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Background: Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine. Methods: We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine. Results: Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21308 (30.2%) received codeine and 49299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00). Interpretation: Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery., Opioids are commonly prescribed to treat pain after childbirth, but the amount prescribed often far exceeds what is taken. (1,2) In Ontario, about 40% of people who give birth fill [...]

•The studied structures show excellent structural stability.•Hydrogenation and fluorination can increase the band gap of DB-Silicene.•The DB-SiH/DB-SiF heterostructures exhibit type-II band arrangement.•The DB-SiH/DB-SiF heterostructures show enhanced visible light absorption.

Pancreatic cancer ranks fourth among cancer-related deaths with a low 5-year overall survival rate of less than 13%. At present, treatment of pancreatic cancer is still based on chemotherapy, but the efficacy is limited. Thus, a novel therapeutic agent for pancreatic cancer therapy is urgently needed. A library of compounds was screened, and YKL-06-061, a selective inhibitor of salt-inducible kinases (SIKs), was discovered for its ability of inhibiting the proliferation and metastasis of pancreatic cancer cells in vitroand reducing the growth of xenografts in nude mice in vivo. The results from transcriptome analysis showed that YKL-06-061 influenced the mRNA levels of many genes related to c-Myc and SIK1 signals. Based on this, it was found that YKL-06-061 induced cell cycle arrest at the G1 phase and decreased the levels of c-Myc, CDK4, and cyclin D1 protein. At the same time, YKL-06-061 inhibited invasion and metastasis of cancer cells, increased the levels of SIK1 and E-cadherin protein, and lowered vimentin and ZEB-1. Moreover, YKL-06-061 effectively enhanced the antiproliferation of gemcitabine or doxorubicin in pancreatic cancer cells in a synergistic manner. Collectively, these findings implicate YKL-06-061 as a promising therapeutic agent for patients with pancreatic cancer.

Endometrial cancer has the second highest incidence of malignant tumors in the female reproductive system. Accurate and efficient analysis of endometrial cancer pathology images is one of the important research components of computer-aided diagnosis. However, endometrial cancer pathology images have challenges such as smaller solid tumors, lesion areas varying in morphology, and difficulty distinguishing solid and nonsolid tumors, which would affect the accuracy of subsequent pathologic analyses. An Endometrial Cancer Multi-class Transformer Network (ECMTrans-net) is therefore proposed herein to improve the segmentation accuracy of endometrial cancer pathology images. An ECM-Attention module can sequentially infer attention maps along three separate dimensions (channel, local spatial, and global spatial) and multiply the attention maps and the input feature map for adaptive feature refinement. This approach may solve the problems of the small size of solid tumors and similar characteristics of solid tumors to nonsolid tumors and further improve the accuracy of segmentation of solid tumors. In addition, an ECM-Transformer module is proposed, which can fuse multi-class feature information and dynamically adjust the receptive field, solving the issue of complex tumor features. Experiments on the Solid Tumor Endometrial Cancer Pathological (ST-ECP) data set found that performance of the ECMTrans-net was superior to state-of-the-art image segmentation methods, and the average values of accuracy, Mean Intersection over Union, precision, and Dice coefficients were 0.952, 0.927, 0.931, and 0.901, respectively.

Asymmetric catalysis involving a sulfoxide electrophile intermediate presents an efficient methodology for accessing stereogenic-at-sulfur compounds, such as sulfinate esters, sulfinamides, etc., which have garnered increasing attention in modern pharmaceutical sciences. However, as the aza-analog of sulfoxide electrophiles, the asymmetric issues about electrophilic sulfinimidoyl species remain largely unexplored and represent a significant challenge in sulfur stereochemistry. Herein, we exhibit an anionic stereogenic-at-cobalt(III) complex-catalyzed asymmetric synthesis of chiral sulfinamides via chiral sulfinimidoyl iodide intermediates. Mechanistic investigations reveal that the catalytic cycle is initiated by asymmetric oxidative iodination, generating sulfinimidoyl iodides. These active intermediates subsequently undergo an enantiospecific nucleophilic substitution with water, affording a diverse array of enantioenriched sulfinamides. Notably, these sulfinamides exhibit promising antifungal activities against Sclerotinia sclerotiorumand serve as ideal platform molecules facilitating the stereospecific transformation into various stereogenic aza-sulfur compounds.

Metal–organic frameworks (MOFs) with adjustable structures, diverse chemical functionalities, and excellent CO2capture ability have shown important potential application in the photocatalytic reduction of CO2to valuable fuel to curb the energy crisis. In this work, a series of new isostructural lanthanide-organic frameworks based on hexanuclear {Ln6O8} clusters, {(DMA)2[Ln6(μ3–OH)8(H2O)6(SBTC)3]}n(Ln-MOFs, Ln = Eu, Dy, Gd, Tb, Yb; H4SBTC = 5,5′-(ethene-1,2-diyl) di-isophthalic acid; DMA = dimethylamine cation) were synthesized by the solvothermal method. Ln-MOFs were metal–organic frameworks formed by {Ln6(μ3–OH)8} clusters and poly(carboxylic acid) ligands H4SBTC, which exhibited excellent photocatalytic properties for the reduction of CO2to CO. Among these Ln-MOFs, the production rate of photocatalytic reduction of CO2to CO by Eu-MOFwas 663.00 μmol·h–1·g–1and the selectivity reached 94.2%, utilizing [Ru(bpy)3]Cl2·6H2O as photosensitizers. Experimental characterizations and density functional theory (DFT) calculations unveiled that the effective charge separation, strong CO2binding affinity, weak H2O adsorption energy, as well as low reaction energy barriers for the *COOH intermediates over Eu-MOFplay an important role in possessing superior photoactivity. This study provides insights into the field of Ln-MOF materials for efficient photocatalytic CO2reduction and conversion applications.

Spontaneous Achilles tendon rupture (SATR) predominantly affects middle-aged and elderly individuals with chronic injuries. However, the exact cause and mechanism of SATR remain elusive, and potential therapeutic intervention or prevention is still insufficient. The present study aimed to uncover the key pathological molecules by using iTRAQ proteomics. The results identified 2432 candidate proteins in SATR patients using iTRAQ proteomic analysis. A total of 307 differentially expressed proteins (DEPs) were identified and linked to 211 KEGG signaling pathways including Coronavirus disease (COVID-19), focal adhesion, and ribosomes. GO enrichment analysis highlighted significant enrichment in processes such as biological adhesion, ossification, lipid (APOA4) processes, and extracellular matrix (ECM) organization (collagen). PPI network analysis identified hub genes such as serum albumin (ALB), fibronectin (FN1), and actin cytoplasmic 1. The WB analysis confirmed that FN1 and the receptor for activated C kinase (RACK1) were downregulated in the SATR tendon. Immunohistochemical staining revealed that collagen I and III were suppressed, while collagen II and APOA4 expression were higher in the SATR pathological tissue (P< 0.05). However, the primary cultured tenocytes (PCTs) from SATR patients showed enhanced proliferation and, consistent with tissue staining, reduced collagen I and III and increased collagen II. Our findings reveal vital targets and pathways in SATR’s etiological progression, offering a new perspective on the diagnosis, treatment, and prognosis of this complex disorder.

The transcription factor STAT3 is a promising target for the treatment of non-small cell lung cancer (NSCLC). STAT3 activity is mainly dependent on phosphorylation at tyrosine 705 (pSTAT3-Y705), but the modulation on pSTAT3-Y705 is elusive. By screening a library of deubiquitinases (Dubs), we found that the Otub1 increases STAT3 transcriptional activity. As a Dub, Otub1 binds to pSTAT3-Y705 and specifically abolishes its K48-linked ubiquitination, therefore preventing its degradation and promoting NSCLC cell survival. The Otub1/pSTAT3-Y705 axis could be a potential target for the treatment of NSCLC. To explore this concept, we screen libraries of FDA-approved drugs and natural products based on STAT3-recognition element-driven luciferase assay, from which crizotinib is found to block pSTAT3-Y705 deubiquitination and promotes its degradation. Different from its known action to induce ALK positive NSCLC cell apoptosis, crizotinib suppresses ALK-intact NSCLC cell proliferation and colony formation but not apoptosis. Furthermore, crizotinib also suppresses NSCLC xenograft growth in mice. Taken together, these findings identify Otub1 as the first deubiquitinase of pSTAT3-Y705 and provide that the Otub1/pSTAT3-Y705 axis is a promising target for the treatment of NSCLC.

Background: The impact of postoperative sarcopenia on the Textbook Oncological Outcome (TOO) in locally advanced gastric cancer (LAGC) remains uncertain. This study investigates the relationship between sarcopenia and TOO, explores its long-term prognostic value, and develops a prognostic model incorporating sarcopenia and TOO for survival prediction. Methods: We performed a retrospective analysis of clinical and pathological data from patients with LAGC who underwent radical surgery at two Chinese tertiary referral hospitals. Sarcopenia was defined as an SMI &lt; 36.4 cm2/m2in males and &lt; 28.4 cm2/m2in females. TOO was defined as the addition of perioperative chemotherapy to the textbook outcomes (TO). A nomogram was developed to predict postoperative overall survival (OS) and recurrence-free survival (RFS) in LAGC patients. Results: The study included 972 patients with LAGC. The overall TOO achievement rate was 67.1%. The TOO achievement rate was significantly higher in patients non-sarcopenia compared to those with sarcopenia (68.9% vs. 61.1%, P= 0.031). Logistic regression revealed that age ≥ 65, high ASA score, and sarcopenia were independent risk factors for TOO failure. Cox regression analysis identified TOO, sarcopenia, tumor size, differentiation, vascular invasion, pT stage, and pN stage as independent predictors of OS and RFS. Nomogram models based on sarcopenia and TOO accurately predicted the 3-year and 5-year OS and RFS. Conclusion: Preoperative sarcopenia was an independent predictor of TOO implementation. A prognostic prediction model that integrates preoperative sarcopenia and TOO, which outperforms the current staging system, can aid clinicians in effectively assessing the prognosis of patients with LAGC.

This is a case report of a COL4A1gene mutation which was confirmed by further genetic testing following anomalies observed in prenatal ultrasound and fetal brain magnetic resonance imaging (MRI).

Exploring the effectiveness and safety of n-butyl-2-cyanoacrylate (NBCA) in the transarterial embolization for common endoleak during and after endovascular repair of aortic aneurysm (EVAR).

Manganese single atoms implanted in nitrogen-doped porous carbon nanosheets, featuring Mn–N structures and abundant charge storage sites, have been developed as a cathode in zinc ion hybrid capacitors, exhibits remarkable electrochemical performance.

Based on our previous studies, the reconstruction of interlayer edges of black phosphorene (BP) is identified as a key factor impeding the growth of large-size BP films through the CVD method. In this study, we systematically explore the complex growth mechanisms of BP, specifically focusing on how edge reconstruction influences the growth of BP. The results reveal that BP with reconstructed edges is highly stable. Growth necessitates initially opening a unit at the reconstructed edge, requiring a higher energy barrier than that of pristine BP without reconstructed edges. Despite this challenge, overcoming it facilitates subsequent phosphorus atom additions, thereby promoting favorable growth conditions for reconstructed-edge BP. Overall, our research highlights the interplay between edge reconstruction and BP growth dynamics, offering insights for the rational design and synthesis of large-area, high-quality monolayer BP, thus advancing its potential in electronic and optoelectronic applications.

Inspired by our previous finding that targeting the 150-cavity with a multisite-binding strategy emerged as an effective approach to obtain more potent and selective neuraminidase (NA) inhibitors against influenza virus, we present here the design, synthesis, and optimization of novel boron-containing N-substituted oseltamivir (OSC) derivatives. Exploratory structure–activity relationship (SAR) studies led to the identification of compounds 27cand 33cas the most potent NA inhibitors, surpassing OSC in potency against both wild-type group-1 NAs and oseltamivir-resistant NAs. These compounds demonstrated significant antiviral activity against several wild-type strains and H1N1pdm09 strains (EC50= 0.03 ± 0.005 and 0.03 ± 0.0008 μM, respectively). Additionally, these compounds did not exhibit significant toxicity (CC50> 200 μM in CEF cells; CC50> 250 μM in MDCK cells). These findings highlight 27cand 33cas promising next-generation anti-influenza agents.

Natural images often contain multiple shadow regions, and existing video shadow detection methods tend to fail in fully identifying all shadow regions, since they mainly learned temporal features at single-scale and single memory. In this work, we develop a novel convolutional neural network (CNN) to learn motion-guided multi-scale memory features to obtain multi-scale temporal information based on multiple network memories for boosting video shadow detection. To do so, our network first constructs three memories (i.e., a global memory, a local memory, and a motion memory) to combine spatial context and object motion for detecting shadows. Based on these three memories, we then devise a multi-scale motion-guided long-short transformer (MMLT) module to learn multi-scale temporal and motion memory features for predicting a shadow detection map of the input video frame. Our MMLT module includes a dense-scale long transformer (DLT), a dense-scale short transformer (DST), and a dense-scale motion transformer (DMT) to read three memories for learning multi-scale transformer features. Our DLT, DST, and DMT consist of a set of memory-read pooling attention (MPA) blocks and densely connect these output features of multiple MPA blocks to learn multi-scale transformer features since the scales of these output features are varied. By doing so, we can more accurately identify multiple shadow regions with different sizes from the input video. Moreover, we devise a self-supervised pretext task to pre-training the feature encoder for enhancing the downstream video shadow detection. Experimental results on three benchmark datasets show that our video shadow detection network quantitatively and qualitatively outperforms 26 state-of-the-art methods.

IMPORTANCE: Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. OBJECTIVE: To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. RESULTS: Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. CONCLUSION AND RELEVANCE: The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Recently, intelligent reflecting surface (IRS) has received significant attention due to its ability to smartly reconfigure the wireless environment. However, in practical implementation, the power consumption of the conventional IRS could be prohibitive with the large number of reflecting elements and control circuits employed. To tackle this problem, in this letter, we propose a green heterogeneous-IRS (HE-IRS) structure consisting of both dynamically tunable elements (DTEs) and statically tunable elements (STEs). Compared to the conventional IRS comprising only DTEs, the HE-IRS provides a better trade-off between performance and power consumption by integrating power-free STEs. To show the efficiency of the proposed HE-IRS, we apply it in a multi-input multi-output system and formulate a joint base station precoding, HE-IRS beamforming and user equipment (UE) decoding optimization problem. Furthermore, we propose a two-stage algorithm to solve it. Simulation results show that with the prior information of the UE location area, the HE-IRS can achieve a competitive spectral efficiency as that of the conventional IRS but with much lower power consumption.

Smart structures realize sequential motion and self-assembly through external stimuli. With the advancement of four-dimensional (4D) printing, the programming of sequential motions of smart structures is endowed with more design and manufacturing possibilities. In this research, we present a method for physically programming the timescale of shape change in 4D-printed bilayer actuators to enable the sequential motion and self-assembly of smart structures. The effects of the geometric and printing parameters on the time-dependent behavior of 4D-printed bilayer actuators are investigated. The results show that the thickness of the active layer directly affects the timescale of motion, and increasing the thickness leads to faster motion until the thickness ratio is close to 4:6. Similarly, a higher printing speed results in faster motion. Conversely, a higher printing temperature and a greater layer height result in a slower shape change. The effects of the length-width ratio, line width, and filling ratio on the timescale of motion are not as straightforward. Finally, we demonstrate several smart structures that exhibit sequential motion, including a labyrinth-like self-folding structure that is choreographed to achieve multi-step self-shaping and a flower-shaped structure where each part completes its movement sequentially to avoid collisions. The presented method extends the programmability and functional capabilities of 4D printing.

The microstructure of electrodes significantly affects the performance of lithium-ion batteries (LiBs), and using bi-diameter active particles is a simple but effective way to regulate the microstructure of commercial LiB electrodes. Herein, to optimize the LiB cathode of bi-diameter active particles, a microstructure-resolved model is developed and validated. The results indicate that randomly packing of bi-diameter active particles is optimal when the electrolyte diffusion limitation is mild, as it provides the highest volume fraction of active materials. Under strong electrolyte diffusion limitations, layered packing with small particles near the separator is preferred. This is because particles near the current collector have a low lithiation state. Besides, optimizing the random packing can further improve the energy density. For energy-oriented LiBs, a low volume fraction of small particles (0.2) is preferred due to the higher volume fraction of active materials. For power-oriented LiBs, a high volume fraction of small particles (0.8) is better because it reduces diffusion limitations. This work should serve to guide the optimal design of electrode microstructure for achieving high-performance LiBs.

Tiller number and grain size are important agronomic traits that determine grain yield in rice. Here, we demonstrate that DEFECTIVE TILLER GROWTH 1 (DTG1), a member of the casein kinase 1 protein family, exerts a co-regulatory effect on tiller number and grain size. We identified a single amino acid substitution in DTG1 (I357K) that caused a decrease in tiller number and an increase in grain size in NIL-dtg1. Genetic analyses revealed that DTG1 plays a pivotal role in regulation of tillering and grain size. The DTG1I357Kallelic variant exhibited robust functionality in suppressing tillering. We show that DTG1is preferentially expressed in tiller buds and young panicles, and negatively regulates grain size by restricting cell proliferation in spikelet hulls. We further confirm that DTG1 functioned in grain size regulation by directly interacting with Grain Width 2 (GW2), a critical grain size regulator in rice. The CRISPR/Cas9-mediated elimination of DTG1significantly enhanced tiller number and grain size, thereby increasing rice grain yield under field conditions, thus highlighting potential value of DTG1in rice breeding.

As the most readily accessible N-heterocyclic carbenes (NHCs), imidazolium carbenes have traditionally been ruled out for the design of TADF coinage metal carbene–metal–amine (CMA) complexes due to their high-lying unoccupied π orbitals, which lead to a dark interligand charge transfer (ICT) state. In this work, in cooperation with strong electron-donating acridine ligands, a series of CMAcomplexes featuring imidazolium carbenes are prepared, exhibiting desired blue thermally activated delayed fluorescence (TADF) with high photoluminescent (PL) quantum yields (ΦPL) close to unity and emission decay lifetimes as short as 1.0 μs. The small energy differences between S1and T1(ΔEST) of around 100 meV and the high radiative decay rates of S1on the order of 1 × 107–108s–1contribute to the decent TADF behavior. Solution-processed blue OLEDs based on the Cu(I) emitter show an external quantum efficiency (EQE) exceeding 8.0%, demonstrating the practicality of using imidazolium carbenes in the design of TADF CMAluminophores.

•aMCD belongs to HHV-8–negative MCD, which might be a potential early stage of iMCD.•Patients with aMCD do not need immediate treatment but should be closely monitored.

Hund’s rule, which is powerful in governing the first excited states of closed-shell organic materials, can hardly be violated to get inverted singlet–triplet gap (INVEST) molecules with negative singlet–triplet energy gaps (ΔEST), although INVEST materials have shown extraordinary photophysical properties and promising device performance especially in light-emitting diodes. Here, we propose a facile strategy to construct emissive INVEST molecules by introducing different types of substituents to heptazine in various modes, which can effectively tune the ΔESTto be negative with the enlarged oscillator strength (f) for the high fluorescence rate of the heptazine derivatives. Systematic computational studies show that the double substitution of electron-donating units with another nonconjugated substituent in hybrid substitution mode is the most favorable way in achieving slightly negative ΔESTand large fvalues; the conjugated substituent will compete with heptazine to make the molecule deviate from the INVEST feature. Especially, a series of high-performance heptazine-based INVEST emitters were constructed, exhibiting ΔESTlow to −0.362 eV, fup to 0.0436, as well as a wide range emission color from 339 to 716 nm. Also, the designed molecules were predicted to have fluorescence radiative rates up to 106s–1, along with efficient reverse intersystem crossing rates reaching 108s–1. Importantly, the figure of merit (FM) was first proposed as a parameter to wholly evaluate the performance of INVEST emitters, and the highest FM of 0.198 was found in the triazine and double nonconjugated amine-substituted heptazine. These results highlight the great potential of the heptazine chromophore in constructing INVEST emitters, revealing fundamental structure–property understandings for the material design of efficient anti-Hund organic molecules with improved emission properties.

In this study, we introduced a novel approach by using natural calcium phosphate-based ceramic whitlockite as the matrix, natural silicon-based ceramic wollastonite fiber as the secondary phase, and desktop-level DLP 3D printing as the fabrication method to develop an all-natural ceramic porous bone scaffold with excellent mechanical, degradable, biomineralization, and cell responses. The results demonstrated that, at a solid loading of 75 wt% and a sintering temperature of 1000 °C, the compressive strength of the whitlockite porous scaffold reached 20.0 MPa. With the incorporation of wollastonite fiber, the compressive strength of the composite ceramic scaffold further increased to 31.0 MPa, achieving a top-tier level for desktop-level DLP-printed porous ceramic bone scaffolds. This mechanical enhancement effect was mainly attributed to the grain refinement effect of WF on whitlockite and the fiber reinforcement effect of WF. Additionally, the degradation rate of the composite ceramic scaffold increased with higher WF content, attributed to the rapid degradation rate of WF and the microstructural changes in the whitlockite matrix induced by WF doping. Furthermore, the biomineralization capability and cellular response of the composite ceramic scaffold were enhanced with WF doping, due to the improved degradation ability promoting the release of calcium, phosphate, and silicon ions. This study further validates the applicability of desktop-level DLP for fabricating ceramic bone scaffolds and provides evidence of the potential of all-natural ceramic whitlockite/WF as bone scaffold materials.

In the context of new energy vehicles, it is common for the compressor to be directly powered by an electric motor. However, the demanding operational circumstances frequently lead to substantial variations in motor speed. This work presents a novel approach for the speed control system of air conditioning compressors, which involves the utilization of a virtual unmodeled dynamics robust predictive control with time-delay compensation. The initial step involves analyzing the conversion mechanism between the angular velocity of the compressor and the duty ratio, while considering the delay effects resulting from inertia. Subsequently, a state space model is constructed, incorporating unmodeled dynamics. In addition, in light of the uncertain attributes of the unmodeled dynamics, a signal processing function is formulated for the unmodeled dynamics through a time compensation data strategy and an interval differential compensation strategy. Furthermore, a robust predictive controller with time delay and unmodeled dynamics compensation techniques is presented. This controller integrates an unmodeled dynamics time compensation unit and a differential compensation unit, utilizing adaptive backstepping control design techniques. Namely, the control signal is compensated using the unmodeled dynamics signal processing function. The effectiveness and feasibility of the suggested technique are evaluated by simulation and real operation on an air conditioning system platform.

In most existing results, event-triggered controllers are designed based on the backstepping design approach for uncertain strict-feedback nonlinear systems (SFNSs). However, the transmitted signals in the event-triggered scheme (ETS) are discontinuous, which makes the repetitive differentiation of virtual control signals undefined. To overcome this deficiency, this article designs an event-triggered adaptive controller for uncertain SFNSs based on the fully actuated system (FAS) approach. Since the system states and the adaptive parameters are only updated at each triggering instant, the original dynamics cannot be completely removed by using the FAS approach, leading to that the asymptotic stability of the control system is difficult to be guaranteed. To handle such a problem, an ETS with the adaptive parameters is constructed based on Lyapunov method to compensate the effect of triggering. As a result, the asymptotic stability of the system can be guaranteed in the presence of nonlinearities without the global Lipschitz condition, and Zeno behavior can be avoided by using the contradiction method. Furthermore, a positive lower bound for interevent intervals can be got by adding a constant into the ETS, which ensures that the system is practically stabilizable under the bounded nonlinearities. Finally, two simulation examples are presented to demonstrate the superiority and effectiveness of the proposed approach.

CO2-based carbon-neutral organics production processes could potentially reshape the chemical industry. However, their feasibility and net carbon footprint rely strongly on the sources of H2. Herein, we present a comprehensive comparative techno-economic analysis of CO2-based methanol (CO2TM) and α-olefins (CO2TO) manufacturing using various feedstock supply modes: (1) the standalone mode with external CO2but H2from on-site water electrolysis, (2) the integrated mode with both CO2and H2recovered from coal-chemical plants, and (3) the integrated mode with recycled CO2but H2from on-site water electrolysis. The integration of CO2TM and CO2TO into coal-to-olefins (CTO) and coal-to-methanol (CTM) facilities is currently cost-effective and can reduce net CO2emissions by 65.7% and 68.5%, resulting in a three-fold and two-fold increase in carbon efficiency, respectively. As carbon tax policies and electrolysis technologies continue to evolve, standalone CO2TM and CO2TO are projected to become more economically competitive than CTO and CTM by 2035–2045.

ABSTRACTImmune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings.

A novel S-scheme 2D/2D boron-doped nitrogen-deficient g-C3N4/ZnIn2S4(BDCNN/ZnIn2S4) heterojunction was successfully fabricated via the in-situ assembly of ZnIn2S4onto BDCNN in an oil bath. To assess the quality and characteristics of the synthesized photocatalysts, a comprehensive range of characterizations were conducted. The innovative S-scheme 2D/2D BDCNN/ZnIn2S4heterojunction, equipped with a deliberately established inter-built electric field, facilitates rapid electron transfer and enhanced separation efficiency of photo-induced carriers. Consequently, this heterojunction demonstrates remarkable enhancements in both H2production and TC degradation under visible-light illumination (λ > 420 nm). The optimized BDCNN/ZnIn2S4heterojunction exhibited impressive photocatalytic performance, achieving a promising H2evolution rate of 2378.8 μmolg−1h−1and a high degradation efficiency exceeding 90 % (k = 0.021 min−1) for TC. This noteworthy improvement in photocatalytic performance is primarily attributed to the synergistic effects of boron-doping and nitrogen-defects within BDCNN, coupled with the unique S-scheme photocatalytic mechanism inherent to the BDCNN/ZnIn2S4heterojunction. Overall, this study introduces a groundbreaking approach for constructing 2D/2D g-C3N4-based heterojunctions that exhibit exceptional visible-light photocatalytic capabilities, thereby offering significant potential for various photocatalytic applications.

Nitrogen-doped carbon frameworks with atomically dispersed Co sites derived from metal-organic framework as activation and protection building blocks for nano silicon in LIBs.

Iodate reduction by dissimilatory iodate-reducing microorganisms (DIRMs) plays a crucial role in the biogeochemical cycling of iodine on Earth. However, the occurrence and distribution of DIRMs in iodine-rich groundwater remain unclear. In this study, we isolated the dissimilatory iodate-reducing bacteriumAzonexus hydrophilusstrain NCP973 from a geogenic high-iodine groundwater of China for the first time. The analysis of genome, transcriptome, and heterologous expression revealed that strain NCP973 uses the dissimilatory iodate-reducing enzyme IdrABP1P2 to reduce dissolved or in situ sediment-bound iodate to iodide. The location of IdrABP1P2 in the conjugative plasmid of strain NCP973 implies that IdrABP1P2 could be spread by horizontal gene transfer and allow the recipient microorganisms to participate in the enrichment of iodide in aquifers. Based on the global iodine-rich groundwater metagenomes and genomes, the identification of idrAshowed that phylogenetically diverse DIRMs are widely distributed not only in geogenic high-iodine groundwater of China but also in radionuclide-contaminated groundwater of USA as well as in subsurface cavern waters in Germany and Italy. Moreover, the abundance of idrAwas found to be higher in groundwater with a relatively high iodine content. Collectively, these results suggest that terrestrial iodine-affected groundwater systems are another important habitat for DIRMs in addition to marine environments, and their activity in aquifers triggers the mobilization and enrichment of iodine in groundwater worldwide.

n-Pentanol is acknowledged as a prospective alternative and a supplement to traditional fossil fuels. H-abstraction reaction assumes a pivotal role in initiating the chain reaction during n-pentanol combustion. To investigate the oxidation characteristics of n-pentanol, the composite quantum chemical methods CBS-QB3 and G4 are employed to obtain thermochemical and kinetic parameters in the H-abstraction reaction of n-pentanol. The calculated isobaric heat capacity provides accurate predictions of the experimental results. Branching ratios underscore that H-abstraction at the Cαsite serves as the primary channel between n-pentanol and Ḣ/ĊH3/ȮH2. For the reaction between n-pentanol and ȮH, the Cβsite emerges as the most favorable channel due to the significant variational effect. The overall rate coefficient for H-abstraction from n-pentanol by ȮH radicals is expressed as k= 3565.11 × T2.93exp (1465.44/T) (cm3mol–1s–1), and the data obtained at the CBS-QB3 level demonstrate good agreement with experimental observations. Furthermore, the original model is modified based on current results, and the improved model demonstrates superior predictive capabilities for jet-stirred reactor (JSR) data and ignition delay times. Reaction path and sensitivity analyses are employed to identify fuel consumption pathways and critical reactions in the combustion of n-pentanol.

A novel integrated approach to remove the free alkalis and stabilize solid-phase alkalinity by controlling the release of Ca from desulfurization gypsum was developed. The combination of recycled FeCl3solution and EDTA activated desulfurization gypsum lowered the bauxite residue pH to 7.20. Moreover, it also improved the residual Ca state, with its contribution to the total exchangeable cations increased (68%−92%). Notably, the slow release of exchangeable Ca introduced through modified desulfurization gypsum induced a phase transition of the alkaline minerals. This treatment stabilized the dealkalization effect of bauxite residue via reducing its overall acid neutralization capacity in abating pH rebound. Hence, this approach can provide guidance for effectively utilizing desulfurization gypsum to achieve stable regulation of alkalinity in bauxite residue.

Eyeglass reflection removal is of great importance to the portrait image processing. However, it remains a challenge to eliminate the reflections on the glass and restore the textual contents of eyes without introducing visual artifacts. Addressing this problem, in this paper, we propose an Eyeglass Reflection Removal Network (ER2Net) by learning reflection elimination and content inpainting jointly. The reflection elimination branch is effective in weak reflection regions, and the content inpainting branch is dedicated to content reasoning in strong reflection regions. We then propose a result fusion module (RFM), which adaptively fuses the elimination result and the inpainting result according to the reflection intensity of each pixel, to produce high-quality result. We also design a memory module for improving the content inpainting result, and propose an eye-symmetry loss to avoid visual artifacts. Additionally, we construct the first Real-world eyeglass Reflection (ReyeR) dataset for eyeglass reflection removal. Extensive quantitative and qualitative experiments demonstrate the superiority of the ER2Net over state-of-the-art methods for eyeglass reflection removal.

Mobile Edge Computing (MEC) has envisioned to be a promising technology to provide more efficient services for computation-intensive but delay-sensitive onboard mobile services. In this paper, the Non-Orthogonal Multiple Access (NOMA) technology is applied in a vehicular edge computing network, in which vehicular users (VUs) can offload partial computation tasks to MEC servers over wireless channels for remote execution. In this network, an optimization problem for the long-term energy consumption of the system is presented and aims to minimize it by jointly optimizing the Successive Interference Cancellation (SIC) ordering of NOMA, the VUs’ transmit power for computation offloading, and computation resource allocation of the MEC server. To deal with the intractable long-term optimization problem, we first transform it into an equivalent instantaneous form based on the Lyapunov optimization theory. Since the transformed problem is still highly non-convex, we further decompose it into the interactive resource allocation and SIC ordering sub-problems. For the resource allocation sub-problem, we exploit its convexity through the transformation and reparameterization, and derive the optimal solution in accordance with the Karush-Kuhn-Tucker (KKT) conditions and the gradient descent algorithm. After that, we propose a low-complexity algorithm by leveraging the Tabu search to obtain the sub-optimal SIC ordering. Simulation results validate the effectiveness of the proposed algorithm and the superiority of NOMA compared to Frequency Division Multiple Access (FDMA).

This article investigates the high-performance position control of servo systems based on high-order fully actuated (HOFA) approach with dynamical compensator and extended state observer (ESO). In the proposed control approach, the dynamics of servo systems is formulated via an HOFA model, in which the electrical subsystem is approximated to an inertia system by using the first-order Taylor expansion and the truncated method. Based on the HOFA model, a composite control law is synthesized to achieve the desired tracking error dynamics, and dynamical compensator is applied to offer additional design degrees of freedom for the control performance improvement. To cope with uncertainties and disturbances, a linear ESO is designed for online state estimation and disturbance compensation. The proposed approach can explicitly solve the control gains in an extremely straightforward and simple way. This brings a great convenience for the control system design, analysis and implementation. Experimental results on a servo motor system validate the superior performance of the proposed controller over some of the-state-of-art methods.

A rice low temperature-induced albino variant was determined by the recessive ltia1and ltia2genes. LTIA1and LTIA2encode highly conserved mini-ribonucleases III located in chloroplasts and expressed in aerial parts of the plant. At low temperature, LTIA1and LTIA2redundantly affect chlorophyll levels, non-photochemical quenching, photosynthetic quantum yield of PS II and seedling growth. LTIA1 and LTIA2 proteins are involved in splicing of atpFand the biogenesis of 16S and 23S rRNA in chloroplasts. Presence/absence variation of LTIA1, the ancestral copy, was found only in japonicabut that of LTIA2in all rice subgroups. Accessions with LTIA2presence tended to be distributed more remote from the equator compared to those with LTIA2absence. LTIA2duplicated from LTIA1at the early stage of divergence of the AA genome Oryzaspecies but deleted againin O. nivara. In cultivated rice, absence of LTIA2is derived from O. nivara. LTIA1absence occurred more recently in japonica.

Stability of marine electric fields measurements is a problem of broad interest in relation to long-term in situ observations, especially in the construction of the Internet of Underwater Things (IoUT), geological exploration, and disaster monitoring. The root of this problem is the drift in electrode potential caused by imbalances in the electrodes’ electrical processes, which are unavoidable in potential-difference measurements based on the conduction current. Here, we propose the variable dielectric polarization (VDP) measurement method, which uses the variation of a dielectric between the electrodes to measure the external electric field. This method modulates the electric field signal to higher frequencies, allowing separation of the signal from the output by demodulation. This not only separates the signal from low-frequency noise, but it also increases the measurement sensitivity by frequency boosting. The results of our experiments show that the VDP system we constructed has a measurement sensitivity of 2.63 V/(V/m) and a measurement resolution of $22.4~\mu $ V/m. Under long-term measurements, the measured drift of the VDP system (106 ( $\mu $ V/m)/day) was found to be only 1/320 of the self-potential (SP) method (34 (mV/m)/day). The proposed VDP method, thus, provides a new approach to the construction of future IoUT devices and the prediction of marine disasters.

A microwave photonic phase detector (MPPD) shows notable advantages in terms of low phase noise, long-term stability, and high power when extracting a microwave signal from a mode-locked laser (MLL). However, the occurrence of amplitude-to-phase (AM-PM) conversion during the optical-to-electrical conversion process poses a challenge. This conversion, where intensity noise or relative intensity noise (RIN) couples to the phase noise of the generated microwave, significantly degrades the purity of the resulting signal. While experimental investigations on suppressing AM-PM conversion in MPPDs have been conducted, a specific theoretical model to AM-PM conversion in an MPPD has not been established. In this study, a comprehensive mathematical model is established to reveal the mechanism of the AM-PM suppression in an MPPD. The proposed model is validated through simulations and experimental verification. The impact of different intensity noise waveforms is also explored for the first time. The results indicate a remarkable suppression of AM-PM conversion, with suppression levels of 113 dB for sine-RIN, 95 dB for sweep-signal-RIN, and 74 dB for white-noise-RIN, representing a significant improvement over previous studies. Such enhanced AM-PM suppression positions a MPPD as a prior candidate for synchronization in advanced scientific instruments. This work not only contributes to the development of the theory of optical-RF phase locking but also provides practical guidance for utilizing MPPDs in scientific instruments.

We sought to evaluate urate‐lowering therapy (ULT) adherence and treatment‐to‐target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT. We performed a population‐based retrospective cohort study in Ontario, Canada in patients with gout aged ≥66 years newly dispensed ULT between 2010 and 2019. We defined successful T2T as patients having SUA levels <360 μmol/L (6 mg/dL) within 12 months after ULT dispensation. We also assessed adherence to ULT. Multilevel logistic regression clustered by ULT prescriber evaluated patient, physician, and prescription factors associated with reaching target SUA levels. Among 44,438 patients (mean ± SD age 76.0 ± 7.3 years; 64.4% male), 30,057 (67.6%) patients had ≥1 SUA test completed. Overall, 52.3% patients reached SUA target within 12 months, improving from 45.2% in 2010 to 61.2% in 2019 (P< 0.0001). ULT adherence was 55.3% overall and improved annually. Key factors associated with achieving T2T included febuxostat treatment (odds ratio [OR] 11.40, 95% confidence interval [95% CI] 5.10–25.43) (was only dispensed in 88 patients), ULT adherence (OR 5.17, 95% CI 4.89–5.47), allopurinol starting doses >50 mg (OR 2.53, 95% CI 2.14–2.99), colchicine/oral glucocorticoids co‐prescription (OR 1.24, 95% CI 1.14–1.34), and ULT prescription from a rheumatologist. Only 52.3% of patients achieved an optimal SUA level within 1 year of ULT initiation. ULT adherence was suboptimal, although improving over time. ULT adherence and higher allopurinol starting doses had the strongest associations of achieving a target SUA level. This study highlights room for improvement in gout management and potential strategies to address care gaps.

Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1–Stat1–importin α–Nlrc5 pathway, enabling BrMs to avoid recognition by T cells. Treatment with roscovitine—a clinically applicable Cdk5 inhibitor—alone or combined with immune checkpoint inhibitors, significantly reduces BrM burden and increases tumour-infiltrating functional CD8+lymphocytes in mice. Thus, astrocyte-induced Cdk5 overexpression endorses BrM immune evasion, whereas therapeutically targeting Cdk5 markedly improves the efficacy of immune checkpoint inhibitors and inhibits BrM growth.

Being essential in animation creation, colorizing anime line drawings is usually a tedious and time-consuming manual task. Reference-based line drawing colorization provides an intuitive way to automatically colorize target line drawings using reference images. The prevailing approaches are based on generative adversarial networks (GANs), yet these methods still cannot generate high-quality results comparable to manually-colored ones. In this article, a new AnimeDiffusion approach is proposed via hybrid diffusions for the automatic colorization of anime face line drawings. This is the first attempt to utilize the diffusion model for reference-based colorization, which demands a high level of control over the image synthesis process. To do so, a hybrid end-to-end training strategy is designed, including phase 1 for training diffusion model with classifier-free guidance and phase 2 for efficiently updating color tone with a target reference colored image. The model learns denoising and structure-capturing ability in phase 1, and in phase 2, the model learns more accurate color information. Utilizing our hybrid training strategy, the network convergence speed is accelerated, and the colorization performance is improved. Our AnimeDiffusion generates colorization results with semantic correspondence and color consistency. In addition, the model has a certain generalization performance for line drawings of different line styles. To train and evaluate colorization methods, an anime face line drawing colorization benchmark dataset, containing 31,696 training data and 579 testing data, is introduced and shared. Extensive experiments and user studies have demonstrated that our proposed AnimeDiffusion outperforms state-of-the-art GAN-based methods and another diffusion-based model, both quantitatively and qualitatively.

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitrohypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase–Akt pathway, thus reducing cardiomyocyte damage. Interestingly, lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested that lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, this research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis.

The transcription factor FOXM1, which plays critical roles in cell cycle progression and tumorigenesis, is highly expressed in rapidly proliferating cells and various tumor tissues, and high FOXM1 expression is related to a poor prognosis. However, the mechanism responsible for FOXM1 dysregulation is not fully understood. Here, we show that ABL1, a nonreceptor tyrosine kinase, contributes to the high expression of FOXM1 and FOXM1-dependent tumor development. Mechanistically, ABL1 directly binds FOXM1 and mediates FOXM1 phosphorylation at multiple tyrosine (Y) residues. Among these phospho-Y sites, pY575 is indispensable for FOXM1 stability as phosphorylation at this site protects FOXM1 from ubiquitin-proteasomal degradation. The interaction of FOXM1 with CDH1, a coactivator of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), which is responsible for FOXM1 degradation, is significantly inhibited by Y575 phosphorylation. The phospho-deficient FOXM1(Y575F) mutant exhibited increased ubiquitination, a shortened half-life, and consequently a substantially decreased abundance. Compared to wild-type cells, a homozygous Cr-Y575F cell line expressing endogenous FOXM1(Y575F) that was generated by CRISPR/Cas9 showed obviously delayed mitosis progression, impeded colony formation and inhibited xenotransplanted tumor growth. Overall, our study demonstrates that ABL1 kinase is involved in high FOXM1 expression, providing clear evidence that ABL1 may act as a therapeutic target for the treatment of tumors with high FOXM1 expression.

To determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions.

Anionic nido-carboranes, as open-cage analogues of closo-carboranes with strong hydrophilicity and higher potential in the development of biomedicines, have been notably more challenging because of their strong interaction with transition metals. While the exo-cage B–H activation reactions of nido-carboranes have been widely studied, there are few reports on the direct functionalization of B–H bonds located on a closed polyhedral sphere. Here, we report an efficient palladium-catalyzed regioselective B(2/3)–H alkenylation of nido-carboranes with various alkenes and alkyne coupling partners, enabled by 3-methylpyridine directing groups, to achieve a regiocontrollable functionalization of B(2/3)–H vertices over highly reactive exo-cage B11–H vertex in nido-carboranes.