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Abstract Encephalomyocarditis virus (EMCV), a potential zoonotic pathogen, poses significant socioeconomic and public health challenges across various host species. Although EMCV rarely triggers severe clinical symptoms in humans, its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics. In this study, we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles (VLPs), both in vitro and in vivo. Using recombinant DNA technology, we engineered a baculovirus system to express EMCVs P12A and 3C, facilitating the production of VLPs in Sf9 cells. These VLPs serve as antigens to immunize mice, leading to the isolation of the monoclonal antibody 45G3. This antibody exhibited high specificity for EMCV conformational epitopes, excluding linear epitopes, and demonstrated potent in vitro neutralizing activity, with an IC50 of 0.01873 μg/mL. Immunoelectron microscopy (IEM) revealed a strong direct interaction between the 45G3 antibody and EMCV particles. Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment, thereby preventing further infection of host cells. These findings further support the notion of a robust interaction between the virus and the antibody. Moreover, in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure. Additionally, posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain, indicating that the 45G3 antibody effectively blocked viral infection, thereby mitigating tissue damage and enhancing survival. These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.

Abstract Despite significant progress in the Prognostics and Health Management (PHM) domain using pattern learning systems from data, machine learning (ML) still faces challenges related to limited generalization and weak interpretability. A promising approach to overcoming these challenges is to embed domain knowledge into the ML pipeline, enhancing the model with additional pattern information. In this paper, we review the latest developments in PHM, encapsulated under the concept of Knowledge Driven Machine Learning (KDML). We propose a hierarchical framework to define KDML in PHM, which includes scientific paradigms, knowledge sources, knowledge representations, and knowledge embedding methods. Using this framework, we examine current research to demonstrate how various forms of knowledge can be integrated into the ML pipeline and provide roadmap to specific usage. Furthermore, we present several case studies that illustrate specific implementations of KDML in the PHM domain, including inductive experience, physical model, and signal processing. We analyze the improvements in generalization capability and interpretability that KDML can achieve. Finally, we discuss the challenges, potential applications, and usage recommendations of KDML in PHM, with a particular focus on the critical need for interpretability to ensure trustworthy deployment of artificial intelligence in PHM.

In recent 20 years, the rapidly development of thermoelectric materials promotes thermoelectric s application in large scale cooling area, i.e. air-conditioner. To provide quiet working environment for the driver of high-speed railway, a kilowatt scale air-conditioner was designed. Firstly, a novel thermoelectric cooler with maximum cooling capacity of 450 W was designed with 199 thermoelectric elements, and the cooling performance were investigated under different cold and hot side heat exchange capacity. Second, the hot and cold side heat exchangers were optimized adopting genetic algorithm. Finally, a high coefficient of performance (COP) thermoelectric air conditioning (TEAC) system was designed for high-speed railway locomotive. The TEAC system comprising 16 TECs achieved a cooling capacity of 2342 W with a COP of 0.5 in cooling mode, and meets one 1HP TEAC requirements. The temperature field inside the locomotive was uniform and exhibited a linear correlation with the supplied air temperature. This research demonstrates the utility of high-power TEAC in high-speed railway carriages, providing valuable insights for the application of TEAC technology.

Abstract The goat, an early domesticated ruminant, is a reliable source of cashmere, meat and milk in global agricultural production. Despite this, the genome of cashmere-rich goats has yet to be characterized. Here, we assembled the nearly complete genome of a cashmere goat from a highly economically valuable Inner Mongolian Cashmere buck, utilizing a combination of PacBio HiFi, ONT ultra-long reads, and Hi-C technologies. The size of this genome is 2.76 Gb, with a contig N50 of 95.22 Mb. All assembled sequences were anchored onto 29 autosomes and both sex chromosomes, with only two gaps present on the X chromosome. We identified 1,333.29 Mb (48.26%) of repetitive sequences and predicted 22,480 protein-coding genes. Assembly quality assessment of the genome demonstrated that our assembled cashmere goat genome surpasses the continuity, completeness, and accuracy of other published goat genomes. Taken together, we provided the first cashmere goat assembly, bridging the gap in the genome of important economic breeds of domestic goats, and providing a valuable reference resource for goat genetics and genome research.

N1-methyladenosine (m1A) modification is an epigenetic change that occurs on RNA molecules, regulated by a suite of enzymes including methyltransferases (writers), demethylases (erasers), and m1A-recognizing proteins (readers). This modification significantly impacts the function of RNA and various biological processes by affecting the structure, stability, translation, metabolism, and gene expression of RNA. Thereby, m1A modification is closely associated with the occurrence and progression of cancer. This review aims to explore the role of m1A modification in tumor immunity. m1A affects tumor immune responses by directly regulating immune cells and indirectly modulating tumor microenvironment. Besides, we also discuss the implications of m1A-mediated metabolic reprogramming and its nexus with immune checkpoint inhibitors, unveiling promising avenues for immunotherapeutic intervention. Additionally, the m1AScore, established based on the expression patterns of m1A modification, can be used to predict tumor prognosis and guide personalized therapy. Our review underscores the significance of m1A modification as a burgeoning frontier in cancer biology and immuno-oncology, with the potential to revolutionize cancer treatment strategies.

Objective As a charismatic species, cashmere goats have rich genetic resources. In the Inner Mongolia Autonomous Region, there are three cashmere goat varieties named and approved by the state. These goats are renowned for their high cashmere production and superior cashmere quality. Therefore, it is vitally important to protect their genetic resources as they will serve as breeding material for developing new varieties in the future. Methods Three breeds including Inner Mongolia cashmere goats (IMCG), Hanshan White cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ) were studied. IMCG were of three types: Aerbas (AEBS), Erlangshan (ELS), and Alashan (ALS). Nine DNA samples were collected for each population, and they were genomically re-sequenced to obtain high-depth data. The genetic diversity parameters of each population were estimated to determine selection intensity. Principal component analysis, phylogenetic tree construction and genetic differentiation parameter estimation were performed to determine genetic relationships among populations. Results Samples from the 45 individuals from the five goat populations were sequenced, and 30,601,671 raw single nucleotide polymorphisms (SNPs) obtained. Then, variant calling was conducted using the reference genome, and 17,214,526 SNPs were retained after quality control. Individual sequencing depth of individuals ranged from 21.13× to 46.18×, with an average of 28.5×. In the AEBS, locus polymorphism (79.28) and expected heterozygosity (0.2554) proportions were the lowest, and the homologous consistency ratio (0.1021) and average inbreeding coefficient (0.1348) were the highest, indicating that this population had strong selection intensity. Conversely, ALS and WZMQ selection intensity was relatively low. Genetic distance between HS and the other four populations was relatively high, and genetic exchange existed among the other four populations. Conclusion The Inner Mongolia cashmere goat (AEBS type) population has a relatively high selection intensity and a low genetic diversity. The IMCG (ALS type) and WZMQ populations had relatively low selection intensity and high genetic diversity. The genetic distance between HS and the other four populations was relatively high, with a moderate degree of differentiation. Overall, these genetic variations provide a solid foundation for resource identification of Inner Mongolia Autonomous Region cashmere goats in the future.

Abstract Background The cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits. Results We estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109–1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P

Summary: Background: Accurate staging of liver fibrosis (LF) is essential for clinical management in chronic liver disease. While non-contrast MRI (NC-MRI) yields valuable information for liver assessment, its effectiveness in predicting LF remains underexplored. This study aimed to develop and validate artificial intelligence (AI)-powered models utilizing NC-MRI for staging LF. Methods: A total of 1726 patients from Shengjing Hospital of China Medical University, registered between October 2003 and October 2022, were retrospectively collected, and divided into development (n = 1208) and internal test (n = 518) cohorts. An external test cohort consisting of 337 individuals from six centers, registered between June 2015 and November 2022, were also included. All participants underwent NC-MRI (T1-weighted imaging, T1WI; and T2-fat-suppressed imaging, T2FS) and liver biopsies. Two classification models (CMs), named T1 and T2FS, were trained on respective image types using 3D contextual transformer networks and evaluated on both test cohorts. Additionally, three CMs—Clinic, Image, and Fusion—were developed using clinical features, T1 and T2FS scores, and their integration via logistic regression. Classification effectiveness of CMs was assessed using the area under the receiver operating characteristic curve (AUC). A comparison was conducted between the optimal models (OMs) with highest AUC and other methods (transient elastography, five serum biomarkers, and six radiologists). Findings: Fusion models (i.e., OM) yielded the highest AUC among the CMs, achieving AUCs of 0.810 for significant fibrosis, 0.881 for advanced fibrosis, and 0.918 for cirrhosis in the internal test cohort, and 0.808, 0.868, and 0.925, respectively, in the external test cohort. The OMs demonstrated superior performance in AUC, significantly surpassing transient elastography (only for staging ≥ F2 and ≥ F3 grades), serum biomarkers, and three junior radiologists for staging LF. Radiologists, with the aid of the OMs, can achieve a higher AUC in LF assessment. Interpretation: AI-powered models utilizing NC-MRI, including T1WI and T2FS, accurately stage LF. Funding: National Natural Science Foundation of China (No. 82071885); General Program of the Liaoning Provincial Department of Education (LJKMZ20221160); Liaoning Province Science and Technology Joint Plan (2023JH2/101700127); the Leading Young Talent Program of Xingliao Yingcai in Liaoning Province (XLYC2203037).

Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is an acute and serious corneal inflammation. As a family of gene regulators, miRNAs play a crucial role in modulating host response after microbial invasion. However, their functions in P. aeruginosa keratitis remain largely unclear. In the present study, we demonstrated that miR-155 expression was significantly increased in macrophages and corneal tissue after P. aeruginosa infection. In vivo studies demonstrated that mice with miR-155 knockdown displayed more resistance to P. aeruginosa keratitis, with a lower bacterial burden. In addition, in vitro and in vivo studies indicated that miR-155 enhanced apoptosis of macrophages after P. aeruginosa infection, and resulted in a susceptible phenotype of P. aeruginosa keratitis. Moreover, miR-155 induced apoptosis through reducing activation of PI3K-Akt signaling pathway. Our data provided evidence of miR-155 mediated apoptosis of macrophage in P. aeruginosa keratitis, which may be an underlying target for the therapy of P. aeruginosa keratitis and other infectious diseases.

Abstract The fleece traits are important economic traits of goats. With the reduction of sequencing and genotyping cost and the improvement of related technologies, genomic selection for goats has become possible. The research collect pedigree, phenotype and genotype information of 2299 Inner Mongolia Cashmere goats (IMCGs) individuals. We estimate fixed effects, and compare the estimates of variance components, heritability and genomic predictive ability of fleece traits in IMCGs when using the pedigree based Best Linear Unbiased Prediction (ABLUP), Genomic BLUP (GBLUP) or single-step GBLUP (ssGBLUP). The fleece traits considered are cashmere production (CP), cashmere diameter (CD), cashmere length (CL) and fiber length (FL). It was found that year of production, sex, herd and individual ages had highly significant effects on the four fleece traits (P

Abstract Geminiviruses are an important group of viruses that infect a variety of plants and result in heavy agricultural losses worldwide. The homologs of C4 (or L4) in monopartite geminiviruses and AC4 (or AL4) in bipartite geminiviruses are critical viral proteins. The C4 proteins from several geminiviruses are the substrates of S-acylation, a dynamic post-translational modification, for the maintenance of their membrane localization and function in virus infection. Here we initiated a screening and identified a plant protein ABAPT3 (Alpha/Beta Hydrolase Domain-containing Protein 17-like Acyl Protein Thioesterase 3) as the de-S-acylation enzyme of C4 encoded by BSCTV (Beet severe curly top virus). Overexpression of ABAPT3 reduced the S-acylation of BSCTV C4, disrupted its plasma membrane localization, inhibited its function in pathogenesis, and suppressed BSCTV infection. Because the S-acylation motifs are conserved among C4 from different geminiviruses, we tested the effect of ABAPT3 on the C4 protein of ToLCGdV (Tomato leaf curl Guangdong virus) from another geminivirus genus. Consistently, ABAPT3 overexpression also disrupted the S-acylation, subcellular localization, and function of ToLCGdV C4, and inhibited ToLCGdV infection. In summary, we provided a new approach to globally improve the resistance to different types of geminiviruses in plants via de-S-acylation of the viral C4 proteins and it can be extendedly used for suppression of geminivirus infection in crops.

NiTi alloys exhibit significant potential for biological applications, and the fabrication of customized NiTi geometries is greatly facilitated by the use of laser powder bed fusion (LPBF) processing. However, there are several challenges with post-processing NiTi specimens processed via LPBF, such as uneven, loosely packed, weakly corrosive surfaces, and low dimensional precision. Therefore, solving the surface problem of metals prepared by LPBF has become the key to the application. In this paper, the influence of the solution and parameters on surface roughness, surface shape and size, composition, and corrosion resistance was studied by adjusting the composition of the polishing solution and polishing parameters. The results show that polishing for 2 h in S2 solution (HNO3: HF: H2O = 40:10:50) produces the smoothest surface with the roughness characteristics Sa is 10.41 ± 0.63 μm and Ra is 0.39 ± 0.30 μm. At the same time, the corrosion resistance of polished samples has been significantly improved in simulated body fluids (SBF), and the corrosion current density (Icorr) reduced by up to one order of magnitude, reaching 5.38 ± 0.24 × 10−8. By altering the polishing process duration, it is possible to achieve a micron-level roughness surface while maintaining dimensional accuracy, making LPBF-NiTi more suitable for implant applications. Ultimately, we conclude with a brief discussion of how chemical polishing affects the handling of materials with complex structures. Between 30 and 1 h, LPBF-NiTi scaffolds were polished in S2 solution to provide porosities and dimensional accuracy that best matched the design parameters.

Abstract H.266/Versatile Video Coding (VVC) is the most recent video coding standard developed by the Joint Video Experts Team (JVET). The quad-tree with nested multi-type tree (QTMT) architecture that improves the compression performance of H.266/VVC is introduced. Moreover, H.266/VVC contains a greater number of intra-prediction modes than H.265/High Efficiency Video Coding (HEVC), totalling 67. However, these lead to extremely the coding computational complexity. To cope with the above issues, a fast intra-coding unit (CU) size decision method and a fast intra-prediction mode decision method are proposed in this paper. Specifically, the trained Support Vector Machine (SVM) classifier models are utilized for determining CU partition mode in a fast CU size decision scheme. Furthermore, the quantity of intra-prediction modes added to the RDO mode set decreases in a fast intra-prediction mode decision scheme based on the improved search step. Simulation results illustrate that the proposed overall algorithm can decrease 55.24% encoding runtime with negligible BDBR.

(1) Background: Cashmere goats, as one of the characteristic species, are rich in genetic resources. Protecting and rationally utilizing these genetic resources is of great significance for the genetic improvement of cashmere goats. (2) Methods: In this study, tissue samples were collected from Inner Mongolia white cashmere goats, which included the Arbas type (ARBS); Erlangshan type (ELS); Alashan type (ALS), Hanshan white cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ). Genomic DNA was extracted and subjected to high-depth genome resequencing. GenoBait technology was used for probe design and site optimization, followed by the synthesis of a low-density liquid phase chip. Finally, a total of 281 individuals from five cashmere goat populations in the Inner Mongolia Autonomous Region were randomly selected to verify the chip. (3) Results: The results showed that a total of 5002 SNP sites were finally screened and retained for the synthesis of the low-density liquid chip for identifying cashmere goats in Inner Mongolia Autonomous Region. Principal component analysis and phylogenetic tree construction indicated that the ARBS, ELS, and ALS populations were clustered into one category. (4) Conclusions: This chip can accurately identify the three breeds: Inner Mongolia white cashmere goats, Hanshan white cashmere goats, and Ujimqin white cashmere goats.

Abstract Cryptococcus is a family of strongly infectious pathogens that results in a wide variety of symptoms, particularly threatening the patients undergoing the immune‐deficiency or medical treatment. Rapidly identifying Cryptococcus subtypes and accurately quantifying their contents remain urgent needs for infection control and timely therapy. However, traditional detection techniques heavily rely on expensive, specialized instruments, significantly compromising their applicability for large‐scale population screening. In this work, we report a portable microwell array chip platform integrated with a deep learning‐based image recognition program, which enables rapid, precise quantification of the specific subtypes of Cryptococcus. The platform features four zones of microwell arrays preloaded with the subtype‐targeted CRISPR–Cas12a system that avoid dependence on slow, instrumental‐mediated target amplification, achieving rapid (10 min), high specificity for identifying the sequence of Cryptococcus. The deep learning‐based image recognition program utilizing segment anything model (SAM) significantly enhances automation and accuracy in identifying target concentrations, which eventually achieves ultra‐low limit of detection (0.5 pM) by personal smartphones. This platform can be further customized to adapt to various scenarios in clinical settings.

Depression is a common psychiatric disorder that belongs to the category of ''Depression Syndrome'' in traditional Chinese medicine (TCM), and its etiology and pathogenesis are complex and unclear. It is characterized by high prevalence, high disability rate, and high recurrence rate, which seriously affect human health, and its treatment has become a research hotspot worldwide. At present, the antidepressants commonly used in the clinic are mainly Western medicine (WM), but there are problems such as frequent side effects and poor efficacy. Studies have found that the use of TCM prescriptions in the treatment of depression can achieve the same effect as WM; and when TCM prescriptions are combined with WM, the efficacy can be enhanced while the adverse effects of WM can be reduced. Pharmacological studies related to the treatment of depression with traditional Chinese medicine prescriptions (TCMPs) have focused on the neurobiochemical system, gut microbes, and energy metabolism in mitochondria. No one has yet reviewed the pharmacological mechanism of TCMPs for depression. So, this paper reviews the pharmacological mechanism of TCMPs for depression from the perspective of TCMPs, introduces the progress of research on classical TCMPs for depression and their antidepressant mechanism. This article aims to promote the application of TCMPs in the clinic and provide a new therapeutic idea for the clinical treatment of depression.

In this study, genome-wide association analysis was performed on the growth traits (body height, body length, chest circumference, chest depth, chest width, tube circumference, and body weight) of Inner Mongolian cashmere goats (Erlangshan type) based on resequencing data. The population genetic parameters were estimated, haplotypes were constructed for the significant sites, and association analysis was conducted between the haplotypes and phenotypes. A total of two hundred and eighty-four SNPs and eight candidate genes were identified by genome-wide association analysis, gene annotation, and enrichment analysis. The phenotypes of 16 haplotype combinations were significantly different by haplotype analysis. Combined with the above results, the TGFB2, BAG3, ZEB2, KCNJ12, MIF, MAP2K3, HACD3, and MEGF11 functional candidate genes and the haplotype combinations A2A2, C2C2, E2E2, F2F2, I2I2, J2J2, K2K2, N2N2, O2O2, P2P2, R1R1, T1T1, W1W1, X1X1, Y1Y1, and Z1Z1 affected the growth traits of the cashmere goats and could be used as molecular markers to improve the accuracy of early selection and the economic benefits of breeding.

Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.

Abstract Ferroelectricity, a spontaneous and reversible electric polarization, is found in certain classes of van der Waals (vdW) materials. The discovery of ferroelectricity in twisted vdW layers provides new opportunities to engineer spatially dependent electric and optical properties associated with the configuration of moiré superlattice domains and the network of domain walls. Here, we employ near-field infrared nano-imaging and nano-photocurrent measurements to study ferroelectricity in minimally twisted WSe2. The ferroelectric domains are visualized through the imaging of the plasmonic response in a graphene monolayer adjacent to the moiré WSe2 bilayers. Specifically, we find that the ferroelectric polarization in moiré domains is imprinted on the plasmonic response of the graphene. Complementary nano-photocurrent measurements demonstrate that the optoelectronic properties of graphene are also modulated by the proximal ferroelectric domains. Our approach represents an alternative strategy for studying moiré ferroelectricity at native length scales and opens promising prospects for (opto)electronic devices.

Abstract Declining physical performance with age and disease is an important indicator of declining health. Biomarkers that identify declining physical performance would be useful in predicting treatment outcomes and identifying potential therapeutics. γ-aminobutyric acid (GABA), a muscle autocrine factor, is a potent inhibitor of muscle function and works as a muscle relaxant. L-α-aminobutyric acid (L-AABA) is a biomarker for malnutrition, liver damage, and depression. We sought to determine if GABA and L-AABA may be useful for predicting physical performance. Serum levels of GABA and L-AABA were quantified in 120 individuals divided by age, sex, and physical capacity into low, average, and high performer groups. Analyses explored correlations between serum levels and physical performance. Both GABA and the ratio of GABA/AABA (G/A), but not AABA, were highly positively associated with age (Pearson correlations r = 0.35, p = 0.0001 for GABA, r = 0.31, p = 0.0007 for G/A, n = 120). GABA showed negative associations in the whole cohort with physical performance [fast gait speed, 6 min walk test (6MWT), PROMIS score, and SF36PFS raw score] and with subtotal and femoral neck bone mineral density. L-AABA was positively associated with usual gait speed, 6MWT, total SPPB score, and SF36PFS raw score in the total cohort of 120 human subjects, also with 6MWT and SF36PFS raw score in the 60 male subjects, but no associations were observed in the 60 females. As both GABA and L-AABA appear to be indicative of physical performance, but in opposite directions, we examined the G/A ratio. Unlike GABA, the G/A ratio showed a more distinct association with mobility tests such as total SPPB score, usual and fast gait speed, 6MWT, and SF36PFS raw score in the males, regardless of age and metabolic status. Serum G/A ratio could be potentially linked to physical performance in the male population. Our findings strongly suggest that GABA, L-AABA, and the G/A ratio in human serum may be useful markers for both age and physical function. These new biomarkers may significantly enhance the goal of identifying universal biomarkers to accurately predict physical performance and the beneficial effects of exercise training for older adults.

Abstract As both L- and D-BAIBA are increased with exercise, we sought to determine if circulating levels would be associated with physical performance. Serum levels of L- and D-BAIBA were quantified in 120 individuals (50% female) aged 20–85 years and categorized as either a “low” (LP), “average” (AP) or “high” performing (HP). Association analysis was performed using Spearman (S) and Pearson (P) correlation. Using Spearman correlation, L-BAIBA positively associated with (1) body mass index BMI (0.23) and total fat mass (0.19) in the 120 participants, (2) total fat mass in the 60 males (0.26), and (3) bone mineral density, BMD, (0.28) in addition to BMI (0.26) in the 60 females. In HP females, L-BAIBA positively associated with BMD (0.50) and lean mass (0.47). D-BAIBA was positively associated with (1) age (P 0.20) in the 120 participants, (2) age (P 0.49) in the LP females and (3) with gait speed (S 0.20) in the 120 participants. However, in HP males, this enantiomer had a negative association with appendicular lean/height (S − 0.52) and in the AP males a negative correlation with BMD (S − 0.47). No associations were observed in HP or AP females, whereas, in LP females, a positive association was observed with grip strength (S 0.45), but a negative with BMD (P − 0.52, S − 0.63) and chair stands (P − 0.47, S − 0.51). L-BAIBA may play a role in BMI and BMD in females, not males, whereas D-BAIBA may be a marker for aging and physical performance. The association of L-BAIBA with BMI and fat mass may reveal novel, not previously described functions for this enantiomer.

To clarify the synergistic effect of well/over-tempered hierarchical martensitic structure and carbides (M23C6 and MX) on austenite growth, the austenite growth during step-heat austenitization for a selected 9Cr steel was investigated by dilatometry, multi-scale characterization and cellular automaton simulation. The austenite grain inherits the geometrical characteristics of the hierarchical martensite substructure to a significant extent through covariant and free growth. In particular, the initially heterogeneous grains with non-uniform martensitic substructure can easily produce mixed and heterogeneous grains. Step isothermal heating under AC1 can promote the evolution of martensitic structure to recrystallized ferrite and recovered equiaxed substructure, associated with coarsening of M23C6 and precipitation of MC. Apart from the recrystallized ferrite promoting the growth of equiaxed austenite grains, the recovered approximate equiaxed substructure decorated with coarse M23C6 and a large amount of MX can promote the subsequent development of fine spherical austenite grains by reducing the abnormal austenite growth and increasing the resistance to interfacial migration. The synergistic effect of the well/over tempered martensitic hierarchical structure and the carbides (M23C6, MX) is critical to the final austenite grain distribution. A window of critical temperature values for step heating austenitization to generate homogeneous austenite grain growth was established by exploiting the inheritance of the equiaxed substructure and reasonably reducing abnormal growth.

Northwest Xizang White Cashmere Goat (NXWCG) is the first new breed of cashmere goat in the Xizang Autonomous Region. It has significant characteristics of extremely high fineness, gloss, and softness. Genome-wide association analysis is an effective biological method used to measure the consistency and correlation of genotype changes between two molecular markers in the genome. In addition, it can screen out the key genes affecting the complex traits of biological individuals. The aim of this study was to analyze the genetic mechanism of cashmere trait variation in NXWCG and to discover SNP locus and key genes closely related to traits such as superfine cashmere. Additionally, the key genes near the obtained significant SNPs were analyzed by gene function annotation and biological function mining. In this study, the phenotype data of the four traits (cashmere length, fiber length, cashmere diameter, and cashmere production) were collected. GGP_Goat_70K SNP chip was used for genotyping the ear tissue DNA of the experimental group. Subsequently, the association of phenotype data and genotype data was performed using Gemma-0.98.1 software. A linear mixed model was used for the association study. The results showed that four fleece traits were associated with 18 significant SNPs at the genome level and 232 SNPs at the chromosome level, through gene annotated from Capra hircus genome using assembly ARS1. A total of 107 candidate genes related to fleece traits were obtained. Combined with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we can find that CLNS1A, CCSER1, RPS6KC1, PRLR, KCNRG, KCNK9, and CLYBL can be used as important candidate genes for fleece traits of NXWCG. We used Sanger sequencing and suitability chi-square test to further verify the significant loci and candidate genes screened by GWAS, and the results show that the base mutations loci on the five candidate genes, CCSER1 (snp12579, 34,449,796, A → G), RPS6KC1 (snp41503, 69,173,527, A → G), KCNRG (snp41082, 67,134,820, G → A), KCNK9 (14:78472665, 78,472,665, G → A), and CLYBL (12: 9705753, 9,705,753, C → T), significantly affect the fleece traits of NXWCG. The results provide a valuable basis for future research and contribute to a better understanding of the genetic structure variation of the goat.

Of all malignancies, pancreatic ductal adenocarcinoma (PDAC), constituting 90% of pancreatic cancers, has the worst prognosis. Glycolysis is overactive in PDAC patients and is associated with poor prognosis. Drugs that inhibit glycolysis as well as induce cell death need to be identified. However, glycolysis inhibitors often fail to induce cell death. We here found that FV-429, a derivative of the natural flavonoid wogonin, can induce mitochondrial apoptosis and inhibit glycolysis in PDAC in vivo and in vitro. In vitro, FV-429 inhibited intracellular ATP content, glucose uptake, and lactate generation, consequently leading to mitochondrial dysfunction and apoptosis in PDAC cells. Furthermore, it decreased the expression of PKM2 (a specific form of pyruvate kinase) through the ERK signaling pathway and enhanced PKM2 nuclear translocation. TEPP-46, the activator of PKM2, reversed FV-429-induced glycolysis inhibition and mitochondrial apoptosis in the PDAC cells. In addition, FV-429 exhibited significant tumor suppressor activity and high safety in BxPC-3 cell xenotransplantation models. These results thus demonstrated that FV-429 decreases PKM2 expression through the ERK signaling pathway and enhances PKM2 nuclear translocation, thereby resulting in glycolysis inhibition and mitochondrial apoptosis in PDAC in vitro and in vivo, which makes FV-429 a promising candidate for pancreatic cancer treatment.

IntroductionInner Mongolia Cashmere Goats (IMCGs) are famous for its cashmere quality and it’s a unique genetic resource in China. Therefore, it is necessary to use genomic selection to improve the accuracy of selection for fleece traits in Inner Mongolia cashmere goats. The aim of this study was to determine the effect of methods (GBLUP, BayesA, BayesB, Bayesian LASSO, Bayesian Ridge Region) and the reference population size on accuracy of genomic selection in IMCGs.MethodsThis study fully utilizes the pedigree and phenotype records of fleece traits in 2255 individuals, genotype of 50794 SNPs after quality control, and environmental data to perform genomic selection of fleece traits. Then GBLUP and Bayes series methods (BayesA, BayesB, Bayesian LASSO, Bayesian Ridge Region) were used to perform estimates of genetic parameter and genomic breeding value. And the accuracy of genomic estimated breeding value (GEBV) is evaluated using the five-fold cross validation method. And the analysis of variance and multiple comparison methods were used to determine the best method for genomic selection in fleece traits of IMCGs. Further the different reference population sizes (500, 1000, 1500, and 2000) was set. Then the best method was applied to estimate genome breeding values, and evaluate the impact of reference population sizes on the accuracy of genome selection for fleece traits in IMCGs.ResultsIt was found that the genomic prediction accuracy for each fleece trait in IMCGs by GBLUP method is highest, and it is significantly higher than that obtained by Bayesian method. The accuracy of breeding value estimation is 58.52% -68.49%. Also, it was found that the size of the reference population has a significant impact on the accuracy of genome prediction of fleece traits. When the reference population size is 2000, the accuracy of genomic prediction for each fleece trait is significantly higher than other levels, with accuracy of 55.47% -67.87%. This provides a theoretical basis for design a reasonable genome selection plan for Inner Mongolia cashmere goats in the later stag.

Cancer cells can alter their metabolism to meet energy and molecular requirements due to unfavorable environments with oxygen and nutritional deficiencies. Therefore, metabolic reprogramming is common in a tumor microenvironment (TME). Aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription factor, which can be activated by many exogenous and endogenous ligands. Multiple AhR ligands can be produced by both TME and tumor cells. By attaching to various ligands, AhR regulates cancer metabolic reprogramming by dysregulating various metabolic pathways, including glycolysis, lipid metabolism, and nucleotide metabolism. These regulated pathways greatly contribute to cancer cell growth, metastasis, and evading cancer therapies; however, the underlying mechanisms remain unclear. Herein, we review the relationship between TME and metabolism and describe the important role of AhR in cancer regulation. We also focus on recent findings to discuss the idea that AhR acts as a receptor for metabolic changes in tumors, which may provide new perspectives on the direction of AhR research in tumor metabolic reprogramming and future therapeutic interventions.

A large number of Web APIs have been released as services in mobile communications, but the service provided by a single Web API is usually limited. To enrich the services in mobile communications, developers have combined Web APIs and developed a new service, which is known as a mashup. The emergence of mashups greatly increases the number of services in mobile communications, especially in mobile networks and the Internet-of-Things (IoT), and has encouraged companies and individuals to develop even more mashups, which has led to the dramatic increase in the number of mashups. Such a trend brings with it big data, such as the massive text data from the mashups themselves and continually-generated usage data. Thus, the question of how to determine the most suitable mashups from big data has become a challenging problem. In this paper, we propose a mashup recommendation framework from big data in mobile networks and the IoT. The proposed framework is driven by machine learning techniques, including neural embedding, clustering, and matrix factorization. We employ neural embedding to learn the distributed representation of mashups and propose to use cluster analysis to learn the relationship among the mashups. We also develop a novel Joint Matrix Factorization (JMF) model to complete the mashup recommendation task, where we design a new objective function and an optimization algorithm. We then crawl through a real-world large mashup dataset and perform experiments. The experimental results demonstrate that our framework achieves high accuracy in mashup recommendation and performs better than all compared baselines.

Abstract Field‐programmable gate array (FPGA)‐based real‐time simulators are often applied in simulations of active distribution networks (ADNs) because of their parallel architectures and low cost. The overall performance of an FPGA‐based real‐time simulator is mainly determined by its kernel solver, which solves the nodal equation at each simulation time step. With the increasing scale of ADNs, real‐time simulations of fast switching dynamics, along with limited computation hardware, have increased the requirements of the solver in terms of both time and resource consumption. In this study, a highly parallel kernel solver is proposed to improve the simulation efficiency of the FPGA‐based real‐time simulator. The multi‐level parallel design and its implementation, including the parallelism at the system and module and element levels, are presented in detail. A modified IEEE 123‐node system with distributed photovoltaics (PVs) is then simulated using a three‐FPGA‐based real‐time simulator. Simulation results are compared with the commercial simulation tool PSCAD/EMTDC to validate the proposed kernel solver.

Abstract The real‐time simulation of active distribution networks (ADNs) can provide an accurate insight into transient behaviours, but faces challenges in simulation efficiency and flexibility brought by larger system scales and wider time‐scale ranges. This paper presents an asynchronous multi‐rate (AMR) method and design for the real‐time simulation of large‐scale ADNs. In the proposed method, the entire ADN was decoupled into different subsystems according to accuracy requirements, and optimized time‐steps were allocated to each subsystem to realize a fully distributed simulation. This not only alleviated the time‐step coordination problem existing in multi‐rate real‐time simulations, but also enhanced the flexible expansion capabilities of the real‐time simulator. To realize the AMR real‐time simulation, a multi‐rate interfacing method, synchronization mechanism, and data communication strategy are proposed in this paper, and their hardware design is also presented in detail. A modified IEEE 123‐node system with photovoltaics and wind turbine generators was simulated on a 3 field‐programmable gate arrays (FPGAs)‐based AMR real‐time simulator. The real‐time results were captured by the oscilloscope and verified with PSCAD/EMTDC, which demonstrated the superiority in simulation flexibility and accuracy compared with the synchronous multi‐rate (SMR) method.

Currently, the coding efficacy of the cutting-edge video coding standard H.266/VVC surpasses that of 3D-HEVC (3D-High Efficiency Video Coding), but the existing VVC (Versatile Video Coding) low-complexity coding algorithm is mainly optimized for 2D video coding and cannot fully utilize the characteristics of the depth map itself. Based on this, we propose a fast decision algorithm employing the CNN (Convolutional Neural Network)-LNN (Lightweight Neural Network) model to diminish the intricacy of depth map intra coding in VVC 3D video. The algorithm treats the CU partitioning process in depth map coding as a two-stage process, first adding a non-local block and spatial pyramid pooling to the CNN model, enabling the proposed CNN model to skip the flat regions in the depth map and perform adaptive partitioning prediction of CUs in the edge regions; then, the LNN model is used to make early decision on TT (Ternary Tree) partition for CUs that need to be partitioned, and skip decisions for CUs that do not need to be partitioned by TT, so as to reduce some unnecessary RDO calculations. Experimental results illustrate that the algorithm achieves a notable reduction in encoding time amounting to 43.23% on average, with a negligible impact on the increase of BDBR.

Abstract A systematic solution is developed to improve the autonomous capability of the quadruped robot with a manipulator, such as navigation, recognition and operation. The developed system adopts novel software, hardware system and system architecture, including a specially designed environment awareness system (EAS). Based on the camera and LiDAR on the EAS, the recognition of multiple common targets, such as the leader, door, window and bag, is achieved. In terms of navigation, a location method is built, that combines the laser odometer and global positioning system. A mapping and path planning module is designed by the Robot‐centric Elevation Mapping algorithm and the rapidly exploring rand tree algorithm. For operation, a real‐time target grasp detection system is proposed based on the You Only Look Once v5 algorithm to improve the success rate of tasks. The whole system is integrated based on the task relevance scheduling strategy to reduce the computational complexity. The tightly integrated system and the subsystems are evaluated by conducting simulations and physical experiments in robot recognition, navigation and operation. Extensive experiments show that the proposed framework can better achieve the autonomous navigation and operation of the quadruped robot with a manipulator. Notably, the proposed framework is still effective when facing dynamic objects. In addition, the system can be easily extended to other forms of mobile robot.

With the development of society and changes in lifestyle, major depressive disorder (MDD) has become a significant disease that plagues many people. Licorice, an excellent natural medicine with a long history of cultivation and application, is found in classical antidepressant prescriptions such as Chaihu Shugan Powder, Ganmai Dazao Decoction, Suanzaoren Decoction, etc. Licorice mainly contains triterpenoids and flavonoids, among which licorice total flavonoids (LF) and liquiritin are the main active components with good antidepressant effects. The pharmacological effects of licorice have been extensively investigated in current studies. However, a review of the antidepressant effects of LF and liquiritin has not been conducted. This article reviews the antidepressant effects of LF and liquiritin, including the biological characteristics of licorice and the pharmacological mechanism of LF and liquiritin in treating MDD. Studies have shown that LF and liquiritin can exert their antidepressant effects by improving depressive behavior, regulating endocrine and hypothalamic-pituitary-adrenal (HPA) axis function, affecting the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling pathway, enhancing synaptic plasticity, increasing monoamine neurotransmitter levels, protecting nerve cells, reducing inflammation, preventing apoptosis, reducing oxidation and other ways. This lays a theoretical foundation for the development of antidepressant drugs.

Background: Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease, which is accompanied by liver damage. However, it remains unknown whether liver damage is associated with SLE progression. Method: ology: HepG2 and L-02 cells were stimulated with cytokines, and FGL1 mRNA and protein expression levels were determined using Real-time PCR and ELISA, respectively. Regulatory T cells (Treg) isolated from healthy individuals as well as patients with SLE and SLE and liver damage (SLE-LD) were cultured with autologous effector CD4+T cells in the presence of a functional antibody or isotype control. The expression levels of LAG3, CD25, PD-1, CXCR5, ICOS and OX40 were evaluated by flow cytometry. FGL1, IL-10, IL-17a and IL-21 levels in serum or culture supernatants were quantified by ELISA. Results: Patients with SLE-LD exhibits higher disease activity indices and anti-dsDNA antibody levels. Importantly, fibrinogen-like protein 1 (FGL1), a key factor released from the injured liver, is up-regulated in patients with SLE-LD and is associated with disease activity. FGL1 expression is induced by the inflammatory cytokine IL-6 signaling in hepatocytes. Higher expression of the FGL1 receptor lymphocyte activation gene 3 (LAG3) is detected in Treg cells from patients with SLE-LD. The FGL1-LAG3 signaling axis inhibits Treg cell proliferation and impairs the suppressive activity of Treg cells by limiting IL-10 secretion. Furthermore, FGL1-LAG3 signaling promotes the production of pathogenic IL-17a and IL-21 by CD4+T cells by reducing IL-10 level produced by Treg in patients with SLE. Conclusions: The FGL1-LAG3 signal axis is a key mechanism that subverts the suppressive function of Treg cells. This may provide a new therapeutic target for SLE and SLE-induced liver damage.

ABSTRACT Biotherapeutic strategies to promote health, including the application of engineered microbes to deliver therapeutic molecules, hold strong promise. However, without precision tools to detect therapeutic microbes and their products, we are hampered in our ability to monitor and fine-tune therapeutic delivery. Here, we adapted a bioluminescent peptide tagging system for use in lactic acid bacteria, a group of organisms whose members are commonly exploited as delivery vehicles of therapeutics and vaccines. As a proof of concept, we developed various Limosilactobacillus reuteri strains that each produced a recombinant therapeutic protein with an 11 amino acid tag, which is essential to yield a luminescent signal. Luminescent-based quantification of recombinant protein was more sensitive than commercially available immunoassays. In addition, we demonstrated that the bioluminescent peptide tagging system allows in situ recombinant protein detection in a continuous-culture parallel bioreactor system. This presents an exciting opportunity to determine recombinant protein production dynamics in response to different stimuli. Finally, following oral administration of recombinant microbes, luminescence in intestinal and fecal samples allowed for rapid detection of microbes with equal sensitivity to conventional plate count. Because we demonstrated the functionality of this bioluminescent peptide tagging system in 12 species encompassing nine genera, our approach will create previously unexplored opportunities in lactic acid bacteria research. IMPORTANCE Lactic acid bacteria constitute a genetically diverse group of microorganisms with significant roles in the food industry, biotechnology, agriculture, and medicine. A core understanding of bacterial physiology in diverse environments is crucial to select and develop bacteria for industrial and medical applications. However, there is a lack of versatile tools to track (recombinant) protein production in lactic acid bacteria. In this study, we adapted a peptide-based bioluminescent tagging system that is functional across multiple genera and species. This system enables tracking of tagged proteins both in vitro and in situ, while it also can be used to enumerate recombinant bacteria from the mouse gastrointestinal tract with accuracy comparable to that of conventional plate counts. Our work expands the lactic acid bacteria genetic toolbox and will facilitate researchers in industry and academia with opportunities to monitor microbes and proteins under different physiologically relevant conditions.

Introduction: Chronic relapsing ulcerative colitis (CRUC) is classified as an inflammatory bowel disease, and traditional Chinese medicine (TCM) has been recognized for its therapeutic benefits in treating CRUC. According to TCM principles, the prevailing syndromes in CRUC are yang deficiency and dampness stagnation (YDDS). The objective of this study is to establish a novel animal model of CRUC exhibiting the YDDS syndrome. Methods: Initially, the rats were administered hydrocortisone succinate sodium through subcutaneous injection, followed by the administration of senna folium granule solution. Subsequently, the rats underwent three cycles of dextran sulfate sodium solution ingestion. Results: Upon completion of the modeling process, it was observed that the disease activity index, colonic mucosal damage index score, colon weight/length ratio, colonic histopathology score, and tissue damage index scores of the model rats were elevated, while the colon length and spleen index exhibited a decrease compared to the control group. The pathological alterations in the model rats included the presence of shallow or deep ulcers and acute or chronic inflammation throughout the process of CRUC modeling. Additionally, our findings indicate a correlation between the proximity of the ulcer to the anal verge, the severity of the lesion, and the presence of precancerous glands, glandular disappearance, crypt abscesses, and tissue destruction. Furthermore, the expression levels of IL6, IL10, IFNG, and TNFA in the colon tissues were significantly elevated in the model rats compared to the control group. Notably, the end-stage lesions observed in CRUC exhibited greater severity when compared to those observed in cases of acute ulcerative colitis. Discussion: In conclusion, we have successfully developed a rat model of CRUC with YDDS syndrome, which can be utilized to investigate the effectiveness and underlying mechanisms of TCM in treating CRUC.

The effect of gravity on the self-similarity of jet shape at late stage of Worthington jet development is investigated by experiment in the study. In addition, the PIV method is introduced to analyze the development of flow field. There is a linear scaling regarding the axial velocity of the jet and the scaling coefficient increases with the Froude number.

In the original publication [...]

Currently, insecticides that target nicotinic acetylcholine receptors (nAChR) are widely used. Studies on the sublethal effects of insecticides have found that they can affect the amount of virus in insects. The mechanism by which insecticides affect insect virus load remain unclear. Here, we show that nAChR targeting insecticide can affect viral replication through the immune deficiency (IMD) pathway. We demonstrate that a low dose of spinosad (6.8 ng/mL), acting as an antagonist to Drosophila melanogaster nicotinic acetylcholine receptor α6 (Dα6), significantly elevates Drosophila melanogaster sigmavirus (DMelSV) virus titers in adults of Drosophila melanogaster. Conversely, a high dose of spinosad (50 ng/mL), acting as an agonist to Dα6, substantially decreases viral load. This bidirectional regulation of virus levels is absent in Dα6-knockout flies, signifying the specificity of spinosad’s action through Dα6. Furthermore, the knockdown of Dα6 results in decreased expression of genes in the IMD pathway, including dredd, imd, relish, and downstream antimicrobial peptide genes AttA and AttB, indicating a reduced innate immune response. Subsequent investigations reveal no significant difference in viral titers between relish mutant flies and Dα6-relish double mutants, suggesting that the IMD pathway’s role in antiviral defense is dependent on Dα6. Collectively, our findings shed light on the intricate interplay between nAChR signaling and the IMD pathway in mediating antiviral immunity, highlighting the potential for nAChR-targeting compounds to inadvertently influence viral dynamics in insect hosts. This knowledge may inform the development of integrated pest management strategies that consider the broader ecological impact of insecticide use.

Due to recent innovations in gene editing technology, great progress has been made in livestock breeding, with researchers rearing gene-edited pigs, cattle, sheep, and other livestock. Gene-editing technology involves knocking in, knocking out, deleting, inhibiting, activating, or replacing specific bases of DNA or RNA sequences at the genome level for accurate modification, and such processes can edit genes at a fixed point without needing DNA templates. In recent years, although clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system-mediated gene-editing technology has been widely used in research into the genetic breeding of animals, the system’s efficiency at inserting foreign genes is not high enough, and there are certain off-target effects; thus, it is not appropriate for use in the genome editing of large livestock such as cashmere goats. In this study, the development status, associated challenges, application prospects, and future prospects of CRISPR/Cas9-mediated precision gene-editing technology for use in livestock breeding were reviewed to provide a theoretical reference for livestock gene function analysis, genetic improvement, and livestock breeding that account for characteristics of local economies.

Cashmere is the fine bottom hair produced by the secondary hair follicles of the skin. This hair is economically important. Previous studies by our research group have shown that exogenous melatonin (MT) can regulate the periodic growth of secondary hair follicles, induce the secondary development of villi, and alter the expression of some genes related to hair follicle development. Few studies on the regulation of villus growth by MT binding receptors have been published. In this study, MT was implanted subcutaneously behind the ear of Inner Mongolia cashmere goats. RT-qPCR, in situ hybridization, Western blot analysis, immunofluorescence and RNAi techniques were used to investigate the receptors and functions of MT in regulating the development of secondary hair follicles in Inner Mongolia cashmere goats. The results showed that MT binds to the nuclear receptor RORα on dermal papilla stimulates hair follicle development and promotes villus growth. The RORα mRNA expression in the skin of Inner Mongolia cashmere goats was periodic and showed a trend of first increasing and then decreasing. The expression began to increase in February, peaked in April, and reached the lowest level in May. RORα significantly affected the mRNA expression of β-catenin gene, a key gene in hair follicle development, in the presence of MT. It will lay a solid molecular foundation for further research on the regulation mechanism between MT receptor and villus growth and development and to achieve artificial regulation of villus growth time and yield to improve the effect of villus production.

Abstract Background Nicotinamide phosphoribosyltransferase (Nampt), a key enzyme in NAD salvage pathway is decreased in metabolic diseases, and its precise role in skeletal muscle function is not known. We tested the hypothesis, Nampt activation by P7C3 (3,6‐dibromo‐α‐[(phenylamino)methyl]‐9H‐carbazol‐9‐ethanol) ameliorates diabetes and muscle function. Methods We assessed the functional, morphometric, biochemical, and molecular effects of P7C3 treatment in skeletal muscle of type 2 diabetic (db/db) mice. Nampt+/− mice were utilized to test the specificity of P7C3. Results Insulin resistance increased 1.6‐fold in diabetic mice compared with wild‐type mice and after 4 weeks treatment with P7C3 rescued diabetes (P

BackgroundPrimary nuclear protein in testis (NUT) carcinoma is a rare malignant tumor originating from the salivary glands that usually occurs in midline structures, such as the head and neck, and has been identified in young patients. Progression of NUT carcinoma is rapid, and there is a high degree of malignant invasion. The median survival time of NUT carcinoma patients is 6 to 9 months, and 80% of the patients die within 1 year after diagnosis.Case descriptionThis case report summarizes the treatment of a 36-year-old male patient with NUT carcinoma of the right parotid gland. The overall survival of the patient was 2 years. We also discuss the applications and outcomes of immune checkpoint inhibitor and targeted therapy combination regimens in the treatment of NUT carcinoma.ConclusionWe suggest that targeted therapy combined with immunotherapy which has long-term clinical benefits and targeted therapy which has high clinical response rate(immunotherapy + dual-targeting three-drug regimens) is an ideal choice for the treatment of patients with rare and/or refractory tumors and will not compromise patient safety.Clinical trial registrationidentifier ChiCTR1900026300.

Abstract Periodically patterned surfaces can cause special surface properties and are employed as functional building blocks in many devices, yet remaining challenges in fabrication. Advancements in fabricating structured polymer surfaces for obtaining periodic patterns are accomplished by adopting “top‐down” strategies based on self‐assembly or physico‐chemical growth of atoms, molecules, or particles or “bottom‐up” strategies ranging from traditional micromolding (embossing) or micro/nanoimprinting to novel laser‐induced periodic surface structure, soft lithography, or direct laser interference patterning among others. Thus, technological advances directly promote higher resolution capabilities. Contrasted with the above techniques requiring highly sophisticated tools, surface instabilities taking advantage of the intrinsic properties of polymers induce surface wrinkling in order to fabricate periodically oriented wrinkled patterns. Such abundant and elaborate patterns are obtained as a result of self‐organizing processes that are rather difficult if not impossible to fabricate through conventional patterning techniques. Focusing on oriented wrinkles, this review thoroughly describes the formation mechanisms and fabrication approaches for oriented wrinkles, as well as their fine‐tuning in the wavelength, amplitude, and orientation control. Finally, the major applications in which oriented wrinkled interfaces are already in use or may be prospective in the near future are overviewed.

Abstract Graphene‐based composites show great potential in the development of lightweight functional devices and systems, and polymers are usually used as binders to enhance the mechanical properties of these composites. Due to the low thermal conductivity of the polymer and the high inherent interfacial thermal resistance between polymer and graphene, however, the developed devices and systems generally possess low thermal conductivity, which seriously limits their further thermal‐related applications. Here, a lightweight two‐phase heat transport device (TPHTD) based on a vapor‐liquid phase transition‐based heat transfer by using a graphene‐based composite material as the casing is generated. The graphene‐based TPHTD has high thermal conductivity of up to 1408 W (mK)−1 and realizes ultra‐high specific thermal conductivity of ≈5600 W (mKg)−1. This graphene‐based device with lightweight and high heat transfer capacity offers new opportunities for efficient thermal management of compact, portable, or wearable electronic and power systems.

Factors affecting sperm freezability in goat seminal plasma were investigated. Based on the total motility of thawed sperm, goats were divided into a high-freezability (HF) group with >60% total motility (n = 8) and a low-freezability (LF) group with 1 and 0.05 < P-value < 0.1. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significant enrichment of central carbon metabolism in cancer, protein digestion and absorption, aminoacyl-tRNA, and other pathways and significant differences in the abundance of seven differential metabolites, including L-glutamine, L-aspartate, L-arginine, phenylpyruvate, benzoic acid, ketoisocaproic acid, and choline between seminal plasma from the HF and LF groups (P-value < 0.05). These significantly differentially-expressed metabolites may be potential biomarkers for sperm freezability. L-glutamine, L-aspartate, and L-arginine may directly affect sperm freezability. Benzoic acid, ketoisocaproic acid, and choline may regulate sperm freezability by participating in anabolic processes involving phenylalanine, leucine, and phosphatidylcholine in sperm.

Introduction: The quality of Chinese herbs is the basis for ensuring their safety and efficacy. However, the quality evaluation system is imperfect. In particular, there is a lack of quality evaluation methods for fresh Chinese herbs during growth. The biophoton is a common phenomenon and provides complete information about the interior of the living system, which is consistent with the holistic concept of traditional Chinese medicine. Therefore, we aim to correlate the biophoton characteristics with the quality states to find the biophoton parameters that can characterize the quality states of fresh Chinese herbs.Methods: The biophoton characteristics of motherwort and safflower were measured and characterized by the counts per second (CPS) in the steady state and the initial intensity (I0) and coherent time (T) of delayed luminescence. The active ingredient content was measured by ultra-high-performance liquid chromatography (UPLC). The pigment content of motherwort leaves was measured by UV spectrophotometry. The t-test and correlation analysis were performed on the experimental results.Results: The CPS and I0 of motherwort and I0 of safflower showed a significant downward trend during the growth process, and their active ingredient content showed a trend that increased and then decreased. The CPS, I0, and the content of active ingredients and pigments in a healthy state were significantly higher than those in a poor state, while T showed the opposite results. The CPS and I0 were all significantly and positively correlated with the content of active ingredients and pigments, while the T of motherwort showed the opposite results.Conclusion: It is feasible to identify the quality states of fresh Chinese herbs by using their biophoton characteristics. Both CPS and I0 have better correlations with the quality states and can be considered characteristic parameters of the quality of fresh Chinese herbs.

Background BK virus (BKV)-associated nephropathy (BKVN) is one of the leading causes of renal dysfunction and graft loss in renal transplant recipients. Early monitoring of BKV in urine is crucial to minimize the deleterious effects caused by this virus on preservation of graft function. Methods We report a simple, rapid, sensitive loop-mediated isothermal amplification (LAMP) assay using an HFman probe for detecting BKV in urine. To evaluate the performance of the assay, a comparison of the HFman probe-based LAMP (HF-LAMP) assay with two qPCR assays was performed using urine samples from 132 HIV-1 infected individuals. We further evaluated the performance of HF-LAMP directly using the urine samples from these HIV-1 infected individuals and 30 kidney transplant recipients without DNA extraction. Furthermore, we combined the HF-LAMP assay with a portable finger-driven microfluidic chip for point-of-care testing (POCT). Results The assay has high specificity and sensitivity with a limit of detection (LOD) of 12 copies/reaction and can be completed within 30 min. When the DNA was extracted, the HF-LAMP assay showed an equivalent and potentially even higher sensitivity (93.5%) than the qPCR assays (74.2–87.1%) for 132 urine samples from HIV-1 infected individuals. The HF-LAMP assay can be applied in an extraction-free format and can be completed within 45 min using a simple heat block. Although some decreased performance was seen on urine samples from HIV-1 infected individuals, the sensitivity, specificity, and accuracy of the extraction-free BKV HF-LAMP assay were 95%, 100%, and 96.7% for 30 clinical urine samples from kidney transplant recipients, respectively. Conclusion The assay has high specificity and sensitivity. Combined with a portable finger-driven microfluidic chip for easy detection, this method shows great potential for POCT detection of BKV.

Abstract Background The role of Numb, a protein that is important for cell fate and development and that, in human muscle, is expressed at reduced levels with advanced age, was investigated; adult mice skeletal muscle and its localization and function within myofibres were determined. Methods Numb expression was evaluated by western blot. Numb localization was determined by confocal microscopy. The effects of conditional knock out (cKO) of Numb and the closely related gene Numb‐like in skeletal muscle fibres were evaluated by in situ physiology, transmission and focused ion beam scanning electron microscopy, three‐dimensional reconstruction of mitochondria, lipidomics, and bulk RNA sequencing. Additional studies using primary mouse myotubes investigated the effects of Numb knockdown on cell fusion, mitochondrial function, and calcium transients. Results Numb protein expression was reduced by ~70% (P