Search

Crohn's disease (CD) is a chronic inflammatory bowel condition, and colon adenocarcinoma (COAD), as one of the most prevalent malignant tumors of the digestive tract, has been indicated by research to have a close association with CD. This study employs bioinformatics techniques to uncover the potential molecular links between CD and COAD. In this study, two data series related to CD were identified from the Gene Expression Omnibus (GEO) database under specific criteria, and relevant COAD gene data were obtained from The Cancer Genome Atlas (TCGA). Weighted Gene Co-expression Network Analysis (WGCNA), differentially expressed genes (DEGs), and protein-protein interaction (PPI) network analysis were conducted. A diagnostic model was established using machine learning. The accuracy of the diagnosis was validated using methods such as the construction of Receiver Operating Characteristic (ROC) curves and nomograms. Gene Set Enrichment Analysis (GSEA) was also employed to enrich the relevant pathways and biological processes. This study identified three genes through machine learning selection: DPEP1, MMP3, and MMP13. The ROC curves demonstrated that the machine learning model constructed with these three genes has a high level of accuracy, confirming their potential as biomarkers. Furthermore, GSEA elucidated that the pathways associated with these three key genes are closely related to cytokines and other factors. This study has identified key biomarker genes for CD and COAD: DPEP1, MMP3, and MMP13, providing additional molecular mechanism associations between the two diseases. It also offers more connections and pathways for reference regarding the progression of CD to COAD., Competing Interests: Declarations. Ethics statement: Ethical approval for NHANES was secured from the NCHSR esearch Ethics Review Board,and each participant willingly provided written informed consent.. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Urban rail transit systems, represented by subways, have significantly alleviated the traffic pressure brought by urbanization and have addressed issues such as traffic congestion. However, as a commonly used construction method for subway tunnels, shield tunneling inevitably disturbs the surrounding soil, leading to uneven ground surface settlement, which can impact the safety of nearby buildings. Therefore, it is crucial to promptly obtain and predict the ground surface settlement induced by shield tunneling construction to enable safety warnings and evaluations. This study collects multi-point surface settlement data from monitoring sections and proposes a data preprocessing method based on tangent circles to transform discrete monitored data into continuous and smooth data. On this basis, the Particle Swarm Optimization (PSO) algorithm is employed to optimize a Back Propagation Neural Network(BPNN) for the subsequent prediction of ground surface settlement. The influence of network structure and prediction mode on prediction accuracy is investigated. The study predicts and verifies the settlement over a 5-day period during both the slow settlement stage and the stable stage to evaluate the predictive performance of the proposed method. The maximum relative error of the prediction based on the data preprocessing method and PSO-BP algorithm is 0.46%, demonstrating a good fitting effect. The study indicates that this method can provide a valuable reference for safety warnings and control of ground surface settlement during shield tunneling construction., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Despite the progress in conventional treatments for head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate remains below 70%. Enhancing immunotherapy outcomes through personalized treatment strategies, particularly by identifying immune-related biomarkers, is critical. The ASXL family are associated with malignancies, but their relationship with HNSCC has not been elucidated. In this study, we found that high expression of ASXL2 is associated with better prognosis in HNSCC patients. Analysis revealed a significant positive correlation between ASXL2 and immune infiltration. Functional analysis suggests that ASXL2 co-expressed genes in HNSCC patients are enriched in the JAK-STAT signaling pathway, and patients with high expression show an even greater enrichment in T cell and B cell receptor signaling pathways. Utilizing the NPC single-cell dataset, ASXL2's widespread expression in the tumor microenvironment was confirmed, and its co-expressed genes were found to be highly associated with immune cell function. Experimental validation showed a correlation between ASXL2 expression and T cell secretion of interferon-γ (IFNγ), confirming that high ASXL2 expression facilitates T cell activation. Overall, our findings underscore the important role of ASXL2 in immune activation, suggesting its potential as a promising biomarker for tailoring immunotherapy strategies in HNSCC patients., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies. Recent advances in proteomic technology and computational sciences now provide opportunities to investigate the intricate biology of the human body at unprecedented resolution and scale. Here we introduce a big-science endeavour called π-HuB (proteomic navigator of the human body). The aim of the π-HuB project is to (1) generate and harness multimodality proteomic datasets to enhance our understanding of human biology; (2) facilitate disease risk assessment and diagnosis; (3) uncover new drug targets; (4) optimize appropriate therapeutic strategies; and (5) enable intelligent healthcare, thereby ushering in a new era of proteomics-driven phronesis medicine. This ambitious mission will be implemented by an international collaborative force of multidisciplinary research teams worldwide across academic, industrial and government sectors., Competing Interests: Competing interests:  R.A. holds shares of Biognosys AG, which operates in the field covered by the article. D.F. is co-founder of MedBiome Inc., a precision nutrition company. K.G. is a shareholder of CYBO, LucasLand, and FlyWorks. T.G. is the founder of Westlake Omics Inc. M.M. is an indirect investor in EvoSep. R.T. is a founder of BayOmics. The other authors declare no competing interests., (© 2024. Springer Nature Limited.)

Aneuploid epithelial cells are common in breast cancer 1,2 ; however, their presence in normal breast tissues is not well understood. To address this question, we applied single-cell DNA sequencing to profile copy number alterations in 83,206 epithelial cells from the breast tissues of 49 healthy women, and we applied single-cell DNA and assay for transposase-accessible chromatin sequencing co-assays to the samples of 19 women. Our data show that all women harboured rare aneuploid epithelial cells (median 3.19%) that increased with age. Many aneuploid epithelial cells (median 82.22%) in normal breast tissues underwent clonal expansions and harboured copy number alterations reminiscent of invasive breast cancers (gains of 1q; losses of 10q, 16q and 22q). Co-assay profiling showed that the aneuploid cells were mainly associated with the two luminal epithelial lineages, and spatial mapping showed that they localized in ductal and lobular structures with normal histopathology. Collectively, these data show that even healthy women have clonal expansions of rare aneuploid epithelial cells in their breast tissues., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Metal nanoparticles have attracted great interest because of their unique near-field enhancement properties, and have important applications in many fields, such as surface-enhanced Raman scattering (SERS), fluorescence enhancement, solar cell efficiency enhancement and so on. In this paper, we use the finite element method to study the local field enhancement characteristics of the coupling system in which the gold ellipsoidal nanoparticles (GENP) on a mirror. In the coupling system, a hot spot will be formed at the gap between the GENP and the mirror under the appropriate incident light excitation. Based on the structural characteristics of GENP, we systematically study the local electric field produced by placing ellipsoids vertically and horizontally on the mirror. Under the excitation of the same polarized incident light, the maximum local electric field of the vertical GENP is 2200 (V/m), while that of the horizontal GENP is more than 9400 (V/m). Our proposed gap coupling system based on metal nanoparticles and thin films may open a new field of interest in the fields of plasmon, sensing, optical limitation and enhancement., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent to participate: All authors accepted., (© 2024. The Author(s).)

The cladding of fast reactor fuel rods, made of stainless steel, presents significant challenges in cutting due to its ductility, which leads to increased tool wear and poor cut quality with traditional mechanical methods. Laser cutting has emerged as a superior alternative, offering non-contact precision, high efficiency, and suitability for radioactive environments. This study systematically investigates the effects of laser cutting parameters-cutting speed, focal position, power, and gas pressure-on the cutting quality of simulated fast reactor fuel rods. The results show that optimal cutting is achieved with a cutting speed of 1 m/min, a focal position between - 20 and - 25 mm, a laser power between 7200 and 9600 W, and a gas pressure of 10 MPa. These parameters provide the best balance between cutting efficiency, surface roughness, and minimal slag formation. This study contributes valuable insights into optimizing laser cutting technology for nuclear fuel rod processing, with potential applications in fuel reprocessing and decommissioning., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBD XBB.1.5 -HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBD XBB.1.5 -HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBD XBB.1.5 -HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (T RM ) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBD XBB.1.5 -HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBD XBB.1.5 -HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBD XBB.1.5 -HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBD XBB.1.5 -HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection., Competing Interests: Competing interests This work was supported by the WestVac Biopharma Co. Ltd. Jingyun Yang, Jiong Li, L.Y., Z.W., W.W., G.S., Jinliang Yang, Z.Z., G.L., and X.W. are also working at the WestVac Biopharma Co. Ltd. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Numerous observational studies suggest associations between proton pump inhibitors (PPIs) and dementia, but causal relationships remain uncertain. Using large-scale genome-wide association study (GWAS) data, we performed univariable Mendelian randomization (UVMR) analysis to assess the causality between five PPI types, and all-cause dementia and its five subtypes. Confounders were controlled through multivariable MR (MVMR) analysis to isolate PPIs' direct effects on dementia. Heterogeneity and pleiotropy assessments, and leave-one-out analysis, were conducted to validate the robustness of our results. Initial UVMR estimates suggested that lansoprazole (odds ratio [OR] 1.291; 95%confidence interval [CI] 1.001-1.665; p = 0.049) and pantoprazole (OR 1.118; 95% CI 1.014-1.233; p = 0.025) potentially increased VD risk, with their respective direct associations also discovered in MVMR. Additionally, FTD was found to reversely increase rabeprazole use (OR 1.086; 95% CI 1.011-1.167; p = 0.023). However, after adjustment for the false discovery rate (FDR), none of these associations remained statistically significant (p FDR > 0.05). The robustness of our results is supported by consistent estimates across complementary MR methods and the absence of pleiotropy. Our study indicates no robust causality between PPI use and increased dementia risk. Thus, it is inappropriate to restrict clinically justified PPI prescriptions merely due to potential cognitive risks., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Automatic analysis of facial expressions has emerged as a prominent research area in the past decade. Facial expressions serve as crucial indicators for understanding human behavior, enabling the identification and assessment of positive and negative emotions. Moreover, facial expressions provide insights into various aspects of mental activities, social connections, and physiological information. Currently, most facial expression detection systems rely on cameras and wearable devices. However, these methods have drawbacks, including privacy concerns, issues with poor lighting and line of sight blockage, difficulties in training with longer video sequences, computational complexities, and disruptions to daily routines. To address these challenges, this study proposes a novel and privacy-preserving human behavior recognition system that utilizes Frequency Modulated Continuous Wave (FMCW) radar combined with Machine Learning (ML) techniques for classifying facial expressions. Specifically, the study focuses on five common facial expressions: Happy, Sad, Fear, Surprise, and Neutral. The recorded data is obtained in the form of a Micro-Doppler signal, and state-of-the-art ML models such as Super Learner, Linear Discriminant Analysis, Random Forest, K-Nearest Neighbor, Long Short-Term Memory, and Logistic Regression are employed to extract relevant features. These extracted features from the radar data are then fed into ML models for classification. The results show a highly promising classification accuracy of 91%. The future applications of the proposed work will lead to advancements in technology, healthcare, security, and communication, thereby improving overall human well-being and societal functioning., Competing Interests: Additional information Correspondence and requests for materials should be addressed to H.H., or Q.H.A. Competing Interests The authors declare no competing interests., (© 2024. The Author(s).)

Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin-sensitive ion channel implicated in pain sensation. While TRPV1 potentiation in hyperalgesia development has been extensively investigated, its functional decline during pain relief remains largely unexplored. Here, by molecular, electrophysiological and in vivo evidence, we reveal that S-palmitoylation fine-tunes TRPV1 function by promoting its degradation via the lysosome pathway thereby facilitating inflammatory pain relief. The palmitoyl acyltransferase ZDHHC4 is identified to physically interact with TRPV1 and to catalyze S-palmitoylation at the cysteine residues C157, C362, C390, and C715 of the channel. Furthermore, we show that TRPV1 palmitoylation is counterbalanced by the depalmitoylase acyl-protein thioesterase 1 (APT1), thereby reinstating pain sensation. These findings provide important mechanistic insights into the relief phase of inflammatory pain., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants. Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury. Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs. This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies., (© 2024. The Author(s).)

L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the preferred treatment for Parkinson's Disease (PD) and is considered the gold standard. However, prolonged use of L-DOPA in patients can result in involuntary movements known as Levodopa-induced dyskinesia (LID), which includes uncontrollable dystonia affecting the trunk, limbs, and face. The role of ΔFosB protein, a truncated splice variant of the FosB gene, in LID has been acknowledged, but its underlying mechanism has remained elusive. Here, using a mouse model of Parkinson's disease treated with chronic levodopa we demonstrate that serum response factor (SRF) binds to the FosB promoter, thereby activating FosB expression and levodopa induced-dyskinetic movements. Western blot analysis demonstrates a significant increase in SRF expression in the dyskinetic group compared to the control group. Knocking down SRF significantly reduced abnormal involuntary movements (AIMS) and ΔFosB expression compared to the control. Conversely, overexpression of SRF led to an increase in ΔFosB expression and worsened levodopa-induced dyskinesia. To shed light on the regulatory role of the Akt signaling pathway in this phenomenon, we administered the Akt agonist SC79 to PD mouse models via intraperitoneal injection, followed by L-DOPA administration. The expression of SRF, ΔFosB, and phosphorylated Akt (p-Akt) significantly increased in this group compared to the group receiving normal saline to signify that these happen through Akt signaling pathway. Collectively, our findings identify a promising therapeutic target for addressing levodopa-induced dyskinesia., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate Laboratory animal care and use protocols approved by the Xuzhou Medical University’s institutional animal care and use committee. This study exclusively utilized mice, therefore consent to participate is not applicable. Consent for publication All authors consent to the publication of this manuscript., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This retrospective study used cone-beam computed tomography to investigated the crown-root morphology and alveolar bone structure in incisors region in subjects with closed deep overbite and comparison the difference between gender and age. The CBCT images for 40 subjects (group C) with Angle II division 2 were selected from patients of the HeFei Stomatological Hospital from November 2023 to March 2024.20 individual normal occlusion subjects (group A),20 patients with Angle II division 1(group B) were included. The crown-root ratio of the maxillary and mandibular anterior teeth, crown-root angle and alveolar bone structure were measured on the CBCT images, the data were statistically analyzed. In addition to mandibular lateral incisor, the crown-root ratio of maxillary and mandibular anterior teeth in the Class II division 2 group was higher than that in the individual normal occlusion group and the Class II division 1 (P < 0. 05). The crown-root angle of maxillary anterior teeth in the Class II division 2 group was smaller than that in the individual normal occlusion group and the Class II division 1 (P < 0. 05). The alveolar bone thickness of the maxillary central incisor was comparatively smaller, while the alveolar bone height was relatively higher in the Class II division 2 group. Age and gender were associated with change in root lengths and crown-root angle for the Class II division 2 group (P < 0. 05). Patients with closed deep overbite malocclusion exhibit a significant difference compared to the controls for most measurements. The patients presenting with Class II division 2 malocclusion exhibit excessive inward positioning of the anterior teeth, resulting in evident crown-root angle, a large crown-root ratio, and minimal labial alveolar bone. In order to keep the tooth movement within the safe range of alveolar bone movement, it is necessary to strictly control the torque and use appropriate orthodontic force to reduce the risk of bone fenestration, bone dehiscence, gingival recession and root resorption., (© 2024. The Author(s).)

This study aimed to evaluate the bioequivalence between test and reference insulin degludec (IDeg) and the effects of body composition on pharmacokinetics and pharmacodynamics of IDeg in Chinese healthy volunteers. In this randomized, open-label, crossover trial, 30 healthy Chinese males were assigned to receive a single subcutaneous dose (0.4 IU/kg) of each formulation under 24-h euglycemic hyperinsulinaemic clamp. Body compositions were analysed prior to administration and blood samples were collected at specific times. The 90% of primary pharmacokinetic parameters and 95% of primary pharmacodynamic parameters confidence intervals for the ratio of the least-squares geometric means were all in the range of 80-125%. As the fat content level increases, C max , AUC 0-12 and GIR-AUC 0-24 decreased whereas AUC 24-96 increased sequentially. Therefore, the equivalence was demonstrated between test and reference, and in healthy Chinese volunteers, higher levels of adiposity are associated with slower rates of insulin absorption and distribution and the poorer glucose-lowering effect., (© 2024. The Author(s).)

Benign prostatic hyperplasia (BPH) as a common geriatric disease in urology, the incidence and prevalence are rapidly increasing with the aging society, prompting an urgent need for effective prevention and treatment of BPH. However, limited therapeutic efficacy and higher risk of complications result in the treatment of BPH remaining challenging. The unclear pathogenic mechanism also hampers further exploration of therapeutic approaches for BPH. In this study, we used multi-omics methods to integrate genomics, transcriptomics, immunomics, and metabolomics data and identify biomolecules associated with BPH. We performed transcriptomic imputation, summary data-based Mendelian randomization (SMR), joint/conditional analysis, colocalization analysis, and FOCUS to explore high-confidence genes associated with BPH in blood and prostate tissue. Subsequently, three-step SMR was used to identify the DNA methylation sites regulating high-confidence genes to improve the pathogenic pathways of BPH. We also used cis-instruments of druggable genes to conduct SMR analysis to find potential drug targets for BPH. Finally, we used MR analysis to explore the immune pathways and metabolomics related to BPH. Multiple analytical methods identified BTN3A2 (Blood: TWAS Z score = 5.02912, TWAS P = 4.93 × 10 -7 ; Prostate: TWAS Z score = 4.89, TWAS P = 1.01 × 10 -6 ) and C4A (Blood: TWAS Z score = 4.90754, TWAS P = 9.22 × 10 -7 ; Prostate: TWAS Z score = 5.084, TWAS P = 3.70 × 10 -7 ) as high-confidence genes for BPH and identified the cg14345882-BTN3A2-BPH pathogenic pathway. We also used druggable gene data to identify 30 promising therapeutic target genes, including BTN3A2 and C4A. For MR analysis of immune pathways, we identified immune cell surface molecules as well as the inflammatory factor IL-17 (OR = 1.25, 95% CI = 1.09-1.43, P FDR  = 0.12, Maximum likelihood) as risk factors for BPH. In addition, we found that disulfide levels of cysteinylglycine (OR = 1.11, 95% CI = 1.05-1.18, P = 5.18 × 10 -4 , Weighted median), oxidation levels of cysteinylglycine (OR = 1.09, 95% CI = 1.04-1.14, P = 3.87 × 10 -4 , Weighted median), and sebacate levels (OR = 1.05, 95% CI = 1.02-1.08, P = 3.0 × 10 -4 , Maximum likelihood) increase the risk of BPH. This multi-omics study explored biomolecules associated with BPH, improved the pathogenic pathways of BPH, and identified promising therapeutic targets. Our results provide evidence for future studies aimed at developing appropriate therapeutic interventions., (© 2024. The Author(s).)

Increasing studies have investigated the link between physical activity (PA) and sedentary behavior with venous thromboembolism (VTE) but the existing findings are not consistent and the independent relationship is uncertain. This meta-analysis aimed to comprehensively assess the shape of dose-response relationship between PA and sedentary behavior with VTE and further explore whether the relationship is independent after mutual adjustment. We systematically searched PubMed, Embase and Web of Science from inception to August 1, 2024. PA exposures were converted into MET-h/wk. Categorical meta-analyses and a cubic spline model were performed to evaluate the association between PA, sedentary behavior and VTE. Twenty-five articles including 31 studies were included. A curvilinear dose-response relationship between PA and VTE was observed, with steeper gradients even at lower PA levels. After adjustment for sedentary behavior, higher level of PA was independently associated with a reduced VTE risk (OR = 0.83, 95%CI:0.77-0.89). Based on population attributable fraction analyses, 2.37% (95%CI: 1.90-2.85%) of incident VTE could have been prevented if all adults had achieved half the PA minimum recommended level. A linear dose-response relationship between sedentary behavior and VTE risk was found, and there was a 2% higher risk of VTE (OR = 1.02, 95%CI: 1.00-1.03) for 1 h increment of sedentary behavior per day. After adjustment for PA, sedentary behavior was independently associated with an increased VTE risk (OR = 1.19, 95CI%:1.01-1.39). Our analyses demonstrated PA and sedentary time were indeed independently associated with the risk of VTE after mutually adjusting for sedentary time or PA, highlighting a unique perspective on their individual contributions. Further studies assessing the effects of different combinations of PA and sedentary time for assessing joint effects on VTE are needed., (© 2024. The Author(s).)

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras 1,2 (LYTACs) and cytokine receptor-targeting chimeras 3 (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor. Here we describe computational design approaches for endocytosis-triggering binding proteins (EndoTags) that overcome these challenges. We present EndoTags for insulin-like growth factor 2 receptor (IGF2R) and asialoglycoprotein receptor (ASGPR), sortilin and transferrin receptors, and show that fusing these tags to soluble or transmembrane target protein binders leads to lysosomal trafficking and target degradation. As these receptors have different tissue distributions, the different EndoTags could enable targeting of degradation to different tissues. EndoTag fusion to a PD-L1 antibody considerably increases efficacy in a mouse tumour model compared to antibody alone. The modularity and genetic encodability of EndoTags enables AND gate control for higher-specificity targeted degradation, and the localized secretion of degraders from engineered cells. By promoting endocytosis, EndoTag fusion increases signalling through an engineered ligand-receptor system by nearly 100-fold. EndoTags have considerable therapeutic potential as targeted degradation inducers, signalling activators for endocytosis-dependent pathways, and cellular uptake inducers for targeted antibody-drug and antibody-RNA conjugates., Competing Interests: Competing interests: B.H., M. Abedi, G.A., I.S., L.S. and D.B. are co-inventors on a provisional patent application that incorporates discoveries described in this manuscript. B.C., I.G., J.O., P.G., L.S. and D.B. are co-inventors on a provisional patent application that incorporates discoveries described in this manuscript., (© 2024. The Author(s).)

Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC., (© 2024. The Author(s).)

Brontispa longissima is a highly destructive pest that affects coconut and ornamental palm plants. It is widely distributed across Southeast and East Asia and the Pacific region, causing production losses of up to 50-70%. While control methods and ecological phenomena have been the primary focus of research, there is a significant lack of studies on the molecular mechanisms underlying these ecological phenomena. The absence of a reference genome has also hindered the development of new molecular-targeted control technologies. In this study, we conducted a karyotype analysis of B. longissima and assembled the first high-quality chromosome-level genome. The assembled genome is 582.24 Mb in size, with a scaffold N50 size of 63.81 Mb, consisting of 10 chromosomes and a GC content of 33.71%. The BUSCO assessment indicated a completeness estimate of 98.1%. A total of 23,051 protein-coding genes were predicted. Our study provides a valuable genomic resource for understanding the mechanisms of adaptive evolution and facilitates the development of new molecular-targeted control methods for B. longissima., (© 2024. The Author(s).)

A high efficiency simulation method for propagation-based phase-contrast imaging, called directional macro-wavefront (DMWF), is developed with the aim of simulating high-energy phase-contrast imaging. This method takes both Monte Carlo and wave optical propagation into consideration. Traditional wave-optics-based simulation methods for phase-contrast imaging encounter unacceptable computational complexity when high-energy radiation is used. In contrast, this method effectively addresses this issue by using macro-wavefront integration. Several simulation examples using typical parameters of inverse Compton scattering sources are presented to illustrate the excellent energy adaptability and efficiency of the DMWF method. This method provides a more efficient approach for phase-contrast imaging simulations, which will drive the advancement of high-energy phase-contrast imaging., (© 2024. The Author(s).)

There is a lack of effective treatments to overcome resistance to EGFR-TKIs in EGFR mutant tumors. A deeper understanding of resistance mechanisms can provide insights into reducing or eliminating resistance, and can potentially deliver targeted treatment measures to overcome resistance. Here, we identified that the dynamic changes of the tumor immune environment were important extrinsic factors driving tumor resistance to EGFR-TKIs in EGFR mutant cell lines and syngeneic tumor-bearing mice. Our results demonstrate that the acquired resistance to EGFR-TKIs is accompanied by aberrant expression of PD-L2, leading a dynamic shift from an initially favorable tumor immune environment to an immunosuppressive phenotype. PD-L2 expression significantly affected EGFR mutant cell apoptosis that depended on the proportion and function of CD8 + T cells in the tumor immune environment. Combined with single-cell sequencing and experimental results, we demonstrated that PD-L2 specifically inhibited the proliferation of CD8 + T cells and the secretion of granzyme B and perforin, leading to reduced apoptosis mediated by CD8 + T cells and enhanced immune escape of tumor cells, which drives EGFR-TKIs resistance. Importantly, we have identified a potent natural small-molecule inhibitor of PD-L2, zinc undecylenate. In vitro, it selectively and potently blocks the PD-L2/PD-1 interaction. In vivo, it abolishes the suppressive effect of the PD-L2-overexpressing tumor immune microenvironment by blocking PD-L2/PD-1 signaling. Moreover, the combination of zinc undecylenate and EGFR-TKIs can synergistically reverse tumor resistance, which is dependent on CD8 + T cells mediating apoptosis. Our study uncovers the PD-L2/PD-1 signaling pathway as a driving factor to mediate EGFR-TKIs resistance, and identifies a new naturally-derived agent to reverse EGFR-TKIs resistance., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

The optimal discrete element model and bonding parameters that match the structural features of cornstalks during harvest were obtained. Based on the differences in mechanical properties of the stem bark and stem pith in the inter-nodal cornstalk, the biomechanical-specific parameters were measured using the compression, shear, and bending tests. The bonded particle models of stem bark and stem pith were constructed using fraction particles with radii of 1 mm and 1.47 mm, which were further bound to form a bilayer-bonded particle model of the cornstalk. The Plackett-Burman, steepest ascent, and response surface tests were conducted to identify the factors and their optimal values that significantly impacted the stem bark-stem bark, stem pith-stem pith, and stem bark-stem pith bonding parameters. The cornstalk's shear and bending mechanical properties were assessed to verify the overall characteristic parameters. The findings revealed that the cornstalk model created, and the calibrated bonding parameters, were highly accurate and capable of simulating the shearing and bending behaviors of the real cornstalk. The inter-nodal cornstalk's bonded particle model created and the identified bonding parameters for the cornstalk could contribute to a theoretical and research basis for the next stage in cornstalk modeling with nodes and other applications., (© 2024. The Author(s).)

To facilitate resource utilization of waste tires (WT) and oily sludge (OS), waste tire-sludge adsorbent (WTSA) was developed using co-pyrolysis technology, and its effectiveness in adsorbing crude oil was investigated. The study revealed that the optimal preparation conditions for WTSA included a 1.5:1 mass ratio of WT to OS, a co-pyrolysis temperature of 600 ℃, a co-pyrolysis holding time of 2 hours, and a co-pyrolysis heating rate of 15 ℃/min. The surface of WTSA exhibited numerous pores and cracks with varying shapes and sizes. The dominant pore structures were found to be mesopores and macropores. The carbon content of WTSA was measured to be 89.95%. Moreover, the BET specific surface area, pore volume, and average pore size were determined to be 686.81 m 2 /g, 0.74 cm 3 /g, and 5.91 nm, respectively. In the crude oil adsorption test, WTSA demonstrated a comparable adsorption capacity to activated carbon (AC), but with a more attractive initial adsorption rate. Furthermore, thermal regeneration treatment was found to significantly enhance the lipophilic properties of WTSA, leading to an increase in its initial adsorption rate. The adsorption capacity of regenerated WTSA was also found to be relatively stable, making it an ideal solution for emergency crude oil spill cleanups. Compared to AC, WTSA can be recycled and reused multiple times, making it a more sustainable and cost-effective option., (© 2024. The Author(s).)

Forecasting stock movements is a crucial research endeavor in finance, aiding traders in making informed decisions for enhanced profitability. Utilizing actual stock prices and correlating factors from the Wind platform presents a potent yet intricate forecasting approach. While previous methodologies have explored this avenue, they encounter challenges including limited comprehension of interrelations among stock data elements, diminished accuracy in extensive series, and struggles with anomaly points. This paper introduces an advanced hybrid model for stock price prediction, termed PMANet. PMANet is founded on Multi-scale Timing Feature Attention, amalgamating Multi-scale Timing Feature Convolution and Ant Particle Swarm Optimization. The model elevates the understanding of dependencies and interrelations within stock data sequences through Probabilistic Positional Attention. Furthermore, the Encoder incorporates Multi-scale Timing Feature Convolution, augmenting the model's capacity to discern multi-scale and significant features while adeptly managing lengthy input sequences. Additionally, the model's proficiency in addressing anomaly points in stock sequences is enhanced by substituting the optimizer with Ant Particle Swarm Optimization. To ascertain the model's efficacy and applicability, we conducted an empirical study using stocks from four pivotal industries in China. The experimental outcomes demonstrate that PMANet is both feasible and versatile in its predictive capability, yielding forecasts closely aligned with actual values, thereby fulfilling application requirements more effectively., (© 2024. The Author(s).)

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The analysis of the differences in metabolic profiles between naturally Ophiocordyceps sinensis (NO) and cultivated Ophiocordyceps sinensis (CO) is an essential process for the medicinal value mining of Ophiocordyceps sinensis. Non-targeted metabolomics was used to compare the differences in metabolite composition and abundance between NO and CO. Total metabolite composition found that NO is rich in organic acids and derivatives, and CO is rich in lipids and lipid-like molecules. HCA found that organooxygen compounds, cinchona alkaloid, and fatty acyls had different abundances in NO and CO. The variable importance in projection value and quantitative analysis of metabolites found that NO was rich in l-iditol, malate, linoleic acid, and oleic acid; CO is rich in sucrose, perseitol, hydroquinidine, nonanoic acid, 1-hydroxy-2-naphthoic acid, hymol-β-d-glucoside, and gly-his-lys. these compounds have the potential to be biomarkers of NO and CO. KEGG enrichment analysis showed that ascorbate and aldarate metabolism, carbon metabolism, pyrimidine metabolism, and fatty acid biosynthesis were the most different metabolic pathways between NO and CO. Therefore, the analysis of the characteristics of NO and CO metabolites has reference value for finding their different medicinal functions., (© 2024. The Author(s).)

With the progress in techniques for correcting errors in quantum computing, quantum low density parity check (QLDPC) codes have gained increasing significance within the field of quantum error correction. This paper focuses on different strategies for the construction of QLDPC codes, which are based on all points and lines as well as partial points and lines from projective geometry. Finally, a series of simulation analyses are presented., (© 2024. The Author(s).)

The study of rock burst tendency of rock masses with different sizes plays a key role in the prevention of rock burst. Through theoretical analysis, it is proposed that uniaxial compressive strength and deformation modulus ratio are the key mechanical parameters affecting rock burst occurrence. In order to find out the size effect of uniaxial compressive strength and deformation modulus ratio, theoretical analysis and uniaxial compression experiment are carried out on rock samples with different heights, different cross-sectional areas and different volumes. The results show that the smaller the uniaxial compressive strength is, the larger the deformation modulus ratio is, and the more likely rock burst are to occur. On the contrary, rock burst is still not easy to generate. The uniaxial compressive strength of rock samples with different heights, different cross-sectional areas and different volumes increases with the increase of rock sample size. The deformation modulus ratio of rock samples with different heights and different volumes shows an upward trend on the whole, while that of rock samples with different cross-sectional areas shows a downward trend on the whole. The fracture forms of rock are analyzed using the energy conversion law in the process of deformation and failure for three kinds of rock with different shapes and sizes., (© 2024. The Author(s).)

We carried out uniaxial compression tests on brittle red sandstone with different heights. The test results show that the uniaxial compressive strength of rock sample increases first and then tends to be stable with the increase of the size, which is approximately stable between 75 and 81 MPa. Both elastic energy and dissipated energy increase with the increase of rock sample size. In order to further analyze the mechanism behind these phenomena, we combined advanced numerical simulation and theoretical analysis to explain these phenomena, and systematically analyzed the end face effect as one of the key factors affecting the uniaxial compression characteristics of brittle red sandstone for the first time. Small sized rock samples are very sensitive to end effect. The middle of the large sized rock samples is in a uniform compression state, and the effect of end effect is weakend. When there are rigid pads at both ends of the rock sample, there is an obvious elastic vertebral body during the loading process of the rock sample. The bearing capacity of rock samples with rigid pads is greater than that of rock samples without rigid pads, and the energy released during instantaneous failure of rock samples without rigid pads is greater than that of rock samples with rigid pads. The findings of this paper make a valuable contribution to establishing optimal study sample sizes and advancing the utilization of laboratory test mechanics parameters in engineering applications., (© 2024. The Author(s).)

The complete cp genomes of Pedicularis chinensis (GenBank accession number: OQ587614) and Pedicularis kansuensis (GenBank accession number: OQ587613) were sequenced, assembled, and annotated. Their chloroplast (cp) genome lengths were 146,452 bp, and 146,852 bp, respectively; 120 and 116 genes were identified, comprising 75 and 72 protein-coding genes (PCGs), 37 and 36 transfer RNA (tRNA) genes, and 8 and 8 ribosomal RNA (rRNA) genes, for P. chinensis and P. kansuensis, respectively. A simple sequence repeat (SSR) analysis revealed that the repetitive sequences were mainly composed of mononucleotide repeats (A/T motif) and dinucleotide repeats (AT/TA motif). Comparative genomics identified several variant genes (rpl22, rps19, rpl12, ycf1, trnH, psbA, and ndhH) and variant regions (trnS-GGA, trnV-UAC, ndhJ-trnV, ycf4-cemA, ndhE-nhdG, and rpl32-trnL) with a high Pi, indicating the potential to serve as deoxyribo nucleic acid (DNA) barcodes for Pedicularis species identification. The results show that the cp genomes of P. chinensis and P. kansuensis were the same as those of other plants in Pedicularis, with different degrees of AT preference for codons. Large differences in the number of SSRs and the expansion of the inverted repeat (IR) region showed strong variability and interspecific differentiation between these two species and other species represented in the genus Pedicularis. A phylogenetic analysis showed that P. kansuensis had the closest relationship with P. oliveriana, and P. chinensis had the closest relationship with P. aschistorhyncha. These results will facilitate the study of the phylogenetic classification and interspecific evolution of Pedicularis plants., (© 2024. The Author(s).)

Tibetan-speaking patients seeking care in predominantly Mandarin-speaking healthcare settings frequently face communication barriers, leading to potential disparities and difficulties in accessing care. To address this issue, we translated, culturally adapted, and validated the Numerical Pain Rating Scale (NPRS) and the Global Rating of Change (GRoC) into Tibetan (NPRS-Tib and GRoC-Tib), aiming to facilitate cross-linguistic and cross-cultural interactions while examining potential challenges in the adaptation process. Using standard translation-backward translation methods, expert review, pilot testing, and validation through a cross-sectional study with a short-term longitudinal component, we engaged 100 Tibetan patients with musculoskeletal trauma for psychometric validation, including 37 women (aged 22-60 years, mean age 39.1 years). The NPRS-Tib and GRoC-Tib exhibited outstanding psychometric properties, with an Intraclass Correlation Coefficient (ICC) of 0.983 for NPRS-Tib indicating superb test-retest reliability, and expert review confirming good content validity for both instruments. A Spearman's correlation coefficient (Rho) of -0.261 (P = 0.0087) revealed a significant, albeit weak, correlation between changes in NPRS-Tib scores and GRoC-Tib scores. The adaptation process also presented notable challenges, including translation discrepancies from translators' diverse backgrounds and levels of expertise, ambiguity in scale options, and the lack of established tools for criterion validity assessment in Tibetan., (© 2024. The Author(s).)

The majority of pigeon paramyxovirus type 1 (PPMV-1) strains are generally non-pathogenic to chickens; however, they can induce severe illness and high mortality rates in pigeons, leading to substantial economic repercussions. The genomes of 11 PPMV-1 isolates from deceased pigeons on meat pigeon farms during passive monitoring from 2009 to 2012 were sequenced and analyzed using polymerase chain reaction and phylogenetic analysis. The complete genome lengths of 11 isolates were approximately 15,192 nucleotides, displaying a consistent gene order of 3'-NP-P-M-F-HN-L-5'. ALL isolates exhibited the characteristic motif of 112RRQKRF117 at the fusion protein cleavage site, which is characteristic of velogenic Newcastle disease virus. Moreover, multiple mutations have been identified within the functional domains of the F and HN proteins, encompassing the fusion peptide, heptad repeat region, transmembrane domains, and neutralizing epitopes. Phylogenetic analysis based on sequences of the F gene unveiled that all isolates clustered within genotype VI in class II. Further classification identified at least two distinct sub-genotypes, with seven isolates classified as sub-genotype VI.2.1.1.2.2, whereas the others were classified as sub-genotype VI.2.1.1.2.1. This study suggests that both sub-genotypes were implicated in severe disease manifestation among meat pigeons, with sub-genotype VI.2.1.1.2.2 displaying an increasing prevalence among Shanghai's meat pigeon population since 2011. These results emphasize the value of developing pigeon-specific vaccines and molecular diagnostic tools for monitoring and proactively managing potential PPMV-1 outbreaks., (© 2024. The Author(s).)

Tunnel cracks are thin and narrow linear targets, and their pixel proportions in images are usually very low, less than 6%; therefore, a method is needed to better detect small crack targets. In this study, a crack detection method based on crack characteristics and an anchor-free framework is investigated. First, the characteristics of cracks are analyzed to obtain the real crack texture, interference noise texture, and targets appearing near each crack as the context information for the model to filter and remove noise. We discuss the crack detection performance of anchor-based and anchor-free algorithms. Then, an optimized anchor-free algorithm is proposed in this paper for crack detection. Based on the advantages of YOLOX-x, we add a semantic enhancement module to better use contextual information. The experimental results show that the anchor-free algorithm performs slightly better than other algorithms in crack detection situations. In addition, the proposed method displays better detection performance for slender and inconspicuous cracks, with an average precision of 0.858., (© 2024. The Author(s).)

Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM's recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research., (© 2024. The Author(s).)

The interactions between white-to-white corneal diameter (WTW) and other ocular biometrics are important for planning of refractive surgery and understanding of ocular structural changes in myopia, but such interactions are rarely investigated in young myopic adults. This is a retrospective study involving 7893 young myopic adults from five centers. WTW and other ocular biometrics were measured by Pentacam. The ocular biometrics included anterior corneal curvature (AK) and posterior corneal curvature (PK), central corneal thickness (CCT) and corneal volume (CV), anterior and corneal eccentricity and asphericity, anterior corneal astigmatism (ACA) and posterior corneal astigmatism, anterior chamber depth (ACD), and anterior chamber volume (ACV). The ocular biometrics were compared among eyes of different WTW quartiles. Multivariate linear regression was used to assess the linear associations between WTW and other ocular biometrics adjusting for age, gender and spherical equivalent. In eyes of different WTW quartiles, other ocular biometrics were also significantly different (all P < 0.05). After adjusting for age, gender and spherical equivalent, WTW was positively correlated to AK (β = 0.26 to 0.29), ACA (β = 0.13), anterior corneal asphericity (β = 0.05), PK (β = 0.33 to 0.34), posterior corneal asphericity (β = 0.13), ACD (β = 0.29), and ACV (β = 40.69), and was negatively correlated to CCT (β = - 6.83), CV (β = - 0.06 to - 0.78), anterior corneal eccentricity (β = - 0.035), and posterior corneal eccentricity (β = - 0.14) (all P < 0.001). In conclusion, we found that in young myopic adults, larger WTW was associated with thinner corneal thickness, flatter corneal curvature, more anterior corneal toricity, less corneal eccentricity and asphericity, and broader anterior chamber. Our findings may fill in the gap of literature, and help us better understand how the anterior segment structures interact with the WTW in myopia., (© 2024. The Author(s).)

Phenotype-guided gene prioritizers have proved a highly efficient approach to identifying causal genes for Mendelian diseases. In our previous study, we preliminarily evaluated the performance of ten prioritizers. However, all the selected software was run based on default settings and singleton mode. With a large-scale family dataset from Deciphering Developmental Disorders (DDD) project (N = 305) and an in-house trio cohort (N = 152), the four optimal performers in our prior study including Exomiser, PhenIX, AMELIE, and LIRCIAL were further assessed through parameter optimization and/or the utilization of trio mode. The in-depth assessment revealed high diagnostic yields of the four prioritizers with refined preferences, each alone or together: (1) 83.3-91.8% of the causal genes were presented among the first ten candidates in the final ranking lists of the four tools; (2) Over 97.7% of the causal genes were successfully captured within the top 50 by either of the four software. Exomiser did best in directly hitting the target (ranking the causal gene at the very top) while LIRICAL displayed a predominant overall detection capability. Besides, cases affected by low-penetrance and high-frequency pathogenic variants were found misjudged during the automated prioritization process. The discovery of the limitations shed light on the specific directions of future enhancement for causal-gene ranking tools., (© 2024. The Author(s).)

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, has been reported as a suppressor in several tumors whereas its role in colorectal cancer (CRC) remains unknown. In this study, we find that ABLIM1 is up-regulated in CRC patients and high levels of ABLIM1 predict short disease-free survival time. Knock-down of ABLIM1 in CRC cell lines by lenti-virus leads to inhibited cell proliferation, migration, and invasion capabilities in vitro and impaired growth of tumor xenografts and liver metastasis lesions in vivo, while ABLIM1 overexpression accelerates tumor growth and invasion in vitro. Mechanistically, we uncover that ABLIM1 activates the NF-ĸB/CCL-20 signaling through modulating IĸBα ubiquitination and proteasomal-mediated degradation. Further co-immunoprecipitation, in vivo and in vitro ubiquitination assays reveal ABLIM1 as a novel ubiquitin E3 ligase binding to IĸBα. Interestingly, The E3 ligase catalysis activity of ABLIM1 depends on its 402-778aa rather than its LIM domains and its interaction with IĸBα relies on the HP domain. Our findings delineate the oncogenic role of ABLIM1 in CRC progression and reveal it as a novel E3 ligase targeting IĸBα, providing new insights into the regulation of NF-ĸB signaling in tumors., (© 2024. The Author(s).)

Calcium-oxygen (Ca-O 2 ) batteries can theoretically afford high capacity by the reduction of O 2 to calcium oxide compounds (CaO x ) at low cost 1-5 . Yet, a rechargeable Ca-O 2 battery that operates at room temperature has not been achieved because the CaO x /O 2 chemistry typically involves inert discharge products and few electrolytes can accommodate both a highly reductive Ca metal anode and O 2 . Here we report a Ca-O 2 battery that is rechargeable for 700 cycles at room temperature. Our battery relies on a highly reversible two-electron redox to form chemically reactive calcium peroxide (CaO 2 ) as the discharge product. Using a durable ionic liquid-based electrolyte, this two-electron reaction is enabled by the facilitated Ca plating-stripping in the Ca metal anode at room temperature and improved CaO 2 /O 2 redox in the air cathode. We show the proposed Ca-O 2 battery is stable in air and can be made into flexible fibres that are weaved into textile batteries for next-generation wearable systems., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Autonomous vehicles (AVs) have the potential to revolutionize transportation safety and mobility, but many people are still concerned about the safety of AVs and hesitate to use them. Here we survey 4112 individuals to explore the relationship between knowledge and public support for AVs. We find that AV support has a positive relationship with scientific literacy (objective knowledge about science) and perceived understanding of AV (self-assessed knowledge). Respondents who are supportive of AVs tended to have more objective AV knowledge (objective knowledge about AVs). Moreover, the results of further experiments show that increasing people's self-assessed knowledge or gaining additional objective AV knowledge may contribute to increasing their AV support. These findings therefore improve the understanding of the relationship between public knowledge levels and AV support, enabling policy-makers to develop better strategies for raising AV support, specifically, by considering the role of knowledge, which in turn may influence public behavioural intentions and lead to higher levels of AV acceptance., (© 2024. The Author(s).)

Small-scale motion detection using non-invasive remote sensing techniques has recently garnered significant interest in the field of speech recognition. Our dataset paper aims to facilitate the enhancement and restoration of speech information from diverse data sources for speakers. In this paper, we introduce a novel multimodal dataset based on Radio Frequency, visual, text, audio, laser and lip landmark information, also called RVTALL. Specifically, the dataset consists of 7.5 GHz Channel Impulse Response (CIR) data from ultra-wideband (UWB) radars, 77 GHz frequency modulated continuous wave (FMCW) data from millimeter wave (mmWave) radar, visual and audio information, lip landmarks and laser data, offering a unique multimodal approach to speech recognition research. Meanwhile, a depth camera is adopted to record the landmarks of the subject's lip and voice. Approximately 400 minutes of annotated speech profiles are provided, which are collected from 20 participants speaking 5 vowels, 15 words, and 16 sentences. The dataset has been validated and has potential for the investigation of lip reading and multimodal speech recognition., (© 2023. The Author(s).)

This study aimed to investigate the relationship between hypertension and Alzheimer's disease (AD) and demonstrate the key role of stroke in this relationship using mediating Mendelian randomization. AD, a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral abnormalities, severely affects the quality of life of patients. Hypertension is an important risk factor for AD. However, the precise mechanism underlying this relationship is unclear. To investigate the relationship between hypertension and AD, we used a mediated Mendelian randomization method and screened for mediating variables between hypertension and AD by setting instrumental variables. The results of the mediated analysis showed that stroke, as a mediating variable, plays an important role in the causal relationship between hypertension and AD. Specifically, the mediated indirect effect value for stroke obtained using multivariate mediated MR analysis was 54.9%. This implies that approximately 55% of the risk of AD owing to hypertension can be attributed to stroke. The results suggest that the increased risk of AD owing to hypertension is mediated through stroke. The finding not only sheds light on the relationship between hypertension and AD but also indicates novel methods for the prevention and treatment of AD. By identifying the critical role of stroke in the link between hypertension and AD, this study provides insights into potential interventions that could mitigate the impact of hypertension on AD. This could help develop personalized treatments and help improve the quality of life of patients with AD who suffer from hypertension., (© 2023. The Author(s).)