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Statement of problem The immediate loading protocol for 2-implant mandibular overdentures has been widely reported. Nevertheless, the clinical effects reported in different articles are quite different. Purpose The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical effects of immediate and delayed loading of 2-implant mandibular overdentures. Material and methods The review followed the guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). PubMed, Cochrane Library, Web of Science, Embase, Scopus, ScienceDirect, CBM, CNKI, and Wan Fang databases were searched electronically for RCTs published before March 25, 2020. Two authors independently conducted literature screening, quality assessment, and data extraction. The outcomes of interest were implant failure rate, marginal bone loss (MBL), implant stability quotient (ISQ), periotest value (PTV), and patient satisfaction. Results A total of 2498 unduplicated records were identified. After full-text analysis, 7 eligible RCTs were included. All studies were followed for at least 12 months, and the meta-analysis was based on this. The meta-analysis showed that the implant failure rate in the immediate group was higher than that in the delayed group, but there was no statistically significant difference (I2=0%; n=7; risk difference [RD]=0.03; 95% confidence interval [CI]=-0.01 to 0.08). The difference of MBL between immediate and delayed loading was not significant (I2=88%; n=6; mean difference [MD]=-0.04; 95% CI=-0.16 to 0.24). Because of the limited articles reporting on ISQ, PTV, and patient satisfaction, no quantitative analysis was conducted for these outcomes. Conclusions Although the implant failure rate was more likely to favor the delayed group, available evidence indicates no statistical difference in implant failure and marginal bone loss between immediate and delayed loading protocols.

Photons with spin angular momentum possess intrinsic chirality which underpins many phenomena including nonlinear optics1, quantum optics2, topological photonics3 and chiroptics4. Intrinsic chirality is weak in natural materials, and recent theoretical proposals5-7 aimed to enlarge circular dichroism by resonant metasurfaces supporting bound states in the continuum that enhance substantially chiral light-matter interaction. Those insightful works resort to three-dimensional sophisticated geometries, which are too challenging to be realized for optical frequencies8. Therefore, most of the experimental attempts9-11 showing strong circular dichroism rely on false/extrinsic chirality by employing either oblique incidence9, 10 or structural anisotropy11. Here, we report on the experimental realization of true/intrinsic chiral response with resonant metasurfaces where the engineered slant geometry breaks both in-plane and out-of-plane symmetries. Our result marks the first observation of intrinsic chiral bound states in the continuum with near-unity chiral dichroism of 0.93 and record-high quality factor exceeding 2663 for visible frequencies. Our chiral metasurfaces promise a plethora of applications in chiral light sources and detectors, chiral sensing, valleytronics and asymmetric photocatalysis.

Central Asia (CA) is one of the most drought-prone regions in the world with complex climate regimes, it is extremely vulnerable to water scarcity. Many studies on drought in CA, as a whole, have been carried out, whereas there is a lack of studies on the drying and wetting trends of different climatic zones within CA. In this study, CA was divided into three different climatic zones based on the Koppen climate classification method, precipitation climatology, and aridity index. These were the temperate continental (Df), dry arid desert (BW), and Mediterranean continental (Ds) climatic zones. The regional drying and wetting trends during the years 1961–2015 were investigated using the monthly gridded Standardized Precipitation Evapotranspiration Index (SPEI). The empirical orthogonal function (EOF) was applied to analyze spatial and temporal variation patterns. EOF mode 1 (EOF1) analysis found increasingly wet conditions throughout CA over the duration of the study, and EOF mode 2 (EOF2) analysis found a contrast between northern and southern CA: as Df became drier and BW and Ds became wetter. EOF mode 3 (EOF3) analysis found a western and eastern inverse phase distribution. The SPEI displayed a decreasing trend from 1961 to 1974 for CA as a whole, before increasing from 1975 to 2015, with a particularly significant increase over the first seven years of that period. On a regional scale, the BW and Ds zones experienced a wetting trend due to increased precipitation during 1961–2015, but the Df zone experienced a drying trend due to reduced evapotranspiration and an increasing temperature, particularly from 1961 to 1978. Thus, the spatio-temporal patterns in dryness and wetness across CA can be categorized according to climatic regions.

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.

Spoken language understanding module is an important part of the human-machine dialogue system, which contains two important subtasks of intent recognition and slot filling. In the current human-machine dialogue system, intent recognition and slot filling are mostly in the form of independent tasks Exist, it is difficult to further mine the latent semantic information in the text. This paper attempts to introduce attention mechanism in the process of intent recognition, and share the latent information of intent recognition and slot filling to improve the result of intent recognition and slot filling. Experiments show that the introduction of attention mechanism and the sharing of hidden information are important for slot filling and intent recognition and have a certain improvement effect.

Aluminum-activated malate transporters (ALMTs) form an anion channel family that plays essential roles in diverse functions in plants. Arabidopsis ALMT12, also named QUAC1 (quick anion channel 1), regulates stomatal closure in response to environmental stimuli. However, the molecular basis of ALMT12/QUAC1 activity remains elusive. Here, we describe the cryo-EM structure of ALMT12/QUAC1 from Glycine max at 3.5-Å resolution. Gm ALMT12/QUAC1 is a symmetrical dimer, forming a single electropositive T-shaped pore across the membrane. The transmembrane and cytoplasmic domains are assembled into a twisted two-layer architecture, with their associated dimeric interfaces nearly perpendicular. Gm ALMT12/QUAC1-mediated currents display rapid kinetics of activation/deactivation and a bell-shaped voltage dependency, reminiscent of the rapid (R)–type anion currents. Our structural and functional analyses reveal a domain-twisting mechanism for malate-mediated activation. Together, our study uncovers the molecular basis for a previously uncharacterized class of anion channels and provides insights into the gating and modulation of the ALMT12/QUAC1 anion channel.

To observe the effect of horizontal penetration needling at vertigo auditory area and balance area on residual dizziness after successful repositioning maneuver in patients with benign paroxysmal positional vertigo (BPPV).Sixty-six patients with residual dizziness after successful repositioning maneuver for BPPV were randomly divided into an observation group (34 cases, 1 case dropped off) and a control group (32 cases, 2 cases dropped off). The patients in the observation group were treated with horizontal penetration needling at vertigo auditory area and balance area, once every other day; three times were taken as a course of treatment, and two courses of treatment were given. The patients in the control group received no acupuncture and medication. The dizziness handicap inventory (DHI) and visual analogue scale (VAS) scores were observed before treatment and after 1 and 2 courses of treatment.Except for the emotional score of DHI in the control group after 1 course of treatment, the sub item scores and total scores of DHI and VAS scores in the two groups after treatment were lower than those before treatment (Whether acupuncture or not, residual dizziness after repositioning maneuver for BPPV can be relieved within 2 weeks; horizontal penetration needling at vertigo auditory area and balance area could improve dizziness symptoms and shorten the course of disease.

Significance Precise chromosome segregation relies on kinetochores. How kinetochores are precisely assembled on centromeres through the cell cycle remains poorly understood. Centromeres in most eukaryotes are epigenetically marked by nucleosomes containing the histone H3 variant, CENP-A. Here, we demonstrated that Ccp1, an anti–CENP-A loading factor, interacts with the N terminus of CENP-T to promote the assembly of the outer kinetochore Ndc80 complex. This work further suggests that competitive exclusion between Ccp1 and Ndc80 at the N terminus of CENP-T via phosphorylation ensures precise kinetochore assembly during mitosis. In addition, CENP-T is critical for Ccp1 centromeric localization, which in turn regulates CENP-A distribution. Our results reveal a previously unrecognized mechanism underlying kinetochore assembly through the cell cycle., Kinetochores, a protein complex assembled on centromeres, mediate chromosome segregation. In most eukaryotes, centromeres are epigenetically specified by the histone H3 variant CENP-A. CENP-T, an inner kinetochore protein, serves as a platform for the assembly of the outer kinetochore Ndc80 complex during mitosis. How CENP-T is regulated through the cell cycle remains unclear. Ccp1 (counteracter of CENP-A loading protein 1) associates with centromeres during interphase but delocalizes from centromeres during mitosis. Here, we demonstrated that Ccp1 directly interacts with CENP-T. CENP-T is important for the association of Ccp1 with centromeres, whereas CENP-T centromeric localization depends on Mis16, a homolog of human RbAp48/46. We identified a Ccp1-interaction motif (CIM) at the N terminus of CENP-T, which is adjacent to the Ndc80 receptor motif. The CIM domain is required for Ccp1 centromeric localization, and the CIM domain–deleted mutant phenocopies ccp1Δ. The CIM domain can be phosphorylated by CDK1 (cyclin-dependent kinase 1). Phosphorylation of CIM weakens its interaction with Ccp1. Consistent with this, Ccp1 dissociates from centromeres through all stages of the cell cycle in the phosphomimetic mutant of the CIM domain, whereas in the phospho-null mutant of the domain, Ccp1 associates with centromeres during mitosis. We further show that the phospho-null mutant disrupts the positioning of the Ndc80 complex during mitosis, resulting in chromosome missegregation. This work suggests that competitive exclusion between Ccp1 and Ndc80 at the N terminus of CENP-T via phosphorylation ensures precise kinetochore assembly during mitosis and uncovers a previously unrecognized mechanism underlying kinetochore assembly through the cell cycle.

Injury of cervical spine is a common injury of locomotor system usually accompanied by spinal cord injury, however the injury mechanism of contusion load to the spinal cord is not clear. This study aims to investigate its injury mechanism associated with the contusion load, with different extents of spinal cord compression. A finite element model of cervical spinal cord was established and two scenarios of contusion injury loading conditions, i.e. back-to-front and front-to-back loads, were adopted. Four different compression displacements were applied to the middle section of the cervical spinal cord. The distributions of von Mises stress in middle transverse cross section were obtained from the finite element analysis. For the back-to-front loading scenario, the stress concentration was found in the area at and near the central canal and the damage may lead to the central canal syndrome from biomechanical point of view. With the front-to-back load, the maximum von Mises stress located in central canal area of gray matter when subject to 10% compression, whilst it appeared at the anterior horn when the compression increased. For the white matter, the maximum von Mises stress appeared in the area of the anterior funiculus. This leads to complicated symptoms given rise by damage to multiple locations in the cervical spinal cord. The illustrative results demonstrated the need of considering different loading scenarios in understanding the damage mechanisms of the cervical spinal cord, particularly when the loading conditions were given rise by different pathophysiological causes.

The known benzonaphthyridine alkaloid, albogrisin A (1), and six new compounds, including two pyrazinone stereoisomers, albogrisin B (2)/B' (2'), together with four 4H-pyrroloquinolinones, two diastereoisomers, albogrisin C (3)/C' (3'), and their methyl esters, albogrisin D (4)/D' (4'), were isolated from mangrove-derived Streptomyces albogriseolus MGR072. 2 and 2' are converted into 1 in acidic aqueous solution but into 3/3' and 4/4' in 0.05% trifluoroacetic acid acetonitrile. 4 and 4' are new indoleamine 2,3-dioxygenase 1 inhibitors.

Objectives TNBG-5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG-5602 in in-vitro and in-vivo models and investigated its possible anticancer mechanism. Methods The antiproliferation effect of TNBG-5602 in vitro was evaluated in human liver cancer cell line QGY-7701. The acute toxicity of TNBG-5602 was evaluated in mice. The anticancer activity of TNBG-5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY-7701. Key findings The results of CCK-8 assay showed that TNBG-5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD50 of TNBG-5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG-5602 could remarkably inhibit the growth of tumours. During in-vitro and in-vivo studies, we noted that TNBG-5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG-5602 may be exerted through activating peroxisome proliferator-activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA). Conclusions Our results suggested that TNBG-5602 might exert potent anticancer activity through increasing the expression of PPARγ.

The mitogen-activated protein kinase ERK1/2 (ERKs, extracellular-regulated protein kinases) plays important roles in a wide spectrum of cellular processes and have been implicated in many disease states. The spatiotemporal regulation of ERK activity has been extensively studied. However, scarce information has been available regarding the quality control of the kinases to scavenge malfunctioning ERKs. Using site-specific mutagenesis and mass spectrometry, we found that the disruption of the conserved H-bond between Y210 and E237 of ERK1 through point mutation at or naturally occurring nitration on Y210 initiates a quality control program dependent on chaperon systems and CHIP (C-terminal of Hsp70-interacting protein)-mediated ubiquitination and degradation. The H-bond is also important for the quality control of ERK2, but through a distinct mechanism. These findings clearly demonstrate how malfunctioning ERKs are eliminated when cells are in certain stress conditions or unhealthy states, and could represent a general mechanism for scavenging malfunctioning kinases in stress conditions.

Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca 2+ from intracellular stores. TRIC activity is controlled by voltage and Ca 2+ modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca 2+ -bound and Ca 2+ -free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. The TRIC channels are symmetric trimers, wherein we find a pore in each protomer that is gated by a highly conserved lysine residue. In the resting state, Ca 2+ binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca 2+ release, luminal Ca 2+ depletion removes inhibition to permit the lysine-bearing and voltage-sensing helix to move in response to consequent membrane hyperpolarization. Diacylglycerol is found at interprotomer interfaces, suggesting a role in metabolic control.

Stomata in leaves regulate gas exchange between the plant and its atmosphere. Various environmental stimuli elicit abscisic acid (ABA); ABA leads to phosphoactivation of slow anion channel 1 (SLAC1); SLAC1 activity reduces turgor pressure in aperture-defining guard cells; and stomatal closure ensues. We used electrophysiology for functional characterizations of Arabidopsis thaliana SLAC1 (AtSLAC1) and cryoelectron microscopy (cryo-EM) for structural analysis of Brachypodium distachyon SLAC1 (BdSLAC1), at 2.97-A resolution. We identified 14 phosphorylation sites in AtSLAC1 and showed nearly 330-fold channel-activity enhancement with 4 to 6 of these phosphorylated. Seven SLAC1-conserved arginines are poised in BdSLAC1 for regulatory interaction with the N-terminal extension. This BdSLAC1 structure has its pores closed, in a basal state, spring loaded by phenylalanyl residues in high-energy conformations. SLAC1 phosphorylation fine-tunes an equilibrium between basal and activated SLAC1 trimers, thereby controlling the degree of stomatal opening.

Due to the remarkable flexoelectric effect of nano structures, the electro-mechanical coupling of nano piezoelectric sensors has been studied. This paper studies polarization distribution and induced voltage (or output voltage) of the functionally graded piezoelectric cantilever nanobeam by the generalized variational principle and linear piezoelectric theory. The equilibrium equation and corresponding general boundary condition of functionally graded sensors are obtained. Based on the graded model, the analytic forms of the deformation and output voltage are given. The numerical result reveals gradient parameters and flexoelectric coefficient have the significant influence on the output voltage and electric polarization for the functionally graded sensor. The strong piezoelectric gradient in sensors would cause the significant effective flexoelectricity, which could generate the large output voltage at the large structural size.

Nucleotide-binding, leucine-rich repeat receptors (NLRs) are major immune receptors in plants and animals. Upon activation, the Arabidopsis NLR protein ZAR1 forms a pentameric resistosome in vitro and triggers immune responses and cell death in plants. In this study, we employed single-molecule imaging to show that the activated ZAR1 protein can form pentameric complexes in the plasma membrane. The ZAR1 resistosome displayed ion channel activity in Xenopus oocytes in a manner dependent on a conserved acidic residue Glu11 situated in the channel pore. Pre-assembled ZAR1 resistosome was readily incorporated into planar lipid-bilayers and displayed calcium-permeable cation-selective channel activity. Furthermore, we show that activation of ZAR1 in the plant cell led to Glu11-dependent Ca2+ influx, perturbation of subcellular structures, production of reactive oxygen species, and cell death. The results thus support that the ZAR1 resistosome acts as a calcium-permeable cation channel to trigger immunity and cell death.

Heterochromatin, a transcriptionally silenced chromatin domain, is important for genome stability and gene expression. Histone 3 lysine 9 methylation (H3K9me) and histone hypoacetylation are conserved epigenetic hallmarks of heterochromatin. In fission yeast, RNA interference (RNAi) plays a key role in H3K9 methylation and heterochromatin silencing. However, how RNAi machinery and histone deacetylases (HDACs) are coordinated to ensure proper heterochromatin assembly is still unclear. Previously, we showed that Dpb4, a conserved DNA polymerase epsilon subunit, plays a key role in the recruitment of HDACs to heterochromatin during S phase. Here, we identified a novel RNA-binding protein Dri1 that interacts with Dpb4. GFP-tagged Dri1 forms distinct foci mostly in the nucleus, showing a high degree of colocalization with Swi6/Heterochromatin Protein 1. Deletion of dri1+ leads to defects in silencing, H3K9me, and heterochromatic siRNA generation. We also showed that Dri1 physically associates with heterochromatic transcripts, and is required for the recruitment of the RNA-induced transcriptional silencing (RITS) complex via interacting with the complex. Furthermore, loss of Dri1 decreases the association of the Sir2 HDAC with heterochromatin. We further demonstrated that the C-terminus of Dri1 that includes an intrinsically disordered (IDR) region and three zinc fingers is crucial for its role in silencing. Together, our evidences suggest that Dri1 facilitates heterochromatin assembly via the RNAi pathway and HDAC.

In this work, in order to reveal the role of crystallographic orientation in the electrochemical and discharge behaviors of the extruded diluted Mg-0.5Sn-0.5Zn-0.5Ca (wt.%) alloy through investigating the longitude surface (LS) and transversal surface (TS). The results show that the LS sample is mainly consisted of (0001) orientated grains, while the TS one is composed of (10-10)/(11–20) orientated grains. Although the self-corrosion rate for TS sample is higher than that of the counterpart as a result of the non-basal planes possess lower surface energy and higher activation energy, the real-time self-discharge rates for both samples are similar at constant applied current density. Nevertheless, the TS sample exhibits a remarkably higher anodic efficiency than that of the LS one, which can be attributed to the uniform dissolution of the substrate along with the weakened chunk effect (CE). Additionally, the Mg-air battery with the TS sample as anode exhibits a more stable discharge course and higher cell voltage due to the loose discharge products as well as enhanced discharge activity.

The Quasi-Elastic Neutron Scattering (QENS) spectra from four cement pastes are re-analyzed by a new revised jump-diffusion and rotation-diffusion model (rJRM). From the QENS fit, it can be seen that the rJRM is an improved model to fit QENS spectra within the whole detected neutron energy transfer and scattering vector. By the rJRM fitting, the structure parameters extracted from QENS spectra show that both the additives aluminum-silicate nanotubes (ASN) and carboxyl group functionalized ASN (ASN-COOH) can improve magnesium-silicate-hydrate (M-S-H) toward calcium-silicate-hydrate (C–S–H) direction in mechanical properties, but the improvement is weakened with decreasing temperatures. The extracted dynamical parameters show that there is a dynamic anomaly near 230 K in not only translational but also rotational diffusion of water confined in all the investigated samples. The anomaly in rotational diffusion is new compared with those results obtained by the QENS fit using other models.

Phase change materials (PCMs) that can store the heat energy obtained from intermittent solar irradiation are very important for solar energy absorption cooling system. In this work, an organic compound that melts at the temperature of 368.2 ± 0.5 K was applied as PCM. The specific heat capacities of the PCM were measured by temperature-modulated differential scanning calorimetry from 198.15 to 431.15 K. The thermodynamic functions of [HT–H298.15] and [ST–S298.15] were then calculated based on the measured heat capacities data. Afterward, the long-term cyclic thermal energy storage stability and thermal stability of the PCM were investigated. The results show that the PCM melted and crystallized at about 368 and 364 K, respectively, with a phase change enthalpy (ΔtransH) of 21 kJ mol−1 (130 J g−1). Additionally, it exhibited good long-term cyclic thermal energy storage stability and thermal stability. Hence, the PCM could be applied as good PCM for solar energy absorption cooling.

The m-Erythritol (erythritol, ME)/ D -mannitol (mannitol, DM) binary system was investigated by differential scanning calorimetry (DSC), and the phase diagram was then obtained. It was found that the eutectic composition was at the mole fraction of erythritol xME = 0.87. The latent heat of fusion (ΔmH) of the eutectic mixture was 322.8 J/g with a peak melting temperature (Tp, m) of 114.4 °C. A cyclic DSC experiment revealed that the ΔmH of the eutectic mixture slightly decreased, and the Tp, m remained stable over 50 DSC cycles. Exfoliated graphite (EG) was then applied to absorb the eutectic mixture to obtain the EG/eutectic composite form-stable phase change material (PCM) and enhance its thermal conductivity. Good form stability could be obtained when the loading of EG in the EG/eutectic composite reached 2.0 wt%. The thermal conductivity of the eutectic mixture was greatly enhanced by EG. When the loading of EG was 10.0 wt%, the thermal conductivity increased by 408% compared to that of the eutectic mixture. Additionally, severe supercooling of the eutectic mixture was also greatly alleviated by EG. The best result was obtained when 3.0 wt% EG was added, for which the degree of supercooling (ΔT) was 62.6 °C and the heat of crystallization (ΔcrH) was 185.7 J/g. X-ray diffraction (XRD) experiments revealed that the eutectic mixture was simply a physical mixture of erythritol and mannitol. Thermal gravimetry (TG) investigations showed that the eutectic mixture and the EG/eutectic composite form-stable PCM exhibited good thermal stability for its applications.

In this study, the microstructural characteristic, electrochemical behavior and discharge performance of extruded Mg-xBi (x = 0.5, 1.0 and 2.0 wt%) anodes are systematically evaluated. The results show that the cell voltage and anodic efficiency deteriorate as the Bi addition increased in galvanostatic discharge process. In addition, intermittent discharge behavior also confirms that the Mg-0.5Bi anode can output both excellent discharge activity and stable discharge process than the counterpart ones. This is attributed to the negative open current potential (OCP) value and thin and loose discharge products film as well as mitigated “chunk effect” (CE). Therefore, extruded Mg-0.5Bi alloy is a promising anode material for Mg-air battery.