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Abstract Objective To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). Methods Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. Results Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p

Abstract Corrosion of electrocatalysts during electrochemical operations, such as low potential - high potential cyclic swapping, can cause significant performance degradation. However, the electrochemical corrosion dynamics, including structural changes, especially site and composition specific ones, and their correlation with electrochemical processes are hidden due to the insufficient spatial-temporal resolution characterization methods. Using electrochemical liquid cell transmission electron microscopy, we visualize the electrochemical corrosion of Pd@Pt core-shell octahedral nanoparticles towards a Pt nanoframe. The potential-dependent surface reconstruction during multiple continuous in-situ cyclic voltammetry with clear redox peaks is captured, revealing an etching and deposition process of Pd that results in internal Pd atoms being relocated to external surface, followed by subsequent preferential corrosion of Pt (111) terraces rather than the edges or corners, simultaneously capturing the structure evolution also allows to attribute the site-specific Pt and Pd atomic dynamics to individual oxidation and reduction events. This work provides profound insights into the surface reconstruction of nanoparticles during complex electrochemical processes.

Abstract Background Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF. Method Patients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model. Results A total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH‐ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

[Objective] This study aimeds to explore the water supply and demand dynamics of cropland from a planting structure perspective, achieve multi-objective optimization adjustments, and provide theoretical references for the principles of “allocating land based on water resources” and sustainable utilization of cropland resources. [Methods] Taking the Hengshao Arid Corridor as the research area and supported by various data sources including baseline meteorological data, land use, crop planting, and agricultural socioeconomic data, this study employed a crop water balance evaluation model to intricately reveal the water balance trends and irrigation requirements under diverse planting structures across various climate years from 1980 to 2020. A multi-objective optimization model for cropland planting structure was constructed under different irrigation water demand scenarios, incorporating multiple constraints related to water-land-crop. This led to the identification of optimized strategies for cropland planting structure. [Results] (1) Double-season rice and rapeseed have a more reliable water supply throughout their growth periods compared to single-season rice and maize. Rice demands higher water supply, especially during drought years, where the average water demand for double-season rice reaches as high as 608.29 mm. (2) The spatial distribution of effective precipitation and water demand patterns differs for rice and maize, exacerbating the drought situation in the southeastern part of the study area, whereas the water balance for rapeseed remains favorable. (3) The water deficit is more pronounced for double-season and single-season rice, with average net irrigation water requirements of 303.68 mm and 257.00 mm, respectively. Water supply-demand conflicts for drought-tolerant crops are less prominent, reducing the reliance on agricultural irrigation during the planting management process. (4) After optimization of the planting structure, the comprehensive benefits of cropland production can be significantly improved after setting water-saving targets and achieving optimal regulation, especially that the expected grain yield can be increased by 5.12% under the wet-year water constraints of the weighted scenario 3; and the net tax-reduced income from crop cultivation can be increased by 22.34% under the wet-year water constraints of the weighted scenarios 1 and 2. [Conclusion] The planting structure of the Hengshao Arid Corridor should basically remain unchanged in dry years. In normal years, the area of single-season rice can be appropriately increased and the proportion of dry crop planting can be reduced. In humid years, the planting area of grain crops can be significantly increased and the area of rapeseed can be reduced to improve the comprehensive benefits of cropland planting.

Refractory high entropy alloys (RHEAs), such as TaWNbMo, demonstrate promising potential for high-temperature applications owing to their excellent mechanical properties. Given the pivotal role of grain boundaries (GBs) in determining the mechanical behavior of RHEAs, it is imperative to investigate their characteristics. In this work, the mechanical response of TaWNbMo RHEA and its components (Ta, W, Nb, and Mo) bicrystal samples with Σ3{112‾} and Σ3{111‾} GB under shear were performed using molecular dynamics simulations to investigate the motion characteristics of GBs and their influence on mechanical properties, as well as the variations brought by high entropy GBs. Both types of GBs were observed to migrate coupled with shear deformation, and the migration mechanism was analyzed based on the theory of interface defects. Additionally, twin nucleation and growth were observed in the samples with Σ3{111‾} GB influenced by the high GB energy, and its mechanism was analyzed. Furthermore, a comparison was made between TaWNbMo and its component element metals, and the influence of high entropy GBs was analyzed. The multicomponent complexity invoked the local interfacial disconnection nucleation in HEA for both Σ3{112‾} and Σ3{111‾} GBs, the inhomogeneity of HEA also influenced the twin growth process from Σ3{112‾} GB to proceed and thicken in a localized and non-uniform manner. These results contribute to a deeper understanding of the GB characteristics of TaWNbMo RHEA.

Ni–Co–B coating was electrodeposited in sulfate bath with dimethylamine borane (DMAB) as reducing agent. The experiment explored the effect of DMAB concentration (CDMAB, 1–10 g/L), current density (Jk, 2–8 A/dm2), bath temperature (Tbath, 30–60 °C) on the coating morphology and hardness, and determined the best parameters: CDMAB = 8 g/L, Tbath = 60 °C, Jk = 4 A/dm2. The average hardness of the crack-free coating is 818 HV, and the B content is about 2 wt%. In order to develop a stress-relieving heat treatment scheme, the effects of heat treatment temperatures (100–500 °C) and holding times (1.5 h and 3 h) on the hardness of Ni–Co–B coating were studied. The highest hardness (1130 HV) is obtained at 350 °C for 1.5 h. The heat-treated Ni–Co–B coating was characterized by XRD, SEM and EPMA, and the second phase Ni3B was detected. In addition, the wear resistance and wear mechanism of the coating at room temperature and high temperature (300 °C) were studied. The results show that the wear volume of Ni–Co–B coating is reduced by more than 55% compared with Ni–Co coating. In general, Ni–Co–B coating can be used as an alternative to Ni–Co wear-resistant coating.

Constructing the magnesium alloy with fine grains, low density of dislocations, and weak crystal orientation is of crucial importance to enhance its comprehensive performance as the anode for Mg-air battery. However, this unique microstructure can hardly be achieved with conventional plastic deformation such as rolling or extrusion. Herein, we tailor the microstructure of Mg-Al-Sn-RE alloy by using the friction stir processing, which obviously refines the grains without increasing dislocation density or strengthening crystal orientation. The Mg-air battery with the processed Mg-Al-Sn-RE alloy as the anode exhibits higher discharge voltages and capacities than that employing the untreated anode. Furthermore, the impact of friction stir processing on the electrochemical discharge behaviour of Mg-Al-Sn-RE anode and the corresponding mechanism are also analysed according to microstructure characterization and electrochemical response.

This paper focus on the variation characteristics of axial force of bolts under alternating temperature. The temperature distribution characteristics of various regions in China were considered, and a typical alternating temperature load (0∼25 °C) was selected. Eight sets of bolt connections were designed with different bolt strength grades, specifications and initial torques, and the experimental study on the variation characteristics of bolt axial force under alternating temperature was conducted. From the perspective of the difference in linear expansion coefficients between bolts and connecting plates, the variation mechanism of bolt axial force under alternating temperature is Proposed. Finally, a corresponding calculation model for the variation of bolt axial force and its evaluation method for axial force relaxation are constructed, and the degree of attenuation of axial force of transmission tower bolts under alternating temperature during their service life is evaluated. The results show that the effect of alternating temperature causes the axial force of the connecting bolts to change interactively, and the axial force of the bolts exhibits a continuous attenuation characteristic as the alternating cycle increases. The greater the initial torques of the bolt and the larger the bolt size, the greater the impact of the alternating temperature on the bolt axial force. Under alternating temperatures, the axial force of transmission tower bolts can decay by up to 3.46 % within the first month and 4.58 % after three months. The greater the alternating temperature difference, the more significant the drop in axial force. The attenuation of bolt axial force under alternating temperature is significantly greater than that under constant temperature. The research results can provide some reference for the operations and maintenance of transmission towers.

Abstract In this study, ZnCo2O4/Ag3PO4 composite catalyst was prepared by the precipitation method, and their performance in the photocatalytic degradation of methyl orange (MO) was studied. The catalysts were characterized by scanning electron microscopy, high‐resolution transmission electron microscopy, X‐ray diffraction, energy‐dispersive X‐ray spectroscopy, selected area electron diffraction, X‐ray photoelectron spectroscopy, and UV‐Vis diffuse reflectance spectroscopy. The results indicate that the 0.1 ZnCo2O4/Ag3PO4 composite system has good photocatalytic activity in the degradation of methyl orange. Under simulated sunlight conditions, the degradation rate can reach 94% after 30 min. The maximum reaction rate constant of 0.1 ZnCo2O4/Ag3PO4 was 0.05301 min−1, which is 3 times and 52 times the rate constant of pure Ag3PO4 and pure ZnCo2O4, respectively. In catalyst recycling experiments, 0.1 ZnCo2O4/Ag3PO4 still degraded methyl orange at a rate of 84.4% after three cycles. Trapping experiments showed that holes and superoxide radicals mostly contributed to the photocatalytic degradation of methyl orange by the catalyst, while hydroxyl radicals played a partial role. The energy level structure of ZnCo2O4/Ag3PO4 is conducive to the effective separation of photogenerated electrons and holes, improving the lifespan of photogenerated charges. In the investigated catalyst series, 0.1 ZnCo2O4/Ag3PO4 demonstrated the best photocatalytic performance.

Cultivated land’s ecological security ensures human well-being and is critical to global food security. However, the unchecked expansion and excessive exploitation of agricultural resources have led to considerable land degradation issues in China, including soil erosion, contamination, and environmental degradation, raising concerns over the cultivated land ecological security (CLES). Current research on cultivated land (CLES is relatively limited, particularly at the national level across different provinces. In addition, a unified and comprehensive CLES evaluation index system has yet to be formed. To fill this research gap, we construct a CLES evaluation system with 35 indicators from three dimensions of “society-natural-economy” based on the DPSIR model framework and entropy weight TOPSIS model. Simultaneously, we conducted a spatial–temporal analysis of CLES in 31 provinces of China from 2012 to 2021 and applied the obstacle degree model to analyze the main factors impeding the CLES in China. The results showed that: (1) During the study period, the CLES and its subsystems showed a good development trend. Spatially, the CLES in China presents a regional difference of “high in the east and low in the west” and a significant regional difference among provinces. (2) The spatial CLES in different provinces of China presents a significant positive correlation, and the spatial clustering effect of CLES is gradually strengthening. The “High-High” clusters are mainly distributed in the northeast and eastern regions, while the “Low-Low” clusters are mainly located in the western region. (3) From the perspective of the criterion level, the state subsystem and the impact subsystem are the main obstacles hindering the improvement of CLES in China. At the indicator level, the common obstacle factors affecting the enhancement of CLES across provinces in China include soil erosion control intensity, number of green food certifications, per capita agricultural loans, per capita cultivated land area, and per capita grain production. Our research results can provide practical policy reference for further improving the ecological protection of cultivated land.

Aim This study aimed to investigate the role of discoidin domain receptor tyrosine kinase 1 (DDR1) in liver hepatocellular carcinoma (LIHC) and to evaluate its prognostic value on patient response to combination therapy. Methods In the current retrospective study, we examined the protein expression of DDR1 in various cancers by standard immunohistochemical (IHC) methods and evaluated its clinical significance in LIHC personalized treatment. Multiple online databases, including The Cancer Genome Atlas (TCGA), TIMER, GEO, ROC Plotter, and Genomics of Drug Sensitivity in Cancer (GDSC), were used. Results DDR1 protein expression was higher in LIHC than in other nine examined cancer types. Additionally, DDR1 exhibited higher expression levels in adjacent normal tissues compared to HBs-positive LIHC tissues. Analysis at single-cell resolution revealed that DDR1 was expressed primarily in epithelial cells but not in stromal and immune cells, and DDR1 expression was lower in HBs-positive LIHC cells in comparison with normal hepatocytes. Correlation of DDR1 upregulation and sorafenib resistance was observed in the patient cohort. Moreover, DDR1 expression positively correlated with the expression of inflammatory response-related genes, ECM-related genes, and collagen formation-related genes, but negatively correlated with the infiltration of CD8 + T cells, NK cells, and dendritic cells in LIHC. Conclusions Our findings suggest that DDR1 expression might be induced by collagen production-related cellular events involved in liver injury and repair, and that DDR1 overexpression might contribute to the resistance to LIHC targeted therapy and immunotherapy, highlighting DDR1 as a potential prognostic biomarker and therapeutic target.

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

To explore the influence of dynamic impacts on the creep properties of underground pillars, an underground coal sample is selected as the research material, and the mechanical response characteristics under dynamic impact are explored by the split Hopkinson pressure bar and high-speed camera. The results show that (1) when the creep stress level is higher, the initial deformation of coal is greater, and the damage to the sample through long-term creep is more severe. (2) With increasing levels of static stress, the dynamic strength and elastic modulus of the coal sample first increase and then decrease, and the dynamic elastic modulus is positively correlated with the impact velocity. (3) The static stress level determines the process of crack propagation and the degree of fracture, while the external dynamic impact determines the propagation speed of the crack. The results of this research enrich the theory of control systems for the prevention of coal pillar failure and instability and provide a theoretical basis for safe and efficient mining of working faces.

BackgroundPercutaneous left atrial appendage closure (LAAC) serves as an alternative prophylactic strategy for patients with non-valvular atrial fibrillation (AF) who cannot undergo anti-coagulation therapy. Proper management of associated complications is crucial to enhancing the procedure's success rate and mitigating perioperative risks and adverse events during follow-up.AimsThis study aims to summarize our center's experience and strategies in managing procedural-related complications encountered in 512 cases of LAAC with or without ablation for AF conducted from January 2020 to December 2023.ResultsWe identified 11 significant intervention-requiring complications associated with LAAC with or without Ablation procedure. These included three cases of intraoperative thrombosis, three instances of pericardial effusion or tamponade, one case of device-related thrombosis, one peri-device leak, one systemic embolism, one bleeding episode, and one additional device-related complication. The categorization of intraoperative thrombosis was as follows: one patient exhibited heparin resistance; one experienced thrombosis due to prolonged device implantation during the LAAC with ablation procedure; and one had unexplained intraoperative thrombosis. The pericardial effusion or tamponade likely resulted from damage to the atrial appendage during LAAC device insertion. Two patients encountered device-related thrombosis and systemic embolism events possibly caused by non-standard postoperative antithrombotic medication use; one patient's peri-device leak may have resulted from incomplete endothelialization of the occluder post-surgery; one patient experienced postoperative bladder bleeding; and one patient's device-related complications occurred due to a dislodged strut frame that damaged the left atrial appendage, leading to pericardial effusion. Our proactive interventions enabled all patients with these surgical-related complications to be safely discharged, with subsequent follow-ups showing no adverse events.ConclusionImplementing targeted interventions for immediate procedural-related complications during the LAAC with or without ablation procedures enhances procedural success rates, diminishes postoperative mortality and patient disability, and bolsters stroke prevention efforts. This approach underscores the importance of a strategic response to complications, affirming the procedure's viability and safety in managing non-valvular AF in patients contraindicated for anticoagulation.

BackgroundSputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma.MethodsThis study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation.ResultsThe levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%).ConclusionThis study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

BackgroundThe implementation of dementia policy is a complex process of translating policy goals to actions to address the changing needs of people living with dementia. Leveraging on others’ experiences would help policy decision-makers and actors better prepare for the challenges.PurposeThis study explored the development, the implementation and the impact of the dementia policy in Macao, a “role model” recognized by the Alzheimer’s Disease International.MethodsA scoping review of policies, strategies, and news articles, as well as scholarly work from 6 scientific databases dated till March 2023 was conducted under the guidance of the Health Policy Triangle Framework.ResultsAccording to 284 documents, the dementia policy in Macao, driven by government leadership and supported with public-private partnership, aimed to integrate health and social services to achieve the goals of “Early prevention, Early detection, Early diagnosis, Early treatment and Early support.” Promoting the preparedness according to the dementia burden trajectory, empowering the public and the service providers with training and education, and encouraging services-related research were among the key actions. With major changes in dementia care configuration, a dementia service network, a dementia-friendly community and a one-stop service model for disease screening, diagnosis, treatment and support have been developed.DiscussionReconfiguring existing resources in the health and social services to form an integrated service network at the community level could be considered a priority of action. Continuous engagement, collaboration and empowerment at different levels across these sectors is crucial for the sustainability of a dementia policy.

Introduction Patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify a lower low-density lipoprotein cholesterol (LDL-C) target for this population. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to effectively reduce LDL-C levels on a statin background. Additionally, several studies have confirmed the role of PCSK9 inhibitors in plaque regression and reducing residual cardiovascular risk in patients with ACS. However, those studies included coronary lesions with a degree of stenosis

Abstract Proteolysis targeting chimeras (PROTACs) have emerged as a promising strategy for drug discovery and exploring protein functions, offering a revolutionary therapeutic modality. Currently, the predominant approach to PROTACs discovery mainly relies on an empirical design–synthesis–evaluation process involving numerous cycles of labor‐intensive synthesis‐purification and bioassay data collection. Therefore, the development of innovative methods to expedite PROTAC synthesis and exploration of chemical space remains highly desired. Here, a direct‐to‐biology strategy is reported to streamline the synthesis of PROTAC libraries on plates, enabling the seamless transfer of reaction products to cell‐based bioassays without the need for additional purification. By integrating amide coupling and light‐induced primary amines and o‐nitrobenzyl alcohols cyclization (PANAC) photoclick chemistry into a plate‐based synthetic process, this strategy produces PROTAC libraries with high efficiency and structural diversity. Moreover, by employing this platform for PROTACs screening, we smoothly found potent PROTACs effectively inhibit triple‐negative breast cancer (TNBC) cell growth and induce rapid, selective targeted degradation of cyclin‐dependent kinase 9 (CDK9). The study introduces a versatile platform for assembling PROTACs on plates, followed by direct biological evaluation. This approach provides a promising opportunity for high‐throughput synthesis of PROTAC libraries, thereby enhancing the efficiency of exploring chemical space and accelerating the discovery of PROTACs.

Abstract DNA is commonly employed as a substrate for the building of artificial logic networks due to its excellent biocompatibility and programmability. Till now, DNA logic circuits are rapidly evolving to accomplish advanced operations. Nonetheless, nowadays, most DNA circuits remain to be disposable and lack of field programmability and thereby limits their practicability. Herein, inspired by the Configurable Logic Block (CLB), the CLB‐based erasable field‐programmable DNA circuit that uses clip strands as its operation‐controlling signals is presented. It enables users to realize diverse functions with limited hardware. CLB‐based basic logic gates (OR and AND) are first constructed and demonstrated their erasability and field programmability. Furthermore, by adding the appropriate operation‐controlling strands, multiple rounds of programming are achieved among five different logic operations on a two‐layer circuit. Subsequently, a circuit is successfully built to implement two fundamental binary calculators: half‐adder and half‐subtractor, proving that the design can imitate silicon‐based binary circuits. Finally, a comprehensive CLB‐based circuit is built that enables multiple rounds of switch among seven different logic operations including half‐adding and half‐subtracting. Overall, the CLB‐based erasable field‐programmable circuit immensely enhances their practicability. It is believed that design can be widely used in DNA logic networks due to its efficiency and convenience.

This long-term study protocol aims to compare the clinical outcomes of patients with severe lower limb trauma undergoing orthoplastic and orthopedic surgeries, focusing on their physical and psychological status. Patients with lower limb injuries and open fractures have been recruited since October 2019 and will be followed up until October 2024. The patients will be divided into two groups: (1) Orthoplastic group, where single-stage debridement, fixation, and soft tissue repair will be performed, and (2) Orthopedic group, where soft tissue repair will be done in a delayed-stage. The follow-up period will be one year, during which clinical data, limb function recovery, psychological scores, and health-related quality of life (HRQOL) will be evaluated to assess postoperative recovery and clinical outcomes. Additional clinical data, such as socio-demographic information, baseline features, Enneking score, Visual Analogue Scale (VAS) score, two-point discrimination score, and blood test parameters will also be collected. The 36-Item Short Form Health Survey (SF-36) will be used to evaluate HRQOL, while the Post-traumatic Stress Disorder Checklist (PCL) will assess the severity of self-reported post-traumatic stress disorder. The results of this study will provide valuable insights into prognostically relevant targets and contribute to improving the management and outcomes of patients with lower limb injuries and open fractures, who often face challenges related to limb disability and potential amputation postoperatively, significantly impacting their psychological and physical well-being.

Advanced machine learning (ML) models are utilized for accurate shear strength prediction of reinforced concrete beams (RCB), but their lack of interpretability makes it unclear how models make specific predictions, reducing their reliability and applicability. Mainstream model-agnostic interpretation methods require numerous additional computing procedures, limiting the interpretation efficiency, and the model prediction process remains unknown. This study proposes an inherently interpretable shear strength prediction model for RCB with stirrups based on Explainable Boosting Machine (EBM) and Bayesian optimization. The EBM algorithm decomposes the predicted shear strength into individual shape functions, thus thoroughly revealing the prediction process. Besides, the ML tasks of selecting a model with optimal hyperparameters are automatically performed by Bayesian optimization to reduce computational cost. The developed model is validated on a database including 372 specimens. Compared with shear design codes, empirical models and prominent ML models, the EBM model obtains most accurate predictions for the test set with R2, MAE, and RMSE of 0.9293, 35.42 kN, and 50.99 kN, respectively. The accuracy of EBM is robust to varying input variables through trend analysis. Its interpretability fully discloses the contribution of individual features to the shear strength, and the model rationality is verified by comparing feature contribution with existing mechanisms. The proposed EBM model achieves inherently interpretable shear strength predictions while maintaining high accuracy, which promotes the model applicability in structural assessment.

Herein, we report a visible-light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε-amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this multicomponent reaction protocol.

In recent years, China's advanced light sources have entered a period of rapid construction and development. As modern X-ray detectors and data acquisition technologies advance, these facilities are expected to generate massive volumes of data annually, presenting significant challenges in data management and utilization. These challenges encompass data storage, metadata handling, data transfer and user data access. In response, the Data Organization Management Access Software (DOMAS) has been designed as a framework to address these issues. DOMAS encapsulates four fundamental modules of data management software, including metadata catalogue, metadata acquisition, data transfer and data service. For light source facilities, building a data management system only requires parameter configuration and minimal code development within DOMAS. This paper firstly discusses the development of advanced light sources in China and the associated demands and challenges in data management, prompting a reconsideration of data management software framework design. It then outlines the architecture of the framework, detailing its components and functions. Lastly, it highlights the application progress and effectiveness of DOMAS when deployed for the High Energy Photon Source (HEPS) and Beijing Synchrotron Radiation Facility (BSRF).

Abstract The occurrence of NAD+ as a non-canonical RNA cap has been demonstrated in diverse organisms. TIR domain-containing proteins present in all kingdoms of life act in defense responses and can have NADase activity that hydrolyzes NAD+. Here, we show that TIR domain-containing proteins from several bacterial and one archaeal species can remove the NAM moiety from NAD-capped RNAs (NAD-RNAs). We demonstrate that the deNAMing activity of AbTir (from Acinetobacter baumannii) on NAD-RNA specifically produces a cyclic ADPR-RNA, which can be further decapped in vitro by known decapping enzymes. Heterologous expression of the wild-type but not a catalytic mutant AbTir in E. coli suppressed cell propagation and reduced the levels of NAD-RNAs from a subset of genes before cellular NAD+ levels are impacted. Collectively, the in vitro and in vivo analyses demonstrate that TIR domain-containing proteins can function as a deNAMing enzyme of NAD-RNAs, raising the possibility of TIR domain proteins acting in gene expression regulation.

The genus Svistella Gorochov, 1987 includes 10 species from Asia, with nine documented in China. In this study, a new species, Svistella yayun He, sp. nov., is described from Xizang, China. Morphologically, it resembles S. rufonotata (Chopard, 1932) but can be distinguished by a smaller inner tympanum, dark-brown setae on the 5th segment of the maxillary palp, and a rounded apex on the ectoparamere. To validate our morphological inferences and support the description of S. yayun sp. nov. as a new species, we performed a PCA based on bioacoustics parameters and molecular analysis. All Svistella species documented in China are distinguished by integrating their songs and DNA barcoding.

Abstract Background Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD. Methods This study included 1464 cognitively intact participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed. Results A total of 1464 individuals (mean age, 61.80 years; age range, 40–89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: β = 0.165, P = 0.037) and neuronal injury (CSF T-tau: β = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aβ42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses. Conclusions The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.

Abstract Protein-modifying enzymes regulate the dynamics of myriad post-translational modification (PTM) substrates. Precise characterization of enzyme-substrate associations is essential for the molecular basis of cellular function and phenotype. Methods for direct capturing global substrates of protein-modifying enzymes in living cells are with many challenges, and yet largely unexplored. Here, we report a strategy to directly capture substrates of lysine-modifying enzymes via PTM-acceptor residue crosslinking in living cells, enabling global profiling of substrates of PTM-enzymes and validation of PTM-sites in a straightforward manner. By integrating enzymatic PTM-mechanisms, and genetically encoding residue-selective photo-crosslinker into PTM-enzymes, our strategy expands the substrate profiles of both bacterial and mammalian lysine acylation enzymes, including bacterial lysine acylases PatZ, YiaC, LplA, TmcA, and YjaB, as well as mammalian acyltransferases GCN5 and Tip60, leading to discovery of distinct yet functionally important substrates and acylation sites. The concept of direct capturing substrates of PTM-enzymes via residue crosslinking may extend to the other types of amino acid residues beyond lysine, which has the potential to facilitate the investigation of diverse types of PTMs and substrate-enzyme interactive proteomics.

Abstract Silicone rubber (SR) is widely used for cable insulation and operates in multi‐stress coupling conditions. Its dielectric properties and ageing performance are the essential factors affecting cable operation. In this study, the frequency domain spectroscopy of unaged SR and SR aged under various conditions is measured. The dielectric responses before and after ageing are analysed in depth by the conjoint analysis via multiple complex planes (permittivity, conductivity, and modulus). Typical conductivity and interfacial polarisation properties, as well as property changes resulting from thermal and tensile ageing, are examined. Experimental results show that tensile ageing promotes conductance and interfacial polarisation, while thermal ageing shows the opposite effects. Based on the multi‐core model and charge carrier hopping transport model, thermal and tensile ageing mechanisms on the conductance and interfacial polarisation behaviours of SR are demonstrated. Both behaviours exhibit positively correlated changing characteristics, suggesting that the two behaviours may originate from a common process. The carrier transport process, promoted by the tensile effect and slightly suppressed by the thermal effect, is the primary factor and considered an important indicator to evaluate the dielectric properties of SR insulation.

A dynamic obstacle avoidance algorithm is proposed for the obstacle avoidance problem in the cruise task of unmanned boat cluster. Firstly, the square grid trajectory cell (SGTC) situation matrix of the waters around the unmanned surface vessle is obtained. Then, based on the principle of bacterial walking foraging, the optimal obstacle avoidance path is dynamically matched in the SGTC set. Finally, on the basis of dynamic obstacle avoidance, the autonomous cruise process of unmanned surface vessle is divided into stages of moving towards the target, dynamic obstacle avoidance, and return replenishment, so as to realize the normal cruise of unmanned surface vessle to the designated waters. The simulation results show that the proposed method has efficient avoidance ability for static point, surface obstacle and moving obstacle. Based on the algorithm, it can realize the normalized unmanned cruise of unmanned boat cluster. The algorithm is not only suitable for obstacle avoidance of unmanned surface vessle, but also has broad application prospects in other heterogeneous unmanned equipment.

Advanced airborne equipment liquid cooling system presents the development trend of multiple pumps in parallel, centralised heat dissipation and high efficiency circulation, but this type of system has the characteristics of many variable parameters and strong non-linearity, which makes the system operation and control become extraordinarily complex, posing a serious challenge to the system performance. Although some progress has been made in the current optimization of liquid cooling system performance, there are still gaps such as insufficient consideration of the multi-objective optimization problem and limited optimization effect. To fill this research gap, this study takes minimum specific energy consumption, minimum flow deviation and minimum impeller load as the optimization objectives, establishment of multi-objective optimization model for liquid-cooled power unit, the optimal solution set of the Pareto model is solved using the multi-objective grey wolf optimization algorithm (MOGWO), and the optimal solution set is substituted for the optimal solution, and the evaluation indexes are designed in combination with the actual working conditions to obtain the optimal schedule. By example analysis, the optimized system under variable operating conditions, the impeller load and specific energy consumption decreased by 16.88% and 3.64% respectively, while the rise in flow deviation was controlled within 0.76%. The newly established optimisation model effectively mitigates potential safety hazards during system operation. Finally, by combining all the indicators, three scheduling options are provided under variable operating conditions, focusing on reliability and economy, overall balance and high-precision flow, respectively, in order to adapt to the diversified requirements of different operating environments.

In recent years, robot-assisted surgery has advanced significantly and has emerged as a vital approach for the treatment of benign and malignant pancreatic diseases. Robotic pancreaticoduodenectomy, one of the most critical pancreatic surgical modalities, is distinguished by its high surgical difficulty and risk. The focus of recent scholarly discussions has been on ensuring the safety and feasibility of the procedure. Drawing from the expertise of our unit's primary diagnostic team, this article provides an overview of the progress in robotic pancreaticoduodenectomy, encompassing patient selections, surgical approaches, identification of significant anatomical structures, and pancreaticojejunostomy techniques.