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RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer‐suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long‐term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise‐induced muscle‐bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10‐week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP‐activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube‐derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae‐mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube‐derived exosomes, as a crucial regulator of exercise‐induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise‐dependent treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

SUMMARY: The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild‐type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII‐VENUS and DR5‐GFP lines) in B‐deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis‐related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport‐related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN‐Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis‐related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition. Significance Statement: While boron (B) deprivation‐induced root growth inhibition is causally associated with auxin accumulation and transport, the underlying mechanisms remain unknown. This work showed that enhanced auxin biosynthesis resulting from upregulation of the expression levels of auxin biosynthesis‐related genes in shoots and increased protein levels of PIN2/3/4 carriers in the plasma membrane mediated by increased transcript levels of PIN2/3/4 genes in roots combined with restrained endocytosis of PIN2/3/4 carriers result in auxin overaccumulation in root apices and consequently root growth inhibition. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of mixed reality (MR) in sentinel lymph node biopsy (SLNB) in patients with breast cancer. Methods: A total of 300 patients with breast cancer who underwent SLNB enrolled and were randomly divided into two groups. In group A, only dye (an injection of methylene blue) was used to detect sentinel lymph nodes, while in group B MR was used for positioning in addition to dye. (MR localization method: Before the surgery, we built a 1:1 3D reconstruction model based on the patient's CT or MRI original data, and after the patient was injected with dye, we completed MR localization by overlapping the pre-marked image with the model.) Results: During surgery, the detection time in group B was significantly shorter than in group A (3.62 ± 1.20 vs.7.87 ± 1.86; p < 0.001). At 1-month post-surgery follow-up, the incidence of pain in group B was lower than that in group A (2.70 vs. 8.28%, p = 0.036). The incidence of upper limb dysfunction was lower in group B than in group A (2.03 vs. 8.97%, p = 0.009). In terms of the incidence of pain, group B was better than group A (0.68 vs. 3.45%, p = 0.094). The satisfaction of the two groups was scored, and the results showed that group B was better than group A (4.04 ± 0.91 vs.3.32 ± 0.94, p < 0.001). Conclusion: The application of MR to SLNB in breast cancer can significantly reduce the detection time and the occurrence of complications and improve patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. Methods: Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single‐cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. Results: Five immune‐related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. Conclusion: A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients. [ABSTRACT FROM AUTHOR]

SUMMARY: The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al‐exposed Arabidopsis roots. In B‐deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al‐inhibited PIN‐FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al‐induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al‐induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole‐3‐acetic acid (IAA), and thus restored the Al‐induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome‐based auxin transport to alleviate Al toxicity in plant roots. Significance Statement: Aluminum toxicity and boron deficiency are limiting factors for agricultural production in acid soils, which make up almost half of the world's arable land. Boron fertilization alleviates aluminum toxicity but the mechanism remains unclear. The study shows that boron supply releases aluminum‐induced root growth arrest by facilitating endosome‐based polar auxin transport via PIN2 polar localization in the upper half of the plasma membrane (shootward). We provide solid support for boron fertilizer in remediating aluminum toxicity in acid soils. [ABSTRACT FROM AUTHOR]

Background and purpose: The association between nonstenotic plaque at the petrous internal carotid artery (ICA) and embolic stroke of undetermined source (ESUS) remains unknown. We aimed to test the hypothesis that the presence of a larger build‐up of petrous plaque is more prevalent in the ipsilateral versus the contralateral side among ESUS patients without plaque in the intracranial and proximal ICA. Methods: From a total of 243 patients with ESUS and 160 patients with small‐vessel disease (SVD) without proximal ICA plaque, we enrolled 88 ESUS and 103 SVD patients without ipsilateral nonstenotic intracranial and proximal ICA plaque in the present study. Targeting the petrous segment of the ICA on two sides, plaque burden including plaque thickness, lumen area, vessel area, wall area, and percentage of luminal stenosis, and composition features (presence/absence of the ruptured fibrous cap, ulcer plaque, thrombus, discontinuity of plaque surface [DPS], intraplaque hemorrhage and complicated plaque) were assessed by high‐resolution magnetic resonance imaging. Results: We found a higher prevalence of petrous plaque thickness ≥3.5 mm ipsilateral versus contralateral to the stroke (25/88 [28.4%] vs. 12/88 [13.6%], odds ratio [OR] 3.60, 95% confidence interval [CI] 1.34–9.70), but this imbalance was not seen in SVD. In patients with plaque thickness ≥3.5 mm, the presence of DPS (OR 4.05, 95% CI 1.11–14.78) and complicated plaque (OR 5.00, 95% CI 1.10–22.82) was more closely related to an index ESUS, a finding that was not evident in the subgroup with petrous plaque <3.5 mm (p for interaction = 0.027). Conclusions: The present study provided the first evidence supporting a potential etiological role of vulnerable petrous plaque in ESUS. [ABSTRACT FROM AUTHOR]

Objective: To investigate an association between percentage lipid‐rich necrotic core (LRNC) and an index ischemic stroke in an embolic stroke of undetermined source (ESUS) cohort. Methods: A total of 167 ESUS patients with 259 non‐stenotic intracranial plaques including 155 ipsilateral and 104 contralateral to stroke were finally enrolled in the current analysis. The multi‐dimensional parameters involving remodeling index (RI), plaque burden (PB), LRNC, discontinuity of plaque surface (DPS), intraplaque hemorrhage (IPH), and vulnerable plaque defined as presence of complicated plaque were evaluated by high‐resolution magnetic resonance imaging. Results: We found that %LRNC was an independent predictor for ESUS in model 1 (OR: 2.574, 95% CI: 1.854–3.573, P < 0.001), and model 2 (OR: 2.550, 95% CI: 1.835–3.545, P < 0.001), but the association was not seen in PB. In receiver operating characteristic curve analysis, the discrimination of LRNC for ESUS was significantly superior to that of PB (absolute difference: 0.121, 95% CI: 0.056–0.205, P < 0.001). Importantly, a significantly positive synergy between the remodeling pattern and LRNC in response to plaque vulnerability was found by Sankey diagram (P for interaction = 0.001). Conclusion: This is the first report that LRNC, beyond PB, may be correlated with an index ESUS, and a synergistic effect between positive remodeling and larger LRNC could promote plaque vulnerability. The findings suggest that a potential target subgroup may benefit from stroke prevention with intensive statin, although this must be confirmed in future. [ABSTRACT FROM AUTHOR]

Background: Cone-beam computed tomography (CBCT) is widely used for daily image guidance in radiation therapy, enhancing the reproducibility of patient setup. However, its application in adaptive radiotherapy (ART) is limited by many imaging artifacts and inaccurate Hounsfield units (HUs). The correction of CBCT image is necessary and of great value for CBCT-based ART. Purpose: To explore the synthetic CT (sCT) generation from CBCT images of thorax and abdomen patients, which usually surfer from serious artifacts duo to organ state changes. In this study, a streaking artifact reduction network (SARN) is proposed to reduce artifacts and combine with cycleGAN to generate highquality sCT images from CBCT and achieve an accurate dose calculation. Methods: The proposed SARN was trained in a self -supervised manner. Artifact-CT images were generated from planning CT by random deformation and projection replacement, and SARN was trained based on paired artifact--CT and CT images. The planning CT and CBCT images of 260 patients with cancer, including 120 thoracic and 140 abdominal CT scans, were used to train and evaluate neural networks. The CBCT images of another 12 patients in late treatment fractions, which contained large anatomy changes, were also tested by trained models. The trained models include commonly used U-Net, cycle-GAN, attention-gated cycleGAN (cycAT), and cascade models combined SARN with cycleGAN or cycAT. The generated sCT images were compared in terms of image quality and dose calculation accuracy. Results: The sCT images generated by SARN combined with cycleGAN and cycAT showed the best image quality, removed the most artifacts, and retained the normal anatomical structure. The SARN+cycleGAN performed best in streaking artifacts removal with the maximum percent integrity uniformity (PIUm) of 91.0% and minimum standard deviation (SD) of 35.4 HU for delineated artifact regions among all models. The mean absolute error (MAE) of CBCT images in the thorax and abdomen were 71.6 and 55.2 HU, respectively, using planning CT images after deformable registration as ground truth. Compared with CBCT, the thoracic and abdominal sCT images generated by each model had significantly improved image quality with smaller MAE (p < 0.05). The SARN+cycAT obtained the minimum MAEs of 42.5 HU in the thorax while SARN+cycleGAN got the minimum MAEs of 32.0 HU in the abdomen. The sCT generated by U-Net had a remarkably lower anatomical structure accuracy compared with the other models. The thoracic and abdominal sCT images generated by SARN+cycleGAN showed optimal dose calculation accuracy with gamma passing rates (2 mm/2%) of 98.2% and 96.9%, respectively. Conclusions: The proposed SARN can reduce serious streaking artifacts in CBCT images. The SARN combined with cycleGAN can generate highquality sCT images with fewer artifacts, high-accuracy HU values, and accurate anatomical structures, thus providing reliable dose calculation in ART. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to investigate the characteristics of non‐stenotic intracranial plaque (NSIP) in embolic stroke of undetermined source (ESUS) subtypes by high‐resolution magnetic resonance imaging. Methods: Consecutive patients with ESUS who were mandatory for high‐resolution magnetic resonance imaging were retrospectively enrolled. Based on the location and arterial supply of the infarct, the ESUS were categorized into three types: cortical ESUS, subcortical ESUS and mixed ESUS. The NSIP parameters including plaque location, morphology (plaque distribution, remodeling index and plaque burden) and composition (thick fibrous cap, discontinuity of plaque surface, intraplaque hemorrhage and complicated plaque) were evaluated amongst the subtypes. Results: Of 243 patients, there were 87 (35.8%) cortical ESUS, 127 (52.3%) subcortical ESUS and 29 (11.9%) mixed ESUS. Significant differences were found in plaque location (p < 0.001), plaque quadrant (p < 0.001), remodeling index (p < 0.001), plaque burden (p < 0.001), discontinuity of plaque surface (p < 0.001), intraplaque hemorrhage (p = 0.001) and complicated plaque (p < 0.001) of ipsilateral NISP amongst the different ESUS subtypes, except for fibrous cap (p = 0.135). However, no differences were found amongst contralateral NISP. In addition, the clinical characteristics of the differences between ESUS subtypes were striking, including age (p = 0.004), initial National Institutes of Health Stroke Scale (p < 0.001), coronary artery disease (p = 0.039), serum urea (p = 0.011) and creatinine (p = 0.002). Conclusion: This is the first report of significantly heterogeneous characteristics of ipsilateral NSIP and clinical findings amongst ESUS subtypes, which may suggest their different underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: GDF15 may be a potential biomarker for neurodegenerative diseases. In this analysis, we aimed to quantitative analysis the levels of GDF15 in patients with neurological diseases and in health control, and then to determine its potential diagnostic utility. Methods: Two researchers separately conducted a systematic search of the relevant studies up to January 2021 in Embase, PubMed, and Web of Science. Effect sizes were estimated to use the standardized mean difference (SMD) with 95% confidence interval (CI). Sensitivity and specificity were calculated by the summary receiver operating characteristics curve (SROC) method. The sensitivity analysis was performed by the "one‐in/one‐out" approach. Considering the considerable heterogeneity among studies, random‐effects model was used for the meta‐analysis investigation. Results: A total of eight articles were included in this meta‐analysis and systematic review. The pooled results of the random effect model indicated GDF15 levels were significantly higher in patients with neurodegenerative disease than healthy people (SMD = 0.92, 95% CI: 0.44–1.40, Z = 3.75, p < 0.001). Sensitivity and specificity of biomarker of GDF15 were 0.90 (95% CI: 0.75–0.97), 0.77 (95% CI: 0.67–0.65), and AUC = 0.87 (95% CI: 0.84–0.90), respectively. Conclusions: GDF15 levels were higher in patients with neurodegenerative disease than healthy people. And serum levels of GDF15 were a better marker for diagnostic utility of neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Summary: Improvement of ewe reproduction is considerable by appropriately increasing litter size and sustaining non‐seasonal breeding. However, their genetic makeups have not been entirely elucidated. Genome‐wide analyses of 821 individuals were performed by combining three genomic approaches (genome‐wide association study, XP‐nSL, and runs of homozygosity). Consequently, 35 candidate genes including three domestication genes (TSHR, GTF2A1, and KITLG) were identified. Other than the FecB mutation at BMPR1B, we described a significant association of a missense mutation rs406686139 at seasonal lambing‐associated TSHR gene with litter size. Some promising novel genes may be relevant for sheep reproduction by multitude biological processes, such as FETUB functioning in fertilization, HNRNPA1 in oogenesis, DCUN1D1 in spermatogenesis, and HRG in fertility outcome. The present study suggests that improvement of ewe reproduction is attributed to selective breeding, and casts light on the genetic basis and improvement of sheep reproduction. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the potential hub genes and pathways of ischaemic cardiomyopathy (ICM) and to investigate the possible associated mechanisms. Two microarray data sets (GSE5406 and GSE57338) were downloaded from the Gene Expression Omnibus (GEO) database. The limma package was used to analyse the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology (DO) and Gene Ontology (GO) annotation analyses were performed. A protein‐protein interaction (PPI) network was set up using Cytoscape software. Significant modules and hub genes were identified by the Molecular Complex Detection (MCODE) app. Then, further functional validation of hub genes in other microarrays and survival analysis were performed to judge the prognosis. A total of 1065 genes were matched, with an adjusted p < 0.05, and 17 were upregulated and 25 were downregulated with|log2 (fold change)|≥1.2. After removing the lengthy entries, GO identified 12 items, and 8 pathways were enriched at adjusted p < 0.05 (false discovery rate, FDR set at <0.05). Three modules with a score >8 after MCODE analysis and MYH6 were ultimately identified. When validated in GSE23561, MYH6 expression was lower in patients with CAD than in healthy controls (p < 0.05). GSE60993 data suggested that MYH6 expression was also lower in AMI patients (p < 0.05). In the GSE59867 data set, MYH6 expression was lower in CAD patients than in AMI patients and lower in heart failure (HF) patients than in non‐HF patients. However, there was no difference at different periods within half a year, and HF was increased when MYH6 expression was low (p < 0.05–0.01). We performed an integrated analysis and validation and found that MYH6 expression was closely related to ICM and HF. However, whether this marker can be used as a predictor in blood samples needs further experimental verification. [ABSTRACT FROM AUTHOR]

The intrinsic conflicts between mechanical performances and processability are main challenges to develop cost‐effective impact‐resistant materials from polymers and their composites. Herein, polyhedral oligomeric silsesquioxanes (POSSs) are integrated as side chains to the polymer backbones. The one‐dimension (1D) rigid topology imposes strong space confinements to realize synergistic interactions among POSS units, reinforcing the correlations among polymer chains. The afforded composites demonstrate unprecedented mechanical properties with ultra‐stretchability, high rate‐dependent strength, superior impact‐resistant capacity as well as feasible processability/recoverability. The hierarchical structures of the hybrid polymers enable the co‐existence of multiple dynamic relaxations that are responsible for fast energy dissipation and high mechanical strengths. The effective synergistic correlation strategy paves a new pathway for the design of advanced cluster‐based materials. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlations between the habit of betel quid and areca nut (BQ‐AN) chewing and the prognosis of oral cancer (OC). Methods: We performed a systematic review and meta‐analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ‐AN chewers and non‐chewers, measured in terms of 5‐year overall survival (OS) and 5‐year disease‐specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5‐year OS and 5‐year DSS was calculated using a fixed‐effects model. Results: Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5‐year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5‐year DSS. Overall, the pooled HR evaluating BQ‐AN chewers was 1.26 (95% CI: 1.09–1.46) for 5‐year OS and 1.40 (95% CI: 1.15–1.70) for 5‐year DSS, compared with non‐chewers. There was a significant association between BQ‐AN chewing and OC survival. Conclusions: Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI). Methods: All patients included were hospitalized at The First Affiliated Hospital and The Second Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2020. Their risk factors, clinical manifestation, stroke mechanisms and short‐term prognosis were analyzed retrospectively. Results: Among the 387 patients enrolled, 266 (68.7%) had LMI, 109 (28.2%) had MMI, and 12 (3.1%) (nine men and three women) had LMI plus MMI. We analyzed the 375 patients of LMI and MMI. The average ages of LMI and MMI were 59.4 years and 62.69 years, respectively. Univariate analysis and multivariable logistic regression was used to investigate the existing risk factors of MMI relative to LMI. Prior infarction, poor glycemic control, and atherosclerosis were more frequently associated with MMI than with LMI. The clinical manifestation was significantly different between LMI and MMI. We used modified Rankin Scale (mRS) score as the short‐term prognostic evaluation criteria, and MMI appeared worse than LMI. Conclusions: This study reveals that: (1) patients with MMI are older than those with LMI; (2) prior infarction, poor glycemic control, and atherosclerosis are independent risk factors of MMI than that of LMI; (3) the clinical manifestations of LMI and MMI are heterogeneous; (4) short‐term prognosis of MMI is worse than LMI. [ABSTRACT FROM AUTHOR]

The Toll‐like receptor (TLR) family acts as a bridge connecting innate and acquired immunity. TLR10 remains one of the least understood members of this family. Some studies have examined TLR10 ligands, dimerization of TLR10 with other TLRs, and downstream signalling pathways and functions, but they have often arrived at conflicting conclusions. TLR10 can induce the production of proinflammatory cytokines by forming homodimers with itself or heterodimers with TLR1 or other TLRs, but it can also inhibit proinflammatory responses when co‐expressed with TLR2 or potentially other TLRs. Mutations in the Toll/Interleukin 1 receptor (TIR) domain of TLR10 alter its signalling activity. Polymorphisms in the TLR10 gene can change the balance between pro‐ and anti‐inflammatory responses and hence modulate the susceptibility to infection and autoimmune diseases. Understanding the full range of TLR10 ligands and functions may allow the receptor to be exploited as a therapeutic target in inflammation‐ or immune‐related diseases. Here, we summarize recent findings on the pro‐ and anti‐inflammatory roles of TLR10 and the molecular pathways in which it is implicated. Our goal is to pave the way for future studies of the only orphan TLR thought to have strong potential as a target in the treatment of inflammation‐related diseases. [ABSTRACT FROM AUTHOR]

Granular materials, composed of densely packed particles, are known to possess unique mechanical properties that are highly dependent on the surface structure of the particles. A microscopic understanding of the structure‐property relationship in these systems remains unclear. Here, supra‐nanoparticle clusters (SNPCs) with precise structures are developed as model systems to elucidate the unexpected elastic behaviors. SNPCs are prepared by coordination‐driven assembly of polyhedral oligomeric silsesquioxane (POSS) with metal‐organic polyhedron (MOP). Due to the disparity in sizes, the POSS‐MOP assemblies, like their classic nanoparticles counterparts, ordering is suppressed, and the POSS‐MOP mixtures will vitrify or jam as a function of decreasing temperature. An unexpected elasticity is observed for the SNPC assemblies with a high modulus that is maintained at temperatures far beyond the glass transition temperature. From studies on the dynamics of the hierarchical structures of SNPCs and molecular dynamic simulation, the elasticity has its origins in the interpenetration of POSS‐ended arms. The physical molecular interpenetration and inter‐locking phenomenon favors the convenient solution or pressing processing of the novel cluster‐based elastomers. [ABSTRACT FROM AUTHOR]

The development of air stable solid chiral catalysts for asymmetric hydrogenation is very attractive for the large‐scale production of chiral compounds. Herein, we reported the synthesis of an ordered macroporous poly(ionic liquid) catalyst integrated with VDPEN‐RuOTf as air stable chiral catalyst for asymmetric hydrogenation of quinoline derivatives. Under ambient conditions, the solid catalyst afforded 97% conversion with 90% ee in the asymmetric hydrogenation of 2‐methylquinoline in water. It was found that the activity and enantioselectivity of poly(ionic liquid) catalyst decreases with surface hydrophobicity increasing, suggesting the important role of surface hydrophilicity in obtaining high activity and enantioselectivity in water. Control experiment suggests that water promotes the anti‐air stability of the poly(ionic liquid) catalyst. The combination of poly(ionic liquid) catalyst and water may provide a new approach for designing heterogeneous chiral catalyst with anti‐air stability. [ABSTRACT FROM AUTHOR]

Background: There are increasing cosmetic adverse reactions in China, mostly cosmetic contact dermatitis, with the development of its cosmetics industry. Aims: To identify the allergens and cosmetics products responsible for cosmetic allergic contact dermatitis (CACD) in Shanghai. Methods: Five hundred and sixty patients, including 342 suspected CACD patients from dermatological clinic and 218 cosmetics consumers with an allergic history, were patch tested with a cosmetic series (C‐1000 series). And 154 patients patched with possible culprit cosmetics. Results: Two hundred and forty‐six subjects showed positive reaction to C‐1000 series. Clinic patients had much higher positive rate than that of cosmetics consumers. Leading allergens were methylisothiazolinone (MI), methylisothiazolinone + methylchloro‐isothiazolinone (MCI/MI), thimerosal, and the positive rates were significantly higher in patients than in cosmetic consumers (P <.001 for all). MCI/MI elicited positive patch test reactions in 73.5% of MI‐positive patients. Of those patched with cosmetic products, 19 patients had 31 positive reactions, including 22 skin care products and 5 color decorating. Conclusions: Preservatives, especially MI, MCI/MI, and thimerosal, were the most common cosmetic allergens, and skin care products occupied the most allergic reaction of CACD. Patch testing is highly recommended for suspected CACD patients. Future comparative investigation with large sample size should benefit cosmetovigilance surveillance. [ABSTRACT FROM AUTHOR]

Direct air capture as the only way for reducing current CO2 concentration in air is very challenging, however, due to the low CO2 concentration (ca. 400 ppm). Herein, we reported an efficient adsorbent for CO2 capture, which was prepared by the encapsulation of polyethylenimine (PEI) in ethane‐silica nanotubes with diameter less than 10 nm. Compared with bulk mesoporous silicas/ethane‐silicas, the PEI tends to be highly dispersed in the nanotubes due to the co‐existence of both tubular channels and intervoid space. Consequently, the PEI encapsulated in nanotubes showed much higher N efficiency (0.22 mol CO2/mol N at 30 °C and 0.1 bar) and CO2 uptake capacity than that encapsulated in the bulk mesoporous silicas. It was also observed that the dispersed PEI not directly interacted with the pore wall, afforded high N efficiency. Results of the breakthrough experiments using simulated air (400 ppm CO2/N2) showed that PEI encapsulated in nanotubes with CO2 uptake capacity of 1.0 mmol/g, fast equilibrium time and high stability are promising for CO2 capture from air. [ABSTRACT FROM AUTHOR]

Phospholipids (PLs) and cholesterol in human milk (HM) are affected by lactation, and differential lipids are closely related to maternal diet. The contents of PLs and cholesterol in Chinese HM are quantified by gas chromatography and high performance liquid chromatography, respectively, and the relationship between differential lipids and the maternal diet is obtained by Pearson. The result shows that SFA, MUFA, and polyunsaturated fatty acid (PUFA) are not affected by lactation and geography for total fatty acids, but almost all sn‐2 fatty acids are influenced by geography and remain unchanged during lactation. Most SFAs show absolute sn‐2 selectivity and the majority of MUFAs and PUFAs are esterified at the sn‐1 position. Cholesterol (13.8–22.6 mg per 100 g milk) and 25‐hydroxycholesterol (0.45–1.01 mg per 100 g milk) increase significantly and remain constant during lactation, respectively, and they are affected by regions. In addition, the differential lipids (22:1n‐9, C9:0, trans‐PUFA, 22:4n‐6, etc.) of PLs are closely related to the maternal diet. PLs and cholesterol content differ from western research and infant formula, which will help to design an infant formula that is more suitable for Chinese babies in the future. Practical Application: Compared with PLs and cholesterol in western countries and infant formula, the specificity of Chinese HM can more accurately target the development of formulas suitable for the growth of Chinese infants. At the same time, according to the influence of the motherʼs diet on the composition of HM, it is more reasonable to guide the diet of the mother. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy and safety of telbivudine on mother‐infant blockade in pregnant women with hepatitis B virus (HBV) DNA. Methods: A total of 141 pregnant women between 24 and 28 weeks of gestation and chronic HBV carriers with HBV DNA ≥106 copies/mL were enrolled, 105 in the treatment group and 36 in the control group. The treatment group was given telbivudine 600 mg/d oral, and the control group did not use antiviral drugs. Hepatitis B immunoglobulin 200 IU intramuscular injection and hepatitis B vaccine (HBVac) 10 μg subcutaneous injection were given to the infants in both groups within 12 hours after birth, and 10 μg of HBVac was subcutaneously injected when the infants were 1‐month and 6‐month old. Safety endpoints including HBV DNA quantification, liver function, CK were observed before treatment, 4 weeks after treatment, before delivery, and 24 weeks after delivery. Results: There was no difference in HBV DNA levels between the two groups before treatment and 6 months after delivery (P > .05). The HBV DNA level in the treatment group was significantly lower than that in the control group before delivery (P < .05). Between the two groups, the HBV positive rate was statistically different between the two groups (P < .05), and the difference of serum HBsAg of infants had statistical significance (P < .05), but the safety of the telbivudine group was not significantly different from that of the control group (P > .05). Conclusion: The application of telbivudine antiviral therapy in the middle and late stage of pregnancy of HBV high‐load pregnant women can significantly reduce the HBV DNA level before delivery, reduce the mother‐to‐child transmission rate of HBV, and have excellent security. [ABSTRACT FROM AUTHOR]

The phenomenon of periodic cross striation of GOA products is discovered as well as the mechanism and influencing factors are studied. Common electrode voltage (Vcom) distortion caused by the same period of CLKs affects the pixel holding voltage. CLK signal as a low frequency AC signal is transmitted to Feed through capacitances (common electrode is CF BM), and then Feed signal has distortion with period as CLK. The Vcom distortion comes from the reverse and amplified Feed distortion by compensators. By reducing the capacitance square (reducing CF BM area and/or Feed line length), the influence of CLK signal on Feed is decreased. By reducing the capacitance permittivity through changing the position and width of Sealant, the signal coupling between CLK and Feed is effectively diminished. [ABSTRACT FROM AUTHOR]

Summary: Two novel phosphorus‐nitrogen‐silicon copolymers (DDSQ‐N‐P‐yne and DDSQ‐N‐P‐ene) were synthesized by hydrosilylation reaction with DDSQ and DOPO derivatives. DOPO derivatives with different end groups were designed and synthesized to compare the flame retardancy and compatibility of phosphorus‐nitrogen‐silicon copolymers by different linkers between DDSQ and DOPO derivatives. The synthesized copolymers have been evidenced by 1H, 29Si nuclear magnetic resonance, and gel permeation chromatography and then introduced into polycarbonate (PC)/acrylonitrile butadiene styrene (ABS) alloy to study their flame retardancy and explore whether they exhibit a synergistic effect on the flame retardancy. The flame‐retardant properties of DDSQ‐N‐P‐yne (or ene) systems as well as the morphology were investigated in detail by using limiting oxygen index, thermogravimetric analysis, UL‐94, microcalorimeter, energy dispersive X‐ray, and scanning electron microscopy, respectively. When DDSQ‐N‐P‐yne (or ene) content is 10 wt%, the composites of PC/ABS are identified to be very effective according to limiting oxygen index, UL‐94, and microcalorimeter. The microstructures of the char were investigated by scanning electron microscopy, and the results indicated a tight and compact graphitized layer shaped, which plays an important role in improving the excellent thermal stability and flame retardancy of PC/ABS alloy. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease (AD) is one of the leading causes of death in elderly people. Its pathogenesis is greatly associated with the abnormality of immune system. However, only a few immune‐relevant AD drug target genes have been discovered up to now, and it is speculated that there are still many potential drug target genes of AD (at least immune‐relevant genes) to be discovered. Thus, this study was designed to identify novel AD drug target genes and explore their biological properties. Methods: A combinatorial approach was adopted for the first time to discover AD drug targets by collectively considering ontology inference and network analysis. Moreover, a novel strategy limiting the distance of reasoning and in turn reducing noise interference was further proposed to improve inference performance. Potential AD drug target genes were discovered by integrating information of multiple popular databases (TTD, DrugBank, PharmGKB, AlzGene, and BioGRID). Then, the enrichment analyses of the identified drug targets genes based on nine well‐known pathway‐related databases were conducted to explore the function of the identified potential drug target genes. Results: Eighteen potential drug target genes were finally identified, and 13 of them had been reported to be closely associated with AD. Enrichment analyses of these identified drug target genes, based on nine pathway‐related databases, revealed that the enriched terms were primarily focus on immune‐relevant biological processes. Four of those identified drug target genes are involved in the classical complement pathway and process of antigen presenting. Conclusion: The well‐reproducible results showed the good performance of the combinatorial approach, and the remaining five new targets could be a good starting point for our understanding of the pathogenesis and drug discovery of AD. Moreover, this study supported validity of the combinatorial approach integrating ontology inference with network analysis in the discovery of novel drug target for neurological diseases. [ABSTRACT FROM AUTHOR]

Abstract: Tough and self‐recoverable hydrogel membranes with micrometer‐scale thickness are promising for biomedical applications, which, however, rarely be realized due to the intrinsic brittleness of hydrogels. In this work, for the first time, by combing noncovalent DN strategy and spin‐coating method, we successfully fabricated thin (thickness: 5–100 µm), yet tough (work of extension at fracture: 105–107 J m−3) and 100% self‐recoverable hydrogel membranes with high water content (62–97 wt%) in large size (≈100 cm2). Amphiphilic triblock copolymers, which form physical gels by self‐assembly, were used for the first network. Linear polymers that physically associate with the hydrophilic midblocks of the first network, were chosen for the second network. The inter‐network associations serve as reversible sacrificial bonds that impart toughness and self‐recovery properties on the hydrogel membranes. The excellent mechanical properties of these obtained tough and thin gel membranes are comparable, or even superior to many biological membranes. The in vitro and in vivo tests show that these hydrogel membranes are biocompatible, and postoperative nonadhesive to neighboring organs. The excellent mechanical and biocompatible properties make these thin hydrogel membranes potentially suitable for use as biological or postoperative antiadhesive membranes. [ABSTRACT FROM AUTHOR]

A novel photonic dual-frequency phase-coded signals generator based on the optical carrier phase shifting and polarisation selection techniques is proposed by using an integrated dual-polarisation quadrature phase shift keying (DP-QPSK) modulator. The key feature of the scheme is the capability to generate dual-frequency phase-coded signals with reconfigurable frequency multiplication factors. In the upper QPSK modulator, an optical binary phase shift keying (BPSK) signal and a carriersuppressed double-sideband optical signal are generated, while in the bottom QPSK modulator, another carrier-suppressed double-sideband optical signal is generated. Thanks to the dual-polarisation property of the integrated modulator, the optical BPSK signal and different optical sidebands can be selected by using polarisation selection. As a result, two phase-coded signals with different frequencies can be achieved simultaneously. By adjusting the bias phases of the submodulators, dualfrequency phase-coded signals with frequencies of one and three, or two and four times the frequency of the RF carrier can be generated. The generation of 2.5 Gbps dual-frequency phase-coded signals with frequencies of 20 and 40 GHz, or 10 and 30 GHz are verified. The proposed scheme is simple, compact, and promising to find applications in future multi-band and multifunctional radars. [ABSTRACT FROM AUTHOR]

Developing solid catalysts with multiple active sites working cooperatively is desirable for efficient chemical transformations. However, most solid catalysts are rigid and impede the cooperation between their spatially isolated active sites. Two flexible porous organic frameworks (POFs) with integrated Co(salen) as active sites have been successfully synthesized for mimicking the cooperative modes of enzymes. The POFs exhibit second-order rate dependence on Co(salen) concentration in the network and afford much higher TOF (3300 versus 2670 h−1) than the homogeneous counterpart in the hydration of propylene epoxide. POFs with a flexible network thus not only facilitate but also enhance the cooperation of nearby Co(salen). Moreover, POFs could catalyze oversized substrates, have a wide substrate scope, and exhibit high stability. [ABSTRACT FROM AUTHOR]

Tough hydrogels have shown strong potential as structural biomaterials. These hydrogels alone, however, possess limited mechanical properties (such as low modulus) when compared to some load-bearing tissues, e.g., ligaments and tendons. Developing both strong and tough soft materials is still a challenge. To overcome this obstacle, a new material design strategy has been recently introduced by combining tough hydrogels with woven fiber fabric to create fiber reinforced soft composites (FRSCs). The new FRSCs exhibit extremely high toughness and tensile properties, far superior to those of the neat components, indicating a synergistic effect. Here, focus is on understanding the role of energy dissipation of the soft matrix in the synergistic toughening of FRSCs. By selecting a range of soft matrix materials, from tough hydrogels to weak hydrogels and even a commercially available elastomer, the toughness of the matrix is determined to play a critical role in achieving extremely tough FRSCs. This work provides a good guide toward the universal design of soft composites with extraordinary fracture resistance capacity. [ABSTRACT FROM AUTHOR]

Sorption and desorption processes control the bioavailability of heavy metals in the environment. Soil incubation and batch experiments were conducted to evaluate the effects of soil amendments on sorption, and desorption of Cu2+ and Cd2+ in a contaminated acidic paddy soil. The study showed that limestone and silicon fertilizer increased Cu2+ and Cd2+ sorption 2.43- and 1.13-fold, which was higher than calcium magnesium phosphate, Chinese milk vetch, pig manure, and peat. The Freundlich equation fitted sorption of Cu2+ and Cd2+ better than the Langmuir and Temkin equations. High desorption percentages of sorbed Cu2+ (mean of 67.1%) and Cd2+ (mean of 78.2%) were observed from the contaminated soil. Limestone and silicon fertilizer significantly decreased the desorption percentage of sorbed Cu2+ to 11.4 and 40.0%, respectively, and significantly decreased the desorption percentage of sorbed Cd2+ to 42.5 and 61.0%, respectively. However, the other four amendments did not show significant impact. Increasing soil pH significantly increased contents of sorbed Cu2+ and Cd2+, and negatively influenced desorption of sorbed Cu2+ and Cd2+. Application of amendments changed Cu and Cd fractions in soils, which might affect the sorption and desorption of Cu2+ and Cd2+. The effects of soil amendments on sorption and desorption of heavy metals may be useful for predication of their remedy efficiency to heavy metal contamination. [ABSTRACT FROM AUTHOR]

The health effects of exposure to electronic waste (e-waste)-derived pollutants are an important issue. The authors explored the association between the hepatic levels of e-waste-derived halogenated contaminants (including polychlorinated biphenyls [PCBs], polybrominated diphenyl ethers [PBDEs], and polybrominated biphenyls [PBBs]) and hepatic ethoxyresorufin- O-deethylase (EROD) activity of the common kingfisher ( Alcedo atthis) from an e-waste site and 2 reference sites in South China. The summed concentrations of PCBs, PBDEs, and PBBs ranged from 620 ng/g to 15 000 ng/g, 25 ng/g to 900 ng/g, and 14 ng/g to 49 ng/g wet weight, respectively, in the kingfishers from the e-waste site, and these values were significantly greater (2-3 orders of magnitude) than those obtained at the 2 reference sites. Correspondingly, significant hepatic EROD induction was observed in the kingfishers from the e-waste site compared with the reference sites. The EROD activity was significantly correlated to the levels of most of the PCB and PBDE congeners examined as well as PBB 153, suggesting that EROD induction may be evoked by these e-waste-derived pollutants. Environ Toxicol Chem 2016;35:1594-1599. © 2015 SETAC [ABSTRACT FROM AUTHOR]

ABSTRACT A new μ-oxamido-bridged dicopper(II) complex, [Cu2(papo)(H2O)- (phen)]Cl·CH3OH·H2O, where H3papo and phen represent N-(2-hydroxyphenyl)- N'-(3-aminopropyl)oxamide and 1,10-phenanthroline, respectively, has been synthesized and characterized by elemental analysis, molar conductivity measurement, infrared and electronic spectra studies, and single-crystal X-ray diffraction. The complex crystallizes in the triclinic space group P-1. Each copper(II) ion is located in a slightly distorted square-pyramidal environment. The Cu···Cu distance through the oxamide bridge is 5.1848(7) Å. The three-dimensional supramolecular structure is built-up by hydrogen bonds and π-π stacking interactions. The dicopper(II) complex exhibits cytotoxic activity against the SMMC-7721 and A549 cell lines. The reactivity toward herring sperm DNA and protein bovine serum albumin (BSA) reveals that the dicopper(II) complex can interact with the DNA by the intercalation mode, and effectively quench the intrinsic fluorescence of BSA via a static mechanism. The influence of hydrophobicity of the bridging ligand on DNA-binding properties and in vitro cytotoxic activities of this kind of dicopper(II) complexes was investigated. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea L.) yield and quality are seriously compromised by consecutive monoculturing in southeastern China. This work investigated the population size and community structure of soil nematodes in 3-, 6-, and 20-yr-old peanut monoculturing systems. A grass pasture was used as the control. The results showed that continuous peanut monocropping had detrimental effects on the soil nematode abundance and functional composition compared with the control. The reductions in the abundance of total and microbivorous nematodes with increasing years of monocropping are likely to reduce bioturbation and nutrient mineralization, and an elevated abundance of plant parasitic nematodes may result in serious damage to peanut roots, thus aggravating root rot. Furthermore, the significant variations in soil nematode functional indices across the three monocropped peanut fields may produce negative effects on sustainable agroecosystems. Our study also contributes to the identification of locally applicable indicator species of soil nematodes, i.e., Tylenchus, Doryllium, and Mesorhabditis, which can be applied in the assessment of soil status within monocropped peanut fields. Our results suggest that the soil nematode community exhibits evident responses to peanut monocropping. [ABSTRACT FROM AUTHOR]

Polyurethane (PU) block copolymers were synthesized using prepared hydroxypropyl terminated polydimethylsiloxane (HTPDMS MW 990) and polyether diols (N-210) as soft segment with 4,4′-diphenylmethane diisocyanate (MDI) and 1,4-butanediol. This low molecular weight polydimethylsiloxanes (PDMS) containing hydroxypropyl end-groups displayed better compatibility with PU than common PDMS. In this article, we illustrate its synthesis routes and confirmed the proposed molecular structures using NMR and infrared radiation (IR). We varied the contents of HTPDMS and N-210 in soft segments (HTPDMS-N-210: 0 : 100, 20 : 80, 40 : 60, 60 : 40, 80 : 20, and 100 : 0) to synthesize a series of PDMS-PU copolymer. IR spectroscopy showed the assignment characteristic groups of each peak in copolymers and confirmed that the desired HTPDMS-PU copolymers have been prepared. The different thermal, dynamic mechanical and surface properties of the copolymers were compared by thermogravimetry, DMA, contact angle and solvent resistance. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 [ABSTRACT FROM AUTHOR]