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Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Abstract Background Broussonetia papyrifera, B. monoica, and B. kaempferi belong to the genus Broussonetia (Moraceae). These three species hold significant economic and research values. However, few molecular markers have been effectively utilized for resource development and molecular genetic breeding of these species. Sequencing of their genomes allowed us to develop genomic markers (e.g. simple sequence repeats (SSRs)) and construct a high-density physical map. Results A total of 369,557, 332,627, and 276,245 SSRs were identified in 13 high-quality assembled pseudochromosomes and their unassembled scaffolds for B. papyrifera, B. monoica, and B. kaempferi, respectively. Among the identified genomic SSRs across the three species, short repeat sequences were more abundant, while long repeat sequences constituted a smaller proportion. Additionally, the predominant repeat motifs in the SSRs of the three Broussonetia species were composed of ‘A’ and ‘T’ repeats. Using B. papyrifera genome as a reference, 4,419 common SSRs were identified among these three species, while 2,048 SSRs were specific to B. kaempferi, and 4,285 SSRs were specific to B. monoica. Distribution analysis indicated a notable similarity in the distribution patterns of SSRs across the pseudochromosomes of these three species. Furthermore, of the identified SSRs, 28%, 31%, and 24% were mapped to genes in B. papyrifera, B. kaempferi, and B. monoica, respectively. Genic-mapped SSRs may regulate biological processes by influencing gene activity and protein function. To verify SSRs polymorphism, we selected 30 ones from 10,752 potentially polymorphic SSRs loci for PCR amplification among these three species, all of which were successfully amplified and exhibited polymorphism across these three species. Conclusions These findings are helpful for further research on the origin, evolution, and migration of Broussonetia species and also laid the foundation for the precise identification, systematic evaluation, and efficient utilization of the germplasm resources of Broussonetia species.

Abstract Background The advancement of nanotechnology underscores the imperative need for establishing in silico predictive models to assess safety, particularly in the context of chronic respiratory afflictions such as lung fibrosis, a pathogenic transformation that is irreversible. While the compilation of predictive descriptors is pivotal for in silico model development, key features specifically tailored for predicting lung fibrosis remain elusive. This study aimed to uncover the essential predictive descriptors governing nanoparticle-induced pulmonary fibrosis. Methods We conducted a comprehensive analysis of the trajectory of metal oxide nanoparticles (MeONPs) within pulmonary systems. Two biological media (simulated lung fluid and phagolysosomal simulated fluid) and two cell lines (macrophages and epithelial cells) were meticulously chosen to scrutinize MeONP behaviors. Their interactions with MeONPs, also referred to as nano-bio interactions, can lead to alterations in the properties of the MeONPs as well as specific cellular responses. Physicochemical properties of MeONPs were assessed in biological media. The impact of MeONPs on cell membranes, lysosomes, mitochondria, and cytoplasmic components was evaluated using fluorescent probes, colorimetric enzyme substrates, and ELISA. The fibrogenic potential of MeONPs in mouse lungs was assessed by examining collagen deposition and growth factor release. Random forest classification was employed for analyzing in chemico, in vitro and in vivo data to identify predictive descriptors. Results The nano-bio interactions induced diverse changes in the 4 characteristics of MeONPs and had variable effects on the 14 cellular functions, which were quantitatively evaluated in chemico and in vitro. Among these 18 quantitative features, seven features were found to play key roles in predicting the pro-fibrogenic potential of MeONPs. Notably, IL-1β was identified as the most important feature, contributing 27.8% to the model’s prediction. Mitochondrial activity (specifically NADH levels) in macrophages followed closely with a contribution of 17.6%. The remaining five key features include TGF-β1 release and NADH levels in epithelial cells, dissolution in lysosomal simulated fluids, zeta potential, and the hydrodynamic size of MeONPs. Conclusions The pro-fibrogenic potential of MeONPs can be predicted by combination of key features at nano-bio interfaces, simulating their behavior and interactions within the lung environment. Among the 18 quantitative features, a combination of seven in chemico and in vitro descriptors could be leveraged to predict lung fibrosis in animals. Our findings offer crucial insights for developing in silico predictive models for nano-induced pulmonary fibrosis.

Background Ischemia with nonobstructive coronary arteries (INOCA) has high morbidity, mortality, and poor quality of life. Metabolic syndrome (MetS) is a complex of multiple cardiac metabolic risk factors, significantly increasing the risk of major adverse cardiovascular events in INOCA patients. The study aimed to investigate the aggravating effect of MetS on left ventricular (LV) deformation and function impairment in INOCA patients. Materials and methods This study collected 104 INOCA patients (INOCA [MetS−]: n = 56; INOCA [MetS+]: n = 48) and 41 sex- and age-matched controls. LV function, indexed myocardial energetic efficiency (MEEI), and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured among the three groups. The independent factors of reduced MEEI and impaired LV function and strain parameters for all INOCA patients were assessed using multivariable linear regression analyses. Results In contrast to the INOCA (MetS-) group, the indexed LV stroke volume (LVSVI) (49.57 ± 11.58 mL/m2 vs. 42.58 ± 12.23 mL/m2, p = 0.007), MEEI [0.85(0.70–1.03) ml/s/g vs. 0.75(0.54–0.91) ml/s/g, p = 0.045] and LV global longitudinal peak strain (GLPS) (− 13.26 ± 2.86% vs. -10.95 ± 3.93%, p = 0.001) reduced in the INOCA (MetS+) group. Compared with the controls, LV GLPS decreased in the INOCA (MetS-) group (− 15.14 ± 2.83% vs. −13.26 ± 2.86%, p = 0.017). MetS was negatively associated with LVSVI, MEEI, and LV GLPS (all p

Abstract During the production process of lithium‐ion batteries, there exists a scenario of excessive water inside the battery due to poor water control in the factory environment. In addition, the battery housing may be damaged by corrosion, external vibration etc., which would cause water to enter the battery. To the best of the authors’ knowledge, there is little literature to reveal the influencing mechanism related to the above issue. The effects of excessive water on battery performance and safety were discussed. The results show that when the battery absorbs excessive water, the capacity decreases and the self‐discharging rate increases rapidly. The self‐heating temperature of the battery shows an increasing trend. The thermal runaway temperature decreases significantly with the time from self‐heating to thermal runaway dramatically shortened. The thermal stability of the battery deteriorates throughout the reaction process. This is mainly due to the mechanisms by which the water absorbed in the battery reacts with the electrolyte and the electrode material, resulting in the decrease of the electrolyte conductivity and the corrosion of the electrode material, as well as the thickening of the Solid Electrolyte Interface film and the accumulation of impurities. The findings are of positive significance in demonstrating the quantitative relationship between excessive water and the performance and safety of batteries. Also, it can add to the understanding of the complex scenarios of battery spontaneous failure, which is vital for solving battery self‐thermal runaways.

Abstract The Banna miniature inbred pig (BN) is an intensively inbred line for biomedical research and xenotransplantation due to its low individual variation and stable genetic background. Although it is originated from the Diannan miniature pig (DN), substantial genetic changes have actually occurred. However, the lack of a BN reference genome has limited studies on the complete genomic architecture and utilization as a biomedical model. Here, we present a high-quality genome for BN using PacBio HiFi and Hi-C sequencing technologies, with a total length of 2.66 Gb, a scaffold N50 of 143.60 Mb, and 97.59% of the sequences anchored to chromosomes. Its BUSCO score is 96.30%, higher than porcine reference assembly and DN. The genome contains 48.49% of repeats, 19,756 protein-coding genes, and 7,207 non-coding RNAs according to our annotation. The OMArk score shows a proteome completeness and consistency of 99.58% and 93.62%, respectively. These findings indicate that the chromosome-scale genome of BN provides a valuable resource for studying the genetic basis of inbreeding, facilitating further research and clinical applications.

Abstract The Hainan muntjac (Muntiacus nigripes) is a wild animal endemic to Hainan, China. Its species distribution and the diversity of muntjac karyotypes have attracted much attention. Although genomic resources have increased in recent years, relevant genome assembly data of Hainan muntjac are still lacking. Meanwhile, molecular evidence for the taxonomic units of this species remains lacking. In this study, we successfully assembled the Hainan muntjac haplotype genome at the chromosome level using Pacbio long read and long sequencing technologies and Hi-C data. The final assembly size was 2.66 Gb, with allele and scaffold N50 values of 29.27 and 700.27 Mb, respectively, and we scaffolded the genome sequence onto three chromosomes. The genome contains a total of 21,451 genes and 10,056 gene families. Phylogenetic analysis using single-copy gene families revealed that Hainan muntjac is most closely related to red muntjac, with a divergence time of 8–11 Ma. This new genomic resource of Hainan muntjac will be crucial for future comparative genomic analyses and genetic evolutionary studies.

Abstract The primary cause of viral encephalitis (VE) is invasion of the central nervous system (CNS) by the virus, which leads to neuroinflammation and poses a significant threat to global public health. Microglia, as CNS-resident macrophages, play a crucial role in neuroinflammation and are often identified as the preferred target for the prevention or treatment of VE. In this study, we used pseudorabies virus (PRV)-induced VE in mice and pigs as a model to investigate the regulation of microglial responses during viral encephalitis and explored the mechanism of microglial activation. Cellular experiments revealed that microglial activation was accompanied by cell migration, characteristic morphological changes, phagocytosis, inflammatory cytokine production, and antigen presentation. Transcriptome analysis revealed that genes related to inflammation in PRV-infected BV2 cells were significantly enriched. The expression of the NOD1 gene in BV2 cells was significantly increased during PRV infection, after which NOD1 in BV2 cells was silenced by siRNA and overexpressed via a plasmid. NOD1 was found to be involved in the secretion of cytokines in BV2 cells by regulating the MAPK/NF-κB signalling pathway. Mouse and pig experiments have shown that NOD1 is involved in the secretion of cytokines by microglia by regulating the MAPK/NF-κB signalling pathway during PRV infection.

In breast cancer grading, the subtle differences between HE-stained pathological images and the insufficient number of data samples lead to grading inefficiency. With its rapid development, deep learning technology has been widely used for automatic breast cancer grading based on pathological images. In this paper, we propose an integrated breast cancer grading framework based on a fusion deep learning model, which uses three different convolutional neural networks as submodels to extract feature information at different levels from pathological images. Then, the output features of each submodel are learned by the fusion network based on stacking to generate the final decision results. To validate the effectiveness and reliability of our proposed model, we perform dichotomous and multiclassification experiments on the Invasive Ductal Carcinoma (IDC) pathological image dataset and a generated dataset and compare its performance with those of the state-of-the-art models. The classification accuracy of the proposed fusion network is 93.8%, the recall is 93.5%, and the F1 score is 93.8%, which outperforms the state-of-the-art methods.

Abstract Background Few studies investigated the implications of post-PCI QFR and post-PCI ΔQFR (absolute increase of QFR) in de novo lesions of small coronary disease after drug-coated balloon (DCB). Objectives We sought to investigate the prognostic implications of post-PCI QFR and post-PCI ΔQFR in patients who received DCB only. Methods Patients were divided according to the optimal cutoff value of the post-PCI QFR and the post-PCI ΔQFR. The primary outcome was major adverse cardiovascular events (MACE), including target vessel revascularization (TVR), cardiac death, and myocardial infarction (MI). Results The optimal cutoff values of QFR and ΔQFR for the MACE rate were 0.86 and 0.57, respectively. There were 175 patients (61.2%) with a high QFR (≥ 0.86) and 113 patients (39.5%) with a high ΔQFR (≥ 0.57) after PCI. The MACE rate was significantly higher in patients with a low QFR compared to a high QFR (5.7% vs. 27.0%, hazard ratio [HR]: 3.632, 95% confidence interval [CI]: 1.872 to 7.044, P

Abstract Loeffler's endocarditis (LE) is the cardiac manifestation of hypereosinophilic syndrome. We present a case of LE in a 45‐year‐old female, resulting in diffuse endothelial fibrosis and severe right‐sided heart failure. The patient was admitted with dyspnoea and oedema, with haematology revealing an absolute eosinophil count of 20.9 × 109. Imaging showed near‐complete obliteration of the right ventricular apical and formation of thromboses. Endomyocardial biopsy indicated diffuse fibrous hyperplasia of the endocardium with fibrinous thrombi rich in eosinophils. Molecular and cytogenetic analyses of bone marrow cells showed no signs of FIP1L1‐PDGFRA fusion, PDGFRB mutation, abnormal myeloid maturation, or a lymphoproliferative disorder. Flow cytometry indicated no clonality, ruling out chronic eosinophilic leukaemia. Gene mutation screening discovered a p.L583_A586delinesS mutation in the JAK2 gene. Following treatment with ruxolitinib, the patient's eosinophil levels normalized, but unfortunately, the damage to the heart was irreversible. The patient was hospitalized multiple times due to right heart failure and resistance to diuretics. After thorough discussions with the medical team, it was determined that a heart transplantation would be the most effective treatment. Following the surgery, the patient successfully navigated the postoperative critical period with the support of an intra‐aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), and ventilator‐assisted ventilation but subsequently developed an acquired Intensive care unit‐acquired weakness (ICU‐AW) and a depressive state. Fortunately, the patient gradually recovered from these complications.

Abstract The linear Doppler effect and angular Doppler effect in vortex electromagnetic wave radar echoes can be used to extract comprehensive micro‐motion parameters. However, the analytical solution of micro‐motion parameters for rotating targets in vortex EM wave radar has not been obtained. To solve the above problems, the analytical solution of micro‐motion parameters is derived, and a micro‐motion parameter extraction method is proposed. Firstly, the shape and properties of the angular Doppler curve in various cases are discussed. Subsequently, the properties of three points on the angular Doppler curve are derived. The micro‐motion parameters are obtained based on the three points. The simulations demonstrate that the proposed method can greatly reduce the computational complexity and improve the accuracy of micro‐motion parameter extraction.

Abstract Pancreatic cancer is highly lethal and has limited treatment options available. Our team had previously developed ZZW-115, a promising drug candidate that targets the nuclear protein 1 (NUPR1), which is involved in pancreatic cancer development and progression. However, clinical translation of ZZW-115 was hindered due to potential cardiotoxicity caused by its interaction with the human Ether-à-go-go-Related Gene (hERG) potassium channel. To address this, we have performed a high-throughput screening of 10,000 compounds from the HitFinder Chemical Library, and identified AJO14 as a lead compound that binds to NUPR1, without having favorable affinity towards hERG. AJO14 induced cell death through apoptosis, necroptosis, and parthanatos (induced by the poly-ADP ribose polymerase (PARP) overactivation), driven by mitochondrial catastrophe and decreased ATP production. This process seemed to be mediated by the hyperPARylation (an excessive modification of proteins by PARP, leading to cellular dysfunction), as it could be reversed by Olaparib, a PARP inhibitor. In xenografted mice, AJO14 demonstrated a dose-dependent tumor reduction activity. Furthermore, we attempted to improve the anti-cancer properties of AJO14 by molecular modification of the lead compound. Among the 51 candidates obtained and tested, 8 compounds exhibited a significant increase in efficacy and have been retained for further studies, especially LZX-2-73. These AJO14-derived compounds offer potent NUPR1 inhibition for pancreatic cancer treatment, without cardiotoxicity concerns.

Abstract Ni-rich layered oxides (LiNi x Co y Mn1−x−y O2, x > 0.8, NCM) are technologically important cathode (i.e., positive electrode) materials for next-generation high-energy batteries. However, they face challenges in cycle stability and durability due to internal strain accumulation and particle fracture as the batteries cycle. Here we report a simple molten-salt-assisted synthesis route to introduce gradiently distributed pores into the polycrystalline NCM secondary particles. The gradient porous strategy creates void spaces to buffer the anisotropic volume change of the primary particles, effectively mitigating the intergranular fracture and limiting the impedance growth. It not only increases the maximum accessible capacity of the NCM cathodes but also greatly enhances their cycle stability in practical pouch-type batteries and all-solid-state-batteries. It further enables a high nickel, low cobalt cathode (LiNi0.96Co0.02Mn0.02O2) with a combination of high specific energy (941.2 Wh kg−1 based on cathode weight at 0.1 C and 25 °C, 1 C = 245 mA g−1) and high stability during cycling (80.5% capacity retention after 800 cycles at 1 C relative to that of the first cycle) and high-temperature storage (reversible capacity retention >95.5% after 42-day storage at 60 °C at the fully charged state) in pouch cells.

Abstract Non-Hermitian physical systems have attracted considerable attention in recent years for their unique properties around exceptional points (EPs), where the eigenvalues and eigenstates of the system coalesce. Phase transitions near exceptional points can lead to various interesting phenomena, such as unidirectional wave transmission. However, most of those studies are in the classical regime and whether these properties can be maintained in the quantum regime is still a subject of ongoing studies. Using a non-Hermitian on-chip superconducting quantum circuit, here we observe a phase transition and the corresponding exceptional point between the two phases. Furthermore, we demonstrate that unidirectional microwave transmission can be achieved even in the few-photon regime within the broken symmetry phase. This result holds some potential applications, such as on-chip few-photon microwave isolators. Our study reveals the possibility of exploring the fundamental physics and practical quantum devices with non-Hermitian systems based on superconducting quantum circuits.

Abstract MicroRNAs(miRNAs) are promising biomarkers for early esophageal squamous cell carcinoma (ESCC) detection and prognostic prediction. This study aimed to explore the potential biomarkers and molecular pathogenesis in the early diagnosis of ESCC. Firstly, 48 differentially expressed miRNAs (DEMs) and 1319 differentially expressed genes (DEGs) were identified between 94 ESCC tissues and 13 normal esophageal tissues in TCGA. From miRNA–mRNA regulatory network, there are 6558 target genes of the 48 DEMs, where 400 target genes are also among 1319 DEGs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicate that the 400 DEGs significantly enriched in cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and oocyte meiosis. And there are 66 DEGs among these six biological pathways, which we called GO-DEGs. From miRNA–mRNA regulatory network, 32 DEMs regulated the 66 GO-DEGs, where 22 DEMs were verified by different types of experiments in ESCC tissues, cells, or serum from the literature. For the other novel 10 DEMs, single-factor Cox regression analysis show that only hsa-miR-34b-3p showed no significant correlation with the overall survival of ESCC patients. Finally, we obtained the novel 9 ESCC-related DEMs, where three are down-regulated, and six are up-regulated. We analyzed the expression trends of target genes for five miRNAs and identified three significantly different miRNAs (hsa-miR-205-3p, hsa-miR-452-3p, and hsa-miR-6499-3p) confirmed by qPCR. Moreover, the stage-specific miRNAs were also suggested. These three qPCR validated miRNAs are also specific to the early stages of ESCC: hsa-miR-452-3p is specific to Stage I, II and III; hsa-miR-205-3p is specific in Stage II and III; and hsa-miR-6499-3p is Stage II specific. They might be the potential biomarkers for ESCC stage diagnosis. This study identified three novel miRNA markers potentially related to the diagnosis of ESCC and participated in the occurrence and development of ESCC through cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and signaling pathway for oocyte meiosis.

Abstract Background Postoperative sore throat (POST) is a common complaint after general anaesthesia. The prevalence of POST caused by a neural integrity monitor electromyography endotracheal tube (NIM-EMG-ETT) is high. This study aimed to determine whether ultrasound-guided internal branch of superior laryngeal nerve block (iSLNB) could alleviate POST associated with a NIM-EMG-ETT. Methods This randomized controlled trial plans to enroll 182 patients scheduled to undergo general anaesthesia with a NIM-EMG-ETT. Patients will be randomly allocated into the iSLNB group or the control group according to randomized numbers generated by Excel. After induction, patients in the iSLNB group will undergo ultrasound-guided iSLNB with ropivacaine, and patients in the control group will undergo the same procedure with normal saline. The prevalence, severity, visual analogue scale score of POST, and postoperative acoustic analysis will be recorded. Discussion To the best of our knowledge, this is the first study to evaluate the effect of ultrasound-guided iSLNB with ropivacaine on the mitigation of POST induced by NIM-EMG-ETT. Our study will provide clinical answers to alleviate POST induced by NIM-EMG-ETT. The results of this study may provide a safe method to prevent POST caused by NIM-EMG-ETT. Trial registration Chinese Clinical Trial Registry, ChiCTR2300076393. Registered on October 24, 2023, http://www.chictr.org.cn/index.aspx .

Purpose: Explore the causal relationship between the gut microbiota and erectile dysfunction (ED) at phylum, class, order, family, and genus levels, and identify specific pathogenic bacteria that may be associated with the onset and progression of ED. Materials and Methods: The genetic variation data of 196 human gut microbiota incorporated in our study came from the human gut microbiome Genome Wide Association Studies (GWAS) dataset released by the MiBioGen Consortium. The GWAS statistics for ED were extracted from one study by Bovijn et al., which included 223,805 participants of European ancestry, of whom 6,175 were diagnosed with ED. Subsequently, Mendelian randomization (MR) analysis was carried out to explore whether a causal relationship exists between the gut microbiota and ED. Additionally, bidirectional MR analysis was performed to examine the directionality of the causal relationship. Results: Through MR analysis, we found that family Lachnospiraceae (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.05–1.52, p=0.01) and its subclass genus LachnospiraceaeNC2004 group (OR: 1.17, 95% CI: 1.01–1.37, p=0.04) are associated with a higher risk of ED. In addition, genus Oscillibacter (OR: 1.17, 95% CI: 1.02–1.35, p=0.03), genus Senegalimassilia (OR: 1.32, 95% CI: 1.06–1.64, p=0.01) and genus Tyzzerella3 (OR: 1.14, 95% CI: 1.02–1.27, p=0.02) also increase the risk of ED. In contrast, the inverse variance weighted estimate of genus RuminococcaceaeUCG013 (OR: 0.77, 95% CI: 0.61–0.96, p=0.02) suggests that it has a protective effect against the occurrence of ED. Conclusions: This study preliminarily identified 6 bacterial taxa that may have a causal relationship with ED, including family Lachnospiraceae, genus Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella 3 and Ruminococcaceae UCG013. These identified important bacterial taxa may serve as candidates for microbiome intervention in future ED clinical trials.

Abstract Catalytic activity of metal particles is reported to originate from the appearance of nonmetallic states, but conductive metallic particles, as an electron reservoir, should render electron delivery between reactants more favorably so as to have higher activity. We present that metallic rhodium particle catalysts are highly active in the low-temperature oxidation of carbon monoxide, whereas nonmetallic rhodium clusters or monoatoms on alumina remain catalytically inert. Experimental and theoretical results evidence the presence of electronic communications in between vertex atom active sites of individual metallic particles in the reaction. The electronic communications dramatically lower apparent activation energies via coupling two electrochemical-like half-reactions occurring on different active sites, which enable the metallic particles to show turnover frequencies at least four orders of magnitude higher than the nonmetallic clusters or monoatoms. Similar results are found for other metallic particle catalysts, implying the importance of electronic communications between active sites in heterogeneous catalysis.

Abstract Ancient buildings possess significant artistic and cultural value. The digitization of these structures is a crucial aspect of their restoration, providing foundational data for subsequent stress and health analyses. However, creating accurate models of ancient buildings is a challenging endeavor, even for experienced researchers, especially when dealing with a large number of structures. A pressing issue that needs addressing is how to quickly obtain accurate models of ancient buildings while ensuring both precision and efficiency. Currently, one of the more precise methods for reconstructing models of ancient buildings involves the use of scanned point clouds and manual reconstruction through modeling software. However, this method suffers from poor accuracy and low efficiency, making the modeling process complex and time-consuming. In this article, we will refer to the model generated from the point cloud of real components as the "current state model", and the unforced mesh model of the ancient building as the "standard model". An algorithm is proposed to construct the current state model of ancient buildings by guiding the deformation of the unforced standard model using the scanned point cloud model. First, this paper designs an automatic modeling method for ancient building components as the foundational data before deformation, addressing the issue of low modeling efficiency for ancient buildings. Second, it proposes a method for automatically calculating deformation control point pairs based on the characteristics of ancient buildings, solving the problem of manually locating control points. Finally, the proposed adaptive weight Laplacian deformation algorithm is applied to deform the standard model into the current state model.

Marine battlefield environment is the important condition that restricts the effectiveness of maritime weapons and the conduct of military operations. Accurate assessment of environmental impact is the "soft power" for improving maritime combat capability and battlefield construction. Firstly, this paper briefly introduces the marine battlefield environment and its impact assessment. Then, the assessment methods and modeling techniques of battlefield environment are summarized into four categories: dynamic simulation-based assessment method, decision science-based assessment method, data science-based assessment method and uncertain artificial intelligence-based assessment methods, and the above methods are described in detail. Finally, the different methods are compared and the application prospect is analyzed.

Abstract Objectives To quantitatively investigate the anatomy of the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for surgical reconstruction procedures in chronic ankle instability (CAI). Methods 3D MRI was performed on five fresh-frozen cadaveric ankles using six different spatial resolutions (0.3 × 0.3 × 0.3 mm3, 0.45 × 0.45 × 0.45 mm3, 0.6 × 0.6 × 0.6 mm3, 0.75 × 0.75 × 0.75 mm3, 0.9 × 0.9 × 0.9 mm3, 1.05 × 1.05 × 1.05 mm3). After comparing the MRI results with cadaver dissection, a resolution of 0.45 × 0.45 × 0.45 mm³ was selected for bilateral ankles MRI on 24 volunteers. Classification of the ATFL and four distances of surgically relevant bony landmarkers were analyzed (distance 1 and 3, the fibular origin of the ATFL and CFL to the tip of fibula, respectively; distance 2, the talar insertion of the ATFL to the bare zone of talus; distance 4, the calcaneal insertion of the CFL to the peroneal tubercle). Results In subjective evaluation, the interobserver ICC was 0.95 (95% confidence interval (CI): 0.94–0.97) between two readers. The spatial resolution of 0.3 × 0.3 × 0.3 mm3 and 0.45 × 0.45 × 0.45 mm3 received highest subjective score on average and demonstrated highest consistency with autopsy measurements in objective evaluation. Measurements on the 48 volunteer ankles, distance 1 in type I and II were 12.65 ± 2.08 mm, 13.43 ± 2.06 mm (superior-banded in Type II) and 7.69 ± 2.56 mm (inferior-banded in Type II) (means ± SD), respectively. Distance 2 in type I and II were 10.90 ± 2.24 mm, 11.07 ± 2.66 mm (superior-banded in Type II), and 18.44 ± 3.28 mm (inferior-banded in Type II), respectively. Distance 3 and 4 were 4.71 ± 1.04 mm and 14.35 ± 2.22 mm, respectively. Conclusion We demonstrated the feasibility of quantifying the distances between bony landmarkers for surgical reconstruction surgery in CAI using high-resolution 3D MRI. Critical relevance statement High-resolution 3D MRI examination may have a guiding effect on the preoperative evaluation of chronic ankle instability patients. Key Points Spatial resolutions of 0.3 × 0.3 × 0.3 mm3 and 0.45 × 0.45 × 0.45 mm3 demonstrated highest consistency with autopsy measurements. The spatial resolution of 0.45 × 0.45 × 0.45 mm3 was conformed more to clinical needs. 3D MRI can assist surgeons in developing preoperative plans for chronic ankle instability. Graphical Abstract

Abstract Computationally derived volcano curve has become the gold standard in catalysis, whose practical application usually relies on empirical interpretations of composition or size effects by the identical active site assumption. Here, we present a proof-of-concept study on disclosing both the support- and adsorbate-induced restructuring of Pt-Co bimetallic catalysts, and the related interplays among different interfacial sites to propose the synergy-dependent volcano curves. Multiple characterizations, isotopic kinetic investigations, and multiscale simulations unravel that the progressive incorporation of Co into Pt catalysts, driven by strong Pt-C bonding (metal-support interfaces) and Co-O bonding (metal-adsorbate interfaces), initiates the formation of Pt-rich alloys accompanied by isolated Co species, then Co segregation to epitaxial CoOx overlayers and adjacent Co3O4 clusters, and ultimately structural collapse into amorphous alloys. Accordingly, three distinct synergies, involving lattice oxygen redox from Pt-Co alloy/Co3O4 clusters, dual-active sites engineering via Pt-rich alloy/CoOx overlayer, and electron coupling within exposed alloy, are identified and quantified for CO oxidation (gas-phase), ammonia borane hydrolysis (liquid-phase), and hydrogen evolution reaction (electrocatalysis), respectively. The resultant synergy-dependent volcano curves represent an advancement over traditional composition-/size-dependent ones, serving as a bridge between theoretical models and experimental observations in bimetallic catalysis.

Abstract This study evaluates the survival outcomes of segmental ureterectomy (SU) combined with chemotherapy in patients with high-grade non-metastatic ureteral cancer (UC) using data from the SEER database. A total of 1757 patients with Grade III-IV non-metastatic UC were analyzed. Overall survival (OS) was assessed through Kaplan–Meier analysis, and independent prognostic factors were identified via Cox regression. A Nomogram model was developed and evaluated using the concordance index, area under the time-dependent ROC curve, calibration curves, and decision curve analysis. The 1-, 3-, and 5-year OS rates were 82.8%, 55.6%, and 42.8%, respectively. Age, treatment protocol, T stage, and N stage were significant prognostic factors. Both SU + chemotherapy and radical nephroureterectomy (RNU) + chemotherapy demonstrated comparable survival outcomes, outperforming surgery alone, particularly in patients aged 70 and older. The Nomogram demonstrated high predictive accuracy and clinical utility. These findings suggest that SU + chemotherapy offers survival benefits similar to RNU + chemotherapy, making it a viable option, especially for elderly patients or those with impaired renal function.

Abstract Background The urinary albumin to creatinine ratio (UACR) is associated with adverse cardiovascular outcomes, even when within the normal range. However, the potential modification of this effect by metabolic abnormalities remains unclear. This study explored whether metabolic abnormalities modify the association between normal-range UACR and cardiovascular mortality. Methods This cohort study included 27,298 U.S. adults from the National Health and Nutrition Examination Survey 1999–2018, with mortality follow-up through December 31, 2019. Normal UACR (

Abstract Objectives This study aimed to compare the temperature rise, time consuming and cut quality of apicectomy using three different methods. Materials and methods Twenty-four single-rooted teeth were collected and divided into four groups operating apicectomy with a NINJA tip of a piezoelectric device (G1), a diamond bur with 300,000 rpm (G2), and Er: YAG laser at 200 mJ/ 30 Hz (G3) as well as 250 mJ/ 30 Hz (G4). The temperature elevation and time were recorded and the cut quality was evaluated via stereomicroscope and scanning electronic microscopy (SEM). Results The temperature increases for G1 was significantly higher than for G2. However, there was no significant difference between G1 and G2 with laser groups respectively. The median time for apicectomy was: 100.14s for G1, 22.65s for G2, 33.58s for G3, and 21.80s for G4. G1 is the most time-consuming group and there was no statistically significance in the comparisons with G2, G3 and G4. Cut quality was assessed by crack occurrence, smear layer formation and dentinal tubules exposed. The percentage of cracked teeth in G1 and G2 was 33.33% and for laser groups the percentage was 16.67% each. SEM showed that no smear layer formed and almost all dentinal tubules were exposed on resected surfaces for G3&G4, surfaces from G2 were partly covered by smear layer, and surfaces from G1 were fully covered by smear layer and with no dentinal tubules exposed. Conclusions Er: YAG laser and conventional rotary instruments were safe and efficient for apicectomy and with a better cut quality when compared with piezoelectric equipment. Er: YAG laser could be a promising technique for apicectomy and further studies are necessary, especially larger sample in vivo investigations, to verify the feasibility of Er: YAG laser in endodontic surgery.

Abstract Background Pulmonary embolism (PE) is life-threatening and requires timely and accurate diagnosis, yet current imaging methods, like computed tomography pulmonary angiography, present limitations, particularly for patients with contraindications to iodinated contrast agents. We aimed to develop a quantitative texture analysis pipeline using machine learning (ML) based on non-contrast thoracic computed tomography (CT) scans to discover intensity and textural features correlated with regional lung perfusion (Q) physiology and pathology and synthesize voxel-wise Q surrogates to assist in PE diagnosis. Methods We retrospectively collected 99mTc-labeled macroaggregated albumin Q-SPECT/CT scans from patients suspected of PE, including an internal dataset of 76 patients (64 for training, 12 for testing) and an external testing dataset of 49 patients. Quantitative CT features were extracted from segmented lung subregions and underwent a two-stage feature selection pipeline. The prior-knowledge-driven preselection stage screened for robust and non-redundant perfusion-correlated features, while the data-driven selection stage further filtered features by fitting ML models for classification. The final classification model, trained with the highest-performing PE-associated feature combination, was evaluated in the testing cohorts based on the Area Under the Curve (AUC) for subregion-level predictability. The voxel-wise Q surrogate was then synthesized using the final selected feature maps (FMs) and model score maps (MSMs) to investigate spatial distributions. The Spearman correlation coefficient (SCC) and Dice similarity coefficient (DSC) were used to assess the spatial consistency between FMs or MSMs and Q-SPECT scans. Results The optimal model performance achieved an AUC of 0.863 during internal testing and 0.828 on the external testing cohort. The model identified a combination containing 14 intensity and textural features that were non-redundant, robust, and capable of distinguishing between high- and low-functional lung regions. Spatial consistency assessment in the internal testing cohort showed moderate-to-high agreement between MSMs and reference Q-SPECT scans, with median SCC of 0.66, median DSCs of 0.86 and 0.64 for high- and low-functional regions, respectively. Conclusions This study validated the feasibility of using quantitative texture analysis and a data-driven ML pipeline to generate voxel-wise lung perfusion surrogates, providing a radiation-free, widely accessible alternative to functional lung imaging in managing pulmonary vascular diseases. Clinical trial number Not applicable.

Abstract Ferroptosis is a promising strategy for cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIPPCPO) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIPPCPO is found to boost lysosomal Fe2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in glutathione peroxidase 4 (GPX4) suppression, glutathione depletion and ferroptosis in breast cancer cells and xenografts. Importantly, LIPPCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 cancer cell lines. Furthermore, a strong synergistic ferroptosis effect is observed between LIPPCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIPPCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing ferroptosis and highlight the potential of LIPPCPO as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.

Abstract Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.

Abstract Background To investigate the association between metabolic syndrome (MetS) and its components with sarcopenia, and to explore the extent to which insulin resistance (IR) mediates this association, using data from the National Health and Nutrition Examination Survey (NHANES). Methods We analyzed cross-sectional data from 15,779 adults in the NHANES from 1999 to 2006 and 2011–2018. Multivariable logistic regression models were used to determine the odds ratios (ORs) between MetS, its components, the number of MetS components, and sarcopenia. Mediation analysis was performed to explore the role of the homeostatic model assessment of insulin resistance (HOMA-IR) in MetS and its components-induced sarcopenia. Result In the fully adjusted model, MetS increased the prevalence of sarcopenia by 1.96-fold (95% CI: 1.73–2.22). Among the individual components, central obesity, hypertension, and hyperglycemia were associated with an increased prevalence of sarcopenia. Sarcopenia prevalence also increased linearly with the number of MetS components, with the highest prevalence observed in the presence of all five components (OR: 3.80, 95% CI: 2.79–5.16). Sex-stratified analysis showed that the prevalence of MetS for sarcopenia was higher in males than females. The mediating effects of HOMA-IR on the association between MetS and its components (central obesity, hypertension, and hyperglycemia) with sarcopenia were significant, with mediation effects of 51.7%, 30.7%, 33.2%, and 79.1%, respectively. There was no significant direct association between hyperglycemia and sarcopenia beyond the HOMA-IR pathway. Conclusion MetS and its individual components, excluding hypertriglyceridemia and low high density lipoprotein cholesterol, were associated with a higher prevalence of sarcopenia, especially in males. This association was partially or fully mediated by IR.

Abstract The electrocatalytic valorization of polyethylene terephthalate-derived ethylene glycol to valuable glycolic acid offers considerable economic and environmental benefits. However, conventional methods face scalability issues due to rapid activity decay of noble metal electrocatalysts. We demonstrate that a dynamic potential cycling approach, which alternates the electrode potential between oxidizing and reducing values, significantly mitigates surface deactivation of noble metals during electrochemical oxidation of ethylene glycol. This method enhances catalyst activity by 20 times compared to a constant-potential approach, maintaining this performance for up to 60 h with minimal deactivation. In situ Raman and X-ray absorption spectroscopy show that this effectiveness results from efficient removal of surface oxide during the reaction. The strategy is applicable to polyethylene terephthalate hydrolysates and various noble metals, such as palladium, gold, and platinum, with palladium showing a high conversion rate in recent studies. Our approach offers an efficient and durable method for electrochemical upcycling of biomass-derived compounds.

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband’s spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Abstract Introduction Methadone has shown effectiveness in pain control in patients with cancer who are intolerant to other opioids in China. However, the optimal strategy for methadone conversion from previous high doses of opioids in refractory cancer pain remains debatable. This study aimed to describe the efficacy and safety of a 3-day switch (3DS) strategy for methadone conversion in patients with refractory cancer pain on high doses of opioids. Methods We retrospectively reviewed 30-day medical records of 70 patients with refractory cancer pain who used a 3DS strategy for methadone conversion from previous high doses of opioids from July 2018 to December 2022. The 3DS strategy indicated that the methadone dose was increased by one third every day for 3 days. Data on the rate of successful conversion, the time to stable analgesia after conversion, the conversion efficiency, the corrected QT (QTc) interval, the actual conversion ratios, adverse events (AEs), and quality of life were analyzed. Results Seventy patients received 3DS methadone conversion and 64 patients were eligible for analysis. Fifty patients (78%) achieved stable analgesia, and the median time to stable analgesia was 8.14 ± 2.70 (range 6–14) days. The average dose of methadone was 77.94 ± 42.74 mg. The most common AEs (≥ 10%) included constipation, dry mouth, nausea, and cold sweats. The incidence of constipation was reduced post-methadone conversion, and a statistically significant but asymptomatic prolongation of the QTc interval was observed. Additionally, the actual conversion ratios were lower than Ayonrinde's recommended ratios. Conclusions The 3DS strategy for methadone conversion is applicable in Chinese patients with refractory cancer pain on high doses of opioids.

IntroductionSepsis is a global health threat that has a high incidence and mortality rate. Early prediction of sepsis onset can drive effective interventions and improve patients’ outcome.MethodsData were collected retrospectively from a cohort of 2,329 adult patients with positive bacteria cultures from a tertiary hospital in China between October 1, 2019 and September 30, 2020. Thirty six clinical features were selected as inputs for the models. We trained models in predicting sepsis by machine learning (ML) methods, including logistic regression, decision tree, random forest (RF), multi-layer perceptron, and light gradient boosting. We evaluated the performance of the five ML models and the evaluation metrics were: area under the ROC curve (AUC), accuracy, F1-score, sensitivity and specificity. The data of another cohort of 2,286 patients between October 1, 2020 and April 1, 2022 were used to validate the performance of the model performing best in the in the internal validation set. Shapley additive explanations (SHAP) method was applied to evaluate feature importance and explain the predictions of this model.ResultsOf the five machine learning models developed, the RF model demonstrated the best performance in terms of AUC (0.818), F1 value (0.38), and sensitivity (0.746). The RF model also has a comparable AUC (0.771) in the external validation set. The SHAP method identified procalcitonin, albumin, prothrombin time, and sex as the important variables contributing to the prediction of sepsis.DiscussionThe RF model we developed showed the greatest potential for early prediction of sepsis in admitted patients, which could aid clinicians in their decision-making process. Our findings also suggested that male patients with bacterial infections and high procalcitonin levels, lower albumin levels, or prolonged prothrombin times were more likely to develop sepsis.

Distiller's grains (DGs) is the by-product during liquor brewing, can be utilized as a renewable fuel by pyrolysis and gasification techniques, promoting energy conservation and emissions reduction. The pyrolysis kinetics and air-steam gasification performances were examined through thermogravimetric analysis (TGA) and fixed-bed reactor experiments. The TGA results indicated that, the DGs pyrolysis roughly occurred at 140.0–400.0 °C, and two splitting peaks at about 310.0 °C and 350.0 °C, corresponded to the cracking of cellulose and lignin, respectively. The second and third pyrolysis stages separately had the activation energies of 188.0 and 148.1 kJ/mol, and could be severally described by (1-x)2 and (1-x)3.5. Air-steam gasification experiments of DGs were conducted to investigate the impacts of gasifying temperature, air volume flow, and steam flow on gas compositions and yields, lower calorific value of syngas (Qgas), efficiencies of carbon conversion and gasification (ηC and ηG). All performance parameters first grew and then reduced with temperature rising, and the highest values of Qgas, ηC and ηG all reached at 750 °C. The equivalence ratio (ER) of 0.4 and steam-to-DGs ratio of 0.5 were suggested for DGs gasification. The results of this study could provide useful information for the energy utilization of distiller's grains through pyrolysis and gasification.

ABSTRACT Background Pain is a prevalent comorbidity in numerous clinical conditions and causes suffering; however, the mechanism of pain is intricate, and the neural circuitry underlying pain in the brain remains incompletely elucidated. More research into the perception and modulation of pain within the central nervous system is essential. The nucleus accumbens (NAc) plays a pivotal role in the regulation of animal behavior, and extensive research has unequivocally demonstrated its significant involvement in the occurrence and development of pain. NAc receives projections from various other neural nuclei within the brain, including the paraventricular nucleus of the thalamus (PVT). In this experiment, we demonstrate that the specific glutamatergic neural circuit projection from PVT to NAc (PVTGlut→NAc) is implicated in the modulation of inflammatory pain in mice. Methods We compared the difference in pain thresholds between complete Freund's adjuvant (CFA)‐induced inflammatory pain models and controls. Then in a well‐established mouse model of CFA‐induced inflammatory pain, immunofluorescence staining was utilized to evaluate changes in c‐Fos protein expression within PVT neurons. To investigate the role of PVTGlut→NAc in the modulation of pain, we used optogenetics to modulate this neural circuit, and nociceptive behavioral tests were employed to investigate the functional role of the PVTGlut→NAc circuit in the modulation of inflammatory pain. Results In the mice with the inflammatory pain group, both the paw withdrawal latencies (PWLs) and paw withdrawal thresholds (PWTs) of the right hind paw were decreased compared to the control group. In addition, compared to the control group, CFA‐induced inflammatory pain led to increased c‐Fos protein expression in PVT, which means that some of the neurons in this area of the brain region have been activated. Following the injection of retrograde transport fluorescent‐labeled virus into NAc, glutamatergic neurons projecting from the PVT to NAc were observed, confirming the projection relationship between PVT and NAc. In the experiments in optogenetic regulation, normal mice exhibited pain behavior when the PVTGlut→NAc circuit was stimulated by a 473 nm blue laser, resulting in decreased PWLs and PWTs compared to the control group, which means activating this neural circuit can lead to painful behaviors. In the CFA‐induced pain group, inhibition of the PVTGlut→NAc circuit by a 589 nm yellow laser alleviated pain behavior, leading to increased PWLs and PWTs compared to the control group, representing the fact that inhibition of this neural circuit relieves pain behaviors. Conclusions The findings unveil a pivotal role of the PVTGlut→NAc circuit in modulating inflammatory pain induced by CFA in mice.

ABSTRACT It is well known that gut microbial imbalance is a potential factor for the occurrence and development of diabetes mellitus (DM) and its complications. Moreover, the heart and gut microbiota can regulate each other through the gut–metabolite–heart axis. In this study, metagenomics, metabolomics, and transcriptomics were chosen to sequence the changes in gut microbiota, serum metabolite levels, and differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice and analyze the correlation between serum metabolites and gut microbiota or DEGs. According to the results, there were significant differences in the 1,029 cardiac genes and 353 serum metabolites in diabetic mice of the db/db group, including DEGs enriched in the PPAR signaling pathway and increased short-chain carboxylic acids (CAs), when compared with the normal db/m group. According to metagenomics, the gut microbiota of mice in the db/db group were disrupted, and particularly Lachnospiraceae bacteria and Oscillospiraceae bacteria significantly decreased. Also, according to the Pearson correlation analysis, a significant positive correlation was found between CAs and PPAR signaling pathway-related DEGs, and a negative correlation was found between CAs and the abundance of the above-mentioned species. To sum up, type 2 diabetes mellitus (T2DM) can upregulate the expression of partial cardiac genes through the levels of serum short-chain CAs affected by gut microbiota, thus playing a role in the occurrence and development of diabetic cardiomyopathy (DCM).IMPORTANCEOur research results clearly link the changes in heart genes of T2DM and normal mice with changes in serum metabolites and gut microbiota, indicating that some genes in biological processes are closely related to the reduction of protective microbiota in the gut microbiota. This study provides a theoretical basis for investigating the mechanism of DCM and may provide preliminary evidence for the future use of gut microbiota therapy for DCM.

Gastrointestinal perforation in patients with juvenile dermatomyositis has been reported as a life-threatening complication in the literature. However, effective treatment of juvenile dermatomyositis with gastrointestinal perforation remains challenging. We report the case of a patient who developed intestinal perforation 5 months after being diagnosed with anti-nuclear matrix protein 2 antibody-positive juvenile dermatomyositis. We systematically reviewed the literature on the medical and/or surgical treatment of gastrointestinal perforation in juvenile dermatomyositis. In addition to our case, as of October 2023, we identified 29 cases of gastrointestinal perforation in patients with juvenile dermatomyositis. Current treatment options for gastrointestinal perforation in juvenile dermatomyositis mainly include corticosteroids, methylprednisolone pulses, rituximab, intravenous immunoglobulin, cyclophosphamide, methotrexate, cyclosporine A, mycophenolate mofetil, and other traditional disease-modifying anti-rheumatic drugs. Notably, juvenile dermatomyositis complicated by gastrointestinal perforation is always associated with disease severity and activity. However, these are extremely severe patients who may not respond to treatment with methylprednisolone pulses and rituximab. Given the limited efficacy of conventional high-intensity systemic immunosuppressive therapy for juvenile dermatomyositis with gastrointestinal perforation, there is an urgent need to explore novel therapeutic approaches. We report on the successful use of vedolizumab in combination with corticosteroids, cyclophosphamide, and intravenous immunoglobulin as a novel therapeutic strategy for treating juvenile dermatomyositis complicated by gastrointestinal perforation. Importantly, up to now, there has been no report of juvenile dermatomyositis with gastrointestinal perforation treated with vedolizumab combined with traditional disease-modifying anti-rheumatic drugs in children.

New epoxy (EP)-based sandwich composites have enhanced mechanical performance and optimized cost-effectiveness, as a result of composites’ increasing popularity. This study aims to develop composites with 3, 5, and 7 layers of woven carbon fibers (WCFs) layered on 3D rayon-based graphite felt (3D RGF) as the core of the sandwich composites. Using WCFs as face sheet layers increases flexural strength and modulus. Flexural strength increases to 226.92 MPa, and modulus increases to 15.18 GPa with 3 WCFs layers. Five layers increase modulus to 25.43 GPa and flexural strength to 370.21 MPa. Seven layers provide the highest modulus of 31.38 GPa and flexural strength of 405.07 MPa. Diverse concentrations of nanosilica (0.01, 0.1, 0.5, and 0.8 wt%) were embedded within the core to bolster its mechanical properties. Using an in situ casting method, an EP resin solution was infused into the structure, forming a bicontinuous composite. This method significantly enhances the toughness and adhesion between the fibers and the EP resin, resulting in superior mechanical properties. EP alone has 57-MPa tensile strength, but three layers of WCFs increase it to 531.38 MPa, five layers increase it to 647.24 MPa, and seven layers increase it to 764.40 MPa. The minimum tensile modulus of EP is 2.75 ± 0.5 GPa. The modulus increases significantly when layers of WCFs are added, reaching 9.75 GPa with three layers, 14.96 GPa with five layers, and a maximum value of 23.44 GPa with seven layers. When a little amount of nanosilica was added, the flexural properties of composites were significantly affected. Among all concentrations, 0. 5 wt% nano-SiO2 yielded the highest enhancement of flexural strength and modulus. At 0.1 wt% nanosilica, the flexural strength and modulus of the sandwich composites increase to 493.5 MPa and 30.5 GPa (23.4% and 24.5%). The peak occurs at 0.5 wt%, reaching 645.7 MPa and 41.5 GPa (61.4% and 69.4%). However, at 0.8 wt%, values drop to 560.1 MPa and 30.4 GPa, still showing 40.0% and 24.1% improvements. This study provides a new solution for reinforcing the mechanical properties of EP sandwich composites. Increasing the performance with nanofiller concentrations is also emphasized.

The growing energy crisis has intensified the need for efficient energy storage solutions. Biomass has emerged as a promising resource for novel energy storage devices. Lignosulfonate, a byproduct of the forestry and pulp industries, contains quinone groups and has enormous potential for electrochemical energy storage. However, due to its poor electrical conductivity, this material must be combined with conductive materials to improve the energy storage efficiency. Carbon materials, particularly porous carbon, are ideal conductive substrates because of their high electrical conductivity, affordability, and ease of fabrication. This study demonstrates the synergistic effects of lignosulfonate/nanocarbon composites (LS/NC), in which heteroatom doping, high specific surface area, and quinone groups considerably enhance their electrochemical performance. Nanocarbon (NC) provides ion diffusion channels with low internal resistance and a large double-layer reaction area, promoting efficient electrolyte ion diffusion and transport. In addition, the introduction of oxygen and sulfur heteroatoms not only increases the material's hydrophilicity but also provides polar surfaces and accessible pseudocapacitive sites. Under acidic conditions, the LS/NC composite achieved a specific capacitance of 571 F g−1 at a discharge rate of 1 A g−1—approximately double that of NC alone (279 F g−1). These findings provide notable advancements in the development of efficient energy storage devices.

Background: Resting tremor in Parkinson’s disease (PD) is associated with the activity in the basal ganglia and cerebello-thalamo-cortical circuits/network. However, most insights stem from functional MRI research, and structural studies, which can provide basis for and constrain functional activity, remains limited. Methods: We investigated the structural change in PD patients with resting tremor (PD-WR) from a network perspective. 42 early-stage PD-WR, 27 PD patients without resting tremor (PD-NR), and 56 healthy controls (HC) were included. Results: PD-WR showed lower cortical thickness in several motor-related lobules. Compared to HC, significant atrophy was found in right lobule VIIA (t = -3.076, p = 0.016, Cohen's d = 0.627), left lobule VI (t = -3.323, p = 0.007, Cohen's d = 0.678), and right lobule VI (t = -3.052, p = 0.017, Cohen's d = 0.623) in PD-WR. Compared to PD-NR, left lobule V also had a significant reduction (t = -2.958, p = 0.023, d = −0.657). PD-WR had higher fractional anisotropy in cerebello-cortical connection compared to HC (t = 3.209, p = 0.009, d = 0.926), with reduced radial (t = -2.561, p = 0.046, d = 0.739) and mean (t = 2.614, p = 0.046, d = 0.871) diffusivity compared to PD-NR. At the network level, better hierarchy (rho = 0.598, p = 0.004), small-worldness (rho = 0.621, p = 0.003), and increased nodal involvement of the thalamus (rho = 0.718, p = 0.031) and motor cortex (rho = 0.660, p = 0.055) were positively correlated with tremor amplitude. Conclusion: Our study supports the alternation of the cerebello-thalamo-cortical circuit in PD-WR. However, further research with other forms of PD, a wide range of disease stage and larger sample size is needed.

Abstract Polymer nanofibers exhibit unique nanoscale effects, high specific strength and modulus, exceptional design flexibility, large aspect ratios, and substantial specific surface areas. These characteristics have drawn significant attention in emerging fields such as flexible electronics, 5G communications, and new energy vehicles. Notably, poly(p‐phenylene benzobisoxazole) nanofibers (PNFs) present the best thermal stability and flame retardancy among all known polymer nanofibers. Furthermore, due to the highly oriented molecular chains and orderly structure, PNFs demonstrate superior thermal conductivity compared to conventional polymer nanofibers, thus garnering significant attention and favor from researchers. This paper summarizes the latest research progress of PNFs, detailing three preparation methods (electrospinning, mechanical dissociation, and protonation) along with their respective advantages and disadvantages. It also elucidates the current development status of PNFs in applications such as flame retardancy, thermal conduction, electrical insulation, electromagnetic shielding, and battery separators, and discusses the challenges and prospects faced by PNFs. This paper aims to provide theoretical guidance for the preparation and application of PNFs, enhancing their potential in advanced applications, and further expanding their application scope.

IntroductionWe investigated the relationship between systematic regulators of inflammation and the risk of age-related macular degeneration (AMD), both wet and dry forms, by using bidirectional, two-sample Mendelian randomization (MR).MethodsWe performed bidirectional two-sample Mendelian randomization analysis using genome-wide study (GWAS) data for 91 plasma proteins from 14,824 individuals of European descent across 11 study groups. Next, we utilized data from the FinnGen consortium to study AMD using the inverse- variance-weighted approach for Mendelian randomization. Additional analyses involved MR-Egger, Weighted median, Weighted mode, MR-PRESSO, and MR- Steiger filtering techniques.ResultsWe identified 16 cytokines associated AMD outcomes and post FDR correction, higher levels of fibroblast growth factor 19 and leukemia inhibitory factor receptor were associated with decreased risk for AMD, while higher levels of tumour necrosis factor ligand superfamily member 14 were associated with increased risk for AMD. Additionally, higher levels of interleukin-10 receptor subunit alpha were associated with decreased risk for wet AMD, higher levels of leukemia inhibitory factor receptor were associated with decreased risk for dry AMD, and higher levels of signaling lymphocytic activation molecule were associated with increased risk for dry AMD. Genetic susceptibility to AMD was associated with elevated levels of TNF-related activation-induced cytokines (TNFSF11), and genetic susceptibility to wet AMD was associated with elevated levels of TNFSF11, interleukin-18 receptor 1 (IL18R1), and CUB domain-containing protein 1 (CDCP1).DiscussionThis research enhances our understanding of systemic inflammation in AMD, providing insights into etiology, diagnosis, and treatment of AMD and its forms.

Abstract Citrate esters have become the main alternatives to traditional plasticizers in food packaging materials. However, there is a lack of understanding of their toxic effects, particularly the combined effects and inner mechanisms has not been well studied. Our group pioneered the study on combined toxicity of tributyl citrate (TBC) and acetyl triethyl citrate (ATEC), two commonly co‐used citrate esters in food packaging materials. The results showed that exposure to TBC and ATEC can decrease the viability of HepG2 cells in a dose dependent manner. When the mixtures of ATEC and TBC exposed to HepG2 cells, they exhibited antagonism effect. Therefore, ATEC was selected to investigate the molecular mechanisms with multi‐omics techniques at its 1/4 EC50 concentration. A total of 31 metabolites with significant changes were found as potential biomarkers. The LIPG (Lipase G, endothelial type) and GCLM (glutamate‐cysteine ligase modifier subunit) were identified as differentially expressed genes based on transcriptomic analysis. Moreover, downregulated l‐glutamate and l‐glutamine which participate in TCA cycle, resulting in the collapse of energy production and cytotoxicity. These findings on major metabolic pathways will provide insight into the mechanism of cytotoxicity of HepG2 cells after ATEC exposure.

Fabricating biofavorable nanostructures on Ti6Al4V abutment surface is a promising strategy for improving gingival soft tissue integration (STI) in order to prevent bacteria invasion. Although some structures show both biocompatible and bacterial repulsive, the decades exposure in oral cavity cannot guarantee zero infection. Therefore, developing bioactive and rigid layer is a realistic strategy for clinical scenario. In this study, the dealloying technique was introduced to create nano-grass layer on Ti6Al4V surface by removing Al element. The average size of 30 nm surface could induce the highest and aligned extracellular matrix (ECM) secretion in primary human gingival fibroblasts, accompanied by extensive focal adhesions formation. The epithelial layer in the gingiva-abutment interface was condenser and crosslinked, as indicated by more ECM proteins expression and resistant to HRP invasion. Mechanistically, the cdc42 upregulation and ERK activation account for actin filaments rearrangement and focal adhesions enrichment. Moreover, the grass-like surface showed slight bacteria repulsive property. Thanks to the advantages of dealloying technique, the rigid layer did not show significant damage after conventional scaling by plastic dental scaler. In conclusion, the dealloying technique may be a novel convenient and realistic strategy creating rigid nanoporous surface for both enhancing STI and resistant to physical biofilm removal.

Magnesium oxysulfate (MOS) cement, with its low carbon footprint, faces challenges in water resistance and volume stability. This study examines how fly ash (FA) and ground granulated blast-furnace slag (GGBS) improve MOS cement properties. Findings show that adding FA and GGBS significantly enhances the mechanical properties, water resistance, and volume stability of MOS cement. An optimal admixture content of 45 % and an FA to GGBS ratio of 2:1 increase compressive and flexural strengths to 71.8 MPa and 16.5 MPa. The study also reveals that FA and GGBS do not introduce new hydration crystalline phases and limited secondary reactions occur due to the low alkalinity of MOS cement. The improvement of MOS cement is primarily attributed to the micro-aggregate effect, which optimizes the pore structure by reducing harmful pores and total porosity. The findings suggest that FA and GGBS are effective in enhancing the performance of MOS cement.

Enzymes provide attractive targets for drug development. Quantitative analysis of enzyme reactions can lead to rational drug discovery. For undergraduates majoring in biochemistry or pharmacy and engaged in drug discovery-related work, it is essential to acquire a comprehensive understanding of enzyme kinetics, including experimental methods and the fundamental principles of drug screening. Being overexpressed in cancer, MTHFD2 is an emerging anticancer drug target. Herein, we used MTHFD2 to develop a high-throughput drug screening laboratory course based on enzyme kinetics for upper-division undergraduate students. The learning activities that were designed for students included "Escherichia coli"-based protein expression, protein purification, enzyme activity assay, setting up a high-throughput drug screening assay, and data analysis. The main purpose of this one-week laboratory education course is to provide students with a better understanding of enzyme kinetics, high-throughput drug screening and to help them grasp the relationship between enzyme kinetics and drug discovery. This hands-on course provides students an opportunity to learn how theoretical knowledge is applied in real practice.

Abstract Developing high-performance Pt-based catalysts with low Pt loading is crucial but challenging for CO oxidation at temperatures below 100 °C. Herein, we report a Pt-based catalyst with only a 0.15 wt% Pt loading, which consists of Pt–Ti intermetallic single-atom alloy (ISAA) and Pt nanoparticles (NP) co-supported on a defective TiO2 support, achieving a record high turnover frequency of 11.59 s–1 at 80 °C and complete conversion of CO at 120 °C. This is because the coexistence of Pt–Ti ISAA and Pt NP significantly alleviates the competitive adsorption of CO and O2, enhancing the activation of O2. Furthermore, Pt single atom sites are stabilized by Pt–Ti ISAA, resulting in distortion of the TiO2 lattice within Pt–Ti ISAA. This distortion activates the neighboring surface lattice oxygen, allowing for the simultaneous occurrence of the Mars-van Krevelen and Langmuir–Hinshelwood reaction paths at low temperatures.

Abstract In recent years, with the development of 3D digitization of cultural relics, most cultural sites contain a large number of fine 3D data of cultural relics, especially complex geometric objects such as painted cultural relics. At present, how to automatically extract surface damage information from the fine 3D color model of painted cultural relics and avoid the loss of accuracy caused by reducing the dimension using conventional methods is an urgentproblem. In view of the above issues, this paper proposes an automatic and high-precision extraction method for cultural relics surface shedding diseases based on 3D fine data. First, this paper designs a 2D and 3D integrated data conversion model based on OpenSceneGraph, a 3D engine, which performs mutual conversion between 3D color model textures and 2D images. Second, this paper proposes a simple linear iterative clustering segmentation algorithm with an adaptive k value, which solves the problem of setting the superpixel k value and improves the accuracy of image segmentation. Finally, through the 2D and 3D integrated models, the disease is statistically analyzed and labeled on the 3D model. Experiments show that for painted plastic objects with complex surfaces, the disease extraction method based on the 3D fine model proposed in this paper has improved geometric accuracy compared with the current popular orthophoto extraction method, and the disease investigation is more comprehensive. Compared with the current 3D manual extraction method in commercial software, this method greatly improves the efficiency of disease extraction while ensuring extraction accuracy. The research method of this paper activates many existing 3D fine data of cultural protection units and converts conventional 2D data mining and analysis into 3D, which is more in line with the scientific utilization of data in terms of accuracy and efficiency and has certain scientific research value, leading value and practical significance.