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Abstract Background Overexpression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) contributes to cancer cell proliferation, survival and migration, playing crucial roles in tumor development. ROR1 has been proposed as a potential therapeutic target for cancer treatment. This study aimed to develop novel humanized ROR1 monoclonal antibodies and investigate their anti-tumor effects. Methods ROR1 expression in tumor tissues and cell lines was analyzed by immunohistochemistry and flow cytometry. Antibodies from mouse hybridomas were humanized by the complementarity-determining region (CDR) grafting technique. Surface plasmon resonance spectroscopy, ELISA assay and flow cytometry were employed to characterize humanized antibodies. In vitro cellular assay and in vivo mouse experiment were conducted to comprehensively evaluate anti-tumor activity of these antibodies. Results ROR1 exhibited dramatically higher expression in lung adenocarcinoma, liver cancer and breast cancer, and targeting ROR1 by short-hairpin RNAs significantly inhibited proliferation and migration of cancer cells. Two humanized ROR1 monoclonal antibodies were successfully developed, named h1B8 and h6D4, with high specificity and affinity to ROR1 protein. Moreover, these two antibodies effectively suppressed tumor growth in the lung cancer xenograft mouse model, c-Myc/Alb-cre liver cancer transgenic mouse model and MMTV-PyMT breast cancer mouse model. Conclusions Two humanized monoclonal antibodies targeting ROR1, h1B8 and h6D4, were successfully developed and exhibited remarkable anti-tumor activity in vivo.

Abstract Mechanochemistry studies the effect of mechanical force on chemical bonds, bringing opportunities for synthesizing alloys, ceramics, organics, polymers, and biomaterials. A vital issue of applying macro-scale mechanical force to manipulate crystal structures is finding ways to precisely adjust the force directions to break micro-scale target chemical bonds. Inspired by a common technique of driving a wedge into the wood to make wood chopping much easier, a wedging strategy of splitting three-dimensional structured crystalline frameworks and then converting them to nanosheets was proposed, where specific molecules were wedged into crystalline frameworks to drive the directional transmission of mechanical force to break chemical bonds. As a result, various crystalline framework nanosheets including metal−organic framework nanosheets, covalent organic framework nanosheets, and coordination polymer nanosheets were fabricated. This wedging crystal strategy exhibits advantages of operability, flexibility and designability, and furthermore, it is expected to expand mechanochemistry applications in material preparation.

Abstract Coupling by metal–carbene transfer enables the formation of several different bonds at the carbenoid site, enabling prochiral Csp 3 centers that are fundamental three-dimensional substructures for medicines to be forged with increased efficiency. However, strategies using bulk chemicals are rare because of the challenge of breaking two unactivated geminal bonds. Herein, we report the reactivity of ethers to form metal–carbene intermediate by cleavage of α-Csp 3–H/Csp 3–O bonds, which achieve selective coupling with arylmagnesium bromides and chlorosilanes. These couplings are catalysed by cyclic (alkyl)(amino)carbene-chromium complex and enable the one-step formation of 1,n-arylsilyl alcohols and α-arylated silanes. Mechanistic studies indicate that the in-situ formed low-valent Cr might react with iodobenzene to form phenyl radical species, which abstracts the α-H atom of ether in giving α-oxy radical. The latter combines with Cr by breaking α-Csp 3–O bond to afford metal–carbene intermediate, which couples with aryl Grignard and chlorosilane to form two σ-bonds.

Abstract Objectives Rheumatoid arthritis (RA) is a severe and common autoimmune disease. Conventional diagnostic methods are often subjective, error-prone, and repetitive works. There is an urgent need for a method to detect RA accurately. Therefore, this study aims to develop an automatic diagnostic system based on deep learning for recognizing and staging RA from radiographs to assist physicians in diagnosing RA quickly and accurately. Methods We develop a CNN-based fully automated RA diagnostic model, exploring five popular CNN architectures on two clinical applications. The model is trained on a radiograph dataset containing 240 hand radiographs, of which 39 are normal and 201 are RA with five stages. For evaluation, we use 104 hand radiographs, of which 13 are normal and 91 RA with five stages. Results The CNN model achieves good performance in RA diagnosis based on hand radiographs. For the RA recognition, all models achieve an AUC above 90% with a sensitivity over 98%. In particular, the AUC of the GoogLeNet-based model is 97.80%, and the sensitivity is 100.0%. For the RA staging, all models achieve over 77% AUC with a sensitivity over 80%. Specifically, the VGG16-based model achieves 83.36% AUC with 92.67% sensitivity. Conclusion The presented GoogLeNet-based model and VGG16-based model have the best AUC and sensitivity for RA recognition and staging, respectively. The experimental results demonstrate the feasibility and applicability of CNN in radiograph-based RA diagnosis. Therefore, this model has important clinical significance, especially for resource-limited areas and inexperienced physicians.

Abstract Malignant tumors have increasing morbidity and high mortality, and their occurrence and development is a complicate process. The development of sequencing technologies enabled us to gain a better understanding of the underlying genetic and molecular mechanisms in tumors. In recent years, the spatial transcriptomics sequencing technologies have been developed rapidly and allow the quantification and illustration of gene expression in the spatial context of tissues. Compared with the traditional transcriptomics technologies, spatial transcriptomics technologies not only detect gene expression levels in cells, but also inform the spatial location of genes within tissues, cell composition of biological tissues, and interaction between cells. Here we summarize the development of spatial transcriptomics technologies, spatial transcriptomics tools and its application in cancer research. We also discuss the limitations and challenges of current spatial transcriptomics approaches, as well as future development and prospects.

To investigate the impact response and damage mechanism of CFRP composite materials for high-speed trains under high-speed impact from foreign objects of different shapes and sizes, high-speed impact experiments and simulations were conducted on CFRP composite laminate at a velocity of 163 m/s. A finite element simulation model was established in Abaqus/Explicit. This model adopts the 3D-Hashin failure criterion considering strain rate effects to simulate the failure of fibers and matrix. Bonded elements with zero thickness were inserted along the fiber direction in the laminate to replicate the damage phenomena of fiber bundle debonding and pull-out. The effectiveness of the finite element model was validated by high-speed photography of the impact process and ultrasonic C-scan damage images recorded during the experiments. Based on this simulation model, the influence of projectiles of different shapes and sizes on the impact response of CFRP composite materials was studied. Projectiles of different shapes exhibit their own characteristics in terms of the time of peak force occurrence, manifestation, and characteristics of laminar damage. The peak force of the cylindrical projectile is 245.01% greater than that of the spherical one, while the conical projectile is 52.26% smaller than the spherical one. When the projectile size increases from 10 mm to 20 mm, the peak force of the spherical projectile, conical projectile, and cylindrical projectile increases by 79.67%, 120.12%, and 283.13% respectively. The total area of delamination in laminated plates is positively correlated with the size of the impacting body.

Abstract Skyrmions in existing 2D van der Waals (vdW) materials have primarily been limited to cryogenic temperatures, and the underlying physical mechanism of the Dzyaloshinskii–Moriya interaction (DMI), a crucial ingredient for stabilizing chiral skyrmions, remains inadequately explored. Here, we report the observation of Néel-type skyrmions in a vdW ferromagnet Fe3−x GaTe2 above room temperature. Contrary to previous assumptions of centrosymmetry in Fe3−x GaTe2, the atomic-resolution scanning transmission electron microscopy reveals that the off-centered FeΙΙ atoms break the spatial inversion symmetry, rendering it a polar metal. First-principles calculations further elucidate that the DMI primarily stems from the Te sublayers through the Fert–Lévy mechanism. Remarkably, the chiral skyrmion lattice in Fe3−x GaTe2 can persist up to 330 K at zero magnetic field, demonstrating superior thermal stability compared to other known skyrmion vdW magnets. This work provides valuable insights into skyrmionics and presents promising prospects for 2D material-based skyrmion devices operating beyond room temperature.

Highlights Recent progress on the applications of 2D materials in perovskite solar cells is discussed from the views of bottom interfaces, top interfaces, and electrodes. The roles of van der Waals heterojunction in enhancing the performance of perovskite solar cells are highlighted. The future directions and challenges in development of 2D materials-based perovskite solar cells are provided.

Abstract The chiral antiferromagnetic (AFM) materials, which have been widely investigated due to their rich physics, such as non-zero Berry phase and topology, provide a platform for the development of antiferromagnetic spintronics. Here, we find two distinctive anomalous Hall effect (AHE) contributions in the chiral AFM Mn3Pt, originating from a time-reversal symmetry breaking induced intrinsic mechanism and a skew scattering induced topological AHE due to an out-of-plane spin canting with respect to the Kagome plane. We propose a universal AHE scaling law to explain the AHE resistivity ( $${{\rho }}_{AH}$$ ρ A H ) in this chiral magnet, with both a scalar spin chirality (SSC)-induced skew scattering topological AHE term, $${a}_{sk}$$ a s k and non-collinear spin-texture induced intrinsic anomalous Hall term, $${{b}}_{{in}}$$ b i n . We found that $${{{a}}}_{{{sk}}}$$ a s k and $${{{b}}}_{{{in}}}$$ b i n can be effectively modulated by the interfacial electron scattering, exhibiting a linear relation with the inverse film thickness. Moreover, the scaling law can explain the anomalous Hall effect in various chiral magnets and has far-reaching implications for chiral-based spintronics devices.

Abstract Iso-butene (iso-C4H8) is an important raw material in chemical industry, whereas its efficient separation remains challenging due to similar molecular properties of C4 olefins. The ideal adsorbent should possess simultaneous high uptakes for 1,3-butadiene (C4H6) and n-butene (n-C4H8) counterparts, endowing high efficiency for iso-C4H8 separation in adsorption columns. Herein, a sulfate-pillared adsorbent, SOFOUR-DPDS-Ni (DPDS = 4,4′-dipyridyldisulfide), is reported for the efficient iso-C4H8 separation from binary and ternary C4 olefin mixtures. The rigidity in pore sizes and shapes of SOFOUR-DPDS-Ni exerts the molecular sieving of iso-C4H8, while exhibiting high C4H6 and n-C4H8 uptakes. The benchmark Henry’s selectivity for C4H6/iso-C4H8 (2321.8) and n-C4H8/iso-C4H8 (233.5) outperforms most reported adsorbents. Computational simulations reveal the strong interactions for C4H6 and n-C4H8. Furthermore, dynamic breakthrough experiments demonstrate the direct production of high-purity iso-C4H8 (>99.9%) from C4H6/iso-C4H8 (50/50, v/v), n-C4H8/iso-C4H8 (50/50, v/v), and C4H6/n-C4H8/iso-C4H8 (50/15/35, v/v/v) gas-mixtures.

In this paper, the 316L stainless steel matrix composite strengthened by TiB2 was successfully fabricated using laser cladding additive manufacturing technology. The microstructures of 316L/TiB2 with the addition of TiB2 (mass fractions of 0, 3 and 6, respectively) were characterised. Hardness tests and tensile tests were conducted to evaluate the physical and mechanical properties of the samples. The results indicated that all prepared samples exhibit a complex cellular microstructure composed of sub-grains. The matrix phase was verified as γ austenite with a honeycomb-like reinforcement phases forming along the boundaries. Further analysis revealed the net-like reinforcements were (Fe,Cr)2B and M3B2 (M is Cr, Fe, Mo, Ni, Ti) phases. The Microhardness of the samples with 0 wt%,3 wt% and 6 wt% of TiB2 were 148 HV, 170 HV and 186 HV, respectively. The addition of 3 wt% and 6 wt% TiB2 composites increased the yield strength by 22 % and 29 %, respectively, compared to 316L composite. Also, the tensile strength and modulus of elasticity of the reinforcement composites were improved by 8 % and 13 %, respectively. However, the elongation of the reinforcement composites was reduced by 36 % and 47 %, respectively. The reinforcement with high strength and modulus is formed in 316L/TiB2 composite, which leads to a reduction in grain size while enhancing the density of large-angle grain boundaries. Multiple strengthening effects dominated by Orowan strengthening were simultaneously experienced during the preparation process, which improved the mechanical properties of the composites.

Background: This research aimed to create a predictive model and an innovative risk classification system for patients with gallbladder cancer who undergo radical surgery. Methods: A cohort of 1387 patients diagnosed with gallbladder cancer was selected from the SEER database. The researchers devised a prognostic tool known as a nomogram, which was subjected to assessment and fine-tuning using various statistical measures such as the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve, decision curve analysis (DCA), and risk stratification were included in the catalog of comparisons. An external validation set comprising 93 patients from Nanchong Central Hospital was gathered for evaluation purposes. Results: The nomogram effectively incorporated seven variables and demonstrated satisfactory discriminatory ability, as evidenced by the C-index (training cohort: 0.737, validation cohort: 0.730) and time-dependent AUC (>0.7). Additionally, calibration plots confirmed the excellent alignment between the nomogram and actual observations. Our investigation unveiled NRI scores of 0.79, 0.81, and 0.81 in the training group, while the validation group exhibited NRI values of 0.82, 0.77, and 0.78. Additionally, when evaluating CSS at three-, six-, and nine-year intervals using DCA curves, our established nomograms demonstrated significantly improved performance compared to the old model (P

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear.Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI).Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%–30% range, significant large, low-velocity vortexes resulted in low TAWSS (40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2).Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%–50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%–30% DS near the stenoses and in the proximal LAD, while lesions with 30%–50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

Background The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient‐specific factors predicting the RDN response. Methods and Results We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta‐analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24‐hour systolic BP reduction (weighted mean difference, −4.05 [95% CI, −7.33 to −0.77]; weighted mean difference, −7.20 [95% CI, −9.79 to −4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. Conclusions In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Background Vertical jumping is an important evaluation tool to measure muscle strength and power as well as lower limb symmetry. It is of practical importance and value to develop and utilize a portable and low-cost mobile application (APP) to evaluate jumping. The “My Jump 2” app is an iPhone camera-based application for measuring jumping movements, which is applied to the countermovement jump (CMJ) vertical jumps of the lower limbs of athletes in different sports. The validity of this application and previous versions applied to different forms of vertical jump tests has been preliminarily demonstrated in different population, which has an obvious progress in research. Therefore, the reliability and validity of the jump height, time of flight parameters and symmetry of the CMJ vertical jump of athletes in different sports are needed to be verified by more experiments. Purpose The purpose of this study is to verify whether “My Jump 2” can effectively and reliably assess jump height, flight practice and lower limb symmetry in CMJAM (countermovement jump free arm) tests in fencing, swimming and diving athletes. Methods Seventy-nine fencers, swimmers and divers with training experience participated in this study. They completed a total of three CMJAM vertical jump and lower limb symmetry tests in 1 day, while being assessed by using the “My Jump 2” application and a force platform. The intra-group correlation coefficient (ICC) was used to verify reliability, while the Cronbach’s alpha and coefficient of variation (CV%) was used to analyze the stability of the CMJAM vertical jump test over three jumps. The Pearson correlation coefficient was used to verify the strength of the relationship between methods (i.e., concurrent validity), and the Bland-Altman plot was used to represent consistency, meanwhile, the t-test was used to determine the systematic bias between methods. Results Compared with the force platform, the cumulative height values of the total number of jumps (r = 0.999; p = 0.000), the cumulative time to vacate (r = 0.999; p = 0.000) for the CMJAM test obtained by the “My Jump 2” application, the height (ICC = 0.999–1, p = 0.000), the time to vacate flight (ICC = 0.999–1, p = 0.000), contact time symmetry (ICC = 0.976–0.994, p = 0.000), and flight time symmetry (ICC = 0.921–0.982, p = 0.000), respectively. Showed high correlation between the results of “my jump 2” app and the force platform. Conclusion The “My Jump 2” application is a valid tool to assess CMJAM vertical jump and lower limb symmetry in fencing, swimming and diving athletes with training experience.

Copper (Cu) contamination represents a persistent and significant form of heavy metal pollution in agricultural ecosystems, posing serious threats to organisms in current society. Spiders serve as crucial biological indicators for assessing the impact of heavy metals-induced toxicity. However, the specific molecular responses of spiders to Cu exposure and the mechanisms involved are not well understood. In our study, the wolf pond spiders, Pirata subpiraticus, were exposed to Cu for 21 d, resulting in a notable decline in survival rates compared with the control (n = 50, p < 0.05). We observed an increased expression of enzymes like glutathione peroxidase and superoxide dismutase (p < 0.05), signaling a strong oxidative stress response crucial for counteracting the harmful effects of reactive oxygen species. This response was corroborated by a rise in malondialdehyde levels (p < 0.05), a marker of lipid peroxidation and oxidative damage. Transcriptomic and metabolomic analyses revealed 2004 differentially expressed genes (DEGs) and 220 metabolites (DEMs). A significant number of these DEGs were involved in the glutathione biosynthetic process and antioxidant activity. A conjoint analysis revealed that under the Cu stress, several important enzymes and metabolites were altered (e.g., cathepsin A, legumain, and lysosomal acid lipase), affecting the activities of key biological processes and components, such as lysosome and insect hormone biosynthesis. Additionally, the protein interaction network analysis showed an up-regulation of processes like the apoptotic process, glutamate synthase activity, and peroxisome, suggesting that spiders activate cellular protective strategies to cope with stress and maintain homeostasis. This study not only deepens our understanding of spider biology in the context of environmental stress but also makes a significant contribution to the field of environmental stress biology.

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.

Abstract Background Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect the neuromuscular junction. Several subtypes of CD4+ T cells, including T helper (Th) 17 cells, follicular Th cells, and regulatory T cells (Tregs), contribute to the pathogenesis of MG. However, increasing evidence suggests that CD8+ T cells also play a critical role in the pathogenesis and treatment of MG. Main body Herein, we review the literature on CD8+ T cells in MG, focusing on their potential effector and regulatory roles, as well as on relevant evidence (peripheral, in situ, cerebrospinal fluid, and under different treatments), T-cell receptor usage, cytokine and chemokine expression, cell marker expression, and Treg, Tc17, CD3+CD8+CD20+ T, and CXCR5+ CD8+ T cells. Conclusions Further studies on CD8+ T cells in MG are necessary to determine, among others, the real pattern of the Vβ gene usage of autoantigen-specific CD8+ cells in patients with MG, real images of the physiology and function of autoantigen-specific CD8+ cells from MG/EAMG, and the subset of autoantigen-specific CD8+ cells (Tc1, Tc17, and IL-17+IFN-γ+CD8+ T cells). There are many reports of CD20-expressing T (or CD20 + T) and CXCR5+ CD8 T cells on autoimmune diseases, especially on multiple sclerosis and rheumatoid arthritis. Unfortunately, up to now, there has been no report on these T cells on MG, which might be a good direction for future studies.

Abstract Recently, video summarization (VS) has emerged as one of the most effective tools for rapidly understanding video big data. Dictionary selection based on self‐representation and sparse regularization is consistent with the requirement of VS, which aims to represent the original video with little reconstruction error by a small number of video frames. However, one crucial issue is that the existing methods mainly use a single view feature, which is not sufficient enough for acquiring the full pictorial details and affects the quality of the produced video summary. Although a few methods use more than one features, they only directly concatenate the features, which does not take advantage of the relationship of different features. Considering the complementarity of shallow and deep features, multiview feature co‐factorization based dictionary selection for VS is proposed in this paper to use the common information of both view features for VS. Specifically, two view features are used to fully exploit the full pictorial information of video frames, then the common information of two different views is extracted through coupled matrix factorization to conduct the dictionary selection for VS. Experiments have been carried out on two benchmark datasets, and results have demonstrated the effectiveness and superiority of the proposed method.

Abstract Olefin/paraffin separations are among the most energy-intensive processes in the petrochemical industry, with ethylene being the most widely consumed chemical feedstock. Adsorptive separation utilizing molecular sieving adsorbents can optimize energy efficiency, whereas the size-exclusive mechanism alone cannot achieve multiple olefin/paraffin sieving in a single adsorbent. Herein, an unprecedented sieving adsorbent, BFFOUR-Cu-dpds (BFFOUR = BF4 -, dpds = 4,4’-bipyridinedisulfide), is reported for simultaneous sieving of C2-C4 olefins from their corresponding paraffins. The interlayer spaces can be selectively opened through stronger guest-host interactions induced by unsaturated C = C bonds in olefins, as opposed to saturated paraffins. In equimolar six-component breakthrough experiments (C2H4/C2H6/C3H6/C3H8/n-C4H8/n-C4H10), BFFOUR-Cu-dpds can simultaneously divide olefins from paraffins in the first column, while high-purity ethylene ( > 99.99%) can be directly obtained through the subsequent column using granular porous carbons. Moreover, gas-loaded single-crystal analysis, in-situ infrared spectroscopy measurements, and computational simulations demonstrate the accommodation patterns, interaction bonds, and energy pathways for olefin/paraffin separations.

In this study, a high-strength carbon fiber reinforced composite laminate for rail vehicles was machined as a perforated sample and repaired by bonding a patch of the same material. The mechanical response of the repaired laminate to a low-velocity impact with energies of 25J and 30J was investigated through experiments and simulations with variations in patch thickness, size radius, and off-axis angle. The finite element simulation model was established in Abaqus/Explicit. The model integrated the progressive damage model based on the 3D-Hashin failure criterion, which can simulate the intralaminar damage of the fiber and the matrix. The cohesive zone model was used to simulate the delamination damage. According to the finite element analysis results, the mechanism and process of impact damage of the repaired laminates were analyzed. Based on the validated finite element model, the effect of patch size, thickness and off-axis angle on impact response was investigated. Patch radius reduced to 15 mm or thickness reduced to 2.1 mm can still resist low-velocity impacts with an energy of 30 J. Although the off-axis angle of the patch had little effect on the impact response of the repaired laminate, an off-axis angle of 90° was effective in suppressing delamination damage within the patch.

We report a cast light-weight dual-phase eutectic high-entropy alloy (EHEA) of Ni49Fe28Al17V6 that comprises of alternating FCC and ordered B2 lamellae. Such lamellar EHEA exhibits a superior tensile strength of ∼ 1.3 GPa in combination with a large uniform elongation of ∼ 26%, well surpassing those of other state-of-the-art cast EHEAs. The high strength-ductility synergy originates largely from the extensive dislocation activities in both FCC and B2 lamellae. In addition, the martensitic transformation of the B2 lamellae during deformation further promotes the work hardening capability to enhance the tensile strength and ductility.

Cooperative spatial exploration in initially unknown surroundings is a common embodied task in various applications and requires satisfactory coordination among the agents. Unlike many other research questions, there is a lack of simulation platforms for the cooperative exploration problem to perform and statistically evaluate different methods before they are deployed in practical scenarios. To this end, this paper designs a simulation framework to run different models, which features efficient event scheduling and data sharing. On top of such a framework, we propose and implement two different cooperative exploration strategies, i.e., the synchronous and asynchronous ones. While the coordination in the former approach is conducted after gathering the perceptive information from all agents in each round, the latter enables an ad-hoc coordination. Accordingly, they exploit different principles for assigning target points for the agents. Extensive experiments on different types of environments and settings not only validate the scheduling efficiency of our simulation engine, but also demonstrate the respective advantages of the two strategies on different metrics.

Abstract The application of continuous natural fibers as reinforcement in composite thin-walled structures offers a feasible approach to achieve light weight and high strength while remaining environmentally friendly. In addition, additive manufacturing technology provides a favorable process foundation for its realization. In this study, the printability and energy absorption properties of 3D printed continuous fiber reinforced thin-walled structures with different configurations were investigated. The results suggested that a low printing speed and a proper layer thickness would mitigate the printing defects within the structures. The printing geometry accuracy of the structures could be further improved by rounding the sharp corners with appropriate radii. This study successfully fabricated structures with various configurations characterized by high geometric accuracy through printing parameters optimization and path smoothing. Moreover, the compressive property and energy absorption characteristics of the structures under quasi-static axial compression were evaluated and compared. It was found that all studied thin-walled structures exhibited progressive folding deformation patterns during compression. In particular, energy absorption process was achieved through the combined damage modes of plastic deformation, fiber pullout and delamination. Furthermore, the comparison results showed that the hexagonal structure exhibited the best energy absorption performance. The study revealed the structure-mechanical property relationship of 3D printed continuous fiber reinforced composite thin-walled structures through the analysis of multiscale failure characteristics and load response, which is valuable for broadening their applications.

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

Potential transfer is an essential link in equipotential live-line work (EPLW), which has a potential safety hazard. To ensure the safety of the linemen, this paper conducted experimental research on this process. First, to investigate the discharge characteristics of the potential transfer gap in EPLW, this paper developed a simplified experimental platform to examine the relationship between the transfer voltage and gap distance, as well as the electrode structure, during the potential transfer process. Second, to explore the discharge development process of potential transfer, this paper built a discharge observation experimental platform to observe the discharge process and explore the effects of gap distance and type of the floating electrode on the discharge development process and potential transfer current. The research results are valuable for practical projects and linemen safety.

BackgroundThe COVID-19 pandemic has significantly impacted the mental health of college students, prompting the need for universities to implement measures to mitigate these adverse effects. This study aims to assess the mental health status and mitigation measures of college students, identify the primary factors contributing to their mental health challenges, and provide suggestions for educational institutions to reduce negative psychological impacts.MethodsIn February 2023, a questionnaire survey was conducted among 1,445 college students. Statistical analysis was performed on the survey results, and multiple regression models were used to identify significant influencing factors and optimize the model.ResultsThe study revealed correlations between factors affecting mental health during the pandemic, with interactions observed among some factors. Significant differences in mental health status were found among different groups of college students based on their information-sharing habits through apps and engagement in thesis research. Multiple regression analysis indicated that conducting academic research related to COVID-19 significantly increased the psychological stress of college students during the pandemic (p = 0.043). Among all mitigation measures, playing games demonstrated significant effectiveness in model analysis (p = 0.047). The optimization of the model showed that the multiple regression model considering the interaction of factors was more effective.ConclusionOur research identifies crucial factors influencing the mental health of college students and investigates the mental health status of various student groups. We recommend that educational institutions adopt proactive strategies and a multifaceted approach to support the mental health of college students and address potential issues that may arise.

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

Abstract γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross‐sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post‐radiotherapeutic immunotherapy. These findings are further validated at single‐cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.

Introduction The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients.Objective The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours.Methods and analysis The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal.Trial registration number NCT05790447.

Morphological structure can greatly affect the magnetic domain of magnetic materials, which plays a significant role on regulating the magnetic characteristics and electromagnetic properties. Herein, Fe3O4 nanorings/nanotubes with adjustable aspect ratio were fabricated through a hydrothermal route followed by reduction annealing treatment. The magnetic flux distributions in radial and axial direction were characterized by electron holography, suggesting that the Fe3O4 nanorings/nanotubes show magnetic vortex structure. The magnetic vortex-domain structure is favored to break the Snoek’s limit of Fe3O4, improving the high-frequency permeability and boosting the natural resonance band to 1 ∼ 10 GHz. Meanwhile the complex permittivity is highly sensitive to the aspect ratio. The Fe3O4 nanorings/nanotubes perform excellent comprehensive microwave absorption properties, owing to the special magnetic vortex structure, tunable complex permittivity, big complex permeability, large magnetization and high natural resonance. The Fe3O4 nanorings with the smallest aspect ratio show a minimum reflection loss (RL) value of −47.9 dB at 2.6 mm and EAB of 4 GHz at 3 mm. Besides, rotational orientation by an external magnetic field can cause the parallel arrangement of nanorings/nanotubes, which can increase both the complex permittivity and broad the resonance band. Rotational orientation can realize effective absorption efficiency at a broader frequency range with a thinner thickness, further improving the comprehensive microwave absorption. These findings not only suggest that designing particular magnetic-domain structures by morphologies can break the Snoek’s limit of magnetic materials, but also demonstrate that aspect ratio and magnetic field-assisted rotational orientation is promising ways to regulate the electromagnetic parameters, resulting in high-performance microwave absorption.

A layered double hydroxide (LDH) has been used as precursor for the synthesis of a multimetallic mixed oxide with photocatalytic activity. Thus, a trimetallic CoTiAl LDH has been synthesized as spherical aggregates of nanosheets. Analysis at short synthesis times indicates that CoTiAl-LDH particles grow perpendicular to initially formed oligomeric Ti-lactate nuclei. Calcination of CoTiAl-LDH at 400 °C affords the corresponding CoTiAl mixed oxide (MO) with low crystallinity having a cobaltite structure, while also maintaining the morphology. This CoTiAl-MO exhibits at 200 °C photocatalytic activity for CO2 hydrogenation to CO, accompanied with lesser amounts of CH4, with remarkable apparent quantum yields at 365 nm of 7.0 and 4.6 for CO and CH4, respectively and very low apparent activation energy for 10 kJ/mol. The present results show a promising direction to exploit the potential that the preparation of multimetallic LDH offers for the synthesis of mixed oxides with optimal compositions for an even more enhanced photocatalytic activity.

The analysis of the blast resistance and dynamic responses of gravity dams under extreme loading conditions is crucial in ensuring the safety of hydraulic engineering structures. Recent international conflicts have further emphasized the importance of research in this field. However, the lack of quantitative experimental studies and analysis methods for assessing prototype dam damage has posed significant challenges. To address this gap, experiments and numerical simulations on scaled concrete models were conducted, considering two equivalent detonation loads and four scaling ratios. Utilizing a non-dimensional approach, comprehensive comparisons of the dam's initial fracture locations, fracture paths, and extent of damage were performed, thus leading to the identification of consistent damage patterns and similarities between the different scaled models. The results demonstrated that the primary failure mode caused by the detonation loads on the downstream face was the overall fracture of the dam crest, with a slight downward shift in the initial crack position as the detonation load increased. Remarkably, the fracture paths exhibited satisfying similarities across the different scaling ratios. Furthermore, through further discussion on topics such as the initial fracture locations and the influence of reservoir water, both theoretical and practical insights were obtained for investigating the damage of prototype dams based on similarity laws.

Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively active in ovarian cancer (OC) with homologous recombination (HR) deficiency (HRD) caused by mutations in BRCA1/2 and other DNA repair pathway members. We sought molecular targeted therapy that induce HRD in HR-proficient cells to induce synthetic lethality with PARPi and extend the utility of PARPi. Here, we demonstrate that lysine-specific demethylase 1 (LSD1) is an important regulator for OC. Importantly, genetic depletion or pharmacological inhibition of LSD1 induces HRD and sensitizes HR-proficient OC cells to PARPi in vitro and in multiple in vivo models. Mechanistically, LSD1 inhibition directly impairs transcription of BRCA1/2 and RAD51, three genes essential for HR, dependently of its canonical demethylase function. Collectively, our work indicates combination with LSD1 inhibitor could greatly expand the utility of PARPi to patients with HR-proficient tumor, warranting assessment in human clinical trials.

Abstract Metastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy.

Metal halide perovskite solar cell (PSC) has successfully distinguished itself in optoelectronic field by virtue of the sharp rise in power conversion efficiency over the past decade. The remarkable efficiency breakthrough at such a fast speed can be mainly attributed to the comprehensive study on film deposition techniques, especially the effective management of surface and interfacial defects in recent works. Herein, we summarized the current trends in performance enhancement for PSCs, with a focus on the generally applicable strategies in high-performance works, involving deposition methods, compositional engineering, additive engineering, crystallization manipulation, charge transport material selection, interfacial passivation, optical coupling effect and constructing tandem solar cells. Promising directions and perspectives are also provided.

With the continuous development of flexible transparent electrodes, silver nanowires have been widely used due to their excellent optoelectronic properties and flexibility. However, their progress has been hindered by high contact resistance. In this study, femtosecond laser post-processing was applied to the silver nanowire transparent electrodes, and the effect of laser power density on the welding of silver nanowires was investigated. The results showed that femtosecond laser could achieve welding between silver nanowires, but excessively high laser energy density could cause the melting of the nanowires. When the femtosecond laser energy density reached the critical energy density of approximately 2546 J·m−2, at which nanowires underwent spheroidization, the average sheet resistance of the silver nanowire electrodes was minimized to 18.89 Ω·sq−1, and the figure of merit (FoM) of the electrodes reached its maximum at 126.99, which was close to twice the initial value. Moreover, the non-uniformity factor (NUF) was also small, at 1.6%, indicating good conductivity and uniformity. Additionally, the influence of femtosecond laser irradiation on the transmittance of the silver nanowire transparent electrodes was insignificant, and the number of effective pulses had no obvious effect on the welding efficiency of the silver nanowires.

The 17-4 precipitation-hardened (PH) stainless steel was prepared by laser-powder bed fusion (L-PBF), and the effects of different aging temperatures on the microstructures and properties of 17-4PH stainless steel were systematically studied. The results show that the 17-4PH stainless steel prepared by laser powder bed fusion requires a solid solution treatment in order to obtain the lath martensite structure, and then the niobium carbides and ε-Cu phase nanoparticles were precipitated by aging treatment to improve the strength of 17-4PH stainless steel. When the aging heat treatment parameter is 450 °C/5 h, the mechanical properties of the 17-4PH stainless steel are better, and the ultimate tensile strength (UTS) and elongation (El) are 1387 MPa and 7.3%, respectively. Compared with the as-printed 17-4PH stainless steel, the ultimate tensile strength of aging heat treatment exhibits an increase of 25.2%, and then, as the increase of aging temperature, the niobium carbides and ε-Cu precipitation phase become coarser, resulting in a decrease in the strength of 17-4PH stainless steel and an increase in plasticity.

In this work, a permanent connection of a high-nitrogen steel plate is achieved by using layer-by-layer powder-filled laser welding of high-nitrogen steel powder, and the stability levels of the welding process, microstructures and mechanical properties are analyzed. Compared with other processes, powder-filled laser welding is smooth without bursts and spatters, and the nitrogen content of the welding seam is obviously improved. The welding seam consists mainly of austenite, with few ferrite and manganese oxides. There is a nitrogen concentration gradient between the inside and the upper part of the melt pool, which leads to nitrogen escape. Laser remelting exacerbates this process, resulting in more severe nitrogen loss in the bottom layer than in the upper layer of the welding seam. The differences in the nitrogen solubilities in austenite and ferrite and the high-nitrogen content in the melt pool are the main reasons for the formation of micropores. Tensile experiments and impact experiments are conducted on the welding joint. The average tensile strength and elongation of the welding joint are 1032.36 MPa and 19.70%, respectively, contributing to 94% and 53.4% of the total values for the base metal. The grain refinement and relatively high nitrogen content are the reasons for the better tensile strength relative to other processes. The average impact energy of the welding joint is 24.68 J, which is approximately 63.74% of the base metal. Pores are the main reason for the reduced impact energy of the welding joint.

Material anisotropy caused by crystal orientation is an essential factor affecting the mechanical and fracture properties of crystal materials. This paper proposes an improved ordinary state-based peridynamic (OSB-PD) model to study the effect of arbitrary crystal orientation on the granular fracture in cubic crystals. Based on the periodicity of the equivalent elastic modulus of a cubic crystal, a periodic function regarding the crystal orientation is introduced into peridynamic material parameters, and a complete derivation process and expressions of correction factors are given. In addition, the derived parameters do not require additional coordinate transformation, simplifying the simulation process. Through convergence analysis, a regulating strategy to obtain the converged and accurate results of crack propagation paths is proposed. The effects of crystal orientations on crack initiation and propagation paths of single-crystal materials with different notch shapes (square, equilateral triangle, semi-circle) and sizes were studied. The results show that variations in crystal orientation can change the bifurcation, the number, and the propagation path direction of cracks. Under biaxial tensile loading, single crystals with semi-circular notches have the slowest crack initiation time and average propagation speed in most cases and are more resistant to fracture. Finally, the effects of grain anisotropy on dynamic fractures in polycrystalline materials under different grain boundary coefficients were studied. The decrease in grain anisotropy degree can reduce the microcracks in intergranular fracture and the crack propagation speed in transgranular fracture, respectively.

The exceptional photoelectromagnetic characteristics of rare-earth elements contribute significantly to their indispensable position in the high-tech industry. The exponential expansion of the demand for high-purity rare earth and related compounds can be attributed to the swift advancement of contemporary technology. Nevertheless, rare-earth elements are finite and limited resources, and their excessive mining unavoidably results in resource depletion and environmental degradation. Hence, it is crucial to establish a highly effective approach for the extraction and reclamation of rare-earth elements. Adsorption is regarded as a promising technique for the recovery of rare-earth elements owing to its simplicity, environmentally friendly nature, and cost-effectiveness. The efficacy of adsorption is contingent upon the performance characteristics of the adsorbent material. Presently, there is a prevalent utilization of porous adsorbent materials with substantial specific surface areas and plentiful surface functional groups in the realm of selectively separating and recovering rare-earth elements. This paper presents a thorough examination of porous inorganic carbon materials, porous inorganic silicon materials, porous organic polymers, and metal–organic framework materials. The adsorption performance and processes for rare-earth elements are the focal points of discussion about these materials. Furthermore, this work investigates the potential applications of porous materials in the domain of the adsorption of rare-earth elements.

This study evaluated the effect of 24-week Taichi training and Taichi plus resistance band training on pulmonary diffusion capacity and glycemic control in patients with Type 2 diabetes mellitus (T2DM). Forty-eight patients with T2DM were randomly divided into three groups: Group A-Taichi training: practiced Taichi 60 min/day, 6 days/week for 24 weeks; Group B-Taichi plus resistance band training: practiced 60-min Taichi 4 days/week plus 60-min resistance band training 2 days/week for 24 weeks; and Group C-controls: maintaining their daily lifestyles. Stepwise multiple regression analysis was applied to predict diffusion capacity of the lungs for carbon monoxide (DLCO) by fasting blood glucose, insulin, glycosylated hemoglobin (HbA1c), tumour necrosis factor alpha (TNF-α), von Willebrand Factor (vWF), interleukin-6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), endothelial nitric oxide synthase (eNOS), nitric oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor, and prostaglandin I-2. Taichi with or without resistance band training significantly improved DLCO, increased insulin sensitivity, eNOS and NO, and reduced fasting blood glucose, insulin, HbA1c, TNF-α, vWF, IL-6, ICAM-1, and ET-1. There was no change in any of these variables in the control group. DLCO was significantly predicted (R2 = 0.82) by insulin sensitivity (standard-β = 0.415, P

BackgroundThis study aimed to develop a prognostic model for patients with advanced ductal adenocarcinoma aged ≥50 years.MethodsPatient information was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to screen the model variables. Cases from Nanchang Central Hospital were collected for external validation. The new nomogram and the American Joint Committee on Cancer (AJCC) criteria were evaluated using integrated discrimination improvement (IDI) and net reclassification index (NRI) indicators. Survival curves presented the prognosis of the new classification system and AJCC criteria.ResultsIn total, 17,621 eligible patients were included. Lasso Cox regression selected 4 variables including age, chemotherapy, radiotherapy and AJCC stage. The C-index of the training cohort was 0.721. The C-index value of the validation cohort was 0.729. The AUCs for the training cohorts at 1, 2, and 3 years were 0.749, 0.729, and 0.715, respectively. The calibration curves showed that the predicted and actual probabilities at 1, 2, and 3 years matched. External validation confirmed the model’s outstanding predictive power. Decision curve analysis indicated that the clinical benefit of the nomogram was higher than that of the AJCC staging system. The model evaluation indices preceded the AJCC staging with NRI (1-year: 0.88, 2-year: 0.94, 3-year: 0.72) and IDI (1-year: 0.24, 2-year: 0.23, 3-year: 0.22). The Kaplan–Meier curves implied that the new classification system was more capable of distinguishing between patients at different risks.ConclusionsThis study established a prognostic nomogram and risk classification system for advanced pancreatic cancer in patients aged ≥50 years to provide a practical tool for the clinical management of patients with pancreatic ductal adenocarcinoma.

Introduction Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors.Methods and analysis This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR.Ethics and dissemination The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals.Trial registration This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853.

BackgroundCardiovascular diabetology is an emergent field focusing on all aspects of diabetes/cardiovascular interrelationship and metabolic syndrome. High-quality evidence needs to be provided to determine the efficacy and safety of interventions in cardiovascular diabetology. The heterogeneity of outcomes among trials limits the comparison of results, and some outcomes are not always meaningful to end-users. The cardiovascular diabetology core outcome set (COS) study aims to develop a COS of interventions for cardiovascular diabetology. In this paper, we introduce the methodological framework for developing the COS.MethodsThe COS development will include the following steps: (a) establish the COS groups of stakeholders, including international steering committee, Delphi survey group, and consensus meeting group; (b) systematic reviews of outcomes used in trials of cardiovascular diabetology; (c) semistructured interview of stakeholders for outcomes of cardiovascular diabetology; (d) generate a list of candidate outcomes and determine the original outcome pool; (e) Delphi survey with stakeholders of cardiovascular diabetology to select potential core outcomes; and (f) review and endorse the cardiovascular diabetology COS by expert consensus meeting.ConclusionsThis current study reports the methodological framework to develop a COS in cardiovascular diabetology and will provide evidence for the future development of COS in cardiovascular diabetology.