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Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment. Macrophages are considered a good candidate for cancer cytotherapy because of their phagocytotic capacity, enabling them to deliver cargo to tissues. Here authors engineer macrophages that are targeted to glypican-3-expressing tumour cells and equipped with drug-loaded exosomes and show therapeutic efficiency in a mouse model of hepatocellular cancer. [ABSTRACT FROM AUTHOR]

The way in which climate change-related information is framed can influence not only cognitive outcomes but also emotional responses. This web-based experiment (n = 331) investigated the effects of strategy framing and issue framing on emotions and online climate action intentions in the context of climate relationship between China and the United States. Results indicated that strategy framing increased negative emotions (i.e., anxiety and anger), whereas issue framing triggered more positive emotions (i.e., pride and excitement). No significant difference was observed regarding climate action intentions between two groups. Additionally, anxiety and anger mediated the effects of message framing on online climate action intentions. Habitual worry about climate change and attitude toward China-U.S. climate collaboration moderated the effects of strategy framing and issue framing on discrete emotions. The findings offer theoretical insights regarding emotional responses to strategy framing and practical implications on climate communication. [ABSTRACT FROM AUTHOR]

A fabrication strategy involving the electrostatic self-assembly of positively charged molybdenum disulfide (MoS2) nanosheets and negatively charged graphene oxide (GO) sheets and thermal reduction process is proposed to prepare MoS2/graphene hybrid films. The incorporation of MoS2 nanosheets embedded in graphene sheets serves as spacers, preventing the graphene sheets from restacking. The optimized free-standing MoS2/graphene hybrid film (MoS2/G-2) demonstrates a remarkable areal specific capacitance of 979 mF cm−2 at 1 mA cm−2, which is 2.85 times as much as pure reduced graphene oxide (rGO) (343 mF cm−2). Benefiting from the layer-layer self-assembly structure and good synergistic effect, MoS2/G-2 electrode exhibits enhanced capacitive performance with excellent cycling stability and no capacitance attenuation after 3000 cycles. Furthermore, by utilizing MoS2/G-2 as electrode material for the assembled symmetric supercapacitors (MoS2/G-2//MoS2/G-2), a superior areal energy density of 20 μWh cm−2 at the areal power density of 600 μW cm−2 is achieved. The prepared hybrid film materials hold immense potential in constructing high-performance film electrode for electrochemical energy storage. [ABSTRACT FROM AUTHOR]

Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.Here, the authors report results from a randomized, placebo-controlled phase 3 trial of the tetravalent SARS-CoV-2 protein vaccine SCTV01E, demonstrating a favorable efficacy profile during a time when predominant viral variants were changing from BA.5 and BF.7 to XBB. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) vaccination is a promising step toward cervical cancer elimination. This study was conducted to investigate the knowledge, attitude, and HPV vaccine uptake among female adults in mainland China based on a large e-commerce platform. Methods: We conducted a cross-sectional online survey of female adults between March 4 to April 20, 2022. The survey consisted of sociodemographic information, related knowledge, vaccination uptake, and attitudes toward vaccination. We included women aged 18–45 years in the final analysis. Logistic regressions were conducted to explore influencing factors associated with related knowledge, HPV vaccination uptake, and willingness to be vaccinated. Results: In total, 3,572 female adults (34 years, IQR 30–39) were included in the analysis. The majority of the participants were highly educated (78.7%) with a high monthly family income (79.0%). The median HPV knowledge score was 8.25 out of 11. More than 75% of respondents were unvaccinated, while 95.8% of unvaccinated female adults are willing to be vaccinated. Variables such as age, insurance, vaccination history, and whether one had heard of the HPV vaccine influence HPV vaccination practice (all p-values < 0.05). The main barriers to vaccination were vaccine inaccessibility and the high cost of the vaccine. Conclusion: The findings of our study highlight a moderate knowledge level, poor vaccination rate, and strong willingness to be vaccinated among Chinese female adults who were better educated and wealthier. Targeted health education and practical support should be provided in the future, to reduce gaps between vaccine uptake and vaccine acceptance. Significance: What is already known on this subject?: Sustained high human papillomavirus (HPV) vaccination coverage is crucial for cervical cancer prevention. People's knowledge and acceptance of HPV vaccination largely influence vaccination uptake. Previous studies have indicated a lack of awareness, knowledge, and low vaccine uptake in mainland China. What this study adds?: The findings of our study highlight a moderate knowledge level, poor vaccination rate, and strong willingness to vaccination among Chinese female adults who were better educated and wealthier. This national-level survey may guide future health education and accelerate the HPV vaccination program's further roll-out targeting women at different social levels in mainland China. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.The voltage-gated sodium channel Nav1.7 has a dual role in osteoarthritis—in chondrocytes, it promotes joint damage, and in dorsal root ganglia neurons, it increases pain transmission. [ABSTRACT FROM AUTHOR]

Habitat quality heterogeneity is one of the concrete manifestations of landscape pattern changes caused by human activities, which is of great significance to improve habitat quality by optimizing landscape pattern, thus scientifically protecting biodiversity and promoting ecological civilization construction. The coupling of rapid urbanization and ecological restoration measures has had a significant influence on the habitat quality of fragile and fragmented karst mountainous cities in recent years. In this study, spatiotemporal dynamics and heterogeneity of habitat quality and the impact of landscape patterns on habitat quality are analyzed in Guiyang, a typical karst mountain city in southwest China, mainly using the key methodologies such as the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, Exploratory Spatial Data Analysis (ESDA), and hierarchical partitioning (HP). We found that the habitat quality index of Guiyang City improved from 0.6643 to 0.6988 during 2000–2019; the distribution of habitat quality has significant spatiotemporal heterogeneity and spatial aggregation effect with the low values or the decreased areas concentrated in and around the built-up areas or urbanization expansion areas. Landscape composition had greater contribution than landscape configuration to habitat quality. The increased areas of natural habitat have had a positive effect on habitat quality. Moreover, each landscape configuration had a significant positive or negative correlation with the habitat quality. Therefore, implementing ecological protection and restoration measures in karst mountainous cities might be an effective strategy to improve habitat quality during rapid urbanization. Furthermore, optimizing habitat patterns, reducing the habitats loss, and protecting the natural habitat integrity are crucial to improving and maintaining biodiversity in the study area. [ABSTRACT FROM AUTHOR]

With the widespread and successful application of hyperspectral imaging, the task of classifying hyperspectral images has become a meaningful endeavor. This paper introduces a new approach to clustering hyperspectral images called CTNSC, which incorporates an attention mechanism to improve performance. In comparison to many current convolution-based methods for deep subspace clustering, our approach incorporates an attention mechanism to effectively capture the extensive spatial relationships that exist between objects in hyperspectral images. We combine convolution and attention through the use of Conformer blocks, enabling the network to simultaneously capture both local and global features of objects. As a result, our network can identify a more optimal deep affinity matrix, which can be utilized for spectral clustering to achieve better clustering results. We conducted experiments on three real-world datasets, and the results showed that CTNSC achieved excellent clustering performance compared to many commonly used clustering methods. [ABSTRACT FROM AUTHOR]

MnO2 nanowires/polyaniline composite (MnO2NW/PANI) was prepared by combining one-dimensional MnO2 nanowires (MnO2NW) with conductive polymer PANI surface coating. The MnO2NW were synthesized via a one-pot facile hydrothermal method. The composite MnO2NW/PANI was then prepared by in situ polymerization of aniline monomer on the surface of MnO2NW. The MnO2NW/PANI was able to serve as electroactive material and demonstrated a specific capacitance of 306.7 F/g recorded at a current density is 0.5 A/g, which is 28.4% higher than that of pristine MnO2 (only 238.9 F/g). The reduced electric resistance within MnO2NW/PANI interconnection networks and the good synergistic effect between MnO2NW and PANI for fast ion/charge transfer supports the enhanced capacitance of the composite. In addition, the MnO2NW/PANI composite electrode shows stable cycle performance, with capacity retention of 88.7% after 5000 repeated cycles test at a high current density of 5 A/g. The constructed nanocomposites have great potential in the further development of high-performance electrochemical electrode materials for energy storage application. [ABSTRACT FROM AUTHOR]

Targeting tumour immunosuppressive microenvironment is a crucial strategy in immunotherapy. However, the critical role of the tumour lymph node (LN) immune microenvironment (TLIME) in the tumour immune homoeostasis is often ignored. Here, we present a nanoinducer, NIL-IM-Lip, that remodels the suppressed TLIME via simultaneously mobilizing T and NK cells. The temperature-sensitive NIL-IM-Lip is firstly delivered to tumours, then directed to the LNs following pH-sensitive shedding of NGR motif and MMP2-responsive release of IL-15. IR780 and 1-MT induces immunogenic cell death and suppress regulatory T cells simultaneously during photo-thermal stimulation. We demonstrate that combining NIL-IM-Lip with anti-PD-1 significantly enhances the effectiveness of T and NK cells, leading to greatly suppressed tumour growth in both hot and cold tumour models, with complete response in some instances. Our work thus highlights the critical role of TLIME in immunotherapy and provides proof of principle to combine LN targeting with immune checkpoint blockade in cancer immunotherapy. The tumour lymph node microenvironment is an important contributor to the immune suppressiveness of tumours. Here authors target the tumours and the lymph node simultaneously via a pH and photothermal therapy targeted nanoparticle, and show mobilisation of anti-tumour cytotoxic T cells and NK cells and synergistic therapeutic effect with immune checkpoint blockade. [ABSTRACT FROM AUTHOR]

The optimal control problem with a long run average cost is investigated for unknown linear discrete-time systems with additive noise. The authors propose a value iteration-based stochastic adaptive dynamic programming (VI-based SADP) algorithm, based on which the optimal controller is obtained. Different from the existing relevant work, the algorithm does not need to estimate the expectation (conditional expectation) and variance (conditional variance) of states or other relevant variables, and the convergence of the algorithm can be proved rigorously. A simulation example is given to verify the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

Considering that the conventional subspace clustering methods of sparse subspace clustering (SSC) and low-rank representation (LRR) are only applicable to linear manifolds, we propose a novel subspace clustering framework that generalizes them for nonlinear manifolds. To do this, we integrate a weighting matrix and kernel matrix into the regularization of this framework. The weighting matrix is calculated using the similarities between tangent spaces on data manifolds and the Euclidean distances between data points, so that it can explicitly characterize the intrinsic geometry of data manifolds. Besides, we provide a geometrical interpretation for the effects of weighted ℓ∗-norm involved in the proposed framework, exploiting symmetric gauge function (SGF) of von Neumann theory that establishes a relationship exactly between singular and matrix norm. To solve the regularization with respect to the weighted norm, we design a fixed-point continuation algorithm to obtain an approximate closed solution. Experimental results on three computer vision tasks show the superiority of clustering accuracy over other similar approaches and demonstrate the effectiveness of the weighting matrix. That also proves the proposed method has better interpretability than other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

The inhibition of voltage-gated sodium (NaV) channels in somatosensory neurons presents a promising novel modality for the treatment of pain. However, the precise contribution of these channels to neuronal excitability, the cellular correlate of pain, is unknown; previous studies using genetic knockout models or pharmacologic block of NaV channels have identified general roles for distinct sodium channel isoforms, but have never quantified their exact contributions to these processes. To address this deficit, we have utilized dynamic clamp electrophysiology to precisely tune in varying levels of NaV1.8 and NaV1.9 currents into induced pluripotent stem cell-derived sensory neurons (iPSC-SNs), allowing us to quantify how graded changes in these currents affect different parameters of neuronal excitability and electrogenesis. We quantify and report direct relationships between NaV1.8 current density and action potential half-width, overshoot, and repetitive firing. We additionally quantify the effect varying NaV1.9 current densities have on neuronal membrane potential and rheobase. Furthermore, we examined the simultaneous interplay between NaV1.8 and NaV1.9 on neuronal excitability. Finally, we show that minor biophysical changes in the gating of NaV1.8 can render human iPSC-SNs hyperexcitable, in a first-of-its-kind investigation of a gain-of-function NaV1.8 mutation in a human neuronal background. [ABSTRACT FROM AUTHOR]

In this paper, stochastic resonance effect on the optimal detection under Neyman–Pearson (NP) criterion is investigated for a general nonlinear system. To this end, a noise enhanced detection optimization problem for maximizing the probability of detection under a constant constraint on the probability of false-alarm is formulated, where an additive noise is added to the nonlinear system input and the final decision is made based on the system output according to the NP criterion. Firstly, the noise modified NP decision rule is derived. Since one additive noise corresponds to one noise modified NP decision rule, the noise-modified NP decision rule can be viewed as a function of the additive noise. Then, the improvability of the optimal detection performance under NP criterion via the proposed noise-modified decision solution is simply discussed. The optimal additive noise is deduced as a random signal of no more than two constant vectors and the corresponding noise-modified NP decision rule is also determined. Finally, the performance comparisons between the original and the noise-modified optimal NP decision solutions for the sine transform system and the Amplitude limit system are made to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

Tea gardens can not only improve the local ecological environment but also increase farmers' incomes, thereby alleviating poverty, and thus achieve a win–win situation between economic and ecological benefits. In this research, the quality and value of the ecological benefits of tea gardens in Meitan County, China, were evaluated from there aspects—soil conservation, water conservation, and carbon storage—using data from the 2015 Meitan Country Forestry Resources Second Class Survey, thematic data, socioeconomic data, the Integrated Valuation of Ecosystem Services and Tradeoffs model, and relevant methods of value evaluation. The results showed that: (1) the water conservation of tea garden in Meitan County was 0.61 million m3/a, the carbon storage capacity was 187.65 × 104 t/a, and the soil consolidation was 3.78 × 104 t/a; (2) the ecological benefit value of tea garden in Meitan County was 3.173 billion yuan/a, and the ecological benefit value per unit area was 241,700 yuan/a; (3) among the ecosystem service function values, the value of carbon storage (2.403 billion yuan/a) was greater than that of water conservation (708 million yuan/a) and soil conservation (62 million yuan/a); and (4) of the studied townships, the largest ecological benefits of tea gardens were mainly observed in Yongxing Town, Xinglong Town, Fuxing Town, and Meijiang Town, with the ecological benefits per unit area being largest in Xihe Town and smallest in Xinglong Town. The purpose of this study is to highlight the important value of tea garden ecosystems in Meitan Country, which is not only conducive to the protection of the ecological environment but can also assist government departments to carry out industrial planning and policy-making to promote the harmonious development of the economy and environment. [ABSTRACT FROM AUTHOR]

Phosphorus plays an important role in double rice cropping systems grown on acidic paddy soil. To improve our knowledge and increase crop utilization of applied phosphorus fertilizers in paddy soils, we investigated changes in the content of soil inorganic phosphorus fractions in response to long-term application of chemical and organic phosphorus fertilizers. In this 35-year-long experiment, paddy soil in a double rice cropping system received one of three different fertilizer treatments: (1) cattle manure, M; (2) a chemical fertilizer of nitrogen (N), phosphorus (P), and potassium (K), NPK; and (3) a combination of NPK and M (NPKM) twice per year. Results showed that the maximum contents of Olsen-P in M, NPK and NPKM stabilized at 12.9, 31.7 and 52.7 mg/kg, respectively over 35 years. In contrast, the proportions of soil inorganic phosphorus content in total phosphorus of M, NPK and NPKM changed from 62.2% at the beginning of the experiment to 53.3, 61.9 and 66.2%, respectively. At equal amounts of accumulated phosphorus surplus, the increasing rates of total inorganic phosphorus content and inorganic phosphorus fractions in NPK were much higher than those in M and NPKM. At an average amount of accumulated phosphorus surplus of 100 kg/ha, the total inorganic phosphorus content of the NPK and NPKM treatments increased by 39.6 and 21.6 mg/kg, respectively. Fertilization mainly decreased the ratio of organic phosphorus to inorganic phosphorus and increased the ratio of aluminum-bound-phosphorus (Al-P) to inorganic phosphorus, especially under the NPK and NPKM treatments. Redundancy analysis showed that total phosphorus and Olsen-P were more closely correlated to iron-bound-phosphorus (Fe-P), calcium-bound-phosphorus (Ca-P) and Al-P fractions. This study suggests that the NPK and NPKM treatments increased phosphorus supply and inorganic phosphorus fractions compared to the manure application. Therefore, to avoid accumulation of a surplus of unabsorbed phosphorus and minimize phosphorus-leaching risk from acidic paddy soil, rates of inorganic phosphorus application, such as the combined application of manure and inorganic phosphorus fertilizer, should be reduced. [ABSTRACT FROM AUTHOR]

This paper presents two distributed stochastic source seeking controllers to navigate multiple vehicles to seek the signal source, using the measurements of the signal field at their own positions and information of their neighbors. The first controller utilizes neighbors' measurements of the signal field and the second controller utilizes relative positions between neighbors. The effectiveness of the proposed two controllers is proved by the stochastic averaging theory. The convergence speed of the source seeking system can be calculated for the first controller and it is proved that the convergence speed under the second controller is not slower than that under the first controller. In particular, the distributed controllers are effective for both connected and unconnected graph. Numerical simulations are given to illustrate the effectiveness of the controllers. [ABSTRACT FROM AUTHOR]

The detection and identification of cigarette ash in fire debris can be meaningful in fire investigations caused by burning cigarettes. In this work, a novel analytical method based on negative chemical ionization time-of-flight mass spectrometry (NCI/TOFMS) combined with a phosphoric-acid-enhanced evaporation strategy has been developed for the discrimination of cigarette ash samples (CAs) and common household decoration material ash samples (CHDMAs). A series of characteristic ions representing the acidified products HNCO and formic acid in the CAs were achieved, whose signal responses were enhanced with the help of mechanical agitation operation. To account for both the signal responses of the characteristic ions and acid corrosion of the ion source, the dynamic-purge gas was chosen to be 200 mL/min. The whole time for analysis was only 5 min, which is suitable for high-throughput measurements of large quantities of fire debris. As a result, a preliminary discrimination was achieved between the CAs and CHDMAs by virtue of the chemometric tool of principal components analysis (PCA) based on intensity differences of the characteristic ions. The results are encouraging and highlight the potential of NCI/TOFMS without complicated sample preparation steps for the accurate and high-throughput identification of cigarette ash on substrates in fire debris. [ABSTRACT FROM AUTHOR]

The added data, First, Second, Third, Fourth, Fifth, Sixth should have been deleted before the given names of the authors. The online version of the original article can be found at https://doi.org/10.1007/s12145-023-01031-6 B Earth Science Informatics b https://doi.org/10.1007/s12145-023-01031-6 The names of the authors in the published version of the above article were incorrectly presented. [Extracted from the article]

In this paper, a novel spectral-spatial hyperspectral image classification method has been proposed by designing hierarchical subspace switch ensemble learning algorithm. First, the hyperspectral images are processed by fast bilateral filtering to get the spatial features. The spectral features and spatial features are combined to form the initial feature set. Second, Hierarchical instance learning based on iterative means clustering method is designed to obtain hierarchical instance space. Third, random subspace method (RSM) is used for sampling the features and samples, thereby forming multiple sub sample set. After that, semi-supervised learning (S2L) is applied to choose test samples for improving classification performance without touching the class labels. Then, micro noise linear dimension reduction (mNLDR) is used for dimension reduction. Afterwards, ensemble multiple kernels SVM(EMK_SVM) are used for stable classification results. Finally, final classification results are obtained by combining classification results with voting strategy. Experimental results on real hyperspectral scenes demonstrate that the proposed method can effectively improve the classification performance apparently. [ABSTRACT FROM AUTHOR]

Objective: Whether automated peritoneal dialysis (APD) is a feasible strategy for urgent-start peritoneal dialysis (PD) therapy during the break-in period remains unclear. This study was conducted to compare the efficacy as well as complications among three PD modes during the break-in period.Methods: Ninety-six patients treated with urgent-start PD after catheterization were retrospectively analyzed. Patients were divided into three groups, incremental continuous ambulatory PD (CAPD) group (n = 26); APD group (n = 42); and APD-CAPD group (n = 28). Clinical parameters at the end of the break-in period and 1 month after the initiation of PD treatment were collected and analyzed.Results: Compared with the traditional incremental CAPD, APD and APD-CAPD were superior as they could effectively remove small-molecule uremic toxins and correct electrolyte imbalance (P < 0.05), while did not increase the incidence of early complications during the break-in period (P > 0.05). However, APD led to a significant decline in albumin and pre-albumin, as compared with APD-CAPD and CAPD (P < 0.05). A PD strategy consisting 6 days of APD and 3 days of CAPD showed a great advantage in preventing excessive protein loss. There were no significant differences in all tested biochemical parameters among the three groups at 1 month after treatment (all P > 0.05).Conclusion: Application of APD for urgent-start PD during the break-in period is feasible. A combination of APD and CAPD regimens seems to be a more reasonable mode. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical and histopathological features of non-diabetic renal disease (NDRD) superimposed on diabetic nephropathy (DN) in northeastern Chinese patients with type 2 diabetes mellitus (T2D), and compare the changes with those of pure DN and isolated NDRD. Methods: Single-center retrospective analysis based on medical records of 273 patients (172 men, mean age: 51.1 ± 12.4 years) with T2D who underwent renal biopsy between February 2000 and October 2015. All patients were diagnosed as cases of pure DN, isolated NDRD or NDRD superimposed on DN. Results: Out of the 273 T2D patients, 68 (24.9 %) had DN, 175 (64.1 %) had NDRD, and 30 (11.0 %) had NDRD superimposed on DN. Idiopathic membranous nephropathy (IMN, 29.7 %) was the most common NDRD followed by IgA nephropathy (IgAN, 22.9 %), and hypertensive renal arteriolar sclerosis was the most common lesion in patients diagnosed as NDRD superimposed on DN. Patients with NDRD had a shorter duration of diabetes and lower frequencies of diabetic retinopathy (DR, 6.9 %) and renal failure (28.0 %), which is consistent with higher estimated glomerular filtration rates (eGFR) and lower systolic blood pressure (SBP). No significant between-group differences were observed with respect to proteinuria and hematuria. Conclusion: Renal biopsy is strongly recommended for T2D patients to distinguish DN, NDRD and NDRD superimposed on DN, especially in patients with no signs of DR. This approach may help in early diagnosis and treatment of NDRD and improve renal outcomes in northeastern Chinese T2D patients. [ABSTRACT FROM AUTHOR]

The application of asphalt with low penetration in warm areas to improve rutting-resistance has attracted great interest in recent years. Deoiled asphalt (DOA) and slurry, by-products of solvent deasphalting and fluid catalytic cracking respectively, are utilized with low value-added. The objective of this work was to prepare paving grade asphalt by blending various proportion of FCC slurry with DOA. The effect of chemical composition on viscoelastic characteristics of the blend was investigated and special emphasis was placed on the linear viscoelasticity and viscous flow behavior as well as on empirical tests. The results revealed that SARA fractions of the blends are close to asphalt and are compromise between DOA in which the content of asphaltenes is high and slurry in which is rich in aromatics. Also, SARA fractions have a significant influence on the rheological properties of the blends. Asphaltenes have been proved to enhance the moduli of asphalt and low penetration blends have demonstrated high rutting and deformation resistance especially at high temperatures. Taking into account the balance between workability and in-service performance, application of the 40 wt% slurry in DOA is highly recommended. It is indicated that a more inferior aging resistance with the increase of slurry in DOA. As a result, it is a highly effective and meaningful way to utilize DOA and FCC slurry. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical characteristics and histopathological features of kidney disease in elderly patients. Methods: We retrospectively analyzed the results of 4,185 consecutive renal biopsies, and 288 patients aged >60 years at the Second Hospital of Jilin University from January 1998 to December 2013 were finally included. All patients had been clinically and histologically diagnosed with kidney disease. Results: Nephrotic syndrome was the main clinical indication for biopsy. Twenty-four patients (8.33 %) experienced a minor complication related to their biopsy procedure. Among patients diagnosed as primary glomerulonephritis (GN), membranous nephropathy (MN) was the most frequent subclassification (24.7 %), followed by mesangioproliferative glomerulonephritis (MsPGN, 11.1 %) and IgA nephropathy (IgAN, 8.0 %). Amyloidosis (8.7 %) was the most common secondary GN, followed by antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune GN (5.2 %) and diabetic nephropathy (DN, 3.8 %). Based on renal biopsies results, 143/288 patients received immunosuppressive therapy and showed an overall remission rate (complete plus partial remissions) of 74.1 %. Among 71 MN patients, 29 patients received steroids plus cyclophosphamide and showed a remission rate of 79.3 %, while 42 patients received steroids and tacrolimus and showed a remission rate of 90.5 %. Among 25 patients with amyloidosis, 22 cases received melphalan plus dexamethasone and showed a remission rate of 40.9 %, while three patients received vincristine, adriamycin, and dexamethasone and showed a remission rate of 66.7 %. Conclusion: Making an accurate pathologic diagnosis by renal biopsy is crucial for selecting the proper treatment for elderly patients with kidney disease. [ABSTRACT FROM AUTHOR]

This article reviews the available rodent models of peritoneal dialysis (PD) that have been developed over the past 20 years and the complications associated with their use. Although there are several methods used in different studies, the focus of this article is not to review or provide detailed summaries of these methods. Rather, this article reviews the most common methods of establishing a dialysis model in rodents, the assays used to observe function of the peritoneum in dialysis, and how these models are adapted to study peritonitis and peritoneal fibrosis. We compared the advantages and disadvantages of different methods, which should be helpful in studies of PD and may provide valuable data for further clinical studies. [ABSTRACT FROM AUTHOR]

Mice with chronic graft-versus-host disease (cGVHD) induced by transferring parental BALB/C lymphocytes into (C57BL/6 × BALB/C) F1 (CBF1) hybrids, develop a syndrome characterized by B-cell hyperactivity, autoantibody production, and immune complex-mediated glomerulonephritis. In this model, we evaluated the role of leflunomide on the development of lupus nephritis in system autoimmunity. Daily administration of leflunomide (15 mg/kg/d) from 2 weeks after cGVHD induction can dramatically reduce the production of autoantibodies and immune complex deposition in the kidney, leading to relieved kidney damage and reduced mortality. The therapeutic effect of leflunomide on the lupus-prone mice was partially due to the inhibition of TLR9 signaling pathway, which was an important component of innate immune system. [ABSTRACT FROM AUTHOR]

one-step purification process using flow-through mode ion-exchange chromatography (Ft-IEC) was evaluated for the purification of Immunoglobulin G (IgG) from rabbit and guinea pig serum. A simple protein precipitation with saturated ammonium sulfate was used to pretreated plasma samples. Chromatographic separation was carried out on DEAE Sepharose Fast Flow (F.F.) column at a flow rate of 1 mL min. Ft-IEC using Tris-HCl buffer at pH 7.0 allowed the recovery of 22% of the loaded IgG with purity of 95% existed in flowthrough and washing effluents but not in elution effluents. To be compared, bind-elute mode IEC using Tris-HCl buffer at pH 8.5 based on the routine protocol showed that the recovery of 15% of the loaded IgG with purity of 80% existed in elution effluents. These results indicate that the Ft-IEC is an effective method for purifying IgG from sera of rabbit and guinea pig and may also be suitable for other animal sera by adjusting pH at equilibrium buffer for chromatography column. [ABSTRACT FROM AUTHOR]

GTI-2040 is a potent antisense to the M2 subunit of the ribonucleotide reductase (RNR), an enzyme involved in the de novo synthesis of nucleoside triphosphates. We hypothesized that combination of GTI-2040 with the cytarabine (Ara-C) could result in an enhanced cytotoxic effect with perturbed intracellular deoxynucleotide/nucleotide (dNTP/NTP) pools including Ara-C triphosphate (Ara-CTP). This study aims to provide a direct experimental support of this hypothesis by monitoring the biochemical modulation effects, intracellular levels of Ara-CTP, dNTPs/NTPs following the combination treatment of Ara-C, and GTI-2040 in K562 human leukemia cells. GTI-2040 was introduced into cells via electroporation. A hybridization-ligation ELISA was used to quantify intracellular GTI-2040 concentrations. Real-time PCR and Western blot methods were used to measure the RNR M2 mRNA and protein levels, respectively. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay was used to measure the cytotoxicity following various drug treatments. A non-radioactive HPLC-UV method was used for measuring the intracellular Ara-CTP, while a LC-MS/MS method was used to quantify intracellular dNTP/NTP pools. GTI-2040 was found to downregulate M2 mRNA and protein levels in a dose-dependent manner and showed significant decrease in dNTP but not NTP pool. When combining GTI-2040 with Ara-C, a synergistic cytotoxicity was observed with no further change in dNTP/NTP pools. Importantly, pretreatment of K562 cells with GTI-2040 was found to increase Ara-CTP level for the first time, and this effect may be due to inhibition of RNR by GTI-2040. This finding provides a laboratory justification for the current phase I/II evaluation of GTI-2040 in combination with Ara-C in patients with acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that bind to target mRNAs and regulate their expression. Recent evidence has indicated the involvement of miRNAs in human malignancies. It has been suggested that aberrantly down-regulated or up-regulated miRNAs may be replaced with synthetic miRNAs or antagomiRNAs, respectively, and restore normal cell functions. As therapeutic development requires analytical support, we developed and validated an ultrasensitive and selective assay for quantification of synthetic 2′-methoxyphosphorothiolate-miRNA in mouse plasma and cell lysate for the first time. The method is based on a hybridization-ligation fluorescence enzyme-linked immunosorbent assay and has provided a linear dynamic range of 10-1,000,000 pM for three synthetic miRNAs both singly and in a mixture. The intra- and inter-day coefficients of variation were <20% and the accuracy values nearly 100%. Using this assay, we performed pharmacokinetic studies of three synthetic miRNAs in mice treated with a single i.v. bolus dose of 7.5 mg kg. The 2-methoxyphosphorothiolate-miRNAs reached peak concentrations in the μM and nM ranges in plasma and bone marrow, respectively, and remained measurable at 24 h. These concentrations are in a range that shows biological activities. We conclude that this method provides a general and valuable tool for the pharmacologic study and clinical development of synthetic miRNAs. [ABSTRACT FROM AUTHOR]

Highly luminescent Tb3+-doped CePO4 with 1D nanostructures were prepared by a simple hydrothermal method. The obtained CePO4:Tb has a hexagonal or monoclinic structure under different synthetical process. Uniform 1D nanorods with diameters between 40 and 500 nm, and the length ranging from several hundred nanometres to several micrometres were obtained. It is easy to increase the sizes of the samples by adding some CTAB. Results of the XPS show that there is no Ce4+ in the samples because of the absence of the signal around 917 eV, which is characteristic of Ce4+. The study of the photoluminescence of Tb3+-doped CePO4 indicates that the luminescent properties of these nanophosphors are strongly dependent on their structures and morphologies. [ABSTRACT FROM AUTHOR]

Objective: Objective: To assess the effect and adverse effects of transdermal fentanyl for elderly patients with cancer pain in China. Methods: A total of 1664 elderly patients (aged 65-90 with mean age of 72.6) with cancer pain enrolled in the multicenter study from 136 institutes in China. Of them, 408 (28.8%) patients were 75 years old or older. All patients received transdermal fentanyl for the management of cancer pain. The patients were asked to record the attacks of pain, quality of life, and any side effects of the treatment. Results: Baseline mean of pain intensity was 7.34. On day 1, 3, 6, 9 15, and 30, the pain mean scores were decreased to 3.82, 2.80, 2.43, 2.11, 1.83, 1.64 (P=0.000). The effective rate was 97.18%. The mean doses of fentanyl was 31.34 μg/h (25-150 μg/h) initially, and 40.59 μg/h and 47.50 μg/h (25-200 μg/h) at day 15 and day 30. At treatment day 15, the dose of fentanyl was ranger from 25 to 50 μg/h in 91.8% of patients, 75 to 100 μg/h in 7.5% patients, and 125 to 200 μg/h only in 0.8% patients. The fine quality of life was in 25.4% patients before treatment, and was 71.15% and 73.04% at day 15 and day 30 respectively (P=0.0000). The common side effects were constipation (10.70%), nausea (11.96%), dizzy (6.85%), vomiting (3.85%), sedation (2.40%), Respiratory depression (0.12%). 86.2% patients preferred continue treated by transdermal fentanyl. Conclusions: Transdermal fentanyl for the elderly with cancer pain is effective, safe, convenient, and can improve the quality of life. Transdermal fentanyl can be recommended as a first-line drug for the treatment of elderly patients with moderate to severe cancer pain, and the initial doses is recommended as 25 μg/h. [ABSTRACT FROM AUTHOR]

Gap junctions are conductive channels that connect the interiors of coupled cells. We determined whether gap junctions propagate transcellular signals during metabolic stress and whether such signaling exacerbates cell injury. Although overexpression of the human proto-oncogene bcl2 in C6 glioma cells normally increased their resistance to injury, the relative resistance of bcl2+ cells to calcium overload, oxidative stress and metabolic inhibition was compromised when they formed gap junctions with more vulnerable cells. The likelihood of death was in direct proportion to the number and density of gap junctions with their less resistant neighbors. Thus, dying glia killed neighboring cells that would otherwise have escaped injury. This process of glial 'fratricide' may provide a basis for the secondary propagation of brain injury in cerebral ischemia. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of Bailong Tablet and chemotherapy on treatment of moderate and advanced cancers. Methods: The patients were divided randomly into two groups. The treated group (n= 41) was treated with chemotherapy plus Bailong Tablet; and the control group (n= 22) treated with chemotherapy alone. Treatment effectiveness was measured with Karnofsky scores. Results: Karnofsky performance status in the treated group before and after treatment was 66.0 ± 8.7 and 68.0 ± 5.9 respectively, that in the control group was 67. 0 ± 6.8 and 53. 0 ± 7.3 respectively. The completion rate of chemotherapy in the treated group (92.6%, 38/41) was higher than that in control (77.2%, 17/22, P < 0.05). The side-effects caused by chemotherapy in the treated group were lower than that in the control group ( P < 0.05). CD, CD and CD /CD ratio were higher in the treated group. Conclusion: Bailong Tablet can enhance the therapeutic effect and reduce the side-effects of chemotherapy. One possible mechanism is the modulation of cellular immune function. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy and molecularly targeted therapies is a major problem in current leukemia treatments. Here, we investigated cross-talk between the miR-221 network and P-glycoprotein (P-gp) in doxorubicin-induced drug resistance of leukemia cells. Multifunctional gold nanoparticles were designed and synthesized to co-deliver three anticancer agents, AS1411, doxorubicin and anti-221, for improving leukemia treatment efficacy. These nanoparticles significantly inhibited the proliferation and clonogenic potential, and induced apoptosis of drug-resistant leukemia cells. The decreased growth of drug-resistant cells induced by these nanoparticles was associated with marked downregulation of miR-221 and DNMT1, leading to restored p27kip1 and p15ink4b tumor suppressor expression, as well as miR-221-mediated reduction of P-gp expression. Finally, primary blasts derived from leukemia patients experiencing chemoresistant relapse that were exposed to these nanoparticles were sensitized to doxorubicin, as evidenced by suppression of leukemic cell growth and a significant reduction of the doxorubicin IC50 value. Our findings provide proof of concept that this novel drug delivery system can precisely reverse the multidrug resistant leukemia phenotype based on preclinical models of leukemia, providing the framework for future clinical trials aimed at overcoming drug resistance and improving patient outcome. [ABSTRACT FROM AUTHOR]