Approaching the quantum limit in two-dimensional semiconductor contacts.

The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.

Uniform nucleation and epitaxy of bilayer molybdenum disulfide on sapphire.

Two-dimensional transition-metal dichalcogenides (TMDs) are of interest for beyond-silicon electronics1,2. It has been suggested that bilayer TMDs, which combine good electrostatic control, smaller bandgap and higher mobility than monolayers, could potentially provide improvements in the energy-delay product of transistors3-5. However, despite advances in the growth of monolayer TMDs6-14, the controlled epitaxial growth of multilayers remains a challenge15. Here we report the uniform nucleation (>99%) of bilayer molybdenum disulfide (MoS2) on c-plane sapphire. In particular, we engineer the atomic terrace height on c-plane sapphire to enable an edge-nucleation mechanism and the coalescence of MoS2 domains into continuous, centimetre-scale films. Fabricated field-effect transistor (FET) devices based on bilayer MoS2 channels show substantial improvements in mobility (up to 122.6 cm2 V-1 s-1) and variation compared with FETs based on monolayer films. Furthermore, short-channel FETs exhibit an on-state current of 1.27 mA µm-1, which exceeds the 2028 roadmap target for high-performance FETs16.

Therapy targeting antigen-specific T cells by a peptide-based tolerizing vaccine against autoimmune arthritis.

A longstanding goal has been to find an antigen-specific preventive therapy, i.e., a vaccine, for autoimmune diseases. It has been difficult to find safe ways to steer the targeting of natural regulatory antigen. Here, we show that the administration of exogenous mouse major histocompatibility complex class II protein bounding a unique galactosylated collagen type II (COL2) peptide (Aq-galCOL2) directly interacts with the antigen-specific TCR through a positively charged tag. This leads to expanding a VISTA-positive nonconventional regulatory T cells, resulting in a potent dominant suppressive effect and protection against arthritis in mice. The therapeutic effect is dominant and tissue specific as the suppression can be transferred with regulatory T cells, which downregulate various autoimmune arthritis models including antibody-induced arthritis. Thus, the tolerogenic approach described here may be a promising dominant antigen-specific therapy for rheumatoid arthritis, and in principle, for autoimmune diseases in general.

CXCL16 Promotes Ly6Chigh Monocyte Infiltration and Impairs Heart Function after Acute Myocardial Infarction.

High CXCL16 levels during acute cardiovascular events increase long-term mortality. However, the mechanistic role of CXCL16 in myocardial infarction (MI) is unknown. Here we investigated the role of CXCL16 in mice with MI injury. CXCL16 deficiency increased the survival of mice after MI injury, and inactivation of CXCL16 resulted in improved cardiac function and decreased infarct size. Hearts from CXCL16 inactive mice exhibited decreased infiltration of Ly6Chigh monocytes. In addition, CXCL16 promoted the macrophage expression of CCL4 and CCL5. Both CCL4 and CCL5 stimulated Ly6Chigh monocyte migration, and CXCL16 inactive mice had a reduced expression of CCL4 and CCL5 in the heart after MI. Mechanistically, CXCL16 promoted CCL4 and CCL5 expression by activating the NF-κB and p38 MAPK signaling pathways. Anti-CXCL16 neutralizing Ab administration inhibited Ly6Chigh monocyte infiltration and improved cardiac function after MI. Additionally, anti-CCL4 and anti-CCL5 neutralizing Ab administration inhibited Ly6Chigh monocyte infiltration and improved cardiac function after MI. Thus, CXCL16 aggravated cardiac injury in MI mice by facilitating Ly6Chigh monocyte infiltration.

NAC transcription factor ATAF1 negatively modulates the PIF-regulated hypocotyl elongation under a short-day photoperiod.

Day length modulates hypocotyl elongation in seedlings to optimize their overall fitness. Variations in cell growth-associated genes are regulated by several transcription factors. However, the specific transcription factors through which the plant clock increases plant fitness are still being elucidated. In this study, we identified the no apical meristem, Arabidopsis thaliana-activating factor (ATAF-1/2), and cup-shaped cotyledon (NAC) family transcription factor ATAF1 as a novel repressor of hypocotyl elongation under a short-day (SD) photoperiod. Variations in day length profoundly affected the transcriptional and protein levels of ATAF1. ATAF1-deficient mutant exhibited increased hypocotyl length and cell growth-promoting gene expression under SD conditions. Moreover, ATAF1 directly targeted and repressed the expression of the cycling Dof factor 1/5 (CDF1/5), two key transcription factors involved in hypocotyl elongation under SD conditions. Additionally, ATAF1 interacted with and negatively modulated the effects of phytochrome-interacting factor (PIF), thus inhibiting PIF-promoted gene expression and hypocotyl elongation. Taken together, our results revealed ATAF1-PIF as a crucial pair modulating the expression of key transcription factors to facilitate plant growth during day/night cycles under fluctuating light conditions.

Endothelial TIE1 Restricts Angiogenic Sprouting to Coordinate Vein Assembly in Synergy With Its Homologue TIE2.

BACKGROUND: Vascular growth followed by vessel specification is crucial for the establishment of a hierarchical blood vascular network. We have shown that TIE2 is required for vein development while little is known about its homologue TIE1 (tyrosine kinase with immunoglobulin-like and EGF [epithelial growth factor]-like domains 1) in this process. METHODS: We analyzed functions of TIE1 as well as its synergy with TIE2 in the regulation of vein formation by employing genetic mouse models targeting Tie1, Tek, and Nr2f2, together with in vitro cultured endothelial cells to decipher the underlying mechanism. RESULTS: Cardinal vein growth appeared normal in TIE1-deficient mice, whereas TIE2 deficiency altered the identity of cardinal vein endothelial cells with the aberrant expression of DLL4 (delta-like canonical Notch ligand 4). Interestingly, the growth of cutaneous veins, which was initiated at approximately embryonic day 13.5, was retarded in mice lack of TIE1. TIE1 deficiency disrupted the venous integrity, displaying increased sprouting angiogenesis and vascular bleeding. Abnormal venous sprouts with defective arteriovenous alignment were also observed in the mesenteries of Tie1-deleted mice. Mechanistically, TIE1 deficiency resulted in the decreased expression of venous regulators including TIE2 and COUP-TFII (chicken ovalbumin upstream promoter transcription factor, encoded by Nr2f2, nuclear receptor subfamily 2 group F member 2) while angiogenic regulators were upregulated. The alteration of TIE2 level by TIE1 insufficiency was further confirmed by the siRNA-mediated knockdown of Tie1 in cultured endothelial cells. Interestingly, TIE2 insufficiency also reduced the expression of TIE1. Combining the endothelial deletion of Tie1 with 1 null allele of Tek resulted in a progressive increase of vein-associated angiogenesis leading to the formation of vascular tufts in retinas, whereas the loss of Tie1 alone produced a relatively mild venous defect. Furthermore, the induced deletion of endothelial Nr2f2 decreased both TIE1 and TIE2. CONCLUSIONS: Findings from this study imply that TIE1 and TIE2, together with COUP-TFII, act in a synergistic manner to restrict sprouting angiogenesis during the development of venous system.

Whole-genome resequencing of Chinese indigenous sheep provides insight into the genetic basis underlying climate adaptation.

BACKGROUND: Chinese indigenous sheep are valuable resources with unique features and characteristics. They are distributed across regions with different climates in mainland China; however, few reports have analyzed the environmental adaptability of sheep based on their genome. We examined the variants and signatures of selection involved in adaptation to extreme humidity, altitude, and temperature conditions in 173 sheep genomes from 41 phenotypically and geographically representative Chinese indigenous sheep breeds to characterize the genetic basis underlying environmental adaptation in these populations. RESULTS: Based on the analysis of population structure, we inferred that Chinese indigenous sheep are divided into four groups: Kazakh (KAZ), Mongolian (MON), Tibetan (TIB), and Yunnan (YUN). We also detected a set of candidate genes that are relevant to adaptation to extreme environmental conditions, such as drought-prone regions (TBXT, TG, and HOXA1), high-altitude regions (DYSF, EPAS1, JAZF1, PDGFD, and NF1) and warm-temperature regions (TSHR, ABCD4, and TEX11). Among all these candidate genes, eight ABCD4, CNTN4, DOCK10, LOC105608545, LOC121816479, SEM3A, SVIL, and TSHR overlap between extreme environmental conditions. The TSHR gene shows a strong signature for positive selection in the warm-temperature group and harbors a single nucleotide polymorphism (SNP) missense mutation located between positions 90,600,001 and 90,650,001 on chromosome 7, which leads to a change in the protein structure of TSHR and influences its stability. CONCLUSIONS: Analysis of the signatures of selection uncovered genes that are likely related to environmental adaptation and a SNP missense mutation in the TSHR gene that affects the protein structure and stability. It also provides information on the evolution of the phylogeographic structure of Chinese indigenous sheep populations. These results provide important genetic resources for future breeding studies and new perspectives on how animals can adapt to climate change.

Identification of potential cell death-related biomarkers for diagnosis and treatment of osteoporosis.

BACKGROUND: This study aimed to identify potential biomarkers for the diagnosis and treatment of osteoporosis (OP). METHODS: Data sets were downloaded from the Gene Expression Omnibus database, and differentially programmed cell death-related genes were screened. Functional analyses were performed to predict the biological processes associated with these genes. Least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest (RF) machine learning algorithms were used to screen for characteristic genes, and receiver operating characteristics were used to evaluate the diagnosis of disease characteristic gene values. Gene set enrichment analysis (GSEA) and single-sample GSEA were conducted to analyze the correlation between characteristic genes and immune infiltrates. Cytoscape and the Drug Gene Interaction Database (DGIdb) were used to construct the mitochondrial RNA-mRNA-transcription factor network and explore small-molecule drugs. Reverse transcription real-time quantitative PCR (RT-qPCR) analysis was performed to evaluate the expression of biomarker genes in clinical samples. RESULTS: In total, 25 differential cell death genes were identified. Among these, two genes were screened using the LASSO, SVM, and RF algorithms as characteristic genes, including BRSK2 and VPS35. In GSE56815, the area under the receiver operating characteristic curve of BRSK2 was 0.761 and that of VPS35 was 0.789. In addition, immune cell infiltration analysis showed that BRSK2 positively correlated with CD56dim natural killer cells and negatively correlated with central memory CD4 + T cells. Based on the data from DGIdb, hesperadin was associated with BRSK2, and melagatran was associated with VPS35. BRSK2 and VPS35 were expectably upregulated in OP group compared with controls (all p < 0.05). CONCLUSIONS: BRSK2 and VPS35 may be important diagnostic biomarkers of OP.

Substrate engineering for wafer-scale two-dimensional material growth: strategies, mechanisms, and perspectives.

The fabrication of wafer-scale two-dimensional (2D) materials is a prerequisite and important step for their industrial applications. Chemical vapor deposition (CVD) is the most promising approach to produce high-quality films in a scalable way. Recent breakthroughs in the epitaxy of wafer-scale single-crystalline graphene, hexagonal boron nitride, and transition-metal dichalcogenides highlight the pivotal roles of substrate engineering by lattice orientation, surface steps, and energy considerations. This review focuses on the existing strategies and underlying mechanisms, and discusses future directions in epitaxial substrate engineering to deliver wafer-scale 2D materials for integrated electronics and photonics.

Whole genome sequencing revealed genetic diversity, population structure, and selective signature of Panou Tibetan sheep.

BACKGROUND: The detection of selective traits in different populations can not only reveal current mechanisms of artificial selection for breeding, but also provide new insights into phenotypic variation in new varieties and the search for genes associated with important traits. Panou sheep is a cultivated breed of Tibetan sheep in China with stable genetic performance, consistent appearance and fast growth and development after decades of artificial selection and cultivation. Due to long-term adaptation to the high altitude, cold and hypoxic environment in the plateau area, they may have formed a unique gene pool that is different from other Tibetan sheep breeds. To explore the genetic resources of Panou sheep, we used next-generation sequencing technology for the first time to investigate the genome-wide population structure, genetic diversity, and candidate signatures of positive selection in Panou sheep. RESULTS: Comparative genomic analysis with the closely related species Oula sheep (a native breed of Tibetan sheep in China) was used to screen the population selection signal of Panou sheep. Principal component analysis and neighbor joining tree showed that Panou sheep and Oula sheep had differences in population differentiation. Furthermore, analyses of population structure, they came from the same ancestor, and when K = 2, the two populations could be distinguished. Panou sheep exhibit genetic diversity comparable to Oula sheep, as shown by observed heterozygosity, expected heterozygosity and runs of homozygosity. Genome-wide scanning using the Fst and π ratio methods revealed a list of potentially selected related genes in Panou sheep compared to Oula sheep, including histone deacetylase 9 (HDAC9), protein tyrosine kinase 2 (PTK2), microphthalmia-related transcription factor (MITF), vesicular amine transporter 1 (VAT1), trichohyalin-like 1 (TCHHL1), amine oxidase, copper containing 3 (AOC3), interferon-inducible protein 35 (IFI35). CONCLUSIONS: The results suggest that traits related to growth and development and plateau adaptation may be selection targets for the domestication and breeding improvement of Tibetan sheep. This study provides the fundamental footprints for Panou sheep breeding and management.

Identification of copy number variation in Tibetan sheep using whole genome resequencing reveals evidence of genomic selection.

BACKGROUND: Copy number variation (CNV) is an important source of structural variation in the mammalian genome. CNV assays present a new method to explore the genomic diversity of environmental adaptations in animals and plants and genes associated with complex traits. In this study, the genome-wide CNV distribution characteristics of 20 Tibetan sheep from two breeds (10 Oula sheep and 10 Panou sheep) were analysed using whole-genome resequencing to investigate the variation in the genomic structure of Tibetan sheep during breeding. RESULTS: CNVs were detected using CNVnator, and the overlapping regions of CNVs between individual sheep were combined. Among them, a total of 60,429 CNV events were detected between the indigenous sheep breed (Oula) and the synthetic sheep breed (Panou). After merging the overlapping CNVs, 4927 CNV regions (CNVRs) were finally obtained. Of these, 4559 CNVRs were shared by two breeds, and there were 368 differential CNVRs. Deletion events have a higher percentage of occurrences than duplication events. Functional enrichment analysis showed that the shared CNVRs were significantly enriched in 163 GO terms and 62 KEGG pathways, which were mainly associated with organ development, neural regulation, immune regulation, digestion and metabolism. In addition, 140 QTLs overlapped with some of the CNVRs at more than 1 kb, such as average daily gain QTL, body weight QTL, and total lambs born QTL. Many of the CNV-overlapping genes such as PPP3CA, SSTR1 and FASN, overlap with the average daily weight gain and carcass weight QTL regions. Moreover, VST analysis showed that XIRP2, ABCB1, CA1, ASPA and EEF2 differed significantly between the synthetic breed and local sheep breed. The duplication of the ABCB1 gene may be closely related to adaptation to the plateau environment in Panou sheep, which deserves further study. Additionally, cluster analysis, based on all individuals, showed that the CNV clustering could be divided into two origins, indicating that some Tibetan sheep CNVs are likely to arise independently in different populations and contribute to population differences. CONCLUSIONS: Collectively, we demonstrated the genome-wide distribution characteristics of CNVs in Panou sheep by whole genome resequencing. The results provides a valuable genetic variation resource and help to understand the genetic characteristics of Tibetan sheep. This study also provides useful information for the improvement and breeding of Tibetan sheep in the future.

Phosphorescent Carbon Dots as Long-Lived Donors To Develop an Energy Transfer-Based Sensing Platform.

Employing long-lived luminescent materials to design a chemical sensing platform can eliminate real-time excitation and background fluorescence. However, the realization of long-lived emissions in aqueous media was limited to transition-metal complexes, doped quantum dots, organic crystals, and inorganic persistent phosphors, which suffer from the drawbacks of large size, expensive elements, and poor dispersibility. In this work, phosphorescent carbon dots (CDs) were covalently immobilized in a silica matrix (CDs@SiO2) to achieve afterglow emission in an aqueous dispersion. CDs@SiO2 with long lifetime (∼1.6 s) was utilized as an energy donor to fabricate nonradiative energy transfer systems with various organic dyes through the surface micelle self-assembly method. Benefiting from the high energy transfer efficiency between CDs@SiO2 and organic dyes, multicolor afterglow emissions were successfully obtained in aqueous media. As a proof of concept, a ratiometric phosphorescent probe using CDs@SiO2 as a donor and Hg2+-responsive rhodamine derivative as an acceptor was designed. Hg2+ triggered the energy transfer process between the donor-acceptor pair, leading to the sensitive detection of Hg2+ ions. The work presented here provides opportunities to develop chemical sensors with low background interferences and easily recognizable signals.

BRASSINOSTEROID-INSENSITIVE 2 regulates salt stress tolerance in Arabidopsis by promoting AGL16 activity.

Salt stress is a negative environmental factors to affecting plants. Salinity inhibits seed germination and root growth, which reduces the biomass of agricultural plants. BRASSINOSTEROID-INSENSITIVE2 (BIN2) functions as a signalling hub to integrate the perception and transduction of plant growth and stress tolerance by the phosphorylation of target proteins. However, only a small number of target molecules have been discovered thus far. In this study, we present evidence that BIN2 controls the post-transcriptional activity of AGL16. BIN2 interacts and phosphorylates AGL16, which increases AGL16 stability and transcriptional activity. Genetic testing showed that the agl16 mutant can restore the reduction in the seed germination rate and primary root growth of the bin2-1 mutant, while the overexpression of AGL16 in the bin2-3bil1bil2 mutant reduced the salt tolerance compared with bin2-3bil1bil2 in response to salt stress. Taken together, our data identify a BIN2-AGL16 core protein module that is mediates the inhibition of seed germination and primary root growth under salt stress.

Self-Catalytic Ternary Compounds for Efficient Synthesis of High-Quality Boron Nitride Nanotubes.

The large-scale synthesis of high-quality boron nitride nanotubes (BNNTs) has attracted considerable interests due to their applications in nanocomposites, thermal management, and so on. Despite decades of development, efficient preparation of high-quality BNNTs, which relies on the effective design of precursors and catalysts and deep insights into the catalytic mechanisms, is still urgently needed. Here, a self-catalytic process is designed to grow high-quality BNNTs using ternary W-B-Li compounds. W-B-Li compounds provide boron source and catalyst for BNNTs growth. High-quality BNNTs are successfully obtained via this approach. Density functional theory-based molecular dynamics (DFT-MD) simulations demonstrate that the Li intercalation into the lattice of W2 B5 promotes the formation of W-B-Li liquid and facilitates the compound evaporation for efficient BNNTs growth. This work demonstrates a high-efficient self-catalytic growth of high-quality BNNTs via ternary W-B-Li compounds, providing a new understanding of high-quality BNNTs growth.

Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage.

OBJECTIVES: To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). METHODS: IgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. RESULTS: Peptide GPI293-307 was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI293-307 epitopes, and high affinity anti-GPI293-307 IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI293-307 IgG antibodies induced arthritis in mice. Moreover, anti-GPI293-307 IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI293-307-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI293-307 antibodies. CONCLUSIONS: We have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.

The trace that is valuable: serum copper and copper to zinc ratio for survival prediction in younger patients with newly diagnosed acute myeloid leukaemia.

PURPOSE: No data on predicting the survival of AML patients based on the level of trace elements in the serum have been presented to date. The aims of this prospective cohort study were as follows: (i) to evaluate the serum Cu and Zn levels in people from Northeast China, (ii) to assess the association between the serum Cu level (SCL) and Cu to Zn ratio (SCZR) and clinical and nutrition data, and (iii) to investigate the predictive values of the SCL and SCZR in newly diagnosed de novo AML patients. METHODS: A total of 105 newly diagnosed AML patients and 82 healthy controls were recruited. The serum Cu and Zn levels were determined by inductively coupled plasma spectrometry. The associations of SCL and SCZR with the survival of these AML patients were assessed by Cox proportional hazards models. RESULTS: Both SCL and SCZR were positively related to the blast percentage of bone marrow and C-reactive protein, negatively related to albumin level and CEBPA double mutation and were significantly associated with worse overall survival and disease-free survival. Meanwhile, patients with higher SCL had worse CTCAE levels, and patients with higher SCZR showed less complete remission during the first course of induction chemotherapy. Moreover, higher SCZR was positively associated with ELN risk stratification, and was negatively associated with haemoglobin level and prognostic nutritional index (PNI). CONCLUSION: The SCL and SCZR are associated with long-term survival in patients with newly diagnosed AML undergoing intensive induction and may serve as important predictive biomarkers.

Characteristics of B cells and immunoglobulin profile in Takayasu's arteritis.

OBJECTIVES: Disorders of humoral immunity in Takayasu's arteritis (TAK) have not been well explored. This study describes the characteristics of B cells and immunoglobulin (Ig) profile in patients with TAK. METHODS: Peripheral B cell populations assessed using flow cytometry and serum Ig levels assessed using a biochemical analyser in 98 newly diagnosed patients with TAK were analysed and compared with those of 31 patients with systemic lupus erythematosus (SLE) and 60 healthy controls (HCs). CD19+ B cell and IgG infiltration to the aortic tissue was evaluated by immunohistochemical staining. RESULTS: The proportion of peripheral CD3-CD19+ B cells and levels of serum IgG in TAK were lower than those in SLE, but higher than those in HCs. CD3-CD19+ B cell counts were higher in TAK than in HCs. Serum IgG and IgG1 levels were higher in active TAK than in non-active TAK. In TAK, positive correlations of serum IgG levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Kerr score, and Indian Takayasu Clinical Activity Score (ITAS2010, ITAS-A) were observed before immunotherapy. After 6 months of immunotherapy, serum Ig levels significantly decreased. Positive correlations between the changes in IgG levels and values of ESR, CRP, Kerr score, and ITAS-A were detected. Immunohistochemical staining confirmed CD19+ B cell and IgG infiltration to the aortic wall in patients with TAK. CONCLUSIONS: Enhanced B cells might contribute to the pathogenesis of TAK, and serum IgG levels could serve as a simple, useful biomarker to assess disease activity and monitor treatment response in TAK.

Platelet count as a potential predictor in refractory Takayasu arteritis.

Platelet parameters have been recognized as important markers for disease severity in various types of diseases. The aim of our study was to investigate whether platelet count could be used as a potential predictor of refractory Takayasu arteritis (TAK). In this retrospective study, fifty-seven patients were selected as development data group to identify the associated risk factors and potential predictors of refractory TAK. Ninety-two TAK patients were included in the validation data group to verify the predictive value of platelet count for refractory TAK. Refractory TAK patients had higher levels of platelet (PLT) than non-refractory TAK patients (305.5 vs. 272.0 × 109/L, P = 0.043). For PLT, the best cut-off value was 296.5 × 109/L to predict refractory TAK. Elevated PLT (> 296.5 × 109/L) was found to be statistically related to refractory TAK (OR [95%CI] 4.000 [1.233-12.974], p = 0.021). In the validation data group, the proportion of refractory TAK in patients with elevated PLT was significantly higher than that in patients with non-elevated PLT (55.6% vs. 32.2%, P = 0.037). The 1-, 3- and 5-year cumulative incidence of refractory TAK were 37.0%, 44.4% and 55.6% in patients with elevated PLT, respectively. Elevated PLT (p = 0.035, hazard ratio (HR) 2.106) was identified as a potential predictor of refractory TAK. Clinicians should pay close attention to platelet levels in patients with TAK. For TAK patients with PLT greater than 296.5 × 109/L, closer monitoring of the disease and comprehensive assessment of disease activity are recommended to be alert to the occurrence of refractory TAK.

Brassinosteroids regulate root meristem development by mediating BIN2-UPB1 module in Arabidopsis.

Plant steroid hormones brassinosteroids (BRs) regulate plant growth and development at many levels. While negative regulatory factors that inhibit development and are counteracted by BRs exist in the root meristem, these factors have not been characterized. The functions of UPB1 transcription factor in BR-regulated root growth have not been established, although its role in regulating root are well documented. Here, we found that BIN2 interacts with and phosphorylates the UPB1 transcription factor consequently promoting UPB1 stability and transcriptional activity. Genetic analysis revealed that UPB1 deficiency could partially recover the short-root phenotype of BR-deficient mutants. Expression of a mutated UPB1S37AS41A protein lacking a conserved BIN2 phosphorylation sites can rescue shorter root phenotype of bin2-1 mutant. In addition, UPB1 was repressed by BES1 at the transcriptional level. The paclobutrazol-resistant protein family (PRE2/3) interacts with UPB1 and inhibits its transcriptional activity to promote root meristem development, and BIN2-mediated phosphorylation of UPB1 suppresses its interaction with PRE2/3, and subsequently impairing root meristem development. Taken together, our data elucidate a molecular mechanism by which BR promotes root growth via inhibiting BIN2-UPB1 module.

Differential tissue expression of sex steroid-synthesizing enzyme CYP11A1 in male Tibetan sheep (Ovis aries).

Steroid metabolism is a fundament to testicular development and function. The cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) is a key rate-limiting enzyme for catalyzing the conversion of cholesterol to pregnenolone. However, despite its importance, what expression and roles of CYP11A1 possesses and how it regulates the testicular development and spermatogenesis in Tibetan sheep remains largely unknown. Based on this, we evaluated the expression and localization patterns of CYP11A1 in testes and epididymides of Tibetan sheep at three developmental stages (three-month-old, pre-puberty; one-year-old, sexual maturity and three-year-old, adult) by quantitative real-time PCR (qPCR), western blot and immunofluorescence. The results showed that CYP11A1 mRNA and protein were expressed in testes and epididymides throughout the development stages and obviously more intense in one- and three-year-old groups than three-month-old group (except for the caput epididymidis). Immunofluorescence assay showed that the CYP11A1 protein was mainly located in Leydig cells and epididymal epithelial cells. In addition, positive signals of CYP11A1 protein were observed in germ cells, epididymal connective tissue and sperms stored in the epididymal lumen. Collectively, these results suggested that the CYP11A1 gene might be mainly involved in regulating spermatogenesis and androgen synthesis in developmental Tibetan sheep testis and epididymis.