUs), are difficult to manage, often leading to prolonged wound repair and even amputation. Wound management in people with diabetes is an extremely clinical and social concern. Nowadays, physical interventions gain much attention and have been widely developed in the fields of tissue regeneration and wound healing. Magnetic fields (MFs)‐based devices are translated into clinical practice for the treatment of bone diseases and neurodegenerative disorder. This review attempts to give insight into the mechanisms and applications of MFs in wound care, especially in improving the healing outcomes of diabetic wounds. First, we discuss the pathological conditions associated with chronic diabetic wounds. Next, the mechanisms involved in MFs’ effects on wounds are explored. At last, studies and reports regarding the effects of MFs on diabetic wounds from both animal experiments and clinical trials are reviewed. MFs exhibit great potential in promoting wound healing and have been practised in the management of diabetic wounds. Further studies on the exact mechanism of MFs on diabetic wounds and the development of suitable MF‐based devices could lead to their increased applications into clinical practice., The possible mechanism of the effects of MFs on diabetic wound healing.

In the present work, we constructed nanoscale graphene oxide (NGO) as a drug nanocarrier to improve the process of tumor-targeted drug releases, promote cellular uptake and accumulation of chemotherapy drugs in tumor tissues, and reduce the toxic effects of chemotherapy drugs on normal cells. Hence, great stability was obtained in the biological solution. Moreover, we designed an effective nanoparticle system for the doxorubicin (DOX) delivery targeting the oral squamous cell carcinoma (OSCC) by mediating the HN-1 (TSPLNIHNGQKL) through hydrogen and π–π bonds. DOX@NGO-PEG-HN-1 showed significantly higher cellular uptakes and cytotoxicity in OSCC cells (CAL-27 and SCC-25), compared to free DOX. Moreover, HN-1 showed considerable tumor-targeting and competition inhibition phenomenon. As we expected, the nanocarrier showed pH-responsive drug release. In total, our study represented a good technique to construct OSCC-targeted delivery of nanoparticles and improve the anticancer medicines’ efficiency.

Intracranial aneurysm (IA) is a complex disease caused by genetic and environmental factors. Evidence indicates that inflammation plays an important role in IA occurrence. We aimed to explore the associations between inflammatory cytokine gene polymorphisms and IA in a Chinese population. This study enrolled 768 participants of Han ethnicity, including 384 patients with IA and 384 healthy individuals. Sixteen single nucleotide polymorphisms (SNPs) of IL1, IL6, IL12, and TNF-α genes were genotyped using the Sequenom MassARRAY platform. Univariate and multivariate logistic regression analyses were used to analyze the associations. We found IL12B rs3181216 was significantly associated with IA in the recessive and additive models ( OR = 0.46 , 95% CI = 0.23–0.89, P = 0.022 ; OR = 0.74 , 95% CI = 0.56–0.98, P = 0.034 , respectively). TNF-α rs1799964 was associated with IA in dominant and additive models ( OR = 0.67 , 95% CI = 0.46–0.98, P = 0.041 ; OR = 0.71 , 95% CI = 0.51–0.98, P = 0.034 , respectively). IL1A rs17561 was associated with single IA susceptibility (dominant model: OR = 0.52 , 95% CI = 0.31–0.85, P = 0.040 ). The IL12B rs3181216 polymorphism was associated with single IA susceptibility in the recessive model ( OR = 0.41 , 95% CI = 0.18–0.93, P = 0.033 ). The IL12B rs2195940 polymorphism was associated with multiple IAs susceptibility (dominant model: OR = 0.28 , 95% CI = 0.09–0.89, P = 0.031 ; additive model: OR = 0.28 , 95% CI = 0.09–0.90, P = 0.032 ). TNF-α rs1799964 was associated with multiple IAs susceptibility in the dominant model ( OR = 0.54 , 95% CI = 0.30–0.97, P = 0.040 ). No associations were found between other polymorphisms and IA susceptibility. Therefore, IL1A, IL12B, and TNF-α gene polymorphisms are associated with IA susceptibility in a Chinese population.

Hepatocyte nuclear factor 3γ (HNF3γ) is a hepatocyte nuclear factor, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unclear. Herein, we report that HNF3γ expression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival. Moreover, our data suggested that the HNF3γ reduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γ mRNA. HNF3γ expression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells. Interestingly, HNF3γ delivery promoted differentiation of not only HCC cells but also liver CSCs, which led to suppression of HCC growth. Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules, which could synergistically facilitate HCC cell differentiation. More importantly, enforced HNF3γ expression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression, which are major membrane transporters for sorafenib uptake. Clinical investigation showed that patient-derived HCC xenografts with high HNF3γ expression exhibited a sorafenib response and patients with high HCC HNF3γ levels benefited from sorafenib therapy. Together, these results suggest that HNF3γ plays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients.

Objective Cerebral arteriovenous malformation (AVM) is characterised by an abnormal tangle of arteries and veins, the rupture of which is a significant portion of the morbidity and mortality cases, especially in young populations. However, the exact risk factors and pathophysiologic mechanisms of AVM remain poorly understood. RNF213 variants have been identified as obvious susceptible factors of several cerebrovascular disorders, such as Moyamoya disease and intracranial aneurysms. Thus, this study aimed to determine whether there is an association between RNF213 rare variants and AVM. Methods The AVM group included 22 patients with AVM. The control group included 1007 samples from the GeneSky in-house database and 208 samples from the 1000 Genome Project of Chinese Han Population. Genomic DNA samples were extracted from the peripheral blood of the AVM patients, and targeted exome sequencing of RNF213 was performed to assess the existence of low-frequency or rare variants. Sanger sequencing was performed to validate the identified variants. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the candidate variants and risk of AVM. Statistical analyses were performed using SPSS version 21.0. Results The RNF213 c.10997T>C variant (amino acid mutation p.M3666T, NM_001256071) was observed in two AVM patients after filtration. It was significantly associated with AVM in the Chinese population (ORs, 10.30 and 25.08; 95 %; CIs, 1.38–77.10 and 4.34–144.90 compared with 1000 Genome Project of Chinese Han Population and GeneSky in-house database, respectively). Conclusion Rare variants of RNF213 are associated with AVM in the Chinese population, suggesting the important role of RNF213 in AVM. Further studies are needed to verify these findings.

The increased prevalence of obesity significantly affects human health worldwide. Improvement of glycometabolism by dietotherapy/herbal remedy is an effective approach to ameliorate obesity. In this study, high-fat-diet induced obese (DIO) mice were treated with mulberry leaves for 13 weeks. The results showed that mulberry leaves significantly alleviated adiposity of DIO mice including reducing body weight gain, fat accumulation and fasting blood glucose, and improving insulin sensitivity. In addition, mulberry leaves had protective effects on liver and kidneys. The abundant flavonoids, polyphenols and 1-deoxynojirimycin in mulberry leaves were likely responsible for their beneficial effects. Mechanistically, we found that mulberry leaves could alleviate obesity by enhancing brown adipose tissue (BAT) activity partly indicated by elevated thermogenesis and overexpression of uncoupling protein 1 in BAT. Moreover, mulberry leaves significantly increased the Bacteroidetes/Firmicutes ratio and Akkermansia level that were closely associated with obesity development and progression, and decreased the potential proinflammatory Proteobacteria in feces. These findings reveal that the mulberry leaf is an edible plant food with therapeutic potential for obesity and may provide dietotherapy/herbal remedy to the treatment of obesity and its complications.

Brown adipose tissue (BAT) plays an essential role in maintaining body temperature and in treating obesity and diabetes. The adult BAT (aBAT) and neonatal BAT (neBAT) vary greatly in capacity, but the characteristics and differences between them on the molecular level, as well as the related features of BAT as it develops post-delivery, have not yet been fully determined. In this study, we examined the morphological features of aBAT and neBAT of mice by using hematoxylin-eosin (H&amp, E) staining, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We found that neBAT contains a smaller number and size of lipid droplets, as well as more abundant mitochondria, compared with aBAT. The dynamic morphological changes revealed that the number and size of lipid droplets increase, but the number of mitochondria gradually decrease during the post-delivery development, which consisted of some differences in RNA or protein expression levels, such as gradually decreased uncoupling protein 1 (UCP1) expression levels and mitochondrial genes, such as mitochondrial transcription factor A (Tfam). The adipocyte differentiation-related genes, such as transcription factor CCAAT enhancer-binding protein &beta, (CEBP&beta, ), were also continuously upregulated. Additionally, the different features of aBAT and neBAT were analyzed from the global transcription (RNA-Seq) level, which included messenger RNA (mRNA), microRNA, long non-coding RNA (lncRNA), circRNA, and DNA methylation, as well as proteins (proteomics). Differentially methylated region (DMR) analysis identified 383 hyper- and 503 hypo-methylated genes, as well as 1221 new circRNA in ne-BAT and 1991 new circRNA in a-BAT, with significantly higher expression of circRNA in aBAT compared with neBAT. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that mitochondrial activity, protein synthesis, and cell life activity levels were higher in neBAT, and pathways related to ribosomes, spliceosomes, and metabolism were significantly activated in neBAT compared to aBAT. Collectively, this study describes the dynamic changes occurring throughout post-delivery development from the morphological, molecular and omics perspectives. Our study provides information that may be utilized in improving BAT functional activity through gene regulation and/or epigenetic regulation.

Non-orthogonal multiple access mobile edge computing (NOMA-MEC) is proposed to enhance the connectivity between the edge node and users for low- latency computation offloading. However, it is asynchronous for users to complete the task uploading, which complicates the co-channel interference between NOMA users to affect overall offloading delay. In this paper, we first characterize the impact of this asynchronism in task uploading on interference management in NOMA enabled computation offloading. The optimal power allocation is proposed to coordinate the co-channel interference between both NOMA users. Then, we propose a multi- user offloading scheme to jointly optimize offloading decision and NOMA user pairing, aiming to minimize the users' average delay on executing their tasks. The proposed offloading scheme is designed by formulating a binary nonlinear problem, which is solved by the proposed relaxation method and heuristic algorithm. Simulation results demonstrate that compared with other NOMA based schemes, our proposed scheme can effectively reduce the average delay of users and increase the number of users to perform computation offloading.

Obesity is associated with disrupted energy homeostasis and intestinal dysbiosis. Caulis Spatholobi, traditional Chinese medicine for herbal therapy, contains a wide range of bioactive compounds and has a specific pharmacological function. However, its effects on obesity and related metabolic disorder have remained largely unexplored. In this study, we showed that the water extract of Caulis Spatholobi (WECS) has a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, reducing insulin resistance and improving hepatic steatosis in diet-introduced obesity (DIO) mice. Besides, the administration of WECS significantly increased the expression levels of genes involved in the brown adipose tissue (BAT) activation and thermogenesis in DIO mice. Also, the activation of BAT treated with WECS was also confirmed in BAT primary cells. Mechanisms, the improvement of glucose homeostasis and insulin resistance may be related to the upregulated MAPK and AMPK pathways in white adipose tissue (WAT) and BAT. Notably, WECS also improved the obesity-induced gut microbiota dysbiosis, which induced an increase of anti-obesity and anti-diabetes related bacteria genus. In conclusion, Caulis Spatholobi can ameliorate obesity through activating brown adipose tissue and modulating the composition of gut microbiota. Our findings provide a novel perspective on Chinese medicine applications and provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.

Iron, an indispensable element for life, is involved in all kinds of important physiological activities. Iron promotes cell growth and proliferation, but it also causes oxidative stress damage. The body has a strict regulation mechanism of iron metabolism due to its potential toxicity. As a cancer of the bone marrow and blood cells, leukemia threatens human health seriously. Current studies suggest that dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the occurrence and progress of leukemia. Specifically, excess iron promotes the development of leukemia due to the pro-oxidative nature of iron and its damaging effects on DNA. On the other hand, leukemia cells acquire large amounts of iron to maintain rapid growth and proliferation. Therefore, targeting iron metabolism may provide new insights for approaches to the treatment of leukemia. This review summarizes physiologic iron metabolism, alternations of iron metabolism in leukemia and therapeutic opportunities of targeting the altered iron metabolism in leukemia, with a focus on acute leukemia.

Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has been applied for breast cancer treatment. However, its efficacy against glioblastoma has not been well clarified. Here, effects of CDK4/6 inhibitors on various kinds of GBM cell lines are investigated and the functional mechanisms are identified. Data showed that cells with diverse PTEN status respond to palbociclib differently. Gain-of-function and loss-of-function studies indicated that PTEN enhanced the sensitivity of GBM cells to palbociclib in vitro and in vivo, which was associated with suppressions of Akt and ERK signaling and independent of Rb signaling inhibition. Hence, our findings support that palbociclib selectively.

Background Esophagogastric varices (EGV) is a major consequence of portal hypertension highly associated with dreadful variceal hemorrhage, and complete variceal eradication may greatly improve recurrence and prognosis. Little is known about the endoscopic resources invested for EGV eradication in China. This observational study aimed to clarify the practice of variceal eradication by modern combination endoscopic strategies and investigate factors associated with treatment sessions. Methods Clinical data were extracted from the endoscopic recording database and medical charts. Cirrhotic patients underwent the initial endoscopic treatment in our department and followed up for more than 2 months were included between Oct 2011 to Jun 2018. Endoscopic sequential therapy (EST) is an integrated protocol comprising endoscopic cyanoacrylate injection (ECI) sequenced by repeated sessions of endoscopic band ligation (EBL) and/or endoscopic injection sclerotherapy (EIS), and this protocol was performed for every patient. Patients were intensively followed up until complete EGV eradication. Results Among the 337 patients recruited to follow up, 291 (86.4%) who successfully reached variceal eradication were included for analysis. A total of 1029 episodes of endoscopic treatments were performed for the patients. Among them, 132 (45.4%) patients had Child-Pugh class B or C liver disease, and 46 (15.8%) had MELD score equal or over 15. EBL was the most prevalent method used in 283 (97%) patients, followed by ECI for 121 patients (41.6%) and EIS for 53 patients (18.2%). A mean 3.5 sessions of endoscopic therapy was needed to reach complete variceal eradication during an average of 9.6 months (range, 24 days-75 months). The median endoscopic interval between sessions for each patient was 2.0 months (IQR 1.3–3.0). There was a significant positive association between portal vein diameter and both the number of endoscopic sessions (P Conclusions Most cirrhotic patients with EGV undergoing EST would achieve variceal eradication. EVL is the mainstay of the endoscopic method. Portal vein diameter is related to endoscopic resources invested for variceal eradication. Interval between sessions is far from optimal in China and physicians should pay more attention to patient compliance in clinical practice.

Background RNF213 rare variant-p.R4810K (rs112735431) was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. Considering the allelic heterogeneity, we performed target exome sequencing of RNF213 with the aim to identify the rare variants spectrum and their association with ICASO in a Chinese population and further to explore whether the rare variants carrier patients present specific clinical phenotype. Methods Target exome sequencing of RNF213 was performed in 250 ICASO patients using FastTarget sequencing technology. Various filtering process were used to select the candidate variants. Control individuals were obtain from 1000 Genome Project (208 Chinese samples) and GeneSky in-house database (1007 samples). Gene-based association analyses were conducted to identify the association between RNF213 rare variants and ICASO. The clinical characteristics of rare variant carriers and non-carriers were compared using Chi-squared test or Fisher’s exact test. Results After filtration, 18 rare variants were identified in 39 patients. Gene-based association test showed that rare variants of RNF213 were significantly associated with ICASO (Minor allele frequency

Optical coherence tomography (OCT) is a three-dimensional non-invasive high-resolution imaging modality that has been widely used for applications ranging from medical diagnosis to industrial inspection. Common OCT systems are equipped with limited field-of-view (FOV) in both the axial depth direction (a few millimeters) and lateral direction (a few centimeters), prohibiting their applications for samples with large and irregular surface profiles. Image stitching techniques exist but are often limited to at most 3 degrees-of-freedom (DOF) scanning. In this work, we propose a robotic-arm-assisted OCT system with 7 DOF for flexible large FOV 3D imaging. The system consists of a depth camera, a robotic arm and a miniature OCT probe with an integrated RGB camera. The depth camera is used to get the spatial information of targeted sample at large scale while the RGB camera is used to obtain the exact position of target to align the image probe. Eventually, the real-time 3D OCT imaging is used to resolve the relative pose of the probe to the sample and as a feedback for imaging pose optimization when necessary. Flexible probe pose manipulation is enabled by the 7 DOF robotic arm. We demonstrate a prototype system and present experimental results with flexible tens of times enlarged FOV for plastic tube, phantom human finger, and letter stamps. It is expected that robotic-arm-assisted flexible large FOV OCT imaging will benefit a wide range of biomedical, industrial and other scientific applications.

Summary Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a natural product in garlic, has multiple biological and pharmacological functions. However, the role of allicin in the regulation of metabolic organs, particularly BAT activation, has not been well studied. Here, we show that allicin imparts a significant effect by inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in obese mice. These observations strongly correlate with the activation of BAT. Notably, allicin plays a role in BAT activation, which may partly contribute to the Sirt1-PGC1α-Tfam pathway. In addition, allicin can significantly increase the succinylation levels of UCP1 in BAT by inhibiting sirt5, whereas excess allicin induces autophagy/mitophagy and mitochondrial dysfunction. Thus, our findings point to allicin as a promising therapeutic approach for the treatment of obesity and metabolic disorders., Graphical Abstract, Highlights • Allicin reduces adiposity and maintains glucose homeostasis • Allicin activates the brown adipocytes and increases the energy expenditure • Allicin enhances BAT activity partly through SIRT1-PGC1a-Tfam signaling pathway • Allicin regulates mitophagy via suppressed sirt5-mediated succinylation accumulation, Biological Sciences; Human Physiology; Molecular Physiology

With rapid economic development, the prevalence of obesity has increased remarkably worldwide. Obesity can induce a variety of metabolic diseases, such as atherosclerosis, diabetes, hypertension and coronary heart disease, which significantly endanger the health and welfare of individuals. Brown and beige fat tissues play an important role in thermogenesis in mammals. Recent studies have shown that follistatin (FST) can potentially induce the browning of white adipose tissue (WAT). In this study, high-fat diet-induced obese mice were injected with follistatin for one week to explore the effects of follistatin on browning and metabolism and to determine the mechanism. The results showed that follistatin suppressed obesity caused by a high-fat diet and increased insulin sensitivity, energy expenditure, and subcutaneous fat browning. The beneficial effects remained even after a period of withdrawal. Follistatin promoted secretion of irisin from subcutaneous fat via the AMPK-PGC1α-irisin signal pathway, which induces browning of WAT, and activated the insulin pathway in beige fat thereby promoting metabolism.

Background Abnormal neutrophils are involved in many chronic endocrine diseases, including type 2 diabetes mellitus (T2DM), and in periodontitis (PD), which is a chronic inflammatory disease in which neutrophils play a vital role. The p38 mitogen-activated protein kinase (MAPK) signaling pathway participates in the apoptosis of many inflammatory cells. Additionally, 1,25-dihydroxyvitamin-D3 (1,25VitD3) as a regulator can induce responses to infection and tumor cell apoptosis. However, the effect of 1,25VitD3 in the pathogenic relationship between T2DM and PD remains unclear. The aim of this study was to assess the effect of 1,25VitD3 on neutrophil apoptosis in patients with T2DM and PD and the p38-MAPK-relevant signaling pathway mechanism in this process in vitro. Methods Neutrophils were stained with Wright's stain, and apoptosis was detected by flow cytometry and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Apoptosis- and p38-related mRNAs and proteins were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and ELISA. The internal relationships were analyzed using a linear regression equation and Pearson's correlation coefficient. Results The highest rate of neutrophil apoptosis occurred in cultures treated with 10–8 mol/L 1,25VitD3 in the T2DM-PD group. The apoptosis rate in the T2DM-PD-p38 inhibitor group was higher than that in the healthy control group. Western blot, ELISA and qRT-PCR results showed that the mRNA and protein expression profiles of Caspase-3 and Bax were highly up-regulated and that Bcl-2 was down-regulated in the T2DM-PD-p38 inhibitor group. The expression levels of apoptotic mRNAs and proteins in the T2DM and T2DM-PD groups were significantly higher than those in the T2DM-p38 and T2DM-PD-p38 inhibitor groups. 1,25VitD3-induced neutrophil apoptosis and phosphorylated p38 (p-p38) expression were partially inhibited by the p38 inhibitor. Expression levels of apoptosis-related genes and p-p38 in neutrophils were positively associated with increasing concentrations of 1,25VitD3. p-p38 protein expression was positively associated with the level of serum 1,25VitD3. Conclusion 1,25VitD3 could promote peripheral blood neutrophil apoptosis in patients with T2DM and PD through activation of the p38-MAPK signaling pathway in vitro.

Genomic studies have established a set of three core-signaling pathways, receptor tyrosine kinase (RTK), p53 and retinoblastoma (Rb) signaling pathways, contributing glioblastoma (GBM) and revealed that dysregulation of at least two pathways is required for GBM progression. In the present study, we investigate efficacy of combination of palbociclib, cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and erlotinib, epidermal growth factor receptor (EGFR) inhibitor in GBM cell systems with different p53 status. Cell proliferation and colony formation assays showed that the combination treatment synergistically suppressed GBM cell proliferation. LN229 cells with mutant p53 and wild-type PTEN were more sensitive to the combination treatment. Further studies indicated that the synergetic anti-GBM effects were due to cell apoptosis induction and cell cycle arrest at G1 phase. Signaling examination indicated that levels of p-Rb and p-4E-BP1 significantly decreased by the combination treatment; however, Akt and MAPK signaling were differentially suppressed among the three GBM cell lines. Hence, our data demonstrate that palbociclib and erlotinib exert synergistic anti-GBM activity, providing pre-clinical evidence and a proof-ofconcept that usage of the combination of EGFR and CDK4/6 inhibitors for GBM treatment.

Tuberculosis (TB) is a widespread and highly contagious disease that may lead serious harm to patient health. With the development of neural network, there is increasingly attention to apply deep learning on TB diagnosis. Former works validated the feasibility of neural networks in this task, but still suffer low accuracy problem due to lack of samples and complexity of radiograph information. In this work, we proposed an end-to-end neural network system for TB diagnosis, combining preprocessing, lung segmentation, feature extraction and classification. We achieved accuracy of 0.961 in our labeled dataset, 0.923 and 0.890 on Shenzhen and Montgomery Public Dataset respectively, demonstrating our work outperformed the state-of-the-art methods in this area.

Considerable evidence has shown that the Wnt/β-catenin pathway is involved in osteogenic differentiation in various stem cells. However, the role of Wnt/β-catenin pathway in regulating the osteogenic differentiation of rat ectomesenchymal stem cells (EMSCs), which are considered to be the progenitors of dental mesenchymal stem cells, remains unknown. In this study, we demonstrated that nuclear β-catenin was upregulated during EMSC osteogenic differentiation. The Wnt signalling inhibitor IWR-1-endo inhibited EMSC osteogenic differentiation, while the Wnt signalling agonist SKL2001 promoted it. Moreover, nuclear β-catenin was further upregulated by the overexpression of low-affinity nerve growth factor receptor (LNGFR) during EMSC osteogenic differentiation. Further experiments demonstrated that LNGFR overexpression enhanced EMSC osteogenic differentiation, while LNGFR silencing decreased it. Additionally, IWR-1-endo attenuated LNGFR-enhanced EMSC osteogenic differentiation. Collectively, our data reveal that LNGFR targets the Wnt/β-catenin pathway and positively regulates EMSC osteogenic differentiation, suggesting that Wnt/β-catenin pathway may be involved in the development of teeth and that the targeting Wnt/β-catenin pathway may have great potential for applications in dental tissue engineering regeneration.

Aberrant N-glycosylation caused by altered N-acetyl glucosaminyltransferase V (GnT-V) expression is known to regulate tumor invasion and metastasis by modulating multiple cytokine signaling pathways. However, the exact role of GnT-V in the development of liver fibrosis has not been clearly defined. Here, we induced mouse liver fibrosis by ip injections of carbon tetrachloride (CCl4) or thioacetamide (TAA) and observed significant increase of hepatic GnT-V during the processes of liver fibrogenesis. Meanwhile, upregulations of GnT-V were detected in the activated hepatic stellate cells (HSCs) and injured hepatocytes. To knock down hepatic GnT-V expression, adenovirus that expressed the GnT-V siRNA was injected via the tail vein. Adenovirus-mediated delivery of GnT-V siRNA dramatically reduced the GnT-V expression in fibrotic liver and activated HSC in vivo and consequently alleviated CCl4- or TAA-induced liver fibrosis as assessed through collagen deposition and profiles of profibrogenic markers. Furthermore, knockdown of GnT-V in HSCs reduced transforming growth factor beta (TGF-β)/Smad signaling and blunted the activated HSC phenotype. The suppression of TGF-β/Smad signaling in HSCs correlated with the decrease of GnT-V-modified β1,6-branched N-glycan on TGF-β receptors. Knockdown of GnT-V also suppressed platelet-derived growth factor (PDGF)-induced HSC proliferation and migration through inhibiting PDGF/Erk signaling. Finally, we demonstrated that knockdown of GnT-V profoundly suppressed TGF-β1-induced epithelial-mesenchymal transition (EMT) in hepatocytes by morphological assessment and reversal of EMT markers. In conclusion, this study demonstrates that GnT-V is implicated in hepatotoxin-induced liver fibrosis, and targeting GnT-V may be a feasible and promising approach for treating liver fibrosis.

Ameloblastic fibro-odontosarcoma (AFOS) is an extremely rare subtype of odontogenic sarcoma, with no more than 19 cases reported in the English literature to date. AFOS is a biphasic neoplasm, with deposits of dentin and enamel matrix. We herein present a case of AFOS with active epithelial proliferation in a 31-year-old female patient. The patient was referred to the West China Hospital of Stomatology (Chengdu, China) due to a 6-month history of a swelling in the left mandible. Following clinical and radiological examination, the initial preoperative diagnosis was ameloblastoma, with local invasion and the possibility of malignant transformation. Left hemimandibular resection was subsequently performed. The postoperative histopathological diagnosis was AFOS, accompanied by active epithelial proliferation. Immunohistochemically, cytokeratin (CK)14 and CK19 were intensely positive in the epithelium, whereas the mesenchymal cells were strongly positive for vimentin. The Ki-67 labeling index was considerably higher in the mesenchymal component (mean, 40%) compared with that in the epithelial element (mean, 5-8%). Three months after the surgical procedure, the patient remained clinically and radiologically disease-free.

A simple and sensitive gas chromatography method for the simultaneous determination of esbiothrin and D-acetylene C permethrin in electric-mosquito coils using palmitic acid isopropyl as an internal standard was developed. The electric-mosquito coil samples were extracted with petroleum ether (60–90 °C) and then centrifuged at 2,000 r/min for 2.0 min. The supernatant liquids were collected into a glass bottle and 2.0 µL of it was injected into the gas chromatograph. The results showed that the means recoveries of esbiothrin and acetylene c permethrin ranged from 100.2% to 99.8%. The relative standard deviation (n=10) of allylic permethrin and acetylene C permethrin was 0.44% and 0.26%, respectively. This method is a viable alternative tool to the existing gas chromatography methods for analyzing the content of allylic permethrin and D-acetylene C permethrin in electric-mosquito coil samples.

Gastroretentive drug delivery system is a promising option for the treatment of Helicobacter pylori infection, which can prolong gastric residence time and supply high drug concentration in the stomach. In the present study, a low density system of metronidazole-loaded porous Eudragit® RS microparticle with high drug loading capacity (>25%) was fabricated via electrospray method. The porous structure and size distribution of microparticles were affected by polymer concentration and flow rate of solution. FTIR and XRD analyses indicated that drug has been entrapped into the porous microparticles. In addition, sustained release profiles and slight cytotoxicity in vitro were detected. Gamma scintigraphy study in vivo demonstrated that 131I-labeled microparticles retained in stomach for over 8 h, and about 65.50% radioactive counts were finally detected in the region of interest. The biodistribution study confirmed that hotspot of radioactivity was remaining in the stomach. Furthermore, metronidazole-loaded porous microparticles can eradicate H. pylori completely with lower dose and administration frequency of antibiotic compared with pure drug, which were also more helpful for the healing of mucosal damages. These results suggest that prepared porous microparticle has the potential to provide better treatment for H. pylori infection.

The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

Objectives The aim of this study was to investigate whether p75NTR (p75 neurotrophin receptor) regulates differential mineralization capacity of rEMSCs (rat ectomesenchymal stem cells) and underlying mechanisms associated with Mage-D1 (melanoma-associated antigens-D1). Materials and methods Immunohistochemical staining of p75NTR in developing tooth germs was performed on E12.5d (embryonic 12.5 days) and E19.5d (embryonic 19.5 days). E12.5d EMSCs and E19.5d EMSCs were isolated in the same pregnant Sprague-Dawley rats from embryonic maxillofacial processes and tooth germs. p75NTR small-interfering RNA, p75NTR overexpression plasmid, Mage-D1 small-interfering RNA and recombined rat NGF were used to transfect cells. Results p75NTR was expressed in epithelial-mesenchymal interaction areas at E12.5d and E19.5d tooth germ development stages. E19.5d EMSCs had higher p75NTR expression levels and differential mineralization capacity but lower levels of cell proliferation. Under induction by mineralized culture medium, the potential of differential mineralization had identical trends in regulation of p75NTR in EMSCs; Mage-D1 did not fluctuate and TrkA was not expressed. Binding of p75NTR and Mage-D1 were detected. Mage-D1 knockdown significantly down-regulated expression of related genes, which NGF could not rescue. Conclusion p75NTR participated in tooth germ development stages and mediated differential mineralization of EMSCs. p75NTR played a critical role in regulating the potential of differential mineralization of EMSCs. Mage-D1 seemed to act as a bridge in the underlying mechanism of effects of p75NTR.

Epithelial-to-mesenchymal transition (EMT) has been implicated in embryonic development and various pathological events. Snail1 is a well-known E-cadherin-transcriptional repressor that is significantly upregulated during the TGF-β1-induced EMT in hepatocyte. However, the functional involvement of microRNA during the EMT process in hepatocyte remains to be determined. Here, we revealed that while the expression of Snail1 increased during the TGF-β1-induced EMT in AML12 murine hepatocytes, the expression of miR-30 family members exhibited significant downregulation. Computational microRNA target predictions detected a conserved sequence matching to the seed region of miR-30 in the 3'UTR of Snail1 mRNA. Our results demonstrated that miR-30 could negatively regulate the expression of Snail1 by direct targeting the predicted binding site. More importantly, transfection of miR-30b mimics significantly inhibited the TGF-β1-induced EMT in AML12 cells as assessed through cell morphology changes and the expression profiles of Snail1, E-cadherin and other fibroblast markers. Finally, we demonstrated that TGF-β1-induced hepatocyte migration was greatly suppressed in cells transfected with miR-30b mimics. Our results provide a new insight into the role of miR-30 in regulating EMT, which could be of importance in understanding the related physiologic and pathologic processes.