Search

RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs. We then systematically map RNA-binding sites of these RBPs using machine learning-based modeling. Notably, the modeling reveals that the LIM domain as an RNA-binding domain in many RBPs. We validate the LIM-domain-only protein Csrp1 as a tissue-dependent RNA binding protein. Taken together, HARD-AP is a powerful approach that can be used to identify RBPomes from any type of sample, allowing comprehensive and physiologically relevant networks of RNA-protein interactions. RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism. Here the authors introduce a method named HARD-AP that effectively isolates RBPs and their closely associated RNA regulatory complexes from both cultured cells and fresh tissues. [ABSTRACT FROM AUTHOR]

A candidate reference measurement procedure (RMP) for serum theophylline via isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. With a single-step precipitation pretreatment and a 6-min gradient elution, the method achieved baseline separation of theophylline and its analogs on a C18-packed column. A bracketing calibration method was used to ensure repeatable signal intensity and high measurement precision. The intra-assay and inter-assay imprecisions were 1.06%, 0.84%, 0.72% and 0.47%, 0.41%, 0.25% at concentrations of 4.22 µg/mL (23.40 µmol/L), 8.45 µg/mL (46.90 µmol/L), and 15.21 µg/mL (84.43 µmol/L), respectively. Recoveries ranged from 99.35 to 102.34%. The limit of detection (LoD) was 2 ng/mL, and the lowest limit of quantification (LLoQ) was 5 ng/mL. The linearity range extended from 0.47 to 60 µg/mL (2.61–333.04 µmol/L). No ion suppression and carry-over (< 0.68%) were observed. The relative bias for this candidate RMP that participated in 2023 External Quality Control for Reference Laboratories (RELA) conducted by the International Federation of Clinical Chemistry (IFCC) was within a range of 0.17 to 0.93%. Furthermore, two clinical immunoassay systems were compared with this candidate RMP, demonstrating good correlations. The results of the Trueness Verification Plan indicate significant differences among routine systems, highlighting the need for standardization efforts. The developed candidate RMP for serum theophylline serves as a precise reference baseline for standardizing clinical systems and assigning values to reference materials. [ABSTRACT FROM AUTHOR]

Objective: Controversy surrounds the treatment of visceral pleural invasion in lung cancer, and no studies have compared the efficacy of its four main treatment options (i.e., surgery, chemotherapy, targeted therapy, and immunotherapy). This study aims to compare and analyze surgery, chemotherapy, targeted therapy, and immunotherapy outcomes and explore the optimal treatment of visceral pleural invasion in lung cancer. Methods: We searched electronic databases (i.e., Pubmed, Embase, Cochrane Library, CNKI, and Chinese Biomedical Literature Database Search) for relevant studies of treatment options for patients with visceral pleural invasion in stage IIA–IIB lung cancer. Searches times were limited to studies published between January 1, 2000 and February 20, 2021. Meta analysis was performed using RevMan 5.3 software We also downloaded original RNA transcription data about lung cancer invasion in the GEO and TCGA tumor databases, and used R 4.0.3 software to perform differential expression and co-expression gene network analyses. Results: We included a total of 25 high-quality (i.e., Jadad score 4–7) studies. Meta-analysis found that surgical treatment was associated with a 3-year survival rate OR = 3.80 (95% CI 3.53, 4.09; P < 0.0001), 5-year survival rate OR = 4.10 (95% CI 3.72, 4.53; P < 0.0001), and median survival time OR = 2.71 (95% CI 2.53, 2.89; P < 0.0001). Chemotherapy was associated with a 3-year survival rate OR = 2.08 (95% CI 1.93, 2.25; P < 0.0001), 5-year survival rate OR = 1.68 (95% CI 1.49, 1.89; P < 0.0001), and median survival time OR = 1.84 (95% CI 1.66, 2.04; P < 0.0001). Targeted therapy was associated with a 3-year survival rate OR = 2.91 (95% CI 2.65, 3.19; P < 0.0001), 5-year survival rate OR = 1.83 (95% CI 1.39, 2.33; P < 0.0001), and median survival time OR = 1.76 (95% CI 1.59, 1.94; P < 0.0001). Finally, immunotherapy was associated with a 3-year survival rate OR = 1.89 (95% CI 1.73, 2.07; P < 0.0001), 5-year survival rate OR = 1.66 (95% CI 1.46, 1.88; P < 0.0001), and median survival time OR = 2.53 (95% CI 2.27, 2.82; P < 0.0001). After screening differential genes and co-expressed genes in tumor gene databases, we found that AC245595.1, ITGB1-DT and AL606489.1 may be involved in the process of lung cancer invasion, and macrophages M1 and M2, CD4+-Th1, CD8+-Th1 may participate in immune infiltration. Conclusions: In patients with visceral pleural invasion of stage IIA-IIB lung cancer, chemotherapy has shown a significant effect on improving prognosis and enhancing efficacy. However, surgical treatment did not significantly improve the overall prognosis. Therefore, the individual situation of the patient and the comprehensive benefits of the treatment program should be fully considered when developing the treatment program. [ABSTRACT FROM AUTHOR]

Background: Chlorophenoxy compounds represent a group of selective herbicides widely used around the world. Chlorophenoxy herbicides are toxic, chemically stable, and can migrate into groundwater through soil leaching, posing a significant threat to drinking water safety and human health. Chlorophenoxy herbicides in groundwater aquifers are subject to anaerobic processes; however, the pathway and microbiology involved in the attenuation of chlorophenoxy herbicides under anaerobic condition are largely unknown. Here, the anaerobic degradation process of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a typical chlorophenoxy herbicide, was investigated. Results: The initial 52.5 ± 2.3 μM 2,4,5-T was completely degraded by a sediment-derived microbial consortium, with 3,4-dichlorophenol, 2,5-dichlorophenol, 3-chlorophenol (3-CP) and phenol being identified as the intermediate products. Reductive dechlorination of 3-CP to phenol and the subsequent elimination of phenol were the key transformation steps in the overall degradation process of 2,4,5-T. Amplicon sequencing suggested that Dehalobacter, Sulfuricurvum, Bacteroides, Acetobacterium, and Clostridium sensu stricto 7 might contribute to the transformation of 2,4,5-T to phenol, and Smithella, Syntrophorhabdus, Methanofollis and Methanosaeta likely cooperated to accomplish the complete mineralization of phenol. Conclusions: This study reported the anaerobic degradation of 2,4,5-T via reductive dechlorination and the subsequent syntrophic metabolization of phenol, an intermediate product transformed from 2,4,5-T. Dehalobacter was identified as the organohalide-respiring population catalyzing the reductive dechlorination reaction. Syntrophorhabdus and methanogenic populations were likely involved in anaerobic phenol oxidation and facilitated the complete mineralization of 2,4,5-T. [ABSTRACT FROM AUTHOR]

With the increasing application of flexible pipes in deep-sea operations, higher processing accuracy is required for the individual metal layers of these pipes to withstand greater service loads. In the helical winding production of the tensile armour layer, the accuracy of tension control significantly affects the uniformity of the steel strip after winding. To ensure tensile stability during the processing of steel strips, a tensile model for the manufacturing process is proposed. This model can be used to predict the magnitude and trend of tension fluctuations caused by the unwinding device, facilitating the design of a constant tension control system for steel strips based on an integral separation fuzzy PID algorithm. This system can achieve rapid convergence of tension during large tension fluctuations. The experimental results confirm the accuracy of the prediction model and the reliability and effectiveness of the designed tension control system. With this system, the tension fluctuation range is reduced by nearly 40%, and the average value of the standard deviation of the spacing after steel strip winding is decreased by 0.21 mm, demonstrating the potential of this approach for improving the manufacturing quality of the tensile armour layer of flexible pipes. [ABSTRACT FROM AUTHOR]

The global scenario on PVC plasticizer is experiencing a drastic change from petroleum-based, toxic di-(2-ethylhexyl) phthalate (DEHP) toward renewable, non-toxic bio-alternatives. However, replacing diisodecyl phthalate (DIDP), a DEHP analogue specifically intended for plasticizing PVC automotive upholstery, with bio-alternative remains a challenge as few bio-plasticizer volatilizes from PVC as slowly as DIDP, a crucial aspect compulsorily required by automotive industry. Here, we demonstrate that covalently attaching two short esters at the α-position of all components of a traditional epoxidized fatty acid methyl ester via a two-step, hydrogen-to-ester nucleophilic substitution in a one-pot procedure yields an epoxidized fatty acid tri-ester bio-plasticizer with remarkably suppressed volatilization from PVC, and hence an extremely low fogging value comparable to DIDP. With this strategy in hand, DIDP, long deemed irreplaceable despite its toxicity and non-renewable nature, may ultimately be phased out. [ABSTRACT FROM AUTHOR]

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits. Realising scalable entangled photon sources with quantum dots requires compensating for both wavelength mismatches and exciton fine-structure splitting (FSS). So far, multiple QDs with the same emission wavelength and near-zero FSS have not been demonstrated. Here, the authors fill this gap, reaching high entanglement fidelity for multiple QDs tuned into resonance with each other or with Rb atoms. [ABSTRACT FROM AUTHOR]

Semantic segmentation is significant to realize the scene understanding of autonomous driving. Due to the lack of annotated real-world data, the technology of domain adaptation is applied so that the model is trained on the synthetic data and inferred on the real data. However, this domain gap leads to aleatoric and epistemic uncertainty. These uncertainties link to the potential safety issue of autonomous driving in normal weather and adverse weather. In this study, we explore the scientific problem that has received sparse attention previously. We postulate that the Dual Attention module can mitigate the uncertainty in the task of semantic segmentation and provide some empirical study to validate it. Furthermore, the utilization of Kullback-Leibler divergence (KL divergence) helps the estimation of aleatoric uncertainty and boosts the robustness of the segmentation model. Our empirical study on the diverse datasets of semantic segmentation demonstrates the effectiveness of our method in normal and adverse weather. Our code is available at: https://github.com/liubo629/Seg-Uncertainty-dual-attention. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine whether human umbilical cord mesenchymal stem cells (hucMSCs) modified by miRNA-25-3p (miR-25-3p) overexpression could promote venous endothelial cell proliferation and attenuate portal endothelial cell injury. HucMSCs and human umbilical vein endothelial cells (HUVEC) were isolated and cultured from human umbilical cord and characterized. Lentiviral vectors expressing miRNA-25-3p were transfected into hucMSCs and confirmed by PCR. We verified the effect of miR-25-3p-modified hucMSCs on HUVEC by cell co-culture and cell supernatant experiments. Subsequently, exosomes of miR-25-3p-modified hucMSCs were isolated from cell culture supernatants and characterized by WB, NTA and TEM. We verified the effects of miR-25-3p-modified exosomes derived from hucMSCs on HUVEC proliferation, migration, and angiogenesis by in vitro cellular function experiments. Meanwhile, we further examined the downstream target genes and signaling pathways potentially affected by miR-25-3p-modified hucMSC-derived exosomes in HUVEC. Finally, we established a rat portal vein venous thrombosis model by injecting CM-DiR-labeled hucMSCs intravenously into rats and examining the homing of cells in the portal vein by fluorescence microscopy. Histological and immunohistochemical experiments were used to examine the effects of miRNA-25-3p-modified hucMSCs on the proliferation and damage of portal vein endothelial cells. Primary hucMSCs and HUVECs were successfully isolated, cultured and characterized. Primary hucMSCs were modified with a lentiviral vector carrying miR-25-3p at MOI 80. Co-culture and cell supernatant intervention experiments showed that overexpression of miRNA-25-3p in hucMSCs enhanced HUVEC proliferation, migration and tube formation in vitro. We successfully isolated and characterized exosomes of miR-25-3p-modified hucMSCs, and exosome intervention experiments demonstrated that miR-25-3p-modified exosomes derived from hucMSCs similarly enhanced the proliferation, migration, and angiogenesis of HUVECs. Subsequent PCR and WB analyses indicated PTEN/KLF4/AKT/ERK1/2 as potential pathways of action. Analysis in a rat portal vein thrombosis model showed that miR-25-3p-modified hucMSCs could homing to damaged portal veins. Subsequent histological and immunohistochemical examinations demonstrated that intervention with miR-25-3p overexpression-modified hucMSCs significantly reduced damage and attenuated thrombosis in rat portal veins. The above findings indicate suggest that hucMSCs based on miR-25-3p modification may be a promising therapeutic approach for use in venous thrombotic diseases. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Studies exploring the association between obstructive sleep apnoea syndrome (OSA) and gastrointestinal diseases (GID) are important for enhancing clinical outcomes. This study aimed to systematically assess the association between these two diseases. Adhering to PRISMA guidelines, a comprehensive literature search was conducted across databases including PubMed, Web of Science, Willey Library, Cochrane Library and Scopus. This search focused on English literature published up to January 2024. Literature screening, quality assessment (using the NOS scale) and data extraction were performed by two independent researchers. Statistical analyses were performed using the meta-package of the R.4.2.2 software. An initial screening of 2178 papers was conducted and 11 studies were included. Meta-analysis results showed a significant association between OSA and GID (p < 0.01). Subgroup analyses further indicated a stronger association between OSA and GID in Asian populations compared to Europe and the United States. In addition, both benign and malignant GID were significantly associated with OSA, with a pronounced association for malignant GID than for benign GID. The results of publication bias analysis revealed no significant bias (Begg's test p = 0.45, Egger's test p = 0.60). This study uncovers a notable association between OSA and GID, especially in Asian populations, suggesting that clinicians should consider the potential connection between these two diseases during diagnosis and treatment. However, due to the heterogeneity and limitations of the study, these conclusions need to be further validated through more comprehensive research. [ABSTRACT FROM AUTHOR]

Luster is one of the vital indexes in pearl grading. To find a fast, nondestructive, and low-cost grading method, optical coherence tomography (OCT) is introduced to predict the luster grade through the texture features. After background removal, flattening, and segmentation, the speckle pattern of the region of interest is described by seven kinds of feature textures, including center-symmetric auto-correlation (CSAC), fractal dimension (FD), Gabor, gray level co-occurrence matrix (GLCM), histogram of oriented gradients (HOG), laws texture energy (LAWS), and local binary patterns (LBP). To find the relations between speckle-derived texture features and luster grades, four Four groups of pearl samples were used in the experiment to detect texture differences based on support vector machines (SVMs) and random forest classifier (RFC)) for investigating the relations between speckle-derived texture features and luster grades. The precision, recall, F1-score, and accuracy are more significant than 0.9 in several simulations, even after dimension reduction. This demonstrates that the texture feature from OCT images can be applied to class the pearl luster based on speckle changes. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) plays an important role in malignant progression of Triple-negative breast cancer (TNBC). Many studies have confirmed that miRNA-200c-3p is related to EMT. And we found that it is involved in the regulation of EMT, but the exact mechanism is unclear. CRKL is highly expressed in a variety of tumors and plays a role in EMT. In this study, the potential targets of miRNA-200c-3p were searched in miRPathDB, Targetscan and PicTar. And there are 68 potential targets at the intersection of the three databases. Then, bioinformatics and text mining performed by Coremine Medica, and found that among 68 potential targets, CRKL has the strongest correlation with EMT in TNBC. Therefore, we speculated that miRNA-200c-3p involvement in EMT might be related to CRKL. To verify miRNA-200c-3p inhibits the malignant phenotype of TNBC by regulating CRKL, RT‒PCR, western blotting, Clonal formation assays,CCK-8 proliferation assays, transwell invasion assays, Luciferase reporter assay and nude mouse transplantation tumor assay were performed. In this study, we found that miRNA-200c-3p is under-expressed and EMT-related genes are up-regulated in TNBC, and miRNA-200c-3p can inhibit cancer cell proliferation, invasion and the expression of EMT-related genes and proteins in TNBC. Further research confirmed that miRNA-200c-3p could inhibit EMT by inhibiting the expression of CRKL that directly combining CRKL gene. [ABSTRACT FROM AUTHOR]

The implementation of a laparoscope-holding robot in minimally invasive surgery enhances the efficiency and safety of the operation. However, the extra robot control task can increase the cognitive load on surgeons. A suitable interface may simplify the control task and reduce the surgeon load. Foot interfaces are commonly used for commanding laparoscope-holding robots, with two control strategies available: decoupled control permits only one Cartesian axis actuation, known as decoupled commands; hybrid control allows for both decoupled commands and multiple axes actuation, known as coupled commands. This paper aims to determine the optimal control strategy for foot interfaces by investigating two common assumptions in the literature: (1) Decoupled control is believed to result in better predictability of the final laparoscopic view orientation, and (2) Hybrid control has the efficiency advantage in laparoscope control. Our user study with 11 experienced and trainee surgeons shows that decoupled control has better predictability than hybrid control, while both approaches are equally efficient. In addition, using two surgery-like tasks in a simulator, users’ choice of decoupled and coupled commands is analysed based on their level of surgical experience and the nature of the movement. Results show that trainee surgeons tend to issue more commands than the more experienced participants. Single decoupled commands were frequently used in small view adjustments, while a mixture of coupled and decoupled commands was preferred in larger view adjustments. A guideline for foot interface control strategy selection is provided. [ABSTRACT FROM AUTHOR]

Cell migration is an essential manner of different cell lines that are involved in embryological development, immune responses, tumorigenesis, and metastasis in vivo. Physical confinement derived from crowded tissue microenvironments has pivotal effects on migratory behaviors. Distinct migration modes under a heterogeneous extracellular matrix (ECM) have been extensively studied, uncovering potential molecular mechanisms involving a series of biological processes. Significantly, multi-omics strategies have been launched to provide multi-angle views of complex biological phenomena, facilitating comprehensive insights into molecular regulatory networks during cell migration. In this review, we describe biomimetic devices developed to explore the migratory behaviors of cells induced by different types of confined microenvironments in vitro. We also discuss the results of multi-omics analysis of intrinsic molecular alterations and critical pathway dysregulations of cell migration under heterogeneous microenvironments, highlighting the significance of physical confinement–triggered intracellular signal transduction in order to regulate cellular behaviors. Finally, we discuss both the challenges and promise of mechanistic analysis in confinement-induced cell migration, promoting the development of early diagnosis and precision therapeutics. [ABSTRACT FROM AUTHOR]

Prime editing enables the precise modification of genomes through reverse transcription of template sequences appended to the 3′ ends of CRISPR–Cas guide RNAs1. To identify cellular determinants of prime editing, we developed scalable prime editing reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as the strongest mediator of prime editing: the small RNA-binding exonuclease protection factor La. Further investigation revealed that La promotes prime editing across approaches (PE2, PE3, PE4 and PE5), edit types (substitutions, insertions and deletions), endogenous loci and cell types but has no consistent effect on genome-editing approaches that rely on standard, unextended guide RNAs. Previous work has shown that La binds polyuridine tracts at the 3′ ends of RNA polymerase III transcripts2. We found that La functionally interacts with the 3′ ends of polyuridylated prime editing guide RNAs (pegRNAs). Guided by these results, we developed a prime editor protein (PE7) fused to the RNA-binding, N-terminal domain of La. This editor improved prime editing with expressed pegRNAs and engineered pegRNAs (epegRNAs), as well as with synthetic pegRNAs optimized for La binding. Together, our results provide key insights into how prime editing components interact with the cellular environment and suggest general strategies for stabilizing exogenous small RNAs therein.Genome-scale genetic screens identify the small RNA-binding protein La as a strong mediator of prime editing. [ABSTRACT FROM AUTHOR]

Highly integrated electrical components produce intensive heat while in use, which will seriously impact their performance if not properly designed. In this study, an end-to-end heat dissipation structure topology optimization prediction framework considering physical mechanisms was established by using the convolutional neural network (CNN) and the moving morphable components (MMC) method. Aiming at the sparsity of physical field matrix caused by the initial component distribution in MMC method, a CNN model was established taking the temperature gradient information of both homogeneous material and initial component layout as input. Compared with other seven input forms, the CNN model in this study considers both the initial component layout and the physical field information of the structure, which can predict the topology configuration of heat dissipation structure more accurately. In addition, an improved penalty mean square error (PMSE) function was proposed by introducing a penalty factor, which improved the prediction ability of the CNN model on the structural boundary and ensured more accurate and efficient structural heat dissipation performance. Several 2D and 3D numerical examples verified the effectiveness of the proposed framework and the dual temperature gradient input model. The overall framework provides a new method for the innovative and efficient heat dissipation structure topology optimization in packaging structure of electronic equipment. [ABSTRACT FROM AUTHOR]

Highlights: A strategy based on metal-organic decomposition is proposed to enhance the tube-tube interactions of carbon nanotubes (CNTs). The robust tube-tube interactions of CNTs enhance both EMI shielding performance and mechanical properties of CNT film. This innovative approach provides an effective way to obtain high-performance CNT film. The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube–tube interactions of CNTs. Herein, we develop a novel strategy based on metal–organic decomposition (MOD) to fabricate a flexible silver–carbon nanotube (Ag–CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube–tube interactions. As a result, the electrical conductivity of Ag–CNT film is up to 6.82 × 105 S m−1, and the EMI shielding effectiveness of Ag–CNT film with a thickness of ~ 7.8 μm exceeds 66 dB in the ultra-broad frequency range (3–40 GHz). The tensile strength and Young's modulus of Ag–CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag–CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices. [ABSTRACT FROM AUTHOR]

The development of dielectric ceramics for energy storage has received great research attention due to high power density and extremely high charge–discharge speed in recent years. Herein, the lead-free (1-x)(0.92K0.5Na0.5NbO3-0.08Sr0.7Bi0.2TiO3)-xBi(Zn0.5Zr0.5)O3 [(1-x)(0.92KNN-0.08SBT)-xBZZ] ceramics were prepared. The enhanced energy storage performance in the x = 0.15 sample, with large recoverable energy storage density (Wrec) of 3.35 J/cm3 and high energy efficiency (η) of 81.9%, which can export satisfactory in temperatures (25–150 °C) and frequencies (1–100 Hz). It is revealed that the introduction of BZZ can enhance relaxor behaviors and decrease grain size, which are supported by the dielectric tunability, polarization hysteresis, and microstructure. Also, a superfast discharge speed (t0.9 = 27.2 ns) and a high power density (PD = 26.04 WM/cm3), with minimal fluctuation of ≤ 5.6%, are examined ranging from 20 °C to 120 °C. These characteristics render 0.85(0.92KNN-0.08SBT)-0.15BZZ ceramic promising candidate for high power energy storage applications. [ABSTRACT FROM AUTHOR]

The tumor microenvironment is reprogrammed by cancer cells and participates in all stages of tumor progression. Neutral ceramidase is a key regulator of ceramide, the central intermediate in sphingolipid metabolism. The contribution of neutral ceramidase to the reprogramming of the tumor microenvironment is not well understood. Here, we find that deletion of neutral ceramidase in multiple breast cancer models in female mice accelerates tumor growth. Our result show that Ly6C+CD39+ tumor-infiltrating CD8 T cells are enriched in the tumor microenvironment and display an exhausted phenotype. Deletion of myeloid neutral ceramidase in vivo and in vitro induces exhaustion in tumor-infiltrating Ly6C+CD39+CD8+ T cells. Mechanistically, myeloid neutral ceramidase is required for the generation of lipid droplets and for the induction of lipolysis, which generate fatty acids for fatty-acid oxidation and orchestrate macrophage metabolism. Metabolite ceramide leads to reprogramming of macrophages toward immune suppressive TREM2+ tumor associated macrophages, which promote CD8 T cells exhaustion. Ceramide, a central molecule in sphingolipid metabolism, has been shown to affect the development and functionality of myeloid cells. Here the authors report that myeloid deficiency of neutral ceramidase (NcDase), the enzyme converting ceramide into sphingosine, induces an immunosuppressive phenotype of tumor associated macrophages, linked to T cell exhaustion in breast cancer preclinical models. [ABSTRACT FROM AUTHOR]

Background: One-stage jaw reconstruction with fibular flap and prosthetic rehabilitation restores bony and dental continuity simultaneously. It was also called as "jaw-in-a-day (JIAD)" technique. However, bone volume and height of fibular flap may be insufficient for dental implant insertion. The provision of a considerable amount of bone makes an iliac flap the ideal choice in these cases. We present the first case report to document the use of one-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap. Case presentation: We modified the conventional JIAD workflow to make it suitable for iliac flap. Two cases were presented who both underwent segmental mandibulectomy for ameloblastoma. Virtual surgical planning was performed in all cases. The iliac crest was positioned upward to provide cortical bone for achieving primary stability of dental implants. Similar to the "all-on-4" procedure, the iliac bone was placed 12 to 15 mm below the occlusal plane to create adequate space for the implant-retained prosthesis. Immediate implant-based dental rehabilitation was performed at same stage. The surgery was successful in all cases without any short-term complications. In the first postoperative week, patients were given a liquid diet through a nasal feeding tube. The liquid diet is advised until 1 month after the surgery. Thereafter, a soft diet is recommended. Patients were advised to resume routine mastication and normal diet 3 months after the surgery. Peri-implantitis occurred in one patient, and additional gingival graft was required. Postoperative function and esthetics were satisfactory at the last follow-up visit. Conclusions: One-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap are safe and useful for restoring postoperative function and esthetics. It should be used in more cases with a longer follow-up in further studies. [ABSTRACT FROM AUTHOR]

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients. [ABSTRACT FROM AUTHOR]

Coordinating multiple agents to optimize an objective has several real-world applications. In areas such as disaster rescue, environment monitoring and the like, mobile agents may be deployed to work as a team to achieve a joint goal. Recently, multi-agent problems involving mobile sensor teams have been formalized in the literature as DCOP_MSTs. Under this class of problems, DCOP algorithms are applied to enable agents to coordinate the assignment of their physical locations as they jointly optimize the team objective. In DCOP_MSTs, the environment is dynamic, and agents may leave or join the environment at random times. As a result, a predefined interaction topology or graph may not be useful over the problem horizon. Therefore, there is a need to study methods that could facilitate agent-to-agent interaction in such open and dynamic environments. Existing methods require reconstructing the entire graph upon detecting changes in the environment or assume a predefined interaction graph. In this study, we propose a dynamic multi-agent hierarchy construction algorithm that can be used by DCOP_MST algorithms that require a pseudo-tree for execution. We evaluate our proposed method in a simulated target detection case study to show the effectiveness of the proposed approach in large agent teams. [ABSTRACT FROM AUTHOR]

The mammalian gastrointestinal tract is a complex environment that hosts a diverse microbial community. To establish infection, bacterial pathogens must be able to compete with the indigenous microbiota for nutrients, as well as sense the host environment and modulate the expression of genes essential for colonization and virulence. Here, we found that enterohemorrhagic Escherichia coli (EHEC) O157:H7 imports host- and microbiota-derived L-malate using the DcuABC transporters and converts these substrates into fumarate to fuel anaerobic fumarate respiration during infection, thereby promoting its colonization of the host intestine. Moreover, L-malate is important not only for nutrient metabolism but also as a signaling molecule that activates virulence gene expression in EHEC O157:H7. The complete virulence-regulating pathway was elucidated; the DcuS/DcuR two-component system senses high L-malate levels and transduces the signal to the master virulence regulator Ler, which in turn activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence to epithelial cells of the large intestine. Disruption of this virulence-regulating pathway by deleting either dcuS or dcuR significantly reduced colonization by EHEC O157:H7 in the infant rabbit intestinal tract; therefore, targeting these genes and altering physiological aspects of the intestinal environment may offer alternatives for EHEC infection treatment. Here, Liu et al show that enterohaemorrhagic Escherichia coli utilizes host- and microbiota-derived L-malate as an essential nutrient and signalling molecule to promote its growth and colonization in the large intestine. [ABSTRACT FROM AUTHOR]

In this article we develop an analogue of Aubry-Mather theory for time periodic dissipative equation x ˙ = ∂ p H (x , p , t) , p ˙ = - ∂ x H (x , p , t) - f (t) p with (x , p , t) ∈ T ∗ M × T (compact manifold M without boundary). We discuss the asymptotic behaviors of viscosity solutions for the associated Hamilton-Jacobi equation ∂ t u + f (t) u + H (x , ∂ x u , t) = 0 , (x , t) ∈ M × T w.r.t. certain parameters, and analyze the meanings in controlling the global dynamics. We also discuss the prospect of applying our conclusions to many physical models. [ABSTRACT FROM AUTHOR]

We developed and evaluated two-level, namely 2017011 and 2017012, serum-based reference materials (RMs) for 17 beta-estradiol (17 β-E2) by the reference method of isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) from the remaining serum samples after routine clinical tests, to help improve clinical routine testing and provide the traceability of results. This paper describes the development process of these RMs. The National Metrology Institute of Japan (NMIJ) certified reference material (CRM) 6004-a was used as the primary RM for the measurement of 17 β-E2. These serum-based RMs showed satisfactory homogeneity and stability. They also assessed the commutability between the reference method and the three routine clinical immunoassay systems. Besides, a collaborative study was carried out in five reference laboratories, all of which had been accredited by the China National Accreditation Service for Conformity Assessment (CNAS) in accordance with ISO/WD 15725-1. Statistical analysis of raw results and uncertainty assessment obtained certified values: 2017011 was 445.2 ± 39.0 pmol/L, and 2017012 was 761.9 ± 35.5 pmol/L. [ABSTRACT FROM AUTHOR]

Machining time and energy consumption are common process planning evaluation metrics. However, it is difficult to obtain accurate machining time and energy consumption values in the process planning stage, which may result in non-optimal obtaining process routes. To solve these problems, this paper proposes a flexible process planning method based on processing time and energy consumption prediction models. The historical processing data is analyzed, and a prediction model of machining time and energy consumption based on a radial basis function neural network is proposed. Considering the flexibility of multiple processes, a mathematical model of the flexible process planning problem based on the machining time and energy consumption prediction model is established. A multi-objective algorithm using a multidimensional real number coding method is proposed for problem-solving with the completion time and energy consumption minimization as the optimization objective. Two algorithms with better multi-objective optimization performance, the strength Pareto evolution algorithm 2, and the dominance ranking genetic algorithm II are selected for comparative analysis to obtain a better effect of optimization. The better algorithm is selected with the best parameters. Finally, case studies are conducted to verify the validity of the prediction model and the flexible process planning model. [ABSTRACT FROM AUTHOR]

Buffer overflow poses a serious threat to the memory security of modern operating systems. It overwrites the contents of other memory areas by breaking through the buffer capacity limit, destroys the system execution environment, and provides implementation space for various system attacks such as program control flow hijacking. That makes it a wide range of harms. A variety of security technologies have been proposed to deal with system security problems including buffer overflow. For example, No eXecute (NX for short) is a memory management technology commonly used in Harvard architecture. It can refuse the execution of code which residing in a specific memory, and can effectively suppress the abnormal impact of buffer overflow on control flow. Therefore, in recent years, it has also been used in the field of system security, deriving a series of solutions based on NX technology, such as ExecShield, DEP, StackGuard, etc. However, these security solutions often rely too much on the processor architecture so that the protection coverage is insufficient and the accuracy is limited. Especially in the emerging system architecture field represented by RISC-V, there is still a lack of effective solutions for buffer overflow vulnerabilities. With the continuous rapid development of the system architecture, it is urgent to develop defense methods that are applicable to different system application environments and oriented to all executable memory spaces to meet the needs of system security development. Therefore, we propose BOP, A new system memory security design method based on RISC-V extended instructions, to build a RISC-V buffer overflow detection and defense system and deal with the buffer overflow threat in RISC-V. According to this method, NX technology can be combined with program control flow analysis, and NX bit mechanism can be used to manage the executability of memory space, so as to achieve a more granular detection and defense of buffer overflow attacks that may occur in RISC-V system environment. In addition, The memory management and control function of BOP is not only very suitable for solving the security problems in the existing single architecture system, but also widely applicable to the combination of multiple heterogeneous systems. [ABSTRACT FROM AUTHOR]

This study investigates the interaction between long non-coding RNAs (lncRNAs) and metabolic risk factors that contribute to coronary artery disease (CAD). A total transcriptome high throughput sequencing study was conducted on peripheral blood mononuclear cells from five patients with CAD and five healthy controls. Validation assay by qRT-PCR was conducted among 270 patients and 47 controls. Finally, to evaluate the lncRNAs’ diagnostic value for CAD, the Spearman correlation test and receiver operating characteristic curve (ROC) analysis were utilized. Additionally, univariate and multivariate logistic regression along with crossover analyses were conducted to identify the interaction between lncRNA and environmental risk factors. A total of 2149 of 26,027 lncRNAs identified by RNA sequencing were differentially expressed in CAD patients compared to controls. Validation by qRT-PCR showed significantly different relative expression levels for lncRNAs PDXDC1-AS1, SFI1-AS1, RP13-143G15.3, DAPK1-IT1, PPIE-AS1, and RP11-362A1.1 between the two groups (all P<0.05). The area under the ROC values of PDXDC1-AS1 and SFI1-AS1 is 0.645 (sensitivity=0.443 and specificity=0.920) and 0.629 (sensitivity=0.571 and specificity=0.909), especially. Multivariate logistic regression analyses showed that lncRNAs PDXDC1-AS1 (OR=2.285, 95%CI=1.390-3.754, p=0.001) and SFI1-AS1 (OR=1.163, 95%CI=1.163–2.264, p=0.004) were protective factors against CAD. Under the additive model, cross-over analyses demonstrated significant interactions between lncRNAs PDXDC1-AS1 and smoking in relation to CAD risk (S=3.871, 95%CI=1.140–6.599). PDXDC1-AS1 and SFI1-AS1 were sensitive and specific biomarkers for CAD and exhibited synergistic effects with certain environmental factors. These results highlighted their potential use as CAD diagnostic biomarkers for future research. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "In vivo evaluation of Mg–6Zn and titanium alloys on collagen metabolism in the healing of intestinal anastomosis" published in Scientific Reports. The correction states that there were errors in the assembly of Figure 4 and Figure 5 in the original article. The corrected figures and accompanying legends are provided in the correction notice. The authors of the article are Xiao-hu Wang, Jian-shu Ni, Nai-long Cao, Song Yu, Yi-gang Chen, Shao-xiang Zhang, Bao-jun Gu, and Jun Yan. [Extracted from the article]

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH. Analysis of plasma metabolites in virologically suppressed individuals infected with HIV-1 and controls, reveals an association between metabolic plasticity and CD8 + T cell-mediated HIV infection control. [ABSTRACT FROM AUTHOR]

Evolutionary game theory on complex networks provides an effective theoretical tool to explain the emergence of sustained cooperative behavior. Human society has formed various organizational networks. The network structure and individual behavior take on a variety of forms. This diversity provides the basis for choice, so it is crucial for the emergence of cooperation. This article provides a dynamic algorithm for individual network evolution, and calculates the importance of different nodes in the network evolution process. In the dynamic evolution simulation, the probability of the cooperation strategy and betrayal strategy is described. In the individual interaction network, cooperative behavior will promote the continuous evolution of individual relationships and form a better aggregative interpersonal network. The interpersonal network of betrayal has been in a relatively loose state, and its continuity must rely on the participation of new nodes, but there will be certain "weak links" in the existing nodes of the network. [ABSTRACT FROM AUTHOR]

The circadian clock orchestrates a wide variety of physiological and behavioral processes, enabling animals to adapt to daily environmental changes, particularly the day-night cycle. However, the circadian clock's role in the developmental processes remains unclear. Here, we employ the in vivo long-term time-lapse imaging of retinotectal synapses in the optic tectum of larval zebrafish and reveal that synaptogenesis, a fundamental developmental process for neural circuit formation, exhibits circadian rhythm. This rhythmicity arises primarily from the synapse formation rather than elimination and requires the hypocretinergic neural system. Disruption of this synaptogenic rhythm, by impairing either the circadian clock or the hypocretinergic system, affects the arrangement of the retinotectal synapses on axon arbors and the refinement of the postsynaptic tectal neuron's receptive field. Thus, our findings demonstrate that the developmental synaptogenesis is under hypocretin-dependent circadian regulation, suggesting an important role of the circadian clock in neural development. Whether the circadian clock regulates early developmental processes is poorly understood. Here, the authors report the circadian rhythm of synapse formation during early brain development by using the retinotectal system of larval zebrafish as an in vivo model. [ABSTRACT FROM AUTHOR]

China is committed to the targets of achieving peak CO2 emissions around 2030 and realizing carbon neutrality around 2060. To realize carbon neutrality, people are seeking to replace fossil fuel with renewable energy. Thermal energy storage is the key to overcoming the intermittence and fluctuation of renewable energy utilization. In this paper, the relation between renewable energy and thermal energy storage is first addressed. Then, the classifications of thermal energy storage and Carnot batteries are given. The aim of this review is to provide an insight into the promising thermal energy storage technologies for the application of renewable energy in order to realize carbon neutrality. Three types of heat storage methods, especially latent heat storage and thermochemical heat storage, are analyzed in detail. The application of thermal energy storage is influenced by many heat storage properties, such as temperature range, heat storage capacity, cost, stability, and technical readiness. Therefore, the heat storage properties for different heat storage technologies are reviewed and compared. The advantage and challenge of different heat storage technologies and Carnot batteries for carbon neutrality processes are analyzed. Finally, the prospects of different heat storage technologies are summarized. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor that is highly aggressive and ranks fifth among the most common cancers worldwide. Although, the researches that attempted to construct a diagnostic model were deficient in HNSCC. Currently, the gold standard for diagnosing head and neck tumors is pathology, but this requires a traumatic biopsy. There is still a lack of a noninvasive test for such a high—incidence tumor. In order to screen genetic markers and construct diagnostic model, the methods of random forest (RF) and artificial neural network (ANN) were utilized. The data of HNSCC gene expression was accessed from Gene Expression Omnibus (GEO) database; we selected three datasets totally, and we combined 2 datasets (GSE6631 and GSE55547) for screening differentially expressed genes (DEGs) and chose another dataset (GSE13399) for validation. Firstly, the 6 DEGs (CRISP3, SPINK5, KRT4, MMP1, MAL, SPP1) were screened by RF. Subsequently, ANN was applied to calculate the weights of 6 genes. Besides, we created a diagnostic model and nominated it as neuralHNSCC, and the performance of neuralHNSCC by area under curve (AUC) was verified using another dataset. Our model achieved an AUC of 0.998 in the training cohort, and 0.734 in the validation cohort. Furthermore, we used the Cell-type Identification using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm to investigate the difference in immune cell infiltration between HNSCC and normal tissues initially. The selected 6 DEGs and the constructed novel diagnostic model of HNSCC would make contributions to the diagnosis. [ABSTRACT FROM AUTHOR]

Highlights: A flexible freestanding TaS2 film (thickness = 3.1 μm) exhibits an ultralow void ratio of 6.01%, an ultra-high electrical conductivity of 2,666 S cm−1, an electromagnetic interference shielding effectiveness (EMI SE) of 41.8 dB, an absolute EMI SE (SSE/t) of 27,859 dB cm2 g−1, and excellent flexibility withstand 1,000 bends without rupture. The TaS2 composite films exhibit excellent EMI shielding properties and higher tensile strength with better mechanical flexibility, making them suitable for EMI shielding practical applications. Low-dimensional transition metal dichalcogenides (TMDs) have unique electronic structure, vibration modes, and physicochemical properties, making them suitable for fundamental studies and cutting-edge applications such as silicon electronics, optoelectronics, and bioelectronics. However, the brittleness, low toughness, and poor mechanical and electrical stabilities of TMD-based films limit their application. Herein, a TaS2 freestanding film with ultralow void ratio of 6.01% is restacked under the effect of bond-free van der Waals (vdW) interactions within the staggered 2H-TaS2 nanosheets. The restacked films demonstrated an exceptionally high electrical conductivity of 2,666 S cm−1, electromagnetic interference shielding effectiveness (EMI SE) of 41.8 dB, and absolute EMI SE (SSE/t) of 27,859 dB cm2 g−1, which is the highest value reported for TMD-based materials. The bond-free vdW interactions between the adjacent 2H-TaS2 nanosheets provide a natural interfacial strain relaxation, achieving excellent flexibility without rupture after 1,000 bends. In addition, the TaS2 nanosheets are further combined with the polymer fibers of bacterial cellulose and aramid nanofibers via electrostatic interactions to significantly enhance the tensile strength and flexibility of the films while maintaining their high electrical conductivity and EMI SE.This work provides promising alternatives for conventional materials used in EMI shielding and nanodevices. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although tissue-resident memory T (TRM) cells specific for previously encountered pathogens have been characterized, the induction and recruitment of brain TRM cells following immune therapy has not been observed in the context of glioblastoma. Here, we show that T cells expressing fibrinogen-like 2 (FGL2)–specific single-chain variable fragments (T-αFGL2) can induce tumor-specific CD8+ TRM cells that prevent glioblastoma recurrence. These CD8+ TRM cells display a highly expanded T cell receptor repertoire distinct from that found in peripheral tissue. When adoptively transferred to the brains of either immunocompetent or T cell-deficient naïve mice, these CD8+ TRM cells reject glioma cells. Mechanistically, T-αFGL2 cell treatment increased the number of CD69+CD8+ brain-resident memory T cells in tumor-bearing mice via a CXCL9/10 and CXCR3 chemokine axis. These findings suggest that tumor-specific brain-resident CD8+ TRM cells may have promising implications for the prevention of brain tumor recurrence. Glioblastoma is an aggressive type of cancer with poor patient prognosis. Here, the authors show that T cells armed with an FGL2-specific scFV can induce antitumour responses mediated by tissue-resident memory T cells in the brain. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = − 0.72, − 0.70, p < 0.001; r = − 0.62, − 0.56, p < 0.05. flexors: r = − 0.37, − 0.43, p < 0.05; r = − 0.39, − 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients. [ABSTRACT FROM AUTHOR]

Treatment of COVID-19 with a soluble version of ACE2 that binds to SARS-CoV-2 virions before they enter host cells is a promising approach, however it needs to be optimized and adapted to emerging viral variants. The computational workflow presented here consists of molecular dynamics simulations for spike RBD-hACE2 binding affinity assessments of multiple spike RBD/hACE2 variants and a novel convolutional neural network architecture working on pairs of voxelized force-fields for efficient search-space reduction. We identified hACE2-Fc K31W and multi-mutation variants as high-affinity candidates, which we validated in vitro with virus neutralization assays. We evaluated binding affinities of these ACE2 variants with the RBDs of Omicron BA.3, Omicron BA.4/BA.5, and Omicron BA.2.75 in silico. In addition, candidates produced in Nicotiana benthamiana, an expression organism for potential large-scale production, showed a 4.6-fold reduction in half-maximal inhibitory concentration (IC50) compared with the same variant produced in CHO cells and an almost six-fold IC50 reduction compared with wild-type hACE2-Fc. [ABSTRACT FROM AUTHOR]

Autonomous driving has attracted significant research interests in the past two decades as it offers many potential benefits, including releasing drivers from exhausting driving and mitigating traffic congestion, among others. Despite promising progress, lane-changing remains a great challenge for autonomous vehicles (AV), especially in mixed and dynamic traffic scenarios. Recently, reinforcement learning (RL) has been widely explored for lane-changing decision makings in AVs with encouraging results demonstrated. However, the majority of those studies are focused on a single-vehicle setting, and lane-changing in the context of multiple AVs coexisting with human-driven vehicles (HDVs) have received scarce attention. In this paper, we formulate the lane-changing decision-making of multiple AVs in a mixed-traffic highway environment as a multi-agent reinforcement learning (MARL) problem, where each AV makes lane-changing decisions based on the motions of both neighboring AVs and HDVs. Specifically, a multi-agent advantage actor-critic (MA2C) method is proposed with a novel local reward design and a parameter sharing scheme. In particular, a multi-objective reward function is designed to incorporate fuel efficiency, driving comfort, and the safety of autonomous driving. A comprehensive experimental study is made that our proposed MARL framework consistently outperforms several state-of-the-art benchmarks in terms of efficiency, safety, and driver comfort. [ABSTRACT FROM AUTHOR]

Chinese Edison pearls, invented and produced in China by the Zhejiang Grace Pearl Jewelry Co., Ltd, are usually large and round with variable but attractive colors. Edison pearls have entered the jewelry market in 2011. However, the fine microstructural characteristics of these pearls remain largely unknown, particularly the thickness of the nacre and the spatial distributions of organic pigment in the nacre. Herein, using X-ray microradiography analysis, field-emission scanning electron microscopy, and Raman spectroscopy, we comprehensively investigated the internal fine-microstructural characteristics of typical colored Edison pearls. Our results indicated that Edison pearls have a typical core–shell structure, in which the core is the nucellus and the shell is the nacre. Average nacre thicknesses varied from 1.00 to 3.60 mm among specimens. Surprisingly, theoretical calculations showed that nacre accounted for about 50–90% of the whole pearl by volume. In addition, multiple prismatic or irregular structures, almost entirely composed of aragonite, coexisted in the nacre of some Edison pearls; one of these structures was closely adjacent to the nucleus. Interestingly, the average thickness of individual aragonite tablets in the nacre gradually decreased from the inner nacre (near the nucleus) to the outer nacre (near the pearl surface). Finally, the intensity ratios of the two peaks in the Raman spectra (I1124–1134/I1085) were non-uniform across nacre regions, and generally increased with distance from the nucleus. This pattern was directly attributed to variations in pigment content among nacre regions. Our results substantially increase our understanding of nacre biomineralization and the gemological characteristics of colored Edison pearls. More importantly, this study identified certain characteristics that can be used to identify color-treated Edison pearls. [ABSTRACT FROM AUTHOR]

The current tumour-node-metastasis (TNM) staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer (GC). Pathomics, which is based on the development of digital pathology, is an emerging field that might improve clinical management. Herein, we propose a pathomics signature (PSGC) that is derived from multiple pathomics features of haematoxylin and eosin-stained slides. We find that the PSGC is an independent predictor of prognosis. A nomogram incorporating the PSGC and TNM staging system shows significantly improved accuracy in predicting the prognosis compared to the TNM staging system alone. Moreover, in stage II and III GC patients with a low PSGC (but not in those with a high PSGC), satisfactory chemotherapy benefits are observed. Therefore, the PSGC could serve as a prognostic predictor in patients with GC and might be a potential predictive indicator for decision-making regarding adjuvant chemotherapy. The current tumour-node-metastasis staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer. Herein, the authors propose a pathomics signature that was derived from multiple features of haematoxylin and eosin-stained slides. [ABSTRACT FROM AUTHOR]

We present a methodology for preparing a novel aluminum bronze composite reinforced with micro-size tungsten particles through aluminothermic reduction. To synthesize the aluminum bronze composite ingot, the adiabatic temperature (Tad) and thermodynamic equilibrium of the Al–CuO–WO3 system were calculated. The aluminum bronze composites with different target W contents were synthesized and systematically characterized. The results indicate that it is feasible to synthesize aluminum bronze composites reinforced with micro-tungsten particles via aluminothermic reduction. However, temperatures higher than 2000 K were not conducive to the forward reduction reaction. The microstructure of the aluminum bronze composite primarily comprises a gray matrix, white spherical tungsten particles, and black inclusions. With the increasing ratio of WO3 in the raw materials, the average size of the tungsten particles in the aluminum bronze composite ingots increased from 0.59mm to 2.06 mm, and the tungsten particle size increasingly tended toward normal distribution. The Al content decreased from 9.20% to 4.90%, while the O and Ca content increased slightly. The number of oxide inclusions in the aluminum bronze composites increased slightly. The slag obtained after aluminothermic reduction was comprised of CaAl4O7, W17O47, and Cu2O. [ABSTRACT FROM AUTHOR]

Oxidative degradation of chitin, initiated by lytic polysaccharide monooxygenases (LPMOs), contributes to microbial bioconversion of crystalline chitin, the second most abundant biopolymer in nature. However, our knowledge of oxidative chitin utilization pathways, beyond LPMOs, is very limited. Here, we describe a complete pathway for oxidative chitin degradation and its regulation in a marine bacterium, Pseudoalteromonas prydzensis. The pathway starts with LPMO-mediated extracellular breakdown of chitin into C1-oxidized chitooligosaccharides, which carry a terminal 2-(acetylamino)−2-deoxy-D-gluconic acid (GlcNAc1A). Transmembrane transport of oxidized chitooligosaccharides is followed by their hydrolysis in the periplasm, releasing GlcNAc1A, which is catabolized in the cytoplasm. This pathway differs from the known hydrolytic chitin utilization pathway in enzymes, transporters and regulators. In particular, GlcNAc1A is converted to 2-keto-3-deoxygluconate 6-phosphate, acetate and NH3 via a series of reactions resembling the degradation of D-amino acids rather than other monosaccharides. Furthermore, genomic and metagenomic analyses suggest that the chitin oxidative utilization pathway may be prevalent in marine Gammaproteobacteria. Lytic polysaccharide monooxygenases contribute to microbial degradation of chitin, but how the resulting oxidized chitooligosaccharides are utilized by microbes is unclear. Here, the authors describe a complete pathway for oxidative chitin utilization in marine bacteria. [ABSTRACT FROM AUTHOR]

Microbially induced calcite precipitation (MICP) through the bio-stimulation approach is a promising ground improvement technique that can improve the engineering performance of calcareous sand. This study investigated the shear response of bio-cemented calcareous sand (with 16.2% and 54.6% initial relative density) treated by bio-stimulated MICP. The calcareous sand samples, prepared at two initial relative densities, were firstly subjected to the enrichment and cementation treatment to gain various cementation levels. Biochemical parameters including viable cell number, urea and ammonium concentration, and cementation content were measured during the two stages. The direct shear tests were then conducted at five different normal stresses, and the peak stress ratio, cohesion intercept, peak dilation angle, and stress-dilatancy relationship were obtained. The Mohr–Coulomb linear and bilinear failure envelopes were adopted to obtain the shear parameters. The results were further substantiated by microstructural observations. Finally, a conceptual framework was proposed to analyze the peak state shear behavior of bio-cemented calcareous sand. The interdependence between external influential factors (cementation level, initial relative density, and normal stress) and strength components (interparticle friction, interlocking (dilatancy), particle rearrangement, interparticle bonds and particle crushing) at the peak state were discussed in detail. [ABSTRACT FROM AUTHOR]

The observation of the Higgs boson solidified the standard model of particle physics. However, explanations of anomalies (for example, dark matter) rely on further symmetry breaking, calling for an undiscovered axial Higgs mode1. The Higgs mode was also seen in magnetic, superconducting and charge density wave (CDW) systems2,3. Uncovering the vector properties of a low-energy mode is challenging, and requires going beyond typical spectroscopic or scattering techniques. Here we discover an axial Higgs mode in the CDW system RTe3 using the interference of quantum pathways. In RTe3 (R = La, Gd), the electronic ordering couples bands of equal or different angular momenta4–6. As such, the Raman scattering tensor associated with the Higgs mode contains both symmetric and antisymmetric components, which are excited via two distinct but degenerate pathways. This leads to constructive or destructive interference of these pathways, depending on the choice of the incident and Raman-scattered light polarization. The qualitative behaviour of the Raman spectra is well captured by an appropriate tight-binding model, including an axial Higgs mode. Elucidation of the antisymmetric component is direct evidence that the Higgs mode contains an axial vector representation (that is, a pseudo-angular momentum) and hints that the CDW is unconventional. Thus, we provide a means for measuring quantum properties of collective modes without resorting to extreme experimental conditions.Detection of an axial Higgs mode by quantum pathway interference reveals an unconventional charge density wave phase in RTe3. [ABSTRACT FROM AUTHOR]

Recent studies have revealed the significant role of the competing endogenous RNA (ceRNA) network in human diseases. However, systematic analysis of the ceRNA mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) is limited. In this study, we constructed a competitive endogenous RNA (ceRNA) network and identified a potential regulatory axis in CRSwNP based on bioinformatics analysis and experimental verification. We obtained lncRNA, miRNA, and mRNA expression profiles from the Gene Expression Omnibus. After analysis of CRSwNP patients and the control groups, we identified 565 DE-lncRNAs, 23 DE-miRNAs, and 1799 DE-mRNAs by the DESeq2 R package or limma R package. Enrichment analysis of 1799 DE-mRNAs showed that CRSwNP was associated with inflammation and immunity. Moreover, we identified 21 lncRNAs, 8 miRNAs and 8 mRNAs to construct the lncRNA-miRNA-mRNA ceRNA network. A potential MIAT/miR-125a/IRF4 axis was determined according to the degree and positive correlation between a lncRNA and its competitive endogenous mRNAs. The GSEA results suggested that IRF4 may be involved in immune cell infiltration. The validation of another dataset confirmed that MIAT and IRF4 were differentially expressed between the CRSwNP and control groups. The area under the ROC curve (AUC) of MIAT and IRF4 was 0.944. The CIBERSORT analysis revealed that eosinophils and M2 macrophages may be involved in the CRSwNP process. MIAT was correlated with dendritic cells and M2 macrophages, and IRF4 was correlated with dendritic cells. Finally, to validate the key genes, we performed in-silico validation using another dataset and experimental validation using immunohistochemistry, immunofluorescence, and Western blot. In summary, the constructed novel MIAT/miR-125a/IRF4 axis may play a critical role in the development and progression of CRSwNP. We believe that the ceRNA network and immune cell infiltration could offer further insight into novel molecular therapeutic targets for CRSwNP. [ABSTRACT FROM AUTHOR]