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Drug delivery nanoplatforms have been applied in bioimaging, medical diagnosis, drug delivery and medical therapy. However, insolubility, toxicity, instability, nonspecific targeting and short retention of many hydrophobic drugs limit their extensive applications. Herein, we have constructed a passive targeting and long retention therapeutic nanoplatform of core-shell gefitinib/poly (ethylene glycol)-polytyrosine nanocomplexes (Gef-PY NCs). The Gef-PY NCs have good water-solubility, non-toxicity (correspond to 1/10 dosage of effective gefitinib (hydrochloride) (Gef·HCl) (normal drug administration and slow-release) and high stability (120 days, 80% drug retention at 4 or 25 °C). The core-shell Gef-PY NCs present unexpected kidney targeting and drug slow-release capacity (ca. 72 h). The good water-solubility, non-toxicity and high stability of Gef-PY NCs effectively solve the bottleneck question that Gef-based therapy could be used only in intraperitoneal injection due to its insolubility and severe toxicity. Such excellent properties (e.g., water-solubility, non-toxicity, high stability, kidney targeting and long retention) of Gef-PY NCs create their prominent anti-fibrosis capabilities, such as decreasing approximately 40% tubulointerstitial fibrosis area and 68% expression of collagen I within 7 days. This therapeutic efficacy is well-matched with that of 10 times the dosage of toxic Gef·HCl. It is very hopeful that Gef-PY NCs could realize clinical applications and such a strategy offers an effective route to design high-efficiency treatments for kidney- and tumor-related diseases.

This study uses “big” data to empirically investigate a highly effective, but underexamined way of reducing one’s exposure toward air pollution—short-term travel. We determine subscribers’ ...

While there is abundant evidence demonstrating that residents permanently migrate in search of locations with cleaner air, there are considerably fewer studies that investigate if travellers also take short-term trips to reduce their exposure to air pollution. In this study, we use a complete dataset of flights at Beijing International Airport to investigate if travel patterns are indeed correlated with air quality-differences across cities in China. Our identification strategy is aided by instrumenting air quality using thermal inversions. We find that a one-unit increase in the Air Pollution Index of origin over destination city would lead to a 0.36% increase in number of passengers on the flight. When considered separately by cabin-class, the number of first-class passengers increased about three-times faster than economy-class. Using lagged air quality information, we also find that averting-related travel decisions are most sensitive to destination’s air quality on day-of-travel. This indicates that flight passengers likely rely on air quality forecast information to make air pollution-induced travel decisions.

Grain size is a key constituent of grain weight and appearance in rice. However, insufficient attention has been paid to the small-effect QTLs on grain size. In the present study, residual heterozygous populations were developed for mapping two genetically linked small-effect QTLs for grain size. After genotyping and phenotyping of five successive generations, qGS7.1 was dissected into three QTLs and two were selected for further analysis. qTGW7.2a was finally mapped into a 21.10-kb interval containing four annotated candidate genes. Transcript levels assay showed that the expression of candidates LOC_Os07g39490 and LOC_Os07g39500 were significantly reduced in the NIL- qTGW7.2a BG1 . Cytological observation indicated that qTGW7.2a regulated grain width through controlling cell expansion. Use the same strategy, qTGW7.2b was fine mapped into a 52.71-kb interval, showing a significant effect on grain length and width with opposite allelic directions but little on grain weight. Our study provides new genetic resources for yield improvement and fine-tunes of grain size in rice.

Chlamydia psittaci is an important zoonotic factor associated with human and animal atypical pneumonia. Resisting host cell apoptosis is central to sustaining Chlamydia infection in vivo. Chlamydia can secrete inclusion membrane proteins (Incs) that play important roles in their development cycle and pathogenesis. CPSIT_0846 is an Inc protein in C. psittaci identified by our team in previous work. In the current study, we investigated the regulatory role of CPSIT_0846 in HeLa cell apoptosis, and explored potential mechanisms. The results showed that HeLa cells treated with CPSIT_0846 contained fewer apoptotic bodies and exhibited a lower apoptotic rate than untreated cells either with Hoechst 33258 fluorescence staining or flow cytometry with or without induction by staurosporine (STS). CPSIT_0846 could increase the phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) or stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathways, and the Bcl-2 associated X protein (Bax)/B cell lymphoma 2 (Bcl-2) ratio, levels of cleaved caspase-3/9 and cleaved Poly-ADP-ribose polymerase (PARP) were significantly up-regulated following inhibition of ERK1/2 or SAPK/JNK pathways with U0126 or SP600125. After carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment, the mitochondrial membrane potential (MMP) of cells was significantly decreased in control group, but stable in the CPSIT_0846 treated one, and less cytochrome c (Cyt.c) was released into the cytoplasm. Inhibition of the ERK1/2 or SAPK/JNK pathway significantly decreased the JC-1 red-green fluorescence signal, and promoted Cyt.c discharge into the cytoplasm in HeLa cells treated with CPSIT_0846. In conclusion, CPSIT_0846 can regulate mitochondrial pathway-mediated apoptosis in HeLa cells by activating the ERK/JNK signaling pathway.

Background Plant cell walls are the main physical barrier encountered by pathogens colonizing plant tissues. Alteration of cell wall integrity (CWI) can activate specific defenses by impairing proteins involved in cell wall biosynthesis, degradation and remodeling, or cell wall damage due to biotic or abiotic stress. Polygalacturonase (PG) depolymerize pectin by hydrolysis, thereby altering pectin composition and structures and activating cell wall defense. Although many studies of CWI have been reported, the mechanism of how PGs regulate cell wall immune response is not well understood. Results Necrosis appeared in leaf tips at the tillering stage, finally resulting in 3–5 cm of dark brown necrotic tissue. ltn-212 showed obvious cell death and accumulation of H2O2 in leaf tips. The defense responses were activated in ltn-212 to resist bacterial blight pathogen of rice. Map based cloning revealed that a single base substitution (G-A) in the first intron caused incorrect splicing of OsPG1, resulting in a necrotic phenotype. OsPG1 is constitutively expressed in all organs, and the wild-type phenotype was restored in complementation individuals and knockout of wild-type lines resulted in necrosis as in ltn-212. Transmission electron microscopy showed that thicknesses of cell walls were significantly reduced and cell size and shape were significantly diminished in ltn-212. Conclusion These results demonstrate that OsPG1 encodes a PG in response to the leaf tip necrosis phenotype of ltn-212. Loss-of-function mutation of ltn-212 destroyed CWI, resulting in spontaneous cell death and an auto-activated defense response including reactive oxygen species (ROS) burst and pathogenesis-related (PR) gene expression, as well as enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo). These findings promote our understanding of the CWI mediated defense response.

BackgroundLong bones of limbs are formed through endochondral bone formation, which depends on the coordinated development of growth plates. Our previous studies have demonstrated that dysfunction of mitogen-activated protein kinase 7 (MAPK7) can cause skeletal dysplasia. However, little is known about the role of MAPK7 in the regulation of proliferation and differentiation of chondrocytes during growth plate development.ResultsAblation of MAPK7 expression in chondrocytes led to growth restriction, short limbs and bone mass loss in postnatal mice. Histological studies revealed that MAPK7 deficiency increased the apoptosis and decreased the proliferation of chondrocytes in the center of the proliferative layer, where the most highly hypoxic chondrocytes are located. Accordingly, hypertrophic differentiation markers were downregulated in the central hypertrophic layer, beneath the site where abnormal apoptosis was observed. Simultaneously, we demonstrated that hypoxic adaptation and hypoxia-induced activation of hypoxia-inducible factor 1 subunit α (HIF1α) were impaired when MAPK7 could not be activated normally in primary chondrocytes. Concomitantly, vascular invasion into epiphyseal cartilage was inhibited whenMapk7was deleted.ConclusionsWe demonstrated that MAPK7 is necessary for maintaining proliferation, survival, and differentiation of chondrocytes during postnatal growth plate development, possibly through modulating HIF1α signaling for adaptation to hypoxia. These results indicate that MAPK7 signaling might be a target for treatment of chondrodysplasia.

Pogostone analogous XW-12 displays an inhibitory effect on Staphylococcus aureus. However, the insolubility of the compound has restricted its further applications. This work aims to improve the water-solubility of XW-12, we used previously synthesised pogostone derivatives XW-12, forming nanoparticles with PLGA-PEG by a single-emulsion solvent-evaporation technique. Characterisations of XW-12 nanoparticles were performed. The in vitro and in vivo experiments confirmed its antimicrobial efficacy and toxicity. The results revealed that the XW-12 NPs had a particle size of approximately 200.0 nm, a slower and sustained release. An antibacterial experiment showed that XW-12 NPs had a lower minimal inhibitory concentration value of 1 μg/mL. In the mouse systemic infection model of MRSA, XW-12 NPs indicated high antibacterial activity. In addition, in vivo, toxicity studies declared that XW-12 NPs had a low cytotoxicity. Therefore, this study suggested that XW-12 NPs may be a great potential antibacterial agent in the treatment of clinical MRSA infection.

Summary Minimally invasive surgery (MIS) is emerging as a burgeoning mode of medical treatment and is widely adopted in practical clinical operations. Here, we report a soft manipulator that can actively deform and navigate through a narrow and constrained environment. Stiffness tunability, tremor filtration, and motion scaling capabilities are incorporated to ensure the position and posture of the manipulator during operation. Based on teleoperation through a handle shank, we demonstrate the capability of navigating through a complex, constrained, and narrow space of the human skeleton. By attaching a camera and syringe needle at the front tip of the soft manipulator, the capability of acupuncture treatment and in vivo drug delivery in a medical mannequin is further demonstrated. Finally, autonomous recognition and tracking systems are developed to ensure the surgeon can effortlessly teleoperate the soft manipulator to enter the human body.

Hyperglycemia promotes podocyte apoptosis and contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms of hyperglycemia‑induced podocyte apoptosis remain unknown. Recent studies have implicated Src‑associated substrate during mitosis of 68 kDa (Sam68) in various cellular processes including RNA metabolism, apoptosis, signal transduction. This study sought to examine the effect of Sam68 on high glucose (HG)‑induced podocytes apoptosis, and the mechanism underlying this effect. Immortalized mouse podocytes were exposed to medium containing normal glucose, or HG and Sam68 siRNA, respectively. The expression of Sam68 in podocytes was determined by fluorescence quantitative PCR (qPCR), immunofluorescence and immunoblotting. The role of Sam68 in HG‑induced podocyte apoptosis was further evaluated by inhibiting Sam68 expression by Sam68 siRNA and performing flow cytometry. The mRNA and protein expression of pro‑apoptosis gene Bax and anti‑apoptotic gene Bcl‑2 were assessed by qRCR and immunoblotting. In the present study, it was first demonstrated that Sam68 was upregulated in a time and dose‑dependent manner in in vitro HG‑treated podocytes. Pretreatment with Sam68 siRNA markedly decreased nuclear Sam68 expression. Moreover, the effects of HG‑induced apoptosis were also abrogated by Sam68 knockdown in cultured podocytes. Furthermore, HG increased Bax and decreased Bcl‑2 protein expression in cultured podocytes, and this effect was blocked by Sam68 knockdown. The results of the present study revealed that Sam68 mediated HG‑induced podocyte apoptosis, probably through the Bax/Bcl‑2 signaling pathway, and thus may be a potential therapeutic target for DN.

Lesion mimic mutants are excellent models for research on molecular mechanisms of cell death and defense responses in rice. We identified a new rice lesion mimic mutant lmm24 from a mutant pool of indica rice cultivar &ldquo, ZhongHui8015&rdquo, The LMM24 gene was identified by MutMap, and LMM24 was confirmed as a receptor-like cytoplasmic kinase 109 by amino acid sequence analysis. The lmm24 mutant displayed dark brown lesions in leaves and growth retardation that were not observed in wild-type ZH8015. The results of histochemical staining and TUNEL assays showed enhanced ROS accumulation and cell death in lmm24. Chloroplast degradation was observed in lmm24 leaves, with decreased expression of photosynthesis-related genes and increased expression of the senescence-induced STAYGREEN (SGR) gene and other senescence-associated genes. Furthermore, lmm24 exhibited enhanced resistance to rice blast fungus Magnaporthe oryzae (M. oryzae) and up-regulation of defense response genes. Our data demonstrate that LMM24 regulates cell death and defense responses in rice.

Chordoma is an extremely rare malignant bone tumor with a high rate of relapse. While cancer stem cells (CSCs) are closely associated with tumor recurrence, which depend on its capacity to self-renew and induce chemo-/radioresistance, whether and how CSCs participate in chordoma recurrence remains unclear. The current study found that tumor cells in recurrent chordoma displayed more dedifferentiated CSC-like properties than those in corresponding primary tumor tissues. Meanwhile, MTNR1B deletion along with melatonin receptor 1B (MTNR1B) down-regulation was observed in recurrent chordoma. Further investigation revealed that activation of Gαi2 by MTNR1B upon melatonin stimulation could inhibit SRC kinase activity via recruiting CSK and SRC, increasing SRC Y530 phosphorylation, and decreasing SRC Y419 phosphorylation. This subsequently suppressed β-catenin signaling and stemness via decreasing β-catenin p-Y86/Y333/Y654. However, MTNR1B loss in chordoma mediated increased CSC properties, chemoresistance, and tumor progression by releasing melatonin's repression of β-catenin signaling. Clinically, MTNR1B deletion was found to correlate with patients' survival. Together, our study establishes a novel convergence between melatonin and β-catenin signaling pathways and reveals the significance of this cross talk in chordoma recurrence. Besides, we propose that MTNR1B is a potential biomarker for prediction of chordoma prognosis and selection of treatment options, and chordoma patients might benefit from targeting MTNR1B/Gαi2/SRC/β-catenin axis.

Arthrogryposis is a group of phenotypically and genetically heterogeneous disorders characterized by congenital contractures of two or more parts of the body; the pathogenesis and the causative genes of arthrogryposis remain undetermined. We examined a four‐generation arthrogryposis pedigree characterized by camptodactyly, limited forearm supination, and loss of myofibers in the forearms and hands. By using whole‐exome sequencing, we confirmed MET p.Y1234C mutation to be responsible for arthrogryposis in this pedigree. MET p.Y1234C mutation caused the failure of activation of MET tyrosine kinase. A Met p.Y1232C mutant mouse model was established. The phenotypes of homozygous mice included embryonic lethality and complete loss of muscles that originated from migratory precursors. Heterozygous mice were born alive and showed reduction of the number of myofibers in both appendicular and axial muscles. Defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts were proven to be responsible for the skeletal muscle dysplasia of mutant mice. Overall, our study shows MET to be a causative gene of arthrogryposis and MET mutation could cause skeletal muscle dysplasia in human beings.

Temozolomide (TMZ) is a standard agent used in the treatment of various types of cancers, including lung carcinoma, but TMZ resistance is common and accounts for many treatment failures. We investigated miRNA-487b-5p (miR-487b-5p) was highly expressed in A549 and H1299 cells which acquired TMZ resistance. Suppression of miR-487b-5p had overt effects on cellular proliferation and migration in the presence of TMZ. On the other hand, knockdown of miR-487b-5p resulted in increased survival and moderate tumor growth in vivo. In addition, the decreased cellular proliferation following miR-487b-5p suppression was linked to enhanced autophagy, evident by drastically increased levels of LC3-II, BECLIN1, and LAMP2 when miR-487b-5p was knocked down. Further analysis revealed that LAMP2 might be the target gene of miR-487b-5p. In conclusion, our study suggested that miR-487b-5p may be a potential biomarker of acquired TMZ resistance in lung cancer cells, and miR-487b-5p inhibition can be further explored as a chemotherapy target in the treatment of TMZ-resistant lung carcinoma.

Lung cancer is the leading cause of cancer-related death throughout the world. We aimed to investigate the role of a novel microRNA-876-5p and its potential molecular target bone morphogenetic protein 4 (BMP-4), in the epithelial–mesenchymal transition (EMT) of lung cancer. Expressions of microRNA-876-5p and its potential target BMP-4 were analysed in lung cancer cells and patient tissues. Luciferase activity assay was conducted to verify direct targeting of microRNA-876-5p to the 3′-UTR of BMP-4 mRNA. Migration, invasion capacities of lung cancer cells expressing microRNA-876-5p were analysed, and characteristics of lung cancer EMT protein markers were also evaluated. A xenograft tumour mouse model was established to address the roles of microRNA-876-5p and BMP-4 in lung cancer EMT in vivo. MicroRNA-876-5p was decreased while BMP-4 was increased in lung cancer cells and tissues. MicroRNA-876-5p directly targeted 3′-UTR of BMP-4 mRNA to inhibit its expression. MicroRNA-876-5p expression significantly inhibited the migration, invasion and EMT of lung cancer cells in vitro, as well as metastasis in vivo, which required BMP-4 expression. MicroRNA-876-5p suppresses EMT of lung cancer by directly down-regulating BMP-4, both of which could serve as potential therapeutic targets in the treatment of lung cancer.

The aim of the present study was to express the recombinant Chlamydophila pneumoniae (C. pneumoniae) protein, Cpn 0810, in Escherichia coli (E. coli) BL21, and investigate the effects of Cpn 0810 on inflammatory and apoptotic processes in human monocytic (THP-1) cells. An ELISA was performed to detect the levels of the proinflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6. In addition, Hoechst 33258 staining and annexin V binding analyses were performed to measure the rates of apoptosis. Purified glutathione S-transferase (GST)-Cpn 0810 recombinant proteins were obtained from the E. coli BL21 cells carrying the pGEX6p-2/Cpn 0810 plasmid, and were shown to stimulate the expression of TNF-α and IL-6 in the THP-1 cells in a dose- and time-dependent manner. TNF-α and IL-6 levels peaked at 24 h after GST-Cpn 0810 stimulation. Furthermore, GST-Cpn 0810 significantly promoted the apoptosis of THP-1 cells. In conclusion, recombinant GST-Cpn 0810 was shown to stimulate the expression of TNF-α and IL-6, inhibit proliferation and induce apoptosis in THP-1 cells. Therefore, Cpn 0810 may interact with host cells following C. pneumoniae infection, functioning as an important pathogenic factor.

Osteosarcoma is the most common primary malignant bone tumor among adolescents worldwide with high mortality rate. Glycogen synthase kinase 3β (GSK3β) is a serine/threonine kinase and is considered as a validated target in osteosarcoma therapy. Therefore, the study of GSK3β inhibitors is one of the most popular fields in anti-osteosarcoma drug development. Here, the tools of bioinformatics were used to screen novel effective inhibitors of GSK3β from ZINC Drug Database. The molecular docking, molecular dynamic simulations, MM/GBSA, and energy decomposition analysis were performed to identify the inhibitors. Finally, ZINC08383479 and ZINC08441251 were selected as potential GSK3β inhibitors. These two inhibitors were evaluated by GSK3β kinase inhibition assay in vitro. The inhibition of cell proliferation was tested in osteosarcoma cell lines U2OS and MG63 in vitro. The result showed that ZINC08383479 and ZINC08441251 had high inhibition activity against GSK3β. We found that CHIR99021 (a known GSK3β inhibitor), ZINC08383479, and ZINC08441251 had significant inhibition activity in U2OS cells and MG63 cells. These findings may provide new ideas for the design of more potent GSK3β inhibitors and therapeutic targets for osteosarcoma.

Background Little is known about the optimal cut-off point of fasting plasma glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese women. This study investigates the relationship between gestational fasting plasma glucose and several variables: neonatal birth weight, prenatal blood pressure and dystocia rate of pregnant women. In this study, we hoped to provide a useful tool to screen gestational diabetes mellitus in pregnant Chinese women. Methods For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22–30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as well as dystocia conditions, were examined. We analysed the correlations between the following: gestational fasting plasma glucose and neonatal birth weight; prenatal blood pressure and gestational fasting plasma glucose as well as dystocia rate and gestational fasting plasma glucose group. Results A modest correlation was observed between gestational fasting plasma glucose and neonatal birth weight (r = 0.093, p = 0.003). The macrosomia rate was smallest when the gestational fasting plasma glucose was in the range 3.51–5.5 mmol/L. Prenatal blood pressure increased linearly with increasing gestational fasting plasma glucose (p = 0.000). There was a significant difference between the dystocia rates in different fasting plasma glucose groups (chi-squared = 13.015, p = 0.043). The results showed that the dystocia rate significantly increased when gestational fasting plasma glucose was >4.9 mmol/L; p = 0.03, OR = 2.156 (95% CI, 1.077–4.318). Conclusion We suggest that the optimal range of gestational fasting plasma glucose for pregnant Chinese women is in the range 3.5–4.9 mmol/L. Copyright © 2014 John Wiley & Sons, Ltd.

Given the important roles of miRNAs in post-transcriptional regulation and its implications for the development of immune tissues and cells, characterization of miRNAs promotes us to uncover the molecular mechanisms underlying the pathway of trisomic chromosome 21 that disrupts the disomic genes expression and immunological defects related to Down syndrome (DS). In the present study, we analyzed global changes and chromosome distribution characteristics of miRNAs expression in lymphocytes from children with trisomy 21 by means of the Illumina high-throughput sequencing technology. Two small libraries were constructed using pool RNA of normal and DS children. The results have been further validated by stem-loop quantitative RT-PCR. Comparison between DS and normal profiles revealed that most of identified miRNAs were expressed at similar levels. The chromosome 21 that contributes to the abundantly expressed miRNAs was small, and not all Hsa21-derived miRNAs were over-expressed with ratios significantly ≥ 1.5 in Down syndrome children lymphocytes. Based on the deep sequencing technology, 108 novel candidate miRNAs have been identified, and 2 of them were derived from human chromosome 21. For the 114 significantly differentially expressed miRNAs, function annotation of target genes indicated that a set of highly abundantly and significantly differentially expressed miRNAs were involved in hematopoietic or lymphoid organ development, thymus development, and T/B cell differentiation and activation. Our results indicated that these abnormally expressed miRNAs might be associated with the mechanisms that trisomy 21 results in dysregulation of disomic genes and involved in the immunological defects seen in DS.

Systemic lupus erythematosus (SLE) is the prototype of complex autoimmune diseases characterized by the production of autoantibodies which results in widespread immunologic abnormalities and immune complex formation. The underlying etiology remains largely unknown. When progressing toward kidney failure, it is becoming a serious public health problem. Kidney transplantation is a feasible therapy, but significant limitations were existed, including shortage of donor organs and lack of funding. To find an alternative proposal for kidney replacement, the induced pluripotent stem cells (iPSCs) technology was adopted. We identified typical SLE patients. Lentiviral transduction of OCT4, SOX2, KLF4, and c-MYC, under feeder conditions, resulted in reprogramming of urine-derived renal tubular cells. We investigated the viability of iPSCs generation from patients with SLE by identification of totipotency and pluripotency. SLE patient renal tubular cells-derived iPSCs exhibited properties of human embryonic stem cells, including morphology, growth properties, alkaline phosphatase, expression of pluripotency, genes and surface markers, and teratoma formation. We demonstrated that generation of SLE-specific iPSCs from urine was not only the first time worldwide, but was feasible and efficient. IPSCs from SLE would provide convenient model to study disease pathogenesis, drugs screening, and gene therapy.

How much of the increase in sex ratio (male to female) at birth since the early 1980s in China is attributed to increased prenatal sex selection? This question is addressed by exploiting the differential introduction of diagnostic ultrasound in the country during the 1980s, which significantly reduced the cost of prenatal sex selection. We find that the improved local access to ultrasound technology has resulted in a substantial increase in sex ratio at birth. Our estimates indicate that roughly 40 to 50 percent of the increase in sex imbalance at birth can be explained by local access to ultrasound examinations.

LIGHT, a costimulatory member of the immunoglobulin superfamily (Ig SF), can greatly impact T cell activation. The role of the LIGHT signaling pathway in chlamydial infection was evaluated in mice following respiratory tract infection with Chlamydia psittaci. Compared with wild type (WT) mice, LIGHT knockout (KO) mice showed significant reduction of body weight, much lower survival rate, higher bacterial burden, prolonged infection time courses and more severe pathological changes in lung tissue. The mRNA levels of IFN-γ, TNF-α, IL-17 and IL-12 in the lung tissue of LIGHT KO mice were significantly lower than those in WT mice. While there was no obvious difference in the percentages of CD4+ and CD8+ T cells in the spleens of the two groups of mice, there was a markedly elevated percentage of CD4+ CD25+ FoxP3+ Treg cells in LIGHT KO mice. Together, these results demonstrate that the LIGHT signaling pathway is not only required for inflammatory cytokine production as part of the host response to chlamydial infection, but also influences the differentiation of CD4+ CD25+ FoxP3+ Treg cells, both of which may be essential for control of C. psittaci respiratory tract infection.

Our aim in this study was to identify and examine the differential expression of microRNAs in patients with systemic lupus erythematosus (SLE).We employed high-quality, high-throughput Solexa sequencing to clone and identify microRNAs in SLE patients and a control group.From the sequencing data, we identified numerous microRNAs displaying significantly different levels of expression in patients with SLE and in healthy controls. The 212 and 199 microRNAs were upregulated and downregulated, respectively. Only 61 novel microRNAs exhibited significantly different levels of expression in the two groups. The target genes of the novel microRNAs identified in the SLE group were found to have cell metabolism functions. We also analyzed the chromosomal locations of the microRNAs with high level of expression between the two groups. A profile comparison revealed that the majority of transcripts were expressed at a similar level. The functional classes of the most abundant microRNAs were equally represented on each chromosome.We identified novel and known microRNAs significantly enhancing our understanding of the microRNA expression profiles of SLE patients. These data also provide insight into the function of microRNAs in SLE and provide new strategies for future therapies.

Rejection is still a major obstacle in long-term allograft survival of renal transplant recipients. Long non‑coding RNAs (lncRNAs) are an important class of pervasive RNAs involved in a variety of biological functions, and which are often found to be differentially expressed between healthy and pathological conditions. The aim of this study was to compare the expression profiles of lncRNAs between samples from acute rejection following kidney transplantation and control samples. Three patients were enrolled, diagnosed by renal biopsy with acute rejection upon kidney transplantation. We used lncRNA microarrays to study the lncRNA expression profiles in the kidney biopsies of these patients and in kidneys from healthy donors. Reverse transcription‑quantitative polymerase chain reaction (RT-qPCR) was used to validate the microarray results. In addition, potential functions of the identified lncRNAs were further explored by searching the UCSC, RNAdb, RefSeq and NRED databases. Five candidate lncRNAs displaying differential expression in acute rejection samples were validated by RT-qPCR. The results were in agreement with the microarray data. Among the identified lncRNAs, certain have been previously identified in relevant conditions, thereby supporting previous evidence, but certain may constitute novel biomarker candidates. This is the first report to date using lncRNA microarrays to identify unique expression signatures of acute rejection in transplant biopsies. Our data indicate that lncRNAs are potentially involved in the pathogenesis of acute rejection. Our results may have important implications in the identification of diagnostic biomarkers, as well as in the understanding and treatment of acute rejection following renal transplantation.

This paper's findings suggest that an arbitrary Chinese policy that greatly increases total suspended particulates (TSPs) air pollution is causing the 500 million residents of Northern China to lose more than 2.5 billion life years of life expectancy. The quasi-experimental empirical approach is based on China’s Huai River policy, which provided free winter heating via the provision of coal for boilers in cities north of the Huai River but denied heat to the south. Using a regression discontinuity design based on distance from the Huai River, we find that ambient concentrations of TSPs are about 184 μg/m 3 [95% confidence interval (CI): 61, 307] or 55% higher in the north. Further, the results indicate that life expectancies are about 5.5 y (95% CI: 0.8, 10.2) lower in the north owing to an increased incidence of cardiorespiratory mortality. More generally, the analysis suggests that long-term exposure to an additional 100 μg/m 3 of TSPs is associated with a reduction in life expectancy at birth of about 3.0 y (95% CI: 0.4, 5.6).

The aim of this study was to investigate the differential expression characteristics and the roles of the genome-wide microRNAs (miRNAs) in immunoglobulin A nephropathy (IgAN) kidney tissues. We used Illumina high-throughput sequencing technology to evaluate the miRNAs expression of six biopsy tissues from IgAN and six normal renal cortex specimens from patients with renal cell carcinoma. We observed a total of 85 miRNAs that were differentially expressed in the six IgAN patients, of which 11 miRNAs were up-regulated and 74 miRNAs were down-regulated in patients' tissues compared with control tissues. Additionally, we identified 55 candidate novel miRNAs in our study, which comprised seven candidates who were detected in the IgAN group and 49 candidates who were detected in the control group. Only one candidate (miR-n-9) was expressed in both groups. The bioinformatics showed that the regulated target genes of differentially expressed miRNAs were associated with immune and renal pathological changes. The identification of specific tissue miRNAs in our study not only helped clarify the genetics or immunology mechanisms involved in the pathogenesis of IgAN but also helped explain the pathological changes in the kidney tissues. We hypothesize that some significant miRNAs might potentially serve as novel diagnostic biomarkers in IgAN patients.

This paper's findings suggest that an arbitrary Chinese policy that greatly increases total suspended particulates (TSP) air pollution is causing the 500 million residents of Northern China to lose more than 2.5 billion life years of life expectancy. The quasi-experimental empirical approach is based on China's Huai River policy, which provided free winter heating via the provision of coal for boilers in cities North of the Huai River but denied heat to the South. Using a regression discontinuity design based on distance from the Huai River, we find that ambient concentrations of TSP are about 184 μg/m3 (95% CI: 61, 307) or 55% higher in the North. Further, the results indicate that life expectancies are about 5.5 (95% CI: 0.8, 10.2) years lower in the North due to an increased incidence of cardiorespiratory mortality. More generally, the analysis suggests that long-term exposure to an additional 100 μg/m3 of TSP is associated with a reduction in life expectancy at birth of about 3.0 years (95% CI: 0.4, 5.6).

Protecting the environment during economic growth is a challenge facing every country. This paper focuses on two regulatory measures that China has adopted to incentivize air quality improvement: publishing a daily air pollution index (API) for major cities since 2000 and linking the API to performance evaluations of local governments. In particular, China defines a day with an API at or below 100 as a blue sky day. Starting in 2003, a city with at least 80% blue sky days in a calendar year (among other criteria) qualified for the “national environmental protection model city” award. This cutoff was increased to 85% in 2007.Using officially reported API data from 37 large cities during 2000-2009, we find a significant discontinuity at the threshold of 100 and this discontinuity is of a greater magnitude after 2003. Moreover, we find that the model cities were less likely to report API right above 100 when they were close to the targeted blue sky days in the fourth quarter of the year when or before they won the model city award. That being said, we also find significant correlation of API with two alternative measures of air pollution – namely visibility as reported by the China Meteorological Administration (CMA) and Aerosol Optical Depth (AOD), corrected for meteorological conditions, from NASA satellites. The discontinuity around 100 suggests that count of blue sky days could have been subject to data manipulation; nevertheless, API does contain useful information about air pollution.

Using 2006 China Agricultural Census (CAC), we examine whether the introduction of the New Cooperative Medical System (NCMS) has affected child mortality, maternal mortality, and school enrollment of the 6-16 years olds. Our data cover 5.9 million people living in eight low-income rural counties, of which four adopted the NCMS by 2006 and four did not adopt it until 2007. Raw data suggest that enrolling in NCMS is associated with better school enrollment and lower mortality of young children and pregnant women. However, using a difference-in-difference propensity score method, we find most of these differences are driven by the endogenous introduction and take-up of NCMS, and out method overcomes classical propensity score matching's failure to address the selection bias. While the NCMS does not affect child mortality and maternal mortality, it does help improve the school enrollment of six-year-olds.

This paper assesses the role of heating entitlements in generating stark air quality differences across China. During the 1950-1980 central planning period, the Chinese government established free winter heating of homes and offices as a basic right via the provision of free coal fuel for boilers. The combustion of coal in boilers is associated with the release of air pollutants, especially total suspended particulates (TSP). Due to budgetary limitations, however, this heating entitlement was only extended to areas to the north of the line formed by the Huai River and Qinling Mountains in central China. We find this procrustean policy led to dramatically higher TSP levels in the north; the difference is roughly 5-8 times current TSP concentrations in the US. This result holds both in a cross-sectional regression discontinuity-style estimation approach and in a panel data setting that compares the marginal effect of winter temperature on TSP in northern and southern China. In contrast, we fail to find evidence that the heating policy has a meaningful impact on sulfur dioxide (SO2) and nitrogen oxide (NOx) concentrations.

In this paper, we examine the effect of maternal education on the health of young children by using a large sample of adopted children from China. As adopted children are genetically unrelated to the nurturing parents, the educational effect on them is most likely to be the nurturing effect. We find that the mother's education is an important determinant of the health of adopted children even after we control for income, the number of siblings, health environments, and other socioeconomic variables. Moreover, the effect of the mother's education on the adoptee sample is similar to that on the own birth sample, which suggests that the main effect of the mother's education on child health is in post-natal nurturing. We also find suggestive evidence that the effect is causal. Our work provides new evidence to the general literature that examines the determinants of health and that examines the intergenerational immobility of socioeconomic status.