AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4.

Diabetic retinopathy (DR) is a common microvascular complication that causes visual impairment or loss. Aquaporin 4 (AQP4) is a regulatory protein involved in water transport and metabolism. In previous studies, we found that AQP4 is related to hypoxia injury in Muller cells. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective cation channel protein involved in the regulation of a variety of ophthalmic diseases. However, the effects of AQP4 and TRPV4 on ferroptosis and oxidative stress in high glucose (HG)-treated Muller cells are unclear. In this study, we investigated the functions of AQP4 and TRPV4 in DR. HG was used to treat mouse Muller cells. Reverse transcription quantitative polymerase chain reaction was used to measure AQP4 mRNA expression. Western blotting was used to detect the protein levels of AQP4, PTGS2, GPX4, and TRPV4. Cell count kit-8, flow cytometry, 5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide staining, and glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits were used to evaluate the function of the Muller cells. Streptozotocin was used to induce DR in rats. Haematoxylin and eosin staining was performed to stain the retina of rats. GSH, SOD, and MDA detection kits, immunofluorescence, and flow cytometry assays were performed to study the function of AQP4 and TRPV4 in DR rats. Results found that AQP4 and TRPV4 were overexpressed in HG-induced Muller cells and streptozotocin-induced DR rats. AQP4 inhibition promoted proliferation and cell cycle progression, repressed cell apoptosis, ferroptosis, and oxidative stress, and alleviated retinal injury in DR rats. Mechanistically, AQP4 positively regulated TRPV4 expression. Overexpression of TRPV4 enhanced ferroptosis and oxidative stress in HG-treated Muller cells, and inhibition of TRPV4 had a protective effect on DR-induced retinal injury in rats. In conclusion, inhibition of AQP4 inhibits the ferroptosis and oxidative stress in Muller cells by downregulating TRPV4, which may be a potential target for DR therapy.

Same effect of biquadratic exchange interaction and Heisenberg linear interaction in a spin spiral.

Monolayer (ML) NiCl2 exhibits a strong biquadratic exchange interaction between the first neighboring magnetic atoms (B1), as demonstrated by the spin spiral model in J. Ni et al., Phys. Rev. Lett., 2021, 127, 247204. This interaction is crucial for stabilizing the ferromagnetic collinear order within the ML NiCl2. However, they neither point out the role of B1 nor discuss the dispersion relation from spin orbit coupling (SOC) in the spin spiral. As we have done in this work, these parameters might theoretically potentially be derived directly by fitting the calculated spin spiral dispersion relation. Here, we draw attention to the fact that B1 is equivalent to half of J3 in Heisenberg linear interactions and that the positive B1 partially counteracts the negative J3's impact on the spin spiral to make the ML NiCl2 ferromagnetic. The comparatively small J3 + 1/2B1 from the spin spiral led us to believe that J3 could be substituted by B1, yet it still exists and plays a crucial function in magnetic semiconductors or insulators. The dispersion relation, which we also obtain from SOC, displays weak antiferromagnetic behavior in the spin spiral.

A survey on the degree of eye discomfort caused by video terminal use among college students in different altitudes.

OBJECTIVE: To analyze the risk factors associated with different levels of eye discomfort due to video terminal use among college students at different altitudes. METHODS: This cross-sectional study was conducted to assess the prevalence and extent of eye discomfort by distributing an questionnaire to university students via the Internet. To analyze the causes and risk factors of eye discomfort among college students at different altitudes after using video terminals. RESULTS: A total of 647 participants who met the criteria were included in this survey, of whom 292 (45.1%) were males and 355 (54.9%) were females. The results of the survey showed 194 (30.0%) participants without eye discomfort and 453 (70.0%) participants with eye discomfort. The results of the univariate comparison of the degree of eye discomfort in the study subjects with different characteristics showed that the differences in the degree of eye discomfort were statistically significant (P < 0.05) for the 7 groups of indicators: gender, region, wearing corneal contact lenses for more than 2 h per day, frequent use of eye drops, sleep time, total time of VDT use per day, and total time per VDT use, while the remaining indicators, including age, profession, and whether refractive surgery or other eye surgery was performed, whether frame glasses were worn for a long time, and duration of daily mask wear were not statistically significant. The results of multi-factor logistic analysis of the degree of eye discomfort in the study subjects with different characteristics showed that gender, region, frequent use of eye drops, sleep time, and total time of VDT use per day were the risk factors affecting the degree of eye discomfort. CONCLUSIONS: Female, high altitude, frequent use of eye drops, shorter daily sleep duration and longer daily VDT use were associated risk factors for the development of severe eye discomfort, where the severity of eye discomfort was significantly negatively correlated with increased sleep duration and significantly positively correlated with increased total time of VDT use.

Cost-Effectiveness of Pit and Fissure Sealing at Schools for Caries Prevention in China: A Markov Modeling Analysis.

The World Health Organization states that the application of pit and fissure sealants (PFSs) is an effective way to prevent dental caries. Estimates of potential health and economic impacts of PFS upon school-age children provide crucial evidence to support the extension of PFS coverage to all target populations. The China Children's Oral Disease Comprehensive Intervention Project was launched in 2009 to provide free oral health examinations, PFS application, and oral health education for children aged 7 to 9 years. However, the national-level health and economic impacts of the program are unclear. To provide higher quality evidence at the national level in China, we developed a multi-perspective, multistate Markov model to estimate the cost and effect of PFS application to prevent dental caries. The total cost of the PFS project was 2.087 billion CNY, which can prevent 16.06 million PFMs from caries lesions. Compared with no intervention, PFS application was cost-effective from payer and society perspectives (BCR = 1.22 from the payer's perspective, BCR = 1.91 from the societal perspective). The incremental cost-effectiveness ratio from both perspectives was negative (-61.46 CNY from the payer's perspective, and -125.75 CNY from the societal perspective), indicating that PFS was cost-effective and cost-saving. Expanding the coverage of PFS application in school can be a more cost-effective strategy for caries prevention in China.

Soy Protein Isolate-Chitosan Nanoparticle-Stabilized Pickering Emulsions: Stability and In Vitro Digestion for DHA.

The purpose of the study was to investigate the stability and oral delivery of DHA-encapsulated Pickering emulsions stabilized by soy protein isolate-chitosan (SPI-CS) nanoparticles (SPI-CS Pickering emulsions) under various conditions and in the simulated gastrointestinal (GIT) model. The stability of DHA was characterized by the retention rate under storage, ionic strength, and thermal conditions. The oral delivery efficiency was characterized by the retention and release rate of DHA in the GIT model and cell viability and uptake in the Caco-2 model. The results showed that the content of DHA was above 90% in various conditions. The retention rate of DHA in Pickering emulsions containing various nanoparticle concentrations (1.5 and 3.5%) decreased to 80%, while passing through the mouth to the stomach, and DHA was released 26% in 1.5% Pickering emulsions, which was faster than that of 3.5% in the small intestine. After digestion, DHA Pickering emulsions proved to be nontoxic and effectively absorbed by cells. These findings helped to develop a novel delivery system for DHA.

Lentinan protects Caenorhabditis elegans against fluopyram-induced toxicity through DAF-16 and SKN-1 pathways.

Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.

Stress granules in the spinal muscular atrophy and amyotrophic lateral sclerosis: The correlation and promising therapy.

Increasing genetic and biochemical evidence has broadened our view of the pathomechanisms that lead to Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases with similar symptoms and causes. Stress granules are dynamic cytosolic storage hubs for mRNAs in response to stress exposures, that are evolutionarily conserved cytoplasmic RNA granules in somatic cells. A lot of previous studies have shown that the impaired stress granules are crucial events in SMA/ALS pathogenesis. In this review, we described the key stress granules related RNA binding proteins (SMN, TDP-43, and FUS) involved in SMA/ALS, summarized the reported mutations in these RNA binding proteins involved in SMA/ALS pathogenesis, and discussed the mechanisms through which stress granules dynamics participate in the diseases. Meanwhile, we described the applications and limitation of current therapies targeting SMA/ALS. We futher proposed the promising targets on stress granules in the future therapeutic interventions of SMA/ALS.

Quantitative analysis of 17 hypoglycemic drugs in fingerprints using ultra-high-performance liquid chromatography/tandem hybrid triple quadrupole linear ion trap mass spectrometry.

RATIONALE: The objective of this study was to develop, optimize, and validate a method for the determination and quantification of 17 hypoglycemic drugs in fingerprints using ultra-high-performance liquid chromatography/tandem hybrid triple quadrupole linear ion trap mass spectrometry (UHPLC/QTRAP-MS/MS). We also aimed to apply the present method to the fingerprints collected from patients with hyperglycemia. METHODS: The scheduled multiple reaction monitoring information-dependent acquisition-enhanced product ion (SMRM-IDA-EPI) scanning mode was utilized. The chromatographic system consisted of an Acquity UHPLC® BEH C18 column (3.0 × 100 mm, 1.7 µm) and a mobile phase of 0.01% (v/v) formic acid in water and methanol. Analytes were extracted via a precipitation protein procedure. The method was validated in accordance with the US Food and Drug Administration (FDA) guidance and applied to the analysis of fingerprint deposits from subjects who had taken the drugs. RESULTS: The limits of detection (LODs) and the lower limits of quantification (LLOQs) of 17 hypoglycemic drugs were 0.001 to 0.020 and 0.002 to 0.050 ng/fingerprint, respectively. The correlation coefficients (r) for the calibration curves were > 0.99 in the range of 0.050-50.000 ng/fingerprint. The matrix effect and recovery of 17 hypoglycemic drugs at three concentrations ranged from 81.1 to 117.3% and 80.0 to 109.6%, respectively. The validation data (intra- and inter-day combined) for accuracy ranged from 85.5 to 117.2%, the CV (%) data were ≤19.7%. All analytes were found to be stable stored in the autosampler (4°C) for 24 h. This validated method was successfully applied to detect hypoglycemic drugs in fingerprints from patients with hyperglycemia. CONCLUSIONS: A quantification method for hypoglycemic drugs in fingerprints was developed, optimized, and validated. This sensitive method could be used for drug monitoring and providing reference information in forensic investigations.

Surgical career choices of medical students in China: does gender bias play a role?

BACKGROUND: Gender bias in career choices has always been a matter of great concern, including in the field of medicine. This study reports on the current situation in this regard in China, including the reasons for Chinese medical students' willingness to engage in surgical careers; investigates their accounts of gender bias; and analyzes the effect of gender bias on their surgical career choices. METHODS: This study invited medical students from Harbin Medical University to fill out a non-mandatory questionnaire on whether they had witnessed gender bias, their surgical career intentions, and factors influencing their career intentions. A one-way analysis of variance was used to compare the differences between continuous variables. Pearson's chi-squared test was used to compare the differences between the categorical variables, the Kendall correlation coefficient (tau) was used to assess the correlation between the reasons rankings reported by gender, and a multiple regression analysis was conducted by logit model. RESULTS: A total of 643 students responded to the questionnaire. Of them, 63.76% expressed a willingness for a surgical career, with "interest" being a key driving factor (73.41%). Almost all respondents (96.27%) answered that there were more male leaders in the surgical departments they had rotated through or had contacted. Only a few respondents reported gender barriers influencing recruitment (32.19%). However, witnessing gender bias (recruitment of male required) was correlated to choice of surgical career (P < 0.05). Females were less willing to pursue a career in surgery if they had witnessed gender barriers in surgical recruitment. Male dominance also correlated to the choice of a surgical career (P < 0.1). Of the respondents, 53.19% believed that surgery was not suitable for females; among female respondents, this number was 56.12%, higher than for male respondents. When females think that the surgical profession is not suitable for them, it reduces the possibility of their pursuing a career in surgery. CONCLUSION: Most medical students were interested in surgical care. Witnessing gender bias decreases females' willingness to pursue a career in surgery. It is necessary to stimulate medical students' interest in surgery when formulating strategies to promote surgical career choices, as well as to reduce gender bias in surgery; in this way, females' surgical careers should be ensured.

miR-196a Upregulation Contributes to Gefitinib Resistance through Inhibiting GLTP Expression.

Tyrosine kinase inhibitor (TKI) therapy has greatly improved lung cancer survival in patients with epidermal growth factor receptor (EGFR) mutations. However, the development of TKI-acquired resistance is the major problem to be overcome. In this study, we found that miR-196a expression was greatly induced in gefitinib-resistant lung cancer cells. To understand the role and mechanism of miR-196a in TKI resistance, we found that miR-196a-forced expression alone increased cell resistance to gefitinib treatment in vitro and in vivo by inducing cell proliferation and inhibiting cell apoptosis. We identified the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) bound to the promoter region of miR-196a and induced miR-196a expression at the transcriptional level. NRF2-forced expression also significantly increased expression levels of miR-196a, and was an upstream inducer of miR-196a to mediate gefitinib resistance. We also found that glycolipid transfer protein (GLTP) was a functional direct target of miR-196a, and downregulation of GLTP by miR-196a was responsible for gefitinib resistance. GLTP overexpression alone was sufficient to increase the sensitivity of lung cancer cells to gefitinib treatment. Our studies identified a new role and mechanism of NRF2/miR-196a/GLTP pathway in TKI resistance and lung tumor development, which may be used as a new biomarker (s) for TKI resistance or as a new therapeutic target in the future.

Quaternary Ammonium Groups Modified Magnetic Cyclodextrin Polymers for Highly Efficient Dye Removal and Sterilization in Water Purification.

Water recovery is a significant proposition for human survival and sustainable development, and we never stop searching for more efficient, easy-operating, low-cost and environmentally friendly methods to decontaminate water bodies. Herein, we combined the advantages of ß-cyclodextrin (ß-CD), magnetite nanoparticles (MNs), and two kinds of quaternary ammonium salts to synthesize two porous quaternary ammonium groups capped magnetic ß-CD polymers (QMCDP1 and QMCDP2) to remove organic pollutants and eradicate pathogenic microorganisms effectively through a single implementation. In this setting, ß-CD polymer (CDP) was utilized as the porous substrate material, while MNs endowed the materials with excellent magnetism enhancing recyclability in practical application scenarios, and the grafting of quaternary ammonium groups was beneficial for the adsorption of anionic dyes and sterilization. Both QMCDPs outperformed uncapped MCDPs in their adsorption ability of anionic pollutants, using methyl blue (MB) and orange G (OG) as model dyes. Additionally, QMCDP2, which was modified with longer alkyl chains than QMCDP1, exhibits superior bactericidal efficacy with a 99.47% removal rate for Staphylococcus aureus. Accordingly, this study provides some insights into designing a well-performed and easily recyclable adsorbent for simultaneous sterilization and adsorption of organic contaminants in wastewater.

UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1.

Uncoupling protein 1 (UCP1) has been implicated in ameliorating metabolic related disorders, of which most symptoms are risk factors for breast cancer. Here, we found that UCP1 was obviously downregulated in basal-like breast cancer (BLBC) and was positively correlated with improved survival. However, the underlying regulatory mechanisms remain largely unknown. Our studies showed that UCP1 inhibited tumor progression via suppressing aldehyde dehydrogenase (ALDH)-positive breast cancer stem cell (BCSC) population in BLBC. Furthermore, we found that UCP1 induced the upregulation of fructose bisphosphatase 1 (FBP1) which was previously blocked by Snail overexpression, and UCP1 decreased ALDH-positive BCSCs via FBP1-dependent metabolic rewiring, which could be reversed by Snail overexpression. In addition, breast cancer cells co-cultured with UCP1-deficient adipocytes had increased proportion of ALDH-positive BCSCs, indicating a potential protection role of UCP1 in tumor microenvironment. These results suggested that UCP1 suppressed BCSCs through inhibiting Snail-mediated repression of FBP1, and that upregulation of UCP1 might be a previously undescribed therapeutic strategy for combating breast cancer. Graphical abstract.

Resource Allocation in Unmanned Aerial Vehicle (UAV)-Assisted Wireless-Powered Internet of Things.

Most of the wireless nodes in the Internet of Things (IoT) environment face the limited energy problem and the way to provide a sustainable energy for these nodes has become an urgent challenge. In this paper, we present an unmanned aerial vehicle (UAV) to power the wireless nodes in the IoT and an investigation on the optimal resource allocation approach based on dynamic game theory. This IoT system consists of one UAV as the power source and information receiver. The wireless nodes can be powered and collected by the UAV. In order to distinguish the wireless nodes, the wireless nodes are divided into two categories based on the energy consumption. The UAV tries to power these two categories of nodes using a different power level based on the proposed approach, where the wireless nodes control the resources for information transmission. Based on Bellman dynamic programming, the optimal allocated resources for power transfer and information transmission are obtained for both the UAV and wireless nodes, respectively. In order to show the effectiveness of the proposed model and approach, we present numerical simulations.

Identification of Natural Compound Radicicol as a Potent FTO Inhibitor.

The fat mass and obesity-associated protein (FTO), as an m6A demethylase, is involved in many human diseases. Virtual screening and similarity search in combination with bioactivity assay lead to the identification of the natural compound radicicol as a potent FTO inhibitor, which exhibits a dose-dependent inhibition of FTO demethylation activity with an IC50 value of 16.04 µM. Further ITC experiments show that the binding between radicicol and FTO was mainly entropy-driven. Crystal structure analysis reveals that radicicol adopts an L-shaped conformation in the FTO binding site and occupies the same position as N-CDPCB, a previously identified small molecular inhibitor of FTO. Unexpectedly, however, the 1,3-diol group conserved in radicicol and N-CDPCB assumes strikingly different orientations for interaction with FTO. The identification of radicicol as an FTO inhibitor and revelation of its recognition mechanism not only opens the possibility of developing new therapeutic strategies for treatment of leukemia but also provide clues for elucidation of the acting mechanisms of radicicol, which is a possible clinical candidate worth in-depth study.

MiR-29b expression is associated with a dexmedetomidine-mediated protective effect against oxygen-glucose deprivation-induced injury to SK-N-SH cells in vitro.

Ischemic cerebral stroke is a leading cause of death and long-term disability world-wide. Neuronal injury following cerebral ischemia initiates a complex series of signaling cascades that lead to neuronal cell death. MicroRNA 29b (miR-29b) has reported involvement in the pathogenic process of ischemic brain injury. Dexmedetomidine (Dex) is a highly selective α2 adrenergic receptor stimulant that exerts a protective effect on brain tissue. To determine whether Dex might directly influence miR-29b expression after an ischemic injury, human neuroblastoma SK-N-SH cells were subjected to oxygen-glucose deprivation (OGD) for the purpose of creating a neuronal injury model that mimics the effects of brain ischemia in vitro. Next, the association of miR-29b with the protective effect of Dex against ischemic brain injury was studied through the enhancement or inhibition of miR-29b expression by transfection with an miR-29b mimic or inhibitor. We demonstrated that Dex treatment could reduce miR-29b expression, increase cell viability, and inhibit cell apoptosis in the OGD-induced neuronal injury model in vitro. Furthermore, down-regulation of miR-29b expression produced effects on OGD-induced neuronal injuries that were similar to those produced by Dex treatment. Moreover, up-regulation of miR-29b reversed the protective effect of Dex treatment against OGD-induced neuronal injury. Therefore, down-regulation of miR-29b expression might play a role in anti-apoptotic signaling similar to that played by Dex. Elucidation of the role played by miR-29b in ischemia, and identification of a definite association between Dex and miR-29b may lead to the development of new strategies for treating ischemic brain injuries.

A content analysis of depression-related discourses on Sina Weibo: attribution, efficacy, and information sources.

BACKGROUND: Depression is a mood disorder that may lead to severe outcomes including mental breakdown, self-injury, and suicide. Potential causes of depression include genetic, sociocultural, and individual-level factors. However, public understandings of depression guided by a complex interplay of media and other societal discourses might not be congruent with the scientific knowledge. Misunderstandings of depression can lead to under-treatment and stigmatization of depression. Against this backdrop, this study aims to achieve a holistic understanding of the patterns and dynamics in discourses about depression from various information sources in China by looking at related posts on social media. METHOD: A content analysis was conducted with 902 posts about depression randomly selected within a three-year period (2014 to 2016) on the mainstream social media platform in China, Sina Weibo. Posts were analyzed with a focus on attributions of and solutions to depression, attitudes towards depression, and efficacy indicated by the posts across various information sources. RESULTS: Results suggested that depression was most often attributed to individual-level factors. Across all the sources, individual-level attributions were often adopted by state-owned media whereas health and academic experts and organizations most often mentioned biological causes of depression. Citizen journalists and unofficial social groups tended to make societal-level attributions. Overall, traditional media posts suggested the lowest efficacy in coping with depression and the most severe negative outcomes as compared with other sources. CONCLUSIONS: The dominance of individual-level attributions and solutions regarding depression on Chinese social media on one hand manifests the public's limited understanding of depression and on the other hand, may further constrain adoption of scientific explanations about depression and exacerbate stigmatization towards depressed individuals. Mass media's posts centered on description of severe outcomes of depression without suggestions of solutions' effectiveness, which may induce more anxiety among depressed individuals. Campaigns promoting comprehensive understandings about depression and popular works translating scientific findings on depression to the public are called for.

Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF. METHODS: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model. RESULTS: Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ - 1.72 × INR - 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)-0.278 × (miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847. CONCLUSIONS: Expression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

Stackelberg Dynamic Game-Based Resource Allocation in Threat Defense for Internet of Things.

With the rapid development of the Internet of Things, there are a series of security problems faced by the IoT devices. As the IoT devices are generally devices with limited resources, how to effectively allocate the restricted resources facing the security problems is the key issue at present. In this paper, we study the resource allocation problem in threat defense for the resource-constrained IoT system, and propose a Stackelberg dynamic game model to get the optimal allocated resources for both the defender and attackers. The proposed Stackelberg dynamic game model is composed by one defender and many attackers. Given the objective functions of the defender and attackers, we analyze both the open-loop Nash equilibrium and feedback Nash equilibrium for the defender and attackers. Then both the defender and attackers can control their available resources based on the Nash equilibrium solutions of the dynamic game. Numerical simulation results show that correctness and effeteness of the proposed model.

Effects of the antiretroviral drug 2'-deoxy-2'-ß-fluoro-4'-azidocytidine (FNC) on P-gp, MRP2 and BCRP expressions and functions.

The purpose of the present study was to dig into recent studies designed to characterize the impacts of 2'-deoxy-2'-ß-fluoro-4'-azidocytidine (FNC) on P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). Specifically, the modulation effects of FNC on P-gp, MRP2 and BCRP protein expressions were assessed by western blot methods. 5 (and 6)-Carboxy-2',7'-dichloroflourescein (CDF) and BODIPY-prazosin were used to provide indications of alterations of MRP2 and BCRP activities. The effects of P-gp, MRP2 and BCRP on FNC were evaluated in the in situ single-pass intestinal perfusion model. The results showed that FNC at higher concentrations and with longer incubation times can upregulate the protein expression of P-gp, MRP2 and BCRP in Caco-2 cells. The upregulated proteins were also functionally active, as revealed by a lower degree of CDF and BODIPY-prazosin uptake by the cell monolayers. The intestinal absorptive coefficient (Peff) was observed to significantly increase with the inhibitors of P-gp, MRP2 and BCRP. These results suggested that FNC could modulate the expressions and functions of P-gp, MRP2 and BCRP, while P-gp, MRP2 and BCRP were involved in the efflux transport of FNC. The inductive effects of FNC on P-gp, MRP2 and BCRP suggested the possibility of FNC to contribute to the inter- and intra-individual variability of itself, as well as to alter the absorption of other drugs that may be administered concomitantly.

High efficiency fabrication of complex microtube arrays by scanning focused femtosecond laser Bessel beam for trapping/releasing biological cells.

In this paper, we present a focused femtosecond laser Bessel beam scanning technique for the rapid fabrication of large-area 3D complex microtube arrays. The femtosecond laser beam is converted into several Bessel beams by two-dimensional phase modulation using a spatial light modulator. By scanning the focused Bessel beam along a designed route, microtubes with variable size and flexible geometry are rapidly fabricated by two-photon polymerization. The fabrication time is reduced by two orders of magnitude in comparison with conventional point-to-point scanning. Moreover, we construct an effective microoperating system for single cell manipulation using microtube arrays, and demonstrate its use in the capture, transfer, and release of embryonic fibroblast mouse cells as well as human breast cancer cells. The new fabrication strategy provides a novel method for the rapid fabrication of functional devices using a flexibly tailored laser beam.