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Objectives: To investigate the implications of frailty as a predictive factor for outcomes among patients with oral and maxillofacial space infection., Methods: A retrospective cohort study was conducted to analyze 348 medical records, gathering data on several key aspects. These included the etiology of infection, the location of inflamed areas, the treatment administered, and the ultimate treatment outcomes. Additionally, the study collected information on the Symptom Severity (SS) score, frailty score, age, gender, the presence of systemic diseases, alcohol consumption, and smoking history., Results: A total of 155 patients were classified as frailty, while 193 patients were classified as non-frailty. We found a significantly different in age, BMI, hospitalization expenses, length of hospital stay, SS, fibrinogen and admission to ICU between the frail group and the non- frail group., Conclusions: Frailty serves as a valuable predictor of outcomes among patients with oral and maxillofacial space infections. By identifying high-risk patients, frailty can be employed as a clinical tool to guide perioperative care, ultimately optimizing patient outcomes. Notably, frail patients often require more ICU treatment., (© 2024. The Author(s).)

The excessive accumulation of dibutyl phthalate (DBP) in soil poses a serious threat to soil ecosystems and crop safety production. Electrokinetic-assisted phytoremediation (EKPR) has been considered as a potential technology for remediating organic contaminated soils. In order to investigate the effect of different electric fields on removal efficiency of DBP, three kinds of electric fields were set up in this study (1 V·cm -1 , 2 V·cm -1 and 3 V·cm -1 ). The results showed that 59 % of DBP in soil was removed by maize (Zea mays L.) within 20 d in low-intensity electric field (1 V·cm -1 ), and the accumulation of DBP in maize tissues decreased significantly compared to the non-electrified treatment group. Interestingly, it could be observed that the low-intensity electric field could maintain ion homeostasis and improve the photosynthetic efficiency of the plant, thereby relieving the inhibition of DBP on plant growth and increasing the chlorophyll content (94.1 %) of maize. However, the removal efficiency of DBP by maize decreased significantly under the medium-intensity (2 V·cm -1 ) and high-intensity electric field (3 V·cm -1 ). Moreover, the important roles of soil enzyme and rhizosphere bacterial community in low-electric field were also investigated and discussed. This study provided a new perspective for exploring the mechanism of removing DBP through EKPR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts., (© 2024 SSIEM.)

Perfluorooctanoic acid (PFOA), a synthetic perfluoroalkyl compound, has caused extensive soil contamination over several decades, posing serious health risks to humans through bioaccumulation in plants and subsequent transfer via the food chain. Due to the durability of PFOA in soil and its propensity to migrate and accumulate in plants, phytoremediation has been recognized as an effective remediation method. However, the phytotoxicity of PFOA and the adsorption of PFOA by soil hindered the efficiency of traditional phytoremediation. Therefore, this research employed plant growth-promoting rhizobacteria (PGPR)-assisted phytoremediation, augmented with the bio-stimulant fulvic acid (FA), to devise an effective soil remediation strategy tailored for PFOA contamination removal. The results indicated that Rhizobium sp. strain ZY2, endowed with PGP traits, significantly increased the root weight and shoot weight of pak choi by 194.67 % and 37.38 %, respectively, versus the non-inoculation treatment. Furthermore, inoculation with strain ZY2 enhanced soil alkaline phosphatase, protease, and cellulase activities, bolstering soil nutrient cycling and resource availability. On the other hand, compared to treatment with strain ZY2 alone, additional exogenous FA drastically reduced the residual fraction of PFOA in soil from 34.1 % to 1.9 %, likely mediated by complex electrostatic and hydrophobic interactions between FA and soil components. Ultimately, FA addition increased PFOA concentration in pak choi by 8.1-fold. Furthermore, FA could increase the relative abundance of beneficial rhizosphere bacteria (Actinobacterota and Methylotener, etc.), thereby creating a more favorable microenvironment for plant growth. In conclusion, the combined use of strain ZY2 and FA in phytoremediation notably strengthened plant resilience to PFOA, minimized soil sorption, and achieved high remediation efficacy, offering an effective system to mitigate PFOA-soil pollution's environmental and health risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Industrial enterprises are major sources of contaminants, making their regulation vital for sustainable development. Tracking contaminant generation at the firm-level is challenging due to enterprise heterogeneity and the lack of a universal estimation method. This study addresses the issue by focusing on hazardous waste (HW), which is difficult to monitor automatically. We developed a data-driven methodology to predict HW generation using wastewater big data which is grounded in the availability of this data with widespread application of automatic sensors and the logical assumption that a correlation exists between wastewater and HW generation. We created a generic framework that used representative variables from diverse sectors, exploited a data-balance algorithm to address long-tail data distribution, and incorporated causal discovery to screen features and improve computation efficiency. Our method was tested on 1024 enterprises across 10 sectors in Jiangsu, China, demonstrating high fidelity (R² = 0.87) in predicting HW generation with 4,260,593 daily wastewater data., (© 2024. The Author(s).)

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Polycyclic aromatic hydrocarbon (PAH) pollution has attracted much attention due to their wide distribution in soil environment and serious harm to human health. In order to establish an efficient and eco-friendly technology for remediation of PAH-contaminated soil, phytoremediation utilizing maize assisted with enzyme remediation was explored in this study. The results showed that the participation of laccase could promote the degradation of phenanthrene (PHE) from soil and significantly reduce the accumulation of PHE in maize. The degradation efficiency of PHE in soil could reach 77.19% under laccase-assisted maize remediation treatment, while the accumulation of PHE in maize roots and leaves decreased by 41.23% and 74.63%, respectively, compared to that without laccase treatment, after 24 days of maize cultivation. Moreover, it was found that laccase addition shifted the soil microbial community structure and promoted the relative abundance of some PAH degrading bacteria, such as Pseudomonas and Sphingomonas. In addition, the activities of some enzymes that were involved in PAH degradation process and soil nutrient cycle increased with the treatment of laccase enzyme. Above all, the addition of laccase could not only improve the removal efficiency of PHE in soil, but also alter the soil environment and reduce the accumulation of PHE in maize. This study provided new perspective for exploring the efficiency of the laccase-assisted maize in the remediation of contaminated soil, evaluating the way for reducing the risk of secondary pollution of plants in the phytoremediation process., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Photodynamic therapy (PDT) has emerged as an efficient approach for non-invasive cancer treatment. However, organic small-molecule photosensitizers are often associated with defects in hydrophobicity, poor photostability, and aggregation-caused quenching, which limit their application. Usually, the carrier-assisted drug delivery system is a common strategy to solve the above obstacles, but additional carrier material could increase the risk of potential biological toxicity. The carrier-free drug delivery system with easy preparation and high drug-loading capability is proposed subsequently as a potential strategy to develop the clinical use of hydrophobic drugs. Herein, we rationally designed three IR780-based carrier-free nanosystems formed by carbon/disulfide/diselenide bond conjugated IR780-based homodimers. The IR780-based homodimers could self-assemble to form nanoparticles (DC-NP, DS-NP, DSe-NP) and exhibited higher reactive oxygen species generation capability and photostability than free IR780, in which DSe-NP with 808 nm laser irradiation performed best and resulted in the strongest cytotoxicity to 4T1 cells. Meanwhile, the glutathione consumption ability of DSe-NP boosted its PDT effect and then induced excessive oxidative stress of 4T1 cells, increasing antitumor efficacy by enhancing immunogenic cell death further. In tumor-bearing mice, DSe-NP displayed obvious tumor site accumulation, which obviously inhibited tumor growth and metastasis, and enhanced the immunological effect by effectively inducing dendritic cells to mature and activating T lymphocytes and natural killer cells. In summary, our study presented an IR780-based carrier-free nanodelivery system for a combination of PDT and immunity therapy and established expanding the application of organic small-molecule photosensitizers by an approach of carrier-free drug delivery system.

Early indicators are needed to predict the prognosis of patients with hemorrhagic fever with renal syndrome (HFRS). Aspartate aminotransferase to platelet ratio index (APRI) has been shown to be related to mortality risk of patients with various diseases. This study evaluated the prognostic value of APRI and other inflammatory scores in HFRS patients. Data of hospitalized HFRS patients from a tertiary hospital in northwest China were collected and the inflammatory scores such as APRI and neutrophil to lymphocyte count ratio (NLR) were calculated at the day of patient admission. Independent factors related to the survival of patients were determined by multivariate logistic regression. Receiver operating characteristic curve was used to analyze the predictive value, and area under the curve (AUC) and 95% confidence interval (CI) were calculated for quantification. Of the 317 HFRS patients included in study, 15 patients died. Age (OR: 1.10, 95% CI: 1.04-1.16, p = 0.001), NLR (OR: 1.11, 95% CI: 1.02-1.19, p = 0.01), and APRI (OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were quantitative objective factors independently associated with the survival of patients. APRI had an AUC of 0.95 (95% CI: 0.91-1.00, p < 0.001) for predicting the prognosis of patients, with a sensitivity of 93.3% and a specificity of 86.8%. The performance of APRI was better than that of age or NLR. Patients with an APRI ≥ 6.15 had significantly decreased survival compared with those with an APRI < 6.15. In conclusion, this simple index APRI calculated at admission can serve as a biomarker to identify HFRS patients at risk of poor prognosis., (© 2023 Wiley Periodicals LLC.)

Peritoneal metastasis (PM) is a fatal state of colorectal cancer, and only a few patients may benefit from systemic chemotherapy. Although hyperthermic intraperitoneal chemotherapy (HIPEC) brings hope for affected patients, the drug development and preclinical evaluation of HIPEC are seriously lagging behind, mainly due to the lack of an ideal in vitro PM model that makes drug development over-reliant on expensive and inefficient animal experiments. This study developed an in vitro colorectal cancer PM model [microvascularized tumor assembloids (vTA)] based on an assembly strategy of endothelialized microvessels and tumor spheroids. Our data showed that the in vitro perfusion cultured vTA could maintain a similar gene expression pattern to their parental xenografts. Also, the drug penetration pattern of the in vitro HIPEC in vTA could mimic the drug delivery behavior in tumor nodules during in vivo HIPEC. More importantly, we further confirmed the feasibility of constructing a tumor burden-controlled PM animal model using vTA. In conclusion, we propose a simple and effective strategy to construct physiologically simulated PM models in vitro, thus providing a basis for PM-related drug development and preclinical evaluation of locoregional therapies. STATEMENT OF SIGNIFICANCE: This study developed an in vitro colorectal cancer peritoneal metastasis (PM) model based on microvascularized tumor assembloids (vTA) for drug evaluation. With perfusion culture, vTA could maintain a similar gene expression pattern and tumor heterogeneity to their parental xenografts. And the drug penetration pattern in vTA was similar to the drug delivery behavior in tumor nodules under in vivo treatment. Moreover, vTA was more conducive to construct PM animal models with controllable tumor burden. In conclusion, the construction of vTA could provide a new strategy for the PM-related drug development and preclinical evaluation of locoregional therapies., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The use of bacteria as living vehicles has attracted increasing attentions in tumor therapy field. The combination of functional materials with bacteria dramatically facilitates the antitumor effect. Here, we presented a rationally designed living system formed by programmed Escherichia Coli MG1655 cells (Ec) and black phosphorus (BP) nanoparticles (NPs). The bacteria were genetically engineered to express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), via an outer membrane YiaT protein (Ec-T). The Ec-T cells were associated with BP NPs on their surface to acquire BP@Ec-T. The designed living system could transfer the photoelectrons produced by BP NPs after laser irradiation and triggered the reductive metabolism of nitrate to nitric oxide for the in situ release at tumor sites, facilitating the therapeutic efficacy and the polarization of tumor associated macrophages to M1 phenotype. Meanwhile, the generation of reactive oxygen species induced the immunogenic cell death to further improve the antitumor efficacy. Additionally, the living system enhanced the immunological effect by promoting the apoptosis of tumor cells, activating the effect of T lymphocytes and releasing the pro-inflammatory cytokines. The integration of BP NPs, MG1655 cells and TRAIL led to an effective tumor therapy. Our work established an approach for the multifunctional antitumor living therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Combination therapy has been widely studied due to its promising applications in tumor therapy. However, a sophisticated nanoplatform and sequential irradiation with different laser sources for phototherapy complicate the treatment process. Unlike the integration of therapeutic agents, we report a FeS 2 @SRF@BSA nanoplatform for the combination of chemo-combined photothermal therapy (PTT) enhanced photodynamic therapy (PDT) and chemodynamic therapy (CDT) to achieve an "all-in-one" therapeutic agent. Ultrasmall FeS 2 nanoparticles (NPs) with a size of 7 nm exhibited higher Fenton reaction rates due to their large specific surface areas. A photodynamic reaction could be triggered and could generate 1 O 2 to achieve PDT under 808 nm irradiation. FeS 2 NPs also exhibited the desired photothermal properties under the same wavelength of the laser. The Fenton reaction and photodynamic reaction were both significantly improved to accumulate more reactive oxygen species (ROS) with an increase of temperature under laser irradiation. Besides, loading of the chemotherapeutic drug sorafenib (SRF) further improved the efficacy of tumor treatment. To realize long blood circulation, bovine serum albumin (BSA) was used as a carrier to encapsulate FeS 2 NPs and SRF, remarkably improving the biocompatibility and tumor enrichment ability of the nanomaterials. Additionally, the tumors on mice treated with FeS 2 @SRF@BSA almost disappeared under 808 nm irradiation. To sum up, FeS 2 @SRF@BSA NPs possess good biocompatibility, stability, and sufficient therapeutic efficacy in combination therapy for cancer treatment. Our study pointed out a smart design of the nanoplatform as a multifunctional therapeutic agent for combination cancer therapy in the near future.

Near-infrared-II (NIR-II) cancer photothermal therapy (PTT) has become more and more attractive as the NIR-II light shows a higher tissue penetrating depth, which leads to better anti-cancer effects. Recently, the members of the MXene family have been reported as NIR-II photothermal agents, possessing a high specific surface area and a fascinating light-to-heat conversion rate at the same time. Herein, we reported a combination of NIR-II photothermal therapy and immune therapy based on the MXene family member niobium carbide (Nb 2 C). First, Nb 2 C nanosheets (NSs) under 50 nm were prepared. They showed a high photothermal conversion efficiency under a 1064-nm laser, and the NIR-II light showed a deeper tissue penetration depth. Then, a nanoplatform with high R837 stability and a high loading rate was obtained after modification with a polydopamine (PDA) layer on the surface of Nb 2 C. With the R837 modification, the percentage of mature dendritic cells (DCs) increased and the immune response enhanced, compared with the immune response caused by PTT only. Finally, a red blood cell (RBC) membrane was applied as a coat over the nanoplatform in order to avoid excessive blood clearance. During in vivo experiments, blood circulation of Nb 2 C@PDA-R837@RBC nanoparticles (NPs) was prolonged, and all primary tumors were eliminated. Secondary tumors were also inhibited effectively due to the strengthened immune response, proving that Nb 2 C@PDA-R837@RBC NPs could inhibit tumor recurrence. All the results above indicated Nb 2 C@PDA-R837@RBC NPs as a potential RBC camouflaged nanoplatform for the combination of effective PTT and immune therapy towards tumor treatment.

Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness. Herein, a targeting multifunctional black phosphorus (BP) nanoparticle, modified by PEGylated hyaluronic acid (HA), was designed for photothermal/photodynamic/photo-immunotherapy. In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility, stability, and sufficient therapeutic efficacy in the combined therapy of photothermal therapy (PTT) and photodynamic therapy (PDT) for cancer therapy. Moreover, the results of in vitro showed that HA-BP down-regulated the expression of CD206 (M2 macrophage marker) by 42.3% and up-regulated the ratio of CD86（M1 macrophage marker）by 59.6%, indicating that HA-BP nanoparticles have functions in remodeling tumor associated macrophages (TAMs) phenotype (from pro-tumor M2 TAMs to anti-tumor M1 macrophages). Fluorescence (FL) and photoacoustic (PA) multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44 + mediated active targeting and passive EPR effect. In vitro and in vivo studies suggested that the combined therapy of PDT, PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death (ICD) and release Damage-associated molecular patterns (DAMPs), which could induce maturation of dendritic cells (DCs) and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment. This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 [The Author/The Authors].)

Evacuating residents out of affected areas is an important strategy for mitigating the impact of natural disasters. However, the resulting abrupt increase in the travel demand during evacuation causes severe congestions across the transportation system, which thereby interrupts other commuters' regular activities. In this article, a bilevel mathematical optimization model is formulated to address this issue, and our research objective is to maximize the transportation system resilience and restore its performance through two network reconfiguration schemes: contraflow (also referred to as lane reversal) and crossing elimination at intersections. Mathematical models are developed to represent the two reconfiguration schemes and characterize the interactions between traffic operators and passengers. Specifically, traffic operators act as leaders to determine the optimal system reconfiguration to minimize the total travel time for all the users (both evacuees and regular commuters), while passengers act as followers by freely choosing the path with the minimum travel time, which eventually converges to a user equilibrium state. For each given network reconfiguration, the lower-level problem is formulated as a traffic assignment problem (TAP) where each user tries to minimize his/her own travel time. To tackle the lower-level optimization problem, a gradient projection method is leveraged to shift the flow from other nonshortest paths to the shortest path between each origin-destination pair, eventually converging to the user equilibrium traffic assignment. The upper-level problem is formulated as a constrained discrete optimization problem, and a probabilistic solution discovery algorithm is used to obtain the near-optimal solution. Two numerical examples are used to demonstrate the effectiveness of the proposed method in restoring the traffic system performance., (© 2019 Society for Risk Analysis.)

The coronary collateral circulation (CCC) is an alternative source of blood supply when the original vessels fail to provide sufficient blood. The accurate detection of CCC is critical for the treatment of ischemic heart disease, especially when the stent surgery is not an option. The assessment of minute vessels such as coronary collateral arteries is challenging. The objective of this study was to assess the feasibility of detection and classification of CCC using the192-slice third-generation dual-source computed tomography angiography (192-slice DSCT CTA).Eight hundred patients (450 men and 350 women, mean age: 56 ± 11 years) with complete or subtotal occlusion of at least 1 major coronary artery were enrolled for our study. February 2016 and September 2018, the patient both 192-slice DSCT CTA and conventional coronary angiography (CAG) were performed in all enrolled patients. The interval between two approaches for a given patient was 6.1 ± 3.7 days (Range: 1-15). The diagnostic accuracy of 192-slice DSCT CTA was evaluated by comparing it with that of CAG. The identified CCC was graded according to the Rentrop classification.The prevalence among patients of having at least 1 CCC was 43.8%. The sensitivity for detecting CCC by 192-slice DSCT was 91.7% (95% CI: 88.3% to 94.3%), specificity was 95.5% (95% CI: 93.1% to 97.2%), positive predictive value was 94.3% (95% CI: 91.5% to 96.2%), and negative predictive value was 93.3% (95% CI: 90.9% to 95.3%). Cohen-Kappa analysis showed that the consistency of the correct classification of CCC using CAG and 192-slice DSCT was very high with the kappa coefficient (κ) of 0.94 (95% CI: 0.91-0.96, P value = .01). Additionally, the radiation dose for 192-slice DSCT was as low as 0.42 ± 0.04 mSv (range, 0.35-0.43 mSv).The 192-slice DSCT CTA is a reliable and sensitive non-invasive method for the evaluation of CCC with low radiation doses.

PR domain zinc finger protein 1 (PRDM1)/B lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor involved in B and T cell responses which are implicated in chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study investigated the association of PRDM1 with clinical diseases of chronic HBV infection and prognosis of HBV -related HCC patients. Serum PRDM1 levels were determined in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC), 70 HBV infection resolvers and 96 healthy control individuals. The PRDM1 levels were analyzed with regard to clinical diseases and overall survival of HCC patients. Serum PRDM1 concentrations in patients with chronic HBV infection were significantly elevated compared with infection resolvers and healthy controls. HBV-related HCC patients had the most significantly elevated PRDM1 levels. PRDM1 levels could considerably differentiate HCC from chronic hepatitis [area under receiver operating characteristic curve (AUC) 0.889, p < 0.001] or cirrhosis (AUC 0.910, p < 0.001). HCC patients with high PRDM1 levels had a poor prognosis (>300 pg/mL vs. ≤300 pg/mL, p = 0.001). High PRDM1 levels were independently associated with increased mortality in HCC patients (hazard ratio 2.997, 95% confidence interval 1.103-4.722, p = 0.003). Overall, this study demonstrated that PRDM1 levels are associated with the clinical diseases of chronic HBV infection. Highly elevated PRDM1 levels are discriminative of HCC from other clinical diseases and indicative of a poor prognosis of HCC patients. The potential association of PRDM1 levels with disease progression and treatment response warrants further investigation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the most common liver cancer and the mechanisms of hepatocarcinogenesis remain elusive., Objective: This study aims to mine hub genes associated with HCC using multiple databases., Methods: Data sets GSE45267, GSE60502, GSE74656 were downloaded from GEO database. Differentially expressed genes (DEGs) between HCC and control in each set were identified by limma software. The GO term and KEGG pathway enrichment of the DEGs aggregated in the datasets (aggregated DEGs) were analyzed using DAVID and KOBAS 3.0 databases. Protein-protein interaction (PPI) network of the aggregated DEGs was constructed using STRING database. GSEA software was used to verify the biological process. Association between hub genes and HCC prognosis was analyzed using patients' information from TCGA database by survminer R package., Results: From GSE45267, GSE60502 and GSE74656, 7583, 2349, and 553 DEGs were identified respectively. A total of 221 aggregated DEGs, which were mainly enriched in 109 GO terms and 29 KEGG pathways, were identified. Cell cycle phase, mitotic cell cycle, cell division, nuclear division and mitosis were the most significant GO terms. Metabolic pathways, cell cycle, chemical carcinogenesis, retinol metabolism and fatty acid degradation were the main KEGG pathways. Nine hub genes ( TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK ) were selected by PPI network and all of them were associated with prognosis of HCC patients., Conclusion: TOP2A, NDC80, CDK1, CCNB1, KIF11, BUB1, CCNB2, CCNA2 and TTK were hub genes in HCC, which may be potential biomarkers of HCC and targets of HCC therapy., (© 2019 Bentham Science Publishers.)

LncRNA DANCR has been proven to be involved in osteoblast differentiation. This study aims to investigate the role of DANCR in osteoclast formation and root resorption in periodontal ligament (PDL) cells induced by compression force (CF). Rat orthodontic tooth movement (OTM) model was established. The molecules expressions in the areas of root resorption form OTM model were measured. The number of osteoclasts was measured using Tartrate-resistant acid phosphatase (TRAP) staining. The bone resorption was detected using pit formation assay. We showed that the expression of DANCR and Jagged1 protein was increased in rat OTM model and human periodontal ligament (hPDL) cells treated with CF, and CF increased the production of Jagged1, RANKL, and IL-6 from the hPDL cells. Moreover, DANCR could positively regulate Jagged1 protein expression. Knockdown of DANCR could change the promotion effect of CF on osteoclastogenesis and bone resorption in vitro and in vivo experiments, while overexpression of Jagged1 reversed si-DANCR effect. Taken together, knockdown of DANCR reduced osteoclast formation and root resorption induced by CF via Jagged1.

Background: Patients with hepatitis C virus (HCV) genotype 3 infection remain a difficult-to-cure population. This study evaluated the efficacy and safety of sofosbuvir-based regimen in genotype 3 patients in a real-world setting., Methods: HCV genotype 3a-infected adults with compensated liver disease were treated with sofosbuvir (SOF)/velpatasvir (VEL) or SOF/daclatasvir (DCV) with or without ribavirin (RBV) for 12 or 24 weeks, respectively. Efficacy was measured by sustained virologic response at post-treatment week 12 (SVR12). Adverse events were evaluated throughout the treatment and follow-up course., Results: A total of 41 genotype 3a-infected patients were included. Of them, 10 patients (24%) had cirrhosis, 3 (7%) had renal impairment, and 2 (5%) failed previous treatment. Nine patients (22%) were treated with SOF/VEL and 32 (78%) with SOF/DCV with or without RBV. SVR 12 was achieved in 100% (9/9) of patients treated with SOF/VEL for 12 weeks and in 97% (31/32) of those treated with SOF/DCV for 12 or 24 weeks. RBV addition and extension of treatment duration did not improve the SVR of SOF/DCV (RR: 1.04; P = 0.99 and RR: 1.09; P = 0.375, respectively). Ten patients with cirrhosis, 1 on hemodialysis and 2 with treatment-experience achieved SVR12. One treatment-naïve non-cirrhotic patient on hemodialysis treated with SOF/DCV for 24 weeks relapsed at week 8 post-treatment. No serious adverse events and relevant laboratory abnormalities were observed., Conclusion: SOF/VEL and SOF/DCV are highly efficacious and well tolerated in genotype 3a-infected patients with or without cirrhosis. RBV coadministration and extension of SOF/DCV treatment appear to add no improvement for efficacy.

Tumor microenvironment, such as hypoxia and presence of immune cells, plays a critical role in cancer initiation, growth as well as progression, and seriously affects antitumor effect. Accordingly, we constructed a kind of multifunctional nanoparticles (NPs) with macrophage transformation and oxygen (O 2 ) generation characteristics, to regulate the tumor microenvironment. Methods: In this study, we synthesized mesoporous Prussian blue (MPB) NPs with low molecular weight hyaluronic acid (LMWHA) surface modification (LMWHA-MPB), and discovered that LMWHA-MPB could be used as an in situ macrophages converter and O 2 generator. Results: In vitro results showed after uptake by M2 macrophages, LMWHA-MPB displayed the potential in remodeling tumor-associated macrophages (TAMs) phenotype (pro-tumor M2→anti-tumor M1), and anti-metastatic effect on 4T1 cells. Furthermore, in vivo visualized near-infrared (NIR) imaging data proved IR783 labeled LMWHA-MPB NPs could selectively accumulate in tumor sites. Then plenty of O 2 generated to alleviate tumor hypoxia via catalytic decomposition of endogenous hydrogen peroxide (H 2 O 2 ). Based on these outstanding characteristics, LMWHA-MPB NPs were adopted as multifunctional nanocarriers to load sonosensitizer hematoporphyrin monomethyl ether (HMME) for O 2 self-provided sonodynamic therapy (SDT). In vivo anti-tumor results showed LMWHA-MPB/HMME could effectively inhibit the proliferation and metastasis of 4T1 tumors by improving tumor microenvironment. Conclusion: The multifunctional NPs can be used as in situ microenvironmental nano-regulators to inhibit the proliferation and metastasis of 4T1 tumor., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC)., Patients and Methods: Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC., Results: The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042-4.581, P = 0.037, P value by Bonferroni correction [P c ] = 0.074) and allele A (OR 1.435, 95% CI 1.023-2.013, P c  = 0.036) than chronic hepatitis patients. In multivariate analyses, rs510432 allele A-containing genotypes (AA+GA) were independently associated with cirrhosis in comparison to chronic hepatitis (OR 1.927, 95%CI 1.011-3.017, P = 0.032). The rs510432 genotypes AA+GA were also independently associated with HCC in comparison to chronic hepatitis (OR 2.583, 95% CI 1.025-3.911, P = 0.006) or chronic HBV infection without HCC (OR 2.632, 95% CI 1.067-3.482, P = 0.032)., Conclusion: These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC., Abbreviations: HBV: hepatitis B virus; HCC hepatocellular carcinoma; TNFSF10: tumor necrosis factor superfamily member 10; ATG5: autophagy-related protein 5; DNA: deoxyribonucleic acid; LDR-PCR: ligase detection reactions-polymerase chain reaction; PCR: polymerase chain reaction; SLE: systemic lupus erythematosus; BD: Behçet's disease; IL-10: interlukin-10; LPS: lipopolysaccharide; PBMC: peripheral blood mononuclear cells; CWP: coal workers' pneumoconiosis; TNF-α: tumor necrosis factor-α.

The present study investigates the protective effect of napabucasin on the expression of apoptosis markers and inflammatory factors in the neuronal rat cells with post-isolation damage. The level of ROS determined by the fluorescence measurement in the neuronal rat cells with post-isolation damage was 310.21 RFU compared to 21.45 RFU in sham cell cultures. Napabucasin treatment decreased ROS level in the neuronal rat cells with post-isolation damage in dose based manner. ROS level decreased to 278.67, 203.65, 163.32 and 26.87 RFU, respectively in 1, 2, 3 and 4 μM napabucasin treated cell cultures. Treatment with napabucasin increased GSH level significantly (P < 0.05) in the neuronal rat cells with post-isolation damage. Napabucasin treatment at with 1, 2, 3 and 4 μM concentrations increased SOD activity to 2.4, 3.6, 5.1 and 6.1 U/mg, respectively. Treatment with napabucasin increased the activity of catalase in dose based manner. Napabucasin treatment increased Gpx in injured brain cells of neonatal rats. A significant (P < 0.05) increase in the activity of AChE was observed in neuronal rat cells with post-isolation damage on treatment with napabucasin. Treatment with napabucasin reduced the level of TNF-α and IL-6 significantly (P < 0.05) compared to untreated group. Napabucasin treatment decreased the expression of Bax, caspase-3 and p53 proteins in the neuronal rat cells with post-isolation damage. Napabucasin treatment protects post-isolation damage in the neuronal cells of neonatal rats by suppression of apoptosis and oxidative stress. Therefore, napabucasin can be used for the treatment of brain injury., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The PD1 (rs2227982, rs41386349, rs6710479, rs7421861, and rs7565639) and TIM3 (rs11134551, rs11742259, rs246871, rs25855, and rs31223) polymorphisms were examined in 362 patients with chronic hepatitis B virus (HBV) infection, 91 HBV infection resolvers, and 158 healthy controls. Univariate logistic regression was carried out by SNPstats to detect the associations. Multifactor dimensionality reduction (MDR) analysis was performed to explore interactions between PD1 and TIM3 polymorphisms. Associations of polymorphisms with clinical disease were also evaluated. Compared with patients with chronic HBV infection and healthy controls, HBV infection resolvers had a lower frequency of PD1 rs41386349 allele A, higher frequency of PD1 rs6710479 allele C, and higher frequency of TIM3 rs246871 genotypes TC and TC + CC. A best MDR model composed of PD1 rs2227982, rs41386349, and rs7421861, and TIM3 rs11134551, rs11742259, rs246871, rs25855, and rs31223 was observed between patients with chronic HBV infection and HBV infection resolvers (maximum testing balance accuracy, 0.5803; maximum cross-validation consistency, 9/10; P = 0.0010). PD1 rs2227982, rs6710479, and rs7421861 were associated with a higher hepatocellular carcinoma risk. These findings suggest that PD1 rs41386349 and rs6710479 and TIM3 rs246871 and interactions between PD1 and TIM3 polymorphisms may affect the susceptibility of chronic HBV infection and PD1 rs2227982, rs6710479, and rs7421861 may implicate in hepatocarcinogenesis.

Numerous studies have investigated the link between oral contraceptives and risk of ulcerative colitis (UC), but the results have been controversial. We systematically reviewed all relevant published studies and evaluated the association between the use of oral contraceptives and the development of UC by meta-analysis. Databases including PubMed, EMbase, CNKI and WanFang data were thoroughly searched from inception to September 2018 to collect the studies on the correlation between oral contraceptives and the risk of UC. The studies were screened according to the inclusion and exclusion criteria by two researchers independently, and the data were extracted and the quality was evaluated. Meta-analysis was performed using Stata 13.0 software. There were 12 studies involving 303,340 participants that reported on the association between oral contraceptives and UC. The pooled odds ratio (OR) of UC in oral contraceptive users was 1.25 [95% confidence interval (CI) 1.04-1.51, p =  0.02]. The risk was significant in the current oral contraceptive users (OR 1.49, 95% CI 1.12-1.96, p = 0.005) whereas the past oral contraceptive use was not significantly associated with UC (OR 1.17, 95% CI 0.95-1.43, p =  0.141). This study provides evidence of an association between the use of oral contraceptives and the onset risk of UC. The study also shows that the risk for patients who stop using the oral contraceptives was decreased. These findings may be used as important reference for the use of oral contraceptives and the management of UC patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Red blood cell distribution width (RDW) has been indicated to be an inflammatory indicator in a variety of diseases. However, no consistent conclusions regarding it's relevance to hepatitis B virus (HBV) -related liver diseases have been made. This meta-analysis was conducted to assess the significance of RDW in HBV-related liver diseases., Methods: A comprehensive literature review was conducted using PubMed, Embase, and China National Knowledge Infrastructure (CNKI) through August 20, 2017 to identify studies that reported the association between RDW and HBV-related liver diseases. The standard mean difference (SMD) and corresponding 95% confidence interval (CI) were used to assess the associations., Results: Twenty-four studies met the eligibility criteria were included in the meta-analysis. These studies included 3272 HBV-infected patients and 2209 healthy controls. Chronic hepatitis B (CHB) patients had significantly increased RDW levels compared with healthy controls (SMD =1.399, 95% CI 0.971-1.827, p < 0.001]. Moreover, acute on chronic liver failure (ACLF) patients (SMD = 1.309, 95% CI 0.775-1.843, p < 0.001) and cirrhotic patients (SMD = 0.948, 95% CI 0.715-1.180, p < 0.001) had significantly elevated RDW levels compared with CHB patients. However, no statistical significance was obtained in RDW levels between cirrhosis and ACLF (SMD = 0.167, 95% CI -0.382 -0.716, p = 0.051)., Conclusion: RDW values were elevated in HBV-related liver diseases and correlated with the disease severity, suggesting that RDW levels may differentiate CHB from healthy controls and ACLF and cirrhosis from CHB but they appear to have no distinguishing characteristic between ACLF and cirrhosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Thrombocytopenia is one of the main characteristics of hemorrhagic fever with renal syndrome (HFRS). This study aimed to evaluate the associations of platelet distribution width (PDW) with the disease severity and critical patients' survival of HFRS. The demographics, clinical data, and white blood cell and platelet parameters including PDW in 260 patients hospitalized for HFRS were analyzed. The results showed that PDW on the first day (PDW1) was positively associated with the disease severity ( p = 0.005). Multiple regression analysis showed that in addition to age (odds ratio [OR], 1.091; 95% confidence interval [CI], 1.015-1.172) and occurrence of sepsis (OR, 22.283; 95% CI, 2.985-166.325), PDW1 (OR, 0.782; 95% CI, 0.617-0.992) was a risk factor of the mortality, having an area under the receiver operating characteristic curve of 0.709 (95% CI, 0.572-0.846, p = 0.013) for predicting mortality, with a sensitivity of 70% and a specificity of 67% at a cutoff of 16.5 fL, in patients with critical HFRS. These results suggest the potential of PDW at the first day of hospitalization as a valuable parameter for evaluating the severity of HFRS and a moderate parameter for predicting the prognosis of critical HFRS patients. A prospective study in large patient population is needed to validate these findings.

Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. To develop a clinically implantable BAP, some key aspects need to be taken into account: encapsulation material, capsule design, and implant site. Among them, the implant site exerts an important influence on the engraftment, stability, and biocompatibility of implanted BAP. Currently, an optimal site for encapsulated islet transplantation may include sufficient capacity to host large graft volumes, portal drainage, ease of access using safe and reproducible procedure, adequate blood/oxygen supply, minimal immune/inflammatory reaction, pliable for noninvasive imaging and biopsy, and potential of local microenvironment manipulation or bioengineering. Varying degrees of success have been confirmed with the utilization of liver or extrahepatic sites in an experimental or preclinical setting. However, the ideal implant site remains to be further engineered or selected for the widespread application of encapsulated islet transplantation.

Objective: This study analyzed the significance of procalcitonin (PCT) in patients with hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus. Methods: The demographics and clinical and laboratory data including PCT at hospital admission in 146 adults with HFRS were retrospectively analyzed. Results: PCT level was significantly higher in severe patients ( n = 72) than in mild patients ( n = 74, p < 0.001) and independently associated with disease severity (OR 2.544, 95% CI 1.330-4.868, p = 0.005). PCT had an area under the receiver operating characteristic curve (AUC) value of 0.738 (95% CI 0.657-0.820, p < 0.001) for predicting severity. PCT level was significantly increased in patients with bacterial infection ( n = 87) compared with those without (n = 59, p = 0.037) and associated with bacterial infection (OR 1.685, 95% CI 1.026-2.768, p = 0.039). The AUC value of PCT for predicting bacterial infection was 0.618 (95% CI 0.524-0.711, p = 0.016). PCT level was significantly elevated in non-survivors ( n = 13) compared with survivors ( n = 133, p < 0.001) and independently associated with mortality (OR 1.075, 95% CI 1.003-1.152, p = 0.041). The AUC value of PCT for predicting mortality was 0.819 (95% CI 0.724-0.914, p < 0.001). Conclusion: PCT concentrations at admission would be predictive of disease severity, secondary bacterial infection and mortality in patients with HFRS caused by Hantaan virus.

Background and Objective: Upregulated T-cell immunoglobulin and mucin domain containing molecule-3 (Tim-3) in hepatitis B virus (HBV)-specific CD8 + T-cells contributes to CD8 + T-cell exhaustion during chronic HBV infection. The membrane-bound Tim-3 can be cleaved from the cell surface by sheddase, yielding soluble Tim-3 (sTim-3). This study investigated serum sTim-3 levels in patients with chronic HBV infection of various liver diseases., Methods: Serum sTim-3 levels were quantitatively determined in 288 patients with chronic HBV infection of various liver diseases. The sTim-3 levels were analyzed in relation to liver diseases including HBV-related hepatocellular carcinoma (HCC) and overall survival of HCC patients., Results: Serum sTim-3 levels in the patients with chronic HBV infection were significantly elevated compared with healthy controls ( P <0.001) and the levels from asymptomatic HBV carrier status, chronic hepatitis, liver cirrhosis to HCC were progressively increased. Serum sTim-3 levels were closely associated with the severity of liver function abnormalities. Importantly, serum sTim-3 levels were independently associated with HCC risk (OR, 4.310; 95% CI, 2.141-8.676, P <0.001) in comparison to non-HCC diseases in chronic HBV infection and significantly associated with the overall survival of HCC patients, with a level >3000 pg/mL being related to shorter overall survival than a level ≤3000 pg/mL ( P =0.019)., Conclusion: Serum sTim-3 is involved in disease progression and HCC development in chronic HBV infection and its quantitative determination may be potentially used as a marker for monitoring the disease progression and predicting the HCC prognosis in chronic HBV infection., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Signal transducer and activator of transcription 3 (STAT3) is involved in hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC). The association between polymorphism rs1053005 and haplotypes formed by rs1053004 and rs1053005 in the 3'UTR of STAT3 and chronic HBV infection has yet to be investigated., Methods: This study included 567 patients with chronic HBV infection (239 chronic hepatitis, 141 liver cirrhosis and 187 HCC), 98 HBV infection resolvers, and 169 healthy controls. STAT3 rs1053004 and rs1053005 polymorphisms were genotyped by TaqMan SNP Genotyping Assays., Results: The rs1053004 genotype CC [P value by Bonferroni correction (P c ) = 0.002] and allele C (P c  = 0.019) were more frequent in patients with chronic HBV infection than in healthy controls. The rs1053005 genotype GG was also more frequent in patients with chronic HBV infection than in healthy controls (P c  = 0.046). The rs1053004-rs1053005 haplotype T-G was less frequent in patients with chronic HBV infection than in healthy controls (P c  < 0.001). Haplotype C-A was more frequent in patients with liver cirrhosis than in patients with HCC (P c  = 0.042). The rs1053004 genotype TC, rs1053005 genotype AG and rs1053004-rs1053005 haplotype T-A were associated with higher HBV DNA levels., Conclusions: STAT3 rs1053004 and rs1053005 polymorphisms and haplotypes formed by rs1053004 and rs1053005 are associated with chronic HBV infection and the haplotypes appear to be also associated with the development of liver disease. Studies in large sample sizes of patients and control populations are required to verify and extend these findings.

Finding an equilibrium state of the traffic assignment plays a significant role in the design of transportation networks. We adapt the path finding mathematical model of slime mold Physarum polycephalum to solve the traffic equilibrium assignment problem. We make three contributions in this paper. First, we propose a generalized Physarum model to solve the shortest path problem in directed and asymmetric graphs. Second, we extend it further to resolve the network design problem with multiple source nodes and sink nodes. At last, we demonstrate that the Physarum solver converges to the user-optimized (Wardrop) equilibrium by dynamically updating the costs of links in the network. In addition, convergence of the developed algorithm is proved. Numerical examples are used to demonstrate the efficiency of the proposed algorithm. The superiority of the proposed algorithm is demonstrated in comparison with several other algorithms, including the Frank-Wolfe algorithm, conjugate Frank-Wolfe algorithm, biconjugate Frank-Wolfe algorithm, and gradient projection algorithm.

Objective: To summarize the research progress on the source and selection of donor cells in the field of islet replacement therapy for diabetes mellitus., Methods: Domestic and abroad literature concerning islet replacement therapy for diabetes mellitus, as well as donor source and donor selection was reviewed and analyzed thoroughly., Results: The shortage of donor supply is still a major obstacle for the widely clinical application of pancreatic islet transplantation (PIT). Currently, in addition to the progress on the allogeneic/autologous donor islet supply, some remarkable achievements have been also attained in the application of xenogeneic islet (from pig donor), as well as islet like cells derived from stem cells and islet cell line, potentially enlarging the source of implantable cells., Conclusion: Adequate and suitable donor cell supply is an essential prerequisite for widely clinical application of PIT therapy for type 1 diabetes mellitus (T1DM). Further perfection of organ donation system, together with development of immune-tolerance induction, gene and bioengineering technology etc . will possibly solve the problem of donor cell shortage and provide a basis for clinical application of cellular replacement therapy for T1DM.

NIR responsive inorganic hybrid (Ti@GO) was synthesized. It could absorb NIR light and convert it into local hyperthermia and ROS synchronously. Ti@GO was firstly developed as a photosensitizer and a photothermal agent to realize tumor PTT and PDT. For anti-tumor application, HA was grafted on Ti@GO simultaneously as water solubility improver and tumor targeting moiety. ICG was chosen as a model drug. Results demonstrated that HA-Ti@GO could remarkably improve ICG stability and drug accumulation in 4T1 cells, enhance tumor phototherapy efficiency and reduce light-associated side effects. HA-Ti@GO/ICG under NIR laser irradiation showed a significant decreased cell viability of 20.7±2.6% and a high DNA damage degree of 82.4±8.3%. Moreover, in vivo results showed that HA-Ti@GO/ICG plus NIR laser achieved almost complete tumor regression on 4T1 tumor-bearing mice, with a tumor volume of 67.0 mm 3 . Taken together, our study provided a promising strategy to realize synergistic PTT/PDT tumor therapy with a single NIR light., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Artemisinin is a kind of Fe 2+ -dependent drugs. Artemisinin and Fe 2+ co-transport systems can improve its anti-tumor effect. In this study, a visible light-sensitive nanoplatform (HA-TiO 2 -IONPs/ART) was developed. Detailed investigation demonstrated that HA-TiO 2 -IONPs/ART could realize Fe 2+ and artemisinin synchronous co-delivery and tumor-responsive release. This feature enhanced the anti-tumor efficiency of artemisinin significantly. In vitro results proved that hyaluronic acid modification could improve the biocompatibility, dispersion stability and cytophagy ability of nanocarriers. Furthermore, this drug delivery system could generate reactive oxygen species under visual light irradiation. In vitro and in vivo experiments demonstrated that HA-TiO 2 -IONPs/ART combining with laser irradiation displayed the best anti-tumor efficacy. This study affords a promising idea to improve the curative efficiency of artemisinin analogs for cancer therapy., Competing Interests: CONFLICTS OF INTEREST There was no potential conflicts of interest.

Fe 2+ plays an essential role for artemisinin (ART)-based drugs in anticancer therapy. As a result, it is important to realize these two agents' cotransport for improving antitumor efficacy. We utilized a kind of alternating magnetic field (AMF) and tumor-responsive material-mesoporous Fe 3 O 4 (mFe 3 O 4 )-to encapsulate ART. After that, the outer surface of mFe 3 O 4 was capped with multifunctional hyaluronic acid (HA), which was used not only as a smart gatekeeper but also as a tumor targeting moiety. In vitro and in vivo studies proved that ART can be encapsulated in HA-mFe 3 O 4 and protected by HA coating which could effectively avoid premature release during in vivo circulation. HA-mFe 3 O 4 /ART could be taken up by MCF-7 tumor cells via CD44 receptor-mediated endocytosis and locate at acidic lysosome. Subsequently, "HA gate" could be degraded by acidity and hyaluronidase. Then this system synchronously released Fe 2+ and ART at the same site. Fe 2+ can nonenzymatically convert ART to ROS for killing cancer cells. Under AMF irradiation, HA-mFe 3 O 4 could not only effectively convert electromagnetic wave into heat for tumor thermal therapy but also generate high levels of reactive oxygen species (ROS) for tumor dynamic therapy. These results demonstrated that the antitumor efficacy of HA-mFe 3 O 4 /ART in vivo significantly enhanced 3.7 times compared with free ART. Combining with AMF, it further improved 3.9 times (V/V0 of 0.11), suggesting the successful combined application of HA-mFe 3 O 4 /ART and AMF for tumor treatment. It is believed that HA-mFe 3 O 4 /ART is a promising system for Fe 2+ -dependent drugs to improve their therapeutic effect.

To achieve tumor-specific delivery of doxorubicin, TiO 2 @Fe 3 O 4 /PEI/delivery of doxorubicin conjugates were designed and synthesized. Fe 3 O 4 could act as magnetically responsive carriers and enhance the visible light photodynamic activities of TiO 2 Delivery of doxorubicin was conjugated via coordination bond. The drug release rate at pH 5.2 was much faster than that at pH 7.4, due to pH-sensitive coordination bond. Besides, TiO 2 @Fe 3 O 4 /PEI/delivery of doxorubicin showed high antitumor efficacy combining with phototherapy, good bio-safety, higher cellular uptake with an external magnetic field, and less toxicity in vitro and in vivo. These results suggested that TiO 2 @Fe 3 O 4 /PEI/delivery of doxorubicin may be promising for high tumor treatment efficacy with minimal side effects in future., (© The Author(s) 2016.)

Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO2@MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO2@MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO2@MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform.

A network design problem is to select a subset of links in a transport network that satisfy passengers or cargo transportation demands while minimizing the overall costs of the transportation. We propose a mathematical model of the foraging behaviour of slime mould P. polycephalum to solve the network design problem and construct optimal transport networks. In our algorithm, a traffic flow between any two cities is estimated using a gravity model. The flow is imitated by the model of the slime mould. The algorithm model converges to a steady state, which represents a solution of the problem. We validate our approach on examples of major transport networks in Mexico and China. By comparing networks developed in our approach with the man-made highways, networks developed by the slime mould, and a cellular automata model inspired by slime mould, we demonstrate the flexibility and efficiency of our approach.

Because most networks are intrinsically directed, the directed shortest path problem has been one of the fundamental issues in network optimization. In this paper, a novel algorithm for finding the shortest path in directed networks is proposed. It extends a bio-inspired path finding model of Physarum polycephalum, which is designed only for undirected networks, by adopting analog circuit analysis. Illustrative examples are given to show the effectiveness of the proposed algorithm in finding the directed shortest path.

This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace III software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.

We review current literature and data on the burden of injury and violence in the Eastern Mediterranean Region (EMR) of the World Health Organization (WHO), with a special focus on the health, economic and social burden they impose on individuals, families and society. Injury-associated mortality and disability is on the rise in EMR, especially among economically productive adults, young males and vulnerable road users. In particular, road traffic injuries, the leading cause of injuries, account for 27% of the total injury and violence mortality in EMR according to WHO. Violence including suicide, homicide and war-related injury has also been increasing over the past two decades for both females and males. There is need for greater interest and efforts in slowing and ultimately halting the trend through interventions, legislative actions, and research that examine the special needs and challenges in the Region.

Background Information: Angiotensin-(1-7) [ANG-(1-7)] mediates vasodilation, antiproliferation, anti-apoptosis and antifibrosis, therefore, it opposes the effects of angiotensin II (ANG II). However, the detailed signal transduction mechanism following the Mas receptor activated by ANG-(1-7) is still poorly understood. Src homology2-containing inositol phosphatase 1 (SHP-1), a redoxsensitive protein tyrosine phosphatase, negatively influences downstream signalling molecules, such as mitogen-activated protein kinases (MAPKs), through dephosphorylation, thereby inhibiting proliferative and profibrotic signalling induced by ANG II. Therefore, we hypothesised that SHP-1 may mediate the antiproliferative signalling of ANG-(1-7) through the regulation of the dynamic balance of MAPKs and SHP-1 in isolated cardiac fibroblasts. Primary culture of neonatal Sprague-Dawley rats cardiac fibroblasts was treated separately with different interventions to investigate this issue., Results: Our data revealed that ANG II increased the phosphorylation of extracellular signal-related kinase (p-ERK1/2) and the ratio of (p-ERK1/2)/(ERK1/2), but ANG-(1-7) decreased them. The effects of ANG-(1-7) on the phosphorylation p-ERK1/2 were blocked by the Mas receptor antagonist A-779. Unlike ANG II, which decreased the activity of SHP-1, ANG-(1-7) increased its activity. Overexpression of SHP-1 attenuated the ANG II-stimulated phosphorylation of c-Src, its downstream molecules ERK1/2, α-smooth muscle actin and transforming growth factor-β1 (TGF-β1). These effects were also inhibited by the specific inhibitor of SHP-1, sodium stibogluconate. ANG-(1-7) had no significant effects on the gene expression of TGF-β1, collagen I or collagen III, but was found to antagonise the stimulatory effects of ANG II on them., Conclusions: ANG-(1-7), through Mas receptor, activates SHP-1 in cardiac fibroblasts, which can negatively modulate ANG II-induced phosphorylation of c-Src and MAPKs, and inhibits profibrotic factors TGF-β1 and collagen production. ANG-(1-7) can thereby serve as a protective role by counteracting the effects of ANG II., (© 2014 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.)

The constrained shortest path (CSP) problem has been widely used in transportation optimization, crew scheduling, network routing and so on. It is an open issue since it is a NP-hard problem. In this paper, we propose an innovative method which is based on the internal mechanism of the adaptive amoeba algorithm. The proposed method is divided into two parts. In the first part, we employ the original amoeba algorithm to solve the shortest path problem in directed networks. In the second part, we combine the Physarum algorithm with a bio-inspired rule to deal with the CSP. Finally, by comparing the results with other method using an examples in DCLC problem, we demonstrate the accuracy of the proposed method.

Shortest path is among classical problems of computer science. The problems are solved by hundreds of algorithms, silicon computing architectures and novel substrate, unconventional, computing devices. Acellular slime mould P. polycephalum is originally famous as a computing biological substrate due to its alleged ability to approximate shortest path from its inoculation site to a source of nutrients. Several algorithms were designed based on properties of the slime mould. Many of the Physarum-inspired algorithms suffer from a low converge speed. To accelerate the search of a solution and reduce a number of iterations we combined an original model of Physarum-inspired path solver with a new a parameter, called energy. We undertook a series of computational experiments on approximating shortest paths in networks with different topologies, and number of nodes varying from 15 to 2000. We found that the improved Physarum algorithm matches well with existing Physarum-inspired approaches yet outperforms them in number of iterations executed and a total running time. We also compare our algorithm with other existing algorithms, including the ant colony optimization algorithm and Dijkstra algorithm.

Objective: Osseointegration of orthodontic microscrew implant is influenced by tooth extraction. This study aims to evaluate the safety margin of the osseointegration of orthodontic implants by investigating the healing process of the implant-bone interface through histopathological studies and quantitative determination., Methods: Twelve male beagles were selected and randomly divided into four groups. An orthodontic microscrew was implanted beside the tooth extraction area. Animals were killed in 1, 3, 8, and, 12 weeks to investigate tissue response. Histomorphological observation and bone implant contact ratio (BIC) tests were performed at different healing time after implantation., Results: A new bone was formed on the implant-bone interface of the control group. Bone resorptions were also detected in the experimental group 3 weeks after implantation. The BIC level of the control groups increased during the first 8 weeks; no change was observed anymore after the 8th week. On the other hand, the BIC value in the experimental group decreased in the first 3 weeks. It then increased rapidly and reached its peak of 80.08% in the 8th week. No significant difference wa s found between the experimental and control groups in the first 3 weeks. After the 3rd week, the BIC value of the experimental group (44.35%) was lower than that of the control group (55.46%) (P < 0.01)., Conclusion: The healing process after implantation was influenced by tooth extraction. Bone resorption was detected at an early stage. However, vigorous bone remodeling was observed subsequently.

How to identify influential nodes is a key issue in complex networks. The degree centrality is simple, but is incapable to reflect the global characteristics of networks. Betweenness centrality and closeness centrality do not consider the location of nodes in the networks, and semi-local centrality, leaderRank and pageRank approaches can be only applied in unweighted networks. In this paper, a bio-inspired centrality measure model is proposed, which combines the Physarum centrality with the K-shell index obtained by K-shell decomposition analysis, to identify influential nodes in weighted networks. Then, we use the Susceptible-Infected (SI) model to evaluate the performance. Examples and applications are given to demonstrate the adaptivity and efficiency of the proposed method. In addition, the results are compared with existing methods.

Background: Facial paralysis is defined as severe or complete loss of facial muscle motor function., Objective: The study was undertaken to explore a bibliometric approach to quantitatively assess the research on clinical treatment of facial paralysis using rehabilitation, physiotherapy and acupuncture using Web of Science from 1992 to 2011., Design: Bibliometric approach., Data Retrieval: A bibliometric analysis based on the publications on Web of Science was performed using key words such as "facial paralysis", "rehabilitation", "physiotherapy" and "acupuncture"., Inclusive Criteria: (1) Research articles on the clinical treatment of facial paralysis using acupuncture or physiotherapy (e.g. exercise, electro-stimulation) and other rehabilitation methods; (2) researches on human and animal fundamentals, clinical trials and case reports; (3) Article types: article, review, proceedings paper, note, letter, editorial material, discussion, book chapter. (4) Publication year: 1992-2011 inclusive., Exclusion Criteria: (1) Articles on the causes and diagnosis on facial paralysis; (2) Type of articles: correction; (3) Articles from following databases: all databases related to social science and chemical databases in Web of Science., Main Outcome Measures: (1) Overall number of publications; (2) number of publications annually; (3) number of citations received annually; (4) top cited paper; (5) subject categories of publication; (6) the number of countries in which the article is published; (7) distribution of output in journals., Results: Overall population stands at 3 543 research articles addressing the clinical treatment of facial paralysis in Web of Science during the study period. There is also a markedly increase in the number of publications on the subject "facial paralysis treatments using rehabilitation" during the first decade of the 21(st) century, except in 2004 and 2006 when there are perceptible drops in the number of articles published. The only other year during the study period saw such a drop is 1993. Specifically, there are 192 published articles on facial paralysis treated by rehabilitation in the past two decades, far more than the output of physiotherapy treatment. Physiotherapy treatment scored only 25 articles including acupuncture treatment, with over 80% of these written by Chinese researchers and clinicians. Ranked by regions, USA is by far the most productive country in terms of the number of publications on facial paralysis rehabilitation and physiotherapy research. Seeing from another angle, the journals that focus on otolaryngology published the most number of articles in rehabilitation and physiotherapy studies, whereas most acupuncture studies on facial paralysis were published in the alternative and complementary medicine journals., Conclusion: Study of facial paralysis remains an area of active investigation and innovation. Further clinical studies in humans addressing the use of growth factors or stem cells continue to successful facial nerve regeneration.