AGC kinases OXI1 and AGC2-2 regulate camalexin secretion and disease resistance by phosphorylating transporter PDR6.

Plant transporters regulating the distribution of secondary metabolites play critical roles in defending against pathogens, insects, and interacting with beneficial microbes. The phosphorylation of these transporters can alter their activity, stability, and intracellular protein trafficking. However, the regulatory mechanism underlying this modification remains elusive. In this study, we discovered two Orthologs of mammalian PKA, PKG, and PKC (AGC) kinases, Oxidative signal-inducible 1 (OXI1) and its closest homologue, AGC subclass 2 member 2 (AGC2-2; 75% amino acid sequence identity with OXI1), associated with the extracellular secretion of camalexin and Arabidopsis (Arabidopsis thaliana) resistance to Pseudomonas syringae and Botrytis cinerea. These kinases can undergo in vitro kinase reactions with three Pleiotropic drug resistance (PDR) transporters: PDR6, PDR8, and PDR12. Moreover, our investigation confirmed PDR6 interaction with OXI1 and AGC2-2. By performing LC-MS/MS and parallel reaction monitoring, we identified the phosphorylation sites on PDR6 targeted by these kinases. Notably, chitin induced PDR6 phosphorylation at specific residues, namely S31, S33, S827, and T832. Additional insights emerged by expressing dephosphorylated PDR6 variants in a pdr6 mutant background, revealing that the target residues S31, S33, and S827 promote PDR6 efflux activity, while T832 potentially contributes to PDR6 stability within the plasma membrane. The findings of this study elucidate partial mechanisms involved in the activity regulation of PDR-type transporters, providing valuable insights for their potential application in future plant breeding endeavors.

O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling.

Sonic hedgehog (Shh) signaling plays a critical role in regulating cerebellum development by maintaining the physiological proliferation of granule neuron precursors (GNPs), and its dysregulation leads to the oncogenesis of medulloblastoma. O-GlcNAcylation (O-GlcNAc) of proteins is an emerging regulator of brain function that maintains normal development and neuronal circuitry. Here, we demonstrate that O-GlcNAc transferase (OGT) in GNPs mediate the cerebellum development, and the progression of the Shh subgroup of medulloblastoma. Specifically, OGT regulates the neurogenesis of GNPs by activating the Shh signaling pathway via O-GlcNAcylation at S355 of GLI family zinc finger 2 (Gli2), which in turn promotes its deacetylation and transcriptional activity via dissociation from p300, a histone acetyltransferases. Inhibition of OGT via genetic ablation or chemical inhibition improves survival in a medulloblastoma mouse model. These data uncover a critical role for O-GlcNAc signaling in cerebellar development, and pinpoint a potential therapeutic target for Shh-associated medulloblastoma.

Kinetic Evaluation on Lithium Polysulfide in Weakly Solvating Electrolyte toward Practical Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

Development of a Decafluorobiphenyl Cyclized Peptide Targeting the NEMO-IKKα/ß Interaction that Enhances Cell Penetration and Attenuates Lipopolysaccharide-Induced Acute Lung Injury.

Aberrant canonical NF-κB signaling has been implicated in diseases, such as autoimmune disorders and cancer. Direct disruption of the interaction of NEMO and IKKα/ß has been developed as a novel way to inhibit the overactivation of NF-κB. Peptides are a potential solution for disrupting protein-protein interactions (PPIs); however, they typically suffer from poor stability in vivo and limited tissue penetration permeability, hampering their widespread use as new chemical biology tools and potential therapeutics. In this work, decafluorobiphenyl-cysteine SNAr chemistry, molecular modeling, and biological validation allowed the development of peptide PPI inhibitors. The resulting cyclic peptide specifically inhibited canonical NF-κB signaling in vitro and in vivo, and presented positive metabolic stability, anti-inflammatory effects, and low cytotoxicity. Importantly, our results also revealed that cyclic peptides had huge potential in acute lung injury (ALI) treatment, and confirmed the role of the decafluorobiphenyl-based cyclization strategy in enhancing the biological activity of peptide NEMO-IKKα/ß inhibitors. Moreover, it provided a promising method for the development of peptide-PPI inhibitors.

A novel enzyme-linked immunosorbent assay tool to evaluate plasma soluble CD226 in primary Sjögren's syndrome.

CD226 is an important receptor constitutively expressed on most immune cells, performing vital functions in immune responses. However, the levels of soluble CD226 (sCD226) and its roles in primary Sjögren syndrome (pSS) remain unclear. In this study, we developed two novel mouse anti-human CD226 monoclonal antibodies (mAbs) and established a novel sandwich enzyme-linked immunosorbent assay (ELISA) system, which proved to be highly effective in detecting human sCD226. We then analyzed the expression of sCD226 in the plasma of pSS patients. Our results showed that the levels of sCD226 were significantly lower in patients with pSS compared to healthy controls. The significant decline was also observed in active group and the patients with high levels of IgG or positive anti-SSB. Additionally, reduced sCD226 was found to be negatively correlated with the disease activity of pSS and several clinical manifestations, including arthralgia, fatigue, decayed tooth and interstitial lung disease (ILD). Furthermore, receiver operator characteristics (ROC) curve analysis showed that sCD226 displayed outstanding capacity in discriminating pSS and predicting the disease activity. Altogether, plasma sCD226 emerges as a promising candidate for diagnostic markers in the context of pSS.

Artificial intelligence-assisted system for the assessment of Forrest classification of peptic ulcer bleeding: a multicenter diagnostic study.

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.

Brønsted Acid-Catalyzed Intramolecular Tandem Double Cyclization of γ-Hydroxy Acetylenic Ketones with Alkynes into Naphtho[1,2-b]furan-3-ones.

A metal-free and atom-economic route for the synthesis of naphtho[1,2-b]furan-3-ones has been realized via p-TsOH·H2O-catalyzed intramolecular tandem double cyclization of γ-hydroxy acetylenic ketones with alkynes in formic acid. The benzene-linked furanonyl-ynes are the key intermediates obtained by the scission/recombination of C-O double bonds. Further, the structural modifications of the representative product were implemented by reduction, demethylation, substitution, and [5 + 2]-cycloaddition.

Clonal Hematopoiesis of Indeterminate Potential Is Associated With Coronary Microvascular Dysfunction In Early Nonobstructive Coronary Artery Disease.

BACKGROUND: Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is a risk factor for cardiovascular disease. The relationship between CHIP and coronary microvascular dysfunction (CMD) is unknown. The current study examines the association between CHIP and CH with CMD and the potential relationships in risk for adverse cardiovascular outcomes. METHODS: In this retrospective observational study, targeted next-generation sequencing was performed for 177 participants with no coronary artery disease who presented with chest pain and underwent routine coronary functional angiogram. Patients with somatic mutations in leukemia-associated driver genes in hematopoietic stem and progenitor cells were examined; CHIP was considered at a variant allele fraction ≥2%; CH was considered at a variant allele fraction ≥1%. CMD was defined as coronary flow reserve to intracoronary adenosine of ≤2. Major adverse cardiovascular events considered were myocardial infarction, coronary revascularization, or stroke. RESULTS: A total of 177 participants were examined. Mean follow-up was 12±7 years. A total of 17 patients had CHIP and 28 had CH. Cases with CMD (n=19) were compared with controls with no CMD (n=158). Cases were 56±9 years, were 68% women, and had more CHIP (27%; P=0.028) and CH (42%; P=0.001) than controls. CMD was associated with independent risk for major adverse cardiovascular events (hazard ratio, 3.89 [95% CI, 1.21-12.56]; P=0.023), and 32% of this risk was mediated by CH. The risk mediated by CH was ≈0.5× as large as the direct effect of CMD on major adverse cardiovascular events. CONCLUSIONS: In humans, we observe patients with CMD are more likely to have CHIP, and nearly one-third of major adverse cardiovascular events in CMD are mediated by CH.

Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays.

OBJECTIVES: Harmonization has been recommended by the International Organization for Standard (ISO) to achieve equivalent results across in vitro diagnostic measurement devices (IVD-MDs). We aim to evaluate the effectiveness of Bland-Altman plot-based harmonization algorithm (BA-BHA) created in this study and compare it with weighted Deming regression-based harmonization algorithm (WD-BHA) proposed in ISO 21151:2020. METHODS: Eighty patient sera were used as the harmonization reference material (HRM) to develop IVD-MD-specific harmonization algorithms. Another panel of 40 patient sera was used to validate the effectiveness of harmonization algorithms. We compared regression slopes, intercepts, Bland-Altman plot layouts, percent differences, limits of agreement (LoAs), between-method coefficients of variation (CV) before and after harmonization. RESULTS: After harmonization by WD-BHA, acceptable slopes and intercepts between measured values and HRM targets were observed in weighted Deming regression, but not in Passing-Bablok analysis. Mean differences were -5.5 to 5.0 % and differences at specific levels were -33.9 to 23.9 %. LoAs were -64.6 to 74.6 %. Between-method CV was 22.9 % (±12.9 %). However, after harmonization by BA-BHA, both weighted Deming and Passing-Bablok regressions equations presented harmonized results. Mean differences were -0.3 to 0.2 % and differences at specific levels were -1.1 to 1.6 %. LoAs were -23.3 to 23.2 %. Between-method CV was 8.4 % (±4.0 %). The data points were evenly distributed at both sides of the mean in Bland-Altman plots. CONCLUSIONS: The inequivalence of test results between different methods can be improved but unacceptable analytical differences at specific levels may be hidden in terms of an acceptable slope and intercept on WD-BHA. The new protocol BA-BHA may be a viable alternative to optimize the harmonization for immunoassays.

Feasibility of Ultrasound-Guided Percutaneous Axillary Artery Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation and its Effect on the Recovery of Spontaneous Heartbeat in Patients with ECPR.

Objective: The measurement of the right and left axillary arteries and aortic arch and their vessels by multi-row spiral CT angiography provides the basis for clinical catheter selection and depth for axillary artery placement. This study reported the clinical experience of 7 patients who successfully underwent ultrasound-guided percutaneous axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: Patients who had CT angiography of the thoracic aorta at our institution between January 2020 and March 2022 were assessed for eligibility and included. The diameters of the cephalic trunk (D1), right common carotid artery (D2), right axillary artery (D3), left common carotid artery (D4), left axillary artery opening (D5), right axillary artery cannulation length (L1), and left axillary artery cannulation length (L2) were measured. The tangential angles α, ß, and γ of the cephalic trunk, left common carotid artery and left subclavian and aorta was measured using an automatic angle-forming tool. The decision to use a 15F cannula for ultrasound-guided percutaneous axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) aims to achieve optimal vascular access. This cannula size strikes a balance, providing sufficient blood flow rates for ECMO support while minimizing the risk of complications associated with larger cannulas. Precise measurements of arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries, play a crucial role in guiding catheter selection and determining the depth of axillary artery placement. These measurements allow for tailored approaches based on individual patient characteristics, enhancing the safety and efficacy of the intervention. Additionally, measuring tangential angles (α, ß, and γ) provides insights into arterial alignment, optimizing the cannula trajectory for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy, minimizing complications, and ensuring the success of ultrasound-guided percutaneous axillary artery cannulation. In summary, the choice of a 15F cannula and precise measurements are essential components of the methodology, emphasizing safety, efficacy, and personalized approaches in VA-ECMO. From March to June 2022, 7 patients (6 males and 1 female) in our intensive care medicine department underwent successful ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with 15F cannula, including 3 cases with extracorporeal cardiopulmonary resuscitation (ECPR) and 4 cases with circulatory collapse. Results: 292 patients met the study criteria, 215 males and 77 females, with a mean age of 67.2±14.2 years. The measurements showed that D1 was (13.1±2.0) mm, D2 was (8.8±2.5) mm, D3 was (6.1±1.2) mm, D4 was (8.3±3.5) mm, D5 was (6.1±1.1) mm, L1 was (114.1±17.8) mm, and L2 was (128.4±20.2) mm. The tangential angles α of the cephalic trunk left common carotid artery and left subclavian artery to the aorta were (43.8°±17.1°), ß was (50.7°±14.8°), and γ was (62.4°±19.1°). Males had significantly wider D3 and D5, longer L1 and L2, and smaller gamma angles than females (P < .05). Three ECPR cases showed no recovery of the spontaneous heartbeat with femoral artery cannulation for VA-ECMO but recovered spontaneous heartbeat after axillary artery cannulation for VA-ECMO was adopted. The measurements in this study have important implications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) procedures. They provide crucial information about arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries. This information guides clinicians in selecting catheters and determining the ideal depth for percutaneous axillary artery cannulation during ECMO interventions. Notable gender differences in arterial dimensions highlight the need for personalized approaches in ECMO procedures. Customizing catheter choices and cannulation depth based on individual patient characteristics, informed by these measurements, improves the safety and effectiveness of the intervention. The measured tangential angles (α, ß, and γ) offer insights into arterial alignment, crucial for optimizing cannula trajectory and ensuring proper alignment for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy and minimizing the risk of complications during ECMO procedures. In summary, these measurements directly enhance the precision and safety of VA-ECMO procedures, underscoring the importance of personalized approaches based on individual anatomical variations and improving overall intervention success and outcomes. Conclusion: Ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with a 15F cannula is clinically feasible. Axillary artery cannulation for VA-ECMO contributes to the restoration of spontaneous heartbeat in ECPR patients more than femoral artery cannulation, and the possible mechanism is a better improvement of coronary blood flow. However, the study has limitations, including a modest sample size and a single-center, retrospective design, impacting its generalizability. To validate and extend these findings, further research with larger and diverse cohorts, including prospective investigations, is necessary to ensure their applicability across various clinical settings and patient demographics in VA-ECMO.

Epidemiology of Maxillofacial Fracture Injury in a Hospital in Xi'an: A 2-Year Retrospective Study.

Despite their limitations, epidemiological studies provide information useful for formulating effective and efficient injury prevention strategies. The aim is to carry out an epidemiology study of maxillofacial fracture in Xijing Hospital. Level of Evidence: Level II-therapeutic study.

Highly Dispersive Gold Nanoclusters Confined within Micropores of Defective UiO-66 for Highly Efficient Aldehyde Oxidation at Mild Conditions.

The oxidative esterification of aldehydes under mild conditions remains a significant challenge. This study introduces a unique defective UiO-66 to achieve gold nanoclusters (AuNCs) for efficient aldehyde oxidation under mild conditions. The construction and characterization of these materials are thoroughly investigated by techniques of XRD, SEM and TEM images, FT-IR, Raman, and XPS spectrum, emphasizing the unique microporous in defective UiO-66 are conducive to the fabrication of AuNCs. The catalytic performance of the prepared materials in aldehyde oxidation reactions is systematically evaluated, demonstrating the remarkable efficiency of dispersed Au@UiO-66-25 with high-content (9.09 wt%) Au-loading and ultra-small size (~2.7 nm). Moreover, mechanistic insights into the catalytic process under mild conditions (70 °C for 1 h) are provided, elucidating the determination of defective UiO-66 in the confined fabrication of AuNCs and subsequent furfural adsorption, which underlie the principles governing the observed enhancements. This study establishes the groundwork for the synthesis of highly dispersed and catalytically active metal nanoparticles using defective MOFs as a platform, advancing the catalytic esterification reaction of furfural to the next level.

The Effect of Syntactic Similarity on Intra-Sentential Switching Costs: Evidence from Chinese-English Bilinguals.

In order to better understand the role of syntactic similarity in a code-switched sentence, the current study explored the effect of similar and different syntactic structures on Chinese-English bilinguals' intra-sentential switching costs. L2 proficiency and switching directions as factors that potentially intervene in bilingual performance were together explored to see if there was any interaction. We manipulated the degree of syntactic similarity by utilizing clauses in active voice (greater similarity) and passive voice (lesser similarity). The study conducted a self-paced reading paradigm as a more natural language reading processing. Results showed overall longer reading times for active sentences than passive counterparts, which supported a syntactic similarity impediment rather than facilitation. The impediment seemed to be predominant irrespective of L2 proficiency. Furthermore, syntactic similarity modulated the asymmetry of switching costs between forward (L1-L2) and backward (L2-L1) direction: word RTs for the 1st and the 2nd switched word yielded greater costs in L2-L1 condition, while greater costs in L1-L2 condition was observed in 3rd switched word RTs and average RTs. The present study observed syntactic similarity impediment rather than facilitation for Chinese-English bilinguals. Notably, syntactic similarity plays a predominant role compared to L2 proficiency, and modulates the asymmetry between switching directions.

Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ-Hydroxy α-Amino Acids and Small Peptides.

An atom- and step-economical and redox-neutral cascade reaction enabled by asymmetric bimetallic relay catalysis by merging a ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with copper-catalyzed asymmetric Michael addition has been realized. A variety of highly functionalized 2-amino-5-hydroxyvaleric acid esters or peptides bearing 1,4-non-adjacent stereogenic centers have been prepared in high yields with excellent enantio- and diastereoselectivity. Judicious selection and rational modification of the Ru catalysts with careful tuning of the reaction conditions played a pivotal role in stereoselectivity control as well as attenuating undesired α-epimerization, thus enabling a full complement of all four stereoisomers that were otherwise inaccessible in previous work. Concise asymmetric stereodivergent synthesis of the key intermediates for biologically important chiral molecules further showcases the synthetic utility of this methodology.

Approaching Sustainable Lithium-Ion Batteries through Voltage-Responsive Smart Prelithiation Separator with Surface-Engineered Sacrificial Lithium Agents.

The surge in lithium-ion batteries has heightened concerns regarding metal resource depletion and the environmental impact of spent batteries. Battery recycling has become paramount globally, but conventional techniques, while effective at extracting transition metals like cobalt and nickel from cathodes, often overlook widely used spent LiFePO4 due to its abundant and low-cost iron content. Direct regeneration, a promising approach for restoring deteriorated cathodes, is hindered by practicality and cost issues despite successful methods like solid-state sintering. Hence, a smart prelithiation separator based on surface-engineered sacrificial lithium agents is proposed. Benefiting from the synergistic anionic and cationic redox, the prelithiation separator can intelligently release or intake active lithium via voltage regulation. The staged lithium replenishment strategy was implemented, successfully restoring spent LiFePO4's capacity to 177 mAh g-1 and a doubled life. Simultaneously, the separator can absorb excess active lithium up to approximately 600mAh g-1 below 2.5 V to prevent over-lithiation of the cathode This innovative, straightforward, and cost-effective strategy paves the way for the direct regeneration of spent batteries, expanding the possibilities in the realm of lithium-ion battery recycling.

Tensile Strain-Mediated Bimetallene Nanozyme for Enhanced Photothermal Tumor Catalytic Therapy.

Nanozymes have demonstrated significant potential in combating malignant tumor proliferation through catalytic therapy. However, the therapeutic effect is often limited by insufficient catalytic performance. In this study, we propose the utilization of strain engineering in metallenes to fully expose the active regions due to their ultrathin nature. Here, we present the first report on a novel tensile strain-mediated local amorphous RhRu (la-RhRu) bimetallene with exceptional intrinsic photothermal effect and photo-enhanced multiple enzyme-like activities. Through geometric phase analysis, electron diffraction profile, and X-ray diffraction, it is revealed that crystalline-amorphous heterophase boundaries can generate approximately 2 % tensile strain in the bimetallene. The ultrathin structure and in-plane strain of the bimetallene induce an amplified strain effect. Both experimental and theoretical evidence support the notion that tensile strain promotes multiple enzyme-like activities. Functioning as a tumor microenvironment (TME)-responsive nanozyme, la-RhRu exhibits remarkable therapeutic efficacy both in vitro and in vivo. This work highlights the tremendous potential of atomic-scale tensile strain engineering strategy in enhancing tumor catalytic therapy.

Inductive Effect on Single-Atom Sites.

Single-atom catalysts exhibit promising electrocatalytic activity, a trait that can be further enhanced through the introduction of heteroatom doping within the carbon skeleton. Nonetheless, the intricate relationship between the doping positions and activity remains incompletely elucidated. This contribution sheds light on an inductive effect of single-atom sites, showcasing that the activity of the oxygen reduction reaction (ORR) can be augmented by reducing the spatial gap between the doped heteroatom and the single-atom sites. Drawing inspiration from this inductive effect, we propose a synthesis strategy involving ligand modification aimed at precisely adjusting the distance between dopants and single-atom sites. This precise synthesis leads to optimized electrocatalytic activity for the ORR. The resultant electrocatalyst, characterized by Fe-N3P1 single-atom sites, demonstrates remarkable ORR activity, thus exhibiting great potential in zinc-air batteries and fuel cells.

Mitogenome analysis reveals predominantly ancient Yellow River origin of population inhabiting Datong agro-pastoral ecotone along Great Wall.

The Datong Basin was an important arena for population movement and admixture between the Yellow River Valley and Eastern Steppe. In historical materials, the region was often the setting for a tug-of-war between Han farmers and non-Han nomads. The genetic makeup and population history of this Datong population has, however, remained uncertain. In this study, we analysed 289 mitogenomes from Datong individuals. Our primary findings were: (1) population summary statistics analysis revealed a high level of genetic diversity and strong signals of population expansion in the Datong population; (2) inter-population comparisons (PCA and Fst heatmap) exhibited a close clustering between the Datong population and Northern Han, especially northern frontier groups, such as the Inner Mongolia Han, Heilongjiang Han, Liaoning Han and Tianjin Han; (3) phylogeographic analysis of complete mitogenomes revealed the presence of different components in the maternal gene pools of Datong population-the northern East Asian component was dominant (66.44%), whereas the southern East Asians were the second largest component with 31.49%. We also observed a much reduced west Eurasian (2.07%) component; (4) direct comparisons with ancient groups showed closer relationship between Datong and Yellow River farmers than Eastern Steppe nomads. Despite, therefore, centuries of Eastern Steppe nomadic control over the Datong area, Yellow River farmers had a much more significant impact on the Datong population.

Electrically tuned active metasurface towards metasurface-integrated liquid crystal on silicon (meta-LCoS) devices.

Active metasurfaces add a new dimension to static metasurfaces by introducing tunability, and this has received enormous attention from industry. Although various mechanisms have been proposed over the past few years in literature, solutions with good practicality are limited. Liquid crystal (LC)-based active metasurface is one of the most promising approaches due to the well-established LC industry. In this paper, an electrically tunable active metasurface was proposed and experimentally demonstrated using photoaligned nematic LC. The good quality of the LC photoalignment on the metasurface was demonstrated. Tunable transmission was obtained for telecommunication C band and the modulation depth in transmission amplitude of 94% was realized for 1530 nm. Sub-millisecond response time was achieved at operating a temperature of 60°C. The progress made here presents the potential of LC-based active metasurfaces for fast-switching photonic devices at optical communication wavelengths. More importantly, this work lays the foundations for the next-generation liquid crystal on silicon (LCoS) devices that are integrated with metasurfaces (meta-LCoS).

The crescent-like Golgi ribbon is shaped by the Ajuba/PRMT5/Aurora-A complex-modified HURP.

BACKGROUND: Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon. METHODS: To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon. RESULTS: The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery. CONCLUSIONS: The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape. Video Abstract.