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Reproductive investment decision is an integral part of life-history theory. Differential allocation hypothesis predicts that females should increase investment when mated to high-quality males, conversely, reproductive compensation hypothesis predicts that females should increase investment when mated to low-quality males. Empirical research dominantly focuses on polygamous species and rarely on serially monogamous species. So, the question remains: which hypothesis does serially monogamous species fit? And if it fits reproductive compensation hypothesis, do females only compensate once or continuously for multiple times when mating to low-quality males? Here, we used a serially monogamous fish, the lined seahorse (Hippocampus erectus), to investigate the reproductive investment pattern of females in relation to male quality (measured by sexual attractiveness). We found that females allocated more resources into eggs when they mated to less-sexually-attractive males, indicating the investment pattern of lined seahorse falls in with the prediction of reproductive compensation hypothesis. This finding may imply that the sex role of seahorses is reversed, and female is the side imposed on a greater sexual selection pressure. On this basis, we compared the investment difference of females in two consecutive breeding events when mated to less-sexually-attractive males. We found that females allocated less resources into eggs in the second breeding than in the first one. Females reduced their reproductive compensation in the second breeding, which may be attributed to the improvement in the quality (e.g., paternal care ability) of their mates after the first breeding, thus eliminating the need for them to invest more in the second breeding., (© 2024. The Author(s).)

Land use changes significantly impact the structure and functioning of ecosystems. The current research focus lies in how to utilize economic and policy instruments to regulate conflicts among stakeholders effectively. The objective is to facilitate rational planning and sustainable development of land utilization resources. The PLUS model integrates a rule-based mining method for land expansion analysis and a CA model based on multi-type stochastic seeding mechanism, which can be used to mine the driving factors of land expansion and predict the patch-level evolution of land use landscapes. Using the PLUS model, a simulation was conducted to study the future land use distribution in the research area over the next 30 years. Based on land use data from Guizhou Province in 2000, 2010, and 2020, a total of 16 driving factors were selected from three aspects: geographical environment, transportation network, and socio-economic conditions. Four scenarios, namely natural development, urban development, ecological conservation, and farmland rotection, were established. Comparative analysis of the simulated differences among the various scenarios was performed. (1) The overall accuracy of the land use simulation using the PLUS model in the study area was 0.983, with a Kappa coefficient of 0.972 and a FoM coefficient of 0.509. The research accuracy meets the simulation requirements. (2) Through the simulation of four different scenarios, the study investigated the land use changes in Guizhou Province over the next 30 years. Each scenario exhibited distinct impacts on land utilization. Comprehensive comparison of the different simulation results revealed that the farmland protection scenario aligns with the sustainable development goals of the research area. Currently, there is a relative scarcity of research on land use simulation, particularly in model application, for Guizhou Province. This study aims to provide a reference for the rational planning of land resources and high-quality urban construction in Guizhou, promoting the high-quality economic development in tandem with advanced ecological and environmental protection., (© 2024. The Author(s).)

In this investigation, pulsed current electro-deposition (PCE) was used to prefabricate Ni-Co/SiC + TiN composite coatings (NCSTCCs) on mild steel surfaces. The research focused on the influence of two electrodeposition parameters, pulse frequency (PF) and duty cycle (DC), on NCSTCF features including microscopic surface morphology, crystal orientation, grain size, microhardness, SiC and TiN nanoparticles (NPs), deposition quantity, and corrosion resistance properties. The results indicated that NCSTCCs produced under a 10% DC showed minimal SiC and TiN contents with a percent volume of just 5.6 v/v% and 5.4 v/v% respectively under the fixed condition of 60 Hz PF. However, the three-dimensional surface diagram indicated that the Ni-Co/SiC + TiN composite film deposited at 50% DC and 10 Hz PF displayed the highest SiC and TiN contents (11.6 v/v% and 11.7 v/v%) among all the films. Furthermore, NCSTCCs deposited under 50% DC and 10 Hz PF had peak microhardness at 667.4 kg/mm 2 , while the composite film achieved a microhardness of 514.1 kg/mm 2 when prepared using 10% DC and 60 Hz PF. Moreover, when the DC and PF were at 50% and 10 Hz respectively, the Ni-Co/SiC + TiN composite film presented the maximum charge transfer resistance (4915.7-4927.2 Ω·cm 2 ), indicating an excellent corrosion resistance., (© 2024. The Author(s).)

This paper explores the feasibility and principle of hepatic parenteral fluorescence imaging technology after retrograde injection of indocyanine green (ICG) through endoscopic nasobiliary drainage (ENBD). The data were collected from 53 patients with cholecystolithiasis and choledocholithiasis, from October 2022 to March 2023, diagnosed by fluorescence imaging technique retrograde biliary approach (FIT-RB). We divided the patients into two groups according to the features of liver parenchyma, the poor group (n = 34, including scattered or no imaging) and the good group (n = 19, regular uniform imaging). We compared and analyzed the perioperative results of the two groups and explored the influencing factors of the success of FIT-RB and the ICG concentration suitable for this imaging technique. The good imaging rate of the 53 enrolled cases was 35.8%. The bilirubin level before ENBD and laparoscopic cholecystectomy in the poor group was significantly higher than that in the good group (P < 0.001). The proportion of higher ICG concentrations (0.5 mg/mL) was significantly higher in the good group (P = 0.028). Our results demonstrated that the success rate of good imaging was 4.53 times higher than that of low-dose ICG (0.125 or 0.25 mg/L) cases at 0.5 mg/ml of ICG. The level of total bilirubin and direct bilirubin were negatively correlated with the imaging effect, and total bilirubin and direct bilirubin levels were important predictors of the efficacy of FIT-RB. FIT-RB is safe and feasible in patients with low site bilirubin levels. An ICG concentration of 0.5 mg/ml may be ideal for implementing this technique., (© 2024. The Author(s).)

Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman's ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra., (© 2024. The Author(s).)

Sarcomas (SARC) are a highly heterogeneous cancer type that is prone to recurrence and metastasis. Numerous studies have confirmed that Siglecs are involved in immune signaling and play a key role in regulating immune responses in inflammatory diseases and various cancers. However, studies that systematically explore the therapeutic and prognostic value of Siglecs in SARC patients are very limited. The online databases GEPIA, UALCAN, TIMER, The Kaplan-Meier Plotter, GeneMANIA, cBioPortal, and STING were used in this study. IHC staining was performed on the collected patient tissues, and clinical data were statistically analyzed. The transcript levels of most Siglec family members showed a high expression pattern in SARC. Compared with normal tissues, Siglec-5, Siglec-10, and Siglec-12 were abnormally highly expressed in tumor tissues. Importantly, Siglec-15 was significantly associated with poor prognosis. Functional enrichment analysis showed that the Siglec family was mainly enriched in hematopoietic cell lineages. The genes associated with molecular mutations in the Siglec family were mainly TP53 and MUC16, among which Siglec-2 and Siglec-15 were significantly associated with the survival of patients. The expression levels of all Siglec family members were significantly correlated with various types of immune cells (B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells). Furthermore, a significant correlation was found between the somatic copy number changes of all Siglec molecules and the abundance of immune infiltrates. Our study paints a promising vision for the development of immunotherapy drugs and the construction of prognostic stratification models by investigating the therapeutic and prognostic potential of the Siglec family for SARC., (© 2024. The Author(s).)

Penile size is closely concerned and short penis contributes serious sexual dysfunction and tremendous psychological problems to couples. Androgen is essential for penile development and testosterone replacement is recommended to patients with micropenis. We previously proved that inhibiting activity of lysyl oxidase (Anti-lysyl oxidase, Anti-LOX) combined with vacuum erectile device (VED) lengthened penis by remodeling tunica albuginea. We thus explored whether HCG supplement could accelerate tunica albuginea remodeling (induced by Anti-LOX + VED) to promote penile growth. Forty-two SD male rats (4 weeks old) were purchased and divided into 7 groups: control, Anti-LOX, HCG, VED (with a negative aspirated pressure of - 300 mmHg), Anti-LOX + VED, HCG + VED, and Anti-LOX + HCG + VED. After an intervention for 4 weeks, all rats' penile length, exposed penile length, and erectile function were measured. Serum samples were collected to detect hormone levels and penile corpus cavernosum were harvested for histo-pathological analysis. All intervention groups showed significantly longer penis than controlled rats. Anti-LOX sharply increased penile length and exposed length by 15% and 9% respectively, this lengthening effect was more obvious in Anti-LOX + VED group (26% and 19%, respectively). Although HCG promoted penile length by 8%, this effect was slight for exposed length (3%). Moreover, Anti-LOX + HCG + VED dramatically increased penile length and exposed length by 22% and 18%, respectively, which was similar with that in Anti-LOX + VED (26% and 19%, respectively). HCG dramatically stimulated testosterone and dihydrotestosterone secretions than control group, whether with or without Anti-LOX and VED; while it induced more AR expression than other groups. Finally, all procedures did not improve or deteriorate normal erectile function. Although we verified that Anti-LOX + VED lengthened penis by inducing tunica albuginea remodeling, however, HCG supplement did not synergize with Anti-LOX + VED to accelerate albuginea remodeling to facilitate penile growth., (© 2023. Springer Nature Limited.)

The evaluation index system is constructed based on the connotation and characteristics of health tourism. Using the entropy method, Thiel index, exploratory spatial data analysis method, spatial Markov chain and spatial econometric model, research is carried out around the development index, difference status, spatial-temporal pattern, dynamic evolution and influencing factors of health tourism. The following results were drawn: (1) The development index of health tourism in China is low, but the development speed is fast. The inter-regional development index shows an eastern China > central China > western China pattern, and the development speed exhibits a western China > central China > eastern China situation. (2) In the overall difference in China's health tourism development, the intra-regional difference is consistently higher than the inter-regional difference. Among the three major regions, the overall difference between eastern China and western China is always higher than that of central China. (3) The development of health tourism in China is positively correlated in the global space, with some local spatial clustering. (4) The dynamic evolution of health tourism development in China shows part of the "Matthew effect" characteristics, with an obvious spatial spillover effect. (5) Various influencing factors produced widely varying direct, indirect and total effects on health tourism development in China, eastern China, central China and western China. Finally, based on the results of the above empirical analysis, policy recommendations to promote the development of health tourism in China are proposed., (© 2023. Springer Nature Limited.)

To reduce the dimensionality of EEG features and improve classification accuracy, we propose an improved hybrid feature selection method for EEG feature selection. First, MIC is used to remove irrelevant features and redundant features to reduce the search space of the second stage. QPSO is then used to optimize the feature in the second stage to obtain the optimal feature subset. Considering that both dimensionality and classification accuracy affect the performance of feature subsets, we design a new fitness function. Moreover, we optimize the parameters of the classifier while optimizing the feature subset to improve the classification accuracy and reduce the running time of the algorithm. Finally, experiments were performed on EEG and UCI datasets and compared with five existing feature selection methods. The results show that the feature subsets obtained by the proposed method have low dimensionality, high classification accuracy, and low computational complexity, which validates the effectiveness of the proposed method., (© 2023. Springer Nature Limited.)

The discontinuous and unstable characteristics of solar energy limit its application in the space heating field, while aquifer thermal energy storage (ATES), as a seasonal thermal energy storage pattern, is a feasible way of solving these problems faced by solar space heating and however, low temperature ATES must not exceed 25-30 °C while high temperature ATES has low recovery efficiency. Here a novel scheme of storing high temperature solar thermal energy into a shallow depth artificial reservoir (SDAR) is proposed. By innovatively storing thermal energy into rocks rather than aquifer, the recovery efficiency improves from 46% for ATES to 90% for SDAR, and the thermal power increases from 309 kW for deep borehole heat exchanger to 1970 kW for SDAR. SDAR has no special requirement to rock temperature and can thus be created in shallow buried depth rocks, leading not only to a reduction of engineering cost but also an expansion of application scope. To further avoid risk of induced seismicity caused by hydraulic fracturing and reduce cost, the abandoned oil and gas fields and mines can be reused as the artificial reservoir., (© 2022. The Author(s).)

Myopic glasses design has critical effects on the match between glasses and individual face. Improper myopic glasses design may affect the try-on comfort and health. It is difficult for the myopic glasses to be adjusted variedly and suitably from people to people with the limitations of traditional manufacturing processes and current design methods. In this paper, an evaluation descriptor named glasses fit score, which contains alignment scores and design scores, is proposed to guide and evaluate the myopic glasses design. Based on the descriptor, a novel approach is presented to complete the myopic glasses design and manufacturing individually. The approach can be divided into three steps: glasses alignment, glasses personalized design and glasses manufacturing. During the glasses alignment, the myopic glasses are aligned to the face to obtain the alignment score of the descriptor based on the face symmetry plane and feature points, including the silent point of the eye and the top point of the ear. After the glasses alignment, the myopic glasses can be deformed to match the face to achieve the design score of the descriptor. The deformations include glasses frame transformation, glasses leg option and glasses personalized mark. In the glasses manufacturing, the designed myopic glasses can be fabricated by a 3D printer. Then, a post processing process is conducted to polish the myopic glasses with oil painted. Finally, the proposed approach is applied to adjust the myopic glasses for several people. The results show that, compared to the previous methods, the approach can make the myopic glasses aligned and deformed to the individual face effectively to obtain an ideal score of the descriptor, thus improving the match between the glasses and the individual face., (© 2022. The Author(s).)

We aimed to explore factors associated with prognosis in patients with metastatic small bowel adenocarcinoma (SBA) as well as to develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Relevant information of patients diagnosed between 2004 and 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms for predicting 1- and 3-year OS and CSS were established with potential risk factors screened from multivariate cox regression analysis. The discrimination and accuracy of the nomograms were assessed by concordance index (C-index), calibration plots, and the area under receiver operating characteristic curve (AUC). In total, 373 SBA patients with M1 category were enrolled. Multivariate analysis revealed that age, size and grade of primary tumor, primary tumor surgery, and chemotherapy were significant variables associated with OS and CSS. The C-index values of the nomogram for OS were 0.715 and 0.687 in the training and validation cohorts, respectively. For CSS, it was 0.711 and 0.690, respectively. Through AUC, decision curve analysis (DCA) and calibration plots, the nomograms displayed satisfactory prognostic predicted ability and clinical application both in the OS and CSS. Our models could be served as a reliable tool for prognostic evaluation of patients with metastatic SBA, which are favorable in facilitating individualized survival predictions and clinical decision-making., (© 2022. The Author(s).)

Primary nocturnal enuresis (PNE) affects children's physical and mental health with a high rate. However, its neural mechanism is still unclear. Studies have found that the paraventricular thalamus (PVT) is among the key brain regions implicated with awakening regulation and its control of the transition between sleep and wakening is dependent on signaling through the PVT-nucleus accumbens (NAc) pathway. So this study analyzed the function of brain regions and their connectivity of PVT and NAc. A total of twenty-six PNE and typically developing (TD) children were involved in the study and the methods of amplitude of low frequency fluctuation (ALFF), degree centrality (DC) and functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI) were used to analyze the brain functions. Results showed that there was no statistical significant difference in ALFF and DC between PNE and TD children in bilateral PVT and NAc. And there was statistical significant difference of the comparison of the FC of left PVT (lPVT) and left NAc (lNAc) between PNE and TD children. Meanwhile, there was negative correlation between awakening score and the FC of rPVT and lNAc, and no obvious correlation between awakening score and the FC of lPVT and lNAc in PNE children. Meanwhile, there was both negative correlation between awakening score and the FC of lPVT, rPTV and lNAc in TD children. Therefore, the FC between rPVT and lNAc was more reliable in assessing the degree of awakening ability in PNE children. This finding could help establish the evaluation index of PNE., (© 2021. The Author(s).)

In order to provide valuable guidelines for the conservation of germplasm of Lateolabrax maculatus, the genetic diversity and population structure analysis were evaluated for eight geographic populations along coastal regions of China, using 11 microsatellite DNA markers. The genetic parameters obtained showed that, eight populations can be clustered into two groups, the Northern group and the Southern group, concordant with their geographical positions. The UPGMA tree constructed according to the Nei's genetic distance along with the structure analysis and discriminant analysis of principal component also supported this result. This might be explained by the geographic separation and the divergent environmental conditions among the populations. It's worth noting that, QD (Qingdao) population from northern area was assigned to the Southern group and showed a close genetic relationship and similar genetic constitution with the southern populations. We speculated that large scales of anthropogenic transportation of wild fries from QD populations to the southern aquaculture areas in history should be the primary cause. The populations from GY (Ganyu), RD (Rudong) and BH (Binhai) had higher genetic diversity and showed limited genetic exchange with other populations, indicating better conservation of the natural resources in these regions. All populations were indicated to have experienced bottleneck events in history., (© 2021. The Author(s).)

An association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC). Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA. VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS. The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool., (© 2021. The Author(s).)

Bacterial culture and drug susceptibility testing are used to identify pathogen infections. Nevertheless, the process requires several days from collection to the identification of bacterial species and drug-resistance patterns. The digital PCR system is a rapidly developing quantitative detection technology widely applied to molecular diagnosis, including copy number variations, single nucleotide variant analysis, cancer biomarker discovery, and pathogen identification. This study aimed to use a droplet digital PCR system to identify bacteria in blood samples and explore its ability to identify pathogen in bacteremia. Then, we designed primers and probes of SWG-9 and COA gene for E. coli and S. aureus to identify in blood samples with the ddPCR system. The system had demonstrated extremely high detection accuracy in blood samples, and the detection rate of E. coli was 13.1-21.4%, and that of S. aureus was 50-88.3%. Finally, blood samples containing both E. coli and S. aureus were tested to evaluate further the accuracy and applicability of this method, indicating the detection rates range from 18.1% to 97%. The ddPCR system is highly promising as a qualitatively and quantitatively screening method for rapidly detecting pathogen.

Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases in children. While clinical outcomes for patients with juvenile JIA have improved, the underlying biology of the disease and mechanisms underlying therapeutic response/non-response are poorly understood. We have shown that active JIA is associated with distinct transcriptional abnormalities, and that the attainment of remission is associated with reorganization of transcriptional networks. In this study, we used a multi-omics approach to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with alterations in CD4+ T cell chromatin, as assessed by ATACseq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved. Overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling important questions regarding the pathobiology of autoimmune diseases.

Tissue fibrosis is an important index of renal disease progression. Diffusion-weighted magnetic resonance imaging's (DWI-MRI) apparent diffusion coefficient (ADC) reveals water diffusion is unobstructed by microstructural alterations like fibrosis. We hypothesized that ADC may indicate renal injury and response to therapy in patients with renovascular disease (RVD). RVD patients were treated with medical therapy (MT) and percutaneous transluminal renal angioplasty (MT + PTRA) (n = 11, 3 bilaterally, n = 14 kidneys) or MT (n = 9). ADC and renal hypoxia (R2*) by blood-oxygen-level-dependent MRI were studied before (n = 27) and 3 months after (n = 20) treatment. Twelve patients underwent renal biopsies. Baseline ADC values were correlated with changes in eGFR, serum creatinine (SCr), systolic blood pressure (SBP), renal hypoxia, and renal vein levels of pro-inflammatory marker tumor necrosis-factor (TNF)-α. Renal oxygenation, eGFR, and SCr improved after MT + PTRA. ADC inversely correlated with the histological degree of renal fibrosis, but remained unchanged after MT or MT + PTRA. Basal ADC values correlated modestly with change in SBP, but not in renal hypoxia, TNF-α levels, or renal function. Lower ADC potentially reflects renal injury in RVD patients, but does not change in response to medical or interventional therapy over 3 months. Future studies need to pinpoint indices of kidney recovery potential.

In experiments that test plant diversity-productivity relationships, the common practice of weeding unsown species and disallowing species colonization may have the unintended consequence of favoring priority effects that maintain niche complementarity in determining productivity. However, in naturally assembled communities where colonization occurs, resource competition may favor dominant traits, which eventually have the greatest influence on productivity. Here, in naturally developed long-term subalpine meadows (from 4-year to at least 40 years meadows) in the Qinghai-Tibetan Plateau, we investigated the relationships between species richness and productivity to testify whether positive diversity-productivity relationships can still exist in naturally developed long-term communities. We also measured five functional traits (specific leaf area, photosynthesis rate, leaf proline content, seed mass and seed germination rate) to calculate two functional diversity indices: community-weighted mean trait values (CWM) and Rao's quadratic entropy (RaoQ) which are highly correlated to functional traits of dominating species and variety of functional trait among all species. Finally, we quantified the relative contribution of species diversity, functional traits of dominating species and functional diversity among all species to productivity along the succession. We demonstrated strong positively diversity-productivity relationships in the natural sub-alpine meadow communities across time. The five traits of dominating species explained a large proportion (54-80%) of the variation in productivity during succession, whereas species diversity and functional diversity (FD) for each of the five traits explained much less (24-48% for species richness and 0-40% for FD for each of the five traits respectively). We found unequivocal evidence that significantly positive diversity-productivity relationships in the natural sub-alpine meadow communities across time are up to superior performers (dominant traits) in naturally developed communities where colonization occurs. As a result, understanding diversity-productivity relationships under the full range of community assembly processes therefore merits further investigation.

Scylla paramamosain is one of the most economically important crabs in China. In this study, the first genome survey sequencing of this crab was performed, and the results revealed that the estimated genome size was 1.21 Gb with high heterozygosity (1.3%). Then, RAD technology was used to construct a high-resolution linkage map for this species. A total of 24,444 single nucleotide polymorphism (SNP) makers were grouped into 47 linkage groups. The total length of the linkage groups was 3087.53 cM with a markers interval of 0.92 cM. With the aid of transcriptome and genome scaffold data, 4,271 markers were linked to genes, including several important growth-related genes such as transforming growth factor-beta regulator I, immune related-gene C-type lectin and ecdysone pathway gene broad-complex-like protein. Further, 442 markers, representing 279 QTLs, associated with 24 traits were identified, and of these markers, 78 were linked to genes. Some interesting genes, such as dedicator of cytokinesis protein 3, tenascin-X and DNA helicase MCM8, were believed to have important relationship with specific traits and merit further exploration. The results of this study will accelerate the genetic improvement and genome sequencing analysis of the mud crab.

Genetic studies have shown that FGF10/FGFR2 signaling is required for airway branching morphogenesis and FGF10 functions as a chemoattractant factor for distal epithelial cells during lung development. However, the detail downstream cellular and molecular mechanisms have not been fully characterized. Using live imaging of ex vivo cultured lungs, we found that tip airway epithelial progenitor cells migrate faster than cleft cells during airway bud formation and this migration process is controlled by FGFR2-mediated ERK1/2 signaling. Additionally, we found that airway progenitor cells that migrate faster tend to become distal airway progenitor cells. We identified that Anxa4 is a downstream target of ERK1/2 signaling. Anxa4 -/- airway epithelial cells exhibit a "lag-behind" behavior and tend to stay at the stalk airways. Moreover, we found that Anxa4-overexpressing cells tend to migrate to the bud tips. Finally, we demonstrated that Anxa4 functions redundantly with Anxa1 and Anxa6 in regulating endoderm budding process. Our study demonstrates that ERK1/2/Anxa4 signaling plays a role in promoting the migration of airway epithelial progenitor cells to distal airway tips and ensuring their distal cell fate.

An initial multiple biogeochemical dataset was acquired from the first discovered asphalt seeps in the Brazil margin during deep-sea dive surveys in 2013 using a manned submersible. These surveys were conducted on the outer escarpment of the North São Paulo Plateau. Sediment cores taken from the submersible were processed for pore water and sediment biogeochemistry. The silica concentration, as a chemical geothermometer, showed a steep gradient in the pore water, which indicates the possibility of an active brine system operating in the seepage area. Rare earth elements were used as powerful tracers of chemical processes. Low rare earth element concentrations in both asphalt and Fe-Mn oxyhydroxide-phase sediments suggests that rare earth elements were released during the oil fractionation and biodegradation processes and further depleted under the reducing environment. The main bacterial communities of the sediment were Proteobacteria in the asphalt sites, while at non-asphalt sites, the main bacterial communities of sediment were Firmicutes. Stable carbon and nitrogen isotopes were used to determine the food sources of the heterotrophs, and results suggest that asphalt probably provides a carbon source for these benthic animals. This study may provide useful information to clarify the impact of heavy hydrocarbon seepage on the marine ecosystem.

Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14). We compared the results to findings from healthy control children (HC, n = 35). We found substantial re-ordering of mRNA and miRNA expression networks after the initiation of therapy. Each disease state was associated with a distinct transcriptional profile, with the ADT state differing the most from HC, and ID more strongly resembling HC. Changes at the mRNA level were mirrored in changes in miRNA expression patterns. The analysis of the expression dynamics from differentially expressed genes across three disease states indicated that therapeutic response is a complex process. This process does not simply involve genes slowly correcting in a linear fashion over time. Computational modeling of miRNA and transcription factor (TF) co-regulatory networks demonstrated that combinational regulation of miRNA and TF might play an important role in dynamic transcriptome changes.

Pancreatic neuroendocrine neoplasms (pNENs) are a group of clinically rare and heterogeneous diseases of the pancreas. However, the prognostic factors for this disease in patients still remain controversial. The purpose of our study is to evaluate the predictive roles of those prognostic factors for pNENs. All related articles published until Sep 17, 2017 were identified via PubMed, EMBASE, Web of Science, Ovid and the Cochrane Library. Studies that examined the prognostic factors of pNENs were enrolled. 17 articles (2822 patients) were finally included in this study. The pooled data suggested that patients with positive surgical resection margin and lymph node, advanced G stage and TMN stage, organ metastasis, vascular invasion and the necrosis of specimens had a decreased overall survival for pNENs. Similarly, patients with functional tumors might have a poor prognosis. However, age, gender, surgical type and size of tumor could not be regarded as prognostic factors for pNENs. Our analytic data demonstrated that surgical resection margin, G stage, TMN stage, lymph node, metastasis, vascular invasion and the necrosis could be prognostic factors for pNENs. Our study may assist doctors to screen patients with different prognosis more efficiently during follow-up and select appropriate treatment measures.

Despite the extensive study of two-dimensional layered KNb 3 O 8 (KN), there still remains some vital problems need to be clarified for future applications in environmental purification. Here we demonstrated the successful preparation of interlayer-controlled KN nanoflakes using alkaline hydrothermal conditions by adjusting the amount of thiourea in the reaction. This process resulted in KN nanoflakes with a larger specific surface area than previously reported. Moreover, the initial pH of dye solution and discrepant preferential orientation of interlayer peak have been proved to significantly influence the adsorption and photocatalysis performances of KN. In addition, relevant photocatalysis mechanisms have been expounded, by combined the first-principles calculation. The present work could be helpful in revealing the intrinsic adsorption-photocatalysis features of KN and other similar niobates.

To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed. Transfer of mitochondria from STC-like cells to TEC was assessed using Mito-trackers, and their viability by mitochondrial membrane potential assays. STC-like cells-derived EV were intra-arterially injected into mice 2 weeks after induction of unilateral renal artery stenosis. Two weeks later, renal hemodynamics were studied using magnetic-resonance-imaging, and renal fibrosis assessed ex-vivo. Cultured STC-like cells released EV that were uptaken by TEC. A protective effect conferred by STC-like cells in AMA-induced TEC injury was partly mimicked by their EV. Furthermore, STC-like cells-EV carried and transferred mitochondrial material to injured TEC, which partly restored mitochondrial function. In vivo, STC-like cells-derived EV engrafted in the stenotic kidney, and improved its perfusion and oxygenation. STC-like cells-EV exert protective effects on injured tubular cells in vitro and in vivo, partly by transferring STC-like cells mitochondria, which remain at least partly functional in recipient TEC.

As the world's most populated and rapidly aging country, there is limited information on sex-related differences in factors regarding uncomplicated colonic diverticulosis in China. We aimed to investigate sex differences in individual risk factor in a northern metropolis. Patients with colonic diverticulosis who underwent indicated colonoscopy were queried with respect to medical history and demographic features. Demographic information, life style factors and co-morbidities were retrieved from a prospective dataset. Multiple regression analyses were performed to determine precipitating factors of diverticula. Of 4,386 enrolled patients, colonic diverticulosis were detected in 218 cases (4.97%). Multiple logistic regression analysis implicated increasing age (OR = 1.05, 95%CI 1.03-1.06, P < 0.001), red meat ≥100 g/d (OR = 2.53, 95%CI 1.72-3.70, P < 0.001), smoking (OR = 2.14, 95%CI 1.05-4.33, P = 0.035), rheumatologic diseases (OR = 3.38, 95%CI 1.09-10.5, P = 0.035) and NSAIDs (OR = 2.11, 95%CI 1.12-3.97, P = 0.020) were significantly associated with diverticulosis in men, whilst advancing age (OR = 1.03, 95%CI 1.01-1.05, P = 0.013), BMI (OR = 1.12, 95%CI 1.04-1.19, P = 0.001), smoking (OR = 10.2, 95%CI 2.81-37.4, P < 0.001), rheumatologic diseases (OR = 8.04, 95%CI 3.05-21.2, P < 0.001), hypertension (OR = 1.76, 95%CI 1.01-3.06, P = 0.047), colonic polyps (OR = 3.12, 95%CI 1.82-5.36, P < 0.001) and antihypertensive medications (OR = 2.99, 95%CI 1.66-5.39, P < 0.001) in women. In conclusion, it is pivotal to take account of differentially sex-related factors in regard to the development of uncomplicated colonic diverticulosis.

Different anti-PD-1 and anti-PD-L1 antibodies bind different epitopes. However, whether the results from the SP142 and 22C3 immunochemistry (IHC) assays can be interchanged to determine patient eligibility for immunotherapy remains largely unknown. Histologic sections from 135 tumor samples were probed with both 22C3 and SP142 antibodies. The concordance of PD-L1 expression determined by the two assays was assessed. Additionally, we evaluated the association of PD-L1 expression detected by different assays with clinicopathological features and prognosis. In total, 105 (77.78%) of 135 samples evaluated by the 22C3-IHC platform produced the same results with the SP142-IHC platform (Kappa value: 0.481, p < 0.001). In addition, 69 (51.11%) of 135 samples evaluated by the SP142-IHC platform produced the same results with the 22C3-IHC platform (Kappa value: 0.324, p < 0.001). PD-L1 expression based on the 22C3-IHC assay was significantly correlated with smoking status, whereas that based on the SP142-IHC assay was correlated with smoking status, sex, and histology. Compared to the SP142-IHC assay, the 22C3-IHC assay usually resulted in an underestimation of PD-L1 expression in tumor cells and immune cells. Thus, the results from the two assays cannot be interchanged. Our data also suggest that the use of different reagents may account for inconsistencies in the literature regarding the association between PD-L1 expression and clinicopathological features.

Diffractive zone plates have a wide range of applications from focusing x-ray to extreme UV radiation. The Gabor zone plate, which suppresses the higher-order foci to a pair of conjugate foci, is an attractive alternative to the conventional Fresnel zone plate. In this work, we developed a novel type of Beynon Gabor zone plate based on perfectly absorbing carbon nanotube forest. Lensing performances of 0, 8 and 20 sector Gabor zone plates were experimentally analyzed. Numerical investigations of Beynon Gabor zone plate configurations were in agreement with the experimental results. A high-contrast focal spot having 487 times higher intensity than the average background was obtained.

Interactions between microtubule (MT) interacting and trafficking (MIT) domains and their binding proteins are important for the accurate progression of many cellular processes that require the AAA+ ATPase machinery. Therefore, knowledge on the structural basis of MIT domain interactions is crucial for understanding the molecular mechanisms underlying AAA+ ATPase function. Katanin is a MT-severing AAA+ ATPase that consists of p60 and p80 subunits. Although, the hexameric p60 subunit is active alone, its association with the p80 subunit greatly enhances both the MT-binding and -severing activities of katanin. However, the molecular mechanism of how the p80 subunit contributes to katanin function is currently unknown. Here, we structurally and functionally characterized the interaction between the two katanin subunits that is mediated by the p60-MIT domain and the p80 C-terminal domain (p80-CTD). We show that p60-MIT and p80-CTD form a tight heterodimeric complex, whose high-resolution structure we determined by X-ray crystallography. Based on the crystal structure, we identified two conserved charged residues that are important for p60-MIT:p80-CTD complex formation and katanin function. Moreover, p60-MIT was compared with other MIT domain structures and similarities are discussed.

Central sensitization and network hyperexcitability of the nociceptive system is a basic mechanism of neuropathic pain. We hypothesize that development of cortical hyperexcitability underlying neuropathic pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation and activity loss, and can be controlled by enhancing cortical activity. In a mouse model of neuropathic pain, in vivo two-photon imaging and patch clamp recording showed initial loss and subsequent recovery and enhancement of spontaneous firings of somatosensory cortical pyramidal neurons. Unilateral optogenetic stimulation of cortical pyramidal neurons both prevented and reduced pain-like behavior as detected by bilateral mechanical hypersensitivity of hindlimbs, but corpus callosotomy eliminated the analgesic effect that was ipsilateral, but not contralateral, to optogenetic stimulation, suggesting involvement of inter-hemispheric excitatory drive in this effect. Enhancing activity by focally blocking cortical GABAergic inhibition had a similar relieving effect on the pain-like behavior. Patch clamp recordings from layer V pyramidal neurons showed that optogenetic stimulation normalized cortical hyperexcitability through changing neuronal membrane properties and reducing frequency of excitatory postsynaptic events. We conclude that development of neuropathic pain involves abnormal homeostatic activity regulation of somatosensory cortex, and that enhancing cortical excitatory activity may be a novel strategy for preventing and controlling neuropathic pain.

A series of porous-carbon adsorbents termed as HDPC (hydrochar-derived pyrolysis char) were prepared from corncob and used for the 1-butanol recovery from aqueous solution. The influences of pyrolysis temperature on properties of the adsorbents were systematically investigated. The results showed that hydrophobicity, surface area, and pore volume of HDPC samples increased with an increase in pyrolysis temperature. Furthermore, the adsorption mechanism of 1-butanol on the adsorbents was explored based on correlation of the samples properties with adsorption parameters extracted from the 1-butanol adsorption isotherms (K F and Q e12 ). Overall, the 1-butanol adsorption capacity increased with a decrease in polarity and an increase in aromaticity, surface area and pore volume of HDPC samples. However, at different pyrolysis temperature, the factors causing the increase of 1-butanol adsorption on the adsorbents are variable. The kinetic experiments revealed that the pores played a vital role in the 1-butonal adsorption process. The intraparticle diffusion model was used to predict the adsorption kinetic process. The simulation results showed that intraparticle diffusion was the main rate-controlling step in the 1-butanol adsorption process.

Constructing the heterojunctions or designing the novel nanostructures are thought as effective methods to improve photocatalytic activities of semiconductors. Herein, a one-step green route was developed to fabricate bismuth oxyiodide/activated carbon (BiOI/C) composite. The prepared BiOI/C exhibit obviously red shifts and increased absorption range of visible light. The presence of Bi-C bonds confirms the heterojunction, on account of which the BiOI nanosheets tightly grew on the surface of carbon and subsequently provided the hierarchical structure, sufficient interfacial interaction and high specific surface area. Significantly, the sufficient interracial interaction is beneficial to the detachment of electrons (e - )-holes (h + ) pairs and the Bi-C bonds work like a bridge to rapidly transmit the e - from BiOI to carbon. What's more, the hierarchical structure of BiOI/C efficiently shortened the diffusion pathways of pollutants and the high S BET provided more exposed reaction sites. Benefiting from multiple synergistic effects, the as-prepared BiOI/C exhibited enhanced photocatalytic activities in degrading Rhodamine B (RhB) solution under visible light irradiation. The degradation rate of optimized BiOI/C reaches up to 95% in 120 min, and the efficiency is 3.36 times higher than pure BiOI. This study provides a promising strategy that activated carbon can be utilized in highly-efficiency photocatalysts.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5 and SRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (including ADARB2-AS1, ANRIL, GLIS3-AS1, LINC00472, MEG3, PANDA, PVT1, and UCA1) had greater accuracy than standard clinical and radiologic features in distinguishing 'aggressive/malignant' IPMNs that warrant surgical removal from 'indolent/benign' IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative 'radiomic' imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.

Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipation and healthy controls were transplanted into the antibiotic depletion mice model. The mice which received fecal microbiota from patients with constipation presented a reducing in intestinal peristalsis and abnormal defecation parameters including the frequency of pellet expulsion, fecal weight and fecal water content. After fecal microbiota transplantation, the SERT expression in the colonic tissue was significantly upregulated, and the content of 5-HT was decreased which negatively correlated with the gastrointestinal transit time. Moverover, fecal microbiota from the mice which received fecal microbiota from patients with constipation also upregulated SERT in Caco-2 cells. Besides, this process accompanied with the decreased abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium and an increased tend of Bacteroides and Akkermansia, which also involved in the impairment of intestinal barrier after FMT. Taken together, intestinal dysbiosis may upregulate the SERT expression and contribute to the development of chronic constipation.

Although numerous studies have revealed significant associations between variants in the nicotinic acetylcholine receptors (nAChR) subunits and nicotine dependence (ND), only few studies were performed in Chinese subjects. Here, we performed association and interaction analysis for 20 single nucleotide polymorphisms (SNPs) in the CHRNB3-CHRNA6 gene cluster with ND in a Chinese Han population (N = 5,055). We found nominally significant associations for all tested SNPs with ND measured by the Fagerström Test for Nicotine Dependence score; of these, 11 SNPs remained significant after Bonferroni correction for multiple tests (p = 9 × 10 -4 ~2 × 10 -3 ). Further conditional analysis indicated that no other SNP was significantly associated with ND independent of the most-highly significant SNP, rs6474414. Also, our haplotype-based association analysis indicated that each haplotype block was significantly associated with ND (p < 0.01). Further, we provide the first evidence of the genetic interaction of these two genes in affecting ND in this sample with an empirical p-value of 0.0015. Finally, our meta-analysis of samples with Asian and European origins for five SNPs in CHRNB3 showed significant associations with ND, with p-values ranging from 6.86 × 10 -14 for rs13280604 to 6.50 × 10 -8 for rs4950 . This represents the first study showing that CHRNB3/A6 are highly associated with ND in a large Chinese Han sample.

Copper ferrites are emerging transition metal oxides that have potential applications in energy storage devices. However, it still lacks in-depth designing of copper ferrites based anode architectures with enhanced electroactivity for lithium-ion batteries. Here, we report a facile synthesis technology of copper ferrites anchored on reduced graphene oxide (CuFeO 2 @rGO and Cu/CuFe 2 O 4 @rGO) as the high-performance electrodes. In the resulting configuration, reduced graphene offers continuous conductive channels for electron/ion transfer and high specific surface area to accommodate the volume expansion of copper ferrites. Consequently, the sheet-on-sheet CuFeO 2 @rGO electrode exhibits a high reversible capacity (587 mAh g -1 after 100 cycles at 200 mA g -1 ). In particular, Cu/CuFe 2 O 4 @rGO hybrid, which combines the advantages of nano-copper and reduced graphene, manifests a significant enhancement in lithium storage properties. It reveals superior rate capability (723 mAh g -1 at 800 mA g -1 ; 560 mAh g -1 at 3200 mA g -1 ) and robust cycling capability (1102 mAh g -1 after 250 cycles at 800 mA g -1 ). This unique structure design provides a strategy for the development of multivalent metal oxides in lithium storage device applications.

13 C-labeled glucose combined with chromatography and mass spectrometry enables us to decipher the percentage of lactate generated from various metabolic pathways. We showed that lactate derived from glycolysis, pentose phosphate pathway, Krebs cycle, and other sources accounted for 82-90%, 6.0-11%, 0.67-1.8% and 1.5-7.9%, respectively, depending on different types of cells. When using glucose isotopomers ([1- 13 C]-, [3- 13 C]-, [4- 13 C]-, and [6- 13 C]glucose) or isotopologues ([1,2- 13 C 2 ]- and [1,2,3- 13 C 3 ]glucose) for tracing, the ratio of lactate derived from glucose carbon 1, 2, 3 over 4, 5, 6 via glycolysis varied significantly, ranging from 1.6 (traced with [1,2- 13 C 2 ]glucose) to 0.85 (traced with [6- 13 C]glucose), but the theoretical ratio should be 1. The odd results might be caused by intramolecular 13 C, which may significantly affect lactate fragmentation under tandem mass spectrometry condition, leading to erroneous quantification. Indeed, the fragmentation efficiency of [U- 13 C]lactate, [2,3- 13 C]lactate, and [3- 13 C]lactate were 1.4, 1.5 and 1.2 folds higher than lactate, respectively, but [1- 13 C]lactate was similar to lactate, suggesting that carbon-13 at different positions could differentially influence lactate fragmentation. This observed phenomenon was inconsistent with the data based on theoretical calculation, according to which activation energies for all lactate isotopomers and isotopologues are nearly identical. The inconsistency suggested a need for further investigation. Our study suggests that calibration is required for quantifying metabolite isotopolugues and isotopomers.

A simple one-pot hydrothermal method is developed for fabrication of MoS 2 @rGO nanoflakes using the economical MoO 3 as the molybdenum source. Benefiting from the unique nanoarchitecture, high MoS 2 loading (90.3 wt%) and the expanded interlayer spacing, the as-prepared MoS 2 @rGO nanoflakes exhibit greatly enhanced sodium storage performances including a high reversible specific capacity of 441 mAh g -1 at a current density of 0.2 A g -1 , high rate capability, and excellent capacity retention of 93.2% after 300 cycles.

Active and widely controllable phase transition optical materials have got rapid applications in energy-efficient electronic devices, field of meta-devices and so on. Here, we report the optical properties of the vanadium dioxide (VO 2 )/aluminum-doped zinc oxide (Al:ZnO) hybrid n-n type heterojunctions and the corresponding electro-optic performances of the devices. Various structures are fabricated to compare the discrepancy of the optical and electrical characteristics. It was found that the reflectance spectra presents the wheel phenomenon rather than increases monotonically with temperature at near-infrared region range. The strong interference effects was found in the hybrid multilayer heterojunction. In addition, the phase transition temperature decreases with increasing the number of the Al:ZnO layer, which can be ascribed to the electron injection to the VO 2 film from the Al:ZnO interface. Affected by the double layer Al:ZnO, the abnormal Raman vibration mode was presented in the insulator region. By adding the external voltage on the Al 2 O 3 /Al:ZnO/VO 2 /Al:ZnO, Al 2 O 3 /Al:ZnO/VO 2 and Al 2 O 3 /VO 2 /Al:ZnO thin-film devices, the infrared optical spectra of the devices can be real-time manipulated by an external voltage. The main effect of joule heating and assistant effect of electric field are illustrated in this work. It is believed that the results will add a more thorough understanding in the application of the VO 2 /transparent conductive film device.

Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequencing fidelity. Genome wide SNP density analysis identified 18 SNP hotspots with comparison to the 1000 Genome Projects (1KGP) data. A subset of the genes adjacent to SNP hotspots showed statistically significant enrichment in immunological processes. Genes adjacent to indel hotspots were functionally related to G-protein coupled signaling pathways. Further analyses elucidated significantly more JIA SNPs with regulatory potential compared to 1KGP data. Furthermore, SNPs located within linkage disequibilium (LD) blocks containing previously identified JIA-associated SNPs demonstrated higher regulation potential compared to SNPs outside LD blocks. We also demonstrated enrichment of novel JIA variants in histone modification peaks and DNase hypersensitivity sites in B cells. This study greatly expands the number of genetic variants that may contribute to JIA and give us some clues into what may trigger this disease. To date, this study is the first deep WGS effort on children with JIA and provides useful genetic resources for research communities particularly in understanding JIA etiology.

This corrects the article DOI: 10.1038/srep46244.

Two-dimensional layered K 4 Nb 6 O 17 (KN) was easily formed as a secondary phase caused by the volatilization of alkali metal ions, when preparing ferroelectric K x Na 1-x NbO 3 based ceramics and films. In this work, it was believed that KN film is with weak ferroelectricity and has a little effect on the ferroelectric properties of K x Na 1-x NbO 3 based films. Moreover, temperature dependent (77-500 K) dielectric functions of KN film have been firstly extracted by fitting ellipsometric spectra with the Adachi dielectric function model and a four-phase layered model. The high-frequency dielectric constant linearly increases and optical band gap slightly decreases with increasing the temperature. We also research its photoelectrochemical properties and its application in high-efficient light-induced H 2 evolution. In addition, X-ray photoelectron spectroscopy, Raman scattering, temperature dependent transmittance and infrared reflectance spectra, and first-principles calculation were conjointly performed to further reveal the intrinsic optoelectronic features and relevant mechanisms of KN.

Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4B DCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor-p21 Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4B DCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21 Cip1 , inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4B DCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21 Cip1 and regulates cell cycle progression in human osteosarcoma cells.

Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated. Following siRNA screening of 47 upregulated proteins indicated that the knockdown of BMK1 showed the most significant ability to inhibit the proliferation of CIBM resistant cells. It was found that phosphorylation of BMK1 was enhanced in resistant cells, which suggested an association of BMK1 with drug resistance. Further study indicated that phospho-activation of BMK1 by MEK5D enhanced the resistance to CIBM. Conversely, inhibition of BMK1 by shRNAi or BMK1 inhibitor (XMD8-92) impaired not only the acquirement of resistance to CIBM, but also the proliferation of CIBM resistant cells. Further kinome-scale siRNA screening demonstrated that SRC\MEK5 cascade promotes the phospho-activation of BMK1 in response to CIBM. Our study not only provides a global phosphoproteomic view of CIBM in melanoma, but also demonstrates that inhibition of BMK1 has therapeutic potential for the treatment of melanoma.

H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status. ChIP and luciferase reporter assays showed that Hif-1α induced H19 transcription through directly binding to the H19 promoter. Furthermore, Hif-1α upregulated specific protein 1 (SP1) expression in glioblastomas cells in vitro and in vivo, and SP1 also strongly interacted with the H19 promoter to promote H19 expression under hypoxia. We also showed that H19 acts as a molecular sponge that binds miR-181d, relieving inhibition of β-catenin expression. Therefore, H19 participates in hypoxia-driven migration and invasion in glioblastoma cells. In summary, our results uncover the mechanisms that stimulate H19 expression under hypoxia to promote malignant effects in glioblastomas and suggest H19 might be a promising therapeutic target.

Carbon coated TiO 2 (TiO 2 @C) is fabricated by a convenient and green one-pot solvothermal method, in which ethylene glycol serve as both the reaction medium and carbon source without the addition of any other carbon additives. During the solvothermal process, ethylene glycol polymerize and coordinate with Ti 4+ to form the polymeric ligand precursor, then the polymer brushes carbonize and convert to homogeneous carbon layer firmly anchored on the TiO 2 nanoparticles (~1 nm thickness). The polymerization and carbonization process of the ethylene glycol is confirmed by FT-IR, Raman, TG and TEM characterizations. Benefiting from the well-dispersed nanoparticles and uniform carbon coating, the as-prepared TiO 2 @C demonstrate a high reversible capacity of 317 mAh g -1 (94.6% of theoretical value), remarkable rate capability of 125 mAh g -1 at 3.2 A g -1 and superior cycling stability over 500 cycles, possibly being one of the highest capacities reported for TiO 2 .

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 destabilizes Smo in a phosphorylation independent manner. Mechanistically, we discover that excessive Krz, the Drosophila β-arrestin 2, inhibits Smo sumoylation and prevents Smo accumulation through Krz regulatory domain. Krz likely facilitates the interaction between Smo and Ulp1 because knockdown of Krz by RNAi attenuates Smo-Ulp1 interaction. Finally, we provide evidence that Cos2 is also sumoylated, which counteracts its inhibitory role on Smo accumulation in the wing. Taken together, we have uncovered a novel mechanism for Smo activation by sumoylation that is regulated by Hh and Smo interacting proteins., Competing Interests: The authors declare no competing financial interests.

The enhanced light-harvesting capacity and effective separation of photogenerated carriers in fantastic hierarchical heterostructures enjoy striking attention for potential applications in the field of solar cells and photocatalysis. A three-dimensional (3D) dandelion-shaped hierarchical Bi 2 S 3 microsphere compactly decorated with wing-shaped few layered MoS 2 lamella (D-BM) was fabricated via a facile hydrothermal self-assembly process. Especially, polyethylene glycol (PEG) has been proven as the vital template to form D-BM microsphere. Importantly, the as-prepared D-BM microsphere presents pH-dependent superior adsorption behavior and remarkable visible light photocatalytic activity for degradation of organic dyestuffs (Rhodamine B/RhB and Methylene blue/MB), far exceeding those for the pure Bi 2 S 3 and MoS 2 . It is understandable that D-BM with high surface area possesses more active sites and promotes light utilization due to the unique porous structure with outspread wings. Besides, based on the experiments and theoretical calculations, the staggered type II band alignment of D-BM permits the charge injection from Bi 2 S 3 to MoS 2 , subsequently accelerates the separation and restrains the recombination of carriers, leading to excellent photocatalytic activity, as well as the photoconductance and photoresponse performance (with I light /I dark ratio 567).