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Land use changes have significant impacts on the carbon balance in an urban ecosystem. When there is rapid development in urbanizing regions, land use changes have a dramatic effect on vegetation carbon storage (VCS). This study investigates the impact of land use change on VCS in a period of rapid urbanization in Hangzhou, China. The results show that: 1) from 2000 to 2015, land use in Hangzhou underwent huge changes, mainly reflected in decrease in cropland and wetland and the increased settlement. More than 34.58% of the land was transformed, and the land use changes are primarily characterized by a significant decrease in cropland due to the occupation by settlement. 2) over the 15 years, changes in land use led to a decrease of 3.93 × 105 t of VCS in the urban ecosystem. The large-scale transformation of cropland and wetland, which have a comparatively high carbon density, into land for settlement exerted a negative impact on VCS. 3) The central city, which with the Circle-E/I/O mode, had the lowest comprehensive land use dynamic degree, leading to moderate land use change and an increase in VCS; Yuhang and Xiaoshan, which with Multicore-E/O/I mode and Fan-E/O/I modes, had a higher comprehensive land use dynamic degree, drastic changes in land use, and a decrease in VCS. This study proposes a reliable method of estimating changes in VCS, clarifies the relationship between land use change and VCS during rapid urbanization, and provides recommendations for sustainable urban development.

The management of osteoarthritis (OA) is a clinical challenge due to the particular avascular, dense, and occluded tissue structure. Despite numerous clinical reports and animal studies, the pathogenesis and progression of OA are still not fully understood. On the basis of traditional drugs, a large number of new drugs have been continuously developed. Intra-articular (IA) administration for OA hastens the development of targeted drug delivery systems (DDS). OA drugs modification and the synthesis of bioadaptive carriers contribute to a qualitative leap in the efficacy of IA treatment. Nanoparticles (NPs) are demonstrated credible improvement of drug penetration and retention in OA. Targeted nanomaterial delivery systems show the prominent biocompatibility and drug loading-release ability. This article reviews different drugs and nanomaterial delivery systems for IA treatment of OA, in an attempt to resolve the inconsonance between in vitro and in vivo release, and explore more interactions between drugs and nanocarriers, so as to open up new horizons for the treatment of OA.

This study investigates the effect of different mixing strategies on anaerobic digestion of food waste in order to make the anaerobic digestion waste-to-energy process more energy efficient. Results showed that intermittent mixing is an alternative strategy to continuous mixing or unmixing for high efficient biogas production and energy saving. Through computational fluid dynamics modelling of fluid flow in anaerobic digesters, the mixing time was optimized to 2 mins/hr, at which point the reaction mixture is almost entirely homogeneous. The results of the model was validated with the experimental data. At an organic loading rate of 2.4 g VSFW/L/day, the semi-continuously mixed reactor maintains a higher specific methane yield of 437 mL CH4/g VSFW in comparison with the other controls. In addition, the semi-continuously mixed reactor has a larger proportion of Bacteroides and Methanocuelles. Based on the results of the bench scale experiment, the energy balance of the hybrid AD waste-to-energy system was simulated and evaluated. The calculated AD efficiency of the semi-continuously mixed reactor is 74.4%, which is higher than the AD efficiencies of the continuously mixed (66.9%) and unmixed reactors (14.9%). The energy balance investigated the electricity generated and the net heat output generated, in addition to self-sustaining and meeting the energy requirements of the various AD processes investigated. Based on the analysis, it was found the semi-continuous mixing is more energy efficient and sustainable to generate sufficient biogas output for the energy system to provide a net positive heat and electricity output.

The increasing challenge in waste disposal and high dependency on imported fossil fuel has compelled Singapore to make continuous efforts in advancing waste to energy (WTE) technology, which could ensure sustainable development on one hand and energy resilience on the other hand. This paper summarizes the current WTE practices and research trends in Singapore, covering anaerobic digestion (AD), gasification, combustion-based biomass combined heat and power (CHP) production, and incineration, with the aim to define future perspectives of Singapore WTE application. Among the different aspects assessed, source-separated food waste (FW) and brown water present the biggest energy potential if AD is adopted instead of incineration. Given that the purity of source separated waste determines the extent of recovered energy, suggestions are made to increase the participating rate in source separation among Singapore residents, such as environmental education through social media and phone apps and proper facilities installation at household and community. Moreover, additional benefits can be credited to WTE system if the waste to material practice is also conducted on top of energy production.

Ample proof showed that non-coding RNAs (ncRNAs) play a crucial role in proliferation and differentiation of osteoblasts and bone marrow stromal cells (BMSCs). Varied forms of biophysical stimuli like mechanical strain, fluid shear stress (FSS), microgravity and vibration are verified to regulate ncRNAs expression in osteogenic differentiation and influence the expression of target genes associated with osteogenic differentiation and ultimately regulate bone formation. The consequences of biophysical stimulation on osteogenic differentiation validate the prospect of exercise for the prevention and treatment of osteoporosis. In this review, we tend to summarize the studies on regulation of osteogenic differentiation by ncRNAs beneath biophysical stimulation and facilitate to reveal the regulatory mechanism of biophysical stimulation on ncRNAs, and provide an update for the prevention of bone metabolism diseases by exercise.

This work studied the use of a horizontal high-solid digester for the decentralized anaerobic treatment of horticultural waste (fallen leaves), where the effect of intermittent mixing by a modified double helical ribbon impeller was investigated. Before experimental verification, the flow pattern and theoretical mixing time were first characterized by CFD simulation. Subsequently, three mixing time intervals (i.e., 3 min/3 hr; 18 min/3 hr; 108 min/3 hr) and one control setup (i.e., without mixing) were compared for their performance during start-up and semi-continuous operation. It was found that minimal mixing was necessary for an efficient digester’s start-up but increased mixing intensity for semi-continuous operation. The results were further interpreted by correlating the digester performance and microbial communities. Those microorganisms sensitive to increased mixing intensity were highlighted and analysed.

Research into the diagnosis, treatment and prevention of childhood-related diseases is the key to reducing their morbidity and mortality. Circular RNAs (circRNAs) play critical roles, both in physiology and pathology, and there is ample evidence to show that they play varying roles in tissue development and gene regulation. Studies on circRNAs in different childhood-related diseases have confirmed their great potential for disease prevention and treatment. These breakthroughs highlight the pathological role of circRNAs in cancers, as well as cardiovascular and hereditary childhood illnesses. In this review, we summarize the role of circRNAs in childhood-related diseases and cancer, and provide an update of the possible diagnostic and therapeutic application of circRNAs.

This study evaluated the mixing – activate carbon nexus in anaerobic digestion with the aim of accelerating start-up of thermophilic anaerobic co-digestion of food waste and chicken manure using mesophilic anaerobic sludge as inoculum. Results showed that the methane yield in the continuous stirred reactor is 71.3% higher than that of intermittent agitated reactor, and the addition of activated carbon can further improve the yield of methane by 18.2%. Continuous mixing mode followed by intermittent mixing was proved to be an alternative strategy to accelerate start-up of thermophilic anaerobic digestion. The optimum mixing time of 120 s/hour were obtained using computational fluid dynamics modeling. Analysis of genomic annotation metabolism indicated that the addition of activated carbon enhanced the dominant metabolism pathways of amino acid, methane and energy. Results of enzymes gene expression suggested that carbohydrates esterases, glycoside hydrolases and glycosyl transferases were dominant, respectively.

Interleukin-22 (IL-22) is a recently identified regulator of inflammation, but little is known about its role in liver transplantation. Therefore, in this study, we explored the roles and the underlying mechanisms of IL-22 in acute allograft rejection by using a rat allogeneic liver transplantation model. Results showed that allograft liver transplantation led to damage of the parent liver and to significantly increased IL-22 expression in the allograft liver and plasma of the recipient rats compared with the rats who received isografts. Moreover, the significantly increased IL-22 expression was accompanied by markedly increased level of phospho-STAT3 in the allogeneic liver tissues after transplantation. Of note, neutralization of the IL-22 protein in recipient rats significantly worsened the function of the allograft liver at 1 day post-transplantation (ischemia-reperfusion injury, IRI) but improved the function at 7 days post-transplantation (acute rejection, AR). At IRI stage, IL-22 protected liver function through the increase of anti-apoptosis and pro-regeneration cytokines. However, IL-22 led to the increase of pro-inflammation factors at AR stage, accompanied by the marked increase of the Th17 and the marked decrease of Treg cells in allograft recipient rats through modulating the expression of chemokines for different cell types, which however were reversed by in vivo IL-22 neutralization. Results indicate the dual roles of IL-22 and suggest the differential potential clinical application of IL-22 at different stage of allograft liver transplantation.

Sewage sludge treatment & disposal pose environmental challenges in populated-dense urban environments. Due to its poor digestibility and dewaterability, sewage sludge contains high water content and concentrated nutrients (carbon, nitrogen, and phosphorus) even after conditioning and mechanical thickening. Regarding this, a pretreatment step and downstream anaerobic digestion (AD) are often required. To meet our societal goal towards a circular economy, system integration of hydrothermal pretreatment and AD now present an attractive approach for recovering resources from the wet sewage sludge biomass. In this study, such system integration together with struvite precipitation was applied for valorizing sewage sludge. Firstly, hydrothermal conditions of different temperatures (160 °C–230 °C) and duration (2 h–12 h) were compared to their performance of nutrients solubilization. Subsequently, the hydrothermal condition of 220°C-3 h was selected for further investigations of struvite recovery and bioenergy production. Through AD comparisons, the integrated process improved the ultimate biomethane yield by 38%. Interestingly, a lag phase occurred in the midst of the AD, which indicated the need for microbial acclimatization after the hydrothermal process. The long-term microbial monitoring revealed the efficient biomethane re-generation was closely related to the late enrichment of Syntrophus for potential H2-syntrophy. Therefore, on one hand, this study investigated an efficient and integrated approach of sewage sludge valorization. On other hand, it uncovered the microbial bottlenecks and potential biotechnological means for further system improvement. Further research about nutrients speciation in the integrated system would be desired.

Human activity recognition has been of interest in the field of urban planning. This paper established a general framework by which expected human activity intensity (HAI) measured by the built environment and factual HAI measured by the Baidu thermal chart were estimated and comparatively analyzed so as to identify abnormal human activities in Hanghzou, China. Three elements of the built environment (i.e., residential density, road connectivity, and land-use mixing degree) from multi-source data with high precision are selected to assess the expected HAI. Results indicate Hangzhou has evolved into a polycentric city with three urban clusters. In addition, a significant positive correlation exists between the two types of HAIs. However, there are areas with spatial mismatches, particularly in the &ldquo, urban village&rdquo, and new towns, suggesting human activities are not equally distributed all over the city. Research implications, limitations, and future research needs are discussed.

Powdered activated carbon (AC) is commonly used as an effective additive to enhance anaerobic digestion (AD), but little is known about how the metabolic pathways resulting from adding AC change the microbial association network and enhance food waste treatment. In this work, the use of AC in an anaerobic digestion system for food waste was explored. Using bioinformatics analysis, taxonomic trees and the KEGG pathway analysis, changes in microbial network and biometabolic pathways were tracked. The overall effect of these changes were used to explain and validate improved digestion performance. The results showed that AC accelerated the decomposition of edible oil in food waste, enhancing the conversion of food waste to methane with the optimized dosage of 12 g AC per reactor. Specifically, when AC was added, the proponoate metabolic pathway that converts propanoic acid to acetic acid became more prominent, as measured by 16S rRNA in the microbial community. The other two metabolic pathways, Lipid Metabolism and Methane Metabolism, were also enhanced. Bioinformatics analysis revealed that AC promoted the proliferation of syntrophic microorganisms such as Methanosaeta and Geobacter, forming a highly intensive syntrophic microbial network.

A 28-year-old man complained of intermittent irritable dry cough for 2 months with occasional bloody sputum. Positron emission tomography-computed tomography (PET-CT) suggested multiple heterogeneous soft tissue masses in the inferior lobes of both lungs, with heterogeneous increases in 18F-FDG uptake. No metabolic disorders were found in the rest of the body. CT-guided percutaneous lung puncture and biopsy and immunohistochemical study confirmed pulmonary primitive neuroectodermal tumor (PNET). PNET is characterized by small round blue cells and positive CD99 expression. After six cycles of chemotherapy with ifosfamide, dacarbazine and cisplatin, the lesions diminished substantially. At 2 months after the last cycle of chemotherapy, the patient complained of exertional dyspnea. PET-CT and echocardiogram suggested a space-occupying lesion in the right atrium. Autopsy revealed that this space-occupying lesion had the same pathomorphology and immunophenotype with pulmonary PNET, suggesting metastasis of pulmonary PNET to the right atrium. Here, we reported this rare case of pulmonary PNET metastasizing, instead of direct infiltrating or extending, into the heart.

Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(49-57) using FITC-labeled E7(49-57) as the tracer. Inoculation of the mHSP110-E7(49-57) complex was capable of priming strong epitope-specific immune response as determined by its ability to elicit an epitope-specific splenocytes proliferation and a cytotoxic T cell response, and IFNgamma production in splenocytes. Results also showed that immunization with the mHSP110-E7(49-57) complex completely protected mice against subsequent challenge with tumor cells. More importantly, immunization of this complex also significantly inhibited the growth of established tumors and prolonged the survival time of the tumor-bearing animals. Thus, mHSP110-E7(49-57) complex vaccine represents a potentially powerful approach for use in the immunotherapy of cervical cancer associated with HPV16 infection. More importantly, the multi-epitopes derived from E7 and other E proteins can be applied to the strategy described in this study to form a multi-antigenic vaccine to induce an improved antitumor immune response to cervical cancer in the future.

The synovial sarcoma X breakpoint (SSX) gene family contains nine members. The SSX proteins are CT (cancer/testis) antigens and can be expressed in many tumor types. T cell immune response against SSX protein can be detected in tumor patients and mice expressing any SSX. Screening predominant protective epitopes might improve the low immunogenicity against these "self" CT antigens. Herein, we predicted HLA-A*0201-restricted epitopes for all nine SSX family members, followed by validation with epitope molecular modeling, peptide/HLA-A*0201 affinity, and binding stability assays. We obtained four highly homologous candidate epitopes with the high immunogenicity scores designated P1, P4, P5 and P6, from the nine SSX members. Each of the four candidates could elicit strong epitope-specific CTL immune responses, but P4 could evoke more interferon gamma (IFN-gamma)-producing T cells and more potent CTLs that could lyse more target cells. Importantly, almost all of the four epitopes induced CTLs could cross-lyse the mutual targets both in vitro in human PBMCs and HLA-A2.1/K(b) transgenic mice, but P4 showed superiority to other epitopes in term of cross-cytolysis. All of these results demonstrate that P4 can induce anti-tumor immunity in a fashion superior to other candidates, and may be the "common" CTL epitope among all SSX-expressing tumors. Due to its documented responses herein, P4 has potential application in peptide-mediated immunotherapy.

This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both theBrucella abortusL7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular immune responses. The specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T-cell proliferative response and induced a large amount of gamma interferon-producing T cells upon restimulation in vitro with recombinant fusion protein L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune response in vivo. This divalent DNA vaccine could also induce a significant level of protection against challenge with the virulent strainB. abortus544 in BALB/c mice. Furthermore, the protection level induced by the divalent DNA vaccine was significantly higher than that induced by the univalent DNA vaccines pcDNA3.1-L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for the first time that the Omp16 gene can be a candidate target for a DNA vaccine against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12 and Omp16 genes can elicit a stronger cellular immune response and better immunoprotection than the relevant univalent vaccines can.

Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(49-57) using FITC-labeled E7(49-57) as the tracer. Inoculation of the mHSP110-E7(49-57) complex was capable of priming strong epitope-specific immune response as determined by its ability to elicit an epitope-specific splenocytes proliferation and a cytotoxic T cell response, and IFNgamma production in splenocytes. Results also showed that immunization with the mHSP110-E7(49-57) complex completely protected mice against subsequent challenge with tumor cells. More importantly, immunization of this complex also significantly inhibited the growth of established tumors and prolonged the survival time of the tumor-bearing animals. Thus, mHSP110-E7(49-57) complex vaccine represents a potentially powerful approach for use in the immunotherapy of cervical cancer associated with HPV16 infection. More importantly, the multi-epitopes derived from E7 and other E proteins can be applied to the strategy described in this study to form a multi-antigenic vaccine to induce an improved antitumor immune response to cervical cancer in the future.

The aetiological agent for severe acute respiratory syndrome (SARS) has been determined to be a new type of coronavirus (SARS-CoV) that infects a wide range of mammalian hosts. Up to now, there have been no specific drugs to protect against SARS-CoV infection, thus developing effective strategies against this newly emerged viral infection warrants urgent efforts. Adoptive immune therapy with pathogen-specific heterologous immunoglobulin has been successfully used to control the dissemination of many viral infections. To investigate whether a neutralizing antibody against SARS-CoV raised in an artiodactylous host can have a protective role on primate cells, we prepared serum IgGs and their pepsin-digested F(ab’)2 fragments from horses inoculated with purified SARS-CoV (BJ-01 strain). The protective effect of the F(ab’)2 fragments against SARS-CoV infection was determined in cultured Vero E6 cells by cytopathic effect (CPE), MTT and plaque-forming assays and in a Balb/c mouse model by CPE and quantitative RT-PCR. The results showed the neutralization titres of F(ab’)2 from three horses all reached at least 1:1600, and 50 μg of the F(ab’)2 fragments could completely neutralize 1x104 TCID50 SARS-CoV in vivo. Additionally, we observed that F(ab’)2 against BJ-01 strain could also protect cells from infection by the variant GZ-01 strain in vitro and in vivo. Our work has provided experimental support for testing the protective equine immunoglobulin in future large primate or human trials.