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Author(s): N. Mannella (corresponding author) [1, 2]; W. L. Yang [1, 2]; X. J. Zhou [1, 2]; H. Zheng [3]; J. F. Mitchell [3]; J. Zaanen [1, 4]; T. P. [...]

Author(s): X. J. Zhou (corresponding author) [1, 2]; T. Yoshida [1, 3]; A. Lanzara [1, 2]; P. V. Bogdanov [1]; S. A. Kellar [1]; K. M. Shen [1]; W. L. [...]

In order to effectively control the large deformation of coal pillar and roadway during entry retained along gob side with small coal pillar, taking 1311 and 1312 working faces of a coal mine in Shanxi Province as engineering background, the structural characteristics of overlying rock are studied, and the stress source of entry retained along gob side with small coal pillar and the principle of roof cutting and pressure relief are analyzed, then the roof cutting and pressure relief technology of shaped charge blasting with combined and grouped of deep and shallow holes is put forward. According to the geological conditions of 1311 working face, through the calculation of caving zone and crack zone height of the working face, the analysis of roof breaking and instability conditions and the calculation of crack zone blasting radius, the key parameters of roof cutting by deep and shallow hole combined blasting are determined. Through the numerical simulation and analysis of roof cutting and pressure relief in different key strata, the variation law of vertical stress acting on small coal pillar is obtained, as follows: no roof cutting > only cut layer 2 > only cut layer 1 > cut layer 3 + partial layer 2 > cut layer 1 ~ 3; Based on these, a cooperative control scheme of "roof cutting and pressure relief by shaped charge blasting with combined and grouped of deep and shallow holes" + "anchor-cable combined support" + "coal pillar strengthened" is put forward. The field industrial test results show that the control effect of small coal pillar and roadway surrounding rock is good., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval Not applicable. Consent to publish All authors of this article consent to publish., (© 2024. The Author(s).)

Wide-Field Small Aperture Telescopes (WFSAT) are widely used for surveilling space objects. Due to their wide-field of view (FOV) characteristics, these telescopes can cover a large areas of the sky at once, improving observation efficiency. However, a wide-field optical telescope is highly sensitive to external stray light (such as moonlight and thin clouds), which can significantly reduce the quality of observation data. In severe cases, it can cause the telescope to malfunction and inaccurately position the object. In response to this problem, this paper proposes a model for suppressing stray light in astronomical images based on deep learning: the Pyramid Deformable Large Kernel Attention (PD-LKA) Model. This model expands the receptive field through a pyramid structure, captures multi-scale features, and improves the model's robustness to various scales of stray light interference. Meanwhile, through the Deformable Large Kernel Attention (D-LKA), the model can more accurately locate and enhance the feature extraction ability in areas affected by stray light interference, thereby better suppressing stray light.Using simulated astronomical image pairs to train the model, the tests achieved a PSNR of up to 32.540 and an SSIM of up to 0.938. Finally, the model is applied to a image sequence with real stray light interference. The restored images undergo astronomical positioning and orbital association processing. The results show that the positioning accuracy of the object is better than 5 arcseconds. This indicates that the model proposed in this paper not only recovers the object and background stars but also effectively preserves their gray values, shapes, and positional information., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Predicting the backbone torsion angles corresponding to each residue of a protein from its amino acid sequence alone is a challenging problem in computational biology. Existing torsion angle predictors mainly use profile features, which are generated by performing time-consuming multiple sequence alignments, for torsion angle prediction. Compared with traditional profile features, embedding features from pretrained protein language models have significant advantages in prediction performance and computational speed. However, embedding features usually have higher dimensions and different embedding features have significantly different dimensions. To this end, we design a novel parameter-efficient deep torsion angle predictor, PHAngle, specifically for embedding features. PHAngle is a parameterized hypercomplex convolutional network consisting of parameterized hypercomplex linear and convolutional layers whose weight parameters can be characterized as the sum of Kronecker products. Experimental results on six benchmark test sets including TEST2016, TEST2018, TEST2020_HQ, CASP12, CASP13 and CASP-FM demonstrate that PHAngle achieves the state-of-the-art torsion angle performance with the fewest parameters compared to the nine existing methods. The source code and datasets are available at https://github.com/fengtuan/PHAngle ., (© 2024. The Author(s).)

Machinery operation is a major source of carbon emissions in building deconstruction. Early intervention through Design for Deconstruction (DfD) is crucial for emission reduction, yet the factors influencing these emissions are underexplored. This study integrates parametric BIM with multi-objective optimization (MOO) to assess mechanical carbon emissions in deconstruction. Using the Octopus solver in Grasshopper for Rhino, the study analyzes independent variables-possible working hours (PWH), vertical speed (VS), and horizontal speed (HS)-and dependent variables-minimum mechanical carbon emissions (MCE (min)), minimum deconstruction period (DP (min)), and maximum working efficiency (WE (max)). A lightweight steel roof truss structure is analyzed, comparing real-world deconstruction with optimized DfD schemes. Sensitivity analysis for BIM-MOO optimized results reveal that: (1) Adjusting PWH, VS, and HS significantly affects WE and DP, though with limited impact on carbon emissions; (2) VS influences WE and DP more than HS; (3) Limiting DP is essential for balancing WE, DP, and MCE, with WE adjusted to 20-60% and modifications to PWH and VS achieving balanced management. This study underscores the importance of early design and real-time adjustments for efficient, low-emission deconstruction, supporting the advancement of green building practices., (© 2024. The Author(s).)

Electrohydrodynamic (EHD) printing has critical merits in micro/nanoscale additive manufacturing because of its ultrahigh resolution and wide ink compatibility, making it an advantageous choice for electronics manufacturing, high-resolution prototyping, and biological component fabrication. However, EHD printing is currently limited by its rather low throughput due to the lack of high-frequency and high-density multi-nozzle printheads. This paper presents a novel EHD printhead with a protruding polymer-based nozzle design. An insulated, hydrophobic, and protruding polymer nozzle array with an appropriate geometric structure can effectively address key problems in multi-nozzle jetting, such as electrical crosstalk, electrical discharge, liquid flooding, and nonuniform jetting. By investigating the influence of the electrical and geometric characteristics of the nozzle arrays on the electrical crosstalk behavior and fabricating the optimized nozzle array via MEMS technology, we achieve an EHD printhead with a large scale (256), high density (127 dpi), and high jetting frequency (23 kHz), and addressable jetting can be realized by adding independently controllable extractors underneath the nozzle array. Many functional materials, such as quantum dots, perovskite, and nanosilver inks, can be ejected into high-resolution patterns through the optimized nozzle array, demonstrating the great prospects of our designed printhead in electronics manufacturing. This MEMS-compatible printhead design lays the foundation for high-throughput fabrication of micro/nanostructures and promotes practical applications of EHD printing in functional electronics and biomedical/energy devices., (© 2024. The Author(s).)

Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells is a principal mechanism for systemic glucose homeostasis, of which regulatory mechanisms are still unclear. Here we show that kinesin molecular motor KIF5B is essential for GSIS through maintaining the voltage-gated calcium channel Ca V 1.2 levels, by facilitating an Hsp70-to-Hsp90 chaperone exchange to pass through the quality control in the endoplasmic reticulum (ER). Phenotypic analyses of KIF5B conditional knockout (cKO) mouse beta cells revealed significant abolishment of glucose-stimulated calcium transients, which altered the behaviors of insulin granules via abnormally stabilized cortical F-actin. KIF5B and Hsp90 colocalize to microdroplets on ER sheets, where Ca V 1.2 but not K ir 6.2 is accumulated. In the absence of KIF5B, Ca V 1.2 fails to be transferred from Hsp70 to Hsp90 via STIP1, and is likely degraded via the proteasomal pathway. KIF5B and Hsc70 overexpression increased Ca V 1.2 expression via enhancing its chaperone binding. Thus, ER sheets may serve as the place of KIF5B- and Hsp90-dependent chaperone exchange, which predominantly facilitates Ca V 1.2 production in beta cells and properly enterprises GSIS against diabetes., (© 2024. The Author(s).)

During the operation of load cell, heat is generated by the strain gauge and the electronics on the PCB board, which leads to temperature gradients within the sensor itself. These temperature gradients are unstable at different ambient temperatures. Compensation inaccuracies can also occur when compensating for sensor measurements at different temperatures This paper proposes a method to change the position of temperature compensation resistors to address errors caused by the temperature field effect of the strain gauge sensor itself. Without affecting the sensor's strain measurement, the correctness of the proposed method is demonstrated through steady-state thermal simulation results in ANSYS and experimental results, effectively addressing errors caused by unstable temperature gradients during the operation of strain gauge sensors., (© 2024. The Author(s).)

The abrasive water-jet (AWJ) erosion process involves the complex interaction between fluid medium, abrasive particles and solid material, which brings great challenges to the establishment of numerical model. Because traditional grid-based methods are not suitable for the problems of local deformation and material removal, the meshfree method smoothed particle hydrodynamics (SPH), based on the unresolved coupling and the discrete element method (DEM), is adopted to establish the model for AWJ study. The fluid medium is treated as a weakly compressible viscous liquid, the solid material is treated as an elastic-plastic material, and the abrasives are treated as rigid bodies. The fluid and solid phases are discretized with SPH particles, and the abrasives are described with DEM particles. The Johnson-Cook (J-C) and Johnson-Holmquist-II (JH-2) constitutive models are used to describe the stress-strain behavior of ductile and brittle materials, respectively. The effectiveness of the numerical model is further verified by AWJ impact experiments. The plastic deformation and cumulative failure characteristics of ductile materials, and the crack formation and propagation characteristics of brittle materials are systematically analyzed. The results provide insight for the AWJ research and lay a foundation for investigation of other complex fluid-particle flow in a numerical way., (© 2024. The Author(s).)

This paper proposes a novel piezo-MEMS pitch/roll gyroscope that co-integrates piezoelectric and electrostatic effects, for the first time achieves electrostatic mode-matching operation for piezoelectric gyroscopes. Movement of operated out-of-plane (OOP) mode (n = 3) and in-plane (IP) mode (n = 2) are orthogonal, ensuring that the OOP amplitude is not significantly limited by parallel plates set at nodes of IP mode. Therefore, a large OOP driving amplitude actuated by piezoelectric and frequency tuning in the IP sense mode trimmed by electrostatic can be achieved together with a low risk of pull-in, hence releases the trade-off between the tuning range and the linear actuation range. At a tuning voltage of 66 V, the frequency split decreased from 171 Hz to 0.1 Hz, resulting in a 167x times improvement in sensitivity. The mode-matched gyroscope exhibits an angle random walk (ARW) of 0.41°/√h and a bias instability (BI) of 8.85°/h on a test board within a customized vacuum chamber, marking enhancements of 68x and 301x, respectively, compared to its performance under mode-mismatch conditions. The BI performance of the presented pitch/roll gyroscope is comparable to that of the highest-performing mechanically trimmed piezo-MEMS yaw gyroscopes known to date, while offering the unique advantage of lower cost, better mode-matching resolution, and the flexibility of real-time frequency control., (© 2024. The Author(s).)

The objective of this study was to ascertain the relationship between the weight-adjusted waist index (WWI) and the risk of stroke in an elderly hypertensive population, a relationship that has not been previously elucidated. The Cox regression model was employed to assess the correlation between baseline WWI measurements and the incidence of stroke. To further elucidate the shape of the association between baseline WWI and stroke, restricted cubic splines were employed. Furthermore, subgroup analyses and interaction tests were carried out to investigate potential heterogeneities. Our study cohort comprised 4962 hypertensive individuals aged 60 years or older with no prior history of stroke. Over a median follow-up of 3.2 years, we found 547 new-onset stroke cases. After adjusting for confounding variables, the Cox regression analysis revealed a positive association between baseline WWI and the risk of stroke, with hazard ratios (HRs) escalating progressively as WWI values increased. When compared to the lowest quartile of WWI, the highest quartile demonstrated an HR of 1.87 (95% CI, 1.44-2.42) for stroke. Subgroup analyses confirmed the consistency of this relationship across different demographic and clinical strata. The study findings indicate that an elevated WWI is significantly related with a higher risk of new-onset stroke among elderly patients with hypertension. These results underscore the importance of WWI as a potential risk stratification tool. To confirm these results and explore the causal mechanisms behind the observed correlation, more study is necessary., (© 2024. The Author(s).)

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) may cause adverse birth outcomes. Thyroid hormones may play a key role in mediating the effects of PFAS. We enrolled 374 mother-infant pairs from the Ezhou birth cohort study between 2019 and 2020. Eight PFASs and six thyroid hormones were measured in maternal serum during the first trimester of pregnancy. Neonatal growth metrics, including birth weight, length, head circumference, and gestational age, were acquired. Multivariate linear regression was performed to determine the associations between maternal serum PFAS and thyroid hormone levels and birth outcomes and a mediation analysis was also conducted. Except for perfluoroheptanoic acid (41.2%), the other seven PFAS detection rates were more than 85%, and the highest median concentration was observed for PFOSA with levels of 5.21 ng/mL. After controlling for typical confounders, we observed a decrease in birth length (cm) with increasing serum concentrations of perfluorononanoic acid (PFNA) (β = -0.54; 95% CI = -1.0, -0.08) and perfluorohexane sulfonate (PFHxS) (β = -0.64; 95% CI = -0.86, -0.42). Additionally, a decrease in birth head circumference was observed with increasing concentrations of perfluorooctanote (PFOA) (β = -0.73, 95% CI = -1.19, -0.27) and PFHxS (β = -0.30; 95% CI = -0.53, -0.07). Maternal free triiodothyronine (FT3) mediated 36.7% of the negative association between PFNA and birth length, and free thyroxine (FT4) mediated 30.8% of the effect of PFOA on head circumference. When performing stratified analysis by infant sex, the associations might differ between boys and girls. Our study suggested prenatal exposure to some PFASs was negatively associated with birth length and circumference, and FT3 and FT4 may partly mediate the association., (© 2024. The Author(s).)

Tea gray blight disease is a significant threat to the tea industry. In this study, a biological activity approach was utilized to investigate the efficacy of green fungicides from Magnolia officinalis stem bark against Neopestalotiopsis ellipsospora. The active compounds were isolated and purified, and their structures were elucidated. In vitro and in vivo activity screenings revealed that the n-hexane extract, which contained magnolol and honokiol, exhibited strong activity against N. ellipsospora, showing complete inhibition at 100 mg/L. The EC 50 values of magnolol and honokiol were 5.11 and 6.09 mg/L, respectively. Mechanistically, magnolol was found to disrupt N. ellipsospora invasion by damaging the cell membrane, increasing permeability, and causing leakage of intracellular substances. Transcriptome analysis revealed that magnolol treatment downregulates membrane-related genes and leads to the enrichment of lipid metabolism pathway genes. This study revealed that magnolol inhibits N. ellipsospora growth by affecting lipid metabolism and compromising cell membrane integrity., (© 2024. The Author(s).)

Purpose This randomized controlled study aims to compare the effects of cluster training versus traditional plyometric lower limb training on vertical and horizontal jump performance, as well as the reactive strength index, in young female artistic gymnasts., Methods: A total of 54 female artistic gymnasts (15.4 ± 1.2 years) participated voluntarily this study. Participants were assigned to one of three groups: (i) cluster training (PLYct); (ii) traditional training (PLYtr); and (iii) a control group (not exposed to plyometric training). The intervention spanned 8 weeks, with evaluations conducted before and after the intervention period for the following variables: (i) squat jump; (ii) countermovement jump; and (iii) reactive strength index in a drop jump test., Results: Significant interactions time × group were found in SJ (p < 0.001; =0.505), CMJ (p<0.001; =0.241) and RSI (p < 0.001; =0.492). The time × group analysis in post-intervention revealed significantly greater performance in SJ of PLYct (3.0 cm; p < 0.001) and PLYtr (2.5 cm; p=0.001) in comparison to control group. Significantly higher CMJ height were observed for the PLYct group comparing to PLYtr (1.3 cm; p=0.008) and control (2.9 cm; <0.001), while PLYtr was significantly better than control (1.6 cm; p=0.001). PLYct had significantly greater RSI than PLYtr (0.07 RSI; p = 0.014) and control (0.10 RSI; p<0.001), while PLYtr was significantly better than control (0.10 RSI; p = 0.024)., Conclusion: Cluster sets were significantly more effective than traditional sets in improving the stretch-shortening cycle as measured by the CMJ and enhancing the reactive strength of gymnasts. It is recommended to incorporate cluster sets while applying plyometric training to maximize performance with favorable adaptations., (© 2024. The Author(s).)

Linezolid binds to the 50S subunit of the bacterial ribosome, inhibiting bacterial protein synthesis by preventing the formation of the initiation complex. Oxazolidinone antimicrobial drugs represent the last line of defense in treating Staphylococcus aureus infections; thus, resistance to linezolid in S. aureus warrants high priority. This article examines the major mechanisms of resistance to linezolid in S. aureus, which include: mutations in the domain V of 23S rRNA (primarily G2576); chromosomal mutations in the rplC, rplD, and rplV genes (encoding the ribosomal uL3, uL4, and uL22 proteins, respectively); the exogenous acquisition of the methylase encoded by the chloramphenicol-florfenicol resistance (cfr) gene; the endogenous methylation or demethylation of 23S rRNA; the acquisition of optrA and poxtA resistance genes; and the existence of the LmrS multidrug efflux pump. In conclusion, these mechanisms mediate resistance through mutations or modifications to the bacterial target, thereby reducing the affinity of linezolid for the peptidyl transferase center (PTC) binding site or by preventing the binding of linezolid to the PTC through a ribosomal protective effect. The existence of additional, unexplained resistance mechanisms requires further investigation and verification., (© 2024. The Author(s).)

The leaves of Cyclocarya paliurus (Batalin) Iljinskaja, an endemic tree with a scattered distribution in subtropical China, are rich in flavonoids with beneficial, health-promoting properties. To understand the impact of environment and genetic similarity on the variation pattern of flavonoids in this species, we analyzed C. paliurus germplasm resources from 26 different populations previously sampled from the main distribution area. Environmental, genetic and biochemical data was associated by genetic structure analysis, non-parametric tests, correlation analysis and principal component analysis. We found that populations with higher flavonoid contents were distributed at higher elevations and latitudes and fell into two groups with similar genetic diversities. Significant accumulations of isoquercitrin and kaempferol 3-O-glucoside were detected in the higher flavonoid-content resources. In addition, the genetic clusters with higher flavonoid contents exhibited broader environmental-adaptive capacities. Even in the presence of environmental factors promoting C. paliurus flavonoid accumulation, only those populations having a specific level of genetic similarity were able to exploit such environments., (© 2024. The Author(s).)

Due to the harsh underground environment during coal mining, the quality of images collected by cameras is not sufficient, and the acquired images are greatly affected by noise, affecting visual observation; to a certain extent, subsequent intelligent mining is limited. A morphological Sobel coal-rock boundary recognition algorithm is proposed according to the different gray levels of coal-rock images to solve the problem of coal image quality. First, the details of the coal and rock images are smoothly preprocessed to improve the contrast between the feature boundaries and surrounding pixels, and the gray-level adaptive threshold is applied after processing. Morphological corrosion theory is used to process the morphological structure in an image, and the corresponding boundary in the image is extracted for recognition. Compared with the boundary points identified by each algorithm, the area error of coal and rock identification is calculated by using the boundary point fitting curve. The morphological Sobel algorithm is used to calculate the identification area error of coal and rock at different angles according to the camera range. The experimental results show that the boundaries identified by the morphological Sobel algorithm have the best degree of overlap with the boundaries of the original image. The identification error area is only about 10% of the Sobel operator and Canny operator algorithm. Monitoring coal and rock specimens can enable the effective identification of coal and rock boundaries from various angles., (© 2024. The Author(s).)

Previous studies suggest that a high body mass index (BMI) may be a risk factor for keratoconus (KC), but the causal relationship remains unclear. This study used Mendelian randomization (MR) to investigate this connection and explore the mediating role of circulating serum metabolites and inflammatory factors in this association. Two-sample MR analysis was conducted to assess the relationship between BMI and KC. The study employed a two-step MR approach to evaluate the mediating roles of 91 inflammatory markers and 249 serum metabolites in the BMI-KC relationship. Inverse variance weighting (IVW) was the primary method, and multiple sensitivity analyses were performed to ensure robustness. IVW analysis revealed a positive causal relationship between BMI and KC (OR IVW = 1.811, 95% CI 1.005-3.262, P = 0.048). Although IL-12β and IL-4 were causally associated with KC, they did not mediate the BMI-KC relationship. Five serum metabolites were identified as potential mediators, with HDL cholesterol and triglyceride ratios showing significance. This study clarified the causal relationship between high BMI and KC, suggesting that high BMI may induce KC through lipid metabolism abnormalities. These findings underscore the importance of managing BMI for KC prevention., (© 2024. The Author(s).)

The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman's correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model's discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer-Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications., (© 2024. The Author(s).)

Elevated intracellular lipid synthesis is important for hepatocellular carcinoma (HCC) progression. Our study aimed to identify the role of nucleoporin 37 (NUP37) in lipid synthesis and HCC progression. The expression of NUP37 was significantly upregulated in HCC and associated with a poor prognosis. NUP37 silencing suppressed lipid synthesis, proliferation, migration, and invasion of HCC cells in vitro, and restrained tumor growth in xenograft mouse models in vivo. Next, we found the high expression of NUP37 in HCC was related to post-translational modifications. Tripartite motif-containing 28 (TRIM28) was identified as an interacting protein of NUP37 and upregulated its protein level. The subsequent analysis revealed that TRIM28-mediated SUMOylation of NUP37 at Lys114/118/246 inhibited K27-linked polyubiquitination of NUP37, which is one reason for its high expression level in HCC. In conclusion, TRIM28 SUMOylates NUP37 to prevent its ubiquitination and proteasomal degradation, increasing the stability of the NUP37 protein, thereby promoting lipid synthesis and the progression of HCC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2024. The Author(s).)

To report the correlation between corneal biomechanical parameters and age in healthy Chinese individuals. This cross-sectional study was conducted on 864 eyes of 543 healthy participants. A comprehensive ophthalmic examination and corneal biomechanics examination using Corneal Visualization Scheimpflug Technology (Corvis ST) were conducted. Based on age, all participants were further divided into five age groups (n) as follows: group A, 11-20 years (105); group B, 21-30 years (112); group C, 31-40 years (113); group D, 41-50 years (100); and group E, > 50 years (113). Using Corvis ST, we examined 35 corneal biomechanical parameters and compared them across the different age groups. Spearman's correlation coefficients and stepwise multivariate linear regression models were used to investigate whether the corneal biomechanical parameters were related to demographic and ocular characteristics. A correlation analysis between the left and right eyes revealed that 13 parameters were significantly associated with eye differences. Among the 35 corneal biomechanical parameters, 28 exhibited significant differences across the age groups, with stiffness parameter at applanation 1(SPA1) showing an upward trend after the age of 30 and stress-strain index (SSI) demonstrates a statistically significant upward trend when comparing the five age groups in the study. Additionally, Spearman's correlation analysis and stepwise multivariate linear regression analysis revealed that 11 corneal biomechanical parameters were positively correlated with age and 10 were negatively correlated with age. Corvis biomechanical index (CBI) was significantly negatively correlated with intraocular pressure (IOP) and central corneal thickness (CCT), SSI was significantly positively correlated with age and IOP, and SPA1 were positively correlated with IOP and CCT. In conclusion, most corneal biomechanical parameters showed a significant correlation with age, with corneal stiffness progressively increasing alongside advancing age, IOP, or CCT., (© 2024. The Author(s).)

Metabolic dysregulation is prominent in triple-negative breast cancer (TNBC), yet therapeutic strategies targeting cancer metabolism are limited. Here, utilizing multiomics data from our TNBC cohort (n = 465), we demonstrated widespread splicing deregulation and increased spliceosome abundance in the glycolytic TNBC subtype. We identified SNRNP200 as a crucial mediator of glucose-driven metabolic reprogramming. Mechanistically, glucose induces acetylation at SNRNP200 K1610, preventing its proteasomal degradation. Augmented SNRNP200 then facilitates splicing key metabolic enzyme-encoding genes (GAPDH, ALDOA, and GSS), leading to increased lactic acid and glutathione production. Targeting SNRNP200 with antisense oligonucleotide therapy impedes tumor metabolism and enhances the efficacy of anti-PD-1 therapy by activating intratumoral CD8 + T cells while suppressing regulatory T cells. Clinically, higher SNRNP200 levels indicate an inferior response to immunotherapy in glycolytic TNBCs. Overall, our study revealed the intricate interplay between RNA splicing and metabolic dysregulation, suggesting an innovative combination strategy for immunotherapy in glycolytic TNBCs., (© 2024. The Author(s).)

E3 ubiquitin ligases are very important for regulating antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and IAV, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-β and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 presented decreased susceptibility to H9N2 and H1N1 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation of TBK1 and IRF3 and downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator that controls the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

To adequately prepare for potential hazards caused by emerging and reemerging infectious diseases, the WHO has issued a list of high-priority pathogens that are likely to cause future outbreaks and for which research and development (R&D) efforts are dedicated, known as paramount R&D blueprints. Within R&D efforts, the goal is to obtain effective prophylactic and therapeutic approaches, which depends on a comprehensive knowledge of the etiology, epidemiology, and pathogenesis of these diseases. In this process, the accessibility of animal models is a priority bottleneck because it plays a key role in bridging the gap between in-depth understanding and control efforts for infectious diseases. Here, we reviewed preclinical animal models for high priority disease in terms of their ability to simulate human infections, including both natural susceptibility models, artificially engineered models, and surrogate models. In addition, we have thoroughly reviewed the current landscape of vaccines, antibodies, and small molecule drugs, particularly hopeful candidates in the advanced stages of these infectious diseases. More importantly, focusing on global trends and novel technologies, several aspects of the prevention and control of infectious disease were discussed in detail, including but not limited to gaps in currently available animal models and medical responses, better immune correlates of protection established in animal models and humans, further understanding of disease mechanisms, and the role of artificial intelligence in guiding or supplementing the development of animal models, vaccines, and drugs. Overall, this review described pioneering approaches and sophisticated techniques involved in the study of the epidemiology, pathogenesis, prevention, and clinical theatment of WHO high-priority pathogens and proposed potential directions. Technological advances in these aspects would consolidate the line of defense, thus ensuring a timely response to WHO high priority pathogens., (© 2024. The Author(s).)

At present, biopharmaceuticals have received extensive attention from the society, among which recombinant proteins have a good growth trend and a large market share. Chinese hamster ovary (CHO) cells are the preferred mammalian system to produce glycosylated recombinant protein drugs. A highly efficient and stable cell screening method needs to be developed to obtain more and useful recombinant proteins. Limited dilution method, cell sorting, and semi-solid medium screening are currently the commonly used cell cloning methods. These methods are time-consuming and labor-intensive, and they have the disadvantage of low clone survival rate. Here, a method based on semi-solid medium was developed to screen out high-yielding and stable cell line within 3 weeks to improve the screening efficiency. The semi-solid medium was combined with an expression vector containing red fluorescent protein (RFP) for early cell line development. In accordance with the fluorescence intensity of RFP, the expression of upstream target gene could be indicated, and the fluorescence intensity was in direct proportion to the expression of upstream target gene. In conclusion, semi-solid medium combined with bicistronic expression vector provides an efficient method for screening stable and highly expressed cell lines., (© 2024. The Author(s).)

The study of hydrogen concentration distribution law of hydrogen-doped methane pipeline is directly related to the safety and stability of hydrogen-doped methane pipeline network. Based on the theory of fluid dynamics, this paper established a model of hydrogen-doped methane pipeline and simulated the operation and shutdown status of hydrogen-doped methane pipeline by adopting the computational fluid dynamics method and selecting the mixture multiphase model and standard k - ε turbulence model. This paper investigates the hydrogen concentration distribution law in hydrogen-doped methane pipelines as well as the influence law of different hydrogen-doping ratios, operating flow velocities, operating pressures, shutdown time and gas usage on the hydrogen concentration distribution in gas pipeline. The results show that: under the operation condition, there is a weak uneven distribution of hydrogen in the pipeline, the hydrogen-doping ratio, flow velocity, pressure on the hydrogen volume fraction of the change in the 0.9% or less, the effect can be ignored; in the shutdown status, there is a clear stratification phenomenon, the hydrogen-doping ratio increased from 10 to 25%, the change in the volume fraction of hydrogen in the 11.2% or less, a positive correlation; with the extension of the shutdown time to 900s, the pipeline firstly appeared obvious stratification phenomenon in the branch pipe, the thickness of the gas with hydrogen volume fraction above 40% on the upper wall surface of the branch pipe increased to 0.7 mm, and after the shutdown time was extended to 10 h, obvious stratification phenomenon appeared in the main pipeline, and the volume fraction of hydrogen near the top of the main pipe of about 16.5 mm was above 30%, which was positively correlated; In the shutdown status, the shutdown time has the greatest effect on the stratification phenomenon in the pipe, followed by the hydrogen-doping ratio, and the gas usage has the least effect., (© 2024. The Author(s).)

Sprint interval training (SIT) is a potent exercise strategy to enhance athletes' anaerobic capacity in a time-efficient manner. This study aimed to investigate the impact of low-volume, court-based SIT on the anaerobic capacity and sport-specific performance in competitive tennis players. Twenty-four competitive collegiate tennis players were randomly assigned to either the SIT group (n = 12; three sessions per week of court-based repeated-sprint training) or the traditional endurance training (ET) group (n = 12; three sessions per week of 45-min continuous treadmill running, n = 12) for a 6-weeks intervention. Baseline and post-intervention assessments included the Wingate Anaerobic Test, elimination rate of blood lactate (BLAer), tennis-specific repeated sprint ability (RSA), and the Yo-Yo Intermittent Recovery Test Level 2 (YoYo-IR2). The results showed that SIT group demonstrated significant improvements in peak and average power during the Wingate test (p = 0.07; p < 0.001), along with a notable increase in YoYo-IR2 performance (7.8% increase, p = 0.04). Significant decreases were observed in both mean (5.1% decrease, p = 0.02) and sum RSA time (5.2% decrease, p = 0.02) in the tennis-specific RSA assessments. Additionally, the SIT group showed significantly higher effective training time and TRIMP in the 90-100% HRmax zone compared to the ET group (p < 0.01). This study underscores the potential benefits of low-volume, court-based SIT in enhancing anaerobic capacity and sport-specific performance in competitive tennis players, in comparison to traditional ET., (© 2024. The Author(s).)

Polygonatum kingianum Collett & Hemsl., is one of the most important traditional Chinese medicines in China. The purpose of this study is to investigate the relationship between herb quality and microbial-soil variables, while also examining the composition and structure of the rhizosphere microbial community in Polygonatum kingianum, the ultimate goal is to provide a scientific approach to enhancing the quality of P. kingianum. Illumina NovaSeq technology unlocks comprehensive genetic variation and biological functionality through high-throughput sequencing. And in this study it was used to analyze the rhizosphere microbial communities in the soils of five P. kingianum planting areas. Conventional techniques were used to measure the organic elements, pH, and organic matter content. The active ingredient content of P. kingianum was identified by High Performance Liquid Chromatography (HPLC) and Colorimetry. A total of 12,715 bacterial and 5487 fungal Operational Taxonomic Units (OTU) were obtained and taxonomically categorized into 81 and 7 different phyla. Proteobacteria, Bacteroidetes, and Acidobacteriae were the dominant bacterial phyla Ascomycota and Basidiomycota were the dominat fungal phyla. The key predictors for bacterial community structure included hydrolysable nitrogen and available potassium, while for altering fungal community structure, soil organic carbon content (OCC), total nitrogen content (TNC), and total potassium content (TPOC) were the main influencing factors. Bryobacter and Candidatus Solibacter may indirectly increase the polysaccharide content of P. kingianum, and can be developed as potential Plant Growth Promoting Rhizobacteria (PGPR). This study has confirmed the differences in the soil and microorganisms of different origins of P. kingianum, and their close association with its active ingredients. And it also broadens the idea of studying the link between plants and microorganisms., (© 2024. The Author(s).)

Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit. We show how this strategy can be used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging signal transduction pathway-responsive cis-regulatory elements, we also demonstrate time- and concentration-dependent genomic recording of WNT, NF-κB and Tet-On activities. By coupling ENGRAM to sequential genome editing via DNA Typewriter 1 , we stably record information about the temporal dynamics of two orthogonal signalling pathways to genomic DNA. Finally we apply ENGRAM to integratively record the transient activity of nearly 100 transcription factor consensus motifs across daily windows spanning the differentiation of mouse embryonic stem cells into gastruloids, an in vitro model of early mammalian development. Although these are proof-of-concept experiments and much work remains to fully realize the possibilities, the symbolic recording of biological signals or states within cells, to the genome and over time, has broad potential to complement contemporary paradigms for how we make measurements in biological systems., (© 2024. The Author(s).)

Preoperatively predicting extensive intraductal component in invasive breast cancer through imaging is crucial for informed decision-making, guiding surgical planning to mitigate risks of incomplete resection or re-operation for positive margins in breast-conserving surgery. This study aimed to characterize intra- and peri-tumor heterogeneity using high-spatial resolution ultrafast DCE-MRI to predict the extensive intraductal component in invasive breast cancer (IBC-EIC) preoperatively. A retrospective analysis included invasive breast cancer patients who underwent preoperative high-spatial resolution ultrafast DCE-MRI, categorized based on intraductal component status (IBC-EIC vs. IBC without EIC). Propensity score matching (PSM) was employed to balance clinicopathological covariates between the groups. Personalized kinetic intra-tumor heterogeneity (ITH kinetic ) and peri-tumor heterogeneity (PTH kinetic ) scores were quantified using clustered voxels with similar enhancement patterns. An image combined model, incorporating MRI features, ITH kinetic , and PTH kinetic scores, was developed and assessed. Of 368 patients, 26.4% (97/368) had IBC-EIC. PSM yielded well-matched pairs of 97 patients each. After PSM, ITH kinetic and PTH kinetic scores were significantly higher in the IBC-EIC group (ITH kinetic : 0.68 ± 0.23; PTH kinetic : 0.58 ± 0.19) compared to IBC without EIC (ITH kinetic : 0.32 ± 0.25; PTH kinetic : 0.42 ± 0.18; p < 0.001). Before PSM, ITH kinetic (0.71 ± 0.20 vs. 0.49 ± 0.28, p < 0.001) and PTH kinetic (0.61 ± 0.18 vs. 0.50 ± 0.20, p < 0.001) scores remained higher in the IBC-EIC group. The Image Combined Model demonstrated good predictive performance for IBC-EIC, with an AUC of 0.91 (95% CI 0.86-0.95) after PSM and 0.85 (95% CI 0.81-0.90) before PSM. Inclusion of ITH kinetic and PTH kinetic scores significantly improved prediction capability. ITH kinetic and PTH kinetic characterization from high-spatial resolution ultrafast DCE-MRI kinetic curves enhances preoperative prediction of IBC-EIC, offering valuable insights for personalized breast cancer management., (© 2024. The Author(s).)

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis., (© 2024. The Author(s).)

Dietary intake of live microbes may benefit human health, but less is known about the role in insulin resistance. This study was developed with the goal of evaluating potential relationships between IR and dietary live microbes. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged to collect data from 6,333 subjects 18 + years of age. The Sanders system for the classification of dietary live microbe intake (containing Low (< 10 4  CFU/g), Medium (10 4 -10 7  CFU/g), or High (> 10 7  CFU/g) levels of live microbes) was then used to separate these patients into three groups (low, medium, or high). Fasting blood glucose and insulin levels were used to approximate IR based on the homeostasis model of insulin resistance (HOMA-IR). Weighted linear regressions were used to assess the relationship between IR and live microbe intake. After fully adjusting for confounding factors, subjects in the groups exhibiting medium and high levels of live microbe intake exhibited HOMA-IR scores that were below those of subjects in the low group. The relationship between live microbe intake and HOMA-IR scores was also potentially impacted by ethnicity. In summary, a negative correlation was detected between dietary live microbe intake and HOMA-IR values., (© 2024. The Author(s).)

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC., (© 2024. The Author(s).)

Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese., (© 2024. The Author(s).)

The extraction of underground coal resources induces the fracture and movement of overlying strata, leading to geological hazards such as surface deformation, cracks, and even subsidence. Utilizing the analogous hyperbola model of overlying strata movement, we conducted a mechanical analysis to examine the asymmetric fracture mechanism resulting from coal seam mining in thick loose strata. An asymmetric analogous hyperbola model was established by introducing distinct virtual half-axis lengths (b). The thickness impact of thick loose layers (H) and bedrock layer (h) on the asymmetric movement of overlying rock during mining was also discussed. Similarity model tests were conducted to research the migration characteristics and surface subsidence patterns of overburdened rock and thick loose layers at different mining stages and validate the hypothesis of asymmetric overburdened rock migration. Additionally, the discrete element numerical model for thick and loose layers mining was established by using UDEC and discussed the asymmetric analogous hyperbola behaviour of overburden movement and surface subsidence. The comparison results show that the established asymmetric hyperbolic model can effectively predict the movement law of overlying strata and surface subsidence characteristics. Therefore, the proposed model can provide valuable theoretical support for predicting the movement patterns of overburden under thick loose layers and mitigating surface subsidence disasters., (© 2024. The Author(s).)

The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model 1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications 4-8 . Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La 4 Ni 3 O 10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (T c ) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below T c , indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Reservoir computing (RC) is a bio-inspired neural network structure which can be implemented in hardware with ease. It has been applied across various fields such as memristors, and electrochemical reactions, among which the micro-electro-mechanical systems (MEMS) is supposed to be the closest to sensing and computing integration. While previous MEMS RCs have demonstrated their potential as reservoirs, the amplitude modulation mode was found to be inadequate for computing directly upon sensing. To achieve this objective, this paper introduces a novel MEMS reservoir computing system based on stiffness modulation, where natural signals directly influence the system stiffness as input. Under this innovative concept, information can be processed locally without the need for advanced data collection and pre-processing. We present an integrated RC system characterized by small volume and low power consumption, eliminating complicated setups in traditional MEMS RC for data discretization and transduction. Both simulation and experiment were conducted on our accelerometer. We performed nonlinearity tuning for the resonator and optimized the post-processing algorithm by introducing a digital mask operator. Consequently, our MEMS RC is capable of both classification and forecasting, surpassing the capabilities of our previous non-delay-based architecture. Our method successfully processed word classification, with a 99.8% accuracy, and chaos forecasting, with a 0.0305 normalized mean square error (NMSE), demonstrating its adaptability for multi-scene data processing. This work is essential as it presents a novel MEMS RC with stiffness modulation, offering a simplified, efficient approach to integrate sensing and computing. Our approach has initiated edge computing, enabling emergent applications in MEMS for local computations., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2024.)