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Abstract Angiogenesis, metastasis, and resistance to therapy are all facilitated by cancer-associated fibroblasts (CAFs). A CAF-based risk signature can be used to predict patients’ prognoses for Lung adenocarcinoma (LUAD) based on CAF characteristics. The Gene Expression Omnibus (GEO) database was used to gather signal-cell RNA sequencing (scRNA-seq) data for this investigation. The GEO and TCGA databases were used to gather bulk RNA-seq and microarray data for LUAD. The scRNA-seq data were analyzed using the Seurat R program based on the CAF markers. Our goal was to use differential expression analysis to discover differentially expressed genes (DEGs) across normal and tumor samples in the TCGA dataset. Pearson correlation analysis was utilized to discover prognostic genes related with CAF, followed by univariate Cox regression analysis. Using Lasso regression, a risk signature based on CAF-related prognostic genes was created. A nomogram model was created based on the clinical and pathological aspects. 5 CAF clusters were identified in LUAD, 4 of which were associated with prognosis. From 2811 DEGs, 1002 genes were found to be significantly correlated with CAF clusters, which led to the creation of a risk signature with 8 genes. These 8 genes were primarily connected with 41 pathways, such as antigen paocessing and presentation, apoptosis, and cell cycle. Meanwhile, the risk signature was significantly associated with stromal and immune scores, as well as some immune cells. Multivariate analysis revealed that risk signature was an independent prognostic factor for LUAD, and its value in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the stage and CAF-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of LUAD. CAF-based risk signatures can be effective in predicting the prognosis of LUAD, and they may provide new strategies for cancer treatments by interpreting the response of LUAD to immunotherapy.

Abstract Background β-Propeller protein-associated neurodegeneration (BPAN) is a genetic neurodegenerative disease caused by mutations in WDR45. The impairment of autophagy caused by WDR45 deficiency contributes to the pathogenesis of BPAN; however, the pathomechanism of this disease is largely unknown. Lipid dyshomeostasis is involved in neurogenerative diseases, but whether lipid metabolism is affected by Wdr45 deficiency and whether lipid dyshomeostasis contributes to the progression of BPAN are unclear. Methods We generated Wdr45 knockout SN4741 cell lines using CRISPR‒Cas9-mediated genome editing, then lipid droplets (LDs) were stained using BODIPY 493/503. Chaperone-mediated autophagy was determined by RT-qPCR and western blotting. The expression of fatty acid synthase (Fasn) was detected by western blot in the presence or absence of the lysosomal inhibitor NH4Cl and the CMA activator AR7. The interaction between Fasn and HSC70 was analyzed using coimmunoprecipitation (Co-IP) assay. Cell viability was measured by a CCK-8 kit after treatment with the Fasn inhibitor C75 or the CMA activator AR7. Results Deletion of Wdr45 impaired chaperone-mediated autophagy (CMA), thus leading to lipid droplet (LD) accumulation. Moreover, Fasn can be degraded via CMA, and that defective CMA leads to elevated Fasn, which promotes LD formation. LD accumulation is toxic to cells; however, cell viability was not rescued by Fasn inhibition or CMA activation. Inhibition of Fasn with a low concentration of C75 did not affect cell viability but decreases LD density. Conclusions These results suggested that Fasn is essential for cell survival but that excessive Fasn leads to LD accumulation in Wdr45 knockout cells.

This study focused on the research progress of the toxicity of microplastics to marine medaka. By consulting the relevant literatures, the annual change and regional distribution of the published papers were statistically analyzed. In addition, the type, size and concentration of microplastics, exposure time and mode, and selection of marine medaka were studied. Besides, this paper summarizes six aspects of the research results: metabolism in vivo, intestinal injury, growth and developmental toxicity, reproductive toxicity, genetic toxicity and amplification or mitigation effect to other marine pollutants. In the end, it is suggested that experimental time, selection of microplastics and toxicological mechanism need to be considered in future study.

ABSTRACTForest Stock Volume (FSV) is one of the key indicators in forestry resource investigation and management on local, regional, and national scales. Limited by the saturation problems of optical satellite remote-sensing imagery in the retrieving of stock volume, and the high cost of Light Detection And Ranging (LiDAR) data, it is still challenging to estimate FSV in a large area using single-sensor remote-sensing data. In this paper, a method integrated multispectral satellite imagery and LiDAR data was developed to map stock volume in a large area. A random forest model was adopted to estimate the stock volume of larch forest in China based on the training samples from the Airborne Laser Scanning (ALS)-derived stock volume and corresponding Sentinel-2 imagery. Validation using National Forest Inventory (NFI) data, ALS-derived stock volume and ground investigation data demonstrated that the estimated stock volume had a high accuracy (R2 = 0.59, RMSE = 59.69 m3/ha, MD = 39.96 m3/ha when validated with NFI data; R2 ranged from 0.77 to 0.85, RMSE ranged from 38.68 m3/ha to 67.38 m3/ha, MD ranged from 24.90 m3/ha to 37.27 m3/ha when validated with ALS stock volume; R2 = 0.42, RMSE = 79.10 m3/ha, MD = 62.06 m3/ha when validated with field investigation data). Results of this paper indicated the applicability of estimating stock volume of larch forest in a large area by combining Sentinel-2 data and airborne LiDAR data.

Solar energy may now be captured in two ways: heat extraction in solar collectors and electricity generation in photovoltaic panels. It may effectively reduce the degradation of PV cell efficiency caused by overheating of the battery by collecting the heat from the PV/T system. The heat dissipation cooling fin is directly mounted to the rear of the solar panel in this study and coated with an insulating layer to create an air-cooling channel. The heat dissipation fin transfers heat from the back of the photovoltaic panel to a certain mass flow of air in the flow channel, resulting in combined heat and power. The electrical and thermal capabilities of three distinct fin numbers were studied by monitoring electrical power and temperature data. A fixed mass flow rate (0.011 kg/s) for air, three different numbers of fins (0-5-10) and solar irradiance (200 W/m2–600 W/m2) are the experimental conditions. After the system was run stably for 10 min, the average temperature of the back of the PV panel, the device’s inlet and outlet temperatures, and the PV panel’s electric power were recorded. These figures are used to calculate the PV/T system’s electrical and thermal efficiency. When the median electrical efficiency of the three types of fins is compared with varying solar irradiation, it is discovered that the electric efficiency value of the three types of fins is approximately 16%, with a difference of less than 0.6%. The comprehensive efficiency of five groups of fins and ten groups of fins was 61.08% and 69.85%, respectively, based on the median comparison of photoelectric photothermal comprehensive efficiency. The overall efficiency of the zero groups of fins was 26.27%, which was only 14.59% greater than the control plate, and there was a considerable difference between the five and ten groups of fins. This suggests that selecting the right number of fins has a substantial impact on improving PV/T thermal performance. This research will assist in further optimizing the design of PV/T systems for heat collection and will provide valuable information for PV/T system application in building integration.

The long-term changes of heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in sediments can reflect the ecological risks (ER) caused by their pollution sources in different historical periods. This is of great significance to the improvement of environmental protection policies in the future. The study area is located in Taihu Lake, China. 137Cs and 210Pb were used for dating. Indicators related to local socio-economic development were introduced to optimize source identification in the absolute principal component score multiple linear regression (APCS-MLR) model. On this basis, the mean effect range median quotient (M-ERM-Q) method was used to evaluate the ER of source-oriented HMs and PAHs at different ages. The HMs content was relatively stable from 1949 to 2015, and then increased significantly. The PAH contents were on the rise during the whole historical period. The average contribution rate of traffic emission and fertilization to HMs was 50.59 % and 49.41 %. Ecological risk caused by Traffic emitted pollutants was relatively stable before 2015, then increased sharply, and finally reached a medium–high level. However, fertilization ER has always maintained an increasing trend and accelerated after 1980, ultimately reaching medium–low ER. The contribution rates of coal combustion, mixed sources (biomass and coal) and gasoline combustion to PAHs were 13.20 %, 52.45 % and 34.36 %, respectively. The ER of mixed sources and gasoline combustion showed a gradually increasing trend before 2007, and then began to decrease. However, coal combustion ER has been increasing, and the increase accelerated in 2000. Nevertheless, the ER of these three sources was still low. Overall, a certain degree of HMs pollution has been caused by traffic emissions and fertilization in recent years. Local governments should prioritize the control of these two sources to protect the Taihu Lake ecosystem.

The Amu Darya River, as one of the important flows of the Aral Sea located in the semi-arid area of Central Asia, also performed as the primary water supply for Uzbekistan. Therefore, the residues and risks of anthropogenic-related persistent organic pollutants (POPs) in waters of the Amu Darya River were conducted in the present study to elucidate their possible effects on the water safety in such a specific area as well as on the Aral Sea Crisis from a new perspective. Thirty-nine water samples distributed along the Amu Darya River to the coastal of the Aral Sea were analyzed for both polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) occurrence, showing the total concentrations of ΣOCPs and ΣPAHs in the range of 1.16–22.75 ng/L and 3.18–506.26 ng/L, respectively. Spatial differences showed higher levels for both OCPs and PAHs along the lower reaches of the Amu Darya River due to intense human activities. Source identification performed by isomer ratios indicated that dichlorodiphenyltrichloroethanes (DDTs) probably originated from recent use, while hexachlorocyclohexanes (HCHs), chlordanes, and endosulfans originated mainly from historical usage. Furthermore, the principal component analysis showed PAHs were from coal and petroleum combustion (65.2%), biomass combustion (27.2%), and industrial chemical combustion (7.64%). The human health risk assessment demonstrated no carcinogenic or non-carcinogenic risks at present. However, moderate to high ecological risks to aquatic organisms especially were observed along the lower reaches, especially the delta area. The results obtained would not only provide important basic data for such a semi-arid area but also show us the possible toxic effects induced by such pollutants, which should attract more attention in the shrinking case of the Aral Sea.

Phenol red (PR) is a standard acid-base indicator in cell and tissue culture media, as well as multiple detection protocols. Meanwhile, catalytic nanomaterials such as nanozymes demonstrate great potential in biomedical applications, but there were few studies about the direct impact of nanozymes on the ubiquitous pH indicators. We demonstrate for the first time the degradation of phenol red by highly active nanoceria. The results provide evidence that phenol red is a redox active molecule and it may be oxidized quickly by nanoceria so that its pH-indicating functionality may be lost. Investigators need to be cautious in their routine use of phenol red, particularly when it is exposed to active nanozymes. Herein, we construct a PR-hydrogel as a protective strategy for phenol red against oxidation. Results show that the PR-hydrogel maintained the quantitative acid-base indicating capability while resisting the degradation by nanoceria. The hydrogel exhibits high stability, good pH sensitivity and recyclability, negligible cytotoxicity and dye leaching, which provides a strong practical resolution to the application of phenol red in future challenges of nanomedicines.

Abstract Background The recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance. Methods We conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM). Results In total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2–190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5–33.8%) in the PCI cohort and 38.5% (32.6–44.5%) in the surveillance cohort (Gray’s p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6–44.0 months) in the PCI cohort versus 32 months (26.4–37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74–1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS. Conclusions Overall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.

ObjectiveTo investigate the effect of embryo stage at the time of transfer on obstetric and perinatal outcomes in programmed frozen-thawed embryo transfer (FET) versus natural FET cycles.DesignSystematic review and meta-analysis.SettingNot applicable.Patient(s)Women with programmed frozen-thawed embryo transfer (FET) and natural FET.Intervention(s)The PubMed, MEDLINE, and EMBASE databases and the Cochrane Central Register of Controlled Trials (CCRT) were searched from 1983 to October 2022. Twenty-three observational studies were included.Primary outcome measureThe primary outcomes were hypertensive disorders of pregnancy (HDPs), gestational hypertension and preeclampsia (PE). The secondary outcomes were gestational diabetes mellitus (GDM), placenta previa, postpartum haemorrhage (PPH), placental abruption, preterm premature rupture of membranes (PPROM), large for gestational age (LGA), small for gestational age (SGA), macrosomia, and preterm delivery (PTD).Result(s)The risk of HDP (14 studies, odds ratio (OR) 2.17; 95% confidence interval (CI) 1.95-2.41; P

Abstract Background Alteration of DNA methylation is an important event in pathogenesis and progression of hepatocellular carcinoma (HCC). DNA methyltransferase (DNMT) 1, the foremost contributor in DNA methylation machinery, was revealed elevated in HCC and significantly correlates with poor prognosis. However, the transcriptional regulation of DNMT1 in HCC remains unknown. Methods Real‐time PCR and immunohistochemistry were performed to detect DNMT1 and zinc finger transcription factor 191 (ZNF191) expressions in HCCs. Transcription activity of DNMT1promoter was analyzed with Luciferase reporter activity assay. The binding capacity of ZNF191 protein to DNMT1 promoter was examined with chromatin immunoprecipitation‐qPCR (ChIP‐qPCR) and electrophoretic mobility shift assay (EMSA). DNA methylation level of hepatoma cells was detected with Methylation array. Results ZNF191 can regulate DNMT1 mRNA and protein expression positively, and increase the transcription activity of the DNMT1 promoter. ChIP‐qPCR and EMSA revealed that ZNF191 protein directly binds to the DNMT1 promoter at nt‐240 AT(TCAT)3TC. Moreover, DNMT1 and ZNF191 expression correlate positively in human HCCs. With methylation array, DNA methylation alteration was observed in hepatoma cells with ZNF191 knockdown, and the differential methylation sites are enriched in the PI3K‐AKT pathway. Furthermore, we proved DNMT1 contributes the effect of ZNF191 on hepatoma cell growth via the PI3K‐AKT pathway. Conclusion ZNF191 is a novel transcription regulator for DNMT1, and the pro‐proliferation effect of ZNF191/DNMT1/p‐AKT axis in hepatoma cells implies that ZNF191 status in HCCs may affect the therapeutic effect of DNMTs inhibitors and PI3K inhibitors for precise treatment of the disease.

Abstract Glomerular endothelial cells (GEnCs) dysfunction occurs at the early stage of diabetic nephropathy (DN). One of its characteristics is endothelial-to-mesenchymal transition (EndMT). Heparanase (HPSE) is the only known mammalian endoglycosidase capable of degrading heparin sulfates and has a prominent role in DN pathogenesis. However, whether HPSE induces EndMT of GEnCs remains unknown. This study aimed to determine the effect and potential mechanism of HPSE on GEnCs phenotype under high-glucose conditions. In the early development of streptozotocin (STZ)-induced diabetic mice, HPSE overexpression was positively correlated with renal injury and the number of GEnCs undergoing EndMT, which was characterized by loss of endothelial marker CD31 and gain of mesenchymal markers including α-SMA and Snail1/2 by double immunofluorescence staining. Bioinformatics analysis revealed a positive correlation between HPSE and ERK. The counts of double positive staining of CD31 and p-ERK1/2 was significantly increased in the glomeruli of STZ-induced diabetic mice compared with sham mice. In cultured GEnCs, high glucose dramatically upregulated the expressions of HPSE and p-ERK1/2, both of which were markedly blocked by HPSE siRNA. Furthermore, recombinant mouse HPSE (rmHPSE) promoted the expressions of mesenchymal markers and p-ERK1/2 in a dosage- and time-dependent manner. U0126, a specific MEK/ERK inhibitor, significantly inhibited either high glucose or rmHPSE-induced EndMT of GEnCs. These data indicate that high glucose induces EndMT of GEnCs at least partially through upregulating HPSE and that HPSE promotes EndMT of GEnCs via activating ERK signaling. This study improves understanding the crucial role of HPSE in DN development and progression.

The loss of podocyte is crucial for diagnosis and prognosis of diabetic kidney disease, whereas commonly two-dimensional methods for quantifying podocyte number existed with issues of low fidelity and accuracy. In this study, clear, unobstructed brain imaging cocktails and computational analysis (CUBIC), one of three-dimensional optical clearing approaches, was used which combines tissue clearing, immunolabeling, and a light-sheet microscope to image and evaluate podocytes in C57BL/6 (C57) and db/db mice. We discovered that 77 podocytes per glomerulus were in C57 mice. On the subject of db/db mice, there were 74 podocytes by the age of 8 w, 72 podocytes by the age of 12 w, and 66 podocytes by the age of 16 w, compared with 76 podocytes in the control group, suggesting that there was a significant decrease in podocyte number in db/db mice with the age of 16 w, showing a trend which positively correlated to the deterioration of kidney function. Sample size estimation using the PASS software revealed that taking 5%, 7.5%, and 10% of the mean podocyte number per glomerulus as the statistical allowable error and 95% as total confidence interval, 33, 15, and 9 glomeruli were independently needed to be sampled in C57 mice to represent the overall glomeruli to calculate podocyte number. Furthermore, in the control group of db/db mice, 36, 18, and 11 glomeruli were needed, compared with 46, 24, and 14 glomeruli in db/db mice by the age of 8 w, 43, 21, and 12 glomeruli by the age of 12 w, and 52, 27, and 16 by the age of 16 w. These findings indicated that precise quantification of podocyte number could judge the progression of diabetic kidney disease. In addition, a small number of glomeruli could be actually representative of the whole sample size, which indicated apparent practicability of CUBIC for clinical use.

Abstract Nod-like receptor protein 3 (NLRP3), as an inflammatory regulator, has been implicated in acute kidney injury (AKI). Failed recovery after AKI can lead to chronic kidney disease (CKD). However, the role of NLRP3 in the AKI-CKD transition is still unknown. A mild or severe AKI mouse model was performed by using ischemia-reperfusion injury (IRI). We evaluated the renal NLRP3 expression in acute and chronic phases of ischemic AKI, respectively. Although serum creatinine (Cr) and blood urea nitrogen (BUN) levels in AKI chronic phase were equivalent to normal baseline, histological analysis and fibrotic markers revealed that severe AKI-induced maladaptive tubular repair with immune cell infiltration and fibrosis. Tubular damage was restored completely in mild AKI rather than in severe AKI. Of note, persistent overexpression of NLRP3 was also found in severe AKI but not in mild AKI. In the severe AKI-induced chronic phase, there was a long-term high level of NLRP3 in serum or urine. Overt NLRP3 was mainly distributed in the abnormal tubules surrounded by inflammatory infiltrates and fibrosis, which indicated the maladaptive repair. Renal Nlrp3 overexpression was correlated with infiltrating macrophages and fibrosis. Renal NLRP3 signaling-associated genes were upregulated after severe AKI by RNA-sequencing. Furthermore, NLRP3 was found increased in renal tubular epitheliums from CKD biopsies. Together, persistent NLRP3 overexpression was associated with chronic pathological changes following AKI, which might be a new biomarker for evaluating the possibility of AKI-CKD transition.

The significance of biodiversity research is to understand the structure and function of the community, and then to protect and monitor the community. The metric of biodiversity is the base of biodiversity conservation. Species richness and evenness are the most common descriptors of biodiversity. Whether it is diversity information measure, probability measure or geometric measure, they all express the combination of species richness and evenness in different ways. This study presents a new biologically meaningful measure of species diversity, which evaluates species richness and evenness independently, designated as DRE. The novelty of our method is to use “absolute discrepancy” to express the dissimilarity between the observed community and the uniform distribution community with the same species composition and same abundance of each species, and then measure the species evenness. The logarithmic transformation of the species number is used to measure species richness with values ranging between 0 and 1. We test the performance of this measure using simulated data and observations of natural and planted forests in different climatic zones. The results showed that the new diversity index (DRE) has superior statistical qualities compared with the traditional indices. Especially, in extremely uneven communities, the new measure describes the causes of diversity changes than the traditional DRE. In addition, DRE is more sensitive to the abundance changes of rare species in the simulated community, and the interpretation of the results is more intuitive and meaningful. It is an improved method to evaluate the species diversity of any ecosystem.

Cepharanthine (CEP), a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata, has been widely used for the treatment of various acute and chronic diseases, including leukopenia, and snake bites. Here, our objective was to investigate the anti-oxidative stress and anti-inflammatory response effects of CEP in lipopolysaccharide (LPS)-induced macrophages as well as dextran sulfate sodium (DSS)-induced colitis mice. Our findings demonstrated that supplementation with CEP effectively mitigates body weight loss and elevation of disease activity index (DAI), reduces the malondialdehyde (MDA) content to 2.45 nM/mL while increasing the reduced glutathione (GSH) content to 35.53 μg/mL, inhibits inflammatory response, and maintains proper intestinal epithelium tight junctions in DSS-induced wild type (WT) mice. However, it failed to provide protective effects in DSS-induced transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) knockout (NRF2−/−) mice. GSH content decreased to 10.85 μg/106 cells following LPS treatment, whereas supplementation with CEP increased the GSH content to 12.26 μg/106 cells. Moreover, CEP effectively attenuated ROS production in LPS-induced macrophages. Additionally, CEP exhibited inhibitory effects on pro-inflammatory cytokines and mediators in LPS-induced macrophages. Furthermore, we observed that supplementation with CEP promoted the expression of NRF2/heme oxygenase 1 (HO-1)/NADPH quinone oxidoreductase-1 (NQO-1) as well as the phosphorylation of the adenosine monophosphate-activated protein kinase alpha 1 (AMPK-α1)/protein kinase B (AKT)/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway in macrophages while inhibiting the phosphorylation of the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B p65 (NF-κB p65) signaling pathway in LPS-induced macrophages. Although CEP did not demonstrate inhibitory effects on oxidative stress or promote the expression of HO-1/NQO-1, it effectively activated the phosphorylation of the AMPK-α1/AKT/GSK-3β signaling pathway which is an upstream regulator of NRF2 in LPS-induced primary peritoneal macrophages from NRF2−/− mice. In summary, our findings suggest that CEP exerts protective effects against oxidative stress and inflammatory response by activating the AMPK-α1/AKT/GSK-3β/NRF2 signaling pathway while concurrently inhibiting the activation of mitogen activated protein kinases (MAPKs) and the NF-κB p65 signaling pathway. These results not only elucidate the mechanisms underlying CEP’s protective effects on colon oxidative stress and inflammation but also provide evidence supporting NRF2 as a potential therapeutic target for IBD treatment.

Abstract Acute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.

Cilia are organelles for cellular signalling and motility. Mutations affecting ciliary function are also associated with cilia-related disorders (ciliopathies). The identification of cilia markers is critical for studying their function at the cellular level. Due to the lack of a conserved, short ciliary localization motif, the full-length ARL13b or 5HT6 proteins are normally used for cilia labelling. Overexpression of these genes, however, can affect the function of cilia, leading to artefacts in cilia studies. Here, we show that Nephrocystin-3 (Nphp3) is highly conserved among vertebrates and demonstrate that the N-terminal truncated peptide of zebrafish Nphp3 can be used as a gratuitous cilia-specific marker. To visualize the dynamics of cilia in vivo, we generated a stable transgenic zebrafish Tg (β-actin: nphp3N-mCherry)sx1001. The cilia in multiple cell types are efficiently labelled by the encoded fusion protein from embryonic stages to adulthood, without any developmental and physiological defects. We show that the line allows live imaging of ciliary dynamics and trafficking of cilia proteins, such as Kif7 and Smo, key regulators of the Hedgehog signalling pathway. Thus, we have generated an effective new tool for in vivo cilia studies that will help shed further light on the roles of these important organelles.

Abstract This study brings insight into interpreting forest structural diversity and explore the classification of individuals according to the distribution of the neighbours in natural forests. Natural forest communities with different latitudes and distribution patterns in China were used. Each tree and its nearest neighbours form a structural unit. Random structural units (or random trees) in natural forests were divided into different sub-types based on the uniform angle index (W). The proportions of different random structural units were analysed. (1) There are only two types of random structural units: type R1 looks similar to a dumbbell, and type R2 looks similar to a torch. These two random structural units coexist in natural forests simultaneously. (2) The proportion of type R1 is far less than that of R2, is only approximately 1/3 of all random structural units or random trees; R2 accounts for approximately 2/3. Furthermore, the proportion of basal area presents the same trend for both random structural units and random trees. R2 has approximately twice the basal area of R1. Random trees (structural units) occupy the largest part of natural forest communities in terms of quantity and basal area. Meanwhile, type R2 is the largest part of random trees (structural units). This study finds that the spatial formation mechanism of natural forest communities which is of great significance to the cultivation of planted forests.

Abstract Background Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. Methods The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. Results MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. Conclusion MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.

Abstract Background A number of hypotheses and theories, such as the Janzen-Connell hypothesis, have been proposed to explain the natural maintenance of biodiversity in tropical and temperate forest ecosystems. However, to date the details of the processes behind this natural maintenance are still unclear. Recently two new nearest-neighbour characteristics were proposed and in this paper we demonstrate how they can contribute to a better understanding of the ontogenesis of global forest structure from localised neighbourhoods. Methods We applied the new species and size segregation functions together with appropriate test procedures to four example woodland data sets from China at Daqingshan, Jiaohe, Jiulongshan and Xiaolongshan forest regions. In addition we quantified the morphology of the new characteristics and modelled a neighbourhood allometric coefficient linking the two functions. Results The results revealed quite different species segregation patterns with both conspecific and heterospecific attraction. We found these to be generally matched by equivalent size segregation patterns of attraction of similar and different sizes. It was straightforward to model the size segregation function from the knowledge of the species segregation function by estimating a neighbourhood allometric coefficient. Conclusions The new characteristics have helped to quantify the extent and rate of decline of neighbourhood interactions in terms of spatial species and size diversity. Through the allometric neighbourhood coefficient the analysis highlighted once more how closely related species and size segregation are, thus supporting the mingling-size hypothesis. Using both a traditional and a restricted random-labelling test has provided a valuable tool for understanding the exact nature of species-mingling and size-inequality relationships.

Abstract Background In recent years, some studies have shown that there is a positive association between the number of oocytes retrieved and the cumulative live birth rate (CLBR) after fresh and frozen cycles of one oocyte retrieval. However, almost no studies have examined the association between the number of oocytes retrieved and the CLBR when using the “freeze-all” strategy. We performed this study to investigate the effects of an extreme oocyte yield during the first “freeze-all” cycle on the cumulative live birth rate among patients younger than 35 years old. Methods This was a retrospective cohort study performed in a university-affiliated reproductive medicine centre. Data obtained from 3276 women aged younger than 35 years who underwent their first “freeze-all” cycle (IVF/ICSI) were collected between January 2009 and December 2016. In all, 5025 frozen cycles took place during the follow-up period from January 2009 to December 2018. Patients were divided into five groups according to oocytes retrieved (group 1: 4–10 oocytes; group 2: 11–20 oocytes; group 3: 21–30 oocytes; group 4: 31–40 oocytes; group 5: > 40 oocytes). The primary outcome was the cumulative live birth rate. Results Unadjusted results showed that the cumulative live birth rate significantly increased as the number of oocytes retrieved increased and reached up to 93.82% in cases with yields of 21–30 oocytes (P 0.05). After adjusting for confounders, our results showed that the number of oocytes retrieved is an independent positive predictor of cumulative live birth rate when using a “freeze-all” strategy. (P

This paper studies the fault-tolerant tracking consistency problem of multi-agent systems with actuator faults and saturation and L2 disturbance. Firstly, a new index is given to describe the anti-disturbance ability and H∞ performance of the multi-agent system. In addition, a new method of designing adaptive fault-tolerant controller is given for multi-agent systems which can guarantee that the closed-loop systems H performance and disturbance tolerance performance are better than the fixed gains method. For this new method, by using the adaptive law, the controller parameters are updated on-line to compensate for the fault effects on multi-agent systems. The results show that the adaptive controller designed can achieve system consistency and better performance in the case of multi-agent system with actuator failure, saturation and L2 disturbance. An example illustrating the validity of the results is given.

Intelligent video surveillance (IVS) technology is widely used in various security systems. However, quality degradation in surveillance images (SIs) may affect its performance on vision-based tasks, leading to the difficulties in the IVS system extracting valid information from SIs. In this paper, we propose a hybrid no-reference image quality assessment (NR IQA) model for SIs that can help to identify undesired distortions and provide useful guidelines for IVS technology. Specifically, we first extract two main types of quality-aware features: the low-level visual features related to various distortions, and the high-level semantic information, which is extracted by a state-of-the-art (SOTA) vision transformer backbone. Then, we fuse these two kinds of features into the final quality-aware feature vector, which is mapped into the quality index through the feature regression module. Our experimental results on two surveillance content quality databases demonstrate that the proposed model achieves the best performance compared to the SOTA on NR IQA metrics.

ObjectivesTo evaluate the combined impact of male and female BMI on cumulative pregnancy outcomes after the first ovarian stimulation.DesignRetrospective cohort study.SettingUniversity-affiliated reproductive medicine center.PatientsA total of 15,972 couples undergoing their first ovarian stimulations from June 2009 to June 2016 were included. During the follow-up period between June 2009 and June 2018, 14,182 couples underwent a complete ART cycle involving fresh embryo transfer and subsequent frozen embryo transfers (FETs) after their first ovarian stimulations. Patients with a BMI

Abstract Background China has a long tradition of managing planted forests. Different species of Populus, Eucalyptus, Larix, Cunninghamia and Pinus are planted to satisfy the local demand for wood products and provide ecological services at the same time. Evidence of the greater resilience of natural forests provides the motivation to develop asymmetric planting patterns, which is the focus of this study. We present a new method for designing plantation patterns that follow those observed in natural ecosystems and to maintain some regularity for operational convenience. Methods Based on the uniform angle index, we analyzed the spatial structure of six natural forests in different regions of China. The uniform angle index describes the degree of spatial uniformity of the n nearest neighbors of a given reference tree. Accordingly, we identified all possible patterns of a neighborhood group within a regular planting pattern and developed a method to optimize planting point arrangements that contain some randomness as well as a minimum degree of regularity. Results (1) There are 13 types of structural units in a regular planting, including seven random units, five even units and one cluster unit; (2) Five near-natural arrangements are presented with a minimum proportion of 50% of random units. These five arrangements represent a combination of regularity for operational convenience and asymmetry. Conclusions The new planting patterns developed in this study are expected to increase the asymmetric competition and resilience of these important ecosystems. Some experimental plantings, based on our findings, have already been established, e.g., in Pinus tabulaeformis plantations in Tianshui, Gansu Province, and in a Populus deltoides plantation in Fangshan near Beijing.

The distribution of hydrophobic organic contaminants (HOCs) in eutrophic ecosystems has been widely studied, but how phytoplankton blooms affect their occurrence and benthic bioaccumulation is poorly understood. To fill this knowledge gap, the biological pump effects of phytoplankton on the fate of organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in sediments and benthos (Corbicula fluminea) from Lake Taihu, a hypereutrophic lake in China, were identified. The spatial-temporal distribution of HOCs suggests that higher phytoplankton biomass, coupled with sediment organic matter (SOM) content, greatly increased the concentration of HOCs in sediments in both winter and summer seasons. This could be attributed to the biological pump effects sequestering more HOCs from water to sediments with settling phytoplankton, especially during the summer. The biological pump effects further promoted the uptake of sediment-bound HOCs by benthos. The significant positive relationships between concentrations of HOCs in sediments and benthos were observed during the winter dormancy phase of benthos. Furthermore, the benthic bioaccumulation of HOCs could be strengthened by phytoplankton, due to their contribution to SOM and the following increased bioavailability of HOCs in sediments. Further research is needed to elucidate the phytoplankton biological pump effects on the fate of HOCs in benthic food chain, especially for hypereutrophic waters.

Volatile organic sulfur compounds (VOSCs) function as a water–atmosphere link in the global sulfur cycle. It is generally believed that the vast majority of VOSCs are released from the ocean. However, due to the pervasive eutrophication and pollution of inland waters, the VOSC production and emission in rivers, lakes and reservoirs are attracting more attention. In this study, the temporal and spatial distributions of three VOSCs, including methanethiol, Dimethyl sulfide, and dimethyl disulfide in Yangcheng Lake, a eutrophic shallow lake, are investigated monthly and seasonally. Results show that VOSCs are higher in summer and autumn, with the western region as a hotspot. Our results show a positive correlation between VOSC and phytoplankton biomass (p < 0.05). Interestingly, from algal phylum composition, all the phylum, except those with low biomass, played a positive effect on VOSCs’ concentration. We did not find any specific phylum or species of cyanobacteria that contributed solely to the VOSCs. The water-air effluxes of Dimethyl sulfide (DMS) are estimated by a stagnant film model. The DMS effluxes from Yangcheng Lakes were higher than deep lakes and similar to the ocean, indicating that VOSCs, particularly DMS, in those eutrophic shallow lakes were non-negligible.

The ADP ribosylation factor (ARF) GTPase activation protein ASAP1 possesses multiple biological functions, including regulation of cytoskeletal dynamics, small GTP-binding protein receptor recycling, and intracellular vesicle trafficking. Recently, ASAP1 polymorphisms have been reported to be associated with human susceptibility to tuberculosis (TB) according to a large-scale genome-wide association study (GWAS); ASAP1 expression affects dendritic cell migration, which may be involved in TB predisposition. However, it remains unclear whether ASAP1 affects TB in vivo. To address this issue, we used zebrafish as a model system to examine the effects of Asap1 against Mycobacterium marinum, an organism closely related to Mycobacterium tuberculosis. Two zebrafish asap1 homologs (asap1a and asap1b) were identified and characterized. By morpholino knockdown of asap1a and asap1b as a whole, we found that the asap1 morphants showed a higher mycobacterial load than the controls, which was almost rescued by injecting asap1 mRNA that confers resistance to mycobacterial infection. These Asap1-depleted zebrafish also exhibited decreased macrophage migration in response to tail injury or upon infection with M. marinum in the hindbrain ventricle, which was also proved in THP1-derived macrophages of knockdown ASAP1. Together, these findings represent a new perspective on the role of Asap1 in resistance to mycobacterial infection.

Abstract Background Mucopolysaccharidosis type I (MPS I) is a rare autosomal storage disorder resulting from the defective alpha‐L‐iduronidase (encoded by IDUA) enzyme activity and accumulation of glycosaminoglycans (GAGs) in lysosomes. So far, more than 100 IDUA causative mutations have been identified leading to three MPS I phenotypic subtypes: Hurler syndrome (severe form), Hurler/Scheie syndrome (intermediate form), and Scheie syndrome (mild form). Methods Whole‐exome sequencing (WES) was performed to identify the underlying genetic mutations. To verify the identified variations, Sanger sequencing was performed for all available family members following PCR amplification. The impact on IDUA protein was analyzed by sequential analysis and homology modeling. Results A novel IDUA heterozygous single base insertion (c.1815dupT, p.V606Cfs51*) and a known missence mutation (c.T1037G, p.L346R) were detected in our patient diagnosed as congenital heart disease with heart valve abnormalities. The novel frameshift mutation results in a complete loss of 48 amino acids in the Ig‐like domain and causes the formation of a putative protein product which might affect the IDUA enzyme activity. Conclusions A novel compound heterozygous IDUA mutation (c.1815dupT, p.V606Cfs51*) was found in a Chinese MPS I family. The identification of the mutation facilitated accurate genetic counseling and precise medical intervention for MPS I in China.

Abstract Negative conspecific density dependence is one of the principal mechanisms affecting plant performance and community spatial patterns. Although many studies identified the prevalence of density dependent effects in various vegetation types by analyzing conspecific spatial dispersal patterns (spatial patterning) of forest trees, interactions between individuals and heterospecific neighboring trees caused by density-dependent effects are often neglected. The effects of negative density dependence lead us to expect that neighbourhood species segregation would increase with increasing tree size and that larger trees would be surrounded by more heterospecific neighbours than would smaller trees. We studied four mapped 1-Ha plots on Changbaishan Mountain in North-eastern China and used marked point pattern analysis to explore whether trees of different sizes exhibited differences in neighbourhood species segregation; we also determined whether larger trees were more likely to have heterospecific neighbours than smaller trees were. Our results show that bigger trees generally have higher species mingling levels. Neighborhood species segregation ranged from lower than expected levels to random or nearly random patterns at small scales as tree size classes increased under heterogeneous Poisson null model tests. This study provides some evidence in support of negative density dependent effects in temperate forests.

Abstract Background Beta‐propeller protein‐associated neurodegeneration (BPAN, OMIM 300894) is an X‐linked neurodegenerative disorder caused by mutations in WDR45. WDR45 is required for autophagy, defect in WDR45 impaired autophagy which contributes for the pathogenesis of BPAN. Previously, we reported a novel de novo mutation (c.1040_1041del, p.Glu347GlyfsTer7) in WDR45 (NM_007075) in a 3‐year‐old Chinese girl with BPAN. Methods The protein structure was constructed using SWISS‐MODEL and the isoelectric point (pI) was predicted by the online pI/Mw tool at ExPASy. The functional effects of this mutation were predicted by two online software programs: PROVEN and MutationTaster. Stable overexpression of Flag‐tagged wild‐type or mutant WDR45 in HeLa cells was constructed. Protein levels of LC3 and p62 were analyzed by western blot upon treatment with/without autophagy inhibitor Bafilomycin A1, the formation of LC3 puncta were analyzed in HeLa cells transfected with mCherry‐LC3 by confocal microscopy. Results The mutation resulted in a shift of pI from 6.74 to 8.84 and was predicted to be pathogenic. The protein levels of LC3‐II and p62 were increased in cells overexpression of wild‐type and mutant WDR45 while the protein levels were not increased in cells overexpression of mutant WDR45 upon treatment with autophagy inhibitor Bafilomycin A1. Results from confocal microscopy revealed that LC3‐positive puncta were increased in cells expressing both wild‐type and mutant WDR45 while the number of LC3‐positive puncta was not increased in cells expressing mutant WDR45 upon treatment with Bafilomycin A1. Conclusion Our study evidenced that this novel mutation in WDR45 impaired autophagy in cells thus this mutation is the cause for BPAN in this patient.

The rapid growth of power grid capacity and the widespread use of a large number of power electronics and non-linear loads have led to harmonics in the power system. Harmonics in the power system will cause safety hazards to the normal operation of power equipment, exacerbate the aging of insulation materials, and reducing the overall operation reliability of the system. In the present work, we used power frequency ac voltage superimposed harmonics to carry out ageing experiments on power cable terminals. Then, we tested the infrared spectra, dielectric spectra, electrical conductivity, and surface potential decay characteristics of silicone rubber insulation materials on the cable terminals aged for different times. The experimental results show that the dielectric constant and dielectric loss of silicone rubber gradually increase with the aging time. In particular, the dielectric loss of silicone rubber changed greatly at low frequencies. The effect of dc conductance of aged silicone rubber on dielectric loss is significantly enhanced at low frequencies, which causes the dielectric loss to increase as the frequency decreases following an inverse power law. The surface potential decay rates of silicone rubber insulation after positive and negative corona charging accelerate with increasing the aging time, which is consistent with the experimental results of electrical conductivity. By analyzing the distribution characteristics of electron and hole traps in silicone rubbers, it is found that the trap energy levels of electron and hole traps become shallower as the operating time increases. The calculation of the carrier hopping conduction model shows that the shallow trap formed with increasing the aging time will lead to increases in both carrier mobility and conductivity. When the conductivity rises to a certain value, the silicone rubber will lose its insulation performance, resulting in insulation failure.

In this paper, low-density parity-check (LDPC)-coded carrierless amplitude and phase (CAP) modulation with spatial diversity is proposed to mitigate turbulence-induced fading in an underwater visible-light communication (UVLC) channel. Generalized-gamma (GG) distribution was used to model the fading, as this model is valid for weak- and strong-turbulence regimes. On the basis of the characteristic function (CHF) of GG random variables, we derived an approximated bit-error rate (BER) for the CAP modulation scheme with spatial diversity and equal-gain combining (EGC). Furthermore, we simulated the performance of the CAP system with diversity and LDPC for various turbulence conditions and validated the analysis. Obtained results showed that the combination of LDPC and spatial diversity is effective in mitigating turbulence-induced fading, especially when turbulence strength is strong.

In this paper, combined with experiments and theoretical calculations, the effect of urban low-calorific value sludge on the slagging characteristics of easy-slagging coals is studied. The results show that when the melting point of sludge ash is lower than that of coal ash, the ash melting point of the mixture after the two blends will be lower than the melting point of raw coal ash. When SiO2 and Al2O3, which are relatively high in sludge, are used as single additives, the ash melting point of coal will first decrease and then increase. As the mixing ratio of sludge increases, coal ash slagging characteristics show a trend of gradual relief. For coals that are prone to slagging and rich in alkali metals, they can be appropriately mixed with sludge rich in silicon and aluminum compounds or additives to improve Slagging characteristics.

Concentrations of polycyclic aromatic hydrocarbons (PAHs) were measured in 22 surface sediment samples and an approximately 100-year scale sediment core collected from Poyang Lake. This valuable sediments enable analysis of spatial and temporal distribution patterns of PAH sources, and determine the anthropogenic impacts on Poyang Lake. Total PAH concentrations in the surface sediments ranged from 73.2 to 367.2 ng/g dw, and higher residues were encountered in regions with high-density populations and intensive human activities. Total PAH concentrations in the sediment core ranged from 42.0 to 334.0 ng/g dw and were grouped in two clusters (pre-1990s and post-1990s to the present). PAH concentrations in sediments changed both temporally and spatially, suggesting a difference in PAH sources. Before the 1990s, major PAH sources in the sediment core were from coal, wood and grass combustion. This finding naturally agrees with open lake conditions on a spatial scale, which were related to agricultural activities. Petroleum combustion from industrialization and urbanization has become the predominant PAH source in the sediment core from the 1990s to the present and corresponds to sources observed in the southwestern lake near the relatively developed Nanchang City. In the northern lake leading to the Yangtze River, certain petroleum-related contaminants from shipping have become the main PAH sources. The different PAH sources observed in sediments generally reflect the degree of socio-economic development in the Poyang Lake valley, which is consistent with the local written records, indirectly validating the connection of sediment PAH records to the history of human activities in and around Poyang Lake.

The Chinese pine (Pinus tabulaeformis Carr.) is an ecologically and economically important evergreen coniferous tree which dominates warm temperate forests throughout northern China. We established two permanent plots within the Chinese pine forest in the Jiulong Mountains, Beijing, China. To understand the structural characteristics and dynamics of these plots, we analyzed the spatial structural characteristics within nearest-neighbor relationships using the bivariate distributions of the stand spatial structural parameters: uniform angle index, W; mingling index, M; dominance index, U; and crowding index, C. Results revealed that most trees in the forest were randomly distributed. The predominant individuals and randomly arranged trees were in very dense areas and surrounded by the same species. In addition, both plots exhibited a uniform size differentiation pattern. The two plots differed mainly in the level of species mixture and dominance. The majority of reference trees in the pure Chinese pine forest (plot 1) exhibited poor species mingling and low dominance, whereas trees in the mixed Chinese pine forest (plot 2) were evenly distributed in each mingling class and most trees were of intermediate dominance. The study results are useful for optimizing forest management activities in the studied stands, promoting tree growth, regeneration and habitat diversity, and improving forest quality at a fine scale.

Summary Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a.

Human activities in and around Lake Wuliangsu, in the upper reaches of the Yellow River, triggered environmental changes for which evidence is preserved in the lake sediments. We investigated the past ~150 years of human impacts on Lake Wuliangsu using high-resolution records of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in the sediments. Prior to the 1950s, there were very low concentrations of contaminants in the lake deposits. In the 1950s, relatively higher OCP concentrations and proportions of low molecular weight (LMW) PAHs were related to the intensification of agricultural activity. Since the 1990s, increases in high molecular weight (HMW) PAH concentrations and their proportions, and decreases in OCP concentrations and proportions of LMW PAHs, indicated human impacts on the lake were dominated by industry and urban development. Thus, there have been three periods of human-mediated environmental change in the Lake Wuliangsu basin, inferred from the PAH and OCP records (pre-1950s, 1950s-1990s, and 1990s to present). The inferred changes are consistent with the local socioeconomic data. The agreement between paleolimnologic records from Lake Wuliangsu and socioeconomic data suggests that the lake sediments provide a reliable archive for investigating the environmental history of human impacts on the lake.

Aim of the study: Neighborhood-based stand spatial structure parameters can quantify and characterize forest spatial structure effectively. How these neighborhood-based structure parameters are influenced by the selection of different numbers of nearest-neighbor trees is unclear, and there is some disagreement in the literature regarding the appropriate number of nearest-neighbor trees to sample around reference trees. Understanding how to efficiently characterize forest structure is critical for forest management.Area of study: Multi-species uneven-aged forests of Northern ChinaMaterial and methods: We simulated stands with different spatial structural characteristics and systematically compared their structure parameters when two to eight neighboring trees were selected.Main results: Results showed that values of uniform angle index calculated in the same stand were different with different sizes of structure unit. When tree species and sizes were completely randomly interspersed, different numbers of neighbors had little influence on mingling and dominance indices. Changes of mingling or dominance indices caused by different numbers of neighbors occurred when the tree species or size classes were not randomly interspersed and their changing characteristics can be detected according to the spatial arrangement patterns of tree species and sizes.Research highlights: The number of neighboring trees selected for analyzing stand spatial structure parameters should be fixed. We proposed that the four-tree structure unit is the best compromise between sampling accuracy and costs for practical forest management.

To obtain accurate underwater target tracking results, an improved kernelized correlation filter (IKCF) algorithm is proposed to track the target in forward-looking sonar image sequences. Specifically, a base sample with a dynamically continuous scale is first applied to solve the poor performance of fixed-scale filters. Then, in order to prevent the filter from drifting when the target disappears and appears again, an adaptive filter update strategy with the peak to sidelobe ratio (PSR) of the response diagram is developed to solve the following target tracking errors. Finally, the experimental results show that the proposed IKCF can obtain accurate tracking results for the underwater targets. Compared to other algorithms, the proposed IKCF has obvious superiority and effectiveness.

Growing evidence suggests that there are many common cell biological features shared by neurons and podocytes; however, the mechanism of podocyte foot process formation remains unclear. Comparing the mechanisms of process formation between two cell types should provide useful guidance from the progress of neuron research. Studies have shown that some mature proteins of podocytes, such as podocin, nephrin, and synaptopodin, were also expressed in neurons. In this study, using cell biological experiments and immunohistochemical techniques, we showed that some neuronal iconic molecules, such as Neuron-specific enolase, nestin and Neuron-specific nuclear protein, were also expressed in podocytes. We further inhibited the expression of Neuron-specific enolase, nestin, synaptopodin and Ubiquitin carboxy terminal hydrolase-1 by Small interfering RNA in cultured mouse podocytes and observed the significant morphological changes in treated podocytes. When podocytes were treated with Adriamycin, the protein expression of Neuron-specific enolase, nestin, synaptopodin and Ubiquitin carboxy terminal hydrolase-1 decreased over time. Meanwhile, the morphological changes in the podocytes were consistent with results of the Small interfering RNA treatment of these proteins. The data demonstrated that neuronal iconic proteins play important roles in maintaining and regulating the formation and function of podocyte processes.

The Hedgehog (Hh) signal is transduced across the membrane by the heptahelical protein Smoothened (Smo), a developmental regulator, oncoprotein and drug target in oncology. We present the 2.3 Å crystal structure of the extracellular cysteine rich domain (CRD) of vertebrate Smo and show that it binds to oxysterols, endogenous lipids that activate Hh signaling. The oxysterol-binding groove in the Smo CRD is analogous to that used by Frizzled 8 to bind to the palmitoleyl group of Wnt ligands and to similar pockets used by other Frizzled-like CRDs to bind hydrophobic ligands. The CRD is required for signaling in response to native Hh ligands, showing that it is an important regulatory module for Smo activation. Indeed, targeting of the Smo CRD by oxysterol-inspired small molecules can block signaling by all known classes of Hh activators and by clinically relevant Smo mutants.

Loss of function mutations of Kif7, the vertebrate orthologue of the Drosophila Hh pathway component Costal2, cause defects in the limbs and neural tubes of mice, attributable to ectopic expression of Hh target genes. While this implies a functional conservation of Cos2 and Kif7 between flies and vertebrates, the association of Kif7 with the primary cilium, an organelle absent from most Drosophila cells, suggests their mechanisms of action may have diverged. Here, using mutant alleles induced by Zinc Finger Nuclease-mediated targeted mutagenesis, we show that in zebrafish, Kif7 acts principally to suppress the activity of the Gli1 transcription factor. Notably, we find that endogenous Kif7 protein accumulates not only in the primary cilium, as previously observed in mammalian cells, but also in cytoplasmic puncta that disperse in response to Hh pathway activation. Moreover, we show that Drosophila Costal2 can substitute for Kif7, suggesting a conserved mode of action of the two proteins. We show that Kif7 interacts with both Gli1 and Gli2a and suggest that it functions to sequester Gli proteins in the cytoplasm, in a manner analogous to the regulation of Ci by Cos2 in Drosophila. We also show that zebrafish Kif7 potentiates Gli2a activity by promoting its dissociation from the Suppressor of Fused (Sufu) protein and present evidence that it mediates a Smo dependent modification of the full length form of Gli2a. Surprisingly, the function of Kif7 in the zebrafish embryo appears restricted principally to mesodermal derivatives, its inactivation having little effect on neural tube patterning, even when Sufu protein levels are depleted. Remarkably, zebrafish lacking all Kif7 function are viable, in contrast to the peri-natal lethality of mouse kif7 mutants but similar to some Acrocallosal or Joubert syndrome patients who are homozygous for loss of function KIF7 alleles.

The conformance testing on the wireless sensor networks (WSNs) is fundamental for the functional large-scale deployment and interconnection with the global Internet. The WSN protocols based on the Internet Protocol version 6 (IPv6) are the major trends of the future applications, which include IEEE 802.15.4, 6LoWPAN, and RPL. These protocols are not only diverse for various applications, but also volatile in the future. Moreover, sensor nodes are resource constrained, application related and lack the standardized test interface. Hence the corresponding conformance testing is seriously insufficient and needs urgently research. In this paper, the IPv6-based WSN protocols are analyzed and the conformance testing techniques and methods for IPv6-based WSNs are investigated towards the standardization of WSNs. A novel conformance test system for IPv6-based WSNs is designed and implemented, which is open, flexible, full featured, and practical. The conformance test system is suitable for the protocol evolution and the various hardware interfaces for the sensor nodes. The related outcomes will promote the standardization and commercialization of WSNs.

To study renalase's expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells. Anti-renalase monoclonal antibodies were successfully prepared by using DNA immunization technique. Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant. Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.

BACKGROUND: OTUB1 is a member of OTUs (Ovarian-tumor-domain-containing proteases), a deubiquitinating enzymes family (DUBs), which was shown as a proteasome-associated DUB to be involved in the proteins Ub-dependent degradation. It has been reported that OTUB1 was expressed in kidney tissue. But its concrete cellular location and function in the kidney remain unclear. Decorin (DCN) in mesangial cells (MC) is considered to be a potentially important factor for antagonizing glomerulonephritides, and its degradation is mediated by ubiquitination. The aim of this study is to investigate the role of OTUB1 expression in MC and its relationship with DCN during glomerulonephritis. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative RT-PCR and Western blot, we demonstrated that OTUB1 mRNA and protein were constitutively expressed in cultured rat MC and found to be upregulated by the stimulation of IL-1β or ATS. OTUB1 overexpression was detected in the mesangial area of glomeruli in some immunocomplex mediated nephritides such as IgA nephropathy, acute diffuse proliferative glomerulonephritis and lupus nephritis by immunohistochemistry. The immunoprecipitation assay demonstrated that OTUB1 interacted with DCN. The overexpression of OTUB1 enhanced the ubiquitination and degradation of DCN in MC. CONCLUSION/SIGNIFICANCE: These data showed the inflammatory injury could up-regulate OTUB1 expression in MC, which might attribute the promoting effect of OTUB1 on glomerulonephritides to the decrease of DCN level.